The effects of immunotherapy and antiepileptic drugs on seizures in autoimmune encephalitis

A group of researchers from the Netherlands investigated the difference in efficacy between immunotherapy and antiepileptic drugs (AEDs) as treatment for seizures in patients with autoimmune encephalitis (e.g. anti-LGI1, anti-NMDA receptor and anti-GABA_BR encephalitis).

Seizures occur frequently in autoimmune encephalitis. In this study of 153 patients with autoimmune encephalitis, 110 of patients manifested with epileptic seizures. Most of these patients received immunotherapy (101 patients) and AEDs (100 patients). Nine patients were treated only with AEDs.

Looking at the effects of AEDs, most seizures were refractory (did not improve/stop) to AEDs even after changing dosage or treatment regimen. In some patients, the use of AEDs was followed by serious manifestations: behavioural changes, psychosis and suicidal thoughts. AED had no influence on faciobrachial dystonic seizures (FBDS) (type of seizures in anti-LGI1 encephalitis). Being on AEDs didn’t prevent relapses which were resolved with immunotherapy within days or weeks.

Comparing the effects of immunotherapy with those of AEDs, immunotherapy resulted in seizure freedom faster (28 days from the start of the treatment) than AEDs (59 days from the start of the treatment) and also more often (53% of patients) than AEDs (14% of patients). Patients treated earlier on in disease course with immunotherapy were seizure-free quicker. For example, almost half of the patients with anti-LGI1 encephalitis became seizure-free within a week after immunotherapy, while they had been resistant to AEDs for longer time.

Overall, 89% of all patients with seizures became seizure-free. Only one patient developed epilepsy after acute stage of encephalitis. Most patients stopped using AEDs successfully after resolution of encephalitis.

This study is very important for a number of reasons. It highlights that:

• Immunotherapy is crucial in autoimmune encephalitis.
• AEDs should be given as an addition to immunotherapy and not as primary treatment in autoimmune encephalitis. The authors suggest using AEDs (like carbamazepine or potentially oxcarbazepine) as first add-on next to immunotherapy in the symptomatic treatment of patients with anti-LGI1 encephalitis and seizures. However, caution is needed on rapid dosage increase due to side-effects (rash).
• The development of epilepsy after autoimmune encephalitis treated with immunotherapy is rare.
• Long-term AEDs use does not appear to be necessary in most patients with autoimmune encephalitis.

Given the importance of early immunotherapy, the authors conclude by emphasizing the need to consider autoimmune encephalitis as cause of drug-resistant seizures especially when patients don’t present with other symptoms specific to autoimmune encephalitis syndromes.

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A.A.M. de Bruijn M., van Sonderen A., van Coevorden-Hameete M.H., et al. (2019) Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology; 92:e2185-e2196. doi:10.1212/WNL.0000000000007475

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