What's Current?

Modified Atkins diet helps children with rare form of epilepsy

Medical News Today - Fri, 02/24/2017 - 09:00
Doose syndrome or myoclonic-astatic epilepsy is a rare syndrome accounting for one to two percent of childhood epilepsies.
Categories: What's Current?

Exposure to AEDs in the Womb Does Not Increase the Frequency of GP Visits

Epilepsy Research - Fri, 02/24/2017 - 08:02

Children whose mothers used antiepileptic drugs (AEDs) while pregnant are not more likely to visit their GP during their childhood, according to a population-based study by Danish scientists.

It is important to note that the study only analyzed the frequency of primary healthcare visits and did not take into account complications such as malformations at birth and neurological and psychiatric disorders later in life, found to be associated with the use of AEDs by the mother, in previous studies.

Instead, the present study only looked at the general health of children whose mothers used AEDs while they were pregnant and compared this to that of children who were not exposed to AEDs before birth.

The team of researchers led by Dr Bodil Hammer Bech, at Aarhus University in Denmark identified all babies born in Denmark between 1997 and 2012 and followed them until 31 December 2013, through the Danish National Patient Register. They found that 963,010 babies were born in this period of time.

The researchers obtained information on whether or not the babies were exposed to AEDs before birth from the Danish Register of Medicinal Product Statistics. This revealed that 4,478 children (0.46%) were exposed to AEDs before birth.

The team then analyzed the number of GP visits for reasons other than routine checks and vaccinations. They found that children who were exposed to AEDs before birth had 3% more GP contacts during the study period compared to children who were not exposed to AEDs before birth. This was primarily in the form of phone contacts. The researchers did not find any difference between children who were exposed to AEDs before birth and those who were not, in terms of specific services provided by the GP.

The first author of the study Anne Mette Lund Würtz said in a press release: ”Our results are generally reassuring for women who need to take anti-epilepsy medicine during their pregnancy”.

The analysis took into account factors such as the child’s gender and date of birth, the mother’s age, the family’s income level, education status, the presence of any mental illnesses, the use of psychiatric medicines and insulin, and substance abuse.

The results were published in the scientific journal BMJ Open.

Author: Özge Özkaya

How do AEDs work? from Rose Thompson on Vimeo.

Categories: What's Current?

Self-management interventions in pediatric epilepsy: What is the level of evidence?

Epilepsia - Fri, 02/24/2017 - 07:26
Summary Objective

To respond to recommendations put forth by the Institute of Medicine to improve self-management resources for youth with epilepsy by conducting a systematic review of the self-management literature in pediatric epilepsy.

Methods

Inclusion criteria: youth birth to 18 years with a seizure disorder or an epilepsy diagnosis and/or their caregivers, published 1985–2014 in English, and conducted in countries with a very high human development index. Abstract and keywords had to explicitly refer to “self-care” (pre-1996) and/or self-management (post-1996). The review was conducted in seven phases: (1) identification of bibliographical search criteria and databases; (2) abstract assessment; (3) full article review; (4) organization of final citations into instrument development, intervention, factors associated with self-management categories; (5) American Academy of Neurology level of evidence (LOE) assessment for intervention studies; (6) CONsolidated Standards of Reporting Trials (CONSORT) evaluation of LOE level III articles utilizing a control group; and (7) categorization of intervention outcomes across four self-management domains.

Results

Of the 87 articles that met eligibility criteria, 24 were interventions and received LOE scores of level III or IV. Most studies (n = 20, 80%) were scored at level III; however, only eight had a control group and adhered to CONSORT guidelines. They largely neglected information on intervention components (e.g., implementation, treatment fidelity), randomization, participant flow, missing data, and effect size or confidence intervals. The 24 intervention studies reported significant impact in four domains: individual (n = 13), family (n = 6), health care system (n = 3), and community (n = 2).

Significance

There are no level I or II studies. No study met full CONSORT guidelines. Outcomes were well described; however, the nature of self-management interventions (e.g., multiple foci, skills targeted) and the observed heterogeneity in outcomes complicates comparisons across studies. Randomized controlled trials (RCTs) that include large sample sizes, impact of the intervention, treatment fidelity, and power analyses are necessary to further this evidence base.

Categories: What's Current?

Carisbamate blockade of T-type voltage-gated calcium channels

Epilepsia - Thu, 02/23/2017 - 07:40
Summary Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload-Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T-type voltage-gated Ca2+ channels.

