2020 American Neuropsychiatric Association Annual Meeting Abstracts

Background: Tetanus is a vaccine-preventable disease, rare in high-income countries but remains a significant cause of morbidity and mortality for children and adults in many low-income countries. The bacterium toxin Clostridium tetani causes the disease. It presents with muscle spasms and autonomic dysfunction. In low-income countries, an increased incidence and disease outbreak is attributed to a low immunization rate compounded by the types of injuries, minimal access to care and supplies, and the delay in treatment without access to mechanical ventilation resulting in higher mortality and morbidity. Methods: A case-series of 5 patients with tetanus related morbidity-mortality presenting over the period of 6 months to the Hargeissa Group Hospital in Hargeissa, Somaliland. Somaliland is a self-proclaimed state in East Africa internationally considered as an autonomous region of Somalia. Cases affect both genders, range from 16 to 50 years old and present with different symptoms and outcomes with a common denominator of total body stiffness and spasms. Patients were often treated with anti-inflammatory medications for their somatic complaints delaying access to the correct life-saving treatment aiming at controlling spasms and autonomic instability, administering wound care, antitoxin, and antibiotics. Recent protocols include intravenous magnesium sulfate, antitoxin administration and access to mechanical ventilation. Patients require long hospitalizations and are vulnerable to increased secondary infections. Conclusion: Neuropsychiatrists practicing or supervising care in low-income countries should be able to recognize tetanus disease and become familiar with life-saving treatment protocols and patients’ immunization. They would educate all healthcare professionals about this serious, yet preventable, disease.

Background: Functional Movement Disorders (FMD’s) are broadly defined as abnormal movements without a known neurological lesion or cause. Dystonia can be classified as either functional or “organic,” with geste antagoniste (or a sensory trick) considered to be a cardinal feature of the latter. This case report demonstrates the use of geste antagoniste to alleviate a myriad of functional movements involving tremor, chorea, and abnormal gait. Case History: The case is a 40-year-old woman with type 2 diabetes, remote history of tremor while undergoing divorce, anxiety, depression, and alcoholism who developed a right-hand tremor after stubbing her right toe. This quickly progressed to disabling whole-body movements of various semiologies, followed by an unremarkable extensive work-up. These movements are responsive to various sensory and motor tricks, which will be demonstrated with video. Despite the above definition, newer research highlights abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and amygdala in FMDs. It has been hypothesized that DLPFC and SMA connectivity are important for the premonitory sensation of the intention to move, which may be bypassed in FMDs due to decreased connectivity and overactivity in the SMA. PET studies have also shown decreased SMA activity with increased activity in the parietal cortex during the use of a sensory trick in sensory trick-responsive cervical dystonias. Conclusion: A reflection of the division between Psychiatry and Neurology as a whole, the observation of geste antagoniste in this case illustrates the arbitrary nature of the division between FMD’s and “organic” movement disorders.

Background: Memory impairments are common chronic and functionally important consequences of traumatic brain injury (TBI) and may reflect persistent posttraumatic cholinergic deficits. Donepezil (an acetylcholinesterase inhibitor) therefore may improve persistent verbal memory problems after TBI. Objective: To evaluate the efficacy of donepezil 10 mg daily on a) verbal memory problems, b) memory-related limitations in everyday function, and c) other cognitive, neuropsychiatric, functional, and caregiver problems in the chronic period following complicated mild, moderate, or severe TBI. Methods: This four-site, randomized, parallel-design, double-blind, placebo-controlled, clinical trial recruited persons with severe, persistent, and functionally limiting verbal memory problems at least six months postinjury. Randomized participants were assessed on study efficacy, safety, and tolerability measures at prescribed intervals over 10 weeks. Results: Seventy-five participants were randomized to treatment (donepezil N=37, placebo N=38). Both the mITT and per protocol analyses demonstrated donepezil efficacy on the primary outcome (HVLT-R Total Trials 1–3) (p=0.034, d=0.44, and p=0.036, d=0.45, respectively). Donepezil and placebo response rates were 42% and 18%, respectively (p=0.027, NNT=3.5). Among donepezil responders, delayed recall and processing speed also improved significantly. Treatment-emergent adverse event rates to donepezil and placebo were 46% and 8%, respectively. The majority (85%) of treatment-emergent adverse events to donepezil were mild or moderate; only diarrhea and nausea were significantly more common in the donepezil group. Conclusion: This study demonstrates donepezil efficacy on severe, persistent memory impairments after predominantly severe TBI as well as a relatively favorable safety and tolerability profile. The clinical implications of these findings are discussed.

Background: Primary neurological illness can mimic severe mental illness with symptoms of hallucinations, behavioral changes, delusional content, and even manic behavior. Patients with these diagnoses are frequently misdiagnosed with primary psychiatric diagnoses due to nonspecific clinical symptoms, lack of pathognomonic imaging findings, and limited availability of rapid testing. This lag in correct diagnosis may negatively impact management and intervention, particularly in the geriatric population. Case History: A 72-year-old female presenting with paranoid delusions and auditory hallucinations, initially diagnosed with schizophrenia. Cognitive testing revealed global cognitive deficits and patient was subsequently diagnosed with major neurocognitive disorder with behavioral disturbance. 63-year-old female presenting with severe cognitive disorganization, mood lability, intrusiveness, paranoia, and inability to care for herself. No response to escalating antipsychotic medications; patient was diagnosed with schizoaffective disorder. She was later found to have a positive serum anti-NMDA receptor antibody thus diagnosed with suspected autoimmune encephalitis. 71-year-old male with premorbid bipolar disorder and history of catatonia who presented with worsening cognition, poor self-care, amnesia, apathy, and dysexecutive syndrome. Initially diagnosed with FTD, later found to have elevated anti-CASPR antibodies in the serum. Diagnosed with autoimmune encephalopathy causing FTD-like symptoms with improvement in cognition following steroid treatment. Conclusion: Patients presenting with cognitive and behavioral disturbance due to neurological illness may be misdiagnosed with primary psychiatric disorders. Delay of diagnoses in this population can cause increased morbidity and mortality. Consideration of age of diagnosis, change from baseline functioning, and response to medication can help indicate need for further cognitive and immunological testing.

Background: Tight correlation between clinical status and tau distribution in Alzheimer’s Disease (AD) patients has been observed in clinicopathological studies. Given that tau progresses serially and sequentially through predictable anatomical regions involved in canonical brain-behavior relationships, we hypothesized that clinical variables could be used to approximate the Braak stage distribution of subjects’ AV-1451 uptake. Objective: Our aim was to evaluate the accuracy of clinically available variables in predicting Braak-like anatomical distribution of AV-1451 with machine learning models. Methods: We included 689 Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects with baseline AV-1451 imaging, amyloid status, MRI hippocampal volume, neuropsychological scores, and clinical questionnaires. In a training subset we used an evolutionary algorithm (PBIL) to select the most important variables for estimating AV-1451 standard uptake value ratios (SUVr). Using PBIL-selected variables for regression, we then estimated each subject’s AV-1451 SUVr values in regions of interest (ROI) correlating with Braak staging. Finally, on a held-out test group we applied SUVr thresholds and ordinal forests regression to Braak ROIs to estimate exact and approximate Braak distribution of tau according to two diagnostic schemata. Results: In the test subset the model estimated exact Braak-like stage with 67.9% accuracy, within-one Braak-like stage with 71.8% accuracy, exact adapted Braak-like stage with 66.7% accuracy, and within one adapted Braak-like stage with 78.2% accuracy. Conclusion: With machine learning models, easily accessible clinical variables are able to estimate Braak-like and adapted Braak-like distribution of AV-1451 positivity with a moderate degree of accuracy.

Background: Moyamoya disease (MMD) is a rare, idiopathic, progressive cerebrovascular disorder characterized by stenosis of the intracranial internal carotid artery, with frequent extension to the anterior and middle cerebral artery and compensatory formation of collateral vessels resulting from reduced blood flow in the anterior circulation of brain. It has a bimodal distribution regarding age with one peak at around 10 and other is at mid-40s. Possible genetic association makes MMD more prevalent in South East Asia than Western countries. Common manifestations of MMD are ischemic stroke, TIA, hemorrhage (common in adult), headache, and seizure. Though coincident complaint of anxiety and depression in adults with focal neurological deficit are reported but isolated neuropsychiatric manifestations in MMD are rare. Especially in children, it is really challenging for clinicians to reach the diagnosis of MMD based on initial neuropsychiatric presentations that precede neurological signs and symptoms. Case History: A 7-year-old Bangladeshi, right handed, school going male child from nonconsanguineous parents with normal birth and developmental history, with PMH of fall (possible TIA) and no psychiatric history presented with sudden onset behavioral changes—irritability, emotional lability, hyperactivity, loss of attention, and poverty of speech. Initial blood works including coagulation studies and echo came negative. MRA was done and suggestive of MMD. Neurosurgical correction was done and patient showed improvement in subsequent follow-ups. Conclusion: Understanding and obtaining the temporal profile of symptoms are very important in MMD as patient might have a wide spectrum of neuropsychiatric manifestation beside focal neurological signs.

Background: Focal brain lesions can cause confabulation, a type of memory error in which false information is conveyed by the patient as true. A common distinction is made between provoked and spontaneous confabulations, the latter being hypothesized to occur in the setting of amnesia with frontal dysfunction. Lesions in several nonoverlapping locations can result in spontaneous confabulation, thus making the neuroanatomic localization difficult to define on a structural basis alone. Objective: To determine if lesions leading to spontaneous confabulation localize to a unique network of brain regions. Methods: 26 cases of spontaneous confabulation were identified in the medical literature. We utilized a technique called lesion network mapping to determine brain regions that were functionally connected to each lesion. We compared this network to a network recently linked to lesions causing amnesia (N=53) using a two-sample t test. Results: Greater than 85% of lesions causing spontaneous confabulation were positively connected to a brain network including bilateral mamillary bodies, anterior cingulate cortex, hippocampus, parahippocampal gyrus, and cerebellar vermis, and negatively connected to the bilateral lateral occipital cortex and superior parietal lobule (t>7, p<10⁻⁶). When compared with a prior network associated with amnesia, we found greater network connectivity in the bilateral orbitofrontal cortex, ventral frontal pole, inferolateral temporal cortex, and inferior cerebellar vermis (FWE, p<0.05). Conclusion: Our results identify a causal substrate for spontaneous confabulation that is dissociable from a network causing amnesia. Future work is planned to use the network defined herein to predict presence of confabulation in an independent dataset.

Background: The effect of levodopa has been measured using regional cerebral blood flow (rCBF) to reflect regional brain activity. Levodopa’s rCBF effects mirror its regional effects on glucose metabolism and are most prominent in pons and midbrain. However, the timing of these responses has never been reported. Clinical effects of levodopa follow different time courses in earlier versus later Parkinson disease (PD). Objective: We hypothesized that levodopa-induced rCBF changes would mirror the time course of its clinical effects, and potentially could provide an objective marker of disease severity (see bioRxiv 817106). Methods: Participants included 17 people with PD who after taking no antiparkinsonian medications after midnight completed structural MR images and up to 2 hours of 3D GRASE pCASL perfusion images (postlabel delay 2.0 s). These were converted to CBF images (each with duration 34 s), normalized, aligned to atlas, and motion scrubbed. After carbidopa 200 mg p.o., levodopa was given intravenously as a 10-min bolus followed by a slow infusion (bioequivalent to about 80mg oral). SPM was used to analyze mean on-drug versus predrug CBF (protocol at osf.io/ezb6n). Results: Motor function improved significantly with i.v. levodopa. rCBF increased significantly in right superior parietal lobule and also increased in midbrain. However, the time courses of midbrain and cortical volumes of interest were quite variable across subjects. Conclusion: Personalized imaging depending on the time course of perfusion responses to levodopa may require improved imaging methods. Alternatively, activity in other brain regions may reflect the timing of levodopa’s clinical effects.

Background: Neurosarcoidosis is a relatively rare form of sarcoidosis which can present with a wide variety of clinical neuropsychiatric manifestations, including psychosis. While neurosarcoidosis presenting as catatonia has not previously been described in the literature, many other central autoimmune disorders have been associated with catatonia, including limbic encephalitis and neuropsychiatric lupus. Case History: A male in his 30s with a medical history of neurosarcoidosis (not on steroids at the time of admission) and no previous psychiatric history was transferred from an outside hospital for mental status changes. Eight years prior to admission (PTA), the patient had a pulmonary workup where a sarcoidosis diagnosis was established. Four years PTA, the patient had an MRI read as neurosarcoidosis. During this time, he was still high functioning and socially engaged. Approximately 12 months prior to admission, however, he developed speech deficits, odd behaviors, hypersomnia, psychomotor slowing, and recurrent falls. A broad infectious and metabolic work-up was negative. CSF studies revealed elevated protein but no other evidence of central autoimmunity or infection. EEG demonstrated moderate encephalopathy without epileptiform activity. MRI of the brain showed diffuse leptomeningeal enhancement consistent with progression of neurosarcoidosis. On psychiatric evaluation, the patient was mute and negativistic. Physical examination was notable for echopraxia, increased muscle tone, and resistance to passive movement. Bush-Francis Catatonia Rating Scale score was 32. Conclusion: To our knowledge, this is the first reported case of catatonia secondary to neurosarcoidosis. Central autoimmune conditions, including neurosarcoidosis, should be on the differential diagnosis of presentations of catatonia.

