The occurrence and characteristics of auras in a large epilepsy cohort.

OBJECTIVES: Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. CONCLUSION: Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities.

Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+.

BACKGROUND: Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. OBJECTIVE: To study the occurrence of mutations in these genes in families with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. MATERIAL AND METHODS: We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. RESULTS: We identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. CONCLUSION: This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia.

Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs.

The contribution of genetic and environmental factors to the occurrence of epilepsy was examined in an unselected sample of twins recruited from the population-based Danish Twin Registry. Information on the occurrence of epilepsy in both members of a twin pair was obtained from 11900 pairs whose ages ranged from 12 to 41 years. Concordance rates, odds ratios and tetrachoric correlations were used to quantify the similarity of monozygotic (MZ) and dizygotic (DZ) twins. The sample was stratified by sex and separated into two age cohorts for analysis. Significantly higher probandwise concordance rates were found for MZ compared with DZ twins (0.37 and 0.08, P<0.01). Odds ratios and tetrachoric correlation showed similar pattern. An etiological model including additive genetic and individual specific environmental factors provided the best overall fit to the data, with 70 and 88% of the liability to develop epilepsy being accounted for by genetic factors in the younger and older cohorts, respectively. Individual specific environmental factors explained the remaining 30 and 12%, respectively. In conclusion, this study has confirmed the substantial impact, which genetic factors have in the etiology of epilepsy. The heritability of epilepsy is high and seems to increase with age.

Evaluation of patients with symptoms suggestive of chronic polyneuropathy.

OBJECTIVES: The aim of this study was to determine the diagnostic yield and to describe the spectrum of diagnosis encountered by evaluation of patients with symptoms suggestive of chronic polyneuropathy. METHODS: We prospectively evaluated 198 patients referred to a department of neurology with symptoms suggestive of polyneuropathy. The evaluation included nerve conduction studies with near-nerve technique, quantitative examination of temperature sensation, blood tests, chest x-rays, and skin biopsies as well as diagnostic tests for differential diagnoses. RESULTS: Polyneuropathy was found in 147 patients, alternative diagnoses in 25, and 26 remained undiagnosed. The etiology of polyneuropathy could not be identified in 25% of the patients with polyneuropathy. In the remaining 75%, the cause of neuropathy was diabetes and/or alcohol abuse (41%), monoclonal gammopathy of undetermined significance (5%), drugs (5%), connective tissue disease (3%), and a number of less frequent conditions. A previously undiagnosed condition was found in 30% of the patients with polyneuropathy. CONCLUSION: Evaluation of patients with symptoms suggestive of polyneuropathy reveals a high fraction of patients with previously undiagnosed conditions both in patients ending up with a polyneuropathy diagnosis and those without this diagnosis.

Diagnostic yield by testing small fiber function in patients examined for polyneuropathy.

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.

Cerebral infarct following carotid endarterectomy. Frequency, clinical and hemodynamic significance evaluated by MRI and TCD.

The purpose of this study was to disclose the frequency of new infarcts after Carotid Endarterectomy (CEA) by MRI and Transcranial Doppler examinations (TCD), and to evaluate the clinical and pathological significance. Of a consecutive series of 41 patients with a symptomatic carotid stenosis exceeding 69%, 33 had MRI and TCD examinations performed before and after the CEA. Pre-operative MRIs revealed Focal High Signal Intensity (FHSI) in 21 patients (64%) on the side of the stenosis, ranging in number from 2 to more than 20 and in size from 0.5 cm to more than 3 cm. After the operation 8 patients (24%) each had acquired from 1-4 new FHSIs, but only 3 patients (9%) suffered from clinical symptoms. In 2 patients, who had had a stroke, the FHSIs were more than 3 cm. In 1 patient, who experienced a Transient Ischemic Attack (TIA), the FHSI was 1-2 cm. The TCD disclosed low Pulsatility Index (PI) values in 2 of the 3 patients who had new FHSIs and clinical symptoms. In all the patients who did not show new FHSIs after the operation, the PI was normal in the MCA of the symptomatic hemisphere after CEA. So new cerebral FHSIs were rather frequent after a CEA, but only FHSIs >1 cm were accompanied by a TIA or stroke, and a low PI in the MCA of the relevant hemisphere was found before or in connection with the operation in 2 of the 3 patients who developed clinical symptoms.

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.

[Genetic aspects of epilepsy]. / Genetiske aspekter ved epilepsi.

Accumulating evidence suggests a significant proportion of the forms of epilepsy to be genetically determined. Several epilepsy syndromes have been mapped on the human genome, though their molecular basis remains unknown. Technical advances in molecular biology now provide a basis for improving our understanding of the molecular mechanisms involved in genetically determined types of epilepsy Genetic mapping will improve the accuracy of genetic counselling. Improved insight into the molecular biology may help to elucidate the underlying epileptogenic mechanisms and pave the way for new developments in pharmacological control of epileptic seizures. Further advances in research on genetics and epilepsy will require national and international cooperation between epileptologists and geneticists in search of informative families for linkage analysis.

Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region.

Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated "EJM1"), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score < -2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, alpha-that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions.

[Progressive myoclonic epilepsy]. / Progressiv myoklon epilepsi.

Progressive myoclonic epilepsy (PME) is a syndrome characterized by myoclonias, epilepsy, progressive dementia and other neurological deficits. PME may be caused by various, rare, incompletely elucidated genetic diseases, and is characterized by age at onset, duration, clinical and pathoanatomical abnormalities. There is ethnic and geographic variation in the frequency of the syndrome. The diseases are frequently autosomal recessive. Research in PME leads to a better understanding of the neurobiological processes of epilepsy. PME should be considered in cases of severe myoclonic epilepsy, progressive neurological disability and poor effect of antiepileptic treatment, and biopsies from skin, mucosa or muscle should be performed. Centralization of treatment of these rare diseases is recommended.