American Neuropsychiatric Association 2023 Annual Meeting Abstracts

Background: While some claim the end of the pandemic is neigh, the reality we see as clinicians could not be further from the truth. The reality of our “postpandemic world” is that of complexity and complications that are only beginning to be deciphered—amongst these is SARS-CoV-2-related autoimmune encephalitis (AE). A literature search demonstrates several systematic reviews and many notable case studies; however, these are generally limited to snapshots in time within a patient’s course. Here we detail a case covering 2 years of data—following a patient from diagnosis to routine follow-up within psychiatry, neurology, and neuropsychology clinics. In doing so, we lend further support to the oftentimes devasting long-term neuropsychiatric effects of COVID-19. Case History: A previously healthy, highly functioning 60-year-old physician was originally admitted in March 2020 for worsening dyspnea in the context of an acute COVID-19 infection complicated by viral pneumonia. Two weeks later, he was discharged home without notable changes in mental status, but over the course of the next few months, he would undergo multiple readmissions for encephalopathy—ultimately receiving the diagnosis of AE, following rapid improvement with rounds of IVIG and guided by the results of PET/CT. Two years following the original insult, he continues to struggle with the cognitive and behavioral changes created by his body’s response to COVID. Conclusion: We will continue to see the long-term neuropsychiatric sequela of COVID-19 long after the pandemic has ended and will need more studies to examine the neurobiological basis of associated cognitive impairment.

Background: The received wisdom among clinicians has been Provisional Tic Disorder (PTD)—tics now but never a year or more ago—is generally short-lived and mild, includes few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience. Objective: To test these views with thorough, prospectively acquired data. Methods: Prospective study of 89 children with tics starting 0–9 months ago (median 4); follow-up at 12 (±24, 36, 48) months after the first tic. Results: Age (mean±SD) 7.4±2.0 years, 25 female, 14 non-White. Most had an anxiety disorder (54), ADHD (39), OCD (17) or enuresis (25). ASD symptoms were not overrepresented (SRS T-score 50.3±10.0). After initial history, PI was confident of a past-week tic in only 49 of 59, but after extended observation all had 2+ current tics and a lifetime total of 6.7±4.2 motor and 2.2±1.7 phonic tics. 42 had had a complex tic and 69 had some tic suppression. Total tic score >13 in 61/89, impairment ≥20 in 13/88, and 53/62 had recent or planned doctor visits for the tics. At 12 months, 79 returned, and 78 still had tics. However, most (67) had no current plans to see a doctor for tics. Most who returned at 2–4 years still had tics known to child and family, but medical impact was low. Conclusion: Our results are consistent with previous observations but overturn clinical lore.

Background: Persistent cognitive, emotional, somatic/sensory, and vestibular symptoms after mild or moderate traumatic brain injury (m-mTBI) are challenging to remediate using traditional treatment approaches. Objective: To evaluate the efficacy of the integrated practice unit (IPU) approach employed by the Marcus Institute for Brain Health (MIBH) during evaluation (Eval) and intensive outpatient program (IOP) on persistent symptoms after m-mTBI among Veterans and first responders. Methods: This retrospective study included patients with persisting symptoms after m-mTBI (>6 months prior to presentation) completing Eval and IOP at MIBH between 2017 and 2022 who had evaluable Neurobehavioral Symptom Inventory (NSI) data at Eval, IOP admission, and IOP discharge, and NSI Validity-10 scores ≤22 at Eval and IOP admission. Efficacy was assessed using t tests of NSI scores (Eval vs. IOP admission, IOP admission vs. discharge), calculation of treatment response rates (using a distribution-based minimal important differences (MID) of seven or more point reduction on the NSI), and Chi-square of treatment response rates after Eval and IOP. Results: The study sample included 109 patients (11 female), age 44.3±9.9 years. NSI total scores decreased from Eval to IOP admission (N=109, t=2.74, p<0.008; Cohen’s d=0.22); 37 (33.9%) exceeded the MID after Eval. NSI total scores further decreased from IOP admission to discharge (n=105, t=11.3, p<0.001; Cohen’s d=1.08); 75 (71.4%) exceeded the MID at IOP discharge (Chi-square=30.12, p<0.001 vs. Eval response rate). Conclusion: The IPU approach to evaluation and management of persistent symptoms after m-mTBI conferred significant benefits, with IOP producing greater symptom reductions and higher responder rates than Eval.

Background: There has always been a quest for alternative and novel supportive therapies to find answers for neurocognitive disorders. They are known to support and augment the current treatment options. Music has been known to heal the human body and soul. Our review shows its healing role for the brain. Objective: This review is aimed at studying the neurogenesis and neuronal repair by music therapy and its possible use and benefit for neurocognition and brain development. Methods: We did a literature search using the MESH terms ([“Music”] AND ([“Neurogenesis”] OR [“Neuronal Repair”])). This yielded 19 results. After excluding the animal studies and studies not focused on our objective, we included six studies in our review. Results: Music therapy is shown to promote neurogenesis and neuronal repair. It is shown to promote the secretion of steroids which helps with the plasticity of brain. The enriching life experiences including music, art and culture bring on neurogenesis as a complimentary healing medicine. In a study where undergraduate students were exposed to music therapy and clinically significant improvement in cognition was noticed. An increased amygdalic response, hippocampal atrophy and hypoactive prefrontal cortex causes the symptoms of Post Traumatic Stress Disorder, PTSD and music therapy can stimulate neurogenesis, neuroplasticity and allows recovery of brain. Evidence shows music is effective in improving coping skills, decreasing depression, and anxiety. Additionally, structural changes are observed in human brain after only 15 months of music training in early childhood. These were correlated with improvements in auditory skills. Conclusion: Music listening promotes neurogenesis, neuroplasticity and improved cognitive skills.

Background: Dementia is an acquired decline in cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. Neurosyphilis is a serious complication of syphilis that can develop 10–25 years after the onset of the infection, and present with neurological symptoms including general paresis, tabes dorsalis, and dementia. If left untreated, it can lead to irreversible neuronal damage. Case History: A 50-year-old African American male with a history of hypertension not compliant with medications, hyperlipidemia, prediabetes, depression, PCP abuse, and tobacco use disorder presented to our clinic with progressive cognitive and functional decline, memory problems, falls, personality and behavioral changes, depressed mood, apathy, anhedonia, belligerence, hyperphagia, hypersomnia, and poor self-care. He had a history of syphilis in 1996 and was treated with antibiotics. CT head showed chronic microvascular changes more than typical for his age. LP showed nonreactive CSF VDRL but with an elevated protein of 51 suggesting neurosyphilis. Our patient was sent to an ID specialist and he received a 14-day course of IV Penicillin G. A month later, he returned to the clinic with reported good control of BP, and his father described an improvement in behavioral issues especially belligerence after treatment with paroxetine but no improvement in cognitive deficits and function. Conclusion: Neurosyphilis should be part of the differential diagnosis of patients showing cognitive deterioration and behavior disturbances. Substance use history should be a part of the dementia workup.

Background: Creutzfeldt-Jakob Disease (CJD) is a rare neurodegenerative spongiform disorder. Prion disease is one of the common causes of rapidly progressive dementia. CJD is generally considered a neurological disorder, but the initial presenting symptoms are often psychiatric; therefore, it is essential to understand the psychiatric manifestations. Here, we describe a case presenting rapidly progressive psychosis, later diagnosed as CJD, and discuss the literature surrounding CJD and psychiatric presentation. Case History: A 51-year-old female nurse and a pharmacy tech with no known past psychiatric history presented to the inpatient psychiatric unit with a complaint of altered mental status, acute onset psychosis, and functional quadriparesis. The CSF results showed greater than 20,000 pg/ml total protein and greater than 160,000 au/ml with a greater than 98% prion disease estimate. The patient was unresponsive and had monoclonal jerks/tremors. CSF on day 12 of admission was RT-QulC positive, 14-3-3 (160,000), and T-tau positive (>20,000), indicating prion disease with clinical and radiographic correlation. Due to the grave prognosis and no treatment modality, palliative care was consulted for further management. The patient passed away shortly. Conclusion: Psychiatric symptoms are considered a rare presentation in CJD. However, our case report emphasizes that psychiatrists have a high level of suspicion and consider the differential diagnosis of prion disease whenever psychiatric symptoms coexist with myoclonus or ataxia or if a rapidly progressive decline or dementia. It is crucial to evaluate and rule out other causes timely, and prion disease should be diagnosed to promote interventions to ease family comfort given 100% mortality.

Background: Down syndrome regression disorder (DSRD) initially reported in 1946 as “catatonic psychosis” is a symptom cluster consisting of neuropsychiatric regression which has primarily been reported in young persons with Down syndrome between ages 10 and 30 years. Clinical phenomenology consists of a subacute loss of previously acquired developmental skills in the areas of language, communication, cognition, executive function, behavioral, and adaptive skills. Other symptoms can include psychiatric manifestations, motor symptoms (stereotypies, extrapyramidal), catatonia, and rapid onset insomnia. Studies show individuals with DSRD had higher rates of autoimmune disease that could potentially cause neuroimmunologic dysfunction. 15%–20% of them had inflammatory markers in their cerebrospinal fluid. An 80% response rate has been reported with high dose steroids and/or intravenous immunoglobulin (IVIG). Case History: An 11-year-old male with Down syndrome, intellectual disability, hypothyroidism and acanthosis nigricans presented with subacute declines in cognitive, social, communicative functioning and self-care skills, psychotic symptoms and symptoms suggesting catatonia started at age 9 and at the beginning of COVID pandemic. He was diagnosed with DSRD. A brief trial of benzodiazepine, lorazepam 1 mg/day showed no improvement of catatonic symptoms and the patient’s parent did not agree with higher dose of lorazepam. The presence of hypothyroidism with elevated Thyroglobulin Ab, acanthosis nigricans and alopecia areata suggest an underlying autoimmune mechanism in this case. Conclusions: This case suggests the diagnostic trajectory of down syndrome with DSRD in early adolescence as opposed to early onset neurocognitive disorder (dementia) and also treatment trajectory of targeting autoimmune response with immunotherapy.

Background: Using clinical neuroscience has become an evidence-based strategy for patient education. Advances in neuroscience of FND may allow for similar approaches given the public health need. This is the last step of our neuroscience-based education research with focus on patient audience (patient module). Objective: We developed a 4-minute online multimedia module with simplified neuroscience-based psychoeducation. It was made to increase public awareness and as a cost-effective tool in Tele-medicine and/or short-staffed clinical settings. We surveyed audiences’ knowledge and willingness to follow treatment options. Methods: The online intervention was developed based on multidisciplinary feedback and includes an animation discussing neuroscience-informed diagnosis and treatment options followed by four questions. Results: 181 participants completed survey within 2 years (10/19/2020–10/01/2022). Participants included 32% patients, 29% clinicians, 25% family members and 13% others. They completed the survey within average of 76 seconds. 97% of participants responded correctly to knowledge-based questions. In response to multiple-choice question for willingness to follow treatment recommendations, 86% agreed, and 14% responded “neither agree not disagree” with a similar response rate in patients (87% and 13%). Conclusion: An online neuroscience-based educational intervention was well-received with positive feedback and high percentage in response to knowledge and willingness to follow treatment recommendations (there were no significant differences between patient subgroup with the rest of participants: chi-square p<0.05). We intentionally made the module and survey short to foster high engagement. To our surprise many clinicians have also watched and found the patient module helpful despite also having a “clinician module” available on our website.

Background: Stanford Neuromodulation Therapy (SNT), which uses fMRI-guided, accelerated rTMS to target the region within the left DLPFC with the greatest anticorrelation with the subgenual ACC, has shown efficacy in treatment resistant depression. The mechanism underlying the rapid improvement in SNT is unclear. Objective: We examined trajectories of individual symptoms to improve mechanistic understanding and outcome prediction. Methods: We analyzed data from 23 TRD subjects from a small RCT (12 active, 11 sham). Individual items from the MADRS were examined at baseline; daily during treatment; and 1-, 2-, and 4-week posttreatment. Outcome was treatment response (50% decrease in symptoms) 4 weeks posttreatment. We used ANOVA to identify active/sham symptom differences at each treatment day, repeated measures GLM to assess between-group differences in symptom trajectory and bootstrapped binary logistic regression to determine if early symptom change predicted outcome. Results: 58% of active patients and 9% of controls responded. The earliest MADRS item to show differences between the active and sham was lassitude (Day 2, F=4.95; p=0.037). GLM showed that lassitude trajectory differed between groups (F=6.09; p=0.024). In logistic regression, lassitude on treatment day 3 was predictive of response (controlling for baseline MADRS) (B=−1.55 p=0.005, 95% CI: [–53.57, −0.69]); model classification accuracy=78.3%, Naegelkerke R²=0.42. Conclusion: Lassitude showed differences first between active and sham SNT; early change was predictive of outcome. Further work will seek to understand the neurobiological and computational significance of this finding.

Background: Rigorous clinical examination is the most valuable tool for clinicians and should always diagnostically prevail. Bedside cognitive testing is essential in the neuropsychiatric realm. When performed appropriately, it can guide diagnostic efforts not only sparing resources but expediting management. In this case, thorough bedside testing was critical to diagnose corticobasal-degeneration, a rare disorder with an incidence of 0.6–0.9/100,000/year. Case History: A 64-year-old retired high school teacher presented to the emergency room with “paranoia and a clumsy hand,” after 6 months exhibiting memory problems, difficulties using her left hand and mood/behavioral changes. Initially seeing by primary doctor and neurologist, standard cognitive testing showed problems with word recollection and brain magnetic resonance imaging (MRI) with no abnormalities. Neuropsychological testing, 2 months prior to presentation, was compatible with mild cognitive impairment versus Alzheimer’s disease with early onset. Routine labs, repeated brain-MRI, CSF analysis with autoimmune panel and electroencephalography were unrevealing. While hospitalized, 40-minute comprehensive bedside testing by a psychiatry resident revealed gross impairment in specific cognitive subdomains, notably: spatial hemineglect, impaired construction and new learning, apathy, agrammatism, perseveration/self-monitoring errors, left upper limb ideomotor apraxia and astereognosis, and slow processing. These findings contrasted the patient’s overall preserved functional status. Conclusion: Diagnosis of probable corticobasal-degeneration (frontal-behavioral-spatial syndrome) was done. Positron emission tomography demonstrated extensive hypometabolism of the right>left parietooccipital lobes and brain-MRI amended with disproportionate parietal volume loss right>left. This case highlights the relevance of comprehensive bedside testing and is used in a workshop for psychiatry trainees at the Massachusetts General Hospital.

Background: The extended reality (XR) technologies (i.e., virtual, augmented, and mixed realities) are progressively being integrated as innovative applications and instructional resources for medical education (e.g., anatomy, neuroanatomy) and clinical care (e.g., neurology, psychiatry, surgery). Immersive experiences can deliver varying levels of perceived physical existence (immersion), interaction and presence within the digital world, increasing active learning via innovation and improved cognitive skills. Objectives: To disseminate current information regarding the applications and benefits of XR immersive experiences to supplement and demystify neuroanatomy instructional nuances. Methods: Foundational neuroanatomical concepts were reviewed, summarized, and integrated with basic clinical information. There was a particular focus on relevant topics of clinical neurosciences (limbic structures and circuits), commonly associated with important mental health disorders. These contents were collated into concise graphic-rich instructional presentations (i.e., Canva) and embedded into highly interactive digital immersive learning modules adapted for Varjo head-mounted (HMD) XR lenses. Results: Neuroanatomical concepts can be intentionally integrated with clinical learning lessons using XR technology paradigms creating highly interactive and engaging learning experiences to improve medical education and supplement clinical training. Conclusion: XR immersive experiences pose as innovations of the medical metaverse with high potential for teaching and learning, specifically for the delivery of challenging clinical neuroanatomy concepts. These innovations may represent an ideal platform to teach neuroanatomy and clinical neurosciences contents within context at varied instructional levels in medicine.

Background: Flibanserin, a serotonin antagonist currently indicated for treating Female Sexual Dysfunction Disorder, has not been described to worsen cerebellar function. Case History: This 60-year-old woman had acute-onset fainting and hit her head without loss of consciousness 8 months prior to presentation. She could not stand up and had left-sided weakness with vomiting, garbled speech, and headache. CT scan showed a left cerebellar parenchymal hemorrhage within the dentate nucleus and extending medially into the cerebellar vermis, with surrounding perilesional edema extending into the middle cerebellar peduncle. After 1 month of physical therapy, her speech, walking, and coordination improved, but she continued to have delayed speech, difficulty standing, and a wide stance. Gait examination revealed heel-walking. There was dystonic posture of the left hand. Tandem gait was unstable and wide based. Cerebellar examination showed finger-to-nose dysmetria, left>right. Slow rapid-alternating-movements (RAM) of the left upper extremity (UE). Due to absent sexual desire, she started 100 mg of flibanserin nightly. After 5 weeks, her coordination markedly worsened, with poorer balance, wider gait, and need for a cane. Physical examination displayed worse cerebellar function, including prominent horizontal titubation and decreased RAM. Markedly positive Holmes Rebound phenomenon in the bilateral UE. A week after stopping flibanserin, gait and cerebellar examination returned to baseline. Conclusion: Since serotonin is essential in cerebellar function, including its action on the cerebellar cortex and deep cerebellar nuclei, this case suggests that flibanserin’s action as a serotonin antagonist may cause cerebellar symptoms. Patients on flibanserin should undergo cerebellar examination.

Background: Cannabis is associated with development of psychotic symptoms in susceptible individuals; however, scant literature exists regarding cannabis-induced catatonia, especially in patients without prior psychiatric history. Mechanisms by which cannabis may induce catatonia have been proposed, but none established. Case History: A 23-year-old man with history of heavy cannabis use presented with two weeks of intermittent auditory hallucinations, paranoia, and marked decline in self-care requiring inpatient hospitalization. He presented 2 days earlier following a presumed fentanyl overdose, though urine toxicology was positive only for cannabis. Amphetamine, synthetic cathinone, or synthetic cannabinoid use was suspected but unproven, and he was discharged home from the emergency department after improvement in mental status. At home, he became progressively less responsive and, upon readmission, had stupor, mutism, negativism, withdrawal, and minimal oral intake. Lab work and neuroimaging were unremarkable except repeat urine drug screen again positive for cannabis. Continued progression of symptoms over several days prompted a trial of lorazepam with immediate improvement. Low-dose haloperidol was added due to suspected psychosis with ongoing disorganized behavior. He experienced eventual resolution of catatonic and psychotic symptoms over four weeks on a combination of lorazepam and haloperidol. Conclusion: This case illustrates an association of catatonia with cannabis use in a patient without previous psychiatric illness. We hypothesize cannabis modulates GABAergic signaling in the basal ganglia and neocortex leading to development of catatonia in some individuals, but more research is needed. Early recognition of catatonia in patients with known cannabis use is imperative for appropriate treatment and recovery.

Background: Individual differences in cognitive test performances are often intercorrelated–a phenomenon explained by a domain-general cognitive factor, g. Network neuroscience has principally linked g to the frontoparietal network. Lesion network mapping (LNM) combines network neuroscience with the inferential strength of lesion-deficit inference, offering a powerful method to expand upon prior work. Objective: This study aimed to perform the first LNM analysis of g. Methods: We derived g for 402 patients with chronic, focal brain lesions. We used multivariate lesion-behavior mapping (LBM) to create statistically weighted maps linking deficits in g to regional brain damage. LBM peaks were used as seeds for structural and functional LNM based on normative diffusion-weighted imaging and resting-state functional connectivity data, respectively. We used 5-fold cross-validation to determine the optimal combination of predictors of g, and applied the final model to predict g in two independent cohorts of patients with focal brain damage (N=95; N=101). Results: LBM indicated that a region of posterior left hemisphere white matter was most strongly associated with g. Structural LNM implicated diffuse left hemisphere white matter. Functional LNM identified a network most closely resembling the dorsal attention network. The optimal model was comprised of demographics, and LBM- and functional LNM-based predictions (R²=0.38). This model predicted deficits in g across cohorts (R²s=0.53, 0.25). Conclusion: Our findings suggest that the dorsal attention network is critical for g. Clinically, our study highlights the importance of considering domain-general cognitive following focal lesions to specific brain networks.

Background: Disrupted sleep is a common sequela of traumatic brain injury (TBI) with profound downstream consequences. Post-TBI alterations in sleep architecture require further study. Objectives: 1) Evaluate polysomnographic measures of sleep architecture in participants with prior TBI compared to controls and as meta-analyses of pooled means. 2) Evaluate effects of timing and severity of TBI on polysomnographic outcomes. Methods: PRISMA compliant systematic review was conducted of MEDLINE, PsycINFO, EMBASE and Scopus. Inclusion criteria: 1) reporting polysomnography in the context of TBI and 2) operationalizing TBI using clear/formalized criteria. Data were pooled in random-effects meta-analyses with outcomes expressed as mean differences (MD). Results: In participants with TBI, sleep was comprised of 19.39% REM sleep, 8.13% N1, 51.18% N2, and 17.53% N3, as determined by meta-analyses of single means. Total sleep time was reduced in chronic (>6 months) TBI compared to acute-intermediate TBI (<6 months) (p=0.01). Compared to controls, participants with TBI differed with increased N1 sleep (MD=0.64%; 95% CI=0.02, 1.25; p=0.04), reduced sleep efficiency (MD=−1.65%; 95% CI=−3.18, −0.12; p=0.03), and reduced sleep latency on the multiple sleep latency test (MD=−5.90 mins; 95% CI=−10.09, −1.72; p<0.01). On subgroup analyses, participants with mild TBI differed from controls with reduced total sleep time (MD=−29.22 mins, 95% CI=−54.16, −4.27; p=0.02). Similarly, participants with acute-intermediate TBI exhibited increased sleep latency compared to controls (MD=8.96 mins; 95% CI=4.07, 13.85; p<0.01) and differed significantly from participants with chronic TBI (X2 [1,N=608]=6.54; p=0.01). Conclusions: Sleep architecture is altered following TBI with potential implications regarding functional outcomes and recovery. These alterations appear to differ based on severity of injury and time since injury.

Background: Since the time of Galen and Hippocrates, there have been reports of febrile illness improving psychiatric symptomatology. More recently, Austrian neuropsychiatrist Wagner Jauregg reported febrile illness curing “paralytic dementia,” commencing widespread use of “pyrotherapy” for neuropsychiatric illness from the 1920s-1940s and for which he received the Nobel Prize in 1927. Though long supplanted by more efficacious and safer treatments, this relic of neuropsychiatric history may still bear relevance in psychiatrically ill patients who develop febrile illness. Case History: A 23-year-old presented to the emergency department with 2 days of fever to 102.6°F, nausea, vomiting, and was found to have COVID-19. On examination, he was cooperative, removed blankets from his head for the interview and was able to converse appropriately, articulating his name, age, location, current circumstances, and the date. Collateral was obtained demonstrating that he had not spoken more than one syllable at a time for 1 year prior to this illness, suffered from florid paranoia, and would defecate in bed, lying in his bowel movement for several days at a time. Fever resolved on hospital day 2 and he declined to his prior psychiatric baseline by hospital day 4. Conclusion: This case illustrates possible fluctuation of psychotic symptom severity in the context of febrile illness. Though the evidence base surrounding the practice of pyrotherapy is sparse, recent evidence demonstrates that high temperatures increase overall neuronal firing, and may effect psychiatric benefit by a similar mechanism as electroconvulsive therapy, even in the absence of febrile seizure.

Background: Persistent genital arousal disorder (PGAD) is an increasingly recognized disorder defined as persistent, intrusive, distressing, and unwanted sensations of genital arousal in the absence of sexual thoughts, or interest, for a minimum of 3 months. PGAD often leads to significant feelings of distress, and may exacerbate depression, or even lead to suicidal ideation. Proposed etiologies for PGAD include psychological, vascular, neurological, and medication-induced. In 2019, an expert panel convened to establish consensus on nomenclature and management. However, since its first report in 2001, knowledge about PGAD, including treatment, has largely been dependent upon case studies. In an effort to add to that body of data, we present the case below. Case History: A 77-year-old female with a past psychiatric history of major depressive disorder, generalized anxiety disorder, and insomnia presents with persistent genital arousal leading to worsening anxiety, depression, and suicidal ideation. Several neurological symptoms were also reported including tremor, unsteady gait, tingling of limbs and lips, and frequent headaches. Neurologic and gynecologic evaluation were unremarkable. We discuss the laboratory and radiologic work-up and management of this patient’s symptoms and the proposed etiologies, diagnosis, and treatment of persistent genital arousal disorder and its psychiatric comorbidities. Conclusion: This case illustrates the importance of recognizing persistent genital arousal disorder as it can cause marked impairment in functioning and mood. Further investigation is needed to develop a better understanding if its etiologies, and to develop universal diagnostic criteria and treatment guidelines.

