The cerebellar seizures of Hughlings Jackson.
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Cerebellar Diseases↗
Biomedical subjects
S F Berkovic
Publications and source records attributed to S F Berkovic.
Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study.
OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.
Adolescent↗
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.
Adult↗
Reorganization of verbal memory and language: a case of dissociation.
Left-to-right reorganization of verbal memory following early left hemisphere damage has been reported in patients whose expressive language is governed by the right hemisphere. We present a case in which verbal memory performance was intact, despite severe left mesial temporal damage, and despite aphasia on left internal carotid sodium amytal ablation. The distribution and degree of left mesial temporal damage was assessed visually and quantitatively on MRI. These findings raise the possibility that verbal memory may shift to the language-nondominant hemisphere as a result of early left mesial temporal damage.
Brain Damage, Chronic↗
Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12.
We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3. 8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (straight theta) 0 with D22S689. The LOD score in the larger family was 5.34 at straight theta=0 with the same marker. The two families share an identical linked haplotype for >/=10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF.
Australia↗
Surgical outcome in patients with epilepsy and dual pathology.
High-resolution MRI can detect dual pathology (an extrahippocampal lesion plus hippocampal atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippocampal lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippocampal lesion); mesial temporal resection (removal of an atrophic hippocampus); and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippocampus). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible.
Adolescent↗
A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2).
Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2; McKusick no. 254780) is an autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration and glycogen-like intracellular inclusion bodies (Lafora bodies). A gene for EPM2 previously has been mapped to chromosome 6q23-q25 using linkage analysis and homozygosity mapping. Here we report the positional cloning of the 6q EPM2 gene. A microdeletion within the EPM2 critical region, present inhomozygosis in an affected individual, was found to disrupt a novel gene encoding a putative protein tyrosine phosphatase (PTPase). The gene, denoted EPM2, presents alternative splicing in the 5' and 3' end regions. Mutational analysis revealed that EPM2 patients are homozygous for loss-of-function mutations in EPM2. These findings suggest that Lafora disease results from the mutational inactivation of a PTPase activity that may be important in the control of glycogen metabolism.
Amino Acid Sequence↗
Genetics of the epilepsies.
Epilepsies, like other common diseases, have complex inheritance, and molecular genetic studies in such conditions are difficult. There has been recent success in identifying the molecular basis of certain epilepsies, particularly in those syndromes with autosomal dominant inheritance. All four genes discovered to date for idiopathic epilepsies code for ion channel subunits, either ligand-gated or voltage-gated. The idiopathic epilepsies thus appear, at least in part, to be a family of channelopathies.
Epilepsy↗
Benign partial seizures of adolescence.
PURPOSE: A benign syndrome of partial seizures in adolescents (BPSA) was described by Loiseau et al. in 1978, but confirmation of this syndrome has been lacking. We sought to identify BPSA among teenagers with new-onset focal seizures enrolled in our prospective first-seizure study and to assess the EEG and magnetic resonance imaging (MRI) findings. METHODS: We searched the study database for patients aged between 10 and 20 years with focal seizures who did not have idiopathic partial epilepsies, epileptogenic lesions on MRI, or recurrent tonic-clonic seizures during 2 years of follow-up. RESULTS: The database contained 92 adolescents, including 37 with partial epilepsy, of whom eight (22%) patients matched the description of BPSA. All eight patients had seizures with a sensory/motor "march." Six had a secondarily generalized seizure and two had simple partial seizures alone. Epileptiform abnormalities were documented in five cases but lacked a distinctive morphology or distribution. No lesions were seen on MRI. CONCLUSIONS: BPSA can be provisionally diagnosed in teenagers with unprovoked focal seizures characterized by a march of sensory/motor symptoms, whose MRI is normal. The psychosocial consequences of chronic epilepsy in adolescence are considerable, so early recognition of this benign syndrome is important.
Adolescent↗
Comparison of antiepileptic drug levels in sudden unexpected deaths in epilepsy with deaths from other causes.