Background: Phenomenon of inattentional blindness is a failing of perception for a salient but unexpected event or feature of the surrounding environment. Inattentional blindness has been studied in individual subjects but few studies have examined if this perceptual phenomenon exists on group level. Objective: This study aimed to synthesize existing data on group level observations of inattentional blindness. Methods: 1) Review of the literature on inattentional blindness; 2) query the literature for evidence of existence of inattentional blindness to perception by groups, and not only in individual subject perception. Results: Groups and teams are susceptible to change blindness just as individuals are. Some evidence suggests that teamwork and communication are beneficial in reducing change blindness susceptibility. Conclusion: These findings are used to consider relationship of individual and group perception, and to consider the implications of group level inattention to certain aspects of our surroundings. As reality-based belief is built upon consensus, revealing the blind spots of our not only individual but also group perceptual capacity is imperative to understanding how reality-based belief is constructed.

Background: Psychosis is more frequently diagnosed in seizure patients when compared with the general population. We conducted a retrospective cohort study to examine risk factors associated with a diagnosis of psychosis not otherwise specified (NOS) among veterans with seizures. Objective: Characterize psychosis NOS in veterans with seizures. Methods: Electronic health records of post-9/11 veterans were extracted (N=801,883) to identify veterans with a diagnosis of epilepsy (N=10,994), psychogenic nonepileptic seizures (PNES) (N=751), and general sample without reported seizures (N=790,068). We conducted multivariate analysis to compare risk factors across the groups. Results: In our cohort, 31% of the PNES, 28% of the epilepsy, and 5% of the general veterans were coded for psychosis NOS. Between the PNES sample and general veteran sample, the following conditions were prevalent, respectively: drug abuse 36%, 27% (OR 1.5, p<0.001), major depression 49%, 36% (OR 1.7, p<0.001), and PTSD 91%, 77% (OR 2.8, p<0.001). Conclusions: When veterans were diagnosed with PNES and drug abuse, mild depression, or PTSD, they were more likely to be coded for psychosis NOS than veterans without seizures. The diagnosis of psychosis NOS in veterans with seizures may reflect clinicians’ uncertainty regarding presenting symptoms or mistaking symptoms of these conditions for psychosis. The large proportion of psychosis NOS may also be due to coding error. Future research will identify specific causes for the diagnosis of psychosis NOS coding in veterans with seizures.

Background: Although rTMS has been FDA approved for treating depression and more recently OCD, we are unclear about how it causes brain changes. A mechanistic rationale is essential to guiding therapeutic approaches. Objective: Animal studies support a hypothesis that 10 Hz rTMS may work through long-term potentiation (LTP), a form of synaptic plasticity. In humans, several studies have found n-methyl-d-aspartate (NMDA) receptor activity, a critical step in the LTP pathway, to be necessary but not sufficient for theta burst stimulation (TBS)-induced motor plasticity. However, pharmacologic studies in unpaired, unpatterned 10 Hz rTMS (as used clinically) have never been reported. We aimed to test the hypothesis that TMS changes the brain through synaptic plasticity. Methods: 10 healthy young adults participated in a randomized, double-blind, crossover study. We excluded those with conditions which would affect plasticity, those with TMS contraindications. Participants received 100 mg d-cycloserine or placebo ∼2 hours before rTMS. Motor-evoked potentials (MEPs) were recorded before rTMS (baseline) and after rTMS at 15-minute intervals to 60 minutes. Results: MEPs obtained after rTMS were further potentiated when participants had been given NMDA receptor partial agonist DCS prior to rTMS, compared with placebo (F=4.48, df=62; p=0.038). We used a general linear mixed model for continuous outcomes with a random effect for repeated measures accounted for in our statistical model of medication effect. Our statistical model also controlled for visit order, time, and condition-time interactions. Conclusion: We report that NMDA receptor partial agonism was sufficient to enhance rTMS-induced motor plasticity, tenably through LTP.

Background: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a commonly used screen of neuropsychological performance. A 5-factor structure is used when scoring this measure, revealing composites used in clinical diagnosis (Immediate Memory; Visuospatial/Constructional; Language; Attention; Delayed Memory). This structure has been supported in a sample of older adults with cognitive impairment. However, a 5-factor structure has not been consistently observed. Rather, in a sample of veterans, a 2-factor solution was noted, as was in a large exploration of past RBANS studies. Objective: We explored the factor structure of the RBANS in patients with Huntington’s Disease (HD). Methods: Participants were 147 patients with HD who presented to an outpatient HD clinic at UConn Health Center, Mage=46.75, SD=13.35; Meducation=13.87, SD=2.63. Results: Exploratory principal component factor analysis with direct Oblimin rotation was conducted. A 2-component structure was found with eigenvalues>1 (65.1% variance). Contrary to expectations from other clinical samples, we did not find the traditional 5-factor solution. Rather, results revealed a 2-factor solution. Factor loadings generally are comprised of visually-loaded versus non-visually-loaded tasks. Conclusion: Results revealed a 2-factor structure of the RBANS in a sample of patients with HD, contrary to the traditional 5-factor solution typically derived into composite scores with this measure. Our findings suggest that HD patients may not perform on the RBANS in a traditional manner. Thus, clinicians evaluating HD patients should exercise caution when using composite scores when considering patient performance on this measure.

Background: Obsessive-compulsive disorder (OCD) is thought to involve hyperactivity in the cortico-striato-thalamo-cortical (CSTC) loops underlying the orbitofrontal cortex (OFC) and the anterior cingulate cortex. The OFC circuit is associated with response inhibition and impulse control. However, variability in treatment response suggests phenotypic heterogeneity. Subtypes are based on symptom profile (motor), affected area (subcortical) or possible causative mechanisms (infection/TBI). Indeed, neurological soft signs are increased in OCD but variable. Objective: Caramelli et al. found 40% (6/15) of OCD patients had bilateral palmomental “frontal release” reflex (PMR). The PMR is a sensitive “frontal” marker which is observed in nonill family members of OCD, Parkinson’s disease and some “normal” volunteers. We sought to determine the prevalence of bilateral PMR in OCD patients. Methods: We selected 493 consecutive outpatients in a CMHC. A diagnosis of OCD made in 23 patients (21 female) with mean age 38.7±9.9 years (range 26 to 63, median 37.1). Comorbid psychiatric diagnosis was present in 22 patients. Records were reviewed for the presence of bilateral PMR on any examination. Results: Bilateral PMR was observed in 19 OCD patients (83%). Three patients had only unilateral PMR, and 1 patient had no PMR. Variability in PMR was observed including unilateral and normalization in all but 2 patients who never normalized (ages 29 and 63). Mild tremor was seen in 13 patients. Conclusion: Bilateral involvement is present in the majority of these OCD patients. Variability is common with PMR. The PMR “frontal release” reflex may identify a subtype of OCD.

Background: Primary progressive aphasia (PPA) is characterized by gradual-onset aphasia associated with left perisylvian damage, and later cognitive deficits. PPA often presents nonclassically. Comorbid neuropsychiatric symptoms complicate diagnosis. To our knowledge, there is only one previously reported case of PPA with psychosis. Here we describe another patient exhibiting PPA symptoms and psychosis. Case History: A 27-year-old male with no prior psychiatric history presented to the Emergency Department (ED) for profound hypoglycemia and visual hallucinations, having been found walking barefoot on a highway. He was hospitalized for acute encephalopathy. Drug screen, CT head, electroencephalogram were negative. Per family, patient became progressively isolated after quitting high school. He was discharged with encephalopathy, hypoglycemia, and mineral deficiencies. Follow-up Montreal Cognitive Assessment (MOCA) was 26/30, with word-salad response on sentence repetition, and unremarkable subsequent MRI. Seven months later, he was readmitted for anxiety, confusion, and rambling incoherently. Neurology suspected PPA, PET scan showed hypometabolism in the right Rolandic operculum and middle frontal gyrus. Lumbar puncture and work up for autoimmune etiologies were inconclusive. He was discharged with Wernicke aphasia, cobalamin deficiency, and acute encephalopathy. He was eventually admitted from the ED to psychiatry two weeks later for new-onset psychotic symptoms, with anxiety, visual hallucinations, and dysarthria. Risperidone was initiated and titrated to 3 mg BID, with improvement of psychosis. Subsequent, MOCA’s ranged 23–24/30 with inconclusive neuropsychiatric evaluation. Conclusions: Diagnosing PPA with comorbid psychosis can be challenging given the difficulty of assessing characteristics of thought in a patient with limited language production.

Background: Psychiatric comorbidity is disproportionately represented in patients with epilepsy compared with the general population and contributes to compromised seizure control, increased adverse effects from antiseizure medications, and increased overall disability. Electroconvulsive therapy (ECT) is an effective treatment for depression, psychosis, and other psychiatric conditions that commonly occur in patients with epilepsy. In patients with epilepsy undergoing ECT, antiseizure medications can limit the ability to induce therapeutic seizures; however, reductions of antiseizure medication dosing to facilitate ECT may increase the risk of potentially harmful epileptic seizures during the course of therapy. Case History: A 51-year-old man with epilepsy, intellectual disability, cerebral palsy, and obsessive compulsive disorder exhibits symptoms of a severe depression with psychotic features. Given historic lack of response and poor tolerability of medications, ECT is pursued. Contrary to the literature which describes adjustment of antiseizure medications to facilitate ECT to be infrequent, this report details numerous alterations that were required to enable effective ECT while minimizing the risk of breakthrough potentially harmful epileptic seizures. Conclusions: At multiple points in treatment, the frequency of ECT and the dosing of antiseizure medication were adjusted after a risk-benefit decision involving neurology, psychiatry, the patient, and his family. These adjustments occurred both in the inpatient and outpatient settings and during both the acute and maintenance phases of ECT. In the future, clearer guidance for antiseizure medication adjustments when necessary to facilitate effective ECT would promote optimal patient care.

Background: SREAT is variable in neurologic/psychiatric presentation. The pathophysiology is poorly understood, however the disease responds to immunosuppressant therapy. Due to ill-defined diagnostic criteria, SREAT is likely under diagnosed. Case History: A 47-year-old woman with hypothyroidism and no psychiatric history presented with subacute bizarre behavior. Due to elevated TPO-Ab she was treated with 250mg IV methylprednisolone followed by 30 mg prednisone for 7 days. Treatment was discontinued due to lack of rapid improvement. Upon transfer to state psychiatric hospital, she displayed rapidly fluctuating mental status and bilateral hippus; concerning for nonconvulsive status epilepticus. EEG was reassuring. MRI revealed bifrontal and caudate lesions. Given her atypical psychiatric presentation, and presumed incomplete treatment for SREAT she was treated with a 7-day course of IV steroids followed by oral prednisone with prolonged taper. She tolerated treatment well, with improved cognition and mood. After completion of taper, she experienced increased psychomotor agitation, tangential thoughts, intrusiveness, paranoia, and decreased sleep. Repeat TPO antibody, TSH, and free-T4 suggested recurrent thyroiditis; MRI was reassuring against structural damage. She was restarted on high dose steroids with good response in cognitive and behavior. Thyroid studies normalized. Conclusions: This case illustrates the importance for a high clinical suspicion and adequate treatment for SREAT in the setting of elevated TPO-Ab and atypical psychiatric symptoms. There is still need for a more thorough understanding of the pathophysiology, diagnosis, and treatment of SREAT.

Background: ADHD is a neurodevelopmental disorder associated with significant morbidity and mortality that affects 5% of children, adolescents and adults worldwide. Pharmacological and behavioral therapies exist, but critical symptoms such as dysexecutive deficits remain unaffected. Objective: To assess the cognitive and physiological effects of transcranial Direct Current Stimulation (tDCS) in adult ADHD patients in order to understand (1) the role of dorsolateral prefrontal cortex (DLPFC) laterality in ADHD dysexecutive deficits, (2) the physiological dynamics sustaining the modulation of executive function by tDCS, and (3) the impact of baseline physiological state on tDCS modulation. Methods: In a randomized, placebo-controlled, double-blind, cross-over study 40 adult ADHD patients performed three experimental sessions in which they received 30 minutes of 2mA tDCS stimulation targeting the left versus right DLPFC versus sham. Before and after each session, half of the participants completed the Flanker task (EFT) and the other half performed the Stop Signal Task (SST) while we assessed behavioral performance and EEG. Results: Anodal tDCS to the left DLPFC modulated cognitive (reaction time) and physiological measures (P300) of cognitive control in the EFT in a state-dependent manner, but there were no significant effects in the Stop-Signal-Reaction-Time of the SST. Conclusions: We describe procognitive effects in adult ADHD patients associated with the modulation of physiological signatures of cognitive control, linking target engagement with clinical benefit, providing mechanistic support for the state-dependent nature of tDCS, and providing empirical evidence of the value of the ERPs as cross-sectional biomarkers of cognitive performance.

Background: Isolated strokes of the anterior cingulate cortex (ACC) are relatively rare, with few case reports in the literature, but they have been known to cause apathy, abulia, and akinetic mutism. It is not uncommon for consulting psychiatrists to be asked to assist in motivation to participate in acute rehabilitation when depression and apathy are present. While poststroke depression is relatively well understood, it can be difficult to know when repeat neuroimaging is warranted in the setting of poststroke depression with new behavioral features. Further, negativism from catatonia and abulia are phenomenologically quite similar. Case History: Shortly after entering rehabilitation for a pontine infarct, a 72 [year old] female with no past psychiatric history developed an acute episode of mutism and abulia after several days of refusing her warfarin. ECT was initially recommended for presumed poststroke major depressive disorder complicated by catatonia, but after a negative lorazepam-challenge and repeat MRI brain, a new infarct in her left anterior cingulate cortex was found, likely explaining her acute behavioral change. She responded quickly to a psychostimulant-challenge with resolution of her akinetic mutism. Conclusions: Acute changes in the quality of depression with abulic features should lead the astute clinician to evaluate for damage to the frontal lobes and basal ganglia. Neuropsychiatric manifestations of anterior cingulate cortex damage, similarities and differences of akinetic mutism and catatonia, and psychostimulant treatment for abulia are discussed.