Background: Diffusion Tensor Imaging (DTI) measures the diffusion of water molecules in axons as an indicator of brain white matter integrity. Abnormalities have been shown after sport-related concussion (SRC). Objective: To compare DTI values between concussed adolescents (CA) and healthy athletic adolescents (HA), and to examine how concussion symptoms relate to regional DTI measures. Methods: CA (N=32) were diagnosed with SRC within 10 days of injury. HA (N=25) were age and sex matched athletes who did not report SRC in the past year. All participants completed the Post-Concussion Symptom Scale, an exercise tolerance test, and DTI at two separate visits. Main outcomes were whole brain and regional Fractional Anisotropy (FA) and Mean Diffusivity (MD). Results: HA did not differ between Visit 1 and two in any DTI values. After post hoc correction, CA had higher parietal lobe FA than HA (0.212 [0.204, 0.221] vs. 0.194 [0.184, 0.204] p=0.023) and higher occipital lobe FA than HA (0.224 [0.209, 0.239] vs. 0.193 [0.183, 0.202] p=0.009). CA had lower MD than HA at Visit 1 (6.74 [6.46, 7.03]*10^–4 vs. 7.62 [6.93, 8.31]*10^–4 p=0.016). After post hoc correction in CA, exercise intolerance was positively correlated with brainstem FA (r=0.51, p=0.003) and anxiety/nervousness was negatively correlated with frontal lobe MD (r=−0.44, p=0.008). Conclusion: Despite some controversy regarding DTI’s clinical utility, this study found a discernable difference in DTI indicators of function between adolescents with and without concussion. The strong relationship between symptoms and brain region white matter function may help clinically validate DTI.

Background: Serotonin syndrome (SS) is a potentially life-threatening condition of increased serotonergic activity. Little is known about the association of SS with cerebral palsy (CP) and/or agenesis of the corpus callosum (ACC). To our knowledge, only four cases reports have been published on SS associated with CP and one case report published on SS in the context of ACC. Here we present a case of a 23-year-old female with CP and ACC who presented with signs and symptoms of SS. Case History: The patient had a history of CP, ACC, intellectual disability, developmental delay, binge eating disorder, and unspecified anxiety and depressive disorders. She was maintained on citalopram and lurasidone for 5 weeks prior to presenting to the emergency department with bilateral tremor, profound diaphoresis, diarrhea, and agitation. Vitals were notable for tachycardia and elevated blood pressure. Physical examination revealed bilateral upper extremity spasticity, hyperreflexia, and ocular clonus. During her hospital stay, she also developed fevers reaching 39.2°. Infectious workup, including lumbar puncture, was nonrevealing. Head imaging and electroencephalography did not reveal any pathology. She was managed initially with lorazepam (up to 28 mg per day) without effect and was then started on cyproheptadine with resolution of symptoms on 16 mg/day. Conclusion: Further research is needed to demonstrate whether CP and/or ACC are risk factors for developing SS, to elucidate neuropathological underpinnings for such an association, and to delineate the ideal management approach.

Background: Alzheimer disease (AD) is most classically known for its late on-set, insidious time course with some variation depending on associated genetic markers, family history and comorbidity. Rapidly progressive AD (rpAD) has been defined by survival time of 2 years or less and a six-point MMSE score decline per year. Per literature review, motor signs, psychotic symptoms, the presence of high total Tau and 14-3-3 protein are predictive but not always present in rpAD. As more cases of rpAD are described, it would be prudent to review the unique features and any new signs. Case History: A 63-year-old woman with no personal/family psychiatric history developed depression and memory difficulties around the end of her romantic relationship with a married man. Her initial Saint Louis University Mental Status (SLUMS) score was 27/30 but it was revealed that her significant alcohol use could have been contributing. She was later diagnosed with a functional gait disorder after thorough work-up. Her behavior became increasingly erratic, making poor financial decisions and perseverating over persecutory delusions. Repeat SLUMS score at 7 months was 11/30. Full dementia work-up showed normal tau/amyloid ratio and phosphorylated tau, but low CSF amyloid, high total tau, and global cortical hypometabolism with a temporoparietal predilection on fluorodeoxyglucose-positron emission tomography (FDG-PET). Conclusion: This case of dementia is unique in its time course, higher premorbid functioning, comorbid functional gait disorder and varying biomarkers. While low amyloid has been correlated with early onset AD, pathological confirmation will be necessary to confirm rpAD.

Background: Catatonia is a diverse, psychomotor disorder with poorly defined pathophysiology that can lead to severe sequelae-rhabdomyolysis, thrombosis, malnourishment. While catatonia is commonly misperceived to only originate from psychiatric illness, a substantial proportion of catatonia cases occurs secondary to various medical illnesses, from sepsis, seizures, benzodiazepine withdrawal to even stroke. While stroke is one of the most prevalent neurological disorders, catatonia related to cerebrovascular events is rarely described in the literature (Seven case reports, most predating modern neuroimaging), likely due to underreporting/misdiagnosis. Given the obscure mechanism of catatonia, it would be helpful to review a case of stroke-related catatonia, specifically cerebral venous sinus thrombosis (CVST). Case History: A 40-year-old man with a history of a remote episode of rhabdomyolysis was transferred from an outside facility for CVST. Neuroimaging showed complete thrombotic occlusion of the left internal jugular vein, left sigmoid, and transverse sinuses with biparieto-occipital infarcts and petechial hemorrhagic transformation. Initial NIH stroke scale was 11 (drowsiness, confusion, and mild, generalized weakness). Two days later, he developed mutism, repetitive eye blinking, hypertension and tachycardia. Repeat head imaging was stable and continuous EEG was normal, so Psychiatry was consulted. Bush Francis Catatonia Rating Scale (BFCRS) 17 (stupor, mutism, staring, stereotypy, rigidity, negativism, withdrawal, Mitgehen), which rapidly responded to ativan (BFCRS 4). Conclusion: This case of CVST-related catatonia can be further extrapolated to the biparietal-occipital location and attentional deficits as in Balint’s syndrome, though visuospatial deficits were difficult to assess. Reviewing stroke localization may further elucidate the pathophysiology of catatonia.

Background: Dissociative amnesia is memory loss that cannot be explained by neurological process. It can be accompanied by dissociative fugue, which is “sudden, unexpected, travel away from home or one’s customary place of daily activities, with the inability to recall some or all of one’s past.” Most dissociative amnesia involve autobiographical memory loss. Traumatic or stressful life events such as natural disasters, physical assault/violence, or military events often precede dissociate fugue. Symptoms last for days to years; the course is varied; most recover their missing memories. Dissociative states have been linked to executive dysfunction. No established evidence-based treatment guidelines exist, though psychotherapy in a supportive, nonskeptical environment is recommended. Case History: An unidentified patient was found unconscious on the streets, and he was brought into the emergency room with signs of sepsis. He was admitted to the hospital, and antibiotics plus fluids were quickly started. His English was heavy accented, despite stating he was an English native. He did not know his reason for admission. He provided fictitious identity and claimed to speak a middle eastern language. Via fingerprints, police identified him. His name gave clues to a central Asian language. With an interpreter, the patient spoke the central Asian language fluently, and he recalled his autobiographical memories. Imaging, blood work, utox, and EEG were unremarkable for cause. Neuropsychology revealed MCI with executive dysfunction. Conclusion: This case highlights that dissociative amnesia/fugue should be on the differential for unexplained memory loss.

Background: CNS lymphoma generally presents with features of raised intracranial pressure, focal neurological deficits, seizures, and neuropsychiatric symptoms such as memory loss, difficulty with attention/concentration, apathy, depression, anxiety, and agitation, with psychosis and disinhibition being the least frequent. Despite being quite rare and underrepresented in the literature, CNS lymphoma can present with psychotic symptoms only, resembling schizophrenia while lacking focal neurological deficit. Case History: Patient was a 67-year-old man with history of prostate cancer s/p prostatectomy, BCC s/p Moh’s, hypertension, hyperlipidemia, and no past psychiatric history who presented with acute-onset psychosis and delusion. He had thought blocking, perseverative thinking, and anxious affect. Neurological examination, initial brain MRI wwo contrast, urine toxicology, EEG, and labs were all unremarkable. However, repeat MRI brain 2 months later revealed a 4-cm region of decreased diffusion centered at the right basal ganglia, extending inferiorly to the anteromedial right temporal lobe and superiorly to the right corona radiata. PET illustrated increased FDG uptake in the bilateral basal ganglia, right more severe than left. LP showed remarkably elevated protein level but no cells. Path result indicated high-grade lymphoma, most consistent with diffuse large B-cell lymphoma with BCL6 rearrangement detected. He underwent HDMTX and XRT. Conclusion: Psychosis can be the only presenting feature of CNS lymphoma. Given that early detection and treatment of CNS lymphoma is crucial in decreasing morality rate and improving quality of life, it is important to have clinical suspicion for neurological disease presenting as pure psychiatric disturbance particularly in elderly patients without psychiatric history. More research will be needed to understand how brain tumors associate with psychiatric symptoms.

Background: Traumatic brain injury (TBI) is the signature injury of modern military conflicts and can result in functional limitation and multiple neuropsychiatric symptoms. Special Operations Veterans (SOV) are particularly susceptible, presumably due to repeated blast and combat exposure. Ibogaine is a naturally occurring psychoactive alkaloid thought to have antiaddiction properties. A recent retrospective study suggested that ibogaine may have therapeutic potential in SOV with a history of TBI (SOV-TBI). With current treatments offering only modest efficacy, some veterans are traveling internationally for ibogaine, but data on its safety and efficacy are lacking. Objective: To assess the safety and therapeutic potential of ibogaine in SOV-TBI. Methods: We prospectively evaluated 30 prescreened SOV-TBI traveling to an ibogaine clinic to receive a maximum of 21 mg/kg oral ibogaine. Participants were assessed at baseline, posttreatment, and 1-month posttreatment. Our primary outcome was change in the World Health Organization Disability Assessment Scale from baseline to 1-month posttreatment. We also assessed for changes in severity of posttraumatic stress disorder (PTSD), depression, and anxiety. Results: There were no safety concerns. Participants experienced a 52% reduction in overall disability at 1-month posttreatment (Cohen’s D=2.19), with only 1/30 scoring above the threshold for mild disability (down from 18/30 at baseline). PTSD, depression, and anxiety severity decreased by 88%, 87%, and 81%, respectively. Conclusion: In a prospective study of pre-screened SOV-TBI, ibogaine was well tolerated and associated with substantial improvements in functioning and neuropsychiatric symptom severity. Controlled trials are needed to further evaluate efficacy and safety.

Ann C. Childress, Scott Kollins, Andrew C. Barrett, Rene Braeckman, Sven Guenther, Travis C. Mickle, Charles Oh, Matthew Brams

Background: Efficacy and safety of SDX/d-MPH have been reported previously in children with ADHD. Objective: To evaluate changes in ADHD severity in children (aged 6–12 years) posttreatment with SDX/d-MPH. Methods: During a 3-week open-label, dose-optimization phase, subjects (N=150) were titrated to a final SDX/d-MPH dose of 26.1/5.2 mg, 39.2/7.8 mg, or 52.3/10.4 mg based on tolerability and individual response. During the subsequent 7-day double-blinded treatment period, subjects received once-daily SDX/d-MPH or placebo. The primary efficacy end point was mean change from baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham-Combined (SKAMP-C) scores averaged over the laboratory classroom day (0.5–13 hours postdose). The Conners 3rd Edition-Parent (C3P) score, an exploratory end point, assessed weekly changes in ADHD severity during the dose-optimization and treatment phases. Results: During the treatment phase, SKAMP-C scores improved significantly with SDX/d-MPH versus placebo (least-squares mean difference [95% CI], −5.4 [−7.1, −3.7]; p<0.001), indicating fewer symptoms with SDX/d-MPH versus placebo. Changes in ADHD severity, based on mean C3P scores, were significantly improved from baseline at each visit during dose-optimization for each subscale (p<0.001). During the treatment phase, C3P scores significantly improved from baseline for SDX/d-MPH versus placebo in the subscales of inattention (−11.2 [−15.7, −6.7]), hyperactivity/impulsivity (−9.9 [−14.4, −5.3]), executive functioning (−9.0 [−13.3, −4.7]), and learning problems (−5.4 [−8.9, −1.8]; all p≤0.003). No significant difference was seen in the subscales of defiance/aggression and peer relations. SDX/d-MPH had no concerning safety signals. Conclusion: SDX/d-MPH demonstrated significant reductions in ADHD severity in children based on the C3P scores.

Background: Acute to subacute behavioral and cognitive changes present a broad differential diagnosis with etiologies spanning both neurology and psychiatry. These include delirium, autoimmune/inflammatory/infectious encephalitis, rapidly progressive dementia, and acute psychosis. Subacute onset of isolated deficits in abstraction and executive functions in the absence of changes in mood, behavior, language and memory represents an unusual clinical presentation and challenges this differential diagnosis. Case History: A 67-year-old retired executive with no prior neurological or psychiatric history presented with 1 month of hyperverbal speech patterns and irritability. Examination revealed a flat affect and robotic speech but no mood disturbance, with tangential and concrete thought processes. For example, “a ruler rules over people and a watch rules over time.” He had otherwise preserved memory, calculation, visuospatial and language function. Brain MRI was normal, and CSF analysis revealed a negative autoimmune and paraneoplastic panel. Empiric treatment with 5 days of intravenous steroids for a presumptive diagnosis of autoimmune encephalitis resulted in improved thought processes—he was less tangential and his abstraction deficits improved partially. The decision was made to start therapeutic plasma exchange. Conclusion: Workup of isolated acute to subacute executive dysfunction should be broad and may require making decisions about empiric treatment based on clinical grounds. The presentation of largely isolated abstraction deficits has neurobiological implications as to how the human brain generates understanding of concepts and semantic processing.

Background: Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder due to current categorical approaches to psychiatric diagnosis. Cognitive profiles in PTSD may provide a phenotype that is useful in predicting treatment response. Objective: This study attempted to replicate the work of Etkin et al. (2019) by identifying a cognitive phenotype (not based on heterogeneous symptoms) associated with resting-state functional connectivity to predict treatment response in PTSD. Methods: Twenty individuals (age M=33.4 years old, SD=7.1 years, 3 females) who met DSM-5 criteria for chronic (>1 year posttrauma) combat-related PTSD completed MRI scans. As in Etkin et al. (2019), patients were classified as cognitively impaired or cognitively intact based on their performance on a delayed recall memory task (the Rey Auditory Verbal Learning Test). All participants underwent blood oxygen level dependent (BOLD) resting-state scans. CONN toolbox (https://web.conn-toolbox.org/) was used for standardized preprocessing of the BOLD resting-state data. Results: We replicated the finding that the cognitively impaired and intact groups did not differ in their clinician-rated PTSD symptoms or self-reported symptoms of a highly comorbid disorder, depression. We replicated the finding that cognitively impaired PTSD patients had differential resting-state, within-salience network connectivity, than controls and cognitively intact PTSD patients (F [2,23]=3.408, p=0.051, η_p²=0.237). We also partially replicated the finding that the interaction between cognitive performance and within-salience network connectivity predicted treatment-related change in PTSD symptoms at a trend level of significance (p=0.093). Conclusion: Our findings support the idea that clinically meaningful, neurocognitive phenotypes can be identified that are not based on symptoms.

Background: SDX/d-MPH is approved for patients with ADHD aged ≥6 years. Objective: To evaluate treatment responder rate (RR) using the ADHD-RS-5 score based on optimized dose level of SDX/d-MPH. Methods: During a 21-day dose optimization phase of a classroom study, 155 patients initiated treatment with 39.2/7.8 mg SDX/d-MPH in the first week and then were titrated to an optimum dose; 5 patients were down-titrated to 26.1/5.2 mg, 76 were up-titrated to 52.3/10.4 mg, and 69 remained at 39.2/7.8-mg during the following 2 weeks. Responder threshold values were 30% and 50% based on the percent change from baseline (day [D] 0) to D7, D14, and D21 in the ADHD-RS-5 score. Results: Of the 5 patients optimized at 26.1/5.2 mg, ≥80% of patients across all days had ≥50% RR. Of the 69 patients optimized at 39.2/7.8 mg, 72.5% had ≥50% RR at D7, and 81.2% had ≥50% RR by D21. Of 76 patients optimized to 52.3/10.4 mg, 22.4% had ≥50% RR at D7 (initiated at 39.2/7.8 mg), and 72.4% had ≥50% RR by D21. Conclusions: Responders are evident after the first week of SDX/d-MPH treatment at the 26.1/5.2-mg and 39.2/7.8-mg final dose levels, with increases in the proportion of responders thereafter. The 52.3/10.4-mg final dose level continued to increase in the proportion of responders after titration to the 52.3/10.4-mg final dose level.

Background: Autoimmune encephalitis is a devastating condition, and we have only begun to understand it in the past several years. One of the more common antibodies seen is anti-NMDA, especially in young women with teratomas. The common course usually involves a viral prodrome, psychotic phase, unresponsive phase, restless phase, and recovery phase. As the disease progresses, patients develop movement disorders, seizures, and autonomic instability. Here, we present a patient who was admitted for presumed brief psychotic episode from multiple stressors and later found to have anti-NMDA encephalitis. Case History: This is a 22-year-old female who initially presented with paranoia, hyperreligiosity, agitation, and disorganized thinking. No clear prodrome. She suddenly decompensated, leading to hospitalization, eventually becoming catatonic. Rapid onset, age, lack of prior psychiatric history, and vital sign instability led to suspicion of medical etiology. She was treated with high dose benzos for catatonia and Zyprexa. Initial workup included negative MRI brain, 24-hour EEG with no acute findings, LP with normal cell count, protein, no infectious etiology, negative serum anti-NMDA, and otherwise negative workup. Given lack of other findings, she was treated for presumed psychosis and underwent 4 rounds of ECT before CSF anti-NMDA returned positive a few weeks later. She was treated with IV steroids/rituximab, and bilateral teratomas were resected. She recovered well and regained her baseline. Conclusion: This case demonstrates the importance of considering underlying medical causes for psychosis in patients with unusual presentations, especially if preliminary workup is negative early in the disease course.

Background: Neurological complications are rare following aesthetic procedures, including liposuction. Amnestic syndrome associated with ataxia is an unusual presentation, and few cases with spontaneous recovery have been reported. Here, we describe clinical characteristics and trajectory in a case of complete recovery from postoperatory amnestic syndrome with ataxia. Case History: A 19-year-old female student developed irresponsiveness, hypoventilation and cyanosis after a cosmetic liposuction procedure, requiring intubation and mechanical ventilation, and being discharged 1 week later. The initial outpatient neurological examination was significant for a 18/30 mini-mental state examination (MMSE) score, abulia and severe axial-locomotor ataxia. She was unable to walk or stand unassisted. Structural MRI was normal, however, reduced N-acetylaspartate (NAA) and increased myoInositol (mI) in the posteromedial cortices was noted in MR-spectroscopy (MRS). In the first 6 months, the patient progressively restarted engaging in daily activities, recovered from axial-locomotor ataxia, and regained ability to walk, and to form new memories. A year later, she scored 30/30 on MMSE, had no significant deficits and spectroscopy showed normalization of NAA and mI. Conclusion: This patient had spontaneous, complete recovery from an amnestic syndrome with ataxia. Although the mechanisms remain uncertain, the patient’s age, progressive improvement, and normal structural MRI may represent signs of favorable long-term prognosis.

Background: During the pandemic, physicians caring for COVID patients were at increased risk of mental health challenges and moral injury. Existing studies have demonstrated that socially marginalized communities were disproportionately affected by COVID-19; however, little is known about the role of physician social identities (e.g., race, gender, immigration status) in susceptibility to moral injury and mental health and functional outcomes. Objectives: To preliminarily describe the association between physician social identities, experiences of moral injury, and mental health and functional outcomes; and to gain physician perspectives on potential interventions. Methods: Seven physicians who cared for COVID patients at the SFVA/UCSF during the COVID-19 pandemic (March 2020-present). Physicians were asked about social identities, how identities influenced care of COVID patients, experiences of moral injury, and ideas about interventions. Thematic qualitative analysis was used to evaluate interviews. Demographics and screening measures for depression, anxiety, PTSD, alcohol use, moral injury, and psychosocial functioning were also collected. Results: Physician self-identified social identities played a critical role in experiences of patient care and moral injury during the pandemic. Physicians would find therapy and mental health support helpful for symptoms of moral injury and distress, but face barriers including concern for professional repercussions, scheduling accessibility, and expense, especially for trainees. Conclusions: It is important to consider the role of social identities when examining the impact of the pandemic on physician experiences, and to consider both general and identity-specific barriers to mental health support for physicians.

Background: Huntington disease-like 2 (HDL2) presents with symptoms similar to Huntington’s disease (HD), including motor dysfunction, cognitive changes, and psychiatric abnormalities, that are clinically indistinguishable from Huntington’s disease (HD). In patients with suspected HD who are negative for CAG repeat expansion testing, HDL2 should be considered, particularly in patients of African descent. We present a case of suspected HDL2 presenting with psychosis in a middle-aged female with a strong family history of HDL2. Case History: A 47-year-old black female with no psychiatric history presented to the emergency department for bizarre behavior. For 5 years, the patient’s family had observed concerning behaviors, including social withdrawal and neglect (of self and dependent children). Over the past year, the patient began to demonstrate symptoms of cognitive decline, including wandering and new onset psychosis with paranoia, delusions, and hallucinations. On assessment, the patient was thin, guarded, and suspicious with flat affect. Neurological examination was unfortunately limited throughout admission due to lack of participation. MRI showed age-advanced parenchymal volume loss, most prominent in the parietal and occipital lobes, and abnormal caudate volume loss, consistent with possible HD. Initial genetic testing for HD was negative. Further investigation revealed a family history of HDL2, rather than HD, in the patient’s mother, sister, and brother. We are awaiting results of genetic testing for HDL2. Her psychosis showed modest improvement on risperidone (up to 2 mg QHS), but improved further with ECT (ongoing). Conclusion: Clinicians should consider testing for HDL2 in a patient presenting with neuropsychiatric symptoms and HD phenotype.

Background: Depression in multiple sclerosis (MS) responds poorly to conventional pharmacotherapy, highlighting the need for clinical TMS trials. However, it is unclear if MS depression is suitable for circuit-targeted therapeutics. Objective: This study developed a technique for identifying treatment targets based on brain circuits derived from symptom-causing brain lesions and tested this technique using published predictive brain circuits connected to lesions associated with greater depression. Methods: We analyzed a recently published “MS depression circuit map” based on the normative connectivity of brain lesions that increase depression risk in MS. We constructed a precomputed functional connectome using mean whole-brain functional connectivity across 1,000 participants. We compared each voxel’s connectivity map to the MS depression circuit map using spatial correlations. Voxels whose connectivity maps most correlate with the MS depression circuit map are identified as potential TMS targets. As a comparator, we conducted the same analysis using a published depression circuit map derived from stroke lesions and penetrating head trauma (N=461). Results: The peak lesion-derived TMS target for MS depression was at MNI coordinates (−38,44,34). This target was within 1cm of the target derived from other lesion types located at (−44,38,30) and a target derived from subgenual cingulate anticorrelations at (−42,44,30). Conclusion: The precomputed functional connectome is a high-resolution atlas of voxel-wise functional connectivity that reveals potential therapeutic neuromodulation targets by comparing their connectivity to a template brain map. Our proposed TMS target for MS depression is near the current clinical TMS targets for depression, suggesting that MS depression may respond to TMS.