PURPOSE: (a) To compare postmortem antiepileptic drug (AED) levels in patients with sudden unexpected death in epilepsy (SUDEP) with those in a control group of subjects with epilepsy. If SUDEP patients more frequently had undetectable or subtherapeutic AED levels, this would suggest that compliance with AED treatment is poorer in this group and that poor compliance is a risk factor for SUDEP. (b) To determine whether a particular AED was detected more commonly in the SUDEP group, suggesting that this AED is associated with a higher risk of SUDEP. METHODS: A retrospective study of coronial cases was performed. Postmortem AED levels in 44 SUDEP cases and 44 control cases were compared. The control group consisted of epileptics who died of causes other than epilepsy, including natural disease (e.g., ischemic heart disease, accidents, and suicide). The AEDs measured included carbamazepine (CBZ), phenytoin, (PHT), valproate (VPA), phenobarbitone (PB), lamotrigine (LTG), clonazepam (CZP), and clobazam (CLB). The number of SUDEP and control cases in which CBZ only was detected were compared, as were the number in which PHT only was detected. RESULTS: Compared with the controls, the SUDEP group showed no difference in the number with no detectable AEDs (13 vs. 11), the number with subtherapeutic AEDs (10 vs. 13), and the number with therapeutic levels (21 in both groups). CBZ only was detected in 11 SUDEPs and 11 controls, and PHT only in five SUDEPs and 10 controls. CONCLUSIONS: Our study suggests the SUDEP group were no less compliant with AED treatment than the control group. This study does not support the hypothesis that poor compliance with AED treatment is a risk factor for SUDEP. There was no evidence that PHT or CBZ is associated with a higher risk of SUDEP.
Adolescent↗
Occurrence of hippocampal sclerosis: is one hemisphere or gender more vulnerable?
PURPOSE: We analyzed a large group of patients investigated for suspected seizures to test whether gender or side are important factors in the origins of hippocampal sclerosis (HS). METHODS: We studied 996 consecutive patients (48% men, 52% women) by using standard hippocampal T2-relaxometry methods. RESULTS: HS was associated with a highly abnormal T2 time (< or =113 ms). Categoric analysis showed that hippocampal T2 time was independent of gender and side. T2 time was bilaterally normal in 81% of men and in 79% of women; it was unilaterally abnormal in 15% of both men and women; and bilaterally abnormal in 4% of men and in 6% of women. Highly abnormal T2 relaxometry, suggesting HS, occurred with equal frequency in men and women and on the right and left sides. Quantitative analysis of hippocampal T2 times showed values not differing significantly between men and women or between the right and left hemispheres. There was no significant interaction between gender and side. CONCLUSIONS: In patients with seizure disorders, hippocampal T2 relaxometry is not different in adult men and women and in the right and left hemispheres.
Adult↗
Behavioural status during the intracarotid amobarbital procedure (Wada test): relevance for surgical management.
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Adult↗
Hippocampal T(2) abnormalities correlate with antecedent events and help predict seizure intractability.
INTRODUCTION: We performed hippocampal T(2) relaxometry as part of a routine magnetic resonance imaging (MRI) examination in 50 normal controls and 127 consecutive patients referred because of suspected seizures. METHODS: On the basis of T(2) values in controls (100.2 +/- 4.2 ms) we defined normal as <110 ms ( 113 ms (>mean + 3 SD). RESULTS: After detailed investigation, 103 of these 127 patients had epilepsy and 24 did not. In the nonepilepsy group, none had abnormal hippocampal T(2) values. Twenty-seven of the 103 patients in the epilepsy group had abnormal values, 7 were borderline and 69 were normal. Only 5 patients with abnormal T(2) values did not have temporal lobe epilepsy: 1 had extratemporal lobe epilepsy, 1 had generalized epilepsy and 3 had unclassified epilepsy. Twenty-two of 27 (81%) patients with abnormal hippocampal T(2) values had intractable epilepsy [compared with 32 of 69 (46%) patients with normal values; p < 0.05, chi(2) test]. Two thirds of patients with abnormal values had a history of a major antecedent event (compared to only 7% of those with normal values, p < 0.05, chi(2) test). CONCLUSION: Abnormal T(2) relaxometry is significantly associated with intractable epilepsy as well as with major antecedent events.