Background: Neuropsychiatric systemic lupus erythematous (NPSLE) refers to the neuropsychiatric involvement found in the autoimmune condition SLE, and carries increased risk of mortality. NPSLE syndrome, which may include headache, mood changes, psychosis, catatonia, and cognitive dysfunction, is more common in pediatric-onset SLE in the first year of diagnosis. SLE is generally treated with steroids and if severe, cytotoxic and immunotherapeutic regimens. NPSLE offers unique challenges, as SLE treatments can exacerbate psychiatric symptoms and psychiatric medications may not provide typical benefit. Case History: A healthy 17-year-old male developed new onset psychosis, catatonia, cognitive dysfunction, fever, rash, and joint pain over 2-weeks, resulting in a diagnosis of NPSLE based on SLE American College of Rheumatology Criteria. Hospitalization (>100 days) was complicated by macrophage activation syndrome, DVT, progressive global atrophy on brain MRI, and severe behavioral disturbance. Management of NPSLE included steroids, cyclophosphamide, rituximab, bortezomib, hydroxychloroquine, and IVIG with minimal effect on the patient’s distressing psychosis and catatonia. Psychosis was challenging to treat as catatonia worsened with multiple low-dose trials of atypical antipsychotics, despite >20mg/day lorazepam therapy. Robust response in cognition, psychosis, and catatonia occurred when electroconvulsive therapy (ECT) was added. Conclusion: This case illustrates potential challenges in treating neuropsychiatric symptoms of NPSLE, with slow time to immunotherapy response and conflicting treatments for psychosis and catatonia. ECT, when combined with medical treatment of SLE, contributed to the rapid and significant improvement of neuropsychiatric symptoms. Considering ECT in the treatment of pediatric patients with NPSLE may offer earlier symptom improvement in complex presentations.

Background: The combination of posttraumatic stress disorder (PTSD) with traumatic brain injury (TBI) produces a syndrome more severe than PTSD or TBI alone based on prior clinical reports. Both PTSD and TBI produce a long-lasting neuroinflammation, which potentially contributes to their chronic affective and cognitive deficits. Objective: To study the interaction of TBI and PTSD using animal models. Methods: Using C57BL/6 mice, five groups of mice received either: 1) Sham-treatment 2) closed head injury (CHI), a model for TBI 3) chronic variable stress (CVS), a model for PTSD, or two models of combined TBI & PTSD that differed in the order of the insults, 4) CHI → CVS, 5) CVS → CHI. Results: The CVS → CHI group had significantly larger cognitive deficits based on performance on a spatial task, Barnes Maze, and acquiring the area of shock zone in the Active Place Avoidance (APA) task. The cognitive and affective deficits of CVS→CHI group were accompanied by increased hippocampal inflammation as measured by Iba−1 and Arginase-1 levels. Conclusion: These results support a central role of neuroinflammation in inducing neurobehavioral deficits. The combined CVS → CHI model had persistent memory and cognitive deficits. The neurobehavioral deficits were accompanied by alteration of Iba−1, tau phosphorylation level, as well as TDP-43.

Background: Lesion studies in primates have shown a critical role of the mediodorsal (MD) thalamus in facilitating rapid reward-guided updating in stochastic reward environments. This manifests as a reduced influence of recent past choices and outcomes on behavior particularly when the environment is in flux. We tested whether human MD thalamic injury produces a similar alteration in decision making. Case History: The patient was a 62-year-old right-handed man with paroxysmal atrial fibrillation who developed sudden onset apathy, retrograde and anterograde amnesia, sleep cycle dysregulation, hypersexuality, paranoia, irritability, dysnomia and pseudobulbar affect following bilateral thalamic injury from an artery of Percheron stroke. We compared the MD patient’s performance on a probabilistic three-arm decision-making task to 22 age- and education-matched Healthy Controls. We also performed an agnostic, data driven whole-brain multivoxel pattern analysis (MVPA) of resting-state functional-connectivity (RsFc) in the MD patient compared with Healthy Controls. Conclusion: Behavioral results showed a significant reduction in the influence of immediate past choices and outcomes on current choice in the MD patient compared with Healthy Controls (p=0.046) suggesting diminished contingent learning. Whole-brain MVPA revealed two clusters of altered connectivity in the right hippocampus and anterior cingulate cortex in the MD patient compared with Healthy Controls (FDR-corrected height threshold p<0.001; cluster-level threshold p<0.05). These findings suggest a possible neurobehavioral mechanism underlying the role of MD thalamus in adaptive decision making in humans.

Background: Neuroimaging is an important step in the diagnostic workup of patients with suspected autoimmune encephalitis. Conventional MRI reveals abnormalities roughly half of the time. Functional neuroimaging, including FDG-PET scans, have an increased ability to detect changes in neuronal activity and have superior efficacy at correlating clinical course in NMDARe as well. Case History: The patient had hemiparesis, catatonic features, perioral-facial dyskinesias, and subclinical status epilepticus. Initial brain MRI scans were unremarkable, but ¹⁸fluorodeoxyglucose-positron emission tomography (FDG-PET) showed global left cerebral hemisphere hypermetabolism in a crossed cerebro-cerebellar diaschisis distribution. Electroencephalography (EEG) revealed extreme delta brush pattern (EDB), characteristic for NMDARe, with blood and csf anti-NMDAR autoantibodies. Prompt treatment was initiated. In eight weeks, the serum autoantibody concentration was nondetectable, FDG-PET and EEG returned to normal, and conventional MRI scan had begun to show mild, faint signal in the right fronto-parietal cortex without any clinical correlate. At discharge, he had residual mild executive functioning deficits including poor problem solving, impulsivity and inattention which slowly improved with outpatient rehabilitative services. Conclusions: NMDARe can be challenging to diagnose when sophisticated neuroimaging tools are not readily available. EEG pattern suggested NMDARe weeks prior to conventional MRI scans showed any, albeit nonspecific, abnormalities. This is the first reported case, to our knowledge, of NMDARe with crossed cerebellar diaschisis and EDB.

Background: Differential diagnosis of abulic, apathetic, akinetic, and catatonic states remains a challenge, as signs and symptoms may appear clinically similar despite different origins. For example, akinesia can be a byproduct of multiple syndromes, including catatonia, disorders of diminished motivation, neurodegenerative conditions, medication side effects, and a variety of toxic/metabolic derangements. While there may be some overlap in the way these syndromes disrupt the frontal-subcortical circuits involved in volitional movements, learning to distinguish between underlying etiologies remains important as treatment recommendations differ. How can a clinician differentiate when a patient does not neatly fit into a specific category? Case History: A 70-year-old woman with a longstanding history of bipolar I disorder was hospitalized due to mental status changes and immobility. Initial exam was notable for stupor, mutism, staring, posturing, and cogwheeling. Evaluation revealed toxic-metabolic derangements and a right parietal/temporal meningioma without mass effect. Due to concern for catatonia, antipsychotic medication was held and patient underwent benzodiazepine trial and prolonged course of ECT with only minimal improvement. After a several-month-long hospitalization, she ultimately achieved symptom remission with a combination of amantadine and methylphenidate. We review the distinguishing clinical features between catatonic states and other disorders of diminished motivation including akinetic mutism, highlighting how the distinction may explain the patient’s response to treatment. Conclusions: This case illustrates some of the difficulties in differentiating catatonia from other disorders of diminished motivation. Clinicians may want to broaden their differential diagnosis when a patient fails to respond to a particular treatment.

Background: We present a case of sero-negative autoimmune encephalitis in a patient with bipolar disorder (BPAD) that demanded broad neuropsychiatric DDx and navigation across multiple services and across a year of inpatient hospitalization. Case History: A 63-year-old woman presented with MS change 2 months after stabilization on lithium and risperidone during an inpatient psychiatric hospitalization. Her family was deeply invested in her newfound psychiatric stability and current pharmacologic regimen. Across 4 hospitalizations and 12 months she experienced episodes of delirium, psychosis, psychomotor slowing, and variable degrees of extended unresponsiveness. Differential diagnoses included encephalopathy, exacerbation of primary psychosis, medication induced psychosis and catatonia. Brain MRI was markedly abnormal and notable for evidence or prior lacunar strokes and extensive small vessel disease. EEG was notable for poorly organized background slowing at 5–6 HZ and focal sharp waves that drove empiric treatment with AEDs. Given her atypical neuro-behavioral course, autoimmune etiologies were considered. Antithyroid antibodies were positive. A lumbar puncture was performed. CSF paraneoplastic and autoimmune studies were negative. CSF protein was >1000 mg/dl driving Tx with immunomodulatory therapies including steroids, IVIG, and eventual rituximab. Initial responses to steroids and IVIG were robust. Empiric anticatatonia therapies included benzodiazepines, memantine, lamotrigine, and withholding of dopamine blockers. She was trialed off of lithium targeting a potential role in a possible Hashimoto’s presentation. Multiple family/team meetings were held exploring diagnostic uncertainty, empiric treatment, and patient, family, provider and hospital system angst. Conclusion: We discuss neuropsychiatric DDx of the hypokinetic, encephalopathic patient with pre-existing psychiatric disease, sero-negative autoimmune encephalitis, and the role of the neuropsychiatrist in complex diagnoses and systems interactions.

Background: Catatonia is a complex neuropsychiatric disorder marked by changes in motor, affective and behavioral domains, and driven by psychiatric, neurologic, and medical processes. Catatonia and delirium are mutually exclusive diagnoses in DSM-5. Evolving neuropsychiatric literature suggests that delirium and catatonia can be comorbid, with catatonia seen as a neurobehavioral syndrome embedded in / driven by the neurocognitive dysfunction of delirium. Diagnoses of hypokinetic delirium and catatonia are clinically and phenomenologically based and share many features. Psychomotor slowing, withdrawal, reduced environmental engagement, and decreased verbal behavior are common to both catatonia and delirium and make differential diagnosis challenging. Catatonia is typically diagnosed with the Bush Francis Catatonia Rating Scale (BFCRS) which has high sensitivity but less specificity—making it easy to score in the positive range. Given the potential reversibility of catatonia, prompt recognition and treatment are important. Treatment of catatonia includes benzodiazepines, other GABA based drugs, antiglutamate agents, and ECT among other strategies. In the face of diagnostic uncertainty, most would opt for empiric treatment of catatonia-like signs in the setting of delirium. Encephalopathic patients are typically elderly and physiologically frail—and treatment with benzodiazepines and ECT needs to be carefully considered to avoid adverse effects and worsening of delirium. Case History: We present 3 cases of possible catatonia embedded in delirium and discuss their evaluation and treatment. Conclusion: We discuss differential diagnostic challenges in the hypoactive encephalopathic patient, the limits of empiricism, and propose an approach of “benign empiricism” that prioritizes use of less risky / less deliriogenic agents before the introduction of benzodiazepines and ECT.

Background: Lamotrigine is used to treat seizure disorders, bipolar disorder and borderline personality disorder. In overdose, most patients experience minimal symptoms. However, serious consequences can occur including seizure, hypotension, wide complex tachycardia, cardiac arrest, serotonin syndrome and death. The long half-life and multiple effects of this medication complicate managing behavioral sequelae of overdose. We present a case of lamotrigine overdose resulting in a prolonged toxidrome with agitated delirium effectively managed with benzodiazepines. Case History: A 22-year-old female with a reported history of borderline personality disorder presented to the hospital with significant agitation. While initially admitted to psychiatry, her agitation escalated and was unresponsive to several rounds of haloperidol and benzodiazepines, with eventual development of low-grade fever. Given refractory agitation and confusion, she was transferred to intensive care for intubation and sedation. Collateral reported an overdose of approximately 6,000mg of lamotrigine. Labs demonstrated elevated CK, WBC, and AST. A nonblanching rash developed over the patient’s extremities. Five days of persistent agitated delirium was managed with high doses of benzodiazepines and propofol. Antipsychotics were avoided. Conclusions: Agitation and altered consciousness are uncommon in lamotrigine overdose. Few treatment recommendations exist. Lamotrigine acts on voltage-gated sodium channels with effects including inhibiting the reuptake of serotonin, norepinephrine, and dopamine. Overdose may result in symptoms resembling serotonin syndrome or neuroleptic malignant syndrome. Here, we highlight the safety and efficacy of benzodiazepines in managing severe, prolonged agitated delirium in lamotrigine toxicity.

Background: Poststroke neuropsychiatric symptoms vary drastically in presentation, dependent on both the territories involved and the premorbid functioning of such areas. Case History: A 63-year-old right hand dominant Caucasian male with prior history of alcohol use disorder presented to the ED with weakness, dizziness, and confusion, found on initial imaging to have a L occipital infarct. He left AMA prior to any further workup, then represented 6 days later with worsening headache, R extremity weakness, R hemibody sensory loss, R visual field cut and mixed aphasia found to have interval increase in his infarct territory to include L MCA and PCA distributions as a result of his posterior circulation relying significantly on his posterior communicating artery (fetal PCA). On this admission he was noted to have mild agitation secondary to aphasia, but was otherwise behaviorally appropriate. He was discharged to SAR, however 2 weeks later became increasingly aggressive and agitated, and was readmitted and subsequently found to have developed frank psychosis. During his stay was observed to describe vivid visual hallucinations and ongoing paranoia, with multiple episodes of aggression toward staff as a result requiring several trials of antipsychotics and an eventual effective regimen of chlorpromazine and divalproex. Conclusion: This case demonstrates a presentation of poststroke psychosis in the setting of a relatively lower frequency anatomic variant of the posterior cerebral artery supply. By continuing to explore the anatomic areas affected by such infarcts, we can further narrow the structures implicated in the origins of psychotic illness.

