Familial genetic predisposition, epilepsy localization and antecedent febrile seizures

PURPOSE: The magnitude of genetic influence in epilepsy may vary in relation to epilepsy classification and localization and factors such as antecedent febrile seizures. We assessed this genetic influence in a large epilepsy population. METHODS: Patients with established epilepsy diagnosis evaluated in the Vanderbilt Epilepsy Program were systematically questioned about family history of epilepsy and febrile seizures, prior febrile seizures and other risk factors for epilepsy. RESULTS: A total of 1994 patients with epilepsy and reliable family history were identified. Patients with prior febrile seizures (FS) were more likely to have a family history of febrile seizures than those without prior FS (p<0.000001) and also had a greater proportion of relatives with febrile seizures. The groups did not differ with respect to family history of epilepsy. Patients with generalized epilepsy were more likely to have first and second degree relatives with epilepsy than those with partial epilepsy (40.2% versus 31.2%, p=0.001), and also had a greater proportion of affected first degree relatives (p<0.000001). The proportion of first degree relatives affected with epilepsy was higher than local published prevalence, for both groups. CONCLUSION: Susceptibility for febrile seizures with subsequent epilepsy may be genetically distinct from susceptibility for afebrile seizures alone. Although family history of epilepsy was more likely with generalized epilepsy, a familial tendency was considerable in partial epilepsy.     

Epilepsy After Febrile Seizures: Twins Suggest Genetic Influence

BackgroundA history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic factors is unclear. This analysis evaluated the relationship between febrile seizures and epilepsy.MethodsInformation on the history of seizures was obtained by a questionnaire from twin pairs in the Mid-Atlantic, Danish, and Norwegian Twin Registries. The information was verified using medical records and detailed clinical and family interviews. The initial study evaluated the genetic epidemiology of febrile seizures in this population. Further information was analyzed and used to evaluate genetic associations of different febrile seizure subtypes.ResultsHistories of febrile seizures were validated in 1051 twins in 900 pairs. The febrile seizure type was classified as simple, complex, or febrile status epilepticus. There were 61% simple, 12% complex, and 7% febrile status epilepticus. There were 78 twins who developed epilepsy. The highest rate of epilepsy (22.2%) occurred in the febrile status epilepticus group. Concordance was highest in simple group.ConclusionA twin with febrile status epilepticus is at the highest risk of developing epilepsy, but simple febrile seizures gave the highest risk for the unaffected twin to develop seizures or other neurological issues. These results are consistent with previous findings. There is a subgroup of febrile seizures that can be associated with long-term consequences. This subgroup can be associated with a significant financial and emotional burden. It is currently not possible to accurately identify which children will develop recurrent febrile seizures, epilepsy, or neuropsychological comorbidities.     

Family studies of individuals with eyelid myoclonia with absences

Purpose: Eyelid myoclonia with absences (EM) is an uncommon type of absence seizure associated with a variety of epilepsy syndromes. The syndrome of epilepsy with EM (EMA) has been proposed to denote the onset of frequent EM induced by eye closure and photic stimulation beginning in childhood. The clinical genetics of EMA has not been well characterized, although a family history of seizures is not infrequent. Methods: Individuals with EMA were ascertained by referral and through the investigators’ clinical practices. All available family members were assessed for seizures using a validated seizure questionnaire. Electroclinical data were obtained on each proband and all affected family members; pedigrees were constructed. Families were analyzed for phenotypic patterns. Key Findings: Eighteen individuals with EMA were recruited. A history of seizures was found in 34 relatives in 15 (83%) of 18 families. In terms of epilepsy syndromes, 9 relatives from 7 of 15 families had febrile seizures. Two relatives had EMA. Classical genetic generalized epilepsy (GGE) syndromes were seen in five relatives: two generalized tonic–clonic seizures alone, two childhood absence epilepsy (CAE), and one juvenile myoclonic epilepsy (JME). Genetic epilepsy with febrile seizures plus (GEFS+) phenotypes occurred in 16 relatives. On review of the epilepsy syndromes within each family, seven families had a pattern consistent with GEFS+, whereas three families had classical GGE. Significance: The clinical genetics of EMA is suggestive of complex inheritance with shared genetic determinants overlapping with both classical GGE and GEFS+. The epilepsy syndromes in relatives of probands with EMA differ from those found in families of probands with CAE, supporting the concept that patients with EMA have a syndrome that is distinct from CAE. This presumably reflects different genetic components contributing to their genetic architecture.     

