Early Immunotherapy Prevents Disability With Limbic Encephalitis

Nancy A. Melville

October 18, 2017

SAN DIEGO — Early immunotherapy for faciobrachial dystonic seizures that precede the onset of limbic encephalitis is highly effective in preventing cognitive impairment and long-term disability, new research suggests.

"Faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment," first author, Sarosh R. Irani, MD, head of the Oxford Autoimmune Neurology Group, University of Oxford, United Kingdom, told Medscape Medical News.

"The latter is especially interesting — we may be able to prevent the development of a full-blown encephalitis with immunotherapy to treat the faciobrachial dystonic seizures, which often start before the cognitive impairment."

The study was presented here at the ANA 2017: 142nd Annual Meeting of the American Neurological Association.

Dr Irani and his colleagues first described the syndrome of faciobrachial dystonic seizures that occur, with or without cognitive impairment, before limbic encephalitis in a study in 2011.

The syndrome is known to be caused by voltage-gated potassium channel complex/LGI1 antibodies, and treatment with immunotherapy, though shown in small studies to be effective, has not been well defined.

To better understand the seizures and the effects of treatment on long-term disability and cognitive impairment, Dr Irani and his colleagues evaluated 103 patients with faciobrachial dystonic seizures and LGI1-antibodies, with and without cognitive impairment.

Sixty-two percent of the patients were male, and the median age was 64 years.

The results showed that treatment with antiepileptic drugs alone was minimally effective, achieving cessation of the seizures in only 9 of 89 patients (10%).

However, among those treated with immunotherapy, as many as 51% had cessation of the seizures within 30 days of initiation of the immunotherapy; the effect was more rapid among those without cognitive impairment (P = .03).

The timing of the immunotherapy was important — for each week of delayed immunotherapy, there was a 5% relative reduction in the probability of cessation of the faciobrachial dystonic seizures.

Meanwhile, a shorter time to immunotherapy predicted reduced disability at a 24-month follow-up (P = .03), as did the absence of cognitive impairment (P = .001).

Among 80 patients who had the seizures as their initial feature, as many as 56% developed cognitive impairment after 90 days of active seizures, whereas only one patient developed cognitive impairment after cessation of the seizures (P < .0001).

"The effect size was a surprise — it was huge," Dr Irani told Medscape Medical News.

"Our more small-scale observations did suggest immunotherapies were going to be more effective than antiepileptic drugs, but the magnitude of the effect was the real surprise."

In terms of other notable patient characteristics, the study showed that 22 of the 103 patients without cognitive impairment typically had normal brain imaging, electroencephalograms, and sodium levels (P < .0001) and almost exclusively IgG4 LGI1 antibodies (P = .009), whereas patients with cognitive impairment frequently had IgG1 antibodies (P = .03).

First author, Julia E. Thompson, from the Oxford Autoimmune Neurology Group at the University of Oxford, noted that  the study demonstrates the natural history of the development of seizures that lead to cognitive impairment in limbic encephalitis — and the urgency of treatment.

"Because these were seizures, some people were initially being treated with antiepileptic drugs, but they just weren't working," she told Medscape Medical News.

"So this study shows that you have to give immunotherapy from the moment of diagnosis, the sooner the better because with every delay there's an increased risk of disability."

David M. Holtzman, MD, president-elect of the American Neurological Association and the Andrew B. and Gretchen P. Jones Professor and Chairman, Department of Neurology, Washington University School of Medicine, St Louis, Missouri, also commented on the findings for Medscape Medical News.

"The clinical significance is that early recognition of this disorder and early treatment appears to result in better outcome," he said.

"This is a rare disorder, so implications for treatment rely on recognition of this syndrome and appropriate lab testing," Dr Holtzman added. "There are risks of immunotherapies. However, this disease untreated often leads to significant morbidity and mortality."

Dr Irani is a coapplicant and receive royalties on patent application WO/2010/046716, titled Neurological Autoimmune Disorders. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other voltage-gated potassium channel complex antibodies. Dr Holtzman has disclosed no relevant financial relationships.

ANA 2017: 142nd Annual Meeting of the American Neurological Association. Abstract S111. Presented October 16, 2017.

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