Seizure: European Journal of Epilepsy

Editorial Board

2010-07-01

Is elevated norepinephrine an etiological factor in some cases of epilepsy?

Paul J. Fitzgerald — 2010-05-21

Abstract: It is well established that the neurotransmitter norepinephrine (NE) has anticonvulsant properties. However, NE may also have proconvulsant properties under some conditions, both in animal epilepsy models and in humans. This paper examines the hypothesis that this neurotransmitter has proconvulsant properties, where much of the pharmaceutical evidence comes from rodent models. In assessing the elevated NE epilepsy hypothesis, the following seven lines of evidence are examined that include studies of: (1) antidepressants that raise the level of NE; (2) clonidine and other alpha 2 adrenergic agonist drugs that lower the level of NE; (3) prazosin and other drugs that affect alpha adrenoceptors; (4) propranolol and other drugs that affect beta adrenoceptors; (5) pheochromocytoma, which is a rare cancer of the adrenal glands that can boost NE levels; (6) comorbidity of epilepsy with bipolar disorder, hypertension, and obesity, where all four conditions may involve elevated NE; and (7) psychological stress, which is associated with increased release of NE. The body of evidence supporting the NE proconvulsant hypothesis is consistent with the notion that elevated, endogenous noradrenergic transmission is an etiological factor in some cases of epilepsy.

Outcome after cortico-amygdalo-hippocampectomy in patients with temporal lobe epilepsy and normal MRI

2010-05-24

Abstract: Rationale: We describe seizure and neuropsychological outcome obtained after CAH in patients with TLE and normal MRI evaluated in the modern imaging era.Methods: Forty-five adult consecutive patients with TLE and normal MRI were studied. All patients had neuropsychological testing, interictal and ictal EEG recordings and MRI. They were divided into two groups: Group 1 (n=18), included patients in whom non-invasive neurophysiological evaluation was lateralizing and Group 2 (n=27) included patients with non-lateralizing neurophysiological data who were submitted to invasive recordings.Results: Seventy-seven percent of the Group 1 patients were rated as Engel I; 11% were rated as Engel II and 11% as Engel III. In Group 2, there were 57% of patients seizure-free, 26% in Engel II and 14% in Engel III. Pre-operatively, mean general IQ was 82 and 78 in Groups1 and 2, respectively; post-operatively, mean general IQ was respectively 86 and 71. Some degree of verbal memory decline was noted in all patients submitted to dominant temporal lobe resection in both Groups 1 and 2. At last follow-up visit, 22% of Group 1 and 11% of Group 2 patients were receiving no antiepileptic drugs (AED).Conclusions: Our data showed that patients with TLE and normal MRI could get good surgical results after CAH although 60% of them would need invasive recordings and their results regarding seizure control and cognition were worse than those obtained in patients with MRI defined temporal lobe lesions. Caution should be taken in offering dominant temporal lobe resection to this subset of patients.

Fractures in epilepsy children

Anna Gniatkowska-Nowakowska — 2010-05-21

Abstract: Purpose: To describe a greater risk of fractures (about 2–6 times more often) in epilepsy children than in children without epilepsy.Methods: This article describe 126 epilepsy children in age 7–16 who were treated with Antiepileptic Drugs (AEDs) in mono and add-on therapy during 5 years. In the control group were 132 children in age 7–16 without epilepsy and not treated with AEDs, observed in Outpatient Clinic due to headache for 5 years. In both groups we measured bone mineral density (BMD), the calcium and phosphate levels in blood and urine and frequency of fractures. We analyzed both groups statistically (Mann–Whitney test).Result: The frequency of fractures is 2–3 times greater in children with epilepsy then in the control group. Osteoporosis and osteopenia is more often present in children who have taken AEDs.Differences in calcium and phosphate levels in blood and urine between study and control group are statistically significant (p<0.001).Conclusion: Fractures are an important adverse effect in children who are taking AEDs.

Partial epilepsy presenting as focal atonic seizure: A case report

Jun Zhao, Pegah Afra, Bola Adamolekun — 2010-06-04

Abstract: A case of atonic seizures localized to the frontal lobe by video-EEG monitoring is reported. The patient is a 38-year-old female with intractable atonic seizures characterized by abrupt onset of facial grimacing and a slow head drop. The onset of atonic seizures was about 6 years before presentation. Video-EEG monitoring showed that her atonic seizures were emanating from the right frontal head region. A high voltage spike and slow wave discharge invariably coincided with the onset of atonic seizures in the patient, similar to the interruption of tonic muscular activity time-locked to a spike on the EEG described in epileptic negative myoclonus; a syndrome associated with epileptic activity in the premotor cortex.Since routine MRI imaging in this patient was normal, diffusion tensor imaging (DTI) was applied to analyze the white matter integrity of the normal-appearing white matter in the frontal lobes of the patient. We compared the fractional anisotropy, parallel diffusivity and perpendicular diffusivity of normal-appearing white matter in the right versus left frontal lobe. Our results showed no significant difference between the two sides. Possible reasons for the normal DTI findings are discussed.

