Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype.

Voltage-gated potassium channel complex antibodies, particularly those directed against leucine-rich glioma inactivated 1, are associated with a common form of limbic encephalitis that presents with cognitive impairment and seizures. Faciobrachial dystonic seizures have recently been reported as immunotherapy-responsive, brief, frequent events that often predate the cognitive impairment associated with this limbic encephalitis. However, these observations were made from a retrospective study without serial cognitive assessments. Here, we undertook the first prospective study of faciobrachial dystonic seizures with serial assessments of seizure frequencies, cognition and antibodies in 10 cases identified over 20 months. We hypothesized that (i) faciobrachial dystonic seizures would show a differential response to anti-epileptic drugs and immunotherapy; and that (ii) effective treatment of faciobrachial dystonic seizures would accelerate recovery and prevent the development of cognitive impairment. The 10 cases expand both the known age at onset (28 to 92 years, median 68) and clinical features, with events of longer duration, simultaneously bilateral events, prominent automatisms, sensory aura, and post-ictal fear and speech arrest. Ictal epileptiform electroencephalographic changes were present in three cases. All 10 cases were positive for voltage-gated potassium channel-complex antibodies (346-4515 pM): nine showed specificity for leucine-rich glioma inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and the cerebrospinal fluid examination was unremarkable in all seven tested. Faciobrachial dystonic seizures were controlled more effectively with immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine cases who remained anti-epileptic drug refractory for a median of 30 days (range 11-200), the addition of corticosteroids was associated with cessation of faciobrachial dystonic seizures within 1 week in three and within 2 months in six cases. Voltage-gated potassium channel-complex antibodies persisted in the four cases with relapses of faciobrachial dystonic seizures during corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive impairment. By contrast, the two who did not develop cognitive impairment received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic seizures can be prospectively identified as a form of epilepsy with an expanding phenotype. Immunotherapy is associated with excellent control of the frequently anti-epileptic drug refractory seizures, hastens time to recovery, and may prevent the subsequent development of cognitive impairment observed in this study.

Epilepsy causing pupillary hippus: an unusual semiology.

Altered pupillary behavior is commonly present during and following epileptic seizures, but symptomatic pupillary hippus as the main feature of a seizure has not been reported in the modern literature. We present the case of a woman with epileptic seizures consisting of sustained fluctuation of perception of brightness. Bilateral pupillary hippus is the main semiologic feature.This autonomic phenomenon is selective for the pupils and does not involve other autonomic-mediated responses. An ictal video illustrates this phenomenon. The epileptogenic region, determined by ictal scalp and intracranial electroencephalography (EEG), is localized in the right posterior parietooccipital areas. Pupillary reflexes can be overridden by cortical input; here authors review the literature and discus the physiologic mechanisms underlying this autonomic phenomenon. Fluctuation in perceptual brightness during epileptic seizures may have a basis in ictal pupillary hippus.

Partial epilepsy with pericentral spikes: a new familial epilepsy syndrome with evidence for linkage to chromosome 4p15.

The genetic analysis of simple Mendelian epilepsies remains a key strategy in advancing our understanding of epilepsy. In this article, we describe a new family epilepsy syndrome, partial epilepsy with pericentral spikes, which we map to chromosome 4p15. We distinguish it clinically, electrophysiologically, and genetically from previously described Mendelian epilepsies. The family described is a large Brazilian kindred of Portuguese extraction in which affected family members manifest a variety of seizure types, including hemiclonic, hemitonic, generalized tonic-clonic, simple partial (stereotyped episodes of epigastric pain), and complex partial seizures consistent with temporal lobe epilepsy. The syndrome is benign, either requiring no treatment or responding to a single antiepileptic medication. Seizure onset is in the first or second decades of life, with seizures in individuals up to the age of 71 years and documented encephalogram changes up to the age of 30 years. A key feature of partial epilepsy with pericentral spikes is a characteristic encephalogram abnormality of spikes or sharp waves in the pericentral region (centroparietal, centrofrontal, or centrotemporal). This distinctive encephalogram abnormality of pericentral spikes unites these several seizure types into a discrete family epilepsy syndrome. As with other familial epilepsies, the inherited nature of this new syndrome may be overlooked because of the variability in penetrance and seizure types among affected family members.