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Long-term outcome and neuroradiologic changes after multiple hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy

Epilepsia - Fri, 04/15/2016 - 03:01
Summary Objective

Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation.

Methods

Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose–positron emission tomography (FDG-PET) studies performed before and >6 months after surgery.

Results

Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level.

Significance

The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

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Once-a-day epilepsy drug may prevent seizures as well as twice-a-day drug

Science Daily - Thu, 04/14/2016 - 17:48
A new study suggests that an epilepsy drug that can be taken once a day may control seizures as well as a drug that must be taken twice a day, according to a preliminary study.
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Once-a-day epilepsy drug may prevent seizures as well as twice-a-day drug

Medical News Today - Thu, 04/14/2016 - 16:00
A new study suggests that an epilepsy drug that can be taken once a day may control seizures as well as a drug that must be taken twice a day, according to a preliminary study presented at the...
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Altered GABA receptor expression in brainstem nuclei and SUDEP in mice associated with epileptic encephalopathy

Epilepsy Research Journal - Wed, 04/13/2016 - 00:00
Sudden unexpected death in epilepsy (SUDEP) is the leading cause for death in individuals with epilepsy. The frequency of SUDEP correlates with the severity of epilepsies and lack of response to antiepileptic drug treatment, but the underlying mechanisms of SUDEP have not been elucidated fully. GABRG2(Q390X) is a mutation associated with the epileptic encephalopathy Dravet syndrome (DS) and with genetic epilepsy with febrile seizures plus (GEFS+) in patients. The Gabrg2+/Q390X knockin (KI) mouse phenocopies the major features of DS and GEFS+ and has SUDEP throughout life.
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A common brain cell shapes the nervous system in unexpected ways

Medical News Today - Tue, 04/12/2016 - 06:00
More than half of our brains are made up of glial cells, which wrap around nerve fibers and insulate them--similarly to how the plastic casing of an electric cable insulates the copper wire...
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GW Pharmaceuticals initiates Phase 3 pivotal study in Tuberous Sclerosis Complex

Medical News Today - Mon, 04/11/2016 - 11:00
GW Pharmaceuticals plc, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, has announced that...
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RARS2 mutations in a sibship with infantile spasms

Epilepsia - Sat, 04/09/2016 - 00:20
Summary

Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl-tRNA synthetase 2 (RARS2). Mutations in this gene have been classically described in pontocerebellar hypoplasia type six (PCH6), a phenotype characterized by early (often intractable) seizures, profound developmental delay, and progressive pontocerebellar atrophy. The electroclinical spectrum of PCH6 is broad and includes a number of seizure types: myoclonic, generalized tonic–clonic, and focal clonic seizures. Our report expands the characterization of the PCH6 disease spectrum and presents infantile spasms as an associated electroclinical phenotype.

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Determinants of brain metabolism changes in mesial temporal lobe epilepsy

Epilepsia - Fri, 04/08/2016 - 07:42
Summary Objective

To determine the main factors influencing metabolic changes in mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS).

Methods

We prospectively studied 114 patients with MTLE (62 female; 60 left HS; 15- to 56-year-olds) with 18F-fluorodeoxyglucose–positron emission tomography and correlated the results with the side of HS, structural atrophy, electroclinical features, gender, age at onset, epilepsy duration, and seizure frequency. Imaging processing was performed using statistical parametric mapping.

Results

Ipsilateral hypometabolism involved temporal (mesial structures, pole, and lateral cortex) and extratemporal areas including the insula, frontal lobe, perisylvian regions, and thalamus, more extensively in right HS (RHS). A relative increase of metabolism (hypermetabolism) was found in the nonepileptic temporal lobe and in posterior areas bilaterally. Voxel-based morphometry detected unilateral hippocampus atrophy and gray matter concentration decrease in both frontal lobes, more extensively in left HS (LHS). Regardless of the structural alterations, the topography of hypometabolism correlated strongly with the extent of epileptic networks (mesial, anterior-mesiolateral, widespread mesiolateral, and bitemporal according to the ictal spread), which were larger in RHS. Notably, widespread perisylvian and bitemporal hypometabolism was found only in RHS. Mirror hypermetabolism was grossly proportional to the hypometabolic areas, coinciding partly with the default mode network. Gender-related effect was significant mainly in the contralateral frontal lobe, in which metabolism was higher in female patients. Epilepsy duration correlated with the contralateral temporal metabolism, positively in LHS and negatively in RHS. Opposite results were found with age at onset. High seizure frequency correlated negatively with the contralateral metabolism in LHS.