Results

In CA3 pyramidal neurons, kainic acid induced significant elevations in [Ca2+]i and long-lasting neuronal hyperexcitability, both of which were reversed in a dose-dependent manner by CRS. Similarly, CRS suppressed spontaneous rhythmic epileptiform activity in hippocampal slices exposed to zero-Mg2+ or 4-aminopyridine. Treatment with CRS also protected murine hippocampal HT-22 cells against excitotoxic injury with glutamate, and this was accompanied by a reduction in [Ca2+]i. Neither kainic acid nor CRS alone altered the mitochondrial membrane potential (ΔΨ) in intact, acutely isolated mitochondria. In addition, CRS did not affect mitochondrial respiratory chain activity, Ca2+-induced mitochondrial permeability transition, and Ca2+ release from the ER. However, CRS significantly decreased Ca2+ flux in human embryonic kidney tsA-201 cells transfected with Cav3.1 (voltage-dependent T-type Ca2+) channels.

Significance

Our data indicate that the neuroprotective and antiseizure activity of CRS likely results in part from decreased [Ca2+]i accumulation through blockade of T-type Ca2+ channels.

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Risk of vigabatrin-associated brain abnormalities on MRI in the treatment of infantile spasms is dose-dependent

Epilepsia - Thu, 02/23/2017 - 07:30
Summary Objective

Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible—and largely asymptomatic—signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena.

Methods

Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure.

Results

We identified 507 brain MRI studies among 257 patients with infantile spasms. VGB treatment was documented in 143 children, with detailed exposure data available for 104, of whom 45 had at least one MRI study during VGB treatment. Among the limited subset of asymptomatic children who underwent MRI (n = 40), 6 exhibited VABAM. Risk of asymptomatic VABAM was dose-dependent, as peak (but not cumulative) VGB dosage was strongly associated with asymptomatic VABAM (p = 0.0028). In an exploratory analysis, we encountered 4 children with symptomatic VABAM among 104 patients with detailed VGB exposure data. Risk of symptomatic VABAM was seemingly dose-independent, and potentially associated with concomitant hormonal therapy (i.e., prednisolone and adrenocorticotropic hormone [ACTH]) (p = 0.039).

Significance

We have demonstrated dose-dependent risk of asymptomatic VABAM and uncovered a possible association between symptomatic VABAM and concomitant hormonal therapy. Caution should be exercised in the use of high VGB dosage (i.e., >175 mg/kg/day), and further study is warranted to confirm the potential impact of hormonal therapy.

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Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies

Epilepsia - Thu, 02/23/2017 - 07:20
Summary

This study aimed at defining clinical predictors of drug resistance in adults with genetic generalized epilepsy (GGE) who were treated with a broad spectrum of antiepileptic drugs. Of a cohort of 137 unselected adult GGE patients with long-term follow up, clinical and demographic data, putative prognostic factors (e.g., psychiatric comorbidities, electroencephalography [EEG]), treatment response, and data indicative of social status were collected. Fifty-eight patients had seizures within the past year. Thirty-three patients met the definition of “drug-resistant epilepsy” according to the International League Against Epilepsy (ILAE) definition. Psychiatric comorbidities, age at first diagnosis, and absences were associated with worse seizure control, whereas focal changes in EEG remained without prognostic impact. Resistance to valproic acid was the most important prognostic factor for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free (mainly with valproic acid). Our data suggest that “drug resistant GGE” must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Categories: What's Current?

Randomized, double-blind, placebo-controlled phase 2 study of ganaxolone as add-on therapy in adults with uncontrolled partial-onset seizures

Epilepsia - Thu, 02/23/2017 - 07:15
Summary Objective

To evaluate the efficacy and safety of ganaxolone as adjunctive therapy in adults with uncontrolled partial-onset seizures despite taking up to three concomitant antiepileptic drugs (AEDs).

Methods

Adults aged 18–69 years and refractory to conventional AEDs were enrolled in a multicenter, double-blind, placebo-controlled trial. After an 8-week baseline period, patients were randomized 2:1 to ganaxolone 1,500 mg/day or placebo for a 10-week treatment period (2-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. The primary endpoint was mean weekly seizure frequency. Secondary endpoints included the proportion of patients experiencing ≥50% reduction in seizure frequency (responder rate), percent change in mean weekly seizure frequency, seizure-free days, and quality of life. Safety and tolerability assessments included adverse events (AEs), treatment discontinuation, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population.

Results

Of 147 randomized patients (98 ganaxolone, 49 placebo), 131 completed the study; 95% of participants titrated up to 1,500 mg/day and 78% maintained this dose. From baseline to endpoint, mean weekly seizure frequency decreased with ganaxolone (6.5–5.2) versus placebo (9.2–10.8), representing an 11.4% decrease versus placebo (p = 0.0489, analysis of covariance [ANCOVA]). Mean percent change from baseline was −17.6% with ganaxolone versus 2.0% with placebo (p = 0.0144, Kruskal-Wallis test). Responder rates were 24% with ganaxolone versus 15% with placebo (p = 0.19). Discontinuation due to adverse events was similar with ganaxolone (7.1%) and placebo (6.1%). Common adverse events were mild to moderate in severity and included dizziness (16.3% vs. 8.2%), fatigue (16.3% vs. 8.2%), and somnolence (13.3% vs. 2.0%).

