A Patient With Anti-LGI-1 Limbic Encephalitis Diagnosed as Conversion Disorder

Mr. X is a 49-year-old Caucasian male with no reported psychiatric history and medical history significant for type 2 diabetes mellitus and untreated obstructive sleep apnea (OSA) who presented to the psychiatric emergency department reporting a 4-month history of episodic memory loss, confusion, anxiety, and involuntary motor movements.

Approximately 4 months prior to psychiatric hospitalization, the patient presented to his primary care provider after 1 week of memory loss, mood lability, and anxiety in the context of psychosocial stressors. He was prescribed a selective serotonin reuptake inhibitor (SSRI) for suspected anxiety and was referred to neurology and psychiatry for further assessment.

The patient was evaluated by neurology 1 month after symptom onset. Neurological exam was nonfocal. MRI of the brain and brainstem with and without contrast showed nonspecific, nonenhancing white matter changes, with a focus seen within the subcortical white matter of the left frontal lobe. Radiology noted the MRI findings were most consistent with chronic small-vessel ischemic change or possible migrainous changes. Electroencephalogram (EEG) was negative for epileptiform activity, and a sleep study confirmed previously diagnosed OSA.

The patient was evaluated by outpatient psychiatry 2 months after symptom onset for a generalized feeling of restlessness and muscle twitching. He was diagnosed with unspecified anxiety disorder and referred to cognitive-behavioral therapy for anxiety. The SSRI was discontinued per the patient’s request due to lack of improvement of anxiety and the adverse effect of erectile dysfunction.

Three months after symptom onset, Mr. X informed neurology of episodes of body shaking, lip quivering, and disorganized speech occurring several times a day. Additionally, he noticed intermittent difficulty holding objects and unsteadiness associated with ground-level falls, one of which resulted in a rib fracture. Seizures were suspected, and lamotrigine was prescribed, with a plan to titrate to 100 mg twice daily. A referral was made to an epilepsy monitoring unit.

One week later, the patient developed involuntary jerking movements of his left arm, three to four times per hour. A 24-hour EEG captured several episodes of limb jerking and vocal outbursts, described as "occasional right more than left upper extremity jerk where arm would fly over and behind his head, sometimes associated with a grimace of his face." EEG was negative for epileptiform activity. Neurology diagnosed functional neurological disorder, also known as conversion disorder. The patient was instructed to continue therapy, lamotrigine titration, and consistent use of a CPAP machine.

The following week, Mr. X and his wife presented to the psychiatric emergency department because the patient had no memory of their son’s wedding months prior and had exhibited confusion at work, where he believed he was climbing into an airplane while getting into a work vehicle. Because the patient had been evaluated on an outpatient basis by neurology and psychiatry with no improvement in symptoms, he was admitted to the psychiatric hospital. During evaluation, family history was notable for a sister, maternal grandmother, and paternal uncle with seizure disorders and paternal grandparent with frontotemporal dementia. Mental status exam showed seconds-long episodes of grimacing, hyperventilating, and shoulder and arm movement. His mood was "mellow," and affect was generally mood congruent, although with one episode of emotional lability. His thought process was linear and goal directed, although tangential at times. His insight into the reason for hospitalization was poor, as he did not recognize the decline in his functional status.

Differential diagnosis included seizures, transient global amnesia, complex migraine, encephalitis, narcolepsy, psychogenic nonepileptic seizures, and frontotemporal dementia. Because the patient had no psychiatric history, his psychiatric symptoms were inconsistent with typical presentations, and his symptoms did not respond to outpatient interventions, encephalitis was included in the differential diagnosis.

During the patient’s 5-day psychiatric hospitalization, complete blood count and comprehensive metabolic panel were unremarkable. Urine drug screen, rapid plasma reagin, and HIV 1 and 2 antibody and antigen screen were negative. Thyroid-stimulating hormone and free thyroxine were within normal limits. Vitamin B12, folate, vitamin D 25-hydroxy, and prolactin were within normal limits. Repeat MRI of brain and brainstem with and without contrast showed new or a more conspicuous focus seen within subcortical white matter of the left frontal lobe, otherwise unchanged from 3 months prior. A 30-minute EEG was unremarkable. CSF analysis was significant for elevated glucose of 141 mg/dL (reference range 40–70) and total protein 57 mg/dL (reference range 15–45). CSF showed no oligoclonal bands. An infectious and autoimmune encephalopathy panel was ordered.