Background: Traumatic Brain Injury (TBI), the “signature injury” of the wars in the Middle East, is often comorbid with chronic pain and posttraumatic stress disorder (PTSD). There is still much to be learned regarding the neuroanatomy, neurophysiology, and clinical assessment/treatment of this clinical triad. Very few teaching materials are available for the neuropsychiatric sequelae of war-related injuries. Objectives: To create and disseminate teaching materials that translate complex concepts into clinically useful knowledge for betterment of patients; To create integrated materials and guided learning experiences that also promote usability of knowledge. Methods: New clinical and research findings relevant to these conditions were reviewed, synthesized, and summarized into graphic rich original teaching materials in which color carries a significant portion of the information, allowing large volumes of new information to be presented without overwhelming the learner. Results: Evaluations from parts I–V of this series (2009, ‘12, ‘14, ’15, ‘16), were very positive and indicated the need for more integrated materials of this type. Incorporating the latest work in war-related injuries, Part VI will further facilitate the translation of “textbook to bedside application”. The connections between functional neuroanatomy, neurophysiology, and clinical presentation will be elicited, allowing learners a deeper insight into individual aspects of each patient, and enhanced appreciation of comorbid pathologies and prognosis. Conclusion: These newly revised tools support guiding learners through the intricacies of this complicated field, promoting development of active, integrated knowledge required for the clinical practice of neuropsychiatry as it relates to war-related TBI.

Background: In Progressive Supranuclear Palsy (PSP), the involvement of the cortical-subcortical circuitries that mediate vertical supranuclear gaze palsy, motor disabilities, and cognitive-behavioral disturbances define the syndrome. Here we present a case that developed after the sixth decade of life and in which the diagnosis was supported by clinical and neuroimaging data. Subtle personality changes, memory problems, and pseudobulbar symptoms, are more evident to the family. Despite PSP being a rapidly progressive neurodegenerative disorder and no effective treatments are available to date, our case illustrates clinically significant improvement in cognition and function with the combination of antidepressant medications and Rivastigmine. Case History: A 72-year-old gentleman was referred to our memory clinic by neurology with a history of progressive memory impairment, gait imbalance with recurrent backward falls, urinary incontinence, dysphagia, axial stiffness, hypomimia, and neuropsychiatric symptoms that included depressive and anxiety features. Brain MRI showed midbrain atrophy with a characteristic Hummingbird sign of PSP. Patient was started on Rivastigmine 1.5 mg po BID, Bupropion XL 150 mg po daily and Escitalopram 10 mg po daily with noted cognitive-behavioral improvement as evidenced by resolution of mood symptoms and improved executive control function, motor disability and global cognition based on Clock Drawing Test performance and MMSE scores pre and posttreatment respectively. Conclusions: PSP is a progressive neurodegenerative disease with no known reversible treatment. The use of combined antidepressants in conjunction with cholinesterase inhibitors improved cognitive function and ameliorated motor and neuropsychiatric symptoms in our patient and hence quality of life was improved.

Background: The insula plays important roles in interoception, self-representation, language, social cognition, and salience processing, among others. The left and right insulae may support a different balance of functions, with the left more involved in language and executive functions and the right in social-emotional cognition. The posterior insula contains an interoceptive map representing body states, and along a posterior-to-anterior gradient the insulae receive information from other neurologic systems regarding homeostatic motor functioning and environmental, hedonic, and motivational/social/cognitive conditions. This highly integrated system is a salience-infused representation of the self in context, and, arguably, a substrate for awareness of complex feeling states, particularly on the right. The presence of bidirectional, interhemispheric connections between the anterior insulae suggests their mutual regulation. Patients with unilateral, focal lesions to the insula provide an opportunity to examine for specialization and lateralization of function. Case History: A 29-year-old woman with treatment-refractory epilepsy was found to have a left anterior insular lesion which was thought to be a seizure focus for which she underwent laser ablation. Following surgery, she developed acute behavioral changes including paranoid ruminations regarding interpersonal relationships, difficulty reading social cues, dysphoria, and “affective reactivity” where she needed to mirror the behavior of others. We suggest her neurobehavioral symptoms may be due to hyperfunctioning of the right insula associated with left-sided disruption. Conclusions: This case highlights the function of the insula and proposes a role for interhemispheric insular regulation in neuropsychiatric symptoms. This mechanism is well-established for other parts of the cortex.

Background: Previous studies have investigated the relationships between the volumes of subcortical structures (e.g. caudate, putamen, thalamus, amygdala, hippocampus) and present tic symptom severity or future tic outcome in the individuals with diagnosed Tourette syndrome (TS). The largest such study found increased hippocampal volume in TS, though others have found the opposite. However, subcortical volumes have not been studied in children in their first year after tic onset. Objective: This study aimed to examine whether the volumes of subcortical structures measured shortly after tic onset can predict tic symptom severity at the one-year anniversary of tic onset, when TS can first be diagnosed. Methods: We enrolled 31 children whose tics had begun within 9 months (median 4.6 months) prior to the first study visit (baseline) and collected structural MRI (MPRAGE with prospective motion correction [vNavs]). We re-examined them at the 12-month anniversary of their first tic (follow-up), assessing tic severity using the YGTSS. We quantified the volumes of subcortical structures using volBrain software. Results: Hippocampal volume measured at the baseline visit correlated positively with tic outcome at 12-month follow-up: larger hippocampus predicted worse tic outcome at follow-up. The volumes of other subcortical structures including the caudate and putamen did not predict tic outcome at follow-up. Conclusion: These findings suggest that hippocampal volume may be an important marker predicting future tic symptom outcome.

Background: Morality, the set of shared attitudes and practices that regulate individual behavior to facilitate cohesion and well-being, is a function of the brain, yet its localization is uncertain. Acquired sociopathy has been reported after both bilateral and unilateral injuries, predominantly right frontotemporal lesions, whereas functional neuroimaging has demonstrated bilateral activation during moral decision-making. Objective: To review evidence from the literature evaluating the role of the right cerebrum in the representation of morality by performing a systematic review of lesional causes of immorality. Methods: We queried PubMed with the search terms: “immoral OR morality OR sociopathy OR empathy OR theory of mind OR mentalizing OR emotion perception” AND “brain damage OR stroke OR hemorrhage OR tumor OR lesion OR brain injury OR dementia”. We limited inclusion to papers in the English language with a sociopathic behavioral change associated with a focal cerebral lesion, and behavior not better explained by another obvious neurologic, psychiatric, or medical disorder. Results: Our search identified 1104 papers; review of abstracts identified 35 full-text articles that met our criteria including a recent excellent review by de Oliveira-Souza et al. Our search strategy identified a total of 110 cases of immoral behavioral associated with focal lesions, while related citations identified during the review yielded an additional 11 cases. In terms of lesion laterality, 51 cases were bilateral, 50 were right-sided, and 20 were left-sided. Conclusion: Immoral behavior is more often associated with unilateral than bilateral cerebral lesions, and the majority of the unilateral lesions are right-sided.

Background: Frontotemporal neurocircuitry modulates cognitive and affective brain processes. Its disruption manifests in depression, anxiety, memory and executive function deficits. Infections provide a means of understanding neurocircuitry through loss of function lesions. Case History: We present three cases that underscore the need for awareness of neuropsychiatric presentations of brain infections. First, a 47-year-old Ecuadoran female with a 25-year history of neurocysticercosis presented with depression, poor memory alongside word finding and attentional difficulties after surgery for a cavernous malformation. Antiepileptic treatment was discontinued as her last generalized seizure was over 20 years ago. Her EEG confirmed continuous left frontotemporal lobe epileptiform discharges. Second, a 69-year old Moroccan female with B12 deficiency and diabetes presented with persistent cognitive complaints a year after completing chemotherapy for colon cancer and a course of treatment for presumed neurosyphilis. She had depression, anxiety with panic, poor balance, and sensory loss up to her knees in addition to memory, visuospatial and executive deficits. Her brain MRI showed white matter disease without atrophy. Lastly, 40 years after an ICU stay for septicemia with multiple brain abscesses from a foot infection, a 70-year old Caucasian male presented with depression, irritability, paranoia, rumination, indecisiveness, word-finding and memory difficulties. His brain MRI showed left temporal lobe encephalomalacia. Conclusions: Although prevention and access to treatment decreased the prevalence of neuroinfectious diseases in the US, neurobehavioral specialists should be familiar with their occurrence, presentation and treatment. Our cases illustrate cognitive and affective presentations linked to frontotemporal neurocircuitry disruption detailing its anatomy and function.

Background: The oldest-old are a fast-growing segment of the population at risk for dementia. Clinical features and neuropathology differ across age groups with higher comorbidity and an imperfect cognitive impairment correlation associated with increasing age. Different mechanisms, risk or resiliency factors may influence cognitive outcomes in this population. Malignancy is more prevalent with increasing age, where pathological mechanisms facilitate abnormal cell growth, and may impact neurodegeneration. Objective: To improve our understanding of demographic and clinical characteristics in nondemented and demented oldest-old. We hypothesize that malignancy will be overrepresented in the nondemented group suggesting possible resiliency factors for neurodegeneration. Methods: Clinical records of 134 autopsied study participants from Mayo Clinic (female N=118) ≥95 years-old at time of death (range 95–105 years-old) were studied. Nondemented (N=66) and demented (N=68) groups were stratified and compared according to demographics and clinical variables, including history of malignancy. Results: Age at death, education, and sex did not differ between nondemented and demented autopsied individuals. APOE ε4 allele presence was lower in the nondemented group approaching significance (p=0.091). No differences were observed in terms of vascular risk factors, smoking, alcohol use, or presence of depression. MMSE scores were higher in the nondemented group (p<0.001). History of malignancy was higher in nondemented compared with demented autopsied individuals (p<0.001). Conclusions: History of malignancy was more common in nondemented compared with demented autopsied individuals in the oldest-old. These findings raise the possibility that cancer survivors may have more active proliferative pathways compared with demented individuals in the oldest-old.

Background: Several cases of protracted amnestic disorder have been characterized in patients following fentanyl overdose. Additionally, overdose from substances other than fentanyl can lead to numerous patterns of end organ failure that compromise the integrity of the hippocampi. With addiction currently a public health crisis, clinicians are caring for patients with comorbid substance use and cognitive impairment across the lifespan. These patients find themselves between two fields, addiction and cognitive specialists, which demands a nuanced approach. This space may also present unanticipated challenges to long-term treatment and disposition, a space perfectly occupied by the neuropsychiatrist. Case History: A 30-year-old man with a history of Bipolar Disorder, Alcohol Use Disorder, and Cocaine Use Disorder was found unresponsive with labs positive for fentanyl, cocaine and alcohol. His hospital course was complicated by respiratory failure, acute renal failure, and hepatic injury. Urine toxicology was confounded by the use of fentanyl for intubation prior to the sample having been obtained. On exam, he evidenced impaired episodic memory. MRI of the brain revealed bilateral hippocampal atrophy. Neuropsychological testing demonstrated profound deficits within the domain of learning and memory. Following medical stabilization, attempts to identify a rehabilitative disposition were complicated by system barriers, highlighting a need for those carrying both diagnoses. Conclusion: This case illustrates the complications of substance use and persistent cognitive impairment, and the challenges inherent to optimal longitudinal care for younger patients with concurrent diagnoses. Further, it emphasizes neuropsychiatry’s role in bridging these subspecialties.

Background: Psychiatry, neurology, neurosurgery, physical medicine and rehabilitation and geriatric medicine have all developed unique approaches to management of brain disorders, resulting in siloed care for patients. Objective: To demonstrate the utility of an interdisciplinary brain medicine approach to complex cases involving brain disorders impacting affect, behavior and cognition (ABC) and the effect of these disorders on functional abilities, quality of life, and relationships. Methods: Cases were drawn from the inaugural University of Toronto Brain Medicine fellow’s clinical roster. The cases were selected with the following criteria in mind: a complex brain disease involving disordered ABC, psychosocial complexity, and requiring a transdisciplinary management approach. Results: Three cases, each with its own unique features, demonstrate the benefits of an interdisciplinary brain medicine approach. We present cases of: traumatic brain injury-induced catatonia requiring neurosurgery, electroconvulsive therapy, pharmacology, and rehabilitation; refractory temporal lobe epilepsy requiring a lobectomy and ongoing pharmacological management, presenting with new-onset depressive symptoms and suicidality in the context of a recent status epilepticus event; and a significant substance use disorder with associated attention-deficit and hyperactivity disorder and chronic pain presenting with pseudoseizures and suicidal ideation. In each of these cases, transdisciplinary brain medicine objectives were identified and the need for an integrated cross-disciplinary effort is highlighted. Conclusion: An interdisciplinary brain medicine approach can transcend the barriers separating brain focused specialties. Competence-based training programs, that build on a trainee’s specialty of origin, can foster the translation of this approach into clinical medicine.

Background: Tau is one of several proteins which can cause frontotemporal dementia (FTD). While knowing which protein is causing a patient’s disease is crucial, no biomarker currently exists for identifying the pathogenic protein in vivo. Objective: This project aims to investigate the potential for the [18F]MK-6240 PET tracer to bind to tau in FTD. Methods: We are enrolling subjects with genetic FTD, who constitute an ideal population for testing because their pathology is already known. Patients with FTD due to MAPT mutations are expected to show tau binding, whereas patients with nontau mutations such as C9orf72, GRN, and VCP are expected to not show [18F]MK-6240 binding. Each participant undergoes tau-PET scanning with [18F]MK-6240, amyloid-PET imaging with [18F]NAV-4694 to rule out confounding Alzheimer’s pathology, high-resolution structural MRI, and neuropsychological testing. Results: Thus far, we have scanned three symptomatic MAPT patients, whose tau-PET scans all demonstrated binding in areas associated with FTD, without significant off-target binding. We have also analyzed two asymptomatic MAPT carriers approximately five years from disease onset; both showed [18F]MK-6240 binding in expected regions. We have additionally scanned three individuals with symptomatic FTD caused by a nontau mutation (one C9orf72; one GRN; one VCP): their scans did not reveal any [18F]MK-6240 binding. All eight amyloid-PET scans were negative. Conclusion: Our preliminary findings of [18F]MK-6240 binding in three symptomatic MAPT patients and two asymptomatic MAPT carriers five years from disease onset are promising, particularly when combined with the absence of binding in participants with nontau mutations. Further patient recruitment is ongoing to determine clinical applicability.

