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Bassel Abou-Khalil

Publications and source records attributed to Bassel Abou-Khalil.

At least 19 recordsLinked to original sources
PubMed2006

Mutations in the GABRA1 and EFHC1 genes are rare in familial juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME), accounting for approximately 25% of idiopathic generalized epilepsies, is genetically heterogeneous. Mutations in the alpha-1 subunit of the GABAA receptor (GABRA1) and EFHC1 genes have been reported in a few families with autosomal dominant (AD) JME. We have investigated the contribution of these two genes to familial JME in our cohort of 54 JME Caucasian families. Syndromic classification of JME was based on previously published criteria. We considered kindreds with at least one affected first-degree relative and the evidence of a vertical transmission as definite AD JME, and families with at least one affected second-degree relative as probable AD JME. We included 33 families meeting criteria for definitive AD JME and 21 that were classified as probable AD JME. None of these families were considered informative enough to analyze candidate loci for JME using linkage analysis. We have systematically screened coding exons of these two genes using temperature gradient capillary electrophoresis. Every heteroduplex with an abnormal mobility was sequenced. No disease-causing mutations in the GABRA1 gene were identified. Analysis of EFHC1 gene found one putative disease-causing mutation R221H that was previously reported as a tandem mutation. Several synonymous and non-synonymous coding polymorphisms were identified but the allelic frequency did not differ between controls and affected individuals. Our data suggests that the majority of familial AD JME is not caused by mutations in the GABRA1 and EFHC1 genes.

Calcium-Binding Proteins↗
PubMed2006

Musicogenic seizures can arise from multiple temporal lobe foci: intracranial EEG analyses of three patients.

PURPOSE: To determine the ictal-onset zone of musicogenic seizures by using intracranial EEG monitoring. METHODS: Musicogenic seizures in three patients with medically intractable musicogenic epilepsy were first localized by using noninvasive methods including, in one patient, ictal magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). The ictal-onset zones in these patients were then further localized using by intracranial EEG monitoring, and the outcomes of the two patients who underwent epilepsy surgery were determined. RESULTS: Patient 1's musicogenic seizures localized to the right lateral temporal lobe, patient 2's originated in the right mesial temporal lobe, and patient 3's arose independently from both mesial temporal lobes. Patients 1 and 2 underwent resective epilepsy surgery and are seizure free (Engel class I). CONCLUSIONS: Musicogenic epilepsy is a heterogeneous syndrome with seizures that can arise from multiple temporal lobe foci. Patients with medically intractable musicogenic epilepsy and with unilateral ictal onset zones may be considered candidates for resective epilepsy surgery.

Adult↗
PubMed2006

Identification of a novel locus for febrile seizures and epilepsy on chromosome 21q22.

PURPOSE: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. BACKGROUND: AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABA(A)-receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown. METHODS: We identified a five-generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome-wide search was performed. RESULTS: Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2-point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion-channel genes within this 6.5-cM locus as a cause of FS and epilepsy in this family. CONCLUSIONS: We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies.

Adult↗
PubMed2006

Rhythmic ictal nonclonic hand (RINCH) motions: a distinct contralateral sign in temporal lobe epilepsy.

PURPOSE: To describe a new ictal sign in temporal lobe seizures-rhythmic ictal nonclonic hand (RINCH) motions and to determine its lateralizing significance and other ictal manifestations associated with it. METHODS: We identified 15 patients with temporal lobe epilepsy who demonstrated RINCH motions and reviewed video-EEG recordings of all their seizures. We analyzed the epilepsy characteristics and all clinical features of recorded seizures, with particular attention to RINCH motions. RESULTS: RINCH motions were unilateral, rhythmic, nonclonic, nontremor hand motions. RINCH motions were usually followed by posturing, sometimes with some overlap. They involved the hand contralateral to the temporal lobe of seizure onset in 14 of 15 patients. CONCLUSIONS: RINCH motions are a distinct ictal sign that could be considered a specific type of automatism. They appear to be a lateralizing contralateral sign and are associated with dystonic posturing in temporal lobe epilepsy.