Adult↗
Hippocampal sclerosis: development in adult life.
Hippocampal sclerosis (HS) is the most common pathological lesion underlying intractable temporal lobe epilepsy. It is not known whether HS exists before the onset of epilepsy or whether it is caused by seizures. Its has been proposed that childhood seizures cause HS. Optimized magnetic resonance imaging (MRI), hippocampal volumes and T(2) signal quantitation were performed 2 weeks and 8 months following at tonic-clonic seizure in a 23-year-old man. MRI 14 days after the seizure showed symmetrical hippocampal volumes (ratio R/L = 1.03) with intact internal architecture bilaterally but marked signal change in the right hippocampus (T(2) right = 121, T(2) left = 103, normal < or = 108 ms). Eight months later this hippocampus showed severe atrophy with a volume ratio of 0.65 and T(2) values of 117 (right) and 109 ms (left). High-resolution imaging showed that volume loss occurred mainly in the CA1 region which showed high signal in the initial study. Characteristic MRI features of HS can develop in adults and HS cannot always be assumed to have its origins in childhood. Hypoxia in the context of seizures may be an important component in hippocampal damage. HS may be a preventable lesion and MRI signal change seen in the neuronal layers of the hippocampus may be an indication for neuroprotection.
Adult↗
Genetics of partial epilepsies.
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Epilepsies, Partial↗
Epilepsy and paroxysmal movement disorders in families: evidence for shared mechanisms.
The epilepsies have been regarded as clinically distinct from the paroxysmal movement disorders. Recently, a variety of ion channel defects have been identified as the biological basis of certain familial epilepsies and paroxysmal movement disorders. We studied two families with the co-occurrence of epilepsy, movement disorders and migraine. Information was obtained on 147 individuals in the two families. In family WF, there was a co-occurrence of epilepsy (benign infantile convulsions, idiopathic generalized epilepsy), episodic ataxia (with cerebellar atrophy and without myokymia) and common migraine. In family CL, epilepsy (febrile seizures, febrile seizures plus), kinesigenic paroxysmal dyskinesia and migraine (including hemiplegic migraine) were observed in various combinations over 3 generations. The observations in these two families, together with review of the literature, suggest that the co-occurrence of epilepsy (particularly benign infantile convulsions), paroxysmal movement disorders and migraine is not due to chance. Thus, these distinct clinical phenomena could have a shared biological basis and ion channel defects are an attractive possibility.
Adolescent↗
Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients.
BACKGROUND: Prognosis and treatment of the first seizure depends on identification of a specific epilepsy syndrome, yet patients with first seizures are generally regarded as a homogeneous group. We studied whether it is possible to diagnose specific epilepsy syndromes promptly by use of standard clinical methods, electroencephalography (EEG) and magnetic resonance imaging (MRI). METHODS: 300 consecutive adults and children presented with unexplained seizures. We systematically collected clinical data from patients and witnesses, and attempted to obtain an EEG within 24 h of the seizure. Where the EEG was negative, a sleep-deprived EEG was done. MRI was done electively. FINDINGS: A generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%) patients. Subsequent analysis showed that only three of these clinical diagnoses were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38 epileptogenic lesions, including 17 tumours. There were no lesions in patients for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were: generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified (19%). INTERPRETATION: An epilepsy syndrome can be diagnosed in most first-seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be done for all patients except for those with idiopathic generalised epilepsies and for children with benign rolandic epilepsy.
Adolescent↗
A potassium channel mutation in neonatal human epilepsy.
Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.
Action Potentials↗