Significance

Ganaxolone 1,500 mg/day reduced partial-onset seizure frequency and was generally safe and well tolerated in this phase 2 study. These results support continued development of ganaxolone for adult patients with refractory partial-onset seizures.

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Novel Candidate Gene Linked to Myoclonic Epilepsy Identified

Epilepsy Research - Thu, 02/23/2017 - 03:55

An international team of researchers identified a new candidate gene linked to myoclonic epilepsy in people while examining dogs with generalised myoclonic epilepsy syndrome. The findings were published in the leading scientific journal Proceedings of the National Academy of Sciences (PNAS).  This discovery might not only help doctors better diagnose myoclonic epilepsy but could also lead to the development of new therapies to treat this type of epilepsy. Moreover, the dog model could help scientists better understand the condition.

What is Myoclonic Epilepsy?

The senior author of the study, Professor Hannes Lohi said in a press release: “The genetic backgrounds of myoclonic epilepsies are not well known yet, and our study provides a new candidate gene, which helps to further characterise the underlying pathophysiology in future studies. This would be important for the development of new treatment scenarios.”

 The co-first author Riika Sarviaho added: “We found a novel epilepsy gene, DIRAS1, which has not been linked to any neurological diseases before. The gene is poorly characterised so far, but some studies suggest that it may play a role in cholinergic neurotransmission, which could be a highly relevant pathway for the myoclonic epilepsies.”

 Cholinergic neurotransmission is the passage of information from one nerve cell to the other via a chemical called acetylcholine, Acetylcholine also plays an important role at the neuromuscular junction, where nerve cells connect with muscle cells controlling their contraction, hence the muscle jerks observed in myoclonic epilepsy.

DIRAS1 is widely expressed in the brain and previous works suggests that it may be regulating the release of acetylcholine and play a role in development of the nervous system. Further research is needed to better understand the role of DIRAS1 in neurotransmission.

Myoclonic epilepsy is one of the most common forms of epilepsy characterised by shock-like jerks in a muscle or groups of muscles. The myoclonic epilepsy observed in the dogs is very similar to human juvenile myoclonic syndrome in many aspects and the study might have meaningful implications for epilepsy research both in dogs and in humans, according to the authors.

Author: Dr Özge Özkaya

Categories: What's Current?

Modified Atkins diet is an effective treatment for children with Doose syndrome

Epilepsia - Thu, 02/23/2017 - 00:05
Summary Objective

Children with myoclonic astatic epilepsy (MAE; Doose syndrome) whose seizures do not respond immediately to standard antiepileptic drugs (AEDs) are at high risk of developing an epileptic encephalopathy with cognitive decline. A classic ketogenic diet (KD) is a highly effective alternative to AEDs. To date, there are only limited data on the effectiveness of the modified Atkins diet (MAD), which is less restrictive and more compatible with daily life. We report findings from a retrospective study on 30 MAE patients treated with MAD.

Methods

Four participating centers retrospectively identified all patients with MAE in whom a MAD had been started before June 2015. Seven children were recruited from a cohort included in an open prospective controlled trial. A retrospective review of all available charts was performed in the other patients.

Results

Thirty patients (24 boys) were included. Mean age at epilepsy onset was 3.1 years (range 1.5–5.6). MAD was started at a mean age of 4.5 years (range 2.2–9.1) after the children had received an average of six different AEDs (range 2–15). Mean MAD observation time was 18.7 months (range 1.5–61.5). Twenty of 30 patients were still on MAD at the end of study (duration range 1.5–61.5, mean 18.5 months). MAD was stopped without relapse in three patients after sustained seizure freedom for >2 years. For the other seven cases, ineffectiveness (three patients), loss of efficacy (two), or noncompliance (two) led to termination. No severe adverse effects were noted. By the end of the observation period, 25 (83%) of 30 patients experienced a seizure reduction by ≥50% and 14 (47%) of 30 were seizure-free. None of the evaluated factors differed significantly between the groups of seizure-free and non–seizure-free children.

Significance

MAD is an effective treatment for MAE. It should be considered as an alternative to AEDs or the more restrictive classic ketogenic diet.

Categories: What's Current?

Presurgical language localization with visual naming associated ECoG high- gamma modulation in pediatric drug-resistant epilepsy

Epilepsia - Wed, 02/22/2017 - 06:50
Summary Objective

This prospective study compared presurgical language localization with visual naming–associated high-γ modulation (HGM) and conventional electrical cortical stimulation (ECS) in children with intracranial electrodes.

Methods

Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography (ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70–116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS.