Predictors of hippocampal, cerebral, and cerebellar volume reduction in childhood epilepsy

PURPOSE: We examined the factors related to brain volume reduction in a pediatric sample of patients that included those with nonintractable epilepsy. METHODS: Entry criteria were children less than 18 years old with epilepsy referred for MRI, including a whole brain volumetric sequence. The sample size was 231. Risk factors were ascertained from interviews and reviews of medical records. Factors included age of onset, seizure years, family history, status epilepticus, intellectual disability, and febrile convulsions. MRI data were obtained for 44 normal childhood control subjects. RESULTS: Cerebral and cerebellar volumes were significantly associated with age, gender, moderate-to-severe intellectual disability (p < 0.001), seizure years, and status epilepticus (p < 0.03). Compared with controls, the brain volume of all patients was reduced by 10% (p < 0.001). Hippocampal volume was significantly associated with total brain volume, age (p < 0.001), focal cerebral ischemic injury, and complex febrile convulsions (p < 0.05). CONCLUSIONS: Significant brain volume reduction is present in children with epilepsy. A component of this reduction is due to acquired insults. The reduction is seen even in children with infrequent seizures over a brief time, suggesting an innate structural abnormality. When evaluating possible etiologic factors in the development of hippocampal volume reduction, one must control for total brain volume. We have confirmed the association of complex febrile convulsions with unilateral hippocampal volume reduction.     

Childhood-onset epilepsy with and without preceding febrile seizures

OBJECTIVE: To identify characteristics in children with epilepsy that differ between those who did versus did not have a history of preceding febrile seizures. BACKGROUND: Febrile seizures precede epilepsy in 10 to 15% of children. Little is known about the specific types of epilepsy associated with febrile seizures. METHODS: In a community-based, prospectively identified cohort of children, the association between prior febrile seizures and characteristics of the children's epilepsy (seizure type, epilepsy syndrome, age at onset, underlying etiology, family history) were examined for 524 of the children who were aged > or =1 year at onset of epilepsy. RESULTS: Seventy-three (13.9%) had febrile seizures. Children with febrile seizures were more likely to have a first-degree or a second-higher-degree relative with febrile seizures and less likely to have childhood absence epilepsy and absence seizures compared with children without febrile seizures. This was especially true for simple febrile seizures. There was no specific association with localization-related forms of epilepsy. Complex, but not simple, febrile seizures were associated with younger age at onset of epilepsy. There was no evidence that focal or prolonged febrile seizures were associated with localization-related epilepsy or temporal lobe epilepsy per se. Of the three children whose initial MRIs demonstrated hippocampal atrophy, none had a history of febrile seizures. CONCLUSIONS: At the time of diagnosis, febrile seizures are not specifically related to temporal lobe epilepsy or localization-related epilepsy in general. A genetic component for febrile seizures is suggested by its positive associations with family history, especially for simple febrile seizures. Complex febrile seizures represent an underlying age-dependent susceptibility.     