Anterior temporal lobectomy combined with anterior corpus callosotomy in patients with temporal lobe epilepsy and mental retardation

Shuli Liang, Anmin Li, Ming Zhao, Hong Jiang, Xiaolun Meng, Yajing Sun — 2010-06-16

Abstract: Aims: To investigate the surgical outcomes of anterior corpus callosotomy (aCCT) combined with anterior temporal lobectomy (ATL) in patients with intractable temporal lobe epilepsy (TLE) and mental retardation (MR).Methods: Sixty patients with TLE and MR were carefully selected and randomly divided into two equal groups: ATL and aCCT, in which they were treated with ATL or ATL combined with aCCT, respectively. Surgical outcomes, including seizure control, IQ and quality of life (QOL) changes, as well as complications were recorded and analyzed 2 years after operation.Results: Seizure-free status had been achieved in 66.7% of all patients. The aCCT group had higher percentage in Engle Classes I–II than the ATL group (96.7% vs. 80.0%, P<0.05). 56.7% of patients in ATL group and 63.3% in aCCT group had improved full scale IQ (FIQ) after surgery, while the decline of FIQ in aCCT group was less than that of ATL group (3.3% vs. 30.0%). Compared with pre-operative score, the mean post-operative score of performance IQ in aCCT group had improved. Significant difference in QOL change had been found between two groups (P<0.001). 73.7% of patients in aCCT group had their QOL improved with no long-term complications.Conclusions: ATL combined with aCCT can improve QOL and performance IQ in patients with TLE and MR.

Temporal Lobe Epilepsy and Matrix Metalloproteinase 9: A tempting relation but negative genetic association

2010-06-04

Abstract: Objective: Neuroplasticity can be defined as the ability of the brain to adapt to environmental impacts. These adaptations include synapse formation and elimination, cortical reorganization, and neurogenesis. In epilepsy these mechanisms may become detrimental and contribute to disease progression. It has been proposed that Matrix Metalloproteinase 9 (MMP-9), a proteinase that cleaves extracellular matrix molecules, may be critically involved in aberrant synaptic formation in hippocampi of patients with Temporal Lobe Epilepsy (TLE). Here we present a case–control study designed to identify possible variants of the MMP-9 gene associated with human TLE.Material and methods: 218 Norwegian patients with TLE and 181 ethnically matched controls were compared in our association analysis. We also studied associations within two subgroups of TLE – Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), and Temporal Lobe Epilepsy with childhood Febrile Seizures (TLE-FS). Single nucleotide polymorphisms (SNPs) were selected from HapMap and dbSNP databases for the MMP-9 gene on chromosome 20. We used standard haplotype analysis and multivariate explorative analysis.Results: There were no statistically significant associations between the analyzed SNPs in the MMP-9 gene and TLE, nor were any significant associations found with the two examined subgroups MTLE-HS and TLE-FS, confirmed by both analyses.Conclusion: We could not identify any polymorphisms of the human MMP-9 gene that were associated with TLE, MTLE-HS or TLE-FS, in the selected SNPs. However, factors that influence MMP-9 gene expression, post-transcriptional modifications, or the balance between activation and inhibition of MMP-9 may play a role in the pathogenesis of TLE and other epileptic syndromes.

ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: A systematic review and meta-analysis

2010-06-04

Abstract: Objective: The C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case–control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.Methods: Databases were obtained from the Cochrane Library, MEDLINE, EMBASE, major American and European conference abstracts, and www.google.my for genetic association studies up to February 2010. All the case–control association studies evaluating the role of ABCB1 C3435T in pharmacoresistance to AEDs were identified. The new definition of treatment outcome from International League Against Epilepsy (ILAE) was used for including studies for sub-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using models of both fixed- and random-effects for comparisons of the alleles and genotypes with co-dominant (C/C vs. T/T, C/T vs. T/T), dominant (C/C+C/T vs. T/T), and recessive (C/C vs. C/T+T/T) models in overall and in ethnicity subgroups. The 19 studies were selected for the next sub-analysis based on the new definition of drug-responsiveness and drug-resistance from ILAE. The same analysis was also performed for treatment outcome and ethnicity subgroups.Results: A total of 22 association studies including 3231 (47.8%) drug-resistant patients and 3524 (52.2%) drug-responsive patients or healthy controls (genotyped for C3435T) were pooled in this meta-analysis. The allelic association of ABCB1 C3435T with risk of drug-resistance was not significant under fixed-effects model, 1.06 (95% CI 0.98–1.14, p=0.12) and random-effects model, 1.10 (0.93–1.30, p=0.28) in overall and in the subgroup analysis by ethnicity. Similar results were also obtained for all genetic models in the stratified analyses by new definition of drug-resistance by ILAE and ethnicity subgroups. There was no publication bias.Conclusion: We failed to show an association between the ABCB1 C3435T polymorphism and the risk of drug-resistance suggesting a revision in contribution of this polymorphism in the multi-drug transporters hypothesis of pharmacoresistance to AEDs in epilepsy.