Background: Wandering is defined as a purposeless act of walking or driving through long distances. It occurs in neuropsychiatric diseases and its neurological background is not entirely known. We report two cases of wandering in subjects with cerebellar lesion and discuss about a possible relationship between them. Case History: A 31-year-old man was evaluated due to a history of manic episodes, psychotic symptoms, impulsive behavior, episodes of wandering for long distances (the patient walked from London to Manchester city; approximately 190 km) and automatic behavior. MRI demonstrated a left choroidal fissure cyst and mild hypoplasia of inferior cerebellar vermis. A 33-year-old man presented with a history of manic episodes, psychotic symptoms, impulsive behavior, hyperactivity and attention deficits, emotional outbursts when confronted, episodes of wandering for long distances (he was walking an average of 30 km per day by foot and 1000 km by car) and automatic behavior. MRI showed extended subarachnoid space in the posterior fossa with increased cisterns magna and cerebellar, as well as atrophy of cerebellar vermis. Conclusions: The Cerebellar Cognitive Affective Syndrome is associated with affective dysregulation and may be related with atypical behavioral syndromes, as reported here. Cerebellar circuitry, especially the posterior cerebellar lobe, may be associated with the pathophysiology of wandering. It is not possible to definitely conclude that the anatomical alterations found in the patients were causing the wandering behavior. However, such cases need to be investigated in order to better understand the role of the cerebellar dysfunction in the pathophysiology of wandering.

Background: Patients with dementia have higher rates of hospitalization-related adverse outcomes, including delirium, compared with cognitively normal peers. Sensitivity to medications with anticholinergic activity is predicted to increase the risk for developing delirium in these individuals. The inpatient rates of delirium among these patients following anticholinergic exposure has yet to be explored. Objective: To test the hypothesis that administration of anticholinergic medications to hospitalized patients with dementia is associated with higher rates of delirium and treatment of behavioral disturbances, including rescue antipsychotics and physical restraints. Methods: We conducted a retrospective study using data from the UCH Data Compass platform, identifying 23,031 patients with Alzheimer’s disease, vascular dementia, or unspecified dementia by diagnosis codes. Queried hospitalizations occurred between 2011–2018. Two-tailed Fisher’s exact tests were used, comparing rates of haloperidol and physical restraints orders for patients who precedingly received a drug with known anticholinergic activity to those patients who did not. Results: 2,333 patients (10.1%) received inpatient anticholinergics with 772 (33.1%) having orders for haloperidol or physical restraints following dose delivery, compared with 14.7% (N=3,033) of 20,698 individuals who did not receive anticholinergics. Significant differences in rates of delirium were observed (p<0.001) with a relative risk of 2.26 (95% CI: 2.11, 2.41). Conclusion: Administration of anticholinergics is associated with delirium in hospitalized patients with dementia. This may represent a modifiable risk factor for delirium prevention and has implications for improving inpatient dementia care. Prospective studies are needed to explore this relationship and reveal other predictors for developing delirium in this patient population.

Background: The Department of Veterans Affairs Suicide Risk Management Consultation Program (SRM) provides consultation to providers serving Veterans at risk for suicide. This program offers free phone or e-mail-based consultation on topics relating to suicide risk assessment and management, and serves as a vehicle for dissemination of suicide prevention best practices. Objective: The SRM team conducts program evaluation to explore program effectiveness and inform programmatic changes to meet evolving needs of providers served. Methods: Data are collected on consultation questions as well as descriptive information about providers and Veterans. Provider satisfaction survey data are obtained at completion of and two months after consultation. This presentation covers program evaluation data from two-month follow-up surveys, including common SRM consultation characteristics and provider satisfaction data. Results: Data from two-month follow-up surveys (N=47) include: 87% of providers endorsed that consult recommendations led to enhanced risk assessment and/or management; 89% of providers reported improved documentation about risk assessment/management and 93% endorsed improved documentation overall; 95% have applied recommendations or resources provided in the consultation to other Veterans served; and 95% reported improved confidence in risk assessment/management skills. Descriptive data regarding consultation questions, provider and Veterans characteristics, and qualitative feedback are reviewed. Conclusion: Data offers some early insight into a novel consultation program for providers who serve Veterans at risk for suicide. Expanding the reach of SRM seems worthwhile given reported positive impact of consultation for both providers and Veterans. Limitations include the self-report and survey-based methods of data collection.

Background: Benzodiazepines constitute the first-line treatment for catatonia. In cases of malignant or refractory catatonia, the recommended treatment is ECT. Physicians administering ECT typically require that patients reduce or stop anticonvulsant medications, including benzodiazepines; however, in severe cases, clinicians sometimes maintain catatonic patients on high-dose benzodiazepines during ECT. Limited evidence (primarily case reports from the 1990s onward) supports the administration of flumazenil (a benzodiazepine receptor antagonist) prior to ECT in individuals on benzodiazepines, in order to lower seizure threshold and increase seizure duration. However, this option is not routinely considered in clinical practice. Case History: A 56-year-old man with bipolar disorder and prior catatonia was hospitalized with recurrent catatonic symptoms. Extensive laboratory and imaging workup were unremarkable. The patient remained profoundly catatonic despite high-dose lorazepam in combination with adjunctive medications. Right unilateral ECT was initiated, resulting in mild clinical improvement, although seizure architecture was poor. Bilateral ECT was administered without any clear clinical change or improvement in seizure architecture. Following addition of flumazenil prior to ECT, seizure architecture improved (intra-ECT EEG examples will be included), and the patient exhibited marked clinical improvement. Conclusions: This case illustrates the clinical dilemma of attempting to administer ECT to a patient on high-dose benzodiazepines. Addition of flumazenil appears to be helpful in improving ECT efficacy in such patients, theoretically by improving seizure duration and architecture. Only a few case reports have examined this use of flumazenil. Further research would be helpful in guiding clinical practice for patients who require both ECT and benzodiazepine treatment.

Background: The most critical aspect in the treatment of Functional Neurologic Disorders (FND) is delivering the diagnosis and providing a thorough explanation of the symptoms. To date, no studies have investigated the utility of incorporating neuroscientific research in this step, or its potential effect at mitigating stigma. Objectives: (i) develop an educational video that models a physician-patient interaction using our current neurobiological understanding of FND; (ii) conduct a workshop to improve knowledge, attitude, and illness perception among clinicians toward patients with FND. Methods: 1-hour workshops (including a 10-minute video, role playing, and pre- and postquestionnaires) were conducted at Stanford University and at the 2019 annual meeting of the American Psychiatric Association. Paired t tests were used to measure differences in responses before and after the workshop. Results: 41 participants completed the teaching activities (31 psychiatrists, 10 neurologists). After completing the workshop, learners demonstrated the following changes in knowledge and attitudes: a clear understanding of treatment options (p=0.043), a positive change in attitudes that includes appreciating that functional symptoms are “real” (p=0.00067) and a larger willingness to want to work with FND patients (p=0.0081). In addition, when comparing pre- and post- Illness Perception (using standardized scale), participants gained an understanding of how much this illness affects patients emotionally (p=0.0087). Conclusions: A brief, educational intervention using neuroscience-based content was found to significantly improve clinicians’ attitudes, knowledge and illness perception in FND. The most sensitive change was an appreciation that functional symptoms are “real.”

Background: Evidence-based migraine preventive behavioral therapies are safe and well-tolerated with enduring benefits. However, adherence to these in-person treatments is poor. Objective: We examined recruitment data to understand reasons for participation/nonparticipation in a smartphone-based biofeedback study for people with migraine. Methods: From 6/2019–10/2019 we recruited for a 2-arm randomized waitlist-controlled trial of patients with ICHD3 migraine and 4–20 headache days/month. Patients had to have a smartphone, be likely to try a smartphone-based intervention, not have done behavioral therapy for migraine (<1 year) and not change preventive medications during the study. One arm received Heartmath app+Inner Balance Sensor at enrollment. The other arm received no intervention. Data on recruitment and baseline characteristics of those enrolled are reported. Results: There were 359/671 (54%) patients approached deemed ineligible at their headache visit. Beyond not having migraine, top reasons for ineligibility were # headache days: 128 (19%); currently/recently done behavioral therapy for migraine (<1 year): 33 (5%); changing preventive medication: 33 (5%). Few cited technology limitations/unlikely to try a smartphone-based intervention: 18 (3%). There were 160 patients (24%) uninterested (main reasons: time and distance from home). We met our recruitment goal N=52 of whom 88% (48) were female. Mean age was 42±13. Eight (16%) tried behavioral therapy (>1 year ago) and 17 (33%) had previously been recommended behavioral therapy but had never attended. Conclusions: Reasons for nonparticipation in a technology-based migraine behavioral study were mainly unrelated to the technology component and were due to traditional trial related inclusion/exclusion criteria.

Background: Historically, cobaltism resulted from ingestion or inhalation of cobalt after vocational exposure to cobalt powder or in beer drinkers. Cobaltism and the subsequent neuropsychiatric symptoms after the corrosion of chrome-cobalt hip implants are less recognized. Here we present a case of Arthroplasty Cobalt Encephalopathy (ACE) in a male after bilateral hip replacement. Case History: Ten years after bilateral hip replacement, a 63-year-old individual with no previous neuropsychiatric history or environmental exposure to cobalt, developed a constellation of symptoms including significant weight loss, insomnia, irritability, short term memory problem, visuospatial deficits, dizziness, tremor, tinnitus and blurry vision. He reported significant hip pain at the same time which led to a visit with his orthopedic surgeon. Cobalt and Chromium serum levels were measured at 9.75 ug/L and 3.13 ug/L respectively both at toxic levels. Other investigations including, complete blood counts, immunology, infection work-up, liver enzymes, creatinine, urea, electrolytes, TSH, T4 and T3 were within normal limit. His comprehensive neuropsychological assessment revealed mild neurocognitive impairment. After revision surgery and treatment with N-acetyl-cysteine, the serums levels for cobalt and chromium gradually dropped to 0.9 ug/L and 2.35 ug/L respectively. Although most of his symptoms are currently resolved, he still struggles with insomnia, dizziness and irritability. Conclusion: This case illustrates that severe neuropsychiatric symptoms can occur at cobalt level of less than 20 ug/L. The overall scope of ACE is still largely undefined. Future studies to shed light into best approach in assessment and management of these patients are needed.

Background: Among Hispanic populations, the difference in progression and neuroimaging between Early and Late Onset Alzheimer’s disease is not well described nor understood. With new causal treatments for neurodegenerative disorders now being developed and tested, a molecular diagnosis is desirable to allow for appropriate and specific clinical intervention. Here, we present two cases in which an accurate diagnosis with modern neuroimaging techniques assisted in clinical decision-making and advanced care planning. Case History: Both cases presented to our clinic with prominent insidious and progressive behavioral, emotional, and cognitive symptoms suggesting a dementia syndrome. Ms. A was 69 years old when first confirmed with EOAD versus Ms. B, who was 83 years old when she was told she had LOAD. We review the distinguishing clinical features between EOAD versus LOAD. Conclusions: These cases illustrate the importance of distinguishing between the two entities of Alzheimer’s disease and the importance of advanced neuroimaging techniques for objective clinical interventions and advanced care planning. Minority Hispanic populations are often marginalized from new neuroimaging technologies and more research is needed to operationalize the need for use of these technologies in clinical practice.

Background: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB) and may be mistaken for seizures. In reality, the prevalence of epilepsy in DLB is lower than in other forms of neurodegenerative dementia, including Alzheimer disease (AD). Objective: Examine the usage and utility of outpatient electroencephalograms (EEGs) in DLB compared with AD. We hypothesized that EEG is relatively over-utilized in DLB patients, given epilepsy’s true prevalence in that population. Methods: Retrospective cohort study utilizing the University of Colorado COMPASS database, capturing all patients with AD or DLB seen between 2011 and 2018. Cohorts underwent multiple analyses of proportions regarding EEG utilization. The DLB group underwent further analysis with respect to epilepsy diagnosis following EEG. Results: Of the 7184 AD patients included, 208 (2.7%) had an EEG performed before and 180 (2.3%) had an EEG performed after the neurodegenerative diagnosis first appeared in the medical record. Of the 929 DLB patients, 48 (5.2%) had an EEG before and 43 (4.6%) had an EEG following their dementia diagnosis, significantly more frequently than the AD patients (p<0.0001). Epilepsy was subsequently diagnosed in 7 (16.3%) of the 43 DLB patients with postdementia-diagnosis EEGs and 15 (31.3%) of the 48 DLB patients with predementia-diagnosis EEGs (difference of 15.0%, p<0.0977). Conclusions: Despite lower prevalence of epilepsy in DLB versus AD, DLB patients undergo outpatient EEGs more frequently, both before and after the diagnosis. EEGs performed following DLB diagnosis were no more likely to lead to epilepsy diagnosis than those performed prior.

