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The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

ABSTRACT: Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

SUBMITTER: Thompson J

PROVIDER: S-EPMC5837230 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

Thompson Julia J Bi Mian M Murchison Andrew G AG Makuch Mateusz M Bien Christian G CG Chu Kon K Farooque Pue P Gelfand Jeffrey M JM Geschwind Michael D MD Hirsch Lawrence J LJ Somerville Ernest E Lang Bethan B Vincent Angela A Leite Maria I MI Waters Patrick P Irani Sarosh R SR

Brain : a journal of neurology 20180201 2

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impair ...[more]

PMID: 29272336

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Project description:BackgroundSCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations.MethodsTo identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth. A detailed clinical history was obtained.ResultsA heterozygous missense mutation of SCN8A was identified in the Chinese family. Six de novo mutations of SCN8A were detected in 6 sporadic patients with epilepsy. In the family, six members developed seizures within a few years after birth. Five of them had milder clinical performance, that they had normal cognition and developmental milestones, and seizure-free was achieved by mono-therapy. The other one affected member presented with refractory epilepsy and developmental regression. She died from sudden unexpected death in epilepsy (SUDEP) at 17-year-old. Clinical features of six sporadic patients with SCN8A mutations were diverse, ranging from severe epileptic encephalopathy to benign epilepsy with normal cognition. Seizures started at the mean age of 3.9 months (from 2 months to 6 months). Seizure-free was achieved in four of them by mono- or multi-antiepileptic drugs. Five of them demonstrated mild or severe psychomotor retardation, whereas the other one was normal in development and intelligence.ConclusionsOur findings extend the spectrum of SCN8A mutations and the clinical features of patients with SCN8A mutations. The majority of SCN8A mutations were de novo, inherited mutations from the heterozygous parents can also occur. The phenotypic spectrum of SCN8A mutation varied largely. Most affected patients manifested as refractory epilepsy and severe intellectual disability, only a small number of patients presented with milder clinical patterns. Additionally, our study confirmed that the same mutation can lead to different phenotypes.

Dataset Information

The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

Publications

The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

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