Clinical genetic study in juvenile myoclonic epilepsy

PurposeTo evaluate clinical features of probands with juvenile myoclonic epilepsy (JME) and affected members of their families in order to study clinical genetics of JME.MethodThirteen unrelated families with at least two members with history of seizures were identified; clinical and genealogic data were collected from JME probands and family members.ResultsAll probands had myoclonic and generalized tonic–clonic seizures (GTCS), while absences occurred in 25% of them. The average age of seizure onset was 13 years. Totally 22 members from 13 families had history of seizures with average age of seizure onset at 18 years. Ten family members had JME, three had epilepsy with GTCS, two had juvenile absence epilepsy, one had adult onset myoclonic epilepsy and six of the affected individuals had unclassified type of epilepsy. In five families, JME was the solely clinical feature. JME dominated among siblings, while phenotypic heterogeneity was observed in second and third degree relatives. In three multi-generation families, members with adult onset genetic generalized epilepsies (GGE) were identified.ConclusionWe found phenotypic heterogeneity regarding epilepsy type and age of seizure onset. Using pedigree analysis, we found no evidence for preferential maternal or any other distinctive inheritance pattern. Further study is needed to confirm and clarify the results.     

Short-term outcomes of children with febrile status epilepticus

Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30-59 min in 103 (58%), 60-119 min in 43 (24%), and > or =120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p = 0.006) and a family history of epilepsy (11% vs. 5%; p = 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p = 0.01) than were children in the comparison group. The short-term morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis.     

Factors predictive of the outcome of frontal lobe epilepsy surgery

PURPOSE: To identify factors that predict the outcome in seizure control after frontal lobe epilepsy surgery (FLES). FLES is the second most frequent type of epilepsy surgery, but the results are generally not as good as those after anterior temporal lobectomy. METHODS: Our cohort consisted of 68 consecutive patients whose first epilepsy surgery involving the frontal lobe occurred between 1987 and 1994. Clinical history and results of imaging and electroencephalographic studies were reviewed in detail. Excellent outcome was defined as being seizure free or having only nondisabling seizures at last follow up. RESULTS: Forty of the 68 patients (58.8%) had an excellent outcome; none of the patients with a history of childhood febrile seizures had an excellent outcome, whereas outcome was excellent in 63% of those without that history (p 相似文献   

Severe Myoclonic Epilepsy of Infancy: Extended Spectrum of GEFS+?

PURPOSE: Severe myoclonic epilepsy of infancy (SMEI) is an intractable epilepsy of early childhood of unknown etiology. It is often associated with a family history of seizure disorders, but epilepsy phenotypes have not been well described. We sought to characterize the seizure phenotypes of relatives to better understand to the genetic basis of SMEI. METHODS: Probands with SMEI were identified, and systematic family studies were performed. Epilepsy syndromes were characterized in affected family members. RESULTS: Twelve probands with SMEI were identified. Eleven of the 12 probands with SMEI had a family history of seizures, and the twelfth was the result of a consanguineous marriage. We found that 16.7% of full siblings and 8.3% of parents had definite seizures. A total of 39 affected family members was identified. The most common phenotype was febrile seizures in 14, febrile seizures plus in seven, partial epilepsy in two, and there were single individuals with SMEI, myoclonic-astatic epilepsy, Lennox-Gastaut syndrome, and 13 cases with unclassified or unconfirmed seizures. CONCLUSIONS: The family history of seizures in SMEI is in keeping with the spectrum of seizure phenotypes seen in generalized epilepsy with febrile seizures plus (GEFS+). Our findings suggest that SMEI is the most severe phenotype in the GEFS+ spectrum.     

Bilateral reductions in hippocampal volume in adults with epilepsy and a history of febrile seizures