Adult↗
PubMed2006

Epilepsy and the impact of an epileptology clinic for patients with mental retardation and associated disabilities in an institutional setting.

PURPOSE: Epilepsy is a common problem in institutionalized patients with multiple handicaps. Limited data exist on the characteristics of epilepsy in this patient population and the impact of systematic evaluation by an epilepsy service. METHODS: We evaluated 138 patients with epilepsy, institutionalized at a facility that cares for 324 patients with multiple handicaps. Evaluation included EEG, MRI, and video-EEG monitoring. The medication regimen was changed according to seizure diagnosis and the status of seizure control. Follow-up was available for >or=6 months in 110 patients, 1 year for 89, and 1.5 years for 49 patients. We analyzed the seizure and epilepsy diagnosis in this population, as well as the seizure frequency after evaluation and treatment. RESULTS: The 76 male and 62 female patients' ages ranged from 14 to 73 years. Seventy-three patients had fewer than one seizure per month, whereas 29 patients had at least one seizure per month. Of 131 patients taking antiepileptic drugs (AEDs), 62 were receiving monotherapy, and 69 were receiving two or more AEDs. At the last follow-up, overall 55% of patients had reduced seizure frequency, including 23% who became seizure free. Two of 36 patients had spontaneous seizure recurrence after being seizure free with no AEDs for 4 months in one patient and 3 years for the other. Attempts were made to discontinue phenobarbital, primidone, and clonazepam in 21 patients. However, these were discontinued in only five patients. CONCLUSIONS: Epilepsy is heterogeneous in institutionalized patients with multiple handicaps. It is often responsive to medical therapy. Evaluation and treatment by epilepsy specialists had an overall favorable impact on seizure control.

Adolescent↗
PubMed2005

Long-term efficacy of levetiracetam for partial seizures.

OBJECTIVE: To obtain descriptive safety and efficacy data for long-term levetiracetam therapy and to allow patients benefiting from add-on levetiracetam to continue treatment until the drug was available commercially. METHODS: This long-term, noncomparative, open-label, follow-up study was conducted at 36 US sites. Patients with refractory partial epileptic seizures were eligible if they had benefited from add-on levetiracetam therapy in a previous study and wished to continue treatment. The levetiracetam dose was individualized over the range of 1,000-4,000 mg/day. Withdrawal of concomitant AEDs to allow levetiracetam monotherapy was permitted. Patients were evaluated every 12 weeks and followed for up to 4 years. Median total seizure frequency per week was the primary efficacy variable. RESULTS: A total of 280 subjects, most of whom had refractory partial seizures with or without secondary generalization, were evaluated. Most were receiving either one (34.6%) or two (53.2%) concomitant antiepileptic drugs (AEDs) at entry. Overall, 199 (71.1%) subjects completed the study and 81 (28.9%) withdrew prematurely, most commonly due to loss or lack of efficacy or adverse events. The median total seizure frequency per week (0.7 at the selection visit) remained stable. The probability of being seizure-free during the first 12 weeks was 13.4% and 3.7% by week 216. Twenty-five (8.9%) subjects received levetiracetam monotherapy for at least 100 days. Levetiracetam was safe and well tolerated; the most common levetiracetam-related adverse events were dizziness (6.8%), convulsion (5.7%), and somnolence (5.0%). CONCLUSION: Efficacy and safety were maintained during long-term levetiracetam treatment of refractory partial seizures.

Adolescent↗
PubMed2005

Mutations in GABRA1, GABRA5, GABRG2 and GABRD receptor genes are not a major factor in the pathogenesis of familial focal epilepsy preceded by febrile seizures.