Laura Duque, Juan Pablo Ospina, Rodolfo Savica, Kemuel L. Philbrick, John D. Port, Balwinder Singh

Background: Catatonia is a heterogeneous neuropsychiatric syndrome characterized by dysregulation of motor, affective and behavioral function. Multiple disorders, including structural brain lesions, systemic diseases, and psychiatric disorders have been linked to this syndrome. It is unclear what the neurological basis of catatonia is, nor to what extent the underlying etiology correlates with the pathophysiological changes exhibited by catatonic patients. Objective: To review the clinical characteristics of patients diagnosed with catatonia that underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and compare the metabolic patterns in catatonia associated with a psychiatric disorder (APD) to those associated with another medical condition (AMC). Methods: We retrospectively identified adult patients hospitalized at Mayo Clinic in Rochester, Minnesota between 2001 and 2021 that were diagnosed with catatonia and evaluated with FDG-PET. Results: A total of 9 of 364 hospitalized patients with a clinical diagnosis of catatonia were assessed with FDG-PET (mean age, 58 years, 44.4% female, N=5 catatonia APD, N=4 catatonia AMC). Catatonia symptom severity assessed by the Bush-Francis Catatonia Scale (BFCS) was similar between patients with catatonia APD and AMC (mean BFCS 16.4 and mean BFCS 17.5 respectively, p=0.826). Patients with catatonia AMC had significant hypometabolism in parietal and temporal regions when compared to catatonia APD (N=3 catatonia AMC and N=0 catatonia APD, p=0.011 in both regions). Conclusion: Data from our case series suggest distinctive brain metabolic patterns in catatonia depending on the associated condition. Further rigorous and well-powered studies are needed to better understand the relationship between clinical characteristics and functional alterations in catatonia.

Background: Ruptured cerebral aneurysm is a common cause of hemorrhagic stroke. Every year over 795 thousand people in the United States have a stroke, and about 610 thousand of these are first-time strokes. Hemorrhagic strokes make up 13% of stroke cases. Stroke is an extremely debilitating condition that sometimes leads to temporary or permanent disabilities. Neuropsychiatric symptoms such as depression, anxiety, fatigue, and apathy are common sequelae of stroke seen in up to 30% of stroke survivors. Psychotic symptoms poststroke are uncommon, with an incidence rate between 1% and 5.3%. Nonetheless, when present especially in patients with no past psychiatric history, they tend to be underdiagnosed, undertreated, or attributed to substance use or other medications despite their poor clinical prognosis. Case History: A 23-year-old female brought to the emergency department due to erratic and impulsive behaviors, pressured speech, and hallucinations. She had no past psychiatric history however, 20 months prior, she had an emergency C/S complicated by complex partial seizures on the operating table secondary to a subarachnoid and intraventricular hemorrhage following a LPCA Aneurysm rupture (seen on CT and CTA). A careful review of this patient’s history and presentation indicates that her symptoms are most likely complications of her hemorrhagic stroke. Conclusion: This case illustrates poststroke first-episode psychosis and its poor outcomes. Psychosis is considered one of the most severe neuropsychiatric complications poststroke, yet it is most often underdiagnosed and undertreated. More research is needed to inform evidence-based practice and guidelines for poststroke psychiatric management.

Background: Anxiety and mood disorders are highly prevalent in epilepsy and even more pronounced in complex epilepsy syndromes, yet few studies have evaluated a comorbid treatment response. The FDA approval of Epidiolex for the treatment of complex epilepsy syndromes suggests pharmaceutical grade cannabidiol may benefit a wide variety of seizure types. Objective: This open label, adjunctive, clinical trial seeks to assesses whether Epidiolex improves anxiety as well as epilepsy in pediatrics. Methods: Participants were between ages 6 and 17 and all had epilepsy requiring medication treatment. Anxiety symptoms impairing function were present at baseline. Titration of 5 mg/kg/day over 4 weeks was implemented, to reach a target dose of 20 mg/kg/day, but flexible dosing was allowed to more closely approximate clinical practice. Given the observational nature of this study, ratings from 20 completers will be used to assess primary outcome measures, including changes from baseline to end-of-study scores in anxiety, as measured by Clinical Global Impression Improvement (CGI-I) ratings, where ratings of a 1 or 2 (on a seven-point scale) will be considered positive responses. Results: Six participants have been enrolled (3 males, 3 females, age 9–17 [Mean=12.67, SD=2.88]). Two participants have completed the study, each showing improvement on the CGI-I (Mean Baseline CGI=6, Mean EOS CGI=1). Anxiety measures include the SCARED, which have shown significant improvement (CR improvement from 37 to 28 and 39 to 35 in the two completers). Conclusion: Interim results suggest that Epidiolex notably improves anxiety and epilepsy symptoms simultaneously.

Anneliese T. Elmer, Emily N. Russel, Catharine H. Johnston-Brooks, James P. Kelly, Christopher M. Filley, Jeffrey R. Hebert, David B. Arciniegas

Background: The Neurobehavioral Symptom Inventory (NSI) assesses self-reported cognitive, emotional, somatic/sensory, and vestibular symptoms after traumatic brain injury (TBI). The degree of change on the NSI (total and symptom domains) necessary to meet or exceed the threshold for minimally important differences (MID) in the Veteran and first responder population served by the Marcus Institute for Brain Health (MIBH) is needed. Objective: To define MID on the NSI total and four symptom domain scores in the Veteran and first responder population receiving care at MIBH. Methods: Veterans and first responders who participated in evaluation (Eval) and/or intensive outpatient program (IOP) at MIBH between 2017 and 2022, had persisting symptoms after mild or moderate TBI (>6 months prior to presentation), and had valid NSI profiles (Validity-10=22) were included. MID_Eval=0.5 standard deviation (SD) of the baseline NSI at Eval and MID_IOP=0.5 SD of NSI at IOP admission. Results: The MID_Eval sample included 350 patients (34 female), age 43.7±10.0 years; the MID_IOP sample included 128 patients (13 female), age 43.6±9.7 years. In both the MID_Eval and MID_IOP samples, the NSI Total MID is seven points. In both the MID_Eval and MID_IOP samples, the Cognitive MID is two points and the Emotional MID is three points. The Somatic/Sensory MID_Eval is three points; Vestibular MID_Eval is one point; Somatic/Sensory MID_IOP is two points; and Vestibular MID_IOP is two points. Conclusion: The reported MIDs identify responders to treatments directed at NSI-assessed symptoms. Concurrent assessment of the clinical relevance of these MIDs will define minimal clinically important differences.

Background: Many military service members and veterans suffer from posttraumatic stress disorder (PTSD) and disordered sleeping. Although many veterans experience significant reduction of PTSD symptoms through evidence-based treatments for PTSD, sleep difficulties frequently remain after these treatments. Objective: We investigated changes in self-reported disordered sleeping in participants who completed an intensive clinical program for PTSD. We further looked at how posttreatment PTSD symptoms were associated with posttreatment sleep problems. Methods: Participants were veterans and service members who attended the Home Base 2-week intensive clinical program (ICP) for PTSD between August 2019 and March 2022. Pre- to posttreatment differences were analyzed through paired t tests. Linear regression was used to test the association between posttreatment PTSD disordered sleep symptoms. Potential confounders such as history of traumatic brain injury, alcohol and marijuana use, and depression were tested. Results: Five hundred nineteen participants were included. Paired t tests demonstrated significant pre- to posttreatment differences on the Pittsburg Sleep Quality Index (PSQI) and PTSD Checklist-5 (PCL-5). However, 88.2% (458/519) of patients reported significant sleep disturbances posttreatment. Posttreatment hyperarousal (p=0.10) and avoidance symptoms (p=0.017) were associated with posttreatment sleep disturbance symptoms. No additional variables met a priori criteria for confounders. Conclusion: Our findings suggest that intensive PTSD programs may improve sleep, although disordered sleep symptoms remain. Posttreatment hyperarousal and sleep symptoms are significantly associated. Further research should investigate whether hyperarousal-directed or sleep-related interventions are associated with further improvement of disordered sleep symptoms after evidence-based treatment for PTSD.

Background: Mixed martial arts (MMA) is a combat sport that can expose fighters to repetitive head injury (RHI). Many professional MMA fighters have previously engaged in other contact sports, such as football, increasing their potential lifetime exposure to RHI. White matter signal abnormalities on MRI, such as T1-hypointensities, have been associated with RHI and can serve as a potential marker of underlying brain injury. Objective: This study aimed to investigate the relationship between T1-hypointensities and football in MMA fighters. Methods: Ninety active, professional MMA fighters from the Professional Fighters Brain Health Study met inclusion criteria for this cross-sectional analysis. Adjusted multivariable linear regression models were utilized to examine the relationship between history of football exposure and total T1-hypointensity volume. Results: A history of playing football and number of years of football played were significantly associated with greater total T1-hypointensity volume. Furthermore, fighters with a history of football were four times as likely to belong in the top 50th percentile and 10 times as likely to belong in the top 25th percentile for total T1-hypointensity volume across all fighters in the sample. Conclusions: A history of football was significantly associated with greater T1-hypointensity volume in professional MMA fighters. MMA fighters who played football may have experienced significantly more RHI and thus, have more markers of neurodegeneration (i.e., T1-hypointensities). Alternatively, though considerably less likely, these differences may have existed at baseline.

Background: Impulsiveness has been linked to greater fight exposure in boxers and mixed martial artists (MMA). Although impulsiveness comorbidity with cocaine use is well-described, cocaine use among professional fighters has yet to be quantified, and the relationship between impulsiveness and cocaine exposure has yet to be studied in athletes. Objectives: This study aims to examine the cross-sectional association between past cocaine use and impulsiveness in professional fighters. We hypothesized that past cocaine use would be associated with higher levels of impulsiveness. Methods: 335 professional fighters (201 boxers, 172 MMA) from the Professional Fighters Brain Health Study (PFBHS) met inclusion criteria. Adjusted multivariable regression analyses were utilized to examine the relationship between cocaine history and impulsiveness (Barratt Impulsiveness Scale Version 11 [BIS-11]) at fighters’ last visit with complete information. Results: 20% of fighters reported using cocaine at least once before. Unadjusted total BIS-11 scores were 66.61 for subjects with cocaine history and 60.55 for subjects without. After demographic adjustment, cocaine history was significantly associated with higher total and subscale (self-control, cognitive complexity, and perseverance) impulsiveness. Conclusions: Cocaine’s prevalence and its significant association with impulsiveness raises questions about the interplay in professional fighters. Given this study’s cross-sectional nature, it is difficult to determine whether fighters with cocaine history experience greater resultant impulsiveness or whether fighters with elevated baseline impulsiveness are predisposed to increased cocaine use. Further studies are warranted to explore the psychosocial and behavioral effects of cocaine use in fighting sports.

Background: Neurobehavioral dysregulation (NBD) is a neuropsychiatric syndrome defined in the NINDS Consensus Diagnostic Criteria as a core clinical feature of Traumatic Encephalopathy Syndrome (TES), the clinical disorder associated with the neurodegenerative disease chronic traumatic encephalopathy (CTE). Objective: To identify distinct profiles of NBD in former American football players. Methods: Data from several standardized neuropsychiatric measures completed by participants in the DIAGNOSE CTE Research Project were used in an expert-informed item-selection process, followed by confirmatory factor analyses, resulting in four NBD subscales representing: explosivity, impulsivity, emotional dyscontrol, and affective lability. A k-means cluster analysis was performed using the four NBD subscales on former professional (N=115) and college (N=59) American football players. Results: Based on statistical and clinical judgement, a four-cluster solution was chosen. One cluster was characterized as asymptomatic (43% of sample) and displayed significantly lower NBD factor scores than the other subgroups. One cluster had elevated explosivity and emotional dyscontrol (20%). Another had elevated affective lability (20%). The final cluster (17%) had high scores on all four NBD subscales. Conclusion: Findings suggest four different profiles of NBD that vary according to levels of explosivity, impulsivity, emotional dyscontrol, and affective lability. Although the construct of NBD appears to be a clinically relevant syndrome within the diagnostic framework of TES, there is variability in symptom profiles. Future directions include the examination of demographics, risk factors, and potential fluid and neuroimaging biomarkers for NBD profiles within TES.

Background: Electroconvulsive therapy (ECT) is a highly effective treatment for major depressive disorder. Optimizing ECT parameters using individual patient characteristics to calculate the induced electric field on the brain (E-Brain) can lead to improvement in depression outcomes. E-Brain values have a known relationship with an increase in hippocampal volume during ECT treatment. Pulse width is not incorporated into E-Brain modeling but may contribute to hippocampal growth during treatment. Objective: Our aim is to describe the contribution of pulse width to hippocampal volume increase during ECT treatment. Methods: 87 participants from two different studies were included in the analysis. Percent hippocampal volume change between visit 1 (prior to first session) and visit 2 (after 6 sessions) was calculated. A linear regression of hippocampal volume change with E-Brain and pulse width was calculated, with age and sex included as covariates. Pulse width was either 0.3 or 1.0 ms. Results: E-Brain was found to significantly contribute to hippocampal volume (beta=0.00028, t=2.85, p=0.005, Cohen’s f2=0.099 [small-medium]). Pulse width was found to contribute nonsignificantly to the model (beta=0.012, t=1.65, p=0.10, Cohen’s f2=0.03 [small]). Conclusion: Our results confirm the significant contribution of E-Brain to hippocampal volume increase during ECT treatment. Our findings suggest pulse width contributes to hippocampal volume increase. While nonsignificant, further investigation is warranted as ECT parameters and hippocampal neuroplasticity are associated clinical outcomes.

Background: Psychiatric medications are frequently used in neuroinflammatory disorders, but little is known about how these affect clinical outcomes. Objective: This retrospective study investigates how treatment with selective serotonin reuptake inhibitors (SSRIs) and antipsychotic medications in neuroinflammatory diseases are associated with differences in hospital length-of-stay (LOS) and mortality. Methods: In collaboration with Atropos Health (www.atroposhealth.com), we retrospectively evaluated all adults in the Stanford Health care system from 2008 to 2022 diagnosed with either encephalitis (defined as “other” encephalitis by ICD codes), multiple sclerosis (MS), or neuromyelitis optica (NMO) and subdivided them into those who did or did not receive SSRI or antipsychotics, followed by measurement of associated length of stay (LOS) and mortality. Results: For individuals with encephalitis (N=193), 47% (N=90) received antipsychotics and had an increased mean LOS (12.69 vs. 21.33 days, p<0.0001). For individuals with MS (N=455), 34% (N=154) of patients were treated with an antipsychotic, which was associated with a significant increase in mean LOS (8.3 vs. 5.2, p<0.00001) and increased mortality (HR 2.04, p=0.02). For individuals with NMO (N=46), 35% (N=16) received antipsychotics, which was associated with an increased mean LOS (16.8 vs. 7.0, p=0.01). Additionally, 18% (N=9) were treated with SSRIs, which was associated with a decreased mean LOS (5.2 vs. 11.4, p=0.02). Conclusion: Treatment with antipsychotics was associated with an increase in LOS in encephalitis, MS, and NMO, but whether this reflects differences between populations or a medication effect remains unclear. SSRI treatment in NMO with decreased mean LOS indicates that these medications may merit further investigation.

Background: In 1974, Waxman and Geschwind recognized that patients affected by temporal lobe epilepsy (TLE) could develop a unique constellation of symptoms characterized by interictal hyperreligiosity or magical experiences, hypergraphia, aberrant sexuality (generally hyposexuality), viscosity or circumstantiality and “intensified mental life,” and was eponymously dubbed Geschwind Syndrome (GS). Case History: Mr. S is a 49 M with complex psychiatric history and no history of epilepsy who presented to a state hospital for capacity restoration on charges of felony stalking. Mr. S has been accruing these charges since the late 1990s. Patient demonstrated persecutory and erotomanic delusions regarding his alleged victim. He engaged in prolific, fastidious writing to his treatment team and various legal bodies. His writing ranged from delusional to reality based and mundane. He had previously self-published a book detailing his unusual religious experiences. Mr. S also noted that he felt that he has had prophetic visions, frequent déjà vu and out of body experiences. An MRI and EEG were obtained to evaluate for the presence of neuroanatomic abnormalities and temporal lobe seizures respectively, and were both unremarkable. Conclusion: Geschwind Syndrome is likely a transdiagnostic phenomenon related to temporal lobe abnormalities. GS has been observed in cases of neurologic malignancy involving the temporal lobe, limbic autoimmune encephalitis, frontotemporal dementia, bipolar disorder and schizoaffective disorder. Despite controversies surrounding the diagnosis, GS is a useful model for broader psychiatric illness for its emphasis of the temporal lobes in subjective experience and behavior and emphasis of a neuroanatomical approach to psychiatric diagnosis.

Background: Pseudobulbar affect (PBA) is a disorder of emotional regulation characterized by involuntary outbursts of crying or laughing in the absence of an emotional trigger (or the presence of a trivial trigger) and is incongruent with the underlying emotional state. It is a distinct neurological condition with varying prevalence reported in various neurological disorders such as amyotrophic lateral sclerosis, stroke, multiple sclerosis, traumatic brain injury, Alzheimer’s dementia, and Parkinson’s disease. Putative pathophysiological mechanisms include dysfunction of cortico-pontine-cerebellar circuits, dysfunction of cerebellar neurons causing impaired affective gatekeeping (affective dysmetria), and serotonergic and glutaminergic neurotransmitter dysregulation. A PubMed and Ovid search for PBA and nfPPA, as well as PBA and PPA, resulted in 0 hits. The case described here is probably the first reported case of PBA in a patient diagnosed with nfPPA. Case History: A 75-year-old white female presented to our neuropsychiatry clinic with a 2–3-year history of effortful, nonfluent speech, grammatical errors, disordered prosody, expressive written language difficulty, pathological crying in the absence of triggers and depressive symptoms, and falls. The workup included a thorough neurological examination, neuropsychological testing, MRI brain, EEG, and PET scan of the brain. We review various data and examination findings. We diagnosed her with nfPPA with PBA and possible corticobasal syndrome. Conclusions: We believe this is the first case report of PBA in nfPPA. Future research regarding the prevalence of PBA in various subtypes of frontotemporal lobar degeneration (FTLD) can further our understanding of the pathophysiological mechanism of this well-known yet poorly understood condition.

Background: Different symptom clusters may respond to different TMS targets connected to distinct circuits, but the symptoms that constitute these clusters remain unclear. Connectivity of brain lesions that modify a symptom can reveal better TMS targets for the same symptom. Objective: To better characterize the symptom clusters that may respond to different TMS targets, we applied a data-driven clustering approach on a large brain lesion data set. Methods: Veterans (N=196) with penetrating brain lesions completed behavioral inventories resulting in 184 neuropsychiatric symptoms and behaviors. The functional connectivity profile of each participant’s lesion location was estimated using a normative connectome database (N=1,000). We then computed whole-brain correlation between lesion connectivity and behavior intensity, yielding “circuit maps” which indicate the connectivity of lesions that modify each behavior. We applied k-means clustering to identify behavioral clusters with similar neural circuitry and tested for significance using permutation testing. Results: We identified two distinct behavioral clusters (p=0.039). Lesions modifying positively valenced traits such as “carefree” and “helpfulness” were connected to a circuit that includes the ventral tegmental area. Lesions modifying negatively valenced symptoms such as “paranoia” and “suspiciousness” were connected to a circuit that includes the dorsolateral prefrontal cortex. Conclusion: Distinct patterns of brain damage can modify distinct symptom clusters, suggesting that the same regions can be stimulated to modify those symptom clusters. Our symptoms grouped into positive and negative affect clusters, each of which mapped to brain circuits commonly associated with those symptom types. Future work may prospectively apply therapeutic brain stimulation to these circuits.

Background: In multiple sclerosis, high rates of neuropsychiatric symptoms heavily impact quality of life. When it is hot and humid, people with multiple sclerosis (PwMS) often report symptomatic worsening. Yet, empirical studies of the connections between the weather and neuropsychiatric symptoms produce mixed results. Objective: This study aimed to determine whether the neuropsychiatric symptoms in PwMS differ by seasons of the year. Methods: Retrospective chart data was extracted for 833 PwMS seen in a neuropsychiatry clinic between 2006 and 2022. Depressive symptoms and anxiety were assessed from Hospital Anxiety and Depression Scale subscales, fatigue from Modified Fatigue Impact Scale, subjective cognitive impairment from Perceived Deficits Questionnaire, and processing speed from Symbol Digit Modalities Test. Through linear regression analyses, these variables were predicted from seasons of the year, adjusting for age, sex, years of education, disease course, and disability. Significant results underwent analyses of variance with post hoc Tukey’s tests. Results: Controlling for confounding variables, seasonality predicted anxiety, F(6,752)=5.28, p = 0.02, R²=0.04. Specifically, anxiety was greater in winter (M=10.08, SD=4.32) compared to summer (M=8.97, SD=4.00), F(3,798)=3.11, p=0.03. Other findings were not significant. Conclusions: Contrary to the hypothesis, PwMS experience greater anxiety in the winter, not the summer. Future studies could explore potential contributors, including fears about injurious accidents in poor weather, reduced recreational activities, or the biological influences of weather changes on anxiety. This finding emphasizes the importance of year-round assessment of anxiety in PwMS.

Background: In people with multiple sclerosis (PwMS), subjective cognitive concerns (SCC) are independently predictive of employment. While SCC can be distressing, findings are mixed regarding the connections between SCC and objective cognitive impairment (OCI). Objective: This study aimed to determine the links between SCC and OCI in MS. Methods: Neuropsychiatry clinic chart data was extracted for 425 PwMS. Participants had completed the Perceived Deficits Questionnaire (PDQ) for SCC, with subscores for attention, retrospective memory, prospective memory, and planning/concentration; and the Minimal Assessment of Cognitive Function in MS (MACFIMS) for OCI. MACFIMS measures include Controlled Oral Association Test (COWAT), Judgment of Line Orientation (JOLO), California Verbal Learning Test Second Edition (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Delis-Kaplan Executive Function Test (D-KEFS). A summative metric of OCI was assessed from the number of tests demonstrating cognitive impairment, quantified as >1.5 SD below the normative mean on each submeasure. Bivariate Pearson correlation analyses were conducted between the PDQ score, the MACFIMS summative metric, and their respective submeasures. Results: SCC was associated with worse COWAT (p<0.01), JOLO (p=0.04), PASAT (p<0.01), and D-KEFS (p=0.03) scores. OCI correlated with perceived retrospective (p=0.02) and prospective (p=0.02) memory deficits. Conclusion: Perceived memory deficits may suggest cognitive dysfunction in MS, and SCC connect to executive functioning and visuospatial processing deficits. For PwMS with memory complaints, these findings emphasize the need to consider neuropsychological assessment.

Background: Biofeedback is a Grade A evidence-based treatment for migraine yet few studies have examined the factors associated with patients’ decisions to pursue biofeedback recommendations. Objective: We sought to examine reasons associated with adherence to referral to biofeedback. Methods: We screened patients with migraine who were referred for biofeedback by a headache specialist/behavioral neurologist. Patients were seen either in-person or by telehealth appointment. We administered baseline questionnaires including demographics, questions about prior headache history, and treatment history. We later followed up with patients to see if they had pursued the recommendation for biofeedback, their reasons for or for not pursuing the recommendation, and their thoughts around the treatment if they had pursued it. Results: Most (68%, or 30/44) patients had been previously referred for behavioral therapy for migraine at prior medical visits, but less than half (44%, 15/34) pursued the recommendation. Of those who had been previously referred for behavioral therapy for headache but did not pursue the recommendation, 65% (11/17) felt that they did not have time and 88% (15/17) endorsed financial obstacles such as treatment cost and/or insurance coverage. About half (47%; 8/17) found it too difficult to schedule an appointment due to limited provider availability. Of the nearly two-thirds (63%; 32/51) of patients who completed their follow-up questionnaire, less than half (40%, 15/32) had contacted biofeedback providers, and only 18% (6/32) were able to participate in biofeedback. Conclusion: Patients with migraine who are recommended for biofeedback face numerous obstacles to pursuing treatment.

Background: The usage and implementation of mobile applications for headache tracking and mind-body treatment of migraine remain ambiguous in the clinical setting. Objective: We sought to understand headache providers’ attitudes and beliefs toward prescribing digital headache diaries and mind-body treatment apps for patients with migraine. Methods: We conducted 20 semistructured interviews with providers across the U.S. from different types of practices to assess the attitudes and beliefs of providers who treat migraine toward prescribing digital headache smartphone apps and/or mind-body treatment apps. Interviews were audio recorded and transcribed. Results: All (20/20) providers asked patients to complete headache diaries, and 95% (19/20) requested that all patients track their headache symptoms in a diary. The vast majority (85%, 17/20) recommended that patients track their headaches using their mobile phones across various means (phone calendar, downloaded app, etc.) and 80% (16/20) recommended apps for mind-body interventions. Just 20% (4/20) of providers reported being unaware of any relevant applications to recommend and just 10% (2/20) had ever recommended a digital program or application for headaches beyond a headache diary. Conclusion: Headache provider interviews provided important information on digital headache diary use and mind-body apps for patients with migraine. Interest in the use of mind-body apps provides key insight into the popularity that mind-body apps specific to migraine might hold in both provider and patient populations.

