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Epilepsia - Mon, 05/18/2015 - 05:18
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Epilepsy has been found to reduce the generation of new neurons

Medical News Today - Mon, 05/18/2015 - 03:00
International research is exploring the potential of neural stem cells in future therapies to fight the diseaseThe mission of neural stem cells located in the hippocampus, one of the main regions...
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LACOSAMIDE MODULATES INTERICTAL SPIKING AND HIGH-FREQUENCY OSCILLATIONS IN A MODEL OF MESIAL TEMPORAL LOBE EPILEPSY

Epilepsy Research Journal - Mon, 05/18/2015 - 00:00
Lacosamide (LCM, (R)-2-acetamido-N-benzyl-3-methoxypropionamide) is a voltage-gated Na+ channel blocker that modulates the slow inactivation component of Na+ channels (Errington et al., 2008; Niespodziany et al., 2013). LCM is effective in patients with pharmacoresistant focal epilepsy (Ben-Menachem et al., 2007, Cross and Curran, 2009, Halasz et al., 2009), and in animal models such as the maximal electroshock model, the amygdala kindling model and the 6Hz model of psychomotor seizures(Brandt et al., 2006, Stohr et al., 2007).
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Effects of Site-Specific Infusions of Methionine Sulfoximine on the Temporal Progression of Seizures in a Rat Model of Mesial Temporal Lobe Epilepsy

Epilepsy Research Journal - Mon, 05/18/2015 - 00:00
Being the most abundant excitatory neurotransmitter in the brain, glutamate is critical for neuronal signaling in health and disease. Because slight elevations of extracellular brain glutamate levels can lead to excessive neurotransmission, seizures, and neuronal death (During and Spencer, 1993; Olney, 1978; Olney et al., 1972), several mechanisms are in place to maintain extracellular glutamate homeostasis. Two of the most important mechanisms are cellular uptake via glutamate transporters (Danbolt, 2001), and intracellular metabolism to less excitatory molecules, such as glutamine (Martinez-Hernandez et al., 1977).
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AAN: Adjunctive perampanel reduces tonic-clonic seizures in refractory patients

Clinical Neurology News - Sat, 05/16/2015 - 17:17

WASHINGTON – The antiepileptic drug perampanel cut the frequency of primary generalized tonic-clonic seizures by 50% versus placebo in patients who were already taking a number of other anti-seizure...

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Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy

Epilepsia - Sat, 05/16/2015 - 03:53
Summary Objective

To evaluate the safety, tolerability, and comparative pharmacokinetics (PK) of intravenous and oral carbamazepine.

Methods

In this phase 1, open-label study, adult patients with epilepsy on a stable oral carbamazepine dosage (400–2,000 mg/day) were converted to intravenous carbamazepine (administered at 70% of the oral dosage). A 28-day outpatient period preceded an up to 10-day inpatient period and a 30-day follow-up period. Intravenous carbamazepine was administered over 15 or 30 min every 6 h on days 1–7; some patients in the 15-min group were eligible to receive four 2- to 5-min (rapid) infusions on day 8. Patients underwent blood sampling to determine the area under the concentration–time curve (AUC) for carbamazepine and metabolite carbamazepine-10,11-epoxide following oral (day 0) and intravenous carbamazepine administration (days 1, 7, and 8). Bioequivalence was evaluated in patients with normal renal function (creatinine clearance >80 ml/min). Safety assessments were conducted through day 38.

Results

Ninety-eight patients enrolled and 77 completed the PK component. The mean daily oral and intravenous carbamazepine dosage for 64 PK-evaluable patients with normal renal function was 962.5 and 675.1 mg (70% of oral dosage), respectively. Steady-state minimum concentration (Cmin) and overall exposure (AUC0–24) for intravenous carbamazepine infused over 30, 15, or 2–5 min were similar to oral carbamazepine. The 90% confidence intervals (CIs) for the ratios of the adjusted means for AUC0–24, maximum concentration (Cmax), and Cmin were within the 80%–125% bioequivalence range for 30-min intravenous infusions versus oral administration, but exceeded the upper limit for Cmax for the 15-min and rapid infusions. All intravenous carbamazepine infusions were well tolerated.

Significance

Intravenous carbamazepine infusions (70% of oral daily dose) of 30-, 15-, and 2- to 5-min duration, given every 6 h, maintained patients’ plasma carbamazepine concentrations. Intravenous carbamazepine 30-min infusions were bioequivalent to oral carbamazepine in patients with normal renal function; rapid infusions were well-tolerated in this study.

