Subtle seizures consisting of brief alteration of consciousness with or without automatisms may go unnoticed in daily life, but can be detected more easily with electroencephalographic (EEG)/video ...recordings. Generalized and partial epileptiform EEG discharges can nevertheless be subclinical (subclinical epileptiform discharges, SEDs). When appropriate complex tasks are presented, it has been shown that even very short SEDs of 0.5 second disrupt cognition. In daily life this has been shown during automobile driving: half of the subjects showed significant deviations in lateral position of the car during SEDs and made more errors in an attention task while driving. Individual differences in the cognitive effects of SEDs are, however, striking and may be partly due to interaction between level of performance and frequency of spontaneous EEG discharges, as has been shown in another driving study: about 75% of subjects showed suppression of SEDs by driving, which is a combination of sensory, mental, and motor activity. Not only can SEDs negatively influence performance, but in some cases mental activities can provoke epileptiform discharges. It is important to realize that these mechanisms exist and that only detailed EEG studies can clarify these issues. In air traffic controllers, brief alterations of consciousness and cognitive impairment have occurred but cannot be accepted for safety reasons; therefore, Eurocontrol has used the EEG as a screening tool since 1995.
Purpose: To investigate the extent and causes of the differences in mortality found in studies on mortality in epilepsy based on a quantitative review of the literature.
Methods: We used MEDLINE ...database and Cumulative Index Medicus for 1960–2001, Excerpta Medica for 1948–1965, and relevant journals and bibliographies. We selected comparative studies investigating mortality in epilepsy patients conducted in the last 100 years. The Standardized Mortality Ratio (SMR) was selected as primary outcome. Nineteen studies were included. Pooled estimates were precision weighted and tested for homogeneity. Sources of variability between risk estimates were explored by using multivariate fixed‐effects models.
Results: SMRs ranged from 1.3 to 9.3. Risk estimates proved heterogeneous (χ2 test statistic: 1,177; df = 18; p < 0.001). The most important determinant was “source population,” explaining half of the variance of the estimates (R2, 0.47; p = 0.006). SMRs in community studies ranged from 1.3 to 3.1, and for institutionalized populations, from 1.9 to 5.1.
Conclusions: Our results show that the mortality risk in patients with epilepsy is dependent on source population of patients. Within the different source populations, considerable unexplained variance remains. Hence no uniform summary estimate for the elevated mortality could be determined.
To investigate the extent and nature of the objective and subjective cognitive deficits and health-related quality of life (HRQOL) in adult outpatients with relatively well-controlled partial ...epilepsy without symptomatic aetiology, who were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of the epilepsy history and medication on various cognitive functions and the HRQOL. 56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy were compared with 56 age-, gender-, and education-matched healthy controls. Patients were tested on attention, memory, speed of information processing, and executive functioning. Questionnaires aimed at measuring self-perceived cognitive functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were used to compare the two groups. Linear regression analysis was performed to identify the epilepsy and medication-related factors that are associated with cognitive functioning and HRQOL. Patients scored lower on measures of attention (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00). Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical functioning was unaffected. These patients also expressed reductions in mental functioning as indicated by a low self-perceived cognitive functioning (P = 0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency, localisation, years on CBZ, and CBZ dosage were not related to cognitive functioning or HRQOL. Patients with partial epilepsy, even when able to maintain regular jobs, have impaired cognition and HRQOL that cannot be attributed to their epilepsy history or CBZ dosage or years of CBZ intake. Therefore, physicians should be more aware of their cognition and HRQOL, in addition to the antiepileptic drug regime.
Purpose: The interaction of genetic predisposition and the environment in the development of epilepsy is often discussed, but, aside from some animal reflex epilepsies, little evidence supports such ...interaction in the development of reflex epilepsy in humans.
Methods: We describe the history of a 16‐year‐old boy in whom photosensitive epilepsy developed after a period of weekly exposures to high‐intensity light flashes.
Results: Both he and his clinically unaffected monozygotic twin were found to be photosensitive.
Conclusions: This case report suggests that some genetic forms of human reflex epilepsy may be elicited by repeated environmental exposure to the appropriate stimulus, similar to some of the stimulus‐induced epilepsies seen in animals.
Visual Stimuli in Daily Life Kasteleijn‐Nolst Trenité, Dorothée G. A.; Van Der Beld, Gerrit; Heynderickx, Ingrid ...