Background: An increasing number of jurisdictions have adopted or decriminalized The Practice of Medical Assistance in Dying (MAiD). MAiD legislations regulate this practice for people with irremediable medical conditions. Malignancies and progressive neurological conditions are the most common examples, but figures from some Jurisdictions also include people with psychiatric illnesses. Functional Neurological Disorder (FND) continues to be classified as a psychiatric disorder. Objectives: To review published data on MAiD as relevant to FND. Methods: We systematically reviewed the literature on MAiD legislation worldwide concerning psychiatric conditions and searched for reports of MAiD applications made by patients with FND. Results: Some jurisdictions, including Belgium, Holland, and Luxemburg, grant some patients with psychiatric illnesses the choice to apply for MAiD; Canada is progressing toward the same. Research is limited, but the number of approved applications in psychiatric illness is low, including a small number of patients with concurrent FND and Structural Neurological Disorders. In addition, at least one patient with the sole diagnosis of a Functional Neurological Disorder was granted medical aid in dying in Canada. Conclusions: There is a pressing need for research into the triage and treatability of FND, especially as more jurisdictions allow patients with psychiatric illnesses to apply for MAiD. There is a risk that treatable patients with FND may attract assessments of irremediability, especially in the absence of treatment services for this patient population. In addition, there is a need for more specialist services for people with FND in communities that legalize medical aid in dying.

Background: Functional Neurological Disorder (FND) can occur following head trauma. The New model of FND emphasizes the role of sensitizing events, including different forms of physical trauma and illnesses, in the etiology of this condition. Objective: The study examined the outcome of the somatic scale and subscales of the Personality Assessment Inventory (PAI) in patients with FND following a mild head injury against control samples of 1) patients without head injury and 2) patients with a confirmed diagnosis of other Structural Neurological Disorders associated with FND. Methods: Thirty-four subjects were included in this study. They were a group of consecutively referred patients with FND who continued to receive follow-up through a specialist FND service 5 years into their presentation. Their diagnosis with FND remained a stable primary diagnosis. Patients’ Personality Assessment Inventory scores were analyzed, focusing on the somatic scale and subscales. Results: On analysis of variance, there was a statistically significant difference between the three groups on the somatic scale and subscales. Following up with post hoc testing, there was a statistically significant difference on the conversion subscale between the groups with and without head trauma, with a mean Conversion T Score of 66 in the former and 84 in the latter (p=0.012), denoting less severe conversion processes post head trauma, but an equally severe somatization and illness anxiety pathologies. Conclusions: Patients with posthead injury FND may have some variations in their psychopathological and symptomatologic presentations. Their treatment may need to be tailored to the specific areas of their psychopathology.

Background: It has been hypothesized that there is a decrease in externally directed attention in patients with FND, with associated distraction and slowed cognitive processing. Patients with FND also show enhanced implicit processing of salient emotional stimuli. Objective: The study examined variations in Reaction Time on exposure to positive emotions, negative emotions, and emotionally neutral cognitive stimuli. Methods: Forty-one consecutively referred patients with FND were included. Patients underwent neuropsychological evaluation with computer-based Stroop Test (ST) and Perception of Emotions Test (POET). Patients with low validity subscores were excluded (N=8). Simple Reaction Time for emotionally neutral cognitive stimuli was obtained from the Stroop Test. Reaction Time to emotional stimuli was obtained from the Perception of Emotions Test. Results: Patients had low Reaction Time scores overall (long Reaction Time), but scores were significantly lower when presented with emotionally neutral cognitive stimuli (mean 18th Percentile) than when presented with emotional stimuli (mean 26th Percentile). Patients’ highest mean Reaction Time scores were in their response to negative emotional stimuli (mean 32nd Percentile). The difference was statistically significant (p<0.001). Additionally, there was a positive correlation between patients’ Reaction Time to positive and negative emotional stimuli, r=0.652, 95% CI [0.39, 0.80], but no significant correlation with emotionally neutral cognitive stimuli. Conclusion: Reaction Time to negative emotional stimuli is significantly shorter in patients with FND than Reaction Time to emotionally neutral stimuli. The difference may contribute to the initiation of primary affective responses, which, in turn, can contribute to the pathogenesis of FND symptoms.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is an increasingly common phenomenon in adolescents. Pre-syncopal episodes or fainting spells may occur in the context of stress or anxiety, overwhelming sensory stimuli, dehydration, or chronic pain. Psychogenic Nonepileptic Seizures (PNES) have similar antecedents, but involve convulsive motor movements that appear like electrical seizures yet do not have epileptiform findings on an electroencephalogram (EEG). Both conditions are commonly seen by pediatric neuropsychiatrists for assessment. Recently, the two conditions have been seen to overlap and necessitate a unified treatment approach in order to address both conditions simultaneously. Case History: A 17-year-old female reported episodes of dizziness that led to tunnel vision and fainting and/or dissociation for several seconds. Despite improvement with midodrine treatment, the episodes persisted and progressed into full-body convulsive episodes which lasted 1–2 minutes, and necessitated emergency medical services. POTS episodes seemed to precede flurries of PNES episodes for several months. EEG and Holter were negative. A tilt table test was strongly positive for POTS. Treatment with fluoxetine was partially effective for anxiety. Treatment with guanfacine led to a marked improvement in POTS episodes as well as PNES episodes. Conclusions: This case suggests the pathophysiologic overlap of two seemingly disparate conditions, POTS and PNES in the context of anxiety. The similarity of the precursors to both events suggests that a pathologic autonomic regulatory process or dysautonomia may underpin both conditions. To our knowledge, the overlap has not been reported in the literature and represents a potentially new neuropsychiatric paradigm of disease.

Background: Since the COVID-19 pandemic, there have been an influx of patients suffering from new onset neuropsychiatric symptoms including psychosis, mania, cognitive impairment, depression, and anxiety. The ages of these patients along with the duration and severity of illness vary greatly. A review of the literature yields very little data on long term patient outcomes. Case History: A 28-year-old female without past psychiatric diagnoses was admitted for first manic episode with psychosis, within two weeks after COVID-19 infection with high fevers. She presented with labile mood, pressured speech, grandiose delusions, hyperreligiosity, decreased need for sleep. She was hospitalized for >2 months and was disorganized, intrusive with staff and patients, endorsed auditory and visual hallucinations, delusions, and somatic complaints. She underwent multiple neuroleptic trials and full work-up for first break psychosis including brain imaging, serum and CSF studies including autoimmune panel, all without remarkable findings. Psychotic and manic symptoms eventually improved with clozapine and depakote, and she was discharged to the outpatient setting. After completion of an IOP and 1 year of outpatient psychiatric follow-up, she has tapered off all psychiatric medications, restarted work and continues to care for her family. She has not had a recurrence of mania or psychosis. Conclusion: This case highlights the impact of potential neuropsychiatric sequalae following COVID-19 infection. It is imperative that we follow these patients longitudinally so that we are better able to track outcomes and guide treatment practices. Future studies should examine whether there are recurrent bouts of neuropsychiatric symptoms after symptom resolution.

Background: In severe traumatic brain injury (TBI), recovery involves emergence from posttraumatic amnesia (PTA) and subsequent rehabilitation. Roughly 70% of TBI patients experience agitation during hospitalization. Although antipsychotics are frequently used to treat agitation, they are approached cautiously in TBI patients. Current literature suggests negative cognitive effects with prolongation of PTA phase of recovery in TBI populations. We review the clinical domains of agitation and explore challenges of optimizing TBI rehabilitation in the setting of agitation. Case History: A 25-year-old male without established psychiatric history was found at roadside wrapped in barbed wire with signs of blunt trauma and penetrating ballistic wounds. Initial imaging demonstrated complex facial fractures, a 4-mm parafalcine subdural hematoma, and scattered subarachnoid hemorrhage within bilateral frontal lobes. During hospitalization, the patient developed significant aggression. The patient’s clinical course included PTA, hyperactive delirium, and establishment of a new behavioral baseline from a bilateral frontal lobe brain injury. Psychiatry was involved with each recovery stage with various trials of medication classes in attempts to avoid high potency antidopaminergic agents. Ultimately the only adequate agitation management that allowed for discharge and transfer to a rehabilitation hospital involved the use of Haloperidol in combination with Olanzapine and Valproic Acid. Conclusion: It is difficult to navigate situations in which a patient experiences PTA but later suffers from hyperactive delirium. Establishing the driving factor of acute agitation is essential to determine the best treatment course. Based on our review of the existing literature, these intricate clinical settings require further research and inquiry.

Background: Pediatric neurodegenerative disorders (PNDs) are rare, profound illnesses occurring at rates of 6.43 per 100,000 person years. Patients often suffer severe neurobehavioral symptoms including aggression, self-injury, and psychosis, in addition to sensory, motor and neurocognitive symptoms. Batten disease (juvenile neuronal ceroid lipofuscinosis type 3, CLN3 disease) is an example of a neurometabolic PND. No one specialty is well equipped to manage the combined medical, palliative, behavioral and psychosocial needs of these patients and their families. Even neuropsychiatry and palliative care, already integrative fields, do not provide training that fully encompasses the necessary treatment skill sets. We use a series of two cases to justify the need for extended integration of care in CLN3 disease and other PNDs. Case Histories: Both patients have pathogenic variants in the CLN3 gene. One is 9 years-old, the other is 19. The former has marked visual impairment, severe irritability, aggression and dangerous impulsivity. The latter has blindness, fine and gross motor impairments, pseudobulbar affect, Parkinsonism and epilepsy controlled on levetiracetam. Challenges to care include complex neuropsychiatric symptoms, polypharmacy, iatrogenic effects complicating disease progression and evidence basis limitations. Approaches to integrated management are discussed, including early involvement of both specialties (palliative care and neuropsychiatry), regular multidisciplinary coordination conferences, psychoeducation/supervision of nonmedical providers, and behavioral therapy approaches. Conclusion: We wish to draw attention to the need for integration of palliative care and neuropsychiatry into the multidisciplinary care of children with PNDs, which will require ongoing, dynamic management of behaviors and psychiatric symptoms as illnesses evolve.

Background: Syphilis has multiple presentations and is aptly called the “great imitator.” The most severe sequela of untreated syphilis is neurosyphilis. Here, we focus on neurosyphilis masquerading as an organic psychiatric illness. Case History: The patient is a 42-year-old male with no relevant history when he first experienced a decreased need for sleep, excessive speech, paranoia, disorganization, and bizarre behavior. He was psychiatrically hospitalized, diagnosed with bipolar I disorder, and discharged on valproate and risperidone. He continued to gradually decline neurobehaviorally over the next 2 years. His family noticed declining cognition and increasing paranoia. He could no longer take care of his own activities of daily living and began experiencing speech difficulties and unsteady gait. He saw a neurologist for his worsening symptoms who ordered a rapid plasma reagin and treponemal antibody tests. These were both reactive. His cerebrospinal fluid also tested positive for GAD65 Ab, confirming the diagnoses of syphilis and encephalitis. The patient was hospitalized and underwent a course of penicillin G. While hospitalized, he began to exhibit catatonia, hallucinations, and compulsive behavior. He was started on lorazepam and received electroconvulsive therapy for catatonia. At the present time, his prognosis remains guarded due to the duration of untreated syphilis. Conclusion: Although the patient presented with symptoms in 2019, he was not evaluated for syphilis until his symptoms significantly worsened in 2022. Earlier treatment may have led to a more favorable prognosis. Neurosyphilis should be on clinicians’ differentials when they encounter young patients with new onset neuropsychiatric symptoms.

Background: Abnormal eating behaviors, such as hyperphagia and increased carbohydrate consumption, contribute to the core clinical criteria of behavioral variant frontotemporal dementia (bvFTD). We present a case of genetic bvFTD with perseverative and compulsive water intake as the primary manifestation of food preference changes and hyperorality. Case History: The patient is a white male in his early 50s with a history of hereditary hemochromatosis referred to the Behavioral Neurology & Neuropsychiatry service for manic symptoms beginning in his 40s, new grandiose delusions, and disorientation manifesting in his 50s. Repeated water drinking from sources such the toilet and shower resulted in disruptive and frequent urination and caregiver distress. The patient also developed malignant catatonia responsive to electroconvulsive therapy; water drinking resumed after resolution of the catatonia, resulting in medical hospitalization for hyponatremia. Iron and ferritin remained normal, or even low, during the course of his polydipsia. Polymerase chain reaction based Chromosome 9 Open Reading Frame 72 (C9ORF72) repeat expansion analysis identified >44 and two repeats. Conclusion: This case contributes to the scant literature on primary polydipsia as a manifestation of bvFTD. Potential mechanisms in relation to the patient’s presentation, comorbidities, and neuroimaging are discussed.

Background: Behavioral neurology and neuropsychiatry (BNNP) fellowship programs have asynchronous application timelines. Objective: Evaluate impressions of program directors (PDs) and fellows regarding the BNNP fellowship application timelines. Methods: A one-time REDCap survey was distributed to all UCNS-accredited BNNP fellowship PDs. PDs were asked to forward the survey to current and incoming fellows. Results: Surveys were completed by 22 PDs (50% response rate) and 17 fellows. Regarding the application process, most programs reported rolling admissions. We noted a span of 17 months between the first application opening (August PGY-3) and the last position offering (January PGY-4), with interviews in the interim. 86.3% of PDs agreed (4 or 5/5 on a Likert scale) that the different application timelines can negatively impact their ability to recruit applicants and 95.5% would be open to having an agreed upon date before which no offers would be made. Only 41.1% of fellows reported that different timelines prevented them from completing interviews for all their desired programs, but 82.4% agreed that the different timelines negatively impacted the ability of programs to recruit applicants; 88.3% supported a unified timeline. 50%–60% of fellows reported anxiety or stress in trying to maintain fellowship offers open while completing all interviews. PDs emphasized the importance of considering the typical fellowship application timelines for both neurology and psychiatry residencies. Conclusion: Most fellows and PDs for BNNP fellowships strongly support creating a unified fellowship application timeline. In light of this widespread agreement, further steps toward the adoption of a common timeline should be considered.

Background: Posterior reversible encephalopathy syndrome (PRES) is characterized by headache, altered mental status, seizures, or loss of vision. It is associated with symmetric hyperintensities on magnetic resonance imaging due to vasogenic edema located in the occipital and parietal regions of the brain. Various comorbidities and drugs have been suggested as triggering factors. PRES has been attributed to uncontrolled hypertension in nearly 75% of patients and strongly correlates with chronic alcoholism and withdrawal. In this case, we discuss a 60-year-old man with a history of bipolar disorder and alcohol use disorder who developed PRES in the context of an acute hypertensive crisis. Case History: A 60-year-old male with a past psychiatric history of bipolar disorder and alcohol use disorder and past medical history of chronic kidney injury, chronic obstructive pulmonary disease (COPD), essential hypertension, peripheral artery disease, hyperlipidemia, vitamin D deficiency, and hypothyroidism was admitted to the emergency room for nausea, vomiting, and generalized weakness. His Magnetic Resonance Imaging findings revealed bilateral cerebellar infarcts suggesting PRES syndrome. He was shifted to the intensive care unit for close control of his blood pressure and required intubation for a period related to alcohol withdrawal. Prompt treatment for hypertensive crisis and alcohol withdrawal was started, and the patient improved. Conclusion: Evidence suggests that chronic alcoholism increases the chance of developing PRES in the context of a hypertensive crisis. Identifying the potential causes and timely management helps ameliorate the symptoms of PRES.

Background: Approximately 4% of the population will experience mania in their lifetimes. Bipolar disorder or schizoaffective disorder are the most common etiologies; however, mania can occur secondary to a neurological process such as stroke, neoplasm, autoimmune disease, or infection. Many areas have been implicated by functional connectivity studies in the pathophysiology of mania including prefrontal cortex, amygdala, anterior cingulate cortex, and basal ganglia. Here we present a case of new-onset mania after a right precentral gyrus infarction thought to be secondary to COVID. Case History: A 60-year-old African American female with a history of anxiety and two lifetime episodes of depression, GERD, chronic pain and cervical radiculopathy presented with mania with psychotic features, including grandiosity, pressured speech, flight of ideas and delusions. She did not have a history of bipolar disorder and the time frame corresponds with COVID and infarction, supporting a diagnosis of secondary mania from infection or infarction. She was treated with Depakote and Olanzapine with minimal improvement in symptoms. We review the clinical and diagnostic features to suggest secondary mania. Conclusion: This case illustrates the importance of awareness of secondary causes of mania. Additionally, it illustrates that multiple etiologies may contribute to the first episode of mania in a patient that is atypical for primary psychiatric illness, including lesions and infection. These etiologies may be spurious or causal and warrant further investigation, as they may shed light on the underlying neuropsychiatry of mania.

Background: During the past 2.5 years, it became noticeable that most communications on long-COVID originated from countries in the Northern hemisphere, particularly from North America and Europe. Objective: To systematically review the literature and study whether Long-COVID is a global concept and whether its symptomatology was prevalent similarly worldwide. Methods: Our search strategy included (“post-COVID” OR “long COVID” OR “long-haul COVID” OR “long hauler syndrome” OR “post-acute COVID” OR “postacute sequelae of SARS CoV-2 infection” OR “PASC” OR “long-term effects of COVID” OR “chronic COVID” OR “postacute covid syndrome” OR “PACS” AND (“COVID” OR “coronavirus”) AND (region of origin/countries) in the following divisions 1. North America 2. South and Central America 3. Europe. 4a. Asia EXCEPT China, Japan and India and other countries in Southeast Asia. 4b. China, Japan and India and Southeast Asia. 5. Africa and Australia. Results: North America N=2,225 down to N=112, South and Central America N=167 to N=7, Asia a. N=50 to N=28, Asia b. N=475 to N=38, Europe N=316 to N=80, Africa, and Australia N=119 to N=13. Google search terms yielded thousands of articles for North America N=13,470 (US only 8,790), China N=11,600, India N=13,000 and Europe N=3,000 compared to the rest of the globe. Most common symptoms were shortness of breath, chronic fatigue, headache, anxiety, depression, and sleep disorders. Conclusion: The global awareness on long-COVID is not translating into similar prevalence and incidence estimates at country and regional levels. Is it time we look at cultural impact on illness behavior and societal symptomatology in addition to clinical ones?

Background: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated neurological disorder of the central nervous system. It is most commonly seen postinfection. This is possibly the first reported case of recreational drug-induced ADEM, specifically after using methylenedioxy-methamphetamine (MDMA) more commonly known as ecstasy. Although the presentation of ADEM is usually with fever, headaches, confusion or seizures, in this case the presenting symptom was new-onset psychosis. Case History: A 36-year-old male presented with 1 week of fever and psychosis. He was very agitated and violent, requiring the use of restraints. This complicated the workup resulting in delays to safely obtain blood work, lumbar puncture and imaging. Due to suspected infection, he was initially started on broad spectrum antibiotics. Sedation was needed to eventually obtain the lumbar puncture and MRI brain. CSF analysis was unremarkable, but MRI brain showed numerous enhancing lesions in a distribution suggestive of acute disseminated encephalitis. He was given high-dose IV steroids and intravenous immunoglobulin (IVIg) for 5 days which resulted in significant improvement of his symptoms. He was safely discharged home. Conclusion: This case illustrated the importance of having a wide differential with new-onset psychosis. There can be difficulties and delays to obtain imaging with uncooperative patients. This case emphasizes the importance of imaging, even if sedation is required. There is a need for more data collection regarding drug-induced ADEM to better understand if there is a causal relationship.

Background: During the COVID-19 pandemic, pediatric neurologists and psychiatrists saw a surge among adolescents presenting with sudden onset tic-like behaviors. The swell in cases included new onset tic disorders, functional tic disorders, and exacerbation of pre-existing disorders such as Tourette Syndrome. This well documented increase has been linked to increased anxiety and depression among adolescents during the pandemic, highlighting the association between affective states and tic behaviors. Heightened social media use further contributed; during the pandemic, tic-related videos received over 5.8 billion views by 2021, correlating with the abrupt increase in cases and highlighting the effects of social influence on both nonaffective (“organic”) tics and functional tics. Case History: Despite physicians’ attempts to distinguish between these conditions, misdiagnoses are frequent. Here we compare 3 cases of 16-year-old females to highlight similarities and differences between tic- and functional tic disorders. We discuss variations in treatment including pharmacology and therapy modalities, as well as the neurocircuitry of tics, specifically the role of dopamine in the thalamo-cortical circuits, the HPA axis, and limbic circuits which are activated during tics and may explain the relationship between affective states and tic behaviors. Finally, we provide preliminary data on a cohort of approximately 50 functional tic patients seen by neurology and psychiatry at our pediatric hospital from 2020 to 2022. Conclusion: These cases highlight the overlapping yet distinct phenomenology of tic versus functional tic disorders and the impact of affective states on tic behaviors, which lies at the intersection of neurology and psychiatry.

Background: Behavioral symptoms, including apathy, are seen with dysexecutive and behavioral subtypes of early onset Alzheimer’s disease (EOAD). In the former, symptoms appear alongside atrophy in the frontal>parietal regions with relative sparing of temporal lobes. Similarly, temporal>parietal atrophy with variable involvement of the frontal lobe is observed in the behavioral subtype. In contrast, behavioral symptoms are infrequent with isolated parietal atrophy, where acalculia, visuospatial deficits and elements of Gerstmann and Balint syndromes are observed. We present a case which challenges these phenotypic boundaries and presents with behavioral changes, dyscalculia and executive function deficits amid parietal atrophy. Case History: A 53-year-old college educated female with no past psychiatric history reported difficulty managing business finances and forgetfulness with her work schedule. Subsequent course involved progressive decline in function and emergence of apathy, anxiety and agitation. Magnetic resonance imaging revealed marked biparietal atrophy with sparing of frontal, occipital and temporal lobes including hippocampi. Analysis of cerebrospinal fluid revealed reduced Aβ42 and elevated T-tau, with a ratio consistent with Alzheimer’s disease. With this context, we review the impact of parietal atrophy toward behavioral symptoms and the implications for diagnostic workup in early onset disease. Conclusion: Behavioral symptoms including apathy may be at the forefront in a subset of patients with EOAD and atrophy limited to the parietal lobes. This can lead to diagnostic overlap with other known clinical phenotypes of EOAD or even behavioral variant frontotemporal dementia. There is opportunity to better characterize this subgroup of patients and the heterogeneity of EOAD.

Background: Acute encephalitis is suspected in patients with altered mental status, acute-onset memory impairments, and behavioral changes. However, a negative infectious, autoimmune, and paraneoplastic workup creates a diagnostic challenge, and the literature exploring this mysterious phenomenon is scant. Case History: A 38-year-old woman with 4 days of worsening mental status presented after being found taking a shower while fully clothed. She had stable vital signs and no neurologic deficits but was oriented only to self. Initial workup including blood counts, electrolytes, liver function, and head CT were negative. She was admitted for further evaluation, where she required constant monitoring due to her significant confusion and bizarre behavior. MRI demonstrated bilateral punctuate infarcts, bilateral periventricular and deep cerebral white matter lesions. Cerebrospinal fluid (CSF) studies revealed an elevated protein level of 105 mg/dL (N 12–60 mg/dl). Continuous EEG monitoring showed occasional bifrontal lateralized rhythmic delta activity and a mild degree of generalized slowing background activity. A 5-day course of IV methylprednisolone was initiated on hospital day 13 with a marked improvement in mental status by hospital day 17. CSF antibody panel was found to be negative after discharge. Conclusion: This case demonstrates the importance of considering seronegative autoimmune encephalitis as part of a differential diagnosis when evaluating acute encephalitis of unclear etiology. Appropriate treatment should be initiated immediately for optimal patient recovery, without waiting for pending serologies. More research is needed to identify causes of seronegative autoimmune encephalitis, and increased clinician awareness is needed to ensure rapid diagnosis and treatment.

