Seizure: European Journal of Epilepsy - Articles in Press

Value of 3.0T MR imaging in refractory partial epilepsy and negative 1.5T MRI - Corrected Proof

2010-07-30

Abstract: Background: High-field 3.0T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0–1.5T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0T patients with refractory partial epilepsy and negative 1.5T MRI.Methods: We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0T MR study after a negative 1.5T MR study. High-field 3.0T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist.Results: Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0T MR study after a 1.5T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5–18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery.Conclusions: The frequency of detection of a new lesion by re-imaging at 3.0T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study.

Does a preference for fatty foods prior to commencing treatment with the ketogenic diet predict the efficacy of this diet? - Corrected Proof

C.F. Dekker, T.A.M. van den Hurk, O. van Nieuwenhuizen — 2010-07-26

Abstract: The ketogenic diet can be effective in children who suffer from drug-resistant epilepsy. However, it is still hard to predict how large an effect this diet will have for an individual child. Previous data suggests a high-fat food preference is more likely in those with epilepsy, as assessed by in-person forced-choice design. The aim of this study is to examine whether a partiality to fatty foods prior to commencing the ketogenic diet can be used as a predictive factor for the efficacy of this diet in children with drug-resistant epilepsy.Data from 43 children aged between 2 and 19 years was used in this retrospective, non-controlled, non-randomised, open study. All children had followed the ketogenic diet for a period of 3 months or more. Before commencing the diet, a food record was collected for each child to determine the percentage of daily energy-intake accounted for by fats. Parents of the participants completed a questionnaire to measure fat-preference in the pre-diet period and received a score to objectify the efficacy of the treatment.The raw scores on the food record and on the questionnaire were divided into subgroups. Subsequently Kendall's tau-b was calculated for the correlation between each combination of variables. A non-significant correlation was found for the relationship between the food record and the questionnaire (p=.939), the relationship between the food record and the efficacy of the treatment (p=.827) and the relationship between the questionnaire and the efficacy of the treatment (p=.539). This means treatment efficacy cannot be predicted by the child's food preference.

Quality of life and treatment satisfaction in Spanish epilepsy patients on monotherapy with lamotrigine or valproic acid - Corrected Proof

2010-07-21

Abstract: Background: Patients suffering from epilepsy have an impaired health related quality of life (HRQoL) because of seizures and treatment adverse events. Epilepsy affects differently both genders, due to hormonal influence in women. The aim of this study is to assess the impact on HRQoL and treatment satisfaction in epilepsy patients treated with stable doses of lamotrigine and valproic acid.Methods: Observational cohort prospective study was conducted in 18 Spanish neurology sites. Patients with clinically stable partial or generalized epilepsy, already receiving lamotrigine or valproic acid on monotherapy, were assessed in two visits: baseline and at 6 months. Socio-demographic and clinical variables were recorded at baseline; HRQoL (QOLIE-10) treatment satisfaction and women image self-perception were assessed at both visits. Impact on HRQoL was assessed in both treatment arms overall and in the women subgroup.Results: A total of 107 patients were evaluated; 53 (14 men, 39 women) on lamotrigine and 54 (27 men, 27 women) on valproic acid. Mean (SD) age was 30.4 (9.1) years and mean (SD) time since epilepsy diagnosis was 8 (8.1) years. Mean (SD) QOLIE-10 score at baseline was 73.9 (15.7) points (76.6 and 71.4 for lamotrigine and valproic, respectively). At follow up, patients reported better HRQoL on both lamotrigine (78.8 points) (p<0.05) and on valproic (72.4 points) in comparison with baseline. Women's HRQoL at follow up was better on the lamotrigine arm compared with valproic acid: 78.8 (12.8) vs. 70.3 (15.9) (p<0.05). Women on the lamotrigine arm declared higher satisfaction with treatment and higher disagreement with the different statements referred to a negative image self-perception.Conclusions: Chronic patients with epilepsy already treated with lamotrigine slightly improved HRQoL at 6 month follow up, whereas no significant changes were observed in the valproic acid group. Lamotrigine impact on patients’ HRQoL seems to be even more positive in the subgroup of women.

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy - Corrected Proof

2010-07-20

Abstract: Objective: The goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI).Methods: A fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided.Results: A fearful face paradigm led to significant amygdalar activation in all but one patient (p<0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipislateral amygdalar fMRI-responses.Conclusion: Unilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.