Bimodal ultradian seizure periodicity in human mesial temporal lobe epilepsy

2010-06-28

Abstract: Background: Mesial temporal lobe epilepsy (mTLE) has been suggested to follow a circadian rhythm. Previous research found an afternoon peak in mTLE seizure occurrence. We evaluated the pattern of seizure occurrence in patients with well-localized mTLE and hypothesized that peak seizure frequency would occur in the afternoon, and that this pattern would not be altered by age, gender, or seizure focus.Methods: We retrospectively identified consecutive mTLE patients with a seizure-free outcome following anterior temporal lobectomy from 1993 to 2004 with video-EEG captured seizures. We recorded and plotted the 24-h clock time for each seizure and performed cosinor analysis. SAS Proc GLIMMIX was used to fit the linearized transform of the cosinor model. Negative binomial regression fitted by the generalized estimating equations (GEE) method was also performed to estimate and compare the mean seizure rates over a 24-h day.Results: Sixty mTLE patients monitored between 2 and 16 days were analyzed. Mean (standard deviation), median number of seizures per subject were 10.47(7.86), 9.00. Cosinor plots indicated that the function had two modes: 7–8a.m. and 4–5p.m. GEE analysis was consistent with peak seizure frequency occurrence at 6–8a.m. (p<0.0001) and 3–5p.m. (p<0.01).Conclusions: We found a bimodal pattern of seizure occurrence in human mTLE, with peak seizure frequencies occurring between 6–8a.m. and 3–5p.m. confirming an afternoon peak, as well as a previously unsuspected morning peak in seizure occurrence that provides rationale for future investigations of antiepileptic drug chronopharmacology and informs patient counseling regarding patterns of seizure occurrence.

Effect of chronic vagal nerve stimulation on interictal epileptiform discharges

2010-06-25

Abstract: We evaluated the effect of vagus nerve stimulation (VNS) on interictal epileptiform discharges (IEDs) in 32 epileptic patients (18 females; 14 males) with an average age of 42.2±11.4 years, all of whom had been suffering from epilepsy for an average of 29.2±14.5 years. All of the patients had received VNS for 5 years. The first EEG was performed prior to the initiation of stimulation; the second EEG was performed at the 5-year follow-up visit. The duration of each EEG was 30min. We compared these two EEGs in terms of the number of IEDs present in each patient and correlated them to other variables.The average total number of IEDs during EEG and the total number of seconds in which IEDs were present decreased significantly after 5 years of stimulation from 97.3±106.9 resp. 80.6±86.1 to 49.4±94.0 resp. 37.8±65.0. Although there was no positive correlation between the reduction of IEDs and the percent of seizure reduction, we found a greater decrease of IEDs in patients who responded to VNS in comparison to those who did not. The decrease of IEDs was more pronounced in patients suffering from temporal lobe epilepsy than in patients suffering from extratemporal epilepsy. No other significant correlations were found.VNS reduced IEDs in patients chronically simulated for epilepsy. The reduction of IEDs was greater in patients who responded to VNS and in patients suffering from temporal lobe epilepsy.

Clinical feasibility of immediate overnight switching from slow-release carbamazepine to oxcarbazepine in Korean patients with refractory partial epilepsy

2010-06-10

Abstract: We assessed the clinical variables predicting the feasibility of immediate overnight switching from slow-release carbamazepine to oxcarbazepine in Korean patients with refractory partial epilepsy. Thirty patients aged 15 years or older with refractory partial epilepsy, who had been treated with slow-release carbamazepine as monotherapy or in combination therapy, were switched overnight from slow-release carbamazepine (mean dose at switching, 900mg/day) to oxcarbazepine. Of these 30 patients, 29 (96.7%) had been treated with a slow-release formulation of carbamazepine. The proportion of patients with polytherapy was 85.3%. Overall, 9 of 30 (30%) switched patients experienced clinically significant adverse events until 2 weeks after switching, including 2 with seizure aggravation. The only clinical variable related to the failure of overnight switching was the number of seizures at baseline.

