The workup of patients with suspected autoimmune etiology should include a magnetic resonance imaging (MRI) scan of the brain, EEG, and lumbar puncture. In patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, MRI abnormalities consisting of nonspecific lesion are seen in 30 % of cases, EEG is abnormal in 90 %, of cases and CSF may show elevated oligoclonal bands. Blood and cerebrospinal fluid (CSF) samples to screen for paraneoplastic and autoimmune antibodies should be obtained. Several companies offer panels of tests for these antibodies. Markers of inflammation like erythrocyte sedimentation rate (ESR), C-reactive protein, and von Willebrand factor antigen may help determine the burden of the inflammatory process. At times, further testing is needed to exclude other etiologies that may be considered in the differential diagnosis of limbic encephalitis including herpes simplex virus (HSV) and human herpesvirus (HHV)-6 encephalitis, systemic lupus erythematosus, Hashimoto thyroiditis, Sjogren syndrome, antiphospholipid syndrome, and primary angiitis of the CNS [4]. In addition, evaluation for an associated neoplastic entity may require doing a computed tomography (CT) of the chest, abdomen, and pelvis or a positron emission tomography (PET) scan and pelvic or scrotal ultrasound.

The EEG in cases of limbic encephalitis is almost invariably abnormal, as noted above. There is often diffuse slowing in the theta to delta range. There may be evidence of epileptiform discharges over one or both temporal lobes. Seizures may be clinical or subclinical, and in some cases NCSE or epilepsia partialis continua (EPC) may be seen [5]. An extreme delta-brush pattern may be seen in some cases of anti-NMDA receptor encephalitis, illustrated in Fig. 1 [6]. The use of cEEG may at times be helpful to identify recurrent NCS. Samples of EEG changes seen in cases of limbic encephalitis, namely, in anti-NMDA receptor and anti-voltage-gated potassium channel (VGKC) complex encephalitides may be found in Figs. 2 and 3. In cases of anti-NMDA receptor encephalitis, abnormal orofacial dyskinesias may mimic seizures, and cEEG shows no associated epileptiform correlates with these events.

In patients with autoimmune limbic encephalitis, it is important to establish whether there is a tumor associated with the encephalitis. If a tumor is found, removal of the tumor allows for neurologic improvement. In many cases a tumor may not be present and immunotherapy is needed. Often, a course of steroids or intravenous immunoglobulin (IVIG) is tried with or without plasma exchange. Many patients also require additional immunotherapy with rituximab, cyclophosphamide, or other immunomodulatory agents. It is well known that autoimmune encephalitides related to cell surface antigens respond to immunotherapy. These patients often recover over few months, and some may require continued use of immunotherapy.