Background: High-inflammation subgroups of psychosis show cognitive deficits and structural alterations. Systemic inflammation alters functional connectivity between and within resting state networks, but effects on cognition remain unstudied. Objective: We aim to determine the association of inflammation subgroups on functional networks and cognition in psychosis. Methods: Serum and resting state-fMRI were collected from psychosis probands and controls from the BSNIP1 (Chicago site) study that were stratified into inflammatory subgroups based on factor and cluster analyses of 15 cytokines (Proband-Low N=65, Proband-High N=29, HC-Low N=32). Nine ICA-derived resting state networks were used to create functional connectivity and multilayer networks, while controlling for motion and SNR. Inter-network connectivity was measured using Fisher z-transformation of loading coefficients. Cognition was assessed using BACS. Linear regressions, Spearman correlations, and clustering coefficients were used for analyses. Results: The anterior default mode network (DMNa) activity was significantly reduced in the Proband-High group compared to Proband-Low (Cohen’s d=−0.74, p=0.002) and HC-Low group (d=−0.85, p=0.0008). The inter-network connectivity between the DMNa and the right-frontoparietal networks was decreased in Proband-High compared to Proband-Low (d=−0.66, p=0.004). Proband-High had decreased negative network clustering coefficient compared to Proband-Low. Decreased anterior default mode network activity was associated with decreased verbal fluency scores in Proband-High. Decreased negative clustering coefficient was associated with decreased verbal memory in Proband-High. Conclusion: Our findings extend support for systemic inflammation as a contributing factor to network dysfunction in psychosis. Furthermore, we used novel multilayer measures that examine positive and negative connections, and found that more diffuse clustering in negative connections are associated with poorer cognitive performance in high-inflammation subgroups.

Background: Forced normalization (FN) is a phenomenon characterized by the emergence of psychiatric symptoms following seizure control or reduction in patients with epilepsy. A range of psychiatric symptoms including psychosis, mood disturbance, anxiety, depersonalization, derealization, motor or sensory dissociation, and abasia may be present in FN. We describe a case of catatonia, postulated to be as part of FN, in a young adult male with Dravet Syndrome whose previously complicated epilepsy improved with antiseizure medication. Case History: An 18-year-old male with Dravet’s Syndrome and SCN1A mutation with epilepsy presented with bizarre body movements, impaired cognition and abnormal speech. History and physical examination were significant for negativism, alternating excitement with stupor, mutism, staring, automatic obedience, ambitendency, catalepsy, verbigeration, impulsivity and perseveration, consistent with a diagnosis of catatonia. Zonisamide was added to a regimen of cannabidiol, clobazam, fenfluramine, levetiracetam and perampanel, and within days, his seizures had become well controlled. However, onset of catatonia symptoms occurred approximately 2 weeks after initiation of zonisamide. Ultimately, his catatonia severity improved with oral lorazepam, with a return of speech close to baseline, less frequent catalepsy and improved excitement as well as stupor. Conclusions: There is minimal literature on the subject of catatonia as a FN manifestation, in a 14-year-old girl with Dravet Syndrome. Our case adds to the literature, as this is the first case of catatonia in the setting of FN that improved with oral benzodiazepine that we are aware of.

Background: Crime exacts a major burden upon society, and new imaging techniques have begun to shed light on neuroanatomical structures associated with criminality. Lesion studies have suggested a number of cerebral and subcortical structures which are most commonly injured in acquired criminality, but the white matter structures implicated are less certain. Objective: To determine the white matter tracts disrupted by well-characterized brain lesions that are associated with acquired criminality. Methods: We included all subjects from a previously performed literature review of acquired criminality which have 1) a case description of criminal behavior, 2) an acquired focal brain lesion and 3) a published lesion image suitable for mapping. A data set of stroke lesions from patients without reported acquired criminality served as controls. Structural disconnection maps were derived for cases of acquired criminality and controls by calculating lesion overlap with a normalized diffusion tensor imaging connectome. Then, a voxelwise two sample t test was performed comparing the structural disconnection maps of acquired criminality versus controls. Results: Multiple white matter disconnections (threshold-free cluster enhancement p<0.01) were associated with acquired criminality (N=40) compared to controls (N=135), including tracts within the prefrontal regions as well as the right uncinate fasciculus and bilateral cingula. Conclusion: White matter tracts disrupted by brain lesions associated with acquired criminality include prefrontal tracts as well as the right uncinate fasciculus (implicated in emotional empathy) and the cingula (implicated in theory of mind).

Isaiah Kletenik, Kyla Gaudet, Michael P. Stanley, Sashank Prasad, Michael D. Fox

Background: Visual anosognosia (also called Anton syndrome or anosognosia for visual loss) is a condition where patients suffer a brain injury that causes vision loss with unawareness of blindness. Due to the rarity of the syndrome, there is limited formal analysis of its neuroanatomical localization. Objective: To determine the neural correlates of lack of awareness of cerebral vision loss in visual anosognosia. Methods: We performed a systematic literature review and included cases where brain injury was associated with: 1) complete vision loss, 2) lack of awareness of vision loss, 3) a bilateral lesion, and 4) a published image of sufficient quality for mapping. Lesions were mapped into standard space and resting-state functional connectivity between each lesion location and all other brain voxels was computed from a large, functional connectome (N=1,000) to produce single-subject connectivity maps. These maps were thresholded at T>10 and assessed for >95% overlap of positive voxels to determine lesion connectivity patterns associated with visual anosognosia. Results: Our systematic literature review identified 24 unique cases of visual anosognosia (mean age 58.7, 16 male). Seventeen cases described visual confabulation. Analysis of functional connectivity maps revealed 100% overlap in the parahippocampus, hippocampus, posterior cingulate and precuneus. Conclusion: Lesions associated with visual anosognosia are functionally connected to a network involved in visual scene construction (parahippocampus), memory (hippocampus) and metacognition (posterior cingulate/precuneus). These data fit a cognitive-awareness model of anosognosia where sensory processing, comparison to prior experience, metacognitive perspective-taking and updating of autobiographical memory are necessary factors for awareness of deficits.

Background: Beta-Propeller Protein-Associated Neurodegeneration (BPAN) is a genetic disorder in the Neurodegeneration with Brain Iron Accumulation (NBIA) family causing developmental delay, seizure, and motor abnormalities. Patients with this disease can have iron deposition in the basal ganglia causing motor symptoms including spasticity, dystonia, and parkinsonism. In patients with this illness who require treatment with dopamine agonist medications, little is known about how dysregulated dopamine in the basal ganglia may cause an increased risk of neuropsychiatric side effects. We report a patient with BPAN and a pituitary prolactinoma who developed cabergoline and bromocriptine induced neuropsychiatric side effects. Case History: A 37-year-old female with a history of intellectual disability, epilepsy, spasticity, anxiety, and a pituitary adenoma recently underwent whole genome exome sequencing revealing a pathologic mutation in the WDR45 gene consistent with BPAN. There was progression of a pituitary microadenoma causing hyperprolactinemia warranting treatment with dopamine agonist medications. Upon initiation of cabergoline, the patient developed disrupted sleep, irritability, and hallucinations that ultimately subsided with discontinuation. Similar side effects occurred with bromocriptine, ultimately justifying surgical resection of the pituitary adenoma. Conclusion: This novel case describes a patient with BPAN and a pituitary prolactinoma who developed cabergoline and bromocriptine induced psychosis. Dysregulated dopamine transmission seen in BPAN may predispose patients to adverse neuropsychiatric side effects of dopamine agonist medications. Further research is needed to better characterize this relationship which may help guide management.

Background: Hashimoto encephalitis or steroid-responsive encephalopathy associated with thyroid disease (SREAT) is an immune-mediated condition with greater prevalence in females. It typically presents with nonspecific neurological symptoms such as AMS, tremors, myoclonus, seizures, ataxia, and rarely with psychosis and stroke-like symptoms. The exact mechanism of SREAT is unknown but it is thought to be caused by an autoimmune vasculitic disease process associated with lymphocytic infiltration causing disruption of cerebral microvasculature. Diagnosis requires elevated TPOAb or TgAb with clinical features of encephalopathy but there is no direct association between Hashimoto thyroiditis and encephalitis. The disease process is usually responsive to glucocorticoid or immunosuppressive therapies. Case History: A 29-year-old female presented with a 3-day history of insomnia, auditory and visual hallucinations, bizarre behavior, and seizures following a febrile illness. Diagnostic workup revealed elevated titers of TgAb, GAD65, and ASO with transaminitis. MRI showed nonspecific changes within the fourth ventricle, while EEG and CSF analysis were noncontributory. IV steroid therapy produced symptomatic improvement and the patient was diagnosed with SREAT. The patient was discharged with a 9-day oral prednisone taper and close follow-up. Conclusion: This case highlights the need for rigorous evaluation of potential causes for encephalopathy, including autoimmune thyroid disease. It is important to check for antibody levels even in patients with a normal thyroid panel and previously undiagnosed thyroid disease when they present with encephalopathy unexplained by other etiologies. Most patients experience complete recovery of neurological function with steroid therapy. However, some patients might experience residual symptoms and relapse even after treatment.

Background: Depression and anxiety are significant problems that reduce quality of life among older adults. Physical activity has numerous psychological and physiological benefits, but it remains unclear whether physical activity decreases incident neuropsychiatric symptoms in old age. Objective: To examine the association between physical activity in midlife and late life with the risk of incident depression and anxiety in older adults. Methods: Longitudinal analysis of the population-based Mayo Clinic Study of Aging, including individuals aged ≥70 years and free of dementia. Physical activity in midlife (50–65 years of age) and late life (1 year prior to baseline) was assessed using a validated self-reported questionnaire. The incidence of clinical depression and anxiety was assessed using Beck Depression (score ≥13) and Anxiety (score ≥10) Inventories. We calculated Cox Proportional Hazard models, adjusted for age (time scale), sex, education, APOEɛ4, and medical comorbidities. Results: 2449 adults (48% women, mean [SD] age 79.0 [5.5] years) were followed for a median of 5.4 years. Higher physical activity in late life was associated with a lower risk of incident clinical depression (HR 0.96; 95% CI 0.92, 0.99; p=0.01) and clinical anxiety (HR 0.95; 95% CI 0.92, 0.98; p<0.01). Midlife physical activity was not associated with the risk of incident clinical depression or anxiety. Conclusion: This prospective cohort study shows that engaging in late-life physical activity may reduce the risk of new-onset clinical depression and anxiety among older adults free of dementia.

Background: There is limited data on the management of neuropsychiatric symptoms in patients with comorbid Parkinson’s Disease (PD) and congenital cardiac disease. We present a unique patient presentation in which a patient with PD whose co-occurring Tetralogy of Fallot had implications for the treatment of her neuropsychiatric symptoms. Case History: We present a 62-year-old female with a history of Tetralogy of Fallot which was surgically corrected as a child. She experienced subsequent arrhythmias, right bundle branch block (RBBB), and prolonged QT corrected for heart rate (QTc). She was diagnosed with Parkinson’s Disease, and motor symptoms stabilized with carbidopa and levodopa. Severe PD-related visual hallucinations and paranoia were initially treated with pimavanserin. While beneficial, this created concern for QTc prolongation and arrhythmias. Cross-titration to aripiprazole was attempted to decrease QTc. Psychosis substantially worsened and QTc remained prolonged. In collaboration with cardiology, it was determined she was not at risk of arrhythmia as long as her QTc remained under 550 ms. Pimavanserin was returned to an optimized dose; aripiprazole was continued for additional treatment of her psychosis as well for the potential to reduce QTc. Conclusion: This case helps to demonstrate the complexities of treating patients with Parkinson’s alongside congenital cardiac pathology. In such patients, collaboration with other members of the patient’s care team is invaluable. We also discuss the importance of weighing the benefits versus the risks to help improve the quality of life in degenerative illnesses.

Background: Tourette syndrome (TS) can have longstanding psychological effects. Self-injurious tics can lead to physical pain and permanent damage. Current guidelines recommend comprehensive behavioral intervention (CBIT) and pharmacologic treatment. One randomized control trial (RCT) compared CBIT to psychoeducation. However, no RCTs have compared CBIT and medication with medication alone. Furthermore, there is a paucity of literature regarding occupational and speech therapy treatment in TS. This case highlights the novel approach of multidisciplinary interventions and care coordination to improve harmful tics. Case History: A 26-year-old male with history of TS, OCD, and past substance use presented with vocal and complex motor tics (tongue biting) which failed medications and jaw wiring, ultimately resulting in tongue amputation and palliative tooth extraction. YGTSS score was 98. Tic medication trials included alpha-2 agonists, antipsychotics, VMAT-2 inhibitors, and topiramate. Psychiatric treatment trials included benzodiazepines, ketamine, SSRIs, tricyclics, and electroconvulsive therapy. The patient was not a candidate for deep brain stimulation. Botulinum toxin injections and transcranial magnetic stimulation were also discussed. During 13 weeks of CBIT with occupational and speech therapy, the patient’s motor tics improved from about 5 tics/hour to <3 tics/week and he reported improvement in quality of life, thus demonstrating the need for coordinating early multidisciplinary interventions. Conclusion: This case highlights the importance of a collaborative approach to treating complex TS. CBIT may still be efficacious even in severe cases of TS, along with medication, and input from multiple specialties is often needed. Early, cohesive treatment may prevent significant consequences.

Background: Pathological laughing and crying (PLC) is a prototypical disorder of affect that neuropsychiatrists may be called upon to diagnose and treat. When this occurs as the sentinel sign of an ischemic stroke it is called fou rire prodromique, or the prodrome of crazy laughter. Historically, this was prodromal to apoplexy and death was common. We present a case with basilar artery occlusion who presented with PLC and a small subacute cerebellar stroke, though with symptom evolution progressed to a clear basilar artery occlusion syndrome. Case History: A 68-year-old right-handed-man with history of recent progressive multifocal ischemic strokes of undetermined source presented with abrupt episodes of uncontrollable laughing and crying, dizziness, and blurry vision. Recent evaluation revealed high grade stenosis of the basilar artery along with acute and subacute infarcts in the posterior circulation on MRI. After having an event suspicious for seizure, subsequent examination revealed cranial nerve deficits concerning for new pontine infarcts. Repeat CTA showed occlusion of the basilar artery and he was urgently taken for mechanical thrombectomy. Conclusion: Pathological laughing and crying is often thought of as an important, but nonemergent, disorder of affect. We present a case of basilar occlusion presenting with fou rire prodromique, which has been described in anterior and posterior circulation ischemic infarction. Neuropsychiatrists should be familiar with this rare, but emergent, form of pathological laughing and crying in patients with significant vascular risk factors.

Background: Neuropsychiatric symptoms are common sequelae of COVID-19. This case examines catatonia, a syndrome which has been increasingly recognized following COVID-19 infection. While the exact pathogenesis remains unknown, it appears likely mediated by immunologic, hematologic, and possibly neurotropic processes. This is a growing field of research that requires an increased examination of unique cases in order to further identify risk factors and the mechanisms underlying postinfectious catatonia. Case History: Two and a half weeks after testing positive for COVID-19, a 70-year-old man with no previous psychiatric history presents to the emergency room for 2 days of diminished spontaneity of speech, increasing paranoia, minimal oral intake, and on-going headache since diagnosis. He was diagnosed with catatonia and responded well to lorazepam. He was able to describe increasing depression with an unrelenting sense of guilt, severe anxiety, irritability, and agitation during COVID-19 infection. He subsequently had two similar presentations to hospital that coincided with attempts to wean down lorazepam and taper off olanzapine. The possibility of an underlying neurocognitive disorder was examined, but workup has not convincingly supported this as a comorbidity. With continued lorazepam and restart of olanzapine, the symptoms of catatonia again abated, and he was successfully discharged to outpatient care. Conclusion: This case contributes to the growing literature about neuropsychiatric complications of COVID-19. In particular, there is limited information about postinfectious new onset catatonia and psychosis, warranting continued research so as to promptly diagnose and effectively treat affected patients.

Background: While delirium is typically characterized by transitory, reversible, fluctuating global brain dysfunction, persistence of delirium affects over 9% of delirious patients, and proves a significant independent predictor of 1-year mortality. In this case, we would like to highlight the implication of status epilepticus in prolonged delirium, and the overlapping symptoms of potentially nonconvulsive subclinical seizures and persistent delirium. Case History: A 64-year-old female with history of resected bifrontal meningioma and breast cancer presented with acute onset aphasia, left gaze preference and right facial twitching, consistent with left frontal seizures status epilepticus, confirmed by 24-hour continuous EEG monitoring. Patient required intubation for 8 days, during which she continued to have intermittent frontal seizures. Two days after extubated, she developed agitated behaviors, hallucinations, and delusions, warranting antipsychotics. Her antiepileptic regimen includes Lacosamide (100 mg BID) and Depakote (500 mg BID). One month after admission, patient became more lethargic, having leukocytosis with left shift. No source of infection was identified, and leukocytosis resolved with empiric antibiotic treatment. However, this presumed infection shifted her illness trajectory from hyperactive delirium to hypoactive delirium, demonstrated in background slowing on EEG. Patient has since exhibited disorientation, somnolence, apathy, withdrawal, and is fully dependent on ADLs. Conclusions: Our case features the multifactorial nature of delirium and further reinforces the presence of multiple, repeated neuropsychiatric insults as predisposing factors for persistent disease. Thorough analysis of preexisting illnesses, medication, and aggressive investigation into treatable underlying causes will facilitate early recognition and management of delirium.

Background: Valacyclovir has been associated with adverse neuropsychiatric effects, especially in the elderly and patients with reduced renal function. However, there is currently limited literature to describe valacyclovir induced catatonia. We present a case of valacyclovir-induced delirium and subsequent catatonia. Case Report: An 80-year-old female with history of end stage renal disease, chronic obstructive pulmonary disease, hypertension, hypothyroidism, and no psychiatric history presented to the emergency room with altered mental status. A day prior to admission, valacyclovir 1,000 mg three times daily was started for treatment of suspected herpes zoster infection. Given that patient’s valacyclovir was not renally dosed, valacyclovir was suspected to contribute to her encephalopathy as workup was otherwise negative. Psychiatry was consulted for catatonia and initial rating on the Bush-Francis Catatonia Rating Scale (BFCRS) was 26. Although hypoactive delirium was considered, the patient’s daughter consented to a trial of intravenous Ativan 1 mg, which lowered patient’s BFCRS score to 14. Patient’s encephalopathy and catatonia improved with Ativan over course of hospitalization. Conclusion: This case highlights the importance of special consideration warranted for populations at higher risk for Valacyclovir induced neurotoxicity (VAN) as similarities in hypoactive delirium and catatonia can lead to delayed consideration and treatment. For populations with increased risk of VAN such as reduced renal clearance, elderly, or populations with history of neurological disease/injury, attention to dosing and monitoring for change in cognitive function is recommended with Valacyclovir use. Further studies are needed to reduce risk of VAN in population at risk for neuropsychiatric effects.

Background: Patients with complex brain disorders experience disturbed affect, behavior, and/or cognition (ABC), requiring multispecialty inputs at separate times. The novel Brain Medicine Clinic (BMC) brings together specialists to see patients in a real-time, virtual, collaborative, and efficient approach, while providing training for brain medicine fellows. Objectives: To describe the clinico-demographic characteristics of patients referred to the BMC and compare relevant variables between patients with low (LSS) versus high-symptom severity (HSS). Methods: After ethics approval, we reviewed electronic medical records and grouped patients into either LSS (with disturbances in A+B/A+C/B+C) or HSS (A+B+C). Forty-three variables were obtained and analyzed statistically. Results: Ninety-two patients from 2020 to mid-2022 were included (mean age: 55 years [18–88]; females: 54%; with partner: 65.9%; completed college: 44.8%; unemployed/retired: 70.1%; no substance use: 52.9%; remarkable family psychiatric history: 32%). The mean age of ABC symptom onset was 50 years (7–83). More than 50% had disturbances in at least two domains of ABC. Patients with LSS (N=51) had a significantly higher mean score (92.6/114) on BNA-SF compared to HSS (N=41; 80.5/114) (p=0.015). The HSS group had significantly more psychotropic medications (p=0.049). Other study variables were not statistically significant. Conclusion: This is the first description of a brain medicine population. Patients with HSS are clinically distinct from LSS in terms of worse cognitive functioning and need for more psychotropic medications. They would, therefore, require more thorough and integrated care as provided by the BMC. Future studies will include patient-, clinician-, and education-reported outcomes.

Background: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder associated with intellectual disability, autism, behavioral abnormalities, and epilepsy. Activation of the Ras-ERK pathway has been implicated in PMS, particularly in seizure generation. AMO-01 is an experimental Ras-ERK inhibitor that significantly reduced audiogenic seizures after a single dose in a PMS mouse model. Objective: The objectives of this pilot, open-label trial were to assess the safety and tolerability, syndromal impact, and seizure attenuation capabilities of AMO-01 in adolescents and adults with PMS. Methods: Six individuals (range 18–23 years, mean 21 years; 3 males), including five with epilepsy, were administered a single 6-hour intravenous infusion of 120 mg/m² of AMO-01, with follow-up over the next 4 weeks. Assessment measures included adverse events (AEs), clinician-completed rating scales, caregiver-completed rating scales, weekly seizure frequency, electrophysiology, plasma-based biomarkers, and blood levels of AMO-01. Results: AMO-01 was well-tolerated—all AEs were mild or moderate in severity and no serious AEs occurred. Five out of six subjects manifested syndromal improvement, including improvement in aberrant behavior and communication. Maximum clinical response occurred after 1–2 weeks. Weekly seizure frequency was significantly reduced at all timepoints, ranging from 38% to 100% per person at Week 1, 18% to 100% at Week 2, and 67%–100% at Week 4. AMO-01 peak plasma concentrations correlated with peak clinical response on multiple measures. Conclusion: This preliminary study provides affirming findings after single-dose administration of AMO-01 in PMS individuals. Further clinical trials appear to be indicated.

Background: Anti-NMDA receptor encephalitis (ANRE) is an autoimmune disorder that presents with neuropsychiatric symptoms. Diagnosis of ANRE can take several weeks, during which time neuroleptics are commonly used as treatment of those symptoms. However, neuroleptic intolerance (NI) has been reported as a sign of ANRE since some patients treated with those medications developed neuroleptic malignant syndrome (NMS). Treatment of the underlying disease involves immune-modifying therapy, which can lead to resolution of neuropsychiatric symptoms. However, there are no clear guidelines on the use of neuroleptics either in the acute or chronic stages of ANRE. Further there is no reliable method of predicting how patients with ANRE will react to neuroleptics. Case History: A 19-year-old woman with no significant past medical history presented with a recent seizure, personality changes, and psychosis. Cerebrospinal fluid studies were positive for anti-NMDA receptor antibodies. Immunological treatment included methylprednisolone and intravenous immunoglobulin. She was given occasional doses of haloperidol and lorazepam for acute agitation, and standing doses of olanzapine and later risperidone for behavioral disturbance. Amelioration of her neuropsychiatric symptoms was attributed partly to regular use of neuroleptics. There were no signs of NI during her hospitalization. The evidence for psychopharmacologic treatment of neuropsychiatric symptoms in ANRE and the risk of NI are reviewed. Conclusion: This case illustrates the potential safety and efficacy of neuroleptics in ANRE. More research is needed to guide appropriate use of psychopharmacological agents in ANRE and identify patients at risk of NI.

Background: The behavioral variant of frontotemporal dementia (bvFTD) is challenging to diagnose as it combines behavioral and personality features, overlapping with characteristics of primary psychiatric disorders (PPD). Serum neurofilament light (sNfL) has emerged as a candidate discriminative biomarker, but large-scale studies of sNfL in PPD are lacking. Objective: The goal of this study is to use the world’s largest biobank of psychiatric emergency patients, to establish a clinical cutoff score to differentiate PPD from bvFTD. Method: PPD patients (N=861) and healthy control (N=69) data were acquired from Biobanque Signature, and bvFTDs (N=82) from both the Amsterdam Medical Center (N=70) and Canadian Consortium on Neurodegeneration in Aging (N=12), all above age 40. sNfL levels were measured using Simoa technology on an HD-X instrument. General linear models were used to test for differences in sNfL between PPD and controls, accounting for covariates. ROC curve analyses were used to determine global and age-specific clinical sNfL cut-offs to distinguish bvFTD from PPD, using the Youden Index. Results: Log-transformed sNfL was slightly higher in PPD versus controls when controlling for age, BMI and diabetes status. ROC curves analyses established a 16.99 pg/mL global cut-off to differentiate bvFTD from PPD (82.9% sensitivity, 74.9% specificity, AUC=0.844). A cutoff of 15.952 pg/mL (80% sensitivity, 79.1% specificity, AUC=0.864) was determined for ages 40–60. Conclusion: The global and age-specific discriminatory accuracies from ages 40 to 60 were good, but accuracy decreases after age 60. Clinical applications of this work may improve the accurate diagnosis of bvFTD from PPD up to age 60.