Mr. X scored 26 out of 30 on the Montreal Cognitive Assessment. Neuropsychological testing, including the Full Scale Intelligence Quotient and Global Deficit Score, revealed impaired immediate and delayed memory, with an impression of mild neurocognitive disorder of uncertain etiology. The neuropsychologist was doubtful that the patient’s symptoms were representative of conversion disorder and recommended return to neurology for further assessment. During hospitalization, the patient was observed enacting his dreams, and one episode resulted in a fall and wrist fracture.

Internal medicine recommended outpatient follow-up with neurology and psychiatry. The patient’s outpatient neurologist recommended outpatient follow-up. The patient was discharged home with a DSM-5 diagnoses of unspecified tic disorder, adjustment disorder, and mild cognitive impairment (2). Upon arriving home, he had a witnessed generalized tonic-clonic seizure and was admitted to the neurology floor. Levetiracetam was started for seizures and a 5-day course of methylprednisolone and intravenous immunoglobulin for suspected encephalitis. The CSF panel was positive for LGI-1 antibody. He was referred to neuroimmunology for anti-LGI-1 limbic encephalitis.

Autoimmune encephalitis is an increasingly studied group of conditions, in which the immune system attacks normal structures within the brain, resulting in various neuropsychiatric symptoms. A subset, classified as limbic encephalitis, is mediated by antibodies that target limbic structures. Common symptoms include mood changes; sleep disturbances, including dream enactment; seizures; and subacute short-term memory loss (3, 4). Impaired stage III sleep contributes to memory loss and decreased attention. MRI findings may be normal or have hyperintensities in medial-temporal structures. EEG usually shows nonspecific abnormalities. CSF findings may include mild pleocytosis and oligoclonal bands. Presence of specific antibodies in CSF can be diagnostic (3).

Conversion disorder may present as sensory or motor deficits, such as weakness, abnormal movements, slurred speech, and nonepileptic seizures. Symptoms of conversion disorder may overlap with autoimmune encephalitis, explaining why autoimmune encephalitis may be initially misdiagnosed. The prevalence of conversion disorder is unknown, and per DSM-5, a diagnosis can be made only if a patient’s symptoms cannot be attributed to any medical condition (2).

Within the limbic encephalitis group, several antibodies have been identified, including LGI-1. Typical symptomatology of LGI-1 limbic encephalitis includes psychiatric symptoms, confusion, hyponatremia, REM sleep disorder, and faciobrachial dystonic seizures (FBDS). Treating sleep symptoms has shown to improve overall mortality rates (4). FBDS are pathognomonic and described as a rapid jerking of one side of the face or upper extremity and may precede other symptoms. FBDS are difficult to control with antiepileptics without treatment of the underlying autoimmune disease. LGI-1 limbic encephalitis is male predominant and typically presents between ages 41 and 78 (5).

First-line treatment includes steroids, intravenous immunoglobulin, and plasmapheresis. Second-line treatment includes rituximab or cyclophosphamide. Prompt initiation of treatment is associated with better results. Failure to recognize the disorder in early stages can result in irreversible changes and poor prognosis. No randomized controlled trials exist to show which treatment modalities have more favorable outcomes. Patients with treated encephalitis may partially or completely recover, but recurrence is common (6).

Patients with autoimmune encephalitis may present with psychiatric symptoms, such as mood changes, bizarre behaviors, paranoia, and memory loss, making psychiatrists a likely initial point of contact. It is imperative that psychiatrists consider autoimmune encephalitis in the differential diagnosis for patients with atypical symptoms that may mimic those of conversion disorder. Some guidelines recommend limiting unnecessary laboratory tests and imaging when diagnosing conversion disorder, because they can prolong the course of illness (7). CSF analysis should be performed if patients exhibit subacute memory loss, sleep disturbances, or FBDS despite negative imaging and serology. In this case, lumbar puncture and CSF analysis was delayed, which caused inaccurate diagnosis of conversion disorder and delayed treatment of LGI-1 limbic encephalitis. Rapid diagnosis and treatment are crucial to prevent permanent neurological complications (8, 9).

The authors have confirmed that details of the case have been disguised to protect patient privacy.