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Evidence for a specific association between migraine and rolandic epilepsy (RE) has been conflicting. Children with migraine frequently have electroencephalographic (EEG) abnormalities, including rolandic discharges, and approximately 50% of siblings of patients with RE exhibit rolandic discharges. We assessed migraine risk in RE probands and their siblings. We used cohort and reconstructed cohort designs to respectively assess the relative risk of migraine in 72 children with RE and their 88 siblings using International Classification of Headache Disorders (ICHD-2) criteria. Incidences were compared in 150 age and geographically matched nonepilepsy probands and their 188 siblings. We used a Cox proportional hazards model, using age as the time base, adjusting hazard ratios (HRs) for sex in the proband analysis, and for sex and proband migraine status in the sibling analysis. Prevalence of migraine in RE probands was 15% versus 7% in nonepilepsy probands, and in siblings of RE probands prevalence was 14% versus 4% in nonepilepsy siblings. The sex-adjusted HR of migraine for an RE proband was 2.46 [95% confidence interval (CI) 1.06–5.70]. The adjusted HR of having ≥1 sibling with migraine in an RE family was 3.35 (95% CI 1.20–9.33), whereas the HR of any one sibling of a RE proband was 2.86 (95% CI 1.10–7.43). Migraine is strongly comorbid in RE and independently clusters in their siblings. These results suggest shared susceptibility to migraine and RE that is not directly mediated by epileptic seizures. Susceptibility gene variants for RE may be tested as risk factors for migraine. [ABSTRACT FROM AUTHOR]

Conflicting evidence about impairment of attention systems and the absence of a working model of attention has contributed to lack of clarity about comorbidity of attention problems in rolandic epilepsy (RE). Impairments in distributed attention systems may inform a disease model for RE, as well as direct interventions. We used a systematic review of the relevant literature published in English from 1990 to 2006 to evaluate impairment in attention in RE. The Mirsky and Posner models of attention were evaluated for applicability, and studies were reviewed for design, instrumentation, and congruence with the Posner model of attention. Fourteen studies were identified: seven using a cross-sectional design (six active EEG abnormalities; one EEG remission) and seven longitudinal studies (abnormal EEGs and follow-up until normalized). According to the Posner model of attention, 12 studies employed measures that tapped the alerting network, 11 studies the orienting network, and eight the executive network. Nearly all controlled studies demonstrated impairments in all tested attention networks. In contrast, uncontrolled studies uniformly did not demonstrate impairments. Follow-up studies demonstrated complete or near complete resolution of attention impairments. The weight of evidence, defined as the majority of studies evaluated, suggests that all three attention systems are impaired in children with active centrotemporal spikes (CTS), implying a more widespread functional cortical disturbance in RE than previously held. These impairments resolve upon EEG remission, suggesting a common pathological basis to the autosomal dominant CTS trait. Sources of methodological variation are discussed with recommendations for future investigations. [ABSTRACT FROM AUTHOR]

Very few genetic associations for idiopathic epilepsy have been replicated and this has tempered enthusiasm for the results of genetic studies in epilepsy. What are the reasons for lack of replication? While type 1 error, population stratification, and multiple testing have been discussed extensively, the importance of genetic heterogeneity has been relatively neglected. In the first part of this review, we explore the sources of genetic heterogeneity and their importance for epilepsy genetic studies. In the second part, we review alternatives to the simple law of replication, revisiting Bradford Hill's guidelines for evidence of causality. A coherence perspective is applied to three examples. We conclude that adopting the perspective of integrating coherent and consistent evidence from different experimental approaches is a more appropriate requirement for proceeding to functional studies. [ABSTRACT FROM AUTHOR]

Associations between rolandic epilepsy (RE) with reading disability (RD) and speech sound disorder (SSD) have not been tested in a controlled study. We conducted a case–control study to determine whether (1) RD and SSD odds are higher in RE probands than controls and (2) an RE proband predicts a family member with RD or SSD, hence suggesting a shared genetic etiology for RE, RD, and SSD. Unmatched case–control study with 55 stringently defined RE cases, 150 controls in the same age range lacking a primary brain disorder diagnosis, and their siblings and parents. Odds ratios (OR) were calculated by multiple logistic regression, adjusted for sex and age, and for relatives, also adjusted for comorbidity of RD and SSD in the proband. RD was strongly associated with RE after adjustment for sex and age: OR 5.78 (95% CI: 2.86–11.69). An RE proband predicts RD in family members: OR 2.84 (95% CI: 1.38–5.84), but not independently of the RE proband's RD status: OR 1.30 (95% CI: 0.55–12.79). SSD was also comorbid with RE: adjusted OR 2.47 (95%CI: 1.22–4.97). An RE proband predicts SSD in relatives, even after controlling for sex, age and proband SSD comorbidity: OR 4.44 (95% CI: 1.93–10.22). RE is strongly comorbid with RD and SSD. Both RD and SSD are likely to be genetically influenced and may contribute to the complex genetic etiology of the RE syndrome. Siblings of RE patients are at high risk of RD and SSD and both RE patients and their younger siblings should be screened early. [ABSTRACT FROM AUTHOR]

Centrotemporal sharp (CTS) waves, the electroencephalogram (EEG) hallmark of rolandic epilepsy, are found in approximately 4% of the childhood population. The inheritance of CTS is presumed autosomal dominant but this is controversial. Previous studies have varied considerably in methodology, especially in the control of bias and confounding. We aimed to test the hypothesis of autosomal dominant inheritance of CTS in a well-designed family segregation analysis study. Probands with rolandic epilepsy were collected through unambiguous single ascertainment. Siblings in the age range 4–16 years underwent sleep-deprived EEG; observations from those who remained awake were omitted. CTS were rated as present or absent by two independent observers blinded to the study hypothesis and subject identities. We computed the segregation ratio of CTS, corrected for ascertainment. We tested the segregation ratio estimate for consistency with dominant and recessive modes of inheritance, and compared the observed sex ratio of those affected with CTS for consistency with sex linkage. Thirty siblings from 23 families underwent EEG examination. Twenty-three showed evidence of sleep in their EEG recordings. Eleven of 23 recordings demonstrated CTS, yielding a corrected segregation ratio of 0.48 (95% CI: 0.27–0.69). The male to female ratio of CTS affectedness was approximately equal. The segregation ratio of CTS in rolandic epilepsy families is consistent with a highly penetrant autosomal dominant inheritance, with equal sex ratio. Autosomal recessive and X-linked inheritance are rejected. The CTS locus might act in combination with one or more loci to produce the phenotype of rolandic epilepsy. [ABSTRACT FROM AUTHOR]

The common forms of idiopathic epilepsies have complex genetic inheritance and are likely to include genes in biologic pathways other than 'channelopathies,' the most frequent cause of their rare Mendelian counterparts. Recent analyses of ELP4 and BRD2 indicate that subtle genetically determined neurodevelopmental deviations may play a part in the pathogenesis of rolandic epilepsy and juvenile myoclonic epilepsy. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at ). [ABSTRACT FROM AUTHOR]