Background: With advances in neuroscience, psychiatry and neurology, there is a need for strengthening cross-disciplinary neuroscience training in psychiatry. In recent surveys, 94% of trainers and residents agreed on the need for more neuroscience education and only 13% of trainees considered themselves strong in neuroscience. Trainees also preferred case-based and interactive teaching. The extent, preferred amount and the longitudinal integration of clinical neuroscience training in psychiatry residency nationally is unclear. Objective: To determine the extent, preferred amount and the longitudinal integration of clinical neuroscience training in psychiatry residency. Methods: To survey stake-holders in psychiatry residency training programs across the US (residents, fellows, faculty, program directors and chairs) about a) the preferred extent of clinical neuroscience training in psychiatry residency; b) the current extent of clinical neuroscience training in US psychiatry residency curricula, and c) the preferred approaches to incorporate clinical neuroscience training in psychiatry programs. To develop and implement an innovative longitudinal approach to teaching clinical neuroscience during psychiatry residency using a neurobiopsychosocial framework and a simulation-based approach. Results: We designed a survey with the feedback from residents, faculty, and consultants to distribute to psychiatry program directors across the US. We have incorporated longitudinal clinical neuroscience curricula into the BIDMC psychiatry residency didactics and will be assessing engagement and learning using anonymous pre- and postsurveys. We are in the process of testing a simulation-based approach to teach clinical neuroscience. Conclusion: The final lessons and teaching plan will be publicly shared to enhance clinical neuroscience teaching among psychiatry residency training programs.

Background: Modafinil and its active R-enantiomer, Armodafinil, are eugeroic medications that have been used to treat neuropsychiatric conditions including CNS hypersomnias, chronic fatigue syndrome, major depressive disorder, bipolar depression, cocaine dependence, and ADHD. Although generally thought of as having low abuse potential, there have been eight case reports reporting modafinil dependence and 1 case report reporting armodafinil dependence. We add to this the second case report of a patient developing dependence to a supratherapeutic dose of armodafinil. Case History: A 64-year-old woman with a long history of depression was referred to neuropsychiatric clinic by her Psychiatric Nurse Practitioner. She had a 30-year history of depression during which she reported failing all medications and even ECT treatment. The only effective medication was armodafinil, requiring escalating doses until reaching 1000 mg daily. She then moved states and indulged in “doctor shopping” due to the difficulty in getting a prescription for her supratherapeutic dose of armodafinil. She eventually established care with a local PMHNP who referred her to our clinic for consultation. An armodafinil taper was initiated. However, this was met with vehement protestations and on more than one occasion, patient took more armodafinil than she was prescribed. She was eventually titrated down to 125mg of armodafinil along with brand-name Prozac and Remeron. She also established with a psychologist for twice weekly therapy. Conclusions: Our case provides evidence that armodafinil has abuse potential. Given the frequency of use in neuropsychiatric clinics, clinicians should be aware of its abuse potential, especially at supratherapeutic doses.

Background: Pulsatile tinnitus (PT) is rare form of tinnitus characterized by the perception of a rhythmic sound. It is important to identify in the clinical setting as patients with PT are often at higher risk for vascular pathology. Due to the broad characterization of its symptoms, atypical presentation of PT may be misdiagnosed as other neurologic or psychiatric disorders. Case History: A 59-year-old male with a past history of ependymoma and meningiomas status post resection and hydrocephalus status post VP shunt placement was admitted to an inpatient psychiatric unit with debilitating auditory hallucinations refractory to multiple antidepressant and neuroleptic trials. The patient described a whooshing sound that resembled a vacuum cleaner or washing machine. Notably, these sounds were exacerbated at bedtime when the patient was recumbent. A review of the patient’s history and evaluation revealed significant hearing loss with no objective evidence of psychosis. CTA of the head and neck were significant for a unilateral osseous dehiscence. This finding along with the patient’s history suggested that PT was the likely etiology of the patient’s symptoms. Conclusion: This case illustrates a rare presentation of PT in a patient with significant neurologic history and hearing loss demonstrating the importance of distinguishing between neurologic and psychiatric symptomatology. A thorough medical work-up including neuroimaging and ENT consultation is crucial to obtain the correct diagnosis and avoid unnecessary medication trials.

Background: The metaverse is a digital platform displaying innovative electronic contents, delivered using advanced technologies (super computers, virtual technology devices, highly immersive software, etc.) employing artificial intelligence (AI) and extended reality (XR). A metaverse research organization, the Acceleration Studies Foundation (ASF), poses the metaverse as a platform where the real and virtual worlds integrate utilizing highly immersive and collaborative environments based on three-dimensional and real-time digital milieus. Objectives: To disseminate new peer-reviewed information regarding the relevance of the medical metaverse; and to increase the level of awareness about its specific technologies, their clinical potential and implications in neurosciences and neuropsychiatry. Methods: Previously known scientific information was reviewed, summarized, and integrated with new clinical evidence regarding the medical metaverse. There was a particular focus on areas relevant to clinical neurosciences and mental health interventions. The most pertinent concepts, including its technologies and how these innovations have opened new horizons in medicine and mental health disciplines were contextualized into graphic-rich instructional resources and other depictions. Results: The metaverse technologies pose as medical innovations with high clinical potential, specifically XR technologies (virtual, augmented, and mixed realities, respectively). Virtual and augmented reality paradigms are among the most used in medicine and mental health interventions. Conclusion: The metaverse technologies may optimize access to clinical services (i.e., increasing the practice of delivering and receiving medical care), and complement medical education and training. Furthermore, these innovations may represent an ideal platform for mental health research and new therapeutic approaches.

Background: Cerebral calcifications are common radiographic findings and can be caused by both benign physiological processes or by a number of clinical conditions. Pathologies commonly associated with cerebral calcifications can be grouped into congenital, neoplastic, infectious, vascular, metabolic, and inflammatory conditions. This is an unusual case of idiopathic psychosis in the context of scattered intracranial lesions, and demonstrates the need to rule out reasonable causes of psychosis prior to establishing a purely psychiatric etiology. Case History: A 45-year-old male with no reported past psychiatric history presented to the emergency department via the police under a Baker Act for bizarre behavior that included sitting in the middle of the road with his feet in a puddle of water saying “there is food seasoning in it.” Prior to the patient’s transfer from the emergency department to the psychiatry department, the patient underwent a noncontrast head CT scan due to his altered mental status, which revealed “no acute intracranial hemorrhage or mass effect, but showed “scattered calcifications which may relate to remote infection”. Conclusion: This case illustrates the utility of neuroimaging during the workup of sporadic cases of psychosis. Furthermore, it demonstrates the importance of using neurological findings in conjunction with psychiatric findings when investigating the possible causes of idiopathic psychosis in previously healthy patients with no past psychiatric history or apparent cause for psychosis.

Background: Hashimoto’s encephalopathy (HE) is a neuroendocrine disorder that can present with various neurologic and psychiatric symptoms. Current diagnostic criteria for HE in adults includes a requirement of subclinical or mild thyroid disease. There are no empirical studies documenting the prevalence of clinical thyroid disease in pediatric patients treated for HE. Recent literature suggests that euthyroid status does not predict response to immunotherapy in this population. Case History: An 18-year-old female with history of mild intellectual disability and hypothyroidism (not taking levothyroxine) was evaluated in the emergency department (ED) for several months history of confusion, withdrawal, mood lability, speech latency, incontinence, limited oral intake, and hallucinations. Routine medical workup including thyroid studies were nondiagnostic, prompting outpatient referral for suspected primary psychiatric etiology. On outpatient examination she displayed stupor, grimacing, withdrawal, staring, negativism, stereotypy, mutism, bilateral ptosis, responding to internal stimuli, and limited nutrition or fluid intake. Medical admission with expanded medical workup showed elevated Thyroperoxidase antibodies (705) and Thyroglobulin antibodies (35), but Thyroid Stimulating Hormone and Free T4 were within normal range. Electroencephalogram (EEG), CSF and autoimmune studies, and MRI brain were unremarkable. A trial of high dose steroids led to significant improvement the following day supporting the diagnosis of Hashimoto’s Encephalopathy. Conclusion: This case adds to a growing literature that HE responsive to steroid treatment can present in euthyroid children and adolescents. Early clinical recognition of HE allows for appropriate treatment and recovery, and further research with consideration of diagnostic criteria in the pediatric population is needed.

Background: Efficacy and safety of SDX/d-MPH have been reported previously in children with ADHD. Objective: To determine sleep behavior during SDX/d-MPH treatment in children with ADHD. Methods: This was a 12-month, dose-optimized, open-label safety study in 6–12-year-old subjects, including new subjects and those rolled over from a previous double-blind study. The primary end point was safety and tolerability. Secondary end point was sleep behavior based on the Children’s Sleep Habits Questionnaire (CSHQ) consisting of eight sleep domains (bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness). Results: Of 282 subjects enrolled (212 new; 70 rolled over), 238 were included in the sleep analysis. At baseline, mean (SD) CSHQ total sleep disturbance score was 53.4 (5.9). After 1-month treatment, the overall mean CSHQ score significantly decreased to 50.5 (5.4; least-squares mean change from baseline [95% CI], −2.9 [−3.5, −2.4]; p<0.0001) and remained significantly decreased for up to 12 months, indicating overall sleep improvement. Mean sleep-score changes from baseline to 12 months were statistically significant (p<0.0001) for 6 of 8 sleep domains. There was no significant worsening for sleep duration and sleep-disordered breathing. Daytime sleepiness and parasomnias sleep domains had the greatest mean improvement from baseline to 12 months (−2.0 [−2.4, −1.7] and−1.1 [−1.3, −0.9], respectively). Conclusions: Significant improvements in most CSHQ sleep domains were observed with SDX/d-MPH use in children with ADHD after 1 month and lasting up to 12 months of treatment. Importantly, the use of SDX/d-MPH did not worsen sleep problems.

Background: Functional Neurological Disorder (FND) is classically described as the presence of neurological symptoms in the absence of an underlying structural cause. However, a growing body of neuroimaging research challenges this conception through description of group-level differences in networks related to interoception, agency, multimodal integration, attention, and sensorimotor processing. Further, it is clinically recognized that functional symptoms regularly co-occur in patients with known lesional disorders such as multiple sclerosis. Yet there remains a paucity of published clinical descriptions of cases in which specific structural lesions present with motor symptoms consistent with FND. Case History: A 42-year-old man with a history of remotely resected left frontotemporal oligoastrocytoma presented with acute-onset left leg paralysis. Upon examination, the weakness demonstrated inconsistency, suggestibility, context-dependence, and a positive Hoover’s sign in keeping with FND. Neuroimaging demonstrated local recurrence of his tumor, and there were no other known acute triggers. The patient benefited from neuropsychiatric psychoeducation and FND physiotherapy and was ambulatory at discharge. We reviewed literature regarding brain network localization of FND and found the patient’s lesion location to be consistent. Conclusion: This case challenges the “functional/structural” dichotomy through demonstration of a clear structural lesion with temporal concurrence and possible mechanistic relation to a functional motor presentation. It is important for clinicians to recognize that the presence of functional symptoms does not always preclude structural etiology. Further, this case demonstrates that patients with classic FND symptoms may benefit from standard neuropsychiatric treatment modalities even in the presence of a related structural cause.

Willa Molho, Nicolas Raymond, David Parker, Rebekah Trotti, Robert R. Reinhart, Matcheri Keshavan, Paulo Lizano

Background: Transcranial electric stimulation (tES) has been shown to improve symptoms and cognition in psychosis spectrum disorders. In a recent study guided by causal lesion network mapping of visual hallucinations, we targeted the bilateral extrastriate visual cortex (V5/MT) with HD-tES and showed improvements in PANSS general symptoms. Objective: We aim to determine if HD-tES to V5/MT can improve visual cognitive performance. Methods: A within-subjects, open label, crossover design, pilot study was performed to characterize the efficacy of cathodal HD-tDCS (direct current) and 2Hz HD-tACS (alternating current) for psychosis treatment. Participants received 20-min of HD-tES twice daily for 5 consecutive days applied bilaterally to V5/MT with a washout between conditions. The Brief Assessment of Cognition in Schizophrenia (BACS) was performed at baseline, 5 days, and 1 month. Six participants with psychosis spectrum disorders received cathodal HD-tDCS while four received 2Hz HD-tACS. Results: HD-tACS resulted in significant improvements (p<0.10) in Tower of London (TL) (executive functioning) (X²_Friedman p=0.06) and Digit Sequencing (DS) (working memory) (X²_Friedman p=0.08). Pairwise comparisons showed improvements from Baseline-5 day (p=0.01, rank biserial=−0.56) and Baseline-1 month (p=0.04, rank biserial=−0.56) for TL as well as improvements from Baseline-1 month (p=0.04, rank biserial=−0.56) and 5 day-1 month (p=0.03, rank biserial=−0.44) for DS. HD-tDCS did not result in significant changes in any BACS scores. Conclusions: HD-tACS targeting V5/MT at delta frequencies may improve cognitive abilities in individuals with psychosis. Delta oscillations are a core mechanism in cortico-cortico communications across brain networks and have been linked to cognition. Future large-scale investigations are needed to further solidify these results.

Background: Symptoms arising from posterior cortical dysfunction are often overlooked. The Montreal Cognitive Assessment (MoCA) alone may be insufficient in detecting cognitive impairment from those who present with posterior cortical dysfunction and therefore the use of the Colorado Posterior Cortical Questionnaire (CPC-Q) has been introduced to increase the detection of posterior cortical dysfunction. Objective: This study aimed to test the hypothesis that composite MoCA scores correlate more strongly with the frontal/temporal (anterior) networks whereas CPC-Q scores correlate more strongly with parietal/occipital (posterior) networks. We further hypothesize that the use of both the MoCA and CPC-Q is superior to the MoCA alone in discriminating cognitive impairment from normal. Methods: Relationships between the MoCA composite scores and CPC-Q scores were compared to diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions localized to anterior and posterior tracts. Results: Correlation between composite MoCA score and anterior tract was 0.542 (p<0.001) and posterior tract was 0.597 (p<0.001). Correlation between CPC-Q score and anterior tract was −0.279 (p=0.033) and posterior tract average −0.307 (p=0.018). Conclusions: Both composite MoCA scores and CPC-Q scores are significantly associated with white matter integrity in both anterior and posterior regions, however CPC-Q scores do not correlate as strongly as the composite MoCA score.

Background: Mania is a syndrome associated with Bipolar Disorder I, which often presents around 20 years of age. However, insults such as stroke, traumatic brain injuries, and mass lesions can also lead to such symptoms. Efforts to localize mania in the brain using human connectome data has implicated the right hemisphere, notably the orbitofrontal cortex, right lateral temporal cortex, and right frontal pole. Case History: Patient is a 53-year-old male with history of occasional marijuana use, low testosterone treated with testosterone injections, and no other past psychiatric history, who developed 2 years of chronic, slowly progressive behavioral changes including increased religiosity and forgetfulness. CT head revealed a 3.6 cm suprasellar lesion with entrapment of the R lateral ventricle and asymmetrical hydrocephalus. Patient underwent VP shunt placement via right frontal approach and revision, complicated by abdominal CSF leak. Per collateral, patient’s behavior worsened after the shunt placement. His psychiatric evaluation was notable for irritability, expansive mood, paranoia, decreased sleep, hyper religiosity, pressured speech, disorganized and tangential thought process, concerning for acute mania. Patient was stabilized on valproic acid 1750 mg total daily dose and risperidone 1 mg twice daily. Conclusion: Patient’s presentation is atypical for primary bipolar disorder given the insidious progression and atypical age of onset. The R lateral ventricular enlargement and VP shunt via a right frontal approach may be affecting networks implicated in mania by human connectome data.

Background: Psychosis in epilepsy can be classified as ictal, interictal or postictal. Postictal psychosis is commonly seen in temporal lobe epilepsy, often presenting following a lucid period. Patients can experience manic symptoms, agitation, hallucinations, and delusions, although first-rank Schneiderian symptoms such as auditory hallucinations and delusions of thought interference are less common. Treatment involves achieving strict seizure control and psychotropics for symptomatic relief. Case History: A 52-year-old male with history of focal frontal lobe epilepsy, TBI and no past psychiatric history presented with new-onset agitation and audiovisual hallucinations. Patient had been maintained on a regimen of clonazepam, levetiracetam, and zonisamide for years, but because of concerns regarding impulsivity and frustration tolerance, clonazepam was weaned off 1 month prior. On evaluation, the patient was noted to be exhibiting ideas of reference, disorganization, and agitation requiring four-point restraints. Collateral was concerning for hyper religiosity and hallucinations. Patient was noted to have periods of confusion concerning for ongoing seizures. Continuous EEG monitoring showed bitemporal focal seizures. Patient had been started on olanzapine, but antipsychotics were stopped as patient’s symptoms abated with resolution of his seizures after cross titration of levetiracetam to lacosamide. Patient has remained free of psychosis since hospitalization. Conclusion: This case illustrates the importance of considering seizures as an etiology for psychosis, especially in patients with epilepsy. It demonstrates both classic features of postictal psychosis, such as association with temporal lobe seizures, and less common features, such as ideas of reference.

Background: Textual hallucinations typically consist of individual characters or nonsensical sequences. Meaningful textual hallucinations (syntacto-semantic visual hallucinations) have been reported only rarely. Here we present two patients with pure alexia and syntacto-semantic visual hallucinations. Case Histories: An 83-year-old woman gradually lost the ability to read except by obscuring all but one letter at a time. She began hallucinating text, e.g., “turn off the T.V.” and “you are losing power.” She also had palinopsia and simultagnosia. MRI showed focal atrophy of the occipital-temporal-parietal regions bilaterally; the diagnosis was posterior cortical atrophy. An 81-year-old woman presented with pure alexia and visual hallucinations in the upper right fields: flashing lights, palinopsia, and words she had just thought about, e.g., “dizziness” and “coffee.” She had a right homonymous superior quadrantanopia. MRI showed acute changes in the medial occipital area and a dural AVM at the junction of the left transverse and sigmoid sinuses. Conclusion: Both patients had pure alexia; however, they comprehended hallucinated text easily. The first patient’s textual hallucinations resembled auditory ones commonly reported with schizophrenia—the messages were commanding or mocking and in the 2nd person. Her preserved ability to read with close attention to letters and phonics was consistent with intact nondominant occiptotemporal functioning. The second patient’s hallucinations were associated with a lesion localizable to the lower left optic radiation. These cases offer exciting clues about the neurobiology of semantic memory and cortical networks involved in auditory hallucinations of schizophrenia.

Background: Depression in stroke survivors has been associated with dire consequences including decline in productivity, joblessness, and even suicide or suicide attempts. Objective: This study sought to investigate the relationship between depression and physical disability among stroke survivors in Nigeria in a bid to promote holistic patient care. Methods: A hospital-based cross-sectional study involving 110 adult out-patients with stroke at the neurology clinic of the University of Port Harcourt Teaching Hospital (UPTH) was employed in this study. Physical disability was determined using the modified Ranking Scale (mRS). Depression was diagnosed based on the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-SCID). Bivariate and multivariate analyses were performed at p<0.05. Results: The stroke survivors had a mean age of 54.49±9.33 years. Seventy-one (64.5%) were males. The mean mRS (physical disability index) score was 2.81±0.55, and the median mRS score was 3. A total of 39 stroke survivors had depression (35.5%). The depression rates were 10.3%, 43.8% and 50.0% for survivors with mRS of 2, 3 and 4 respectively (Chi Square for trend=9.362; p value=0.02). Increasing physical disability index remained significantly associated with depression (aOR=2.72; 95% CI: 1.12–6.67) after controlling for demographic and clinical variables. Conclusion: Depression and physical disability are linked among stroke survivors in Nigeria. The assessment of depression among stroke survivors at neurology out-patient clinics is advocated especially in those with moderate to severe forms of physical disability in order to improve clinical outcome.

Background: Capgras delusion is a rare psychiatric phenomenon where afflicted individuals develop a fixed belief that a specific person, most commonly a loved one or caretaker, has been replaced with an imposter. The “imposter” becomes the target of intense scrutiny and often hostility and violence as the patient fixates on perceived slight differences as evidence of the replacement. The condition is strongly associated with psychiatric comorbidities. Case History: A 30-year-old male was rescued from an attempted suicide by hanging and consequently suffered hypoxic-ischemic brain injury (HIBI). Following stabilization, he moved back to his parents’ house due to persistent cognitive defects. 3 years postdischarge, he presented to the outpatient rehab clinic after developing a Capgras delusion, believing his brother who lived in the home was dead and instead replaced by an imposter. The delusion was refractory to treatment with valproic acid but resolved with the addition of olanzapine. Conclusion: This case represents one of the only reported examples of Capgras syndrome presenting in a patient with HIBI; prior work has associated the condition with focal lesions to the right frontal cortex. Furthermore, this patient’s delusion may have been responsive to olanzapine. While there is no widely recognized standard treatment for Capgras syndrome, it is generally recommended that treatment of underlying psychiatric illnesses may improve the imposter delusion.

Background: People with depression and anxiety commonly report problems with cognition. Perceived problems with cognition can negatively impact overall quality of life. Little is known regarding whether both anxiety and depression independently contribute to self-reported cognitive problems. Objective: To assess the independent and combined effects of self-reported anxiety and depression on perceived cognition in a representative sample of the US adult population. Methods: Data from the National Health Interview Survey (NHIS) 2021 was analyzed. Of 29,482 participants, 23,665 were included in this analysis. Weighted binary and multinomial logistic regression analyses were utilized to assess associations between self-reported anxiety, depression, and perceived cognition. Results: A minority of participants reported depression (N=2,042, 8.63%) and anxiety (N=1,702, 7.19%). Problems with concentration (N=542, 2.29%), memory (N=1,857, 7.85%), or both (N=1,803, 7.62%) were also reported. People who reported anxiety were significantly more likely to report problems with concentration (OR=2.763 95% CI 2.754–2.773) and memory (OR=1.616 CI 1.612–1.621) than people without anxiety. Similarly, people who reported depression were significantly more likely to report problems with concentration (OR=2.806 CI 2.796–2.815) and memory (OR=2.119 CI 2.114–2.124). People who reported BOTH depression and anxiety were most likely to report problem with concentration (OR=4.786 CI 4.773–4.799). Conclusion: Independently and especially when combined, anxiety and depression are significantly associated with higher odds of reporting cognitive problems. Longitudinal research is needed to examine how treatment of depression and anxiety may influence perceived cognition and overall quality of life.

Background: Novelty seeking (NS) is a highly heritable personality trait often associated with risk-taking behavior, thus implicated in various neuropsychiatric illnesses. While the neurobiological correlates of NS have been explored extensively, causal evidence is necessary to identify neurostimulation targets. Objective: We tested whether lesions associated with a specific behavioral measure of NS are connected to a common network. Methods: We applied lesion network mapping to two independent surgical brain lesion datasets (N1=88, N2=48). Each data set included pre- and postlesion scores of NS collected as part of the Temperament and Character Inventory (TCI) self-report. We estimated whole-brain connectivity of each lesion using a normative connectome database (n=1,000). Within each data set, connectivity maps were correlated with NS change, controlling for pre-lesion NS score and lesion size, to produce a lesion network map. We quantified similarity using spatial correlations and tested for significance using permutation testing. Results: Network maps associated with trait NS generated from datasets 1 and 2 were similar (spatial r=0.806, p=0.009). Lesions that decreased novelty seeking were connected to the middle temporal gyrus and posterior cingulate, while lesions that increased novelty seeking were connected to the dorsal anterior cingulate and thalamus. Conclusion: Based on our results, excitatory stimulation sites connected to the dorsal cingulate would be expected to reduce trait NS, while sites connected to the middle temporal gyrus and posterior cingulate would be expected to increase NS. To our knowledge, this is the first study to identify causal neurostimulation targets for a stable personality trait.

