Sudden death in epilepsy: a wake-up call for management.
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Adult↗
Biomedical subjects
W Allen Hauser
Publications and source records attributed to W Allen Hauser.
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies.
Animals↗
Do seizures beget seizures?
There have been suggestions that seizures in some way modify brain function and that each seizure increases the risk for further seizures. Reports thus far on this phenomenon have been flawed because of inappropriate study design. We have evaluated the risk for seizure recurrence following a first unprovoked seizure in a cohort identified at their first unprovoked seizure. Individuals with low risk for a seizure recurrence demonstrate a significant increase in risk for seizure recurrence with increasing numbers of seizures. This is the first time that a progressive increase in risk for seizures with increasing number of seizures has been demonstrated in humans. Since the majority of these cases will ultimately go into remission and discontinue antiseizure medication, there must be competing forces that increase seizure risk and promote seizure suppression. We need appropriate animal models to better understand both processes and their interactions.
Follow-Up Studies↗
Do occasional brief seizures cause detectable clinical consequences?
Seizures, particularly when prolonged or frequent, have been associated with a variety of adverse outcomes. However, epidemiological data provide little evidence for adverse effects of isolated brief seizures per se. Even the animal data is mostly for prolonged or frequent seizures. Febrile seizures lasting < 10 min have not been associated with adverse seizures or cognitive outcomes. Treating either febrile seizures or other acute symptomatic seizures does not reduce the risk of subsequent epilepsy. In subjects with a first unprovoked seizure, seizure duration does not influence recurrence risk. Furthermore, treatment after a first unprovoked seizure reduces recurrence risk, but does not alter long-term prognosis. In epidemiological studies of newly diagnosed epilepsy, the number of seizures prior to therapy does not influence prognosis. There are a variety of specific epilepsy syndromes associated with poor cognitive outcomes and with progressive loss of function. However, the poor outcomes in these syndromes do not appear to be the result of seizures per se but rather to the specific syndrome and to the frequent interictal spike activity seen in these patients. Antiepileptic drugs, while effective in reducing seizure recurrence are also associated with a variety of potential adverse effects. On a risk-benefit basis, the available epidemiologic data do not justify starting treatment after the first seizure to attempt to influence long-term prognosis.
Animals↗
Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24.
PURPOSE: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. METHODS: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. RESULTS: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (theta=0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. CONCLUSIONS: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway.
Adult↗
An estimate of the prevalence of psychogenic non-epileptic seizures.
The prevalence of psychogenic non-epileptic seizures is difficult to estimate. We propose an estimate based on a calculation. We used the following data, which are known or have been estimated, and are generally accepted. A prevalence of epilepsy of 0.5-1%; a proportion of intractable epilepsy of 20-30%; a percentage of these referred to epilepsy centers of 20-50%; and a percentage of patients referred to epilepsy centers that are psychogenic non-epileptic seizures: 10-20%. Using the low estimates, the prevalence of psychogenic non-epileptic seizures would be 1/50 000. Using the high estimates, the prevalence of psychogenic non-epileptic seizures would be 1/3000. The prevalence of psychogenic non-epileptic seizures is somewhere between 1/50 000 and 1/3000, or 2 to 33 per 100 000, making it a significant neurologic condition.
Conversion Disorder↗
Can sudden unexplained death in epilepsy be prevented?
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Bradycardia↗