Focal sensory-motor status epilepticus in multiple sclerosis due to a new cortical lesion. An EEG–fMRI co-registration study - Corrected Proof

2010-07-20

Abstract: A case of focal inferior limb sensory-motor status epilepticus as the only manifestation of a multiple sclerosis (MS) relapse is described. To obtain evidence of the relationship between the seizures, the cortical plaque and the left foot motor area, an EEG–fMRI co-registration study was undertaken demonstrating that seizure-related BOLD signal substantially overlapped with the inflammatory lesion involving the foot sensory-motor cortex. Seizures did not respond to intravenous anti-epileptic drugs (AEDs) but were controlled by steroid therapy.

Absence epilepsy and periventricular nodular heterotopia - Corrected Proof

2010-07-16

Abstract: We report a case of a girl who presented with typical absence seizures at age of 4.5 years. EEG showed absence seizures of sudden onset with 3Hz spike-and-waves that also correlated with the clinical absences. The seizure semiology included subtle deviation of the eyes which prompted MRI investigation of the brain. This showed a periventricular nodular heterotopia in the mid to anterior horn of the right lateral ventricle. Although possibly coincidental, periventricular heterotopia are considered to be epileptogenic and this association has been reported once before. Migration disorders, such as in the periventricular heterotopia of our patient, may influence the formation and excitability of the striato–thalamo–cortical network involved in the generation of 3Hz spike-waves.

Status epilepticus alters hippocampal PKAβ and PKAγ expression in mice - Corrected Proof

Jian Xin Liu, Yong Cheng Tang, Yong Liu, Feng Ru Tang — 2010-07-15

Abstract: Objectives: To investigate the localization and progressive changes of cyclic-AMP dependent protein kinase (cPKA) in the mouse hippocampus at acute stages during and after pilocarpine induced status epilepticus.Methods: Pilocarpine induced status epilepticus mice were sacrificed 30min, 2h or 1 day after the start of a ∼7h lasting status as assessed by video-electroencephalography. Brains were processed for quantitative immunohistochemistry of hippocampal cPKAβ and cPKAγ, and immunohistochemical co-localization of cPKAβ and cPKAγ with calbindin (CB), calretinin (CR), and parvalbumin (PV).Results: Based on anatomical and morphological assessment, cPKAβ was primarily expressed by principal cells and cPKAγ by interneurons. In CA1, cPKAβ co-localized with 76% of CB, 41% of CR, and 95% of PV-immunopositive cells, while cPKAγ co-localized with 50% of CB, 29% of CR, and 80% of PV-immunopositive cells. Upon induction of status epilepticus, cPKAβ expression was transiently reduced in CA1, whereas cPKAγ expression was sustainably reduced.Conclusion: cPKA may play an important role in neuronal hyperexcitability, death and epileptogenesis during and after pilocarpine induced status epilepticus.

Milder phenotype with SCN1A truncation mutation other than SMEI - Corrected Proof

2010-07-15

Abstract: Till now truncation mutations of voltage-gated sodium channel alpha subunit type I (SCN1A) gene were mostly found in severe myoclonic epilepsy of infancy (SMEI) patients. In this research we first identified two novel de novo truncation mutations (S662X and M145fx148) in two patients whose phenotypes were quite milder compared with SMEI patients. One patient was diagnosed as generalized epilepsy with febrile seizures plus (GEFS+); the other had focal seizures. Both patients had good response to anti-epileptic therapy (valproate or the combination of valproate and topiramate). Our findings extended the utility of the SCN1A gene testing and further confirmed the complex relationship between genotype and phenotype of SCN1A mutations. Further work is needed to optimize the protocol for specific genetic testing in children with epilepsy.

Peri-ictal heart rates depend on seizure-type - Corrected Proof

Rainer Surges, Matthew C. Walker — 2010-07-15

We have read with great interest the recent article of Nilsen and colleagues. The authors have investigated heart rates at different peri-ictal time points in non-generalized seizures of patients with partial epilepsy and compared those to peri-ictal heart rates in patients who had had secondarily generalized tonic–clonic seizures (SGTC). Their major finding was that patients with SGTC had higher pre-ictal heart rates.