Background: Studies have identified a correlation between symptom severity and adverse life experience (ALE) burden in functional neurological disorder (FND). While not reported by all, such findings raise the possibility of a FND trauma-subtype. Objective: This study investigated if patients with FND, with or without probable PTSD and/or significant childhood maltreatment, differed in their symptom severity and physical health. Methods: 78 FND patients were recruited. Participants completed self-report measures of symptom severity (SDQ-20, SOMS:CD, PHQ-15), physical health (SF36-physical health), childhood maltreatment (CTQ), and PTSD (PCL-5); a psychometric battery of other predisposing vulnerabilities was also completed. Bonferroni correction was applied to all univariate analyses. Results: Patients with FND and probable PTSD (N=33) versus those without probable PTSD (N=43) had statistically significant increased scores on all symptom severity measures as well as decreased physical health scores. In post hoc regression analyses, findings remained significant adjusting for age, sex, race, college education, and: pathological dissociation; alexithymia; attachment styles; “Big Five” personality characteristics; resilience scores; functional seizures subtype; or moderate-to-severe childhood abuse and neglect scores; SOMS:CD and SDQ-20 findings also held adjusting for depression and anxiety. Separately, patients with FND and moderate-to-severe childhood abuse (N=46) versus those without moderate-to-severe childhood abuse (N=32) showed statistically significant increased SDQ-20 and PHQ-15 scores; in post hoc regressions, finding also held adjusting for demographic and other variables. Stratification by childhood neglect did not relate to severity or physical health scores. Conclusion: This study supports a possible trauma-subtype of FND. Future research should investigate the neurobiological and prognostic relevance of this subgroup.

Background: In patients with developmental disorders and intellectual disability, psychiatric symptoms tend to occur slowly and insidiously delaying its identification and its opportune approach. This in turn complicates the progress of the underlying psychiatric conditions, increasing the severity of its presentation and causing higher functional compromise. It is not infrequent that patients with developmental disorders develop severe psychiatric syndromes like catatonia which have shown higher prevalence in this population. Catatonic symptoms are often mistaken as psychosis prompting the management with antipsychotics that could worsen the catatonic presentation. However, when the condition underlying the catatonic presentation is a psychotic disorder; antipsychotics should be considered. Case History: We present a 26 yo male patient with history of unspecified developmental disorder and intellectual disability who developed 2 months of psychotic symptoms with significant functional compromise. After outpatient management, the symptoms worsened, and he presented to the emergency department where he was noted to be catatonic and underwent a lorazepam challenge which resulted in partial improvement. He persisted with psychosis warranting antipsychotic treatment. We review the challenges in identification and management of psychosis and catatonia in patients with intellectual disability and developmental disorders. Conclusion: This case illustrates how the delay in identification and treatment of psychosis can lead to severe psychiatric syndromes like catatonia. In patients with developmental delay and intellectual disability, clinicians should be alert to behaviors that suggest the presence of psychiatric symptoms.

Background: Traumatic brain injuries (TBI) can lead to various neuropsychiatric complications including depression, anxiety, cognitive deficits, impaired sleep, and agitation. Impulsivity, personality changes, and perturbed sexual functioning are amongst other notable symptoms. The majority of individuals experience a decrease in sexual functioning and relationship quality following TBI, but a small subset experiences an increase in sexual desires. Here, we present a case of compulsive hypersexuality in a patient following a TBI in a motorcycle accident. Case History: A 53-year-old man with a history of depression and anxiety presented to neuropsychiatric clinic to establish care. He had a history of a traumatic brain injury and right frontal lobe damage resulting from a motorcycle accident. He reported a myriad of depressive and anxiety symptoms following the TBI, along with neurocognitive deficits in verbal learning and processing speed. Additionally, he noticed hypersexual activity consisting of preoccupation with obsessive masturbation, immediately after the TBI, where he spent an excessive amount of time watching pornography and masturbating 9–10 times a day over a period of 4–5 months. He had two ongoing sexual partners at the time and even engaged in sexual behaviors with a client of his. The constellation of obsessive sexuality lasted for 2 years and self-resolved without pharmacological intervention. Conclusion: Our case provides evidence of sexual disinhibition following TBI. Given the psychosocial burden of sexual dysfunction and its potential to impair functioning, neuropsychiatric clinics and clinicians should be aware of these symptoms and routinely screen for them in clinical practice.

Background: Lesions causing psychosis provide a unique source of causal information. Mapping the connectivity of these lesions could reveal circuit-based therapeutic neuromodulation targets. Objective: To assess whether lesions causing psychosis map to a common brain circuit. Methods: We performed a literature review for cases of brain lesions resulting in psychosis. Functional connectivity of each lesion was estimated using a human connectome database (N=1,000). We performed a sensitivity analysis using a one-sample t test with family wise error correction for multiple comparisons to identify connections common to lesions causing psychosis. We performed a specificity analysis using a two-sample t test between our functional map and two separate control groups: 490 patients from an observational stroke database and 258 published cases with lesion-induced nonpsychotic symptoms. Results: We identified 152 cases of lesion-induced psychosis. Lesions causing psychosis were functionally connected to the posterior hippocampus, ventral tegmental area, substantia nigra, anterior/medial dorsal nuclei of the thalamus, medial frontal cortex, retrosplenial cortex, and the cerebellar representation of the limbic network. The posterior hippocampus was the strongest peak in the specificity analyses and passed Bonferroni correction. To determine if the effect was driven by lesions intersecting the hippocampus alone or a distributed brain network, we repeated the analysis after excluding lesions intersecting the hippocampus (N=26) and found similar functional connections across the whole brain (r=0.98) with the same peak in the posterior hippocampus. Conclusion: Lesions causing psychosis map to a common brain circuit defined by functional connectivity to the hippocampus. This circuit could provide a new target for neuromodulation.

Background: We report a case of a patient presenting with an isolated lesion in the left intraparietal sulcus (IPS) and vivid hallucinatory phenomena suggestive of peduncular hallucinosis. Lesion-network mapping revealed negatively correlated functional connectivity between the IPS lesion and the extrastriate visual cortex. This is a similar connectivity to classically located peduncular hallucinoses lesions. Case History: 66-year-old, ambidextrous man with a medical history significant for hypertension, hyperlipidemia, and no psychiatric history presented with acute onset of hallucinosis with prominent visual phenomena. Neurological examination, including a detailed eye examination, revealed no deficits. Urine toxicology was negative on admission. An MRI brain performed 48 hours after onset of visual hallucination revealed a bright focus on diffusion weighted imaging. We investigated the functional connectivity of this patient’s IPS lesion and found prominent negative-correlations in the extrastriate visual cortex. We used spatial Pearson correlations across all 228,453 voxels in the brain to assess similarity of our lesion’s connectivity map to 23 peduncular hallucinosis lesion maps. These lesions were likely to be positively correlated with our patient’s lesion by a one sample t test (p=1.45 × 10–5). As a control, we computed the same spatial correlation to compare our patient’s lesion to 576 lesions resulting in nonhallucinatory symptoms. Our patient’s lesion connectivity matched that of other peduncular hallucinosis lesions significantly more than control lesions (p=0.0347). Conclusion: This case illustrates the theory of how visual hallucinations could be produced by a disinhibition of the extrastriate visual cortex.

Background: The differential diagnosis between epilepsy and psychogenic nonepileptic seizures (PNES) remains a medical challenge. Due to videoelectroencefalography (VEEG) monitoring, the psychiatrist’s assessment during the follow-up adds value to the diagnostic accuracy. Objective: This study aimed to give an overview of our service in São Paulo, Brazil. We have one hospital bed in a VEEG unit, used for the evaluation of patients with suspected PNES, associated or not with epilepsy. Methods: Data collection was collected from the review of medical records of all patients evaluated by the neuropsychiatry service from January to October 2022. All patients were evaluated by at least two psychiatrists specialized in epilepsy during the VEEG monitorization. Results: During the aforementioned period, 34 patients were evaluated. On average, they stayed in VEEG unit for 7.8 days. For the final diagnosis, 50% had PNES only, 32.4% had PNES and epilepsy, and 17.6% had epilepsy only. Regarding the 28 patients with PNES (isolated or associated with epilepsy), it is noteworthy that 4 had a diagnosis of occasional or iatrogenic PNES and the other 24 had PNES due to a dissociative-conversive disorder. Nearly 73% had a PNES during suggestive induction. The difference between the first symptoms and the correct diagnosis in these cases was 10.3 years on average. Conclusion: It was observed that the psychiatrist at the VEEG unit was able to optimize hospital bed occupancy without being less efficient in the accuracy of the diagnoses (34 patients in 42 weeks) due to the long stay (7.8 days of hospitalization). Correct diagnosis is essential for optimal treatment.

Background: The presence of psychogenic nonepileptic seizures (PNES) as a manifestation of immunization stress-related response (ISRR) has been observed more frequently over the years. Correct diagnosis is important not only for optimal treatment, but also for confidently supporting vaccines. Case History: Case 1: a 46-year-old woman developed acute symptoms four weeks after a single dose of COVID Janssen vaccine. Symptoms included severe spams of facial muscles and palatal tremors lasting several minutes. There was a progressive worsening that made daily activities impossible. After 3 months and extensive neurological investigation, the patient was monitored in a VEEG unit. Case 2: a 66-year-old woman developed acute symptoms 2 weeks after the first dose of Oxford COVID vaccine. Symptoms included seizures and screamings for several hours. There was a severe worsening with countless PS assessments and intense family distress. After 5 months, the patient was monitored in a VEEG unit. Conclusion: In both cases, the patients and their families believed in a postvaccination neurological reaction and feared the side effects of the COVID vaccine. The extent of the neurological investigation without denying the correlation between the vaccine and the symptoms reinforced their beliefs. Both had normal EEG and positive symptoms provoked by suggestive induction during the VEEG monitoring.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with exposure to repetitive head impacts, such as those sustained in contact sports. The clinical manifestations of underlying CTE pathology, described in the NINDS Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES), include cognitive impairment and neurobehavioral dysregulation (NBD; i.e., poor regulation of emotions and behavior). However, the relationship between the latent construct of NBD and its specific symptoms remains unclear. Objective: To characterize the construct of NBD in former American football players. Methods: Experts previously selected 34 items relevant to NBD from various self-report neuropsychiatric scales administered in the DIAGNOSE CTE Research Project. These items were subjected to confirmatory factor analyses using a weighted least squares estimation method (WLSMV) in a sample of 115 former NFL players, 59 former college football players, and 60 asymptomatic controls. Several putative factor structures were compared qualitatively and with statistical fit criteria. Results: Psychometric evaluation revealed superior fit for a four-factor second-order model (chi-square/df ratio=1.3, CFI=0.95, NNFI=0.94, RMSEA=0.036, SRMR=0.052). First- and second-order factors demonstrated excellent internal consistency: “explosivity” (10 items; α=0.93), “impulsivity” (8 items; α=0.88), “emotional dyscontrol” (4 items; α=0.87), “affective lability” (3 items; α=0.85), and “Total NBD” (25 items; α=0.95). Conclusion: The syndrome of NBD can be conceptualized as a distinct neuropsychiatric construct, even though its constituent clinical features (i.e., explosivity, impulsivity, emotional dyscontrol, and affective lability) are each associated with other psychiatric and neuropsychiatric disorders.

Background: Transcranial electrical stimulation (tES) has been shown to improve symptoms and cognition in psychosis spectrum disorders. However, few investigations have used novel tES approaches, such as high definition tES (HD-tES) to more specifically target brain circuits. Convergent data from neuroimaging, neurophysiological, and cause-effect studies point toward alterations in the extrastriate cortex (V5/MT) in psychosis. Objective: We aimed to determine if causal lesion network guided HD-tES to the extrastriate cortex is efficacious and safe in improving psychosis symptoms, motion processing, and electrophysiology alterations. Methods: Experimental design consisted of a between-participants, open-label, nonrandomized, cross-over pilot study employing cathodal HD-tDCS (transcranial direct current stimulation) and delta frequency HD-tACS (transcranial alternating current stimulation). 20 mins of tES was delivered twice daily for 5 consecutive days to the extrastriate cortex. Results: A total of 6 patients with psychosis were enrolled. HD-tDCS resulted in a significant reduction in psychosis general symptoms and emotion processing as well as steady-state evoked potentials at 5 days, which were directly correlated. HD-tACS resulted in longer term reductions in psychosis general symptoms at 30 days. Both types of tES were well tolerated. Conclusion: Our results provide proof of concept evidence that causal lesion network mapping can enhance brain targeting using tES in psychosis. We showed that stimulation of the extrastriate visual cortex resulted in short term effects with HD-tDCS, while HD-tACS resulted in longer term benefits on symptoms. Further research is needed to determine the clinical efficacy and safety of this type of stimulation.

Background: Complementary therapies are intended to enhance, even accelerate, the effectiveness of other therapies. Equine Assisted Psychotherapy (EAP) is a specialized type of equine-assisted therapy provided by licensed mental health professionals and certified equine professionals. In EAP, horse partners facilitate verbal and nonverbal communication and foster mindful awareness of thoughts and behaviors with the human client. Few studies using EAP as complementary therapy to mental health treatment exist; no studies were found that examine the use of EAP in an adult outpatient population who have chronic mental health problems. Objective: To examine the feasibility of EAP as a complementary therapy to medication management and psychotherapy. Methods: A mixed methods study was conducted December 2017–May 2019. Participants were over age 18, with chronic mental illnesses, stable chronic medical illnesses, using pharmacotherapy. Those engaged in psychotherapy continued with their individual therapist. Participants were offered 12 EAP sessions. Results: 12 individuals (1 male, 11 female); mean age 39.5 years; 7 of the 12 were receiving concomitant psychotherapy; 1–12 EAP sessions were completed. 98 of 144 possible sessions were attended; participants completed 90% of survey items. PHQ-9 scores had a change of −0.59 points per session (p=0.0004); Brief Resilience Scale scores increased 0.04455 points per session (p<0.03). Qualitative interviews revealed improved emotional growth, mindful redirection, and life integration. Conclusion: This study demonstrates that a standardized EAP protocol, across diagnoses, is feasible and results in decreased depressive symptoms and modest improvement in resilience. Participants expressed improved social functioning and psychological flexibility in their conversational reports.

Background: Alzheimer’s disease is the most prevalent neurodegenerative disease worldwide, yet the frontal variant of Alzheimer’s disease (fvAD) is less common. Given the overlapping features with other disorders, this can be a challenging diagnosis to ascertain. Without appropriate investigation, fvAD may be incorrectly attributed to a psychiatric disorder or behavioral-variant frontotemporal dementia. Case History: A 46-year-old female was admitted to the inpatient psychiatric unit for increased restlessness, pacing, muscle aches/stiffness, and pain. Per the family, the patient declined significantly over the past 3 years (inappropriate behaviors, poor relationship with children, divorce, loss of executive job). She had numerous emergency department visits and was hospitalized twice for 30+ days for a psychiatric condition. Her chart noted multiple psychiatric diagnoses, including schizophrenia, bipolar disorder, anxiety, adjustment disorder, and “other psychotic disorder.” Extensive workup, including MRI, FDG-PET, and neuropsychological testing, supported the diagnosis of fvAD. Reduction in medications resolved presenting akathisia, and the patient was discharged with appropriate services. Conclusion: This case illustrates the importance of considering neurodegenerative disorders in patients with “late-onset” neuropsychiatric symptoms, especially those without any previous psychiatric history. Patients who fail to improve with medication therapy also deserve reconsideration and appropriate testing and imaging. Failure to properly diagnose patients with neurodegenerative disorders results in a lack of necessary services and negatively affects patients, families, and society.

Background: Nonfluent aphasia is a language disorder characterized by simplified sentence structures as well as word-level abnormalities such as a reduced use of verbs and function words. According to the predominant account of the disorder, both structural and word-level features are caused by a core deficit in the processing of syntax. Under this account, however, it remains unclear why nonfluent patients choose semantically richer verbs and may have an intact comprehension of verbs and function words. Objective: Here, we propose and test the hypothesis that the word-level features of nonfluency reflect a process that selects lexically richer words to increase the information content of sentences. Methods: We use a computational linguistic method to measure the information content of sentences in the language of patients with nonfluent primary progressive aphasia (nfvPPA) (N=36) and healthy controls (N=133). We measure sentence information using surprisal, a metric calculated by the average probability of occurrence of words in a sentence given their preceding context. Results: We found that by packaging their structurally simple sentences with lower frequency words, nfvPPA patients produce sentences with similar surprisal as that of healthy speakers. Furthermore, we found that higher sentence surprisal in nfvPPA correlates with a lower function-to-all-word ratio, a lower verb-to-noun ratio, and a higher heavy-to-all-verb ratio. Conclusion: Surprisal is an effective quantitative index of sentence information. Using surprisal allows for testing an account of nonfluent aphasia that regards word-level features of nonfluency as adaptive rather than defective symptoms, a finding that may entail revisions in therapeutic approaches to nonfluent speech.

Mathilde Rioux, Andrew K. Howard, David L. Perez, William J. Panenka, Julia Schmidt, Miles T. Byworth, Noah D. Silverberg

Background: Objective memory deficits typically resolve within weeks of a concussion, however, a subgroup of individuals continue to report memory difficulties for months or years. Such subjective memory concerns are frequently associated with impaired daily functioning and reduced well-being. To date, no effective treatments for functional cognitive disorders such as these have been established. Objective: Given that cognitive behavioral therapy (CBT) has been effective in treating other functional neurological disorders, this pilot randomized controlled trial aims to determine the feasibility and preliminary efficacy of a manualized CBT-based treatment program in improving functional memory symptoms after concussion. Methods: Patients with functional memory symptoms persisting for 6–24 months after a concussion will be recruited and randomized (1:1, stratified by memory concern severity) into a manualized CBT group or a cognitive rehabilitation control group. All participants will receive 11×50 minute sessions via videoconferencing, facilitated by clinical psychology graduate students under the supervision of a clinical psychologist. Clinicaltrials.gov registration #NCT05581810. Results: Two patients have been recruited so far, out of a total of N=30 planned. Feasibility outcomes will be reported descriptively. Between-group comparisons on the primary outcome (i.e., memory concern; Multifactorial Memory Questionnaire-Satisfaction subscale) and secondary outcomes will be analyzed by calculating standardized mean differences pre- and postintervention. Conclusion: This pilot study represents the first attempt to create and validate a standardized, manual-based CBT approach to treating postconcussive functional cognitive disorders. Effective treatment of such patients would represent a significant step forward in addressing this common, often debilitating condition.

Background: PET tracers bind to the paired helical filaments of tau in aging and (AD) but their utility in detecting tau aggregates in (FTD) is less certain. Objective: To provide an aggregated quantitative analysis of the value added by tau PET imaging in FTD patients compared to healthy participants. Method: Systematic search was performed in PubMed, Web of Science, Embase, and Scopus until June 2022. 189 FTD patients and 281 healthy controls over nine studies were included. Data were abstracted by four observers and assessed for publication bias. The SUVR in FTD patients and healthy controls with tau PET imaging were compared in the frontal, temporal, and parietal cortices. Result: FTD patients showed an increase in SUVR in frontal (SMD, 0.97, 95% CI, 0.47–1.46), temporal (SMD, 0.93, 95% CI, 0.47–1.38), and parietal (SMD, 0.33, 95% CI, 0.01–1.65) lobes. However, the heterogeneity, shows variation between studies was high in frontal (I2=76%) and temporal lobes (I2=81%). An analysis between five subgroups (svPPA, nfvPPA, bvFTD, MAPT, C9ORF72) suggested svPPA had higher SUVR in frontal (SMD, 1.48, 95% CI, 0.50–2.45) and temporal (SMD, 1.73, 95% CI, 0.92–2.54) lobes than HC, while the SUVR of bvFTD increased in parietal lobe (SMD, 0.50, 95% CI, 0.07–0.93). Conclusion: This is the first meta-analysis of tau PET in FTD and we confirm higher uptake value in FTD in the frontal, temporal and parietal regions compared to controls and provide evidence it may be useful in determining the variant of FTD.

Background: The differential diagnosis of a patient with cognitive, behavioral, and motor symptoms is broad. There is much overlap between neurocognitive disorders due to frontotemporal dementia and other subcortical dementia. A less known diagnosis, cerebellar cognitive affective syndrome (CCAS), should also be considered. CCAS can present with deficits in executive function, spatial attention, and affective dysregulation. Case History: 29-year-old female presented with ataxia and left sided weakness. CSF showed oligoclonal bands, and MRI showed multiple white matter lesions with some atrophy. She was diagnosed with multiple sclerosis (MS). In subsequent years, she received multiple MS treatments. At age 35, she developed frontal lobe symptoms and executive dysfunction; she was diagnosed with MS with bipolar disorder. Neuropsychological evaluation at that time showed significant deficits in multiple cognitive domains. Subsequent MRI showed progressive frontotemporal atrophy. FDG-PET uncovered hypometabolism in the frontotemporal lobes and cerebellum. CSF, EEG, and lab workup were consistent with possible autoimmune encephalitis. Intravenous immunoglobulin was administered with only partial and temporary improvement. At age 38, her behavior got worse with aggression, and she was started on olanzapine. She responded well with decreased agitation and improved motivation and attention. Compared with previous scans, most recent MRI and FDG-PET showed interval increase in cerebellar atrophy with increase in hypometabolism in cerebellum respectively. Conclusion: Based on cerebellar, affective, and subcortical cognitive examination findings, our diagnosis is probable CCAS. Cerebellum should be considered as a possible etiology of frontal subcortical cognitive impairment.

Background: The prevalence of behavioral issues in the population with Autism Spectrum Disorder (ASD) is >50%. There are very few FDA-approved medications for behavioral problems in ASD, which often results in polypharmacy with off-label trials and, therefore, increased risk for side effects. N-Acetyl-L-Cysteine (NAC) is generally well-tolerated with few side effects and is known to modulate the oxidative stress pathway. Objective: We aim to assess NAC’s role in managing behavioral issues in ASD pediatric populations. Methods: A comprehensive search of published studies on NAC use in ASD was conducted on PubMed, PubMed Central, Medline, and APA PsychInfo databases until October 31, 2022, and yielded 169 articles. We included five clinical trials for qualitative synthesis per PRISMA guidelines. Results: According to the Dean et al., 2017 study, repetitive and stereotypic behaviors did not improve in autistic participants taking NAC 500 mg/day for 6 months as an adjunct with treatment as usual (TAU), and these findings were supported with similar results in Wink et al. 2016 trial. However, Hardan et al., in a 2012 clinical trial, found significant improvements in irritability and stereotypic behaviors with NAC. The NAC as adjunctive therapy with Risperidone improved irritability and hyperactivity but had no improvement on repetitive behavior in a comparative 10-week trial by Nikoo et al. and in an 8-week study by Ghanizadeh. Conclusion: NAC may improve irritability and hyperactivity, but the results are mixed in managing stereotypical behaviors. Future randomized controlled trials are needed to determine NAC’s use as sole or adjunct therapy.

Background: Stroke survivors often experience neuropsychiatric symptoms in addition to persistent neurological deficits, contributing to increased morbidity and reduced quality of life. While poststroke depression (35%) and anxiety (25%) are well recognized, a national study exploring the prevalence of neuropsychiatric disorders poststroke is lacking. Objective: We evaluate the prevalence of neuropsychiatric disorders and the association of mood disorders in individuals with a history of stroke. Methods: We utilized National Inpatient Sample (NIS) 2017 data containing 7 million adult inpatient records in the U.S. Univariate and multivariable logistic regression analysis was performed to identify the neuropsychiatric disorders prevalence and odds of mood disorders in patients with a stroke history. Results: The study included 357,551 patients with stroke history (Group A) and 5,514,905 without stroke history (Group B). More patients in Group A had mood disorders (19.8% vs. 17.1%) and anxiety disorders (15.9% vs. 14.6%) compared to Group B. Bipolar disorder prevalence was higher in Group A (16.9% vs. 13.6%) than Group B. Stroke history was associated with 26% more risk of mood disorders (aOR: 1.26, 95% CI: 1.25–1.28). Group A patients in age groups 35–49 (29.5% vs. 21.5%) and 50–64 (26.4% vs. 21.2%) had a higher prevalence of mood disorders than Group B. Conclusion: Stroke and mood disorders may bidirectionally increase the odds of each other. Mood disorders are common after a stroke. Further research is needed to explore factors associated with increased risk of stroke in patients with mood disorders and increased susceptibility to new onset mood disorders following stroke.