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Theory of mind and social functioning in patients with temporal lobe epilepsy

Epilepsia - Sat, 05/16/2015 - 03:52
Summary Objective

This study aimed to explore the effects of theory of mind (ToM) and related potential risk factors, including cognitive functions, psychiatric status, and seizure-related clinical variables, on social functioning in patients with temporal lobe epilepsy (TLE).

Methods

Sixty-seven patients with intractable TLE who were potential candidates for epilepsy surgery and 30 matched controls were included. All participants completed four tasks measuring different levels of ToM (False Belief, Faux Pas Recognition, Implication Stories, and Visual Cartoon), the Symptom Checklist-90-Revised (SCL-90-R), the Social and Occupational Functioning Scale for Epilepsy (SOFSE), and neuropsychological tests.

Results

The patients exhibited impairments in both basic and advanced ToM. Multiple regression analyses revealed the following: (1) the SOFSE total score was significantly predicted by the Faux Pas Recognition (FPR), Global Severity Index (GSI) score of the SCL-90-R, and Full-Scale intelligence quotient (IQ) of the Wechsler Adult Intelligence Scale (WAIS), which accounted for 38%, 11%, and 8% of the variance, respectively; and (2) the FPR was a significant predictor of all SOFSE subscales, whereas the GSI score contributed substantially to the Interpersonal Relationships, Communication, and Occupation subscales of the SOFSE.

Significance

Advanced ToM, measured by impaired faux pas recognition, is a relatively strong predictor of poor social functioning in surgical candidates for intractable TLE. Identifying ToM impairment may help plan nonpharmacologic treatment for improving social functions in patients with intractable TLE.

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Valproate in the treatment of epilepsy in girls and women of childbearing potential

Epilepsia - Sat, 05/16/2015 - 03:52
Summary

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA-ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first-line treatment for focal epilepsy. (5) Valproate may be offered as a first-line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first-line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow-up for ongoing consideration of the most appropriate treatment regimen.

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Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome

Epilepsia - Fri, 05/15/2015 - 10:11
Summary Objective

We evaluated seizure outcome in a large cohort of familial neonatal seizures (FNS), and examined phenotypic overlap with different molecular lesions.

Methods

Detailed clinical data were collected from 36 families comprising two or more individuals with neonatal seizures. The seizure course and occurrence of seizures later in life were analyzed. Families were screened for KCNQ2, KCNQ3, SCN2A, and PRRT2 mutations, and linkage studies were performed in mutation-negative families to exclude known loci.

Results

Thirty-three families fulfilled clinical criteria for benign familial neonatal epilepsy (BFNE); 27 of these families had KCNQ2 mutations, one had a KCNQ3 mutation, and two had SCN2A mutations. Seizures persisting after age 6 months were reported in 31% of individuals with KCNQ2 mutations; later seizures were associated with frequent neonatal seizures. Linkage mapping in two mutation-negative BFNE families excluded linkage to KCNQ2, KCNQ3, and SCN2A, but linkage to KCNQ2 could not be excluded in the third mutation-negative BFNE family. The three remaining families did not fulfill criteria of BFNE due to developmental delay or intellectual disability; a molecular lesion was identified in two; the other family remains unsolved.

Significance

Most families in our cohort of familial neonatal seizures fulfill criteria for BFNE; the molecular cause was identified in 91%. Most had KCNQ2 mutations, but two families had SCN2A mutations, which are normally associated with a mixed picture of neonatal and infantile onset seizures. Seizures later in life are more common in BFNE than previously reported and are associated with a greater number of seizures in the neonatal period. Linkage studies in two families excluded known loci, suggesting a further gene is involved in BFNE.

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Epilepsy has been found to reduce the generation of new neurons

Science Daily - Fri, 05/15/2015 - 08:34
The mission of neural stem cells located in the hippocampus, one of the main regions of the brain, is to generate new neurons during the adult life of mammals, and their function is to participate in certain types of learning and responses to anxiety and stress. New research has discovered that hippocampal neural stem cells in the case of epilepsy stop generating new neurons and are turned into reactive astrocytes, a cell type that promotes inflammation and alters communication between neurons. Now the researchers are exploring the potential of neural stem cells in future therapies to fight the disease.
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