GABA(A) receptors mutations have been reported in few epilepsy families with febrile seizures (FS) followed by generalized epilepsy. It is not known if such mutations may underlie FS followed by partial epilepsy, which is a more common type of epilepsy. We searched for disease-causing mutations in the genes of the alpha1, alpha5, gamma2 and delta subunits of the GABA-A receptor that were previously shown to contain epilepsy-causing mutations or epilepsy susceptibility polymorphisms. All coding and untranslated exons of these four GABA(A) subunit genes were screened in 74 unrelated patients with familial partial epilepsy preceded by FS. Most patients had temporal lobe epilepsy (TLE). We did not detect any disease-causing mutations that would be consistent with missense, nonsense or splice site mutations in any of the four analyzed genes. We conclude that these genes are not a major genetic factor in familial TLE preceded by FS.

Adult↗
PubMed2005

The GABBR1 locus and the G1465A variant is not associated with temporal lobe epilepsy preceded by febrile seizures.

BACKGROUND: Polymorphism G1465A in the GABBR1 gene has been suggested as a risk factor for non-lesional temporal lobe epilepsy (TLE); however, this genetic association study has not been independently replicated. We attempted to replicate this study in our cohort of patients with TLE. Furthermore, we also analyzed the coding sequence of this gene and searched for disease-causing mutations. METHODS: We included 120 unrelated individuals with TLE that was preceded by febrile seizures (FS) who did not have any evidence of structural lesions suggesting secondary epilepsy. 66 individuals had positive family history of TLE epilepsy and 54 were sporadic. Each patient was genotyped for the presence of G1465A polymorphism. All exons of the GABBR1 gene were screened by single strand confirmation polymorphism method. Genotypes were compared with two independent matched control groups. RESULTS: We detected two A alleles of the G1465A polymorphism in one homozygous control subject (0.87% of all alleles) and one A allele in a patient with TLE (0.45%, not significant). Other detected polymorphisms in coding regions had similar frequencies in epilepsy patients and control groups. No disease causing mutations in the GABBR1 gene were detected in patients with sporadic or familial TLE. CONCLUSION: Our results indicate that TLE preceded by FS is not associated with the polymorphisms or mutations in the GABBR1 gene, including the G1465A polymorphism. The proportion of TLE patients with FS in the original study, reporting this positive association, did not differ between allele A negative and positive cases. Thus, our failure to reproduce this result is likely applicable to all non-lesional TLE epilepsies.

Adult↗
PubMed2005

Benefit-risk assessment of levetiracetam in the treatment of partial seizures.

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.

Adult↗
PubMed2004

Resting functional MRI with temporal clustering analysis for localization of epileptic activity without EEG.

We report on the methods and initial findings of a novel noninvasive technique, resting functional magnetic resonance imaging (fMRI) with temporal clustering analysis (TCA), for localizing interictal epileptic activity. Nine subjects were studied including six temporal lobe epilepsy (TLE) patients with confirmed localization indicated by successful seizure control after resection. The remaining three subjects had standard presurgical evaluations with inconsistent results or suspected extratemporal lobe foci. Peaks of activity, presumably epileptic, were detected in all nine subjects, using the resting functional MRI with temporal clustering analysis. In all six patients who underwent resective surgery, the fMRI with temporal clustering analysis accurately determined the epileptogenic hippocampal hemisphere (P = 0.005). In the three subjects without confirmed localization, the technique determined regions of activity consistent with those determined by the presurgical assessments. Though more studies are required to validate this technique, the results demonstrate the potential of the resting fMRI with temporal clustering technique to detect and localize epileptic activity without the need for simultaneous electroencephalography (EEG). The greatest potential benefit of this technique will be in the evaluation of patients with suspected extratemporal lobe epilepsy and patients whose standard assessments are discordant.

Adolescent↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene.

