Neuroimmunology Coordinating Panel on Rare Neurological Diseases

Stopping faciobrachial dystonic seizures can prevent the development of cognitive impairment in people with antibodies to leucine-rich glioma-inactivated 1 and limbic encephalitis

Antibodies to leucine-rich glioma-inactivated 1 (LGI1) are associated with faciobrachial dystonic seizures (FBDS) and limbic encephalitis. Although congnitive impairment are common, FBDS often precedes them. 

Antibodies to leucine-rich glioma-inactivated 1 (LGI1) are associated with faciobrachial dystonic seizures (FBDS) and limbic encephalitis. Although congnitive impairment are common, FBDS often precedes them. It is not clear if early treatment can stop the development of the full limbic encephalitis picture in the early stages ie. in people with FBDS only. Thompson et al. studied 103 patients with FBDS and LGI1 antibodies and sought whether cessation of FBDS can prevent cognitive impairment by treating early with immunotherapies. A number of 22 of 103 patients without cognitive impairment which had normal brain MRI, EEGs and serum sodium levels were treated. Cessation of FBDS with antiepileptic drugs alone occurred in only 10% of them, but more than half showed cessation of FBDS 30 days after addition of immunotherapy. The response was earlier in cognitively normal patients. Importantly, in patients with persistent FBDS, 56% developed cognitive impairment after 90 days. Only one patient developed cognitive impairment after FBDS cessation. The patients with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies. 

Key points

-In subjects with limbic encephalitis with LGI1 antibodies and FBDS, accelerated immunotherapy and normal cognition predict reduced disability at 24 months.

-FBDS response to immunotherapy is time-sensitive. Supressing FBDS can prevent the development of cognitive impairment.

-LGI1-ADAM22 complex internalization is a potential non-inflammatory epileptogenic mechanism in this pateints.

1. Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, Farooque P, Gelfand JM, Geschwind MD, Hirsch LJ, Somerville E, Lang B, Vincent A, Leite MI, Waters P, Irani SR; Faciobrachial Dystonic Seizures Study Group . The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2018 Feb 1;141(2):348-356. doi: 10.1093/brain/awx323

2. van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol. 2017 May;13(5):290-301. doi: 10.1038/nrneurol.2017.43

3. Irani SR , Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, et al.  Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69: 892–900