Epilepsia (Copenhagen),
January 2004, 2004-00-00, 2004-01-00, Letnik:
45, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
People of all ages, but especially children and adolescents, are increasingly exposed to visual stimuli. Typical environmental stimuli that can trigger epileptic seizures in susceptible persons are ...televisions (TVs), computers, videogames (VGs), discothèque lights, venetian blinds, striped walls, rolling stairs (escalators), striped clothing, and sunlight reflected from snow or the sea or interrupted by trees during a ride in a car or train. Less common stimuli are rotating helicopter blades, disfunctioning fluorescent lighting, welding lights, etc. New potentially provocative devices turn up now and then unexpectedly. During the last decades especially, displays have become increasingly dominant in many of our daily‐life activities. We therefore focus mainly on the characteristics of artificial light and on current and future developments in video displays and videogames. Because VG playing has been shown also to have positive effects, a rating system might be developed for provocativeness to inform consumers about the content. It is important that patients with epilepsy be informed adequately about their possible visual sensitivity.
Purpose: Previous linkage studies provided evidence for juvenile myoclonic epilepsy (JME) susceptibility loci at 6p11‐12, HLA‐6p21.3 region, 15q14, and 5q34. These results indicate locus ...heterogeneity or interpopulation differences, thus underlining the importance of replication studies.
Methods: We describe a replication linkage study of the 6p‐q13 region in 18 families ascertained from JME probands of Dutch descent. In the presence of heterogeneity, the definition of the disease status may be crucial, and we therefore used two disease phenotypes: narrow JME/idiopathic generalized epilepsy (IGE)‐“only” and broad (JME/IGE‐plus‐fast EEG background activity).
Results: We found evidence of linkage at 6p11‐12 in multipoint analyses (p < 0.01 in a replication study) for both these disease definitions. Analysis of this region, assuming heterogeneity and autosomal dominant inheritance with a conservative 60% of penetrance, gave a maximum multipoint parametric lod score of 2.07 at D6S1573 for the narrow phenotype and peaked at 2.53 between D6S1623 and D6S1573 for the broad phenotype. The p value for nonparametric linkage reached 0.0013 for the narrow phenotype and 0.0010 for the broad. Significant exclusion (lod score ≤2) was found for the HLA region and for 10 to 30 cM telomeric to HLA. Our results provide evidence for a susceptibility locus for JME/IGE‐plus‐fast EEG background activity at 6p11‐12.
Conclusions: Additionally, by using a narrow definition, we were able to confirm previous evidence for a JME–IGE locus at this location.
Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to ...investigate the burden of rare genetic variants in genetic generalised epilepsy.
For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABA
receptors and was compared to the respective GABA
receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes.
Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABA
receptors in cases (odds ratio OR 2·40 95% CI 1·41-4·10; p
=0·0014, adjusted p
=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 95% CI 1·05-2·03; p
=0·0081, adjusted p
=0·016). Comparison of genes encoding GABA
receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABA
receptor genes in cases compared with controls (OR 1·46 95% CI 1·02-2·08; p
=0·013, adjusted p
=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors.
Functionally relevant variants in genes encoding GABA
receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy.
EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).
We determined whether epileptic clinical manifestations evoked by playing video games (VG) differ from those evoked by intermittent photic stimulation (IPS) or striped patterns (P). We exposed nine ...children who had TV- and VG-evoked seizures in daily life to 12 VG after standardized photic stimulation and pattern stimulation. Their EEGs were recorded continuously, analyzed, and then correlated with a video of their behavior. Similar types of clinical signs were seen during VG, P, and IPS, but the signs we observed were more subtle during the VG. Eight patients showed a clear lateralization. A new observation was the lowering of the eyelids to a state of half-closed. Our study suggests that the type of visual stimulus provoking a photoparoxysmal response or seizure is not particularly relevant. The children belonged to different epilepsy groups, and our findings add to the discussion on the boundaries of the epilepsy types.
Objective
Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission ...and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome.
Methods
In this multicenter retrospective cohort study, we included 267 EEM patients from nine countries. Data on electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy, and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia involving body regions other than eyelids (body‐MYO).
Results
Kernel density estimation revealed a trimodal distribution of AEO, and Fisher–Jenks optimization disclosed three EEM subgroups: early onset (EO‐EEM), intermediate onset (IO‐EEM), and late onset (LO‐EEM). EO‐EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO‐EEM was associated with the highest proportion of body‐MYO and generalized tonic–clonic seizures (GTCS), whereas IO‐EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO‐EEM and LO‐EEM compared with EO‐EEM. In the subset of patients with body‐MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome.
Significance
Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians toward a more accurate classification and prognostic profiling of EEM patients.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors ...of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
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