PURPOSE: Mutations in the leucine rich, glioma inactivated gene (LGI1) were recently described in a small number of families with autosomal dominant lateral temporal epilepsy (ADLTE). ADLTE is characterized by partial seizures with symptoms suggestive of a lateral temporal onset, including frequent auditory aura. Here we report the results of clinical and genetic analyses of two newly identified families with ADTLE. METHODS: We identified two families whose seizure semiology was suggestive of ADLTE. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. The coding sequence of the LGI1 gene from affected subjects from both families was analyzed for evidence of mutation. RESULTS: Each patient had a history of partial seizures, often with secondary generalization earlier in the course. Auditory aura was reported by approximately two thirds of affected patients in each pedigree. Novel mutations in LGI1 were detected in both families. A heterozygous single-nucleotide deletion at position 329 (del 329C) was detected in affected individuals from one family, whereas patients from the second family had a nonsynonymous variation, corresponding to C435G. CONCLUSIONS: We identified two novel mutations in the LGI1 gene. The phenotype of these two families was similar to that of other kindreds with ADLTE, as auditory aura was absent in one third of affected individuals. Our results further support that LGI1 mutations should be considered in patients with a history of partial seizures if the semiology of seizures is consistent with the onset in the lateral temporal lobe.

Adult↗
PubMed2003

Levetiracetam treatment of idiopathic generalised epilepsy.

Levetiracetam (LEV) is effective for treating localisation-related epilepsy, but it is uncertain whether it is effective for treating idiopathic generalised epilepsy. We compared 12-week baseline and LEV treatment periods for patients with generalised seizure types-myoclonic, tonic-clonic and absence seizures--who had failed other anticonvulsants. The majority of 55 patients (76%) had >50% seizure reduction with LEV therapy, 40% became seizure-free; 15% discontinued LEV due to adverse events, mostly sedation. This is preliminary evidence that LEV is effective for treating idiopathic generalised epilepsy.

Adolescent↗
PubMed2003

Long-term experience with levetiracetam.

Although short-term clinical trials provide important data regard-ing efficacy and tolerability, long-term studies are needed to address important aspects of clinical practice, such as long-term efficacy and safety. Long-term studies and post-marketing data show that the efficacy of levetiracetam is sustained over the long term and that this antiepileptic drug continues to be well tolerated, with low withdrawal rates and high retention rates. Patients continue to achieve significant reductions in seizure frequency and may achieve seizure freedom. Levetiracetam may allow patients to decrease the number of concomi-tant antiepileptic medications or withdraw to monotherapy. Add-on therapy with levetiracetam should be considered when additional control of seizures is needed.

Anticonvulsants↗
PubMed2002

In vivo hippocampal metabolic dysfunction in human temporal lobe epilepsy.

BACKGROUND: The nature of functional metabolic disturbances in mesial temporal lobe epilepsy remains unclear. OBJECTIVES: To compare in vivo measures of hippocampal metabolic abnormalities in mesial temporal lobe epilepsy, as acquired with fludeoxyglucose F 18 positron emission tomography and proton magnetic resonance spectroscopic imaging, and to determine the relationship between N-acetylaspartate (NAA) disturbances and well-established derangements of glucose metabolism. DESIGN: Measures of hippocampal glucose metabolism from fludeoxyglucose F 18 positron emission tomography were normalized to whole brain counts to provide a glucose uptake metabolic index. Proton magnetic resonance spectroscopic imaging was performed at 4.1 T, and measures of creatinine/NAA ratio were made from mostly hippocampal-only voxels. Direct comparisons and correlation analysis of measures were performed. SETTING: Presurgical evaluations for treatment of intractable epilepsy. PATIENTS: Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine were studied. RESULTS: The mean ipsilateral hippocampal glucose metabolic index (0.85) was normal, while the contralateral metabolic index (0.95) was nearly significant for an abnormally elevated measure. The mean ipsilateral hippocampal creatinine/NAA (1.26) was abnormally elevated; the mean contralateral creatinine/NAA (0.88) was normal. Hippocampal glucose and creatinine/NAA measures did not correlate; asymmetry measures also did not correlate. CONCLUSIONS: Hippocampal metabolic disturbances in mesial temporal lobe epilepsy as measured by fludeoxyglucose F 18 positron emission tomography vs proton magnetic resonance spectroscopic imaging reflect different mechanisms of biochemical dysfunction. This lack of correlation is hypothesized to reflect a differential effect of varying degrees of disturbed cellular energy metabolism on mechanisms of glucose use and biosynthesis of NAA.

Adolescent↗