Anti-NMDA receptor antibody associated encephalitis as a cause of new-onset neuropsychiatric manifestations in children and adults can represent a significant diagnostic challenge for clinicians. Clinical signs often include encephalopathy, new-onset psychosis, and movement phenomenon. Although orofacial dyskinesias were initially identified as a characteristic movement phenomenon in this type of encephalitis, an expanded range of abnormalities has recently been reported, including isolated ataxia. We report a case of isolated hemiataxia in a young adult with mild initial psychiatric manifestations. A personal and family history of preceding neuropsychiatric symptoms produced diagnostic confusion and resulted in a significant diagnostic and therapeutic delay. Our case confirms the unilateral movement manifestations that have been emphasized in recent reports. Additionally, it confirms the need for involvement of neurologic as well as psychiatric services in the evaluation of such cases and emphasizes the importance of the neurologic examination in presentations with an initial psychiatric predominance.
Anti-NMDA receptor antibody associated encephalitis is an increasingly recognized cause of new-onset neuropsychiatric manifestations in children and adults [
Our patient, an 18-year-old female, was referred to neurology with a diagnosis of schizoaffective disorder after a possible first-time seizure. She had experienced previous mood lability and attentional impairments as a teenager and had been treated for both during that time. However, she had been off medications for 5 years and had been doing well in the recent past. Grades and athletic functioning were above average, and she played three sports in high school and was in mainstream classes. Her family history was notable for a history of maternal depression, psychogenic nonepileptic seizures, and anxiety, as well as a maternal grandmother with a reported history of schizophrenia and bipolar disorder. Eight months prior to the patient’s referral to neurology, she experienced a self-limited illness characterized by diarrhea, headache, and vomiting. This was managed at home, although she was seen by her primary care provider and diagnosed with a viral gastroenteritis. Approximately one month later, she began to experience insomnia, mood lability, and weight loss. Memory issues ensued, and the parents reported that she began to frequently lose objects and had difficulty remembering bus routes. Personal hygiene suffered, and after 4 months of worsening symptoms, she began to experience weekly episodes of urinary incontinence. There were no other autonomic manifestations. Throughout the course of the subacute illness, she experienced a “tremor” of the left upper extremity when attempting to manipulate or reach for objects, as well as dragging her left foot when ambulating. She received ongoing psychiatric treatment and monitoring, and her movement phenomenon was attributed to a psychogenic cause, and a diagnosis of likely schizoaffective disorder was made. After 7 months of symptoms, she experienced a spell, characterized by clonic movements of the left hand, followed by tonic stiffening of her entire body, with right sided head and neck deviation, lasting 30 seconds, followed by confusion and sedation. She recovered to baseline after 30 minutes. After this episode, she was referred to neurology. On initial presentation to our service, her spell was attributed to a first-time seizure by history. Mental status examination demonstrated a distracted and labile demeanor. Cognition was impaired on both bedside and formal neuropsychological testing with impairments in memory, attention, and reasoning. Neurologic examination demonstrated left sided dysmetria as well as gait disturbance arising from left lower extremity coordination impairment. MRI of the brain revealed increased FLAIR signal of the left hippocampus. No cerebellar or contralateral brain findings were identified as potential substrate for her unilateral ataxia. Electroencephalogram was normal. The combination of her ataxia, cognitive decline, and incontinence prompted an extensive laboratory evaluation for systemic conditions as well as inborn errors of metabolism. Spinal tap was performed, with testing for autoimmune and inflammatory conditions. Testing was positive only for the presence of NMDA receptor antibodies in the spinal fluid (NMDA-R Ab IF Titer Assay, CSF Positive 1 : 4 and reference < 1 : 2, Mayo Clinic Laboratories) with no evidence of active infection or inflammation. Extensive evaluation for a neoplastic substrate, specifically ovarian teratoma, was negative. Because of the extended course experienced by the patient she was started on an aggressive regimen of immune modulation, including concurrent intravenous immunoglobulin, IV methylprednisolone, and rituximab. Although her parents report that psychiatric symptoms were improving after 3 months of treatment, she continues to require medical treatment for her psychiatric manifestations and has been unable to return to school or employment. Additionally, her movement abnormalities persist.
Anti-NMDA receptor antibody encephalitis is increasingly identified as an etiology for noninfectious encephalitis in children and adults [
Our patient had mild preexisting manifestations of psychiatric difficulties, as is commonly seen in the general population in childhood, including attentional challenges and anxiety. These were not disabling for this patient and she was functioning appropriately, performing well in academics and athletics. Additional challenging historical aspects included a positive family history of psychiatric conditions in a number of relatives, which suggested a familial etiology in this individual. Although a familial predisposition is often sought in psychiatric and neurologic conditions, caution should be exercised when attributing this to causation of symptoms in the proband [
Our case emphasizes the need for a high index of suspicion for medical conditions in patients with new-onset psychiatric deterioration in childhood and adulthood. Confusing aspects, as in this case, may include a positive family history, or a relatively static or slowly deteriorating course, rather than a catastrophic presentation with acute psychosis progressing to a profound depression of level of consciousness. Inborn errors of metabolism can also present at any age with predominantly psychiatric manifestations and should be included in the differential diagnosis [
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The authors declare that there are no conflicts of interest regarding the publication of this paper.
Video demonstrating initial examination findings and changes during treatment course. At the time of initial evaluation, the patient demonstrates significant dysmetria on left sided finger to object testing. Gait demonstrates hypertonia of the ipsilateral leg with circumduction. As treatment is started she has improvements in the amplitude of the dysmetria, with more exact targeting. Symptoms persist however despite aggressive treatment.