Significance

Epileptic networks, as assessed by electroclinical correlations, appear to be the main determinant of hypometabolism in MTLE. Compensatory mechanisms reflected by a relative hypermetabolism in the nonepileptic temporal lobe and in extratemporal areas seem more efficient in LHS and in female patients, whereas long duration, late onset of epilepsy, and high seizure frequency may reduce these adaptive changes.

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GABAergic networks jump-start focal seizures

Epilepsia - Fri, 04/08/2016 - 07:41
Summary

Abnormally enhanced glutamatergic excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by firm evidence, and it will be challenged here. A general reduction of unit firing has been indeed observed in association with low-voltage fast activity at the onset of seizures recorded during presurgical intracranial monitoring in patients with focal, drug-resistant epilepsies. Moreover, focal seizures in animal models start with increased γ-aminobutyric acid (GABA)ergic interneuronal activity that silences principal cells. In vitro studies have shown that synchronous activation of GABAA receptors occurs at seizure onset and causes sizeable elevations in extracellular potassium, thus facilitating neuronal recruitment and seizure progression. A paradoxical involvement of GABAergic networks is required for the initiation of focal seizures characterized by low-voltage fast activity, which represents the most common seizure-onset pattern in focal epilepsies.

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Epilepsy drug may not increase risk of birth defects

Science Daily - Wed, 04/06/2016 - 16:52
Babies born to pregnant women taking the epilepsy drug lamotrigine may not be at an increased risk of birth defects, such as cleft lip, cleft palate or clubfoot, according to a study.
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Fetal malformation risk not increased after exposure to lamotrigine

Clinical Neurology News - Wed, 04/06/2016 - 16:00

A new analysis of registry data from European countries does not support a risk of orofacial cleft and clubfoot with exposure to lamotrigine monotherapy, in contrast to signals from previous studies...

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Epilepsy drug may not increase risk of birth defects

Medical News Today - Wed, 04/06/2016 - 16:00
Babies born to pregnant women taking the epilepsy drug lamotrigine may not be at an increased risk of birth defects, such as cleft lip, cleft palate or clubfoot, according to a study published in...
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Subclinical epileptic bursts in the brain may affect patients' driving

Medical News Today - Tue, 04/05/2016 - 11:00
Epileptic discharges in the brain that are unaccompanied by obvious clinical signs are regarded as subclinical or interictal.
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Virtual car accidents of epilepsy patients, interictal epileptic activity, and medication

Epilepsia - Mon, 04/04/2016 - 09:56
Summary Objective

To investigate effects of interictal epileptic activity (IEA) and antiepileptic drugs (AEDs) on reactivity and aspects of the fitness to drive for epilepsy patients.

Methods

Forty-six adult patients with demonstration of focal or generalized bursts of IEA in electroencephalography (EEG) readings within 1 year prior to inclusion irrespective of medication performed a car driving computer test or a single light flash test (39 patients performed both). Reaction times (RTs), virtual crashes, or lapses (RT ≥ 1 s in the car or flash test) were measured in an IEA burst–triggered fashion during IEA and compared with RT-measurements during unremarkable EEG findings in the same session.

Results

IEA prolonged RTs both in the flash and car test (p < 0.001) in individual patients up to 200 ms. Generalized IEA with spike/waves (s/w) had the largest effect on RT prolongation (p < 0.001, both tests), whereas mean RT during normal EEG, age, gender, and number of AEDs had no effect. The car test was better than the flash test in detecting RT prolongations (p = 0.030). IEA increased crashes/lapses >26% in sessions with generalized IEA with s/w. The frequency of IEA-associated RT >1 s exceeded predictions (p < 0.001) based on simple RT shift, suggesting functional impairment beyond progressive RT prolongation by IEA. The number of AEDs correlated with prolonged RTs during normal EEG (p < 0.021) but not with IEA-associated RT prolongation or crashes/lapses.

Significance

IEA prolonged RTs to varying extents, dependent on IEA type. IEA-associated RTs >1 s were more frequent than predicted, suggesting beginning cerebral decompensation of visual stimulus processing. AEDs somewhat reduced psychomotor speed, but it was mainly the IEA that contributed to an excess of virtual accidents.

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Epilepsia - Mon, 04/04/2016 - 01:38
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