Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management

DISCUSSION AND SUMMARY

• Positive antibody against intracellular antigen (classical onconeuronal antigens) and typical clinical picture: refer to oncology for treatment and surveillance of tumour if one was found. If no tumour was found, initiate semiannual to annual cancer screening for at least 4 years. Treat neurological relapses with intravenous methyl-prednisolone and/or cyclophosphamide as necessary but avoid long-term immunosuppression.
• Positive antibody against neuronal surface antigen with high clinical relevance and typical clinical picture: consider periodic tumour screening based on the type of antibody and each patient’s cancer risk factors. Some neuronal surface antibodies with higher rates of tumour association may require more frequent screening as in gamma-Aminobutyric acid-B receptor (GABABR)-antibody encephalitis and some may require less frequent screening as in leucine-rich glioma inactivated-1-antibody encephalitis. Consider initiating at least annual cancer screening for an average of 2–4 years based on antibody type. A more selective screening approach could be considered for antibodies with specific tumour associations. Consider long-term immunosuppression preferably with rituximab (based on presumed antibody-mediated immunity and on N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis studies) after a second attack. May consider starting long-term immunosuppression after the first attack in patients with severe initial presentation or risk factors for relapse (eg, persistently positive oligoclonal bands). Overlap with short-term oral corticosteroids after initiation of long-term agent. The duration of long-term immunosuppression depends on relapse rate, relapse severity and tolerability of the immunosuppressive agent.
• Positive antibody against neuronal surface antigen with low clinical relevance to the clinical presentation: evaluate confidence in the clinical relevance of the positive antibody based on clinical and ancillary data. Evaluate for alternative aetiologies. If the diagnosis of autoimmune encephalitis (AE) is felt to be probable and no other aetiology found then follow recommendation 2.
• Seronegative AE: confirm the diagnosis according to published criteria and exclude alternative causes. May consider initiating annual cancer screening for an average of 4 years for seronegative definite autoimmune limbic encephalitis and may consider periodic screening for an average of 2 years for all other neuroanatomical variants. Start long-term immunosuppression with rituximab, mycophenolate mofetil or azathioprine after a second attack. Overlap with short-term corticosteroids after initiation of long-term agent. The duration of long-term immunosuppression depends on relapse rate, relapse severity and tolerability of the immunosuppressive agent. Recommendations for seronegative AE are particularly anecdotal and more research is needed for this subtype of AE.
• For all AE subtypes: treat residual symptoms including seizures, movement disorders, psychiatric symptoms, spasticity, sleep dysfunction and dysautonomia. Also start de-escalation of symptomatic medications when appropriate. Start physical, occupational and speech therapy depending on residual deficits. Strongly consider neuropsychological rehabilitation although the value behind this intervention is in need for further research to establish scientific evidence.