Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis

Abstract

Purpose of review To assess the seizure manifestations and risk of epilepsy in encephalitis associated to antibodies against neuronal cell-surface (AE) or myelin-associated antigens, and to review several chronic epileptic disorders including, Rasmussen’s encephalitis (RE), fever-induced refractory epileptic syndromes (FIRES), and new-onset refractory status epilepticus (NORSE). Recent findings Seizures are a frequent manifestation of AE. Some AE may associate with characteristic features: faciobrachial dystonic seizures (anti-LGI1 encephalitis), EEG extreme delta brush (anti-NMDAR), or multifocal FLAIR-MRI abnormalities (anti-GABAAR). In anti-LGI1 encephalitis, cortical, limbic, and basal ganglia dysfunction results in different types of seizures. AE or myelin-antibody associated syndromes are often immunotherapy-responsive and appear to have a low risk for chronic epilepsy. In contrast patients with seizures related to GAD65-antibodies (an intracellular antigen) frequently develop epilepsy and have suboptimal response to treatment (including surgery). RE or FIRES may occur with autoantibodies of unclear significance and rarely respond to immunotherapy. A study of patients with NORSE showed that 30% developed chronic epilepsy. Summary Although seizures are frequent in all types of AE, the risk for chronic epilepsy is dependent on the antigen: lower if located on the cell-surface, and higher if intracellular. For other disorders (RE, FIRES, NORSE) the prognosis remains poor.

Seizures as a clinical manifestation in somatic autoimmune disorders

“…Antibodies to intracellular proteins may be generated by an immune response to tumor antigens including CNS proteins. Antibodies to extracellular neuronal (or glial) surface antigens such as the N-methyl-Daspartate (NMDAR), and other glutamate receptors, leucine-rich glutamate inactivated 1 (LGI1), contactin-associated protein like 2 (CASPR2), a-methyl-4-isoxazolepropionic acid (AMPA), dipeptidylpeptidase-like protein 6 (DPPX), and gamma-amino butyric acid (GABA) receptors, are thought to be directly pathogenic in AE [19][20][21][22][23][24]. People with these antibodies often improve with immunotherapy [20][21][22].…”

Prevalence and outcome of late‐onset seizures due to autoimmune etiology: A prospective observational population‐based cohort study

“…Due to demographic changes in developed countries the management of late‐onset seizures will be a major future challenge. Autoimmunity is a recently evolving cause of unprovoked seizures . Frequently, it manifests as limbic encephalitis (LE).…”

Early ictal and interictal patterns in FIRES: The sparks before the blaze

“…Adoption of a unified nomenclature (i.e., FIRES), 17 has allowed for researchers to describe the clinical, 4,9 radiologic, [18][19][20] and electrophysiologic characteristics of this unique disorder in pediatrics. 21,22 Gaps remain in the diagnostic criteria, in part due to the lack of an understanding of the underlying etiology. 21,22 Gaps remain in the diagnostic criteria, in part due to the lack of an understanding of the underlying etiology.…”

“…4 Further work is being done to assess for overlap with the New Onset Refractory Status Epilepticus (NORSE) and other inflammatory/immune-mediated epilepsies. 21,22 Gaps remain in the diagnostic criteria, in part due to the lack of an understanding of the underlying etiology. Early diagnostic markers have the potential to advance our knowledge of disorder and enhance clinical care.…”