Background: Migraine is a neurologic disease that often presents with various neurological symptoms. Additionally, current literature has demonstrated a clear effect on neurocognitive abilities. Current treatment options for migraineurs include pharmaceutical and nonpharmaceutical options such as modified diets. Objective: To investigate the neurocognitive outcomes of patients with intractable migraines after treatment. We anticipate that as migraine frequency decreases, we will observe changes in neurocognitive domains. Methods: Neurocognitive tests were performed on 21 adults (18 female; 3 male) who presented with intractable chronic migraines using standardized tests through Cambridge Brain Sciences. Patients were treated with individualized neurocognitive tasks, spinal adjustments with traction, and vibration therapy at the Migraine and Neurological Rehabilitation Center in Provo, Utah. Results: All the patients completed migraine treatment and repeated the neurocognitive testing. The patients’ average percentile on the neurocognitive evaluation overall significantly increased after treatment. Patients’ percentile increased by 14.8 (p=8.81E−05) on the Double Trouble portion, and patients’ percentile increased by 7.6 (p=0.00132) on the Spatial Planning portion of the neurocognitive assessment, which tests their ability to concentrate on relevant information and ability to plan for space needed for repetitive tasks, respectively. Conclusion: In this group of patients, intractable migraines were associated with neurocognitive deficits in specific domains. Patients completed treatment and posttreatment neurocognitive evaluation. In addition to reducing migraine frequency, treatment appears to correlate with improvements to neurocognitive abilities. These findings suggest that neurocognitive outcomes should be closely monitored when treating patients with intractable migraines.

Background: Functional Neurological disorder (FND) also known as Conversion disorder, refers to one or more symptoms that affect the body and cannot be explained by any neurological, medical condition or another mental health disorder. Functional cognitive disorder (FCD) can also occur as a part of the Functional Neurological disorder spectrum. Typical symptoms of FCD include absent-mindedness, losing train of thought, and difficulty retrieving overlearnt memories. Roughly 25% of patients presenting to memory clinic, have FCD. While etiology remains unknown, predisposing factors include trauma, illness exposure, symptom monitoring and neurobiological factors. Case History: At the age of 52, a left-handed male presented for evaluation of an episode of cognitive decline which had resulted in significant impairment. His first episode occurred at age 42 where he experienced forgetfulness and on evaluation was found to have Hashimoto’s thyroiditis, Alcohol Use Disorder, depression and anxiety. There was return to baseline after treatment of the psychiatric conditions. Second episode of cognitive decline presented in the absence of any biological contributing comorbidities, with complains of significant decline in memory and now gait abnormalities. Battery of tests done were all found negative and thorough review of history indicated significant episodes of trauma which preceded both episodes. Conclusion: This case illustrates the importance of the impact of psychological trauma on neurological function and highlights functional cognitive disorder as a part of the spectrum of the functional neurological disorder spectrum. It also stresses the importance of early recognition of FCD, thorough screening and treating of any significant psychological trauma, as this may help in reducing this quite disabling disorder.

Background: About 50% of patients with psychotic disorder experience visual hallucinations and deficits in visual processing. Cerebral blood flow (CBF) alterations have been shown in occipital lobe (OL) and fusiform gyrus (FG) in schizophrenia (SZ) and bipolar disorder with psychosis (BPD). However, previous studies do not report on cytoarchitectonic subregions of OL and FG. Objective: This study aimed to determine CBF differences in OL and FG subregions between SZ, schizoaffective disorder (SAD), BPD and healthy controls (HC) and between biotypes identified in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Methods: Subjects included 167 BPD, 240 SAD, 252 SZ and 410 HC. A Pseudo-Continuous Arterial Spin Labeling (pCASL) scan was acquired during resting state. Four subregions each in OL (hOc1-hOc4) and FG (FG1-FG4) were extracted in each hemisphere and the mean CBF was calculated for each subregion. We used R to perform nonparametric comparisions in the subregions. Results: For SZ there was a decrease in CBF in right-hemisphere (rh) FG1-FG3, hOc1-hOc4 and in left-hemisphere (lh) hOc1 and hOc3 compared to HC. For BPD there was a CBF decrease in rh FG1, FG3, hOc1-hOc3 and in lh hOc3. SAD showed a CBF decrease in rh hOc1-hOc3 and in lh hOc3 compared to HC. Biotype 1 exhibited a decreased CBF in rh FG4, hOc2, hOc3 and lh hOc1, hOc3 compared to Biotype 3. Conclusion: Psychosis spectrum disorders are associated with a decreased CBF in OL and FG subregions. Neurobiologically defined subgroups could be more informative than traditional symptom based diagnostic criteria.

Background: Exposure to repetitive head impacts may be associated with the later-life development of chronic traumatic encephalopathy (CTE), a neurodegenerative disease. The NINDS Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome includes two core clinical features: cognitive impairment and neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome defined by six descriptors: explosiveness, impulsivity, rage, violent outbursts, having a short fuse, and emotional lability. We hypothesized that a combination of questionnaire items from multiple neuropsychiatric scales could measure discrete aspects of NBD. Objective: To leverage expert reasoning to 1) select items relevant to NBD from various neuropsychiatric scales and 2) identify clinically distinct subconstructs for the syndrome of NBD. Methods: All self-reported items from relevant neuropsychiatric scales in the DIAGNOSE CTE Research Project (i.e., BRIEF-A BRI, BIS -11, STAXI-II, CNS-LS) were identified. Forced-choice selection was used such that six experts independently sorted each item into one of the six NBD descriptors or “none of the above.” Item co-occurrence analysis was conducted, examining strength of conceptual associations amongst the six NBD descriptors, and identifying discrete subconstructs of NBD. Items irrelevant to NBD were removed based on expert agreement. Results: Co-occurrence analysis revealed strong conceptual associations amongst four descriptors (explosiveness, rage, violent outbursts, short fuse). These four descriptors were combined to form a single composite subconstruct, termed “explosivity.” Impulsivity and emotional lability remained conceptually separate and were considered independent subconstructs. Expert agreement thresholds were used to select 34 items that effectively represented the three subconstructs of NBD. Conclusion: NBD can be meaningfully divided into three subconstructs: explosivity, impulsivity, and emotional lability.

Background: Depression patients are typically assessed using subjective rating scales, but a neuropsychiatric approach with more objective assessments may be beneficial. Objective: To evaluate negativity bias and processing speed tests as objective measures of depression severity. Methods: 12 major depression patients undertook an implicit negativity bias test (INBT) from a computerized platform (Total Brain) in which they had to recognize a facial emotion. Afterward, two faces were presented, with one face repeated and one face new. Both faces displayed the same emotion, and the task was to select the face seen previously; correct response times for negative emotions were noted. Patients also undertook a processing speed test (PST). Scores from both tests were converted to a percentile based on age, education level, and gender, with percentiles of 1–30 categorized as poor performance. Results: For patients who had severe depression per the PHQ9, the INBT (for those in the poor performance category) had a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 50%. The PPV increased to 100% and the NPV to 77.8% for severe depression if poor performance on the PST was added to the INBT. The INBT alone had a PPV of 100% and an NPV of 33% for moderate to severe depression. Conclusion: In this study, poor performance on the INBT was predictive of moderate to severe depression. Poor performance on both this test and the PST was predictive of severe depression. A larger sample size may help clarify utility in real-world populations.

Background: Brain tumors cause psychiatric symptoms with frequency up to 78% but rarely are the sole manifestation of neoplastic disease. In a meta-analysis, psychotic symptoms occurred in 22% of patients, with pituitary gland and temporal lobes being the most common. There are reports of medullary tumors leading to anxiety, anorexia nervosa, and paroxysmal crying. This report presents first-episode psychosis (FEP) in a patient with a low-grade glioma within the left medulla who was otherwise neurologically intact. Case History: A man in the 5th decade of life, with a history of alcohol use disorder, major depressive disorder, type two diabetes, traumatic brain injury secondary to a physical assault earlier in life, and SARS-CoV-2 infection 2 months prior presented in police custody after stabbing his girlfriend. He reported suicidal ideations along with paranoid delusions of extraterrestrials following him and auditory hallucinations. The only diagnostic abnormality was a low-grade glioma within the left medulla found via magnetic resonance imaging. This lesion created slight mass effect on the foramen of Magendie. The connection between this glioma and the patient’s symptoms was not clear. He responded to sertraline and aripiprazole with no immediate intervention recommended for the glioma. Conclusion: This case highlights the role of neuroimaging in the workup of FEP. While the relation to FEP was unclear in this case, there are cases of medullary tumors leading to psychiatric symptoms. Lesions throughout the brain have been associated with psychosis. This case exemplifies the difficulty in distinguishing the possibility of a causal relationship.

Background: The clinical syndrome associated with chronic traumatic encephalopathy (CTE) is described in the NINDS Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES). One of the core clinical features of TES is neurobehavioral dysregulation (NBD), proposed as a unique neuropsychiatric syndrome. Preliminary steps have been taken to examine the construct of NBD, but further assessment of validity is necessary. Objective: To examine convergent and divergent validity of NBD subconstructs in former American football players. Methods: Factor analyses were performed to extract four subscales of NBD (i.e., explosivity, emotional dyscontrol, impulsivity, and affective lability) using data from the DIAGNOSE CTE Research Project. Pearson’s correlations were calculated between NBD subscales and the following standardized (neuro)psychiatric scales: Neuropsychiatric Inventory-Questionnaire (NPI-Q), Buss-Durkee Hostility Inventory (BDHI), Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA), Beck Hopelessness Scale (BHS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Results: Within the self-report scales, strong relationships were found for NBD-explosivity with BDHI (r=0.74, p<0.001) and BGLHA adult aggression history (r=0.58, p<0.001). Comparisons with external informant-based subscales (NPI-Q) also revealed the following high correlations: NBD-explosivity with agitation (r=0.44, p<0.001), NBD-explosivity with irritability (r=0.49, p<0.001), and NBD-impulsivity with disinhibition (r=0.44, p<0.001). Other comparisons provided evidence of both convergent and divergent validity. All four NBD factor scores showed stronger relationships with the BDI and BAI than with the BHS. Conclusion: The subconstructs of NBD demonstrate adequate construct validity. The results highlight the complex relationship between NBD and other psychiatric and neuropsychiatric symptoms in former American football players.

Background: Vascular depression is a widely accepted but nebulous diagnosis, combining a distinct constellation of clinical symptoms with associated cerebrovascular damage. Magnetic resonance imaging (MRI) techniques are used to diagnose vascular depression. Per recent data, the prevalence of vascular depression in adults over 50 years or older is 3.4% in the United States. Findings such as white matter hyperintensities, subcortical microvascular lesions, and microinfarcts are noticeable features commonly seen in vascular depression patients. Our case demonstrates these findings, and our interpretation and management are documented below. Case History: A 77-year-old lawyer presents to the hospital with 1 week of acute onset paranoia and depression, roughly 1 month after a transcatheter aortic valve replacement without significant complication. MRI demonstrated scattered punctate foci of restricted subcortical diffusion within the right frontal lobe, indicative of foci of evolving subcortical infarction, as well as chronic hyperintensity on FLAIR. These findings concern an underlying embolic etiology, potentially secondary to recent TAVR. The mental status examination of this patient was notable for not making eye contact, being guarded, nihilistic and persecutory delusions that encompass his family’s well-being, as well as a disorganized and tangential thought process. The patient was started on Sertraline and quetiapine and progressively uptitrated to aid with the findings presented above. Conclusion: The final examination showed remission of depressive symptoms and delusions, insight into how his vascular risk factors contribute to his mood and psychotic symptoms, his case will be utilized to present an evidence-based treatment algorithm for the treatment of vascular depression.

Background: Stress is a well-known risk factor to develop functional neurological disorders (FND). Only little is known about the biological stress regulation, and what might be the role of predisposing biological and psychosocial risk factors. Objective: To shed light on the underlying neurobiological mechanisms of FND, we analyzed the relationship between potential dysregulation of the Hypothalamic-Pituitary Adrenal (HPA) axis, trauma history, and structural brain abnormalities. Methods: We set out to study the HPA axis analyzing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure. Results: Patients had a significantly flatter cortisol awakening response (p<0.001) and reported longer (p=0.01) and more severe (p<0.001) emotional neglect as compared to heathy controls. Moreover, volumes of bilateral hippocampus and amygdala were found to be reduced in patients. Using a multivariate correlation analysis, we found an association between different attributes of trauma history and abnormalities in HPA-axis function in FND patients, whilst cortisol did not relate to reduced brain volumes (i.e., neurotoxicity). Conclusion: We suggest that psychological stress acts as a precipitating psychosocial risk factor, whereas a reduced brain volume potentially represents a biological ‘trait marker’ for FND, which might contribute to a reduced resilience to stress.

Background: RT-QuIC is a relatively new test which has been shown to be both sensitive (92%–95%) and specific (98.5%–100%) in the detection of sporadic Creutzfeldt-Jakob disease (sCJD). However, sensitivity is lower in some presentations and polymorphisms. Our case highlights the problems that can arise with overreliance on RT-QuIC in the diagnosis of CJD and discusses the functional neuroanatomy and neuropathology of an atypical CJD phenotype. Case History: A 77-year-old male presented with rapid cognitive decline. His symptoms began as isolated visuospatial impairment and quickly progressed to navigational difficulties, short-term memory impairment, expressive aphasia, parkinsonism, and myoclonic jerks of the upper extremities. MRI brain demonstrated biparietal atrophy but was read as negative for restricted diffusion. CSF testing was negative for RT-QuIC, with positive 14-3-3 protein, total tau 2029 units, and a low amyloid beta 42/40. An initial diagnostic formulation of posterior cortical atrophy with comorbid Alzheimer’s disease and Lewy body disease was made less than 2 years after initial symptom onset. Autopsy found prion disease with severe cortical atrophy with concurrent thalamic and olivary nuclei neuronal loss, most suggestive of an uncommon variant of sCJD with features of fatal insomnia. Conclusion: We present a case of RT-QuIC negative CJD, with subtle restricted diffusion on MRI, and clinical features of posterior cortical atrophy and fatal insomnia. Our case demonstrates the importance of multimodal assessment in rapidly progressive dementia and highlights an unusual clinical presentation of CJD.

Background: Criteria for the behavioral variant of frontotemporal dementia (bvFTD) require at least three of six clinical criteria, in addition to imaging, histopathological or genetic correlates. BvFTD phenocopy is a questionably progressive condition in which patients meet clinical but no other criteria. “BvFTD-by-proxy” is a term describing phenocopy cases in which reported behavioral evidence for bvFTD is provided by one informant, often a spouse in the setting of marital discord, which can make it difficult to obtain a reliable history. While bvFTD-by-proxy is a familiar phenomenon to many dementia specialists, there is a paucity of publications on how to recognize and manage this situation. Case History: We present three cases of patients with symptoms reported by spouses raising concerns for bvFTD. In all, progression was questionable, neuropsychological testing demonstrated mild but stable executive dysfunction, and physical examinations and neuroimaging were unremarkable. Independent evaluation of the patient and alternative explanations for the patient’s symptoms were often met with spousal resistance. Conclusion: The interpersonal and subjective nature of bvFTD diagnostic criteria may contribute to misinterpretation or inaccurate reporting by spouses in settings of marital discord. More insidiously, bvFTD-by-proxy may sometimes represent a form of factitious illness imposed on another or hypochondria-by-adult-proxy, increasing the risk of inappropriate control over the patient’s health care or finances, potentially constituting a form of abuse. Recognition and management of this situation is critical to ensure patient safety and appropriate family support. Best management is often time consuming and requires coordination of multiple health care providers.

Background: Behavioral variant frontotemporal dementia (bvFTD) is the most common clinical subtype of frontotemporal dementia (FTD), comprising approximately half of the cases of FTD. The hallmark of bvFTD is a progressive change in personality and behavior early in the disease course. These symptoms can be manifested similarly to major depressive disorder, obsessive compulsive disorder (OCD) or bipolar disorder. However, there is a limited background describing the overlap of symptoms of OCD versus bvFTD. Case History: A 56-year-old right-handed Caucasian male developed osteomyelitis and empyema after 4 years of compulsive excoriation rituals. However, on deeper investigation of his history, he also demonstrated profound personality changes, apathy, loss of empathy, limited insight, behavioral agitation as well as episodic memory loss. In addition to his progressive behavioral deficits, he had significant difficulties with executive functioning, leading to loss of his job and decreases in his instrumental activities of daily living. Imaging was obtained to aid in diagnosis and magnetic resonance imaging showed asymmetric enlargement of the right lateral ventricle and mild asymmetric parenchymal volume loss in the right hippocampus. 18-FDG-positron emission tomography imaging indicated severe hypometabolism in the right hemisphere. Given the clinical presentation, patient’s history, and neuroimaging findings, we concluded his diagnosis is more consistent with bvFTD. We will review the distinguishing clinical features between bvFTD and primary psychiatric disorders including OCD. Conclusion: The case illustrates the importance of distinguishing symptoms between other psychiatric disorders and bvFTD. More studies are needed to operationalize the distinction of these conditions in earlier stage.

Background: Depression is the most common psychiatric condition seen in PD. Previously, lower synaptic density was found in MDD, but this has not been studied in PDMDD. Here, we use in vivo PET to quantify synaptic density in PD with and without MDD. Objective: To characterize the distribution of (¹¹C)UCB-J, a marker for synaptic density, in Parkinson’s disease (PD) with major depressive disorder (PDMDD) compared to PD without MDD. Methods: We included 10 PDMDD subjects with a mean age (SD) (61 [7]; 4 males) and 12 matched PD subjects without MDD (62 [6]; 5 males). Binding potential value (BP_ND: the binding potential of available receptors) was the primary outcome measure with the centrum semiovale as the reference region. Muller-Gartner partial volume correction was applied to control for possible volumetric differences. Two-tailed t tests were calculated for between-group differences, and p values were uncorrected given the exploratory nature. Spearman correlations were used between (¹¹C)UCB-J BP_ND and Montgomery-Asberg depression rating scale (MADRS). Result: We observed significantly lower synaptic density in the PDMDD group compared to PD in the frontal cortex (−14%, p=0.05) and olfactory cortex (−15%, p=0.03), but higher synaptic density in the substantia nigra (41%, p=0.02). There were also significant negative correlations between MADRS and (¹¹C)UCB-J in the frontal cortex (r=−0.50, p=0.04) and ventromedial prefrontal cortex (r=−0.51, p=0.03). Conclusion: We present preliminary findings from the first study investigating synaptic density in PDMDD. Reduced synaptic density in the frontal cortex might play a role in MDD associated with PD.

Background: A “synaptic toxicity” hypothesis indicates the source of early events that eventually lead to neurodegeneration in bvFTD. Here we use in vivo positron emission tomography (PET) imaging with the synaptic vesicle glycoprotein 2A (SV2A) tracer 18F-SynVestT-1 to measure synaptic density in human. Objective: To examine the distribution pattern of 18F-SynVestT-1 in cortical and subcortical areas in bvFTD patients compared with healthy controls (HC). Methods: Three individuals (mean age [SD]: 69 [14]; two males) with bvFTD and three demographically matched healthy comparison controls (HC; 53 [3]; two males) participated in 18F-SynVestT-1 PET scans. Volume of distribution (VT: distribution of the tracer) was the primary outcome measure and computed with one tissue model. The freesurfer-segmented regions were merged to produce segmented regions. T tests were calculated for between group differences, and p values were one tailed, uncorrected for multiple comparisons given the exploratory nature. Results: We observed lower synaptic density in bvFTD patients compared to HC in multiple areas including the medial orbitofrontal lobes (−13%, p=0.25); frontal pole (−8%, p=0.20); superior temporal gyrus (−17%, p=0.12); middle temporal gyrus (−19%, p=0.12); entorhinal gyrus (−25%, p=0.11); temporal pole (−23%, p=0.15); anterior cingulate cortex (−14%, p=0.12); insula (−16%, p=0.15). Conclusion: These preliminary findings of statistically nonsignificant lower SV2A in bvFTD using 18F-SynVestT-1 PET imaging will be followed up with larger sample size to understand further if this novel imaging has the potential to improve early diagnoses and accurately monitor bvFTD progress.

Background: Delayed neuropsychiatric syndrome (DNS) is a sequela of carbon monoxide (CO) poisoning that occurs days to months after exposure and possesses neuropsychiatric manifestations, including psychosis. Development of DNS corresponds poorly to carboxyhemoglobin (COHb) levels, but most cases occur with loss of consciousness (LOC) during acute exposure. We present a case of new-onset psychosis in a patient with no psychiatric history, no LOC, and high-normal COHb levels after exposure to CO. Case History: A 59-year-old woman presented to the emergency department with a chief complaint of a 4-month history of generalized body aches and tingling in her fingers. She had been living in a government-subsidized apartment for 6 months and was convinced that her neighbors/landlord were poisoning her. Her COHb level was 2.2% in the ED. She was placed under a temporary detainment order and admitted to inpatient psychiatry for the management of paranoia and delusions. She believed there was poison in her showerhead and had been utilizing jugs of water for drinking and bathing. On discussion with her family, they endorsed that the patient had a life-long history of paranoia. Risperidone was added to manage her psychotic symptoms. While hospitalized, the patient’s gas company identified the gas leak and ultimately deemed her home safe. Throughout the admission, the patient showed improvement in paranoid delusions and was safely discharged home. Conclusion: This abstract explores the possible neuropsychiatric manifestations of chronic, sublethal carbon monoxide poisoning. It highlights the importance of discussion and research on CO poisoning, particularly in the socioeconomically disadvantaged.

Background: Language can reorganize to the right hemisphere following left hemisphere injury early in life. In 1969, H. Lansdell showed an inverse association between the age of injury, preservation of verbal skills, and loss of nonverbal skills in a group of patients with left hemisphere injury and right hemisphere speech. We describe two cases of right hemisphere dysfunction in the setting of left hemisphere injury early in life. Case History: Case 1: A 31-year-old man with a history of ruptured left occipital arterial venous malformation at age 8 and intractable left frontotemporal epilepsy presented for evaluation of mood and was found to have reduced social engagement, blunted affect, reduced expressive prosody, and 8/12 correct on Brook’s E test. Case 2: A 30-year-old man with history of left temporal epilepsy due to left temporal cyst resected at age 13 presented for evaluation of psychosis and was found to have abnormal left horizontal saccades, subtle left arm weakness, reduced ability to identify global features on Navon figure, and unawareness of double entendre. Conclusion: These cases suggest a phenomenon we refer to as “cognitive steal” resulting from the prioritization of language development over right hemisphere functions following left hemisphere injury early in life. Right hemisphere deficits may limit life skills, occupational success, relationships, and lead to a potential misdiagnosis as a primary psychiatric disorder. It is important that providers recognize this phenomenon and evaluate right hemispheric functions in patients with left hemisphere injury, particularly when it occurs early in life.

Background: Rapid advancements in the field of neuroscience have not been mirrored by a development of adequate and effective neuroscience teaching in psychiatric training. For learners, a traditional, lecture-based teaching style of neuroscience is often uninteresting and underemphasizes the clinical relevance of neuroscience. Alternative teaching methods are needed. Objective: To evaluate the effectiveness of a case-based, interactive teaching style to teach neuroscience for residents at Beth Israel Deaconess Psychiatry Residency Program. Methods: Five 45-minute-long teaching sessions are implemented for 10 first-year residents at the aforementioned residency. The format of every session includes discussion of a clinical case, role playing, and review of underlying neuroscience concepts. Pre- and postsurveys are administered to assess residents’ level of interest in clinical neuroscience and comfort in discussing learned concepts with patients, using Likert scales from 1 to 5. Results: 7 and 4 participants completed the pre-survey and postsurvey, respectively. A mean and median of 4.14/5 and 3.5/5 in the pre-survey, and 4/5 and 3.5/5 in the postsurvey are reported for level of interest in neuroscience. A mean and median of 2.71/5 and 2/5 in the pre-survey, and 2.75/5 and 3/5 in the postsurvey are reported for comfort level in discussing neuroscience concepts with patients. Conclusion: No significant change in comfort nor interest levels are identified between pre- and postsurvey results. Results are limited by small sample size. Further data collection is underway as teaching sessions will be repeated.