Occipital lobe seizures related to marked elevation of hemoglobin A1C: Report of two cases

Wan-Ling Hung, Peiyuan F. Hsieh, Yi-Chung Lee, Ming-Hong Chang — 2010-06-17

Abstract: Occipital lobe seizures caused by nonketotic hyperglycemia (NKH) have been reported in only a few cases and are not fully characterized. We report two cases of NKH-related occipital lobe seizures with high hemoglobin A1C (HbA1C), epileptiform electroencephalograph (EEG) and MRI abnormalities. Both patients had moderate hyperglycemia (310–372mg/dl) and mildly elevated serum osmolarity (295–304mOsm/kg) but markedly elevated HbA1C (13.8–14.4%). One patient had a clinico-EEG seizure originating from the right occipital region during sleep. The other patient had an interictal epileptiform discharge consisting of unilateral occipital beta activity in sleep. None of the previously reported cases fulfilled the criteria of a nonketotic hyperglycemic hyperosmolar (NKHH) state, or showed any interictal beta paroxysms, spikes, sharp waves, or spike/sharp-slow wave complexes. We suggest that prolonged exposure to uncontrolled hyperglycemia, as indicated by HbA1C, rather than an acute NKHH state is crucial in the development of this peculiar seizure. We also suggest clinicians look for the presence of interictal focal beta paroxysms in addition to the usual epileptiform discharges while reading the EEG of these patients.

Adult convulsive status epilepticus in the developing country of Honduras

2010-06-16

Abstract: Epidemiologic data on convulsive status epilepticus (CSE) is needed to develop preventative strategies. Epilepsy is one of the known risk factors for CSE. A systematic review of epidemiologic studies on status epilepticus (SE) completed in the United States and Europe reports that people with epilepsy account for less than 50% of cases of SE in all age groups. Less is known about the epidemiology of SE in developing countries including those in Central America.A high incidence of epilepsy, widespread non-adherence to anti-epileptic drugs (AED), and common use of complementary and alternative medicines have been shown in all ages in the developing country of Honduras, Central America. In 2003, an epidemiologic study of CSE in Honduran children demonstrated it is common and exhibits a long duration until onset of treatment. The etiologies, treatment, and outcomes of CSE in Honduran adults have not been thoroughly studied. This study is a consecutive case series of 31 adult patients presenting with CSE to the adult medicine emergency department of the tertiary care “Hospital Escuela” in the capital city Tegucigalpa, Honduras. The majority (77.4%) of patients had a prior history of epilepsy. Non-adherence to AED was the most common etiology of CSE (75.0%). The mortality rate in this pilot CSE study was 14.8%, which is similar to studies from industrialized countries where mortality from status epilepticus ranged from 7.6 to 22% for all age groups. However, this rate is concerning given that CSE from epilepsy and AED non-adherence generally carries a good prognosis.Improving AED adherence in this population appears to be the most effective approach in decreasing the rate, and possibly the mortality of Honduran adult CSE.

Gastaut type-idiopathic childhood occipital epilepsy and childhood absence epilepsy: A clinically significant association?

2010-05-14

Abstract: We report an unusual association between idiopathic occipital epilepsy and childhood absence epilepsy in 2 pediatric patients. At first clinical and electroencephalographic evaluation, the patients presented the peculiar signs of idiopathic occipital epilepsy Gastaut type: focal sensory visual seizures, migraine-like symptoms (only in one patient) and unilateral spike–wave discharges over occipital regions. Both children were treated with valproic acid and their seizures were rapidly controlled. After a seizure-free period, the patients presented typical absence with ictal electroencephalographies showing 3cycles/s generalized and symmetrical spike–wave complexes. We discuss the possible association between these two epileptic syndromes and its common pathophysiological mechanisms.

Comment on: Cerebrospinal fluid apolipoprotein E concentration decreases after seizure

Jiang Wu, Ping Liu, Jie Lei, Hong-Liang Zhang — 2010-05-17

We read with great interest the recent article by Wang et al. about apolipoprotein E (apoE) concentration in the cerebrospinal fluid (CSF) of epileptic patients. They found that concentrations of apoE in the CSF of epileptic patients decreased and correlated with gender, etiological factor and seizure types. We agree that further studies with a larger sample size and regular follow-ups are needed to confirm the status of apoE levels in epilepsy. However, we have some concerns regarding the interpretation of their findings proposed by the authors.