OBJECTIVES—To examine the degree and frequency ofreductions in hippocampal volume in patients with temporal lobeepilepsy with and without a history of febrile seizures.
METHODS—In vivo measures of hippocampal volumewere computed from three dimensional gradient echo (FLASH) images in 44 patients undergoing comprehensive evaluations for epilepsy surgery.Twenty one patients (48%) reported a history of febrile seizures. Thevolumes from these patients were compared with those from 23 patientswithout a history of febrile seizures and 34 healthy controls.
RESULTS—The febrile seizure group had significantreductions in volume, both ipsilateral (30% decrease) andcontralateral (15% decrease), to the EEG seizure focus. Twelve of 18 patients with febrile seizures exhibited clinically significantipsilateral volume reductions, defined as volumes falling 2 SD belowthe mean obtained from the control sample. Only four of 19 patientswithout febrile seizures exhibited this degree of reduction. Nosignificant correlations were found between seizure variables (forexample, duration of epilepsy, seizure frequency) and ipsilateralreductions in volume. However, a significant inversecorrelation (r=−0.45, P<0.05) between seizure frequencyand the volume of the hippocampus contralateral to the seizure focuswas found in the febrile seizure group.
CONCLUSION—These results suggest that a historyof febrile seizures is associated with the finding of a smallerhippocampus on the side ipsilateral to the subsequent temporal lobefocus whereas chronic factors seem to be be related to pathologycontralateral to the seizure focus.

     

Predicting seizure frequency after epilepsy surgery

OBJECTIVE: To identify clinical features related to seizure frequency after epilepsy surgery in patients with recurrent seizures. BACKGROUND: No studies have examined the differences between patients who have rare seizures and patients who experience frequent seizures after epilepsy surgery. Since seizure frequency correlates with morbidity and quality of life, it is desirable to know which preoperative clinical features predict postoperative seizure frequency. METHODS: Patients with recurrent seizures were placed in two categories: rare postoperative seizures (< or =2 per year) and frequent postoperative seizures (> or =12 per year) using seizure frequency in the second postoperative year. Variables included preoperative seizure frequency, age of first risk, age at first seizure, epilepsy duration, age at surgery, history of febrile convulsions, tonic-clonic seizures, status epilepticus, or family history, IQ, magnetic resonance imaging (MRI), and positron emission tomography (PET). Variables were analyzed using non-parametric tests to assess relationship to postoperative seizure frequency. RESULTS: Of 475 patients who had epilepsy surgery, 111 had rare or frequent seizures in the second postoperative year. After anterior temporal lobectomy (ATL), age of first risk< or =5 years and presence of mesial temporal sclerosis on MRI were associated with rare seizures (66% of patients), whereas lack of these risk factors was associated with frequent seizures (75% of patients) (p<0.03). For non-ATL operations, preoperative seizure frequency of > or =20 seizures per month was associated with frequent postoperative seizures (p=0.03). No other variables influenced outcome. CONCLUSIONS: Some preoperative clinical features correlate with postoperative seizure frequency in patients with recurrent seizures after epilepsy surgery. This has implications for the surgical decision making process and early postoperative management.     

Risk factors for epilepsy in a rural area in Tanzania. A community-based case-control study.

BACKGROUND AND METHODS: The high prevalence of epilepsy detected in rural Tanzania by Dr. Jilek-Aall since 1960, was verified by the World Health Organization (WHO) survey on neurological and seizure disorders. Neurologists and psychiatrists further interviewed both patients and controls using standard methods. The presence of possible risk factors was complemented by corroborative evidence through interviewing close relatives and scrutinizing medical records. Seizures were classified based on clinical symptoms and the use of EEG. RESULTS: A family history of epilepsy in first-degree relatives was found in 46.6% of patients, but in only 19.6% of controls. The odds ratio for family history with epilepsy was 3.52 (95% confidence interval, CI 2.4-5.74, p < 0.001). A past history of febrile convulsion was found in 44% of patients in comparison to 23% of the control group which was significant (odds ratio 2.4, 95% CI 1.5-3.8; p < 0.001). A history of intrapartum complications was found in 12.1% of patients and 1.8% of controls (odds ratio 7.3, 95% CI 2.5-25.2; p < 0.002). Head injury was not a significant risk factor for epilepsy in this rural community. CONCLUSION: The results indicated a strongly independent association between four factors and the risk of developing epilepsy. It would seem more likely that previous brain insults/diseases play a significant major role in the cause of epilepsy in the Mahenge area. However, a genetic predisposition to low threshold for convulsions cannot be excluded.     

