The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the alpha subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca(2+) sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease.

Summary:We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows: The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed. Key Words: Seizure classification-Ictal semiology-Auras-Motor seizures-Paroxysmal events.The International League Against Epilepsy (ILAE) introduced a seizure classification in 1981 based on clinical semiology, interictal EEG findings, and ictal EEG patterns (1). The assumption behind such a classification, which is actually a classification of electroclinical features, is the existence of a strict one-to-one correlation between clinical-ictal semiology and interictalhctal EEG findings. Detailed analysis of clinical semiology and EEG findings shows, however, that this assumption is frequently incorrect (2), particularly for infants (3).

Few epilepsy surgery outcome data are available from series of pediatric patients. We studied seizure outcome in 136 pediatric patients who had surgery for intractable epilepsy at The Cleveland Clinic between January 1990 and June 1996, with a postoperative follow-up of 1 to 7.5 years (mean, 3.6 years). Sixty-two children (3 months to 12 years old at time of surgery) were compared with 74 adolescents (13-20 years old). Extratemporal or multilobar resections and hemispherectomies were similarly frequent among children (50%) and adolescents (44%), but these procedures strongly predominated in infancy (90% of patients 0-2 years of age). The remaining patients had temporal resection. Cortical dysplasia and low-grade tumor were the most common causes and hippocampal sclerosis was rare. Seizure-free outcome was achieved for 69% of adolescents, 68% of children, and 60% of the infant subgroup, overall; for 23 (74%) of 31 children and 33 (80%) of 41 adolescents after temporal resection; for 11 (58%) of 19 children and 15 (52%) of 29 adolescents after extratemporal or multilobar resection; and for 8 (67%) of 12 children and 3 (75%) of 4 adolescents after functional hemispherectomy. Seizure-free outcome was more frequent after temporal resection (56 of 72, 78%) than after extratemporal or multilobar resection (26 of 48, 54%; 41 of 48 with a focal lesion on magnetic resonance imaging), and among patients with tumor (36 of 44, 82%) versus cortical dysplasia (16 of 31, 52%). The frequency of seizure-free outcome after epilepsy surgery was similar for infants, children, and adolescents, and comparable with results from adult series. Most patients in each age, surgery type, and causal group were free from seizures after surgery. These results suggest that children should be considered for surgical evaluation at whatever age they manifest with severe, intractable, disabling localization-related epilepsy.

Epilepsy surgery may be successful for selected children and adolescents with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG. The diffuse EEG expression may be due to an interaction between the early lesion and the developing brain.