The importance of early immunotherapy in patients with faciobrachial dystonic seizures

Faciobrachial dystonic seizures (FBDS) are the first adult-onset autoantibody-mediated epilepsy. Thompson et al. describe 103 patients with FBDS, and show that seizures are responsive to immunotherapy, with early seizure cessation reducing long-term disability and preventing cognitive impairment. Po...

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Published in:Brain (London, England : 1878) England : 1878), 2018-02, Vol.141 (2), p.348-356
Main Authors: Thompson, Julia, Bi, Mian, Murchison, Andrew G, Makuch, Mateusz, Bien, Christian G, Chu, Kon, Farooque, Pue, Gelfand, Jeffrey M, Geschwind, Michael D, Hirsch, Lawrence J, Somerville, Ernest, Lang, Bethan, Vincent, Angela, Leite, Maria I, Waters, Patrick, Irani, Sarosh R
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Language:English
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Summary:Faciobrachial dystonic seizures (FBDS) are the first adult-onset autoantibody-mediated epilepsy. Thompson et al. describe 103 patients with FBDS, and show that seizures are responsive to immunotherapy, with early seizure cessation reducing long-term disability and preventing cognitive impairment. Potential pathogenic mechanisms include complement fixation and LGI1-ADAM22 complex internalisation. 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. awx323media1 5681705685001
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awx323