Senile myoclonic epilepsy: Delineation of a common condition associated with Alzheimer's disease in Down syndrome - Corrected Proof

2010-07-05

Abstract: In Down syndrome (DS), epilepsy is frequent in all age classes and is recognized as a significant cause of additional handicap and morbidity. Longer life expectancy has led to the recognition of the high incidence of both Alzheimer's disease and seizures in elderly persons with DS. Neuropathological markers of AD are found in all DS brains and clinical symptoms of AD become apparent by the age of 60 years and above in over 50% of DS subjects. Following preliminary description of myoclonic seizures and/or myoclonic epilepsy in isolated cases or small series, we wish to report the diagnostic criteria, treatment and prognosis of a specific and recognizable form of epilepsy associated with AD in a larger group of middle-aged to elderly DS patients. This markedly under-recognized entity may indeed concern an already large and steadily increasing number of patients. We reviewed all medical records of patients with DS referred to our centers (Centre Saint Paul-Gastaut, Marseille; Epilepsy Unit, Montpellier University Hospital; Department of Neurology, Hospital General de Asturias, Oviedo) since 1995. DS had been diagnosed in all at birth, and all presented with the typical morphological changes associated with DS. We selected all cases (18) referred as adults with new onset of myoclonic jerks (MJ) and/or behavioral or cognitive deterioration (CD).

Baccoside A suppresses epileptic-like seizure/convulsion in Caenorhabditis elegans - Corrected Proof

2010-07-05

Abstract: The 1mm long Caenorhabditis elegans is one of the prime research tools to study different human neurodegenerative diseases. We have considered the case in which increase in the surrounding temperature of this multicellular model leads to abnormal bursts of neuronal cells that can be linked to seizure or convulsion. The induction of such seizure/convulsion mechanism was done by gradually increasing the temperature with 1× buffer (100mM NaCl, 50mM MgCl2) in adult C. elegans. In the present experiment it is demonstrated that Baccoside A can significantly reduce the seizure/convulsion in C. elegans at higher temperatures (26–28±1°C). Furthermore, in T-type Ca2+ channel cca-1 mutant worms, no convulsion was recorded. Our experimental results suggest that plant molecules from Bacopa monnieri may be useful in suppressing the seizure/convulsion in worms.

Active seizures are associated with reduced adaptive functioning in children with epilepsy - Corrected Proof

Aimilia Papazoglou, Tricia Z. King, Thomas G. Burns — 2010-07-05

Abstract: Children with epilepsy are at risk of suboptimal adaptive functioning. Research has not yet established how specific seizure and treatment variables may affect adaptive functioning, which would allow clinicians to better identify at-risk children. This study sought to determine the seizure and treatment variables predictive of adaptive functioning. Forty-six children with epilepsy participated in this study. Using multiple regression, active seizures (one or more seizures in the prior year) significantly predicted scores on the General Adaptive Composite of the Adaptive Behavior Assessment System-II. The active seizures variable uniquely explained 19% of the variance in adaptive functioning, with children with active seizures demonstrating significantly poorer adaptive functioning. The number of current AEDs, past AEDs, seizure types, age at seizure onset, and temporal lobectomy were not significant predictors. Post hoc analyses that divided the active seizures group according to seizure frequency in the prior month did not find significant differences in adaptive functioning. The results of this study suggest that children with seizures that are not fully controlled are at greater risk of suboptimal adaptive functioning.

Non-paraneoplastic limbic encephalitis characterized by mesio-temporal seizures and extratemporal lesions: A case report - Corrected Proof

2010-07-02

Abstract: Limbic encephalitis (LE) can be either paraneoplastic or a non-paraneoplastic autoimmune disorder. Magnetic resonance imaging (MRI) of the brain on T2-weighted fluid-attenuated inversion recovery (FLAIR) classically shows hyperintensities of the temporal structures, but multifocal involvement of extratemporal cortex has also been described in paraneoplastic LE. Here we describe a 27-year-old woman whose idiopathic autoimmune (glutamic acid decarboxylase-antibody positive) LE debuted with multiple daily mesio-temporal seizures, amnesia and multifocal extratemporal cortical MRI abnormalities. Mesio-temporal MRI signal increase was found after 20 days. This case report highlights that early diagnosis of non-paraneoplastic LE may be considered in patients with multiple daily mesio-temporal seizures and amnesia even in the absence of early typical MRI abnormalities.