Background: Post stroke depression (PSD) has been identified as a main factor limiting recovery in stroke patients, yet it is clearly predictable and treatable. Exploring the relationship between PSD and quality of life (QoL) will provide insights for instituting evidence-based interventions for the optimal health of stroke survivors. Objective: To assess the influence of post stroke depression on health related quality of life of stroke patients attending the Neurology Outpatient Clinic of the University of Port Harcourt Teaching Hospital in Nigeria, West Africa. Methods: This was a cross-sectional study comprising of 381 stroke patients aged ≥18 years. The Beck’s Depression Inventory-II (BDI-II) was used to screen for poststroke depression. Patients were classified as depressed or nondepressed using a cut-off of 13. Health related quality of life was determined using the Health Related Quality of Life in Stroke Patients-26 (HRQoLSP-26) questionnaire. QoL was dichotomized into satisfied and unsatisfied based on a cut-off of 75%. Bivariate and multivariate analyses were performed at 0.05 significant level. Results: The mean age of stroke patients was 60.5±13.4 years. Two hundred and fourteen (56.2%) were males. Ischemic stroke 87 (22.8%), and left hemispheric lesion location 165 (43.3%) were more common. Unsatisfied QoL was noted in 309 (80.1%) of stroke patients. Depressed stroke patients were eight times more likely to have unsatisfied QoL after adjusting for socio-demographic and stroke-related factors (Adjusted odds ratio=8.4; 95% confidence interval: 3.1–22.8; p=0.0001). Conclusion: PSD is an independent predictor of QoL among stroke survivors. Strategies to improve their QoL should include addressing PSD.

Background: There is substantial evidence of NMDA receptor hypofunction in schizophrenia, but it is unclear if this due to an endogenous abnormality of the receptor. Abnormalities in NMDA receptor expression vary across postmortem studies. Characterizing region-specific and subunit-specific molecular changes in postmortem brains may help elucidate the etiology of glutamatergic dysfunction. Objective: The aim of this review was to evaluate region-specific differences in NMDA subunit expression in postmortem brains of people with schizophrenia compared with healthy controls. Method: Primary studies on the expression of NMDA receptor subunits in patients with schizophrenia were identified from electronic bibliographic searches of Web of Science and PubMed throughout the period of January 1, 1990–December 2, 2019. All full-length English language articles reporting NMDA receptor subunit mRNA or protein expression in postmortem brains were included. Results: Forty eligible studies were identified. The majority reported no change in NMDA subunit expression. Decreased GluN1 expression was reported in 3/13 studies of the DLPFC and 3/10 studies of the hippocampus. Decreased GluN2C expression was reported in 2/4 studies of the DLPFC. An increase in GluN2B expression was reported in 2/7 studies of the hippocampus and 1/4 studies of the thalamus. Conclusion: There is insufficient evidence at this time to conclude that NMDA hypofunction in schizophrenia is the result of endogenous abnormalities of the receptor. Increased expression of GluN2B in the hippocampus and thalamus could represent a compensatory response to glutamatergic deficiency from other etiology.

Background: In 1938, Wilder Penfield described two main types of “mental phenomena” elicited by the electric stimulation of the cerebral cortex: “experiential phenomena,” i.e. autobiographic images or vivid memories in which perception, memory, and emotion are expressed in a unified manner; and “interpretative phenomena,” i.e. interpretation of current situation, including illusions and emotional changes. Here, we present a clinical case of temporo-parieto-occipital epilepsy that comprises both types of mental phenomena according to Penfield’s terminology: experiential and interpretative. Case History: We present the case of a 36-year-old woman with symptomatic epilepsy due to brain cysticercosis. During her adolescence, she developed seizures characterized by metamorphopsia, hallucinations of autobiographic memory and, finally, asomatognosia. Magnetic brain imaging showed a calcified lesion in the right occipitotemporal cortex, and positron emission tomography imaging confirmed the presence of interictal hypometabolism in two regions: the right parietal cortex and the right lateral and posterior temporal cortex. Conclusions: This case illustrates the importance of distinguishing the different expressions of the cortical zones in epilepsy. The magnetic resonance imaging studies revealed the epileptogenic lesion, which in turn is related to the epileptogenic zone. The variety in the clinical symptomatology (metamorphopsia and hallucinations of autobiographic memory) revealed multiple symptomatogenic zones, and the PET scan showed the epileptogenic and the functional deficit zones (asomatognosia).

Background: In order to optimize outcome of depression treatments biomarkers of cognitive and affective brain functions are needed. Furthermore, better understanding of how the most effective treatment of severe depression, electroconvulsive therapy (ECT), impacts executive functions is of great importance. Objective: We studied the impact of ECT on executive functions and aimed at identifying cognitive and affective biomarkers of depression severity. Methods: Twenty-one patients with treatment-resistant MDD performed a computer-based test assessing executive functions and emotional modulation of cognitive performance prior to and post 4-week ECT treatment period. Pre- and posttreatment performance and emotional modulation scores were analyzed and correlated with depression scores (BDI). Emotional modulation scores were obtained by subtracting performance measures, reaction times (RT) and error rates, associated with threat related distractors from those of neutral distractors. Results: Depression scores were significantly reduced (BDI: pre 35.2, post 17.8, p<0.001). Reaction times were prolonged (RT: 467 ms, 512 ms, p=0.03) and the number of errors (2.6% versus 0.8%, OR=0.63) reduced post-ECT. We found pre-ECT BDI to correlate with emotional modulation of reaction time (r=0.56, p=0.030), with emotional modulation of incorrect responses (r=0.67, p=0.006) and with composite score derived them (r=0.71, p=0.003). Conclusion: ECT treatment significantly alleviated patients' depression. Furthermore, improved accuracy of cognitive performance along with slowed responses was observed. Index derived from emotional modulation of cognitive performance shows some promise as an objective biomarker of depression severity.

Background: Unique among humans, the prefrontal cortices are involved in a variety of functions, such as regulation of emotions, social interactions, and personality. The classic example of its damage is that of the Phineas Gage. We present a case report of a patient with a history of remote TBI involving frontal lobes who presented with behavioral symptoms and personality changes. Case History: 67-year-old male with PMH of a TBI due to MVA at the age of 24 was admitted with abdominal distension requiring colectomy, though he declined. His behavior was generally unappreciative, and speech was frequently profane. His attending physician, known for his patience and compassion was frustrated with his repeated episodes of seemingly disrespectful and unappreciative behavior. The psychiatry team was consulted to assess him for these behavioral problems and his capacity to make medical decisions. While he seemed to have capacity to make medical decisions, he demonstrated behavioral and personality changes including emotional lability and exaggerated emotionality. His sister indicated that post TBI he has been sexually disinhibited, lacking social skills and indulging in profane language. These behavior and personality changes seem to correlate with his MRI findings of bilateral frontal lobe encephalomalacia and are reminiscent of the classic case of Phineas Gage. Conclusion: Linking challenging neurobehavioral and neurocognitive changes to remote TBI allowed the treatment team to understand the person within the patient and to understand that they needn’t take these insults personally, which helped them to continue to provide insightful and compassionate care.

Background: Cancer-related cognitive impairment (CRCI) is a phenomenon where cancer patients develop impairment in mental abilities in the context of treatment. Longitudinal studies demonstrate that patients display impairments predating treatment, implicating cancer itself. Current diagnostic tools such as Neuropsychological testing are less accurate in localizing the subtle cognitive difficulties in CRCI. Neuroscientific approaches such as functional imaging studies have provided some explanation for CRCI. Currently, most of our existing knowledge relates to chemotherapy-related CRCI. We examine a case of sudden-onset mild-cognitive impairment (MCI) preceding a diagnosis of Gastrointestinal Stromal Tumor (GIST). Case History: 67-year-old woman with a history of depression and alcohol abuse who presented with sudden onset cognitive impairment. Bedside cognitive testing demonstrated high premorbid baseline with deficits in verbal and visual memory, anterograde amnesia, and notable executive function impairments. She was anosagnostic for her cognitive decline. PET scan demonstrated nonspecific mesiotemporal temporal lobe changes, and LP was positive for Tau/Amyloid Beta 42 ratio, and 14–3-3 protein. Alzheimer’s Disease (AD) was considered given borderline Tau/Amyloid Beta changes, early deficits in speech prosody/cadence, word finding difficulty, and mannerisms. It would not have been unreasonable to consider a paraneoplastic antibody syndrome flare as well. Memory improved and she was discharged to home. Outpatient treatment with AChE Inhibitors was unsuccessful due to GI side effects. Within 9 months of onset of neurocognitive symptoms, patient developed persistent nausea and malaise, worsening of memory, and was eventually diagnosed with Stage II-IIB GIST. Conclusion: This case is complex given numerous possible explanations for MCI but cancer should not be ruled out as a primary contributor. It offers insight into the ongoing limitations of current diagnostic tools in localizing deficits in patients who may have CRCI.

Background: Functional neurological disorders (FND) are highly prevalent in neurology clinics and are subdivided based on presenting symptom. Treatment of FND includes patient education, psychotherapy, physical therapy for motor symptoms, and treatment of comorbid psychiatric disorders. Cognitive behavioral therapy is the psychotherapy treatment modality with the most evidence-based support for FND. Short-term psychodynamic psychotherapy offers a potential alternative psychotherapeutic technique for FND patients. Case History: A 30-year-old man presented to clinic with four-year history of functional movements, inability to work, and increasing isolation from peers. He had completed two-years of supportive therapy without improvement in symptoms or functioning. He was trialed in a twice weekly psychodynamic psychotherapy for 12 weeks modified from a panic-focused psychodynamic intervention. Exploration of intrapsychic conflicts about separation and anger and mobilization of language and metaphor to describe these feelings/symptoms coincided with functional improvement, which remained sustained after 6-month follow-up. Conclusions: This case illustrates a potential alternative psychotherapeutic technique for patients with FND. Psychodynamic psychotherapy should be considered in the setting of psychologically curious patients with functional symptoms. Research is needed to further validate psychodynamic psychotherapy in FND, as well as explore what patient characteristics may predict good outcomes with this modality.

Background: Several clinical trials have shown a significant improvement in depressive symptoms with repetitive transcranial magnetic stimulation (rTMS). Despite improvement in overall response rates, currently no standard of care following a failure of the initial rTMS trial exists. Objective: In this retrospective naturalistic observational study, we studied response rates on continuation of rTMS following failure of the first round of 36 treatments. We explored both conventional and theta-burst stimulation (TBS). The treatment protocol allowed personalization in target, frequency, intensity of stimulation as well as number of pulses and sessions as clinically indicated. Methods: Of 142 patients who received conventional rTMS and 29 who underwent TBS at Massachusetts General Hospital’s TMS clinical service, 27 nonresponders (22 to rTMS and 5 to TBS) opted to continue their treatment beyond session 36. The 17-item Hamilton Depression Rating Scale (HAMD-17) was checked for clinical response. Results: The response rate among nonresponders improved from 5% on treatment number 46 to 23% on treatment number 72. The response rates further improved with limited number of nonresponders who continued their treatments beyond 72. Using TBS, remission rate of 28% on treatment number 46, and 60% in treatment number 72 was achieved. Conclusion: The result of this study shows improvement in clinical response by continuing rTMS beyond 36 treatments. While the number of subjects and study design limit generalization, given the fact that these patients were medication refractory (average antidepressant failure of 7.4), and had failed initial course of rTMS, the result of this study is encouraging.

Background: Despite a finite lexicon of words, we can express a wide range of novel meanings. This ability relies on complex cognitive processes that combine discrete lexical elements into hierarchical structures according to abstract rules. Objective: Here, we measure the variability of syntactic combinatorics in primary progressive aphasia (PPA), a neurodegenerative disease that primarily involves language. We hypothesize that in the nonfluent variant of PPA (nfvPPA) with its core feature of grammatical abnormality, the ability to construct syntactic combinations diminishes. We also analyzed the language of semantic (svPPA) and logopenic (lvPPA) variants of PPA. Methods: We parsed 133 language samples (54 controls, 29 nfvPPA, 26 lvPPA, 24 svPPA) to extract combination rules based on the structure of head-dependent elements in sentences. We then quantified the variability of the distribution (E_dis) of combination rules using the information-theoretic concept of efficiency—the ratio of the entropy of a distribution to its maximum possible entropy. Results: Linear regression analysis indicates that E_dis of combination rules was lower for nfvPPA (b=−0.026, p=0.003) and higher for svPPA (b=0.033, p=0.005) and lvPPA (b=0.025, p<0.001) than controls. We further tested whether this effect depends on verb access difficulty. Interestingly, patients with nfvPPA had higher E_dis for verbs (b=0.065, p<0.001) than controls and used lower frequency verbs compared with all other groups (ps<0.001). Conclusion: Language production in nfvPPA is characterized by a complex interplay between lowered variability of syntactic rules and increased variability of verbs, a pattern that is markedly different from that of controls, svPPA, and lvPPA.

Background: Depressive symptoms are common sequelae of traumatic brain injury (TBI) and neuroimaging has been a highly utilized technique for studying TBI and depression independently of each other. Objective: To complete a systematic review of the literature examining imaging findings unique to co-occurring depressive symptoms in the setting of TBI. Methods: A PRISMA compliant literature search was conducted in PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases prior to May of 2019. The initial database query yielded 4388 unique articles. These articles were narrowed based on specific inclusion criteria (e.g. clear TBI definition, statistically analyzed the relationship between neuroimaging and depression, quantified the time interval between TBI occurrence and acquisition of neuroimaging). Results: A final cohort of 36 articles resulted, comprising the findings from 1892 brain-injured patients. 69% of the studies had civilian samples, 26% military, and 5% sport. TBI severity was 67% mild, 11% mild/moderate, and 22% all-comers with 53% being single TBI and 47% including both single and recurrent injuries. Regionally, frontal involvement constituted the highest number of statistically significant abnormalities associated with increased depression, with the vast majority of these findings being in subacute and/or chronic TBI. The most frequently reported specific localization was the anterior cingulate cortex. Of the statistically significant findings focusing on brain circuits and connectivity between regions, about two thirds also implicated frontal involvement. Conclusion: Additional inquiry with attention to specified imaging timing postinjury, consistent TBI definitions, new onset depression, and control groups is crucial to extrapolating finer discrepancies between primary and TBI-related depression.

