Epilepsy Information

(Abst. 1.135)

Partial seizures and behavioral changes in two patients with anti-nmda autoimmune limbic encephalitis

Authors: Jeffrey Politsky, S. Stoller and J. Halperin

Limbic encephalitis (LE) was initially described as an inflammatory paraneoplastic process over 40 years ago. Scientific advances have revealed that LE consists of multiple related entities characterized by disturbances in behavior and memory function reflecting temporal lobe and limbic involvement. Patients often present with confusion and personality change, but disseminated neurologic involvement including frank psychosis, seizures, and ataxia can occur. The somewhat bizarre presenting symptoms often lead to delays in diagnosis, resulting in significant morbidity and mortality. There is no defined treatment regimen.


We report two patients who presented to the Atlantic Neuroscience Institute Epilepsy Center with acute and progressive changes in personality and behavior, followed by partial seizure activity. Both patients were seen initially and in follow-up by the authors. Immunolabeling of hippocampal neurons from CSF samples was performed at University of Pennsylvania by Dr. Josep Dalmau. We review the initial diagnostic studies, treatment regimen, and clinical outcomes.

The patients included one male and one female and shared the clinical presentation of confusion, behavioral changes, and focal seizures. Both were initially misdiagnosed as having anxiety-related symptoms. Patient 1 was a 36-year old male. Initial investigations including MRI brain, EEG, and CSF were negative. Initial symptoms included difficulty focusing, body undulations, and a draining sensation washing over him in waves. Initial exam revealed micro-square wave jerks, hyper-reflexia, ataxia, and dysautonomia. Within 48 hours of admission, 3 secondarily generalized convulsions were recorded (left temporal lobe onset). The patient declined rapidly. He underwent empiric, but futile treatments with methylprednisolone and plasma exchange therapy. A brain biopsy was negative. Patient 2 was a 20 year old female who presented with a personality change (apathy & poor judgment), language and cognitive dysfunction. Initial EEG revealed focal slowing evolving to frequent runs of left fronto-temporal slowing. Empiric treatment with methylprednisolone failed. In both cases, repeat CSF studies were mildly abnormal due to elevated white count. Subsequent CSF analyses performed at University of Pennsylvania demonstrated anti-NMDA antibodies on the hippcompal neuropil. Ultimately, both patients received therapy with rituximab. Repeated investigations for cryptic neoplasms were negative in both patients. One year after diagnosis and discharge, both patients have returned to 95% normal baseline function, except for mild executive dysfunction: emotional lability (patient 1), mildly impaired judgment (patient 2).

We have reported two patients with non-paraneoplastic anti-NMDA limbic encephalitis with excellent outcomes in response to rituximab. While this diagnosis is uncommon, two cases presented within a six month period. Significant morbidity can be avoided with knowledge of the diagnosis, an appropriate index of suspicion, and access to appropriate testing facilities.