Detection of epileptic spikes by magnetoencephalography and electroencephalography after sleep deprivation - Corrected Proof

M. Heers, S. Rampp, M. Kaltenhäuser, E. Pauli, C. Rauch, M.T. Dölken, H. Stefan — 2010-07-02

Abstract: Introduction: In diagnosis of epilepsies electrophysiological findings play a key role. While spontaneous electroencephalography (EEG) and EEG with sleep deprivation (EEGsd) are widely evaluated and used, application of magnetoencephalography (MEG) in this field is primarily limited to presurgical assessment of focal epilepsies.Methods: In this study we retrospectively compared MEG (M/EEG) and EEGsd in 63 (55) patients with focal and generalized epilepsy with regard to occurrence of epileptic spikes.Results: MEG could record epileptic spikes in 38 patients (60%), while EEGsd recorded spikes in only 32 patients (51%). In a group of 55 patients simultaneous MEG/EEG (M/EEG) was able to record spikes in 38 patients (71%) compared to epileptic spikes in 28 patients (51%) recorded by EEGsd. In a subgroup of 17 MR-negative patients simultaneous M/EEG could record epileptic spikes in all patients, while EEGsd was successful in only 11 (64%) of them.Conclusion: In this study, MEG showed a tendency to record epileptic spikes in more patients than EEGsd. Furthermore, simultaneous M/EEG has been shown to be especially successful in detection of epileptic spikes in patients with MR-negative epilepsy. This might at least in parts be explained by neocortical predominance of MR-negative epilepsy. Thus, this study motivates prospective studies to evaluate the substitutability of EEGsd by MEG more extensively.

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy—The Austrian experience - Corrected Proof

2010-07-02

Abstract: Purpose: To evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies.Methods: Data from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as ≥50% seizure reduction. Treatment effects on EEG, developmental outcome and the “outcome-predictive” value of various clinical factors were also assessed.Results: 50 children (22 boys; mean age 4.5 years±3.55) were included. Mean follow-up was 3.93±2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p=0.014) and a significantly lower rate of epileptic discharges (p=0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p=0.038).Favourable treatment outcome was associated with a shorter disease duration (p=0.025) and generalised tonic clonic seizures (p=0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome.Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p=0.001) and valproate (p=0.046).Conclusion: Despite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.

Astrocytes derived from fetal neural progenitor cells as a novel source for therapeutic adenosine delivery - Corrected Proof

2010-06-18

Abstract: Purpose: Intracerebral delivery of anti-epileptic compounds represents a novel strategy for the treatment of refractory epilepsy. Adenosine is a possible candidate for local delivery based on its proven anti-epileptic effects. Neural stem cells constitute an ideal cell source for intracerebral transplantation and long-term drug delivery. In order to develop a cell-based system for the long-term delivery of adenosine, we isolated neural progenitor cells from adenosine kinase deficient mice (Adk−/−) and compared their differentiation potential and adenosine release properties with corresponding wild-type cells.Methods: Fetal neural progenitor cells were isolated from the brains of Adk−/− and C57BL/6 mice fetuses and expanded in vitro. Before and after neural differentiation, supernatants were collected and assayed for adenosine release using liquid chromatography–tandem mass spectrometry (LC–MS/MS).Results: Adk−/− cells secreted significantly more adenosine compared to wild-type cells at any time point of differentiation. Undifferentiated Adk−/− cells secreted 137±5ng adenosine per 105 cells during 24h in culture, compared to 11±1ng released from corresponding wild-type cells. Adenosine release was maintained after differentiation as differentiated Adk−/− cells continued to release significantly more adenosine per 24h (47±1ng per 105 cells) compared to wild-type cells (3±0.2ng per 105 cells).Conclusions: Fetal neural progenitor cells isolated from Adk−/− mice – but not those from C57BL/6 mice – release amounts of adenosine considered to be of therapeutic relevance.

Antiepileptic treatment in patients with epilepsy and other comorbidities - Corrected Proof

2010-06-16

Abstract: Background: A high number of patients with epilepsy have comorbidities. The type of comorbidity is an important factor in deciding on the most suitable treatment, including that for acute epileptic seizures and chronic antiepileptic treatment. Evidence-based criteria should guide the selection of the appropriate antiepileptic drugs given specific comorbidities.Methods: We performed a comprehensive search of the scientific literature on epilepsy treatment in patients with the following comorbidities: heart disease, lung disease, liver disease, kidney disease, porphyria, organ transplantation, thyroid disease, metabolic disorder, infection, mental disability, psychiatric disorder, cognitive impairment, stroke, and brain tumour.Results: Most of the studies were case series and retrospective analyses. No randomised controlled trials specifically designed for this type of clinical situation were identified. The level of scientific evidence to guide clinical decisions is therefore low.Conclusions: In this review we make recommendations based on the best scientific evidence available for treating epilepsy in patients with other comorbidities, including the treatment of epileptic seizures in acute situations as well as chronic antiepileptic treatment. When no scientific evidence is available, our recommendations are based on pharmacokinetic criteria and tolerability of antiepileptic drugs, using accumulated experience and the consensus of the members of the Andalusian Epilepsy Society.