Seizure Frequency and Duration of Epilepsy are Not Risk Factors for Postoperative Seizure Outcome in Patients with Hippocampal Sclerosis

PURPOSE: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippocampal sclerosis. METHODS: The outcome from surgery was assessed in 56 consecutive patients with proven hippocampal sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. RESULTS: During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. CONCLUSIONS: Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.     

Classification of epilepsy syndromes and role of genetic factors

In this report the types of epilepsy syndromes seen in children in a tertiary referral center in Beirut, Lebanon were studied and the importance of consanguinity and family history in the occurrence of these syndromes was investigated. Records of 230 pediatric patients evaluated during a 1-year period with the diagnosis of single seizure, febrile seizure, or epilepsy were reviewed. Each patient was classified according to the International League Against Epilepsy classification. The occurrence of consanguinity, of family history of febrile seizures or epilepsy, and of other variables was noted. Thirty-six percent of patients were diagnosed with localization-related epilepsy, 21.7% with generalized epilepsy, 11.7% with undetermined generalized or focal, and 24.3% with special syndromes. Twelve percent of patients were diagnosed with idiopathic, 15.1% with symptomatic, and 30.3% with cryptogenic epilepsies. Consanguinity was more common in patients with symptomatic and cryptogenic epilepsies than in patients with idiopathic epilepsies or with incidental seizures (P < 0.05). Family history of epilepsy was more common in patients with symptomatic, cryptogenic, and idiopathic epilepsies than in patients with incidental seizures (P < 0.05). Family history of febrile seizures but not consanguinity was more common in patients with febrile seizures (P < 0.05). We conclude that genetic factors are important not only in idiopathic epilepsies and febrile seizures but also in cryptogenic and symptomatic epilepsies.     

Fieberkrämpfe

Febrile seizures are the most common seizure type in man and may be classified as simple or complex. The overall recurrence rate is 30–35%. Predictors of recurrence include a family history of febrile seizures, age at onset of less than 18 months, and a relatively low body temperature at the time of the seizure. The risk of subsequent epilepsy is only slightly elevated in children with simple febrile seizures. Factors that increase epilepsy risk are complex febrile seizures, abnormal neurological development, and a family history of epilepsy. While older studies did not report increased mortality in children with frebrile seizures, a recent large population-based study found increased mortality during the first 2 years after a febrile seizure in children with complex febrile seizures, seizure onset in the first year of life as well as seizures triggered by a body temperature of less than 39°C. Semiology and prognosis of febrile seizures are heterogeneous. Simple febrile seizures have a good prognosis with diagnostic and therapeutic procedures being uniform at the international level. Children with complex febrile seizures have a poorer prognosis, concerning both risk of epilepsy and mortality within the first 2 years after the first febrile seizure. In these children, decisions concerning diagnostic work-up and medical management are based on the risk profile of the individual patient.     

Generalized epilepsy with febrile seizures plus: A common childhood-onset genetic epilepsy syndrome

We examined the phenotypic variation and clinical genetics in nine families with generalized epilepsy with febrile seizures plus (GEFS⁺). This genetic epilepsy syndrome with heterogeneous phenotypes was hitherto described in only one family. We obtained genealogical information on 799 individuals and conducted detailed evaluation of 272 individuals. Ninety-one individuals had a history of seizures and 63 had epilepsy consistent with the GEFS⁺ syndrome. Epilepsy phenotypes were febrile seizures (FS) in 31, febrile seizures plus (FS⁺) in 15, FS⁺ with other seizure types (atonic, myoclonic, absence, or complex partial) in 8, and myoclonic–astatic epilepsy in 9 individuals. Inheritance was autosomal dominant with approximately 60% penetrance. This study confirms and expands the spectrum of GEFS⁺ and provides new insights into the phenotypic relationships and genetics of FS and the generalized epilepsies of childhood. Moreover, the ability to identify large families with this newly recognized common, childhood-onset, generalized genetic epilepsy syndrome suggests that it should be a prime target for attempts to identify genes relevant to FS and generalized epilepsy. Ann Neurol 1999;45:75–81     

Familial clustering of epilepsy and behavioral disorders: evidence for a shared genetic basis

Purpose: To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders. Methods: We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first‐degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9‐year follow‐up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)–Oriented scales were examined. The association between first‐degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first‐degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations. Key Findings: In probands with uncomplicated epilepsy, first‐degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM‐Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM‐Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first‐degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First‐degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy. Significance: Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.     