Background: Nonconvulsive epileptic status can have many different clinical presentations and making the correct diagnose on time can be challenging. Many psychiatric disorders manifestations can be confounded with nonconvulsive epileptic status, and it is crucial to know when to suspect this condition, because the earlier it is diagnosed, the better the prognosis. Case History: A 82-year-old woman with a previous history of refractory episodes of bipolar disorder was hospitalized with catatonic symptoms. The patient presented with mutism, very poor interaction, but also had agitation with moaning and kept roaming around the ward. The patient had a history of previous catatonic episodes, when she was successfully treated with electroconvulsive therapy, achieving complete remission of the symptoms. But the procedure was contraindicated this time because the patient has suffered a hemorrhagic stroke 3 months before hospital admission, so she received pharmacological therapy. On the first days of her stay, it was noticed by care team that the patient presented unilateral myoclonus around the mouth. A video EEG was performed, which showed a nonconvulsive status. Laboratory exams showed a hyponatremia, which was investigated and was later attributed to the brain injury of the stroke. The patient was treated with phenytoin, with control of the crises and improvement of the symptoms. We review the possible psychiatric presentations of nonconvulsive epileptic status. Conclusions: This case illustrates the importance of distinguishing between psychiatric symptoms and nonconvulsive epileptic status. Elderly patients frequently have atypical presentations of diseases and diagnosing in this population can be more challenging.

Background: Catatonia is a complex syndrome characterized by a broad range of behavioral and motor abnormalities. Diagnosis can be difficult due to its overlap with other neuropsychiatric syndromes, including Parkinsonian and apathy spectrum disorders. We present a patient with catatonia, Parkinsonism, and partial response to electroconvulsive therapy (ECT) to highlight the potential regions of neuroanatomical convergence between catatonia, Parkinsonism, and disorders of diminished motivation and the challenges in diagnosing and treating catatonia. Case History: A 68-year-old patient with a history of a heart transplant for idiopathic dilated cardiomyopathy was admitted for declining speech production and motor function. He met criteria for catatonia per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); lorazepam resulted in slight improvement. Subsequent ECT sessions led to gains in spontaneous motor and speech output per the Bush Francis Catatonia Rating Scale. Magnetic Resonance Imaging revealed chronic ischemic lesions in the right thalamus, basal ganglia and cerebellum. A DaTscan showed asymmetrically decreased radiotracer uptake in the bilateral caudate (left greater than the right) and putamen (right greater than left). Despite these findings, the patient did not show improvement with carbidopa-levodopa 25/250 mg three times daily. He received maintenance ECT with minor symptomatic benefit. Conclusion: Consistent with models of catatonia, Parkinsonism, and apathy spectrum disorders, the patient’s presentation could be explained by dysregulation of cortico-striatal circuits at multiple overlapping sites. A better understanding of the neuroanatomical basis of catatonia is needed to guide treatment and predict response to benzodiazepines and ECT.

Background: Electroconvulsive therapy (ECT) is the most effective treatment for Major Depressive Disorder (MDD). Despite its clinical effectiveness, the mechanism of action of ECT remains unclear. In this study, we used diffusion tensor imaging (DTI) to evaluate the effects of ECT in the medial forebrain bundle (MFB), a prominent fiber pathway of the mesocorticolimbic system. We hypothesize that ECT would lead to variations in DTI measures in the MFB, which would correlate with a decrease in depression severity (syndromal efficacy) and anhedonia (dimensional). Methods: DTI data were acquired in 11 patients with MDD who underwent treatment with ECT. Depression severity was assessed with the Quick Inventory of Depressive Symptoms (QUIDS) and anhedonia with the Snaith Hamilton Pleasure Scale (SHAPS). The MFB was extracted using multitensor tractography. We compared fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and trace diffusivity indices before and after ECT. We also evaluated the associations between changes in DTI measures and clinical response. Results: Analysis revealed that ECT lead to a significant decrease in AD in the right MFB (t=2.81, p=0.018). We observed a significant association between greater AD decrease and improvement in depression severity (r=0.66, p=0.02), and anhedonia levels (r=0.69, p=0.018). Conclusion: ECT is associated with white matter neuroplastic changes in the MFB that explain the syndromal (categorical) response, as well as dimensional improvement in reward processing (anhedonia). Our results suggest that therapeutic response after ECT is achieved through the modulation of pathological networks involved in mood regulation, particularly positive affect and reward pathways.

Background: Alzheimer’s disease (AD) is a devastating disorder associated with neuropsychiatric symptoms (NPS). Behavioral and psychological domains are intricately linked but few studies have examined their interactions with focal gray matter (GM) density in minority Hispanic populations (ADH) compared with non-Hispanic whites (ADW) and Hispanic controls (HCH). Objective: This study aimed to test the hypothesis that increased psychiatric symptoms leads to decreased GM density in subjects with AD compared with HCH. Methods: 35 subjects (23 mild AD [13 ADH & 10 ADW] and 12 HCH) were scanned for anatomical and resting state fMRI in a Siemens 3 Tesla Skyra scanner. All subjects fulfilled the National Institute for Neurological Communicative Disorders and Stroke-Alzheimer`s Disease and Related Disorders Association criteria for probable AD. Anatomical data were processed using Freesurfer to study cortical and subcortical anatomy. Results: ADH subjects had higher frequency of NPS than ADW and HCH on the Neuropsychiatric Inventory Questionnaire (NPI-Q) symptom field for Agitation, Anxiety, Disinhibition, and Appetite. A post hoc t test showed that the Cingulate Cortex (CC) area and Left Hippocampus GM density was different between ADH compared with HCH. Resting state fMRI differences between ADW and ADH showed altered function in ADW when compared with ADH in Motor/Somatosensory cortex and in visual association cortex (Parietal). Conclusion: AD subjects with higher NPS scores on the symptom field of the NPI-Q had a negative correlation with specific brain surface areas, namely, anxiety with focal decrease GM density on left hippocampus and several CC regions. Increase in NPS may lead to neurodegeneration.

Background: According to ancient yoga manual, Hathayoga Pradeepika, Jala Neti is an important cleansing yoga practice which play a pivotal role in managing diseases of ear, nose, throat and head. Previous studies found Jala Neti effective in upper respiratory tract infection. But the therapeutic efficacy of Jala Neti for headache is lacking. Objective: This randomized controlled trial assessed the effectiveness of yoga nasal irrigation (Jalaneti) in the treatment of episodic migraine. Methods: Seventy-two patients diagnosed with episodic migraine were recruitment and randomized into two groups of Jala Neti and usual care. All patients received usual care of pain medication, education session focusing on managing migraine triggers and pain management program. Jala Neti group in addition received 3 times weekly nasal irrigation for 12 weeks. The primary outcomes were change in monthly migraine days (MMD) and the 50% responder rate (RR). Secondary outcomes were evaluated using the monthly migraine attacks (MMA), monthly headache days (MHD), and monthly acute antimigraine drug intake (MAADI). All outcome measurements were performed at treatment initiation to establish a baseline and again after 12 weeks of treatment. Results: At the end of the 12 weeks, the group receiving Jala Neti exhibited statistically significant decrease in the mean MMD compared with control intervention (P < 0.0001). Additionally, the 50% RR was significantly higher in the Jala Neti group (P < 0.0001). Furthermore, the MMA, MHD, and MAADI were also significantly lower in the Jala Neti group. Conclusion: The results of this study demonstrated that Yoga Nasal Irrigation could be effective self-managed intervention for episodic migraine.

Background: Mania can present with elevated mood, agitation, hallucinations, and thought disturbances. Symptoms may overlap with psychosis secondary to neurodegenerative disorders like Parkinson’s Disease (PD) or metabolic conditions including lithium toxicity. Lithium toxicity has been reported to cause persistent delirium in geriatric patients with organic factors such as brain atrophy. We present a manic patient with Bipolar 1 Disorder, PD, and Chronic Kidney Disease (CKD). Case History: A 69-year-old man with bipolar I disorder, PD, and Stage 3 CKD, was admitted for agitation and confusion, after adjustment of parkinsonian medications and mood stabilizers. Three months prior, worsening PD motor symptoms precluded his work and driving. One month prior, he was admitted for confusion and was discharged with a diagnosis of lithium toxicity due to CKD and accidental overdose. Lithium and amantadine were discontinued. Valproate was initiated. Postdischarge, he had visual hallucinations. On follow up, the patient presented with altered mental status, paranoia, pressured speech, grandiosity, agitation, and hypersexuality; and was admitted to the inpatient psychiatry unit. Conclusions: Diagnosis was complicated by potential overlapping symptoms of PD psychosis, PD dementia, persistent delirium triggered by lithium toxicity complicated by CKD, and bipolar 1 manic episode. This complex case may have been precipitated by cognitive impairment secondary to PD leading to accidental overdose. Lithium and kidney functions were not monitored for a decade. This presented as delirious mania, triggered by lithium toxicity. It was exacerbated by suboptimal levels of valproate. Hence, we urge close monitoring of drug levels and comorbid conditions.

Background: Lesion locations and neurostimulation sites can reveal causal links between neuroanatomy and behavior. Objective: To determine whether lesions, transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS) converge on a common “depression circuit.” Methods: We analyzed five lesion datasets (N=465), four TMS datasets (N=151), and five DBS datasets (N=101), each with incidental variance in the precise lesion or stimulation location. Diagnoses included stroke (N=269), penetrating injury (N=196), major depression (N=195), Parkinson disease (N=32), and epilepsy (N=25). Each lesion or stimulation site’s whole-brain connectivity was estimated using a normative resting-state functional connectivity database (N=1000). Connections correlated with depression score (lesion datasets) or change in depression score (stimulation datasets) were identified. Cross-circuit similarity was assessed via permutation testing on mean spatial cross-correlation. Results: Similar depression circuits were identified across all datasets (p<0.001). Circuits derived from brain lesions, TMS sites, and DBS sites all matched one another (p<0.001), as did circuits derived from patients with or without major depression (p<0.001). The combined circuit was correlated with dorsal attention network and anticorrelated with some parts of the subgenual cingulate. Antidepressant efficacy of individual TMS or DBS sites could be predicted using a depression circuit derived from the other 13 datasets (p<0.0001). This prediction outperformed our existing model based on subgenual connectivity (p<0.05). Conclusion: Lesion locations that cause depression, TMS sites that relieve depression, and DBS sites that modulate depression all converge on a common brain circuit. This transdiagnostic and cross-modal depression circuit may serve as a valuable therapeutic target for improved antidepressant treatment.

Background: As the most common cause of CNS infection in patients with untreated AIDS, Toxoplasma gondii can produce highly inflammatory and destructive lesions in brain tissue. The resulting damage can manifest as both neurological deficits and behavioral changes including acute psychosis. Case History: An HIV+Ethiopian female with no previous psychiatric history presented to the hospital with confusion, headaches and generalized weakness with neuroimaging demonstrating diffuse multifocal ring enhancing lesions. On the second day of admission, patient had been refusing HAART and began displaying paranoia resulting in a psychiatric consult. Patient endorsed persecutory delusions that staff was trying to poison her and was observed conversing with the wall which she referred to as her lawyer. Differential considerations included psychosis secondary to toxoplasmosis, CNS lymphoma, and brain abscess. Further workup significant for undetectable CD4 count, seropositive antitoxoplasma IgG, and unremarkable CSF with undetectable toxoplasma on PCR. Given suppressed CD4 count, corticomedullary and basal ganglia predominance of brain lesions, and seropositive toxoplasma, decision was made to treat for CNS toxoplasmosis with sulfadiazine and pyrimethamine. Though patient was initially paranoid starting antimicrobial therapy, olanzapine proved effective in treating psychotic symptoms that contributed to her refusal. Once antimicrobials were initiated, patient had improvement in thought content and behavior with interval reduction of toxoplasmosis lesions on serial MRIs. Conclusions: Patients with AIDS are susceptible to severe and potentially life-threatening infections which can present as psychosis. Although antipsychotics can be acutely beneficial for these manifestations, appropriate diagnosis and treatment of the underlying illness is essential.

Background: The localization of secondary manic symptoms is poorly understood, as mania has been reported following damage to multiple brain locations. Objective: We utilize the human connectome to study cases of mania following focal brain lesions, provide insight into brain regions responsible for manic symptoms, and identify potential therapeutic targets. Methods: We identified two independent patient cohorts with mania attributed to focal brain lesions; a literature cohort from published case-reports (N=41) and a clinical cohort from chart review (N=15). Lesion locations were mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state fMRI, N=1000). Results were compared with lesion locations not associated with mania (N=569), lesion locations associated with symptoms potentially related to mania (N=274), and transcranial magnetic stimulation sites reported to induce/relieve mania symptoms. Results: Lesion locations associated with mania were heterogeneous; no single brain region was lesioned in all or even most cases. However, these lesion locations showed a unique pattern of connectivity to the right-sided orbitofrontal cortex, right inferior temporal gyrus and right frontal pole. This connectivity profile was reproducible across independent cohorts, matched that of lesions associated with comorbid symptoms (criminality and delusions), and aligned with effects of therapeutic brain stimulation on mania symptoms. Conclusions: Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that appears relevant for understanding comorbid symptoms and identifying therapeutic targets.

