Case Presentation: A 55 year-old woman with a history of antibody-mediated autoimmune encephalitis (AME) treated 1 year ago presented to the hospital with confusion and hyperactivity following intentional overdose of amitriptyline and clonazepam. 1 week prior, the patient reported increasing her amitriptyline dose for worsening headache. 5 days later, she took four times the prescribed dose of clonazepam for increasing anxiety and reported a fall on the day of admission. On presentation, her vital signs were T 36.6 oC, HR 96, BP 127/88, RR 16, and O2 saturation 100% on room air. Exam was significant only for an anxious appearing woman with stuttering speech and tangential thought process.

EKG revealed prolonged QTc interval (508 ms). Initial blood work was significant for WBC count 14.42 x 109/L with negative toxicology panel. CT scan of the head was normal. The patient was admitted to telemetry for monitoring following discontinuation of amitriptyline and clonazepam. Over the next 3 days, the patient became progressively agitated and paranoid, which was attributed to benzodiazepine withdrawal. Clonazepam was restarted with some improvement in agitation, but on subsequent evaluation she was delusional with visual hallucinations. The patient complained of intermittent tremors, for which valproic acid was started. An MRI of the brain revealed no abnormalities, and 24 hour VEEG showed no epileptiform activity.

A serum paraneoplastic panel was significant for elevated VGCC antibody and CSF encephalitis panel was significant for VGCC antibody as well as glutamic acid decarboxylase antibody (GAD-65). The patient was started on IVIG and steroids, but continued to experience tremors. She was started on rituximab for recurrent AME and had complete resolution of her symptoms 1 month after discharge.

Discussion: AME is characterized by acute to subacute cognitive dysfunction, mood or behavior changes, and/or seizures in the presence of one or more antibodies against a neuronal target. Symptoms are often non-specific and patients are often misdiagnosed as psychiatric conditions early in the course of disease. Development of neurological symptoms should prompt further evaluation.

Our patient had been misdiagnosed with schizophrenia prior to discovering high titers of VGCC antibody in both serum and CSF samples. Recurrence of disease was masked by amitriptyline overdose, which may present with confusion, agitation, and hallucinations. Benzodiazepine withdrawal can manifest with agitation, delirium and seizures, delaying diagnosis even further. Treatment of AME due to VGCC and GAD-65 antibodies involves IVIG, steroids and rituximab. Plasma exchange has also been reportedly successful.

Conclusions: AME is a disorder characterized by non-specific neuropsychiatric symptoms and is often misdiagnosed on initial presentation. Patients without a known cancer at time of diagnosis should have workup for malignancy.