Prevalence of recurrent symptoms and their association with epilepsy and febrile seizure in school-aged children: a community-based survey in Iceland

We determined the prevalence of common recurrent symptoms in a community-based study of children and investigated whether these symptoms were associated with epilepsy and febrile seizure. A questionnaire was developed and sent to parents of all children attending school in the Reykjavik school district, grades 1-10. The questions assessed personality traits, headache, epilepsy, febrile seizure, and recurrent symptoms. Of the 13,044 questionnaires distributed, 10,578 were returned (81%). We analyzed the subset of 9679 (91%) questionnaires with complete information on relevant factors. The prevalence of epilepsy was 7.7/1000; febrile seizures were reported in 5.1% of children. Prevalence estimates of recurrent symptoms were similar to the published literature. In our cohort, recurrent dizzy spells and recurrent visual disturbances were associated with epilepsy after adjustment for age, migraine and febrile seizure. This association could reflect, only in part, the occurrence of auras in children with epilepsy.     

Clinical genetic studies in benign childhood epilepsy with centrotemporal spikes

Purpose: To accurately determine the frequency and nature of the family history of seizures in patients with benign childhood epilepsy with centrotemporal spikes (BECTS). Method: Participants with BECTS were recruited from the electroencephalography (EEG) laboratories of three pediatric centers and by referral. Pedigrees were constructed for up to three degrees of relatedness for each proband. All available affected and unaffected individuals underwent phenotyping using a validated seizure questionnaire. The proportion of affected relatives according to degree of relatedness was calculated and phenotypic patterns were analyzed. Key Findings: Fifty‐three probands with BECTS had a mean age of seizure onset at 7.8 years (range 2–12 years). Thirty‐four (64%) of 53 patients were male. For 51 participants, pedigrees were available for three degrees of relatedness. Fifty‐seven (2.7%) of 2,085 relatives had a history of seizures: Twenty‐one (9.8%) of 214 first‐degree, 15 (3%) of 494 second‐degree, and 21 (1.5%) of 1,377 third‐degree relatives. Febrile seizures were the most frequent phenotype, occurring in 26 of 57 affected relatives. There were 34 relatives with epilepsy: 6.5% (14 of 214) first‐degree, 1.8% (9 of 494) second‐degree, and 0.8% (11 of 1,377) third‐degree relatives. Of 21 affected first‐degree relatives: 8 of 21 had febrile seizures (FS), 4 had BECTS, 2 had epilepsy‐aphasia spectrum disorder, one had temporal lobe epilepsy with hippocampal sclerosis, 2 had focal epilepsy of unknown cause, 2 had genetic generalized epilepsies, and 3 had miscellaneous. Significance: The frequency of epilepsies in relatives and the heterogeneous syndromes observed suggest that BECTS has a genetic component consistent with complex inheritance. Focal epilepsies are the most common seizure disorder observed in relatives, especially BECTS and epilepsy‐aphasia spectrum disorder. Additional acquired or environmental factors are likely to be necessary for expression of the seizure disorder.     

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis

OBJECTIVES: To examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy. METHODS: Hippocampal volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS-) with proved hippocampal sclerosis, and compared with 98 controls. RESULTS: Ipsilateral and contralateral hippocampal volumes were not significantly different between the FS+ and FS- groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippocampal volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures. CONCLUSIONS: Although febrile seizures was associated with hippocampal sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippocampal atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippocampal sclerosis and are consistent with the hypothesis that hippocampal sclerosis is a pre-existing abnormality.