Background: In low income settings, food insecurity is an important area of concern for people living with HIV (PLHIV). Common mental disorders (CMD; mostly depression and anxiety) are also frequently seen among PLHIV. Although the cross-sectional association between measures of poverty such as food insecurity and poor mental health has been reported, there is lack of data indicating the direction of association between food insecurity and CMD. Objective: To examine the direction of association between food insecurity and symptoms of CMD among PLHIV initiating antiretroviral treatment in Ethiopia. Methods: A total of 348 PLHIV from three public health facilities were recruited at the time of initiation of antiretroviral treatment. Household food insecurity and symptoms of CMD were assessed through face-to-face interviews at baseline, three- and six-month time points. A path model was developed using AMOS software. Results: Two-thirds of the participants were found to have moderate to severe food insecurity. After adjusting for food supplementation status, food insecurity at baseline significantly and consistently predicted high levels of CMD during subsequent assessments (three month: β=0.22; S.E.=0.10, P=0.03 and six month: β=0.30; S.E.=0.11, P<0.01). Higher CMD symptoms at baseline had only marginal (β=0.05; S.E.=0.02, P=0.045) or non-significant (β=0.03; S.E.=0.02, P=0.23) positive associations with subsequent measurements of food insecurity. Conclusions: Our data support the social causation hypothesis rather than the downward social drift hypothesis in the interaction between food insecurity and common mental disorders. Interventions addressing food insecurity may have positive effects on the mental health of PLHIV in low resource settings.

Background: Korsakoff Syndrome (KS) is an amnestic syndrome (anterograde with confabulation) due to thiamine deficiency often associated with heavy alcohol use. Neurobehavioral symptoms and treatment guidelines in KS are not well-delineated. We present a case of probable KS characterized by a typical neurocognitive profile and with atypical impulsive/compulsive behavioral disturbances. Case History: AB is a 66-year-old woman who is pacer dependent due to complex cardiovascular disease with a many-year history of heavy alcohol use culminating in subacute 40-pound weight loss, gait abnormality, and neurocognitive decline. She was found after a period of prolonged immobility, was medically and psychiatrically hospitalized, and treated with mirtazapine, quetiapine, vitamin supplementation, and physical rehabilitation. Gait symptoms resolved and cognition partially improved; however, neuropsychiatric symptoms persisted including impulsive/compulsive behaviors (shoplifting, excoriation, compulsive urination, food-seeking, etc.), apathy, insomnia, and anterograde memory difficulties with confabulation. Neuropsychological and neuropsychiatric evaluations revealed impairments in attention, executive functioning, and all memory stages. Head CT demonstrated frontal-parietal atrophy and anterior white matter abnormalities. Pacemaker precluded MRI. KS was suspected and donepezil initiated which resulted in neurobehavioral improvement. Conclusions: AB’s neuropsychological profile is consistent with KS including deficits in memory, executive function and confabulation. Although disinhibition and apathy have been reported, compulsive behaviors in KS have not been well-described. Frontal and subcortical disruptions (e.g. mammillothalamic tract) due to injury may underlie observed impairments. Improvement in memory abnormalities in KS with donepezil are consistent with prior case-reports; improvement in the described spectrum of behavioral disruption with donepezil has not previously been reported in KS.

Background: Corticobasal degeneration (CBD) is a rare form of dementia that is involves cortex & subcortical structures. Definitive diagnosis is postmortem neuropathological examination. Clinical presentation is highly varied & overlaps with other neurodegenerative disorders. Presentation is characterized by focal signs such as aphasia & apraxia, levodopa nonresponsive rigidity, akinesia & tremors and dementia of frontal type. Clinical diagnosis is challenging and is more often a diagnosis of exclusion. Case History: With a background presentation of unilateral resting tremors since early adulthood, 59-year-old Caucasian male presented with word finding difficulties & slowed speech, that gradually progressed to complete inability to speak in next 5 years. He developed gait issues and frequent falls at the age of 65 and was unable walk by the age of 67. He developed swallowing difficulties and was moved to a nursing care facility. Hallucinations and REM Behavior Disorder manifested during the later stages of illness. He died at 69 with aspiration pneumonia. Maternal uncle was diagnosed with Lewy Body Dementia. Postmortem neuropathological examination was consistent with a diagnosis of frontotemporal lobar degeneration with tauopathy of type CBD. Astrocytic plaques and ballooned neurons were found. Very few amyloid and no neuritic plaques signify low probability of Alzheimer’s Dementia. MAPT gene sequencing and genetic counseling of family members is indicated, in view of positive family history. Conclusion: Clinical and biological criteria are needed to operationalize the antemortem diagnosis of CBD. This might help in a great way in researching therapeutic agents that might benefit CBD.

Background: Psychogenic nonepileptic seizures (PNES) can mimic epileptic seizures, but they have another cause, the most common being conversion disorder. Although there is no typical semiology that differentiates PNES from epilepsy, some atypical clinical presentations require video EEG for investigation. Case History: A 22-year-old female patient with no psychiatric history started seizures 3 years ago. Seizures were described as loss of contact with the environment, starring, evolving to cervical contracture and posterior generalized tonic-clonic seizure, lasting from a few minutes to an hour. The seizures initially occurred once a week and progressed to daily seizures. They were usually triggered for emotional reasons, especially conflicts with his brother, who suffered from epilepsy and intellectual disability. Report of having suffered aggression from her brother from 13 to 18 years old, which usually occurred in the days after her brother presented epileptic seizure. The brother's seizures began in his brother's childhood, and the semiology was almost identical to the patient's, excluding the shorter duration. Patient started using Topiramate and Diazepam, reducing seizure frequency to twice a week. We review the distinguishing clinical features between PNES and epilepsy. Conclusions: This case illustrates the importance of distinguishing between PNES and epilepsy and when to suspect of the former. Patients with PNES tend to mimic other diseases, which occurred in this case between the patient and her brother.

Background: Heautoscopy upon beginning mirtazapine and resolution upon discontinuation of this agent had not heretofore been described. Such a case is presented. Case History: This 19-year-old woman presented with bizarre behavior discovered by police standing outside in the cold staring. She described episodes of epochs of losing track of time and that she would scare others around her and was unaware of what was happening during those episodes. The patient was placed on mirtazapine 15 mg and within two days she had an acute episode which was three minutes in duration in which she felt that her actual face was projected onto the face of her roommate and her hair was projected on the hair of her roommate but, unlike her current black hair, it was red hair (the patient’s hair color several years earlier). During this period, she heard no voices nor did she feel paranoid or out of touch with reality. Mirtazapine was stopped and this episode has not recurred three months since the event. Conclusions: Mirtazapine lowers seizure threshold and may have induced temporal lobe seizures causing the symptoms which resolved when discontinued. The temporal relationship onset and offset associated with mirtazapine use suggests that mirtazapine is the origin for this disorder. Query as to presence of autoscopic an heautoscopic hallucinations in those taking mirtazapine or other antidepressants is warranted.

Background: A patient who's hyposmia and subjective hypogeusia improved with oral vitamin A treatment and which recurred when this treatment was discontinued, is presented. Case History: This 60-year-old right handed male, of eight years prior presentation, over one year, noted a gradual total loss in ability to smell. Concurrent with smell loss was taste loss, to less than 10% of normal. The patient was begun on daily vitamin A, 10,000 units, orally. Over two months his smell gradually improved, from 0% initially to 60% of normal. His taste from 0% to 40% of normal, and persisted beyond the first bite. The vitamin A was discontinued and within one month, his sense of smell and taste vanished. Abnormalities on Baseline Chemosensory testing: Anosmia on: Olfactory testing: Quick Smell Identification Test: 0. Olfactometer Identification Test: left: 6, right: 6. Alcohol Sniff Test: 0. Phenyl Ethyl Alcohol Threshold Testing: Left: greater than –2.0; Right: greater than –2.0. Olfactometer Olfactory Threshold Testing: Left: 4.0; Right: 0. Retronasal Olfactory Testing: Retronasal Smell Index: 1 (anosmia). Gustatory Testing: Propothyrouracil Distaste Test: 9 (normogeusia). Before Vitamin A treatment Pocket Smell Identification Test: 1/4 (anosmia). With Vitamin A treatment: Pocket Smell Identification Test: 3/4 (hyposmia). Conclusions: That this patient’s hyposmia and subjective hypogeusia improved with oral vitamin A treatment, and relapsed after the treatment was discontinued, strongly suggests that vitamin A was the actual therapeutic factor. A trial of oral vitamin A in those who have hyposmia or subjective hypogeusia is warranted.

Background: Chemosensory simultagnosia has not heretofore been reported. Case History: Case 1: This 85-year-old right-handed male sustained a right frontal subdural hematoma and one week later, his smell dropped to 35% and taste to 50% of normal. When presented with two separate flavors, he was unable to taste them combined, but rather as individual flavors. Chemosensory testing: Anosmia on: Phenyl Ethyl Alcohol Threshold Testing: > −2.0, Alcohol Sniff Test: 2 and Retronasal Smell Index: 2. Ageusia on: Propylthiouracil Disc Taste Test: 0. CT scan: Encephalomalacia in bilateral, left greater than right, frontal and temporal lobes. Case 2: This 50-year-old right-handed woman until two years prior to presentation experienced an upper respiratory infection followed by decreased ability to smell to 10% of normal and absent taste. Coffee alone tastes bitter. Cream alone tastes sweet. When she mixes coffee with the cream, they taste as if they are separate and distinct. Chemosensory testing: Anosmia on: Alcohol Sniff Test: 6, Dirhinous Phenyl Ethyl Alcohol Threshold Testing: > −2.0, Olfactometer Identification testing: left: 8, right: 6. Brief Smell Identification Test: 3. Retronasal Smell Index: 5. Gustatory testing: Propylthiouracil Disc Taste Test: 9 (normoguesia). Conclusions: The central processing for flavor is localized to the insula, operculum, anterior cingulate cortex, and orbital frontal cortex. A lesion in these structures may prevent central integration and thus fusion of olfactory and gustatory input. In those who suffer from simultagnosia, query as to chemosensory simultagnosia is warranted.

Background: STAR syndrome is a rare x-linked dominant syndrome associated with syndactyly, telencanthus, anogenital malformations, and renal malformations. Other physical abnormalities, including neuroanatomical malformations, have also been documented. However, the potential neurocognitive sequelae of STAR syndrome have not been examined. Caregivers are therefore provided with limited guidance regarding cognitive development for children with this rare condition. Case History: The authors report findings from a neuropsychological evaluation, magnetic resonance imaging (MRI), and genetic evaluation for a 10-year-old, right-handed Hispanic female with English language dominance. Genetic testing identified a deletion of exons on the FAM58A gene, supporting a diagnosis of STAR Syndrome. The patient experienced multiple medical complications, including syndactyly, tethered cord, anorectal malformation, vesicoureteral reflux, and cardiac abnormalities. MRI of the brain documented moderate ventriculomegaly and global mild cerebral white matter hypoplasia with associated thinning of the corpus callosum. Speech-language delays were noted in the patient and her brother, suggesting a potential genetic contribution. Neuropsychological testing identified a discrepancy between verbal and nonverbal abilities, with stronger nonverbal abilities. The patient’s language-based skills were below age expectation across domains, including learning/recall and reading. Deficits in skills associated with anterior brain networks (e.g. bilateral fine motor coordination, attention, and executive functioning) were also observed. Conclusion: Findings suggest potential neurocognitive risks associated with STAR syndrome. Further, the present case is the second known case to document neuroanatomical abnormalities in patients with this condition. Neuroimaging and neuropsychological assessment may play an important role in comprehensive, quality care for patients with STAR syndrome.

Background: Electrical injury (EI) can result from direct contact with a source of electricity and may result in diverse symptoms from minor burns to extensive, multisystem trauma/damage. EI patients may experience cognitive sequelae, as well as neuropsychiatric disturbances, such as mood symptoms; sleep disturbances, irritability, reduced libido, and distractibility. Objective: This research aimed to characterize the neuropsychiatric manifestations and neuroimaging findings in patients with EI. Methods: This cross-sectional study examined a case series of 30 consecutive EI patients who underwent neuropsychological evaluation and received a 3T brain MRI study as part of postacute evaluation and treatment at an academic medical center. Patients with a history of dementia were excluded. Imaging results were classified as normal and abnormal and depressive symptoms were assessed via the Beck Depression Inventory-2nd edition (BDI-II). Data were analyzed using analysis of variance (ANOVA). Results: The sample consisted of 6 females and 24 males with the mean age of 46.60±9.12, mean education of 12.53±1.43, and mean BDI-II score of 22.48±12.22. Brain MRI studies were reported as normal in 18 of the subjects and abnormal in 12 patients. Abnormal findings were mostly white matter hyperintensities and frontal atrophy. No statistically significant BDI-II score differences emerged between normal and abnormal MRI groups, [F (1, 27)=0.062, p=0.805]. Conclusion: EI patients evidenced moderate depressive symptomology postinjury. Interestingly, no MRI changes were found in the majority of the patients suggesting that depression in EI patients is not associated with detectable structural changes in the brain on standard MRI.

Background: Artificial neural networks (ANN) are biologically-inspired computational models that have recently come to the forefront of both artificial intelligence research and the awareness of the general population, however, few appreciate their origins in neuropsychiatry. Similarly, research into biological neural networks and the human connectome is redefining our understanding of the structure and function of the brain. Objective: Increase the understanding of ANNs within the neuropsychiatric community and demonstrate their usefulness as a conceptualization of how the brain functions in normal and pathological states. Methods: Literature review focusing on the history of ANNs, current use in neuropsychiatric research, and evidence supporting dysfunction of biological networks in pathological states. Utilization of visualizations that facilitate an understanding of ANNs and demonstrate dysfunction of biological networks as represented by ANNs. Results: ANNs have a wide array of applications from learning to play video games to decision methods and classifiers. Recently they have been used to improve understanding of the structure and function of the ventral stream. Similarly, network dysfunction is a growing area of research in neuropsychiatry from depression and functional movement disorders to schizophrenia and neurodegeneration. Conclusion: There is emerging evidence that ANNs may be useful in improving the understanding the human connectome in both normal and pathological states, which warrants further research and consideration.