scholarly journals Genetic Variants in Absence Epilepsy: A Contextual Consideration of Calcium Current Kinetics

2006 ◽  
Vol 6 (3) ◽  
pp. 99-101 ◽  
Author(s):  
Andre Lagrange
Keyword(s):  
Functional Characterization ◽  
Susceptibility Gene ◽  
Absence Epilepsy ◽  
Nucleotide Polymorphisms ◽  
Childhood Absence Epilepsy ◽  
Patch Clamp Recording ◽  
Neuronal Modeling ◽  
Absence Seizures ◽  
Whole Cell Patch Clamp ◽  
Intrinsic Firing

Functional Characterization and Neuronal Modeling of the Effects of Childhood Absence Epilepsy Variants of Cacna1h, a T-Type Calcium Channel Vitko I, Chen Y, Arias JM, Shen Y, Wu XR, Perez-Reyes E J Neurosci 2005;25(19):4844-4855 Sequencing of the T-type Ca2+ channel gene CACNA1H revealed 12 nonsynonymous single nucleotide polymorphisms (SNPs) that were found only in childhood absence epilepsy (CAE) patients. One SNP, G773D, was found in two patients. The present study reports the finding of a third patient with this SNP, as well as analysis of their parents. Because of the role of T-channels in determining the intrinsic firing patterns of neurons involved in absence seizures, it was suggested that these SNPs might alter channel function. The goal of the present study was to test this hypothesis by introducing these polymorphisms into a human Cav3.2a cDNA and then study alterations in channel behavior using whole-cell patch-clamp recording. Eleven SNPs altered some aspect of channel gating. Computer simulations predict that seven of the SNPs would increase firing of neurons, with three of them inducing oscillations at similar frequencies, as observed during absence seizures. Three SNPs were predicted to decrease firing. Some CAE-specific SNPs (e.g., G773D) coexist with SNPs also found in controls (R788C); therefore, the effect of these polymorphisms were studied. The R788C SNP altered activity in a manner that would also lead to enhanced burst firing of neurons. The G773D–R788C combination displayed different behavior than either single SNP. Therefore, common polymorphisms can alter the effect of CAE-specific SNPs, highlighting the importance of sequence background. These results suggest that CACNA1H is a susceptibility gene that contributes to the development of polygenic disorders characterized by thalamocortical dysrhythmia, such as CAE.

Electroclinical features of absence seizures in childhood absence epilepsy

Neurology ◽  
2006 ◽  
Vol 67 (3) ◽  
pp. 413-418 ◽  
Author(s):  
L. G. Sadleir ◽  
K. Farrell ◽  
S. Smith ◽  
M. B. Connolly ◽  
I. E. Scheffer
Keyword(s):  
Absence Epilepsy ◽  
Childhood Absence Epilepsy ◽  
Absence Seizures

scholarly journals Pretreatment seizure semiology in childhood absence epilepsy

Neurology ◽  
2017 ◽  
Vol 89 (7) ◽  
pp. 673-679 ◽  
Author(s):  
Sudha Kilaru Kessler ◽  
Shlomo Shinnar ◽  
Avital Cnaan ◽  
Dennis Dlugos ◽  
Joan Conry ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Absence Epilepsy ◽  
Absence Seizure ◽  
Seizure Freedom ◽  
Childhood Absence Epilepsy ◽  
Short Term ◽  
Short Term Treatment ◽  
Absence Seizures ◽  
Seizure Semiology ◽  
Eye Involvement

Objective:To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes.Methods:For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit.Results:Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%–84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern.Conclusions:Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome.

scholarly journals Absence Semiologies

2009 ◽  
Vol 9 (4) ◽  
pp. 104-107
Author(s):  
Warren T. Blume
Keyword(s):  
Clinical Features ◽  
Child Behavior Checklist ◽  
Absence Epilepsy ◽  
Epilepsy Syndrome ◽  
Childhood Absence Epilepsy ◽  
Psychiatric Interview ◽  
Absence Seizures ◽  
Duration Of Illness ◽  
Eye Opening ◽  
Specific Factors

Factors Influencing Clinical Features of Absence Seizures. Sadleir LG, Scheffer IE, Smith S, Carstensen B, Carlin J, Connolly MB, Farrell K. Epilepsia 2008;49(12):2100–2107. PURPOSE: The clinical features of absence seizures in idiopathic generalized epilepsy have been held to be syndrome-specific. This hypothesis is central to many aspects of epilepsy research yet has not been critically assessed. We examined whether specific factors such as epilepsy syndrome, age, and state determine the features of absence seizures. METHODS: Children with newly presenting absence seizures were studied using video electroencephalography (EEG) recording. We analyzed whether a child's epilepsy syndrome, age, state of arousal, and provocation influenced specific clinical features of their absence seizures: duration, eyelid movements, eye opening, and level of awareness during the seizure. RESULTS: Seizures (509) were evaluated in 70 children with the following syndromes: Childhood absence epilepsy (CAE), 37; CAE plus photoparoxysmal response (PPR), 10; juvenile absence epilepsy (JAE), 8; juvenile myoclonic epilepsy (JME), 6; unclassified, 9. Seizure duration was associated with epilepsy syndrome as children with JME had shorter seizures than in other syndromes, independent of age. Age independently influences level of awareness and eye opening. Arousal or provocation affected all features except level of awareness. Specific factors unique to the child independently influenced all features; the nature of these factors has not been identified. DISCUSSION: The view that the clinical features of absence seizures have syndrome-specific patterns is not supported by critical analysis. We show that confounding variables profoundly affect clinical features and that syndromes also show marked variation. Variation in clinical features of absence seizures results from a complex interaction of many factors that are likely to be genetically and environmentally determined. Childhood Absence Epilepsy: Behavioral, Cognitive, and Linguistic Comorbidities. Caplan R, Siddarth P, Stahl L, Lanphier E, Vona P, Gurbani S, Koh S, Sankar R, Shields WD. Epilepsia 2008 Nov;49(11):1838–1846. PURPOSE: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE. METHODS: Sixty-nine CAE children aged 9.6 (SD = 2.49) years and 103 age- and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL). RESULTS: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems. CONCLUSIONS: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

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