Results

Seventeen patients with mean age of 11.3 years (range 4–19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [CI] 0.78–0.85), and accuracy (0.71, 95% CI 0.66–0.75, p < 0.001), but modest sensitivity (0.47) when ECS interference with naming (aphasia or paraphasic errors) and/or oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78–0.84), and accuracy (0.76, 95% CI 0.71–0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole.

Significance

This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing.

Categories: What's Current?

Treatment of experimental status epilepticus with synergistic drug combinations

Epilepsia - Wed, 02/22/2017 - 06:50
Summary

During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAARs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAARs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAARs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE. High doses of diazepam failed to stop electrographic SE, showing that benzodiazepine pharmacoresistance had developed. The diazepam-ketamine-valproate combination was far more effective in stopping SE than triple-dose monotherapy using the same individual drugs. Isobolograms showed that this drug combination's therapeutic actions were synergistic, with positive cooperativity between drugs, whereas drug toxicity was simply additive, without positive or negative cooperativity. As a result, the therapeutic index was improved by this drug combination compared to monotherapy. These results suggest that synergistic drug combinations that target receptor changes can control benzodiazepine-refractory SE.

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Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy

Epilepsia - Wed, 02/22/2017 - 06:40
Summary Objective

Brain hypothermia controls epileptic discharge and reduces extracellular concentrations of glutamate (Glu), an excitatory neurotransmitter. We aimed to determine the effects of focal brain cooling (FBC) on levels of γ-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. The relationship between Glu or GABA concentrations and the severity of epileptic symptoms was also analyzed.

Methods

Patients with intractable epilepsy underwent FBC at lesionectomized (n = 11) or hippocampectomized (n = 8) regions at 15°C for 30 min using custom-made cooling devices. Concentrations of Glu (n = 18) and GABA (n = 12) were measured in extracellular fluid obtained through microdialysis using high-performance liquid chromatography (HPLC). The reduction rate of neurotransmitter levels and its relationship with electrocorticography (ECoG) signal changes in response to FBC were measured.

Results

We found no relationship between the concentrations of Glu or GABA and seizure severity. There was a significant decrease in the concentration of Glu to 66.3% of control levels during the cooling period (p = 0.001). This rate of reduction correlated with ECoG power (r2 = 0.68). Cortical and hippocampal GABA levels significantly (p = 0.02) and nonsignificantly decreased to 47.7% and 32.4% of control levels, respectively. However, the rate of this reduction did not correlate with ECoG (r2 = 0.11).

Significance

Although the decrease in hippocampal GABA levels was not significant due to wide variations in its concentration, the levels of cortical GABA and Glu were decreased following FBC. FBC suppresses epileptic discharge and the release of both excitatory and inhibitory neurotransmitters. The reduction in Glu levels further contributes to the reduction in epileptic discharge. However, the reduction in the levels of GABA has no impact on ECoG.

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The effects of C5aR1 on leukocyte infiltration following pilocarpine-induced status epilepticus

Epilepsia - Wed, 02/22/2017 - 06:00
Summary

This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine-induced status epilepticus (SE), specifically those of brain-infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and microglia in C5aR1-deficient and wild-type mice. Absence of C5aR1 reduced by 47% the numbers of Ly6G+ neutrophils in the brains of No-SE mice and decreased neutrophil entry after SE to levels found in wild-type brains that did not undergo SE (No-SE). Moreover, C5aR1-deficient mice showed increased interleukin (IL)-4 expression in infiltrating leukocytes, but not in microglia. Increases in IL-4 expression in infiltrating leukocytes coupled with decreased neutrophil invasion in C5aR1-deficient mice after SE is likely to contribute to the reduced neuronal loss previously found in these mice compared to their wild-type littermates. Although other SE models need to be investigated to substantiate our findings, this study provides further evidence that C5aR1 is an inflammatory mediator and may play a role in epileptogenesis.

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Significant epilepsy gene discovery in dogs

Medical News Today - Wed, 02/22/2017 - 03:00
Researh groups from the University of Helsinki, the LMU Munich and the University of Guelph have described in collaboration a novel myoclonic epilepsy in dogs and identified its genetic cause.
Categories: What's Current?

New Scoring Method Could Eliminate Unnecessary Distress to Children with “Staring Spells”

Epilepsy Research - Wed, 02/22/2017 - 01:16

Researchers in the U.S. developed a new scoring system that can help doctors prioritise which patients should receive long-term video-EEG monitoring to evaluate whether staring spells are epileptic seizures.

Staring spells are episodes where children appear to stare into space and do not respond if spoken to or touched. These spells are the main symptom in patients with absence seizures and account for 10-17% of childhood-onset epilepsy. They are a common reason for a child to be referred to neurology services for overnight epilepsy monitoring. However overnight monitoring is time-consuming, expensive, and can cause distress to both children and their families.

Researchers led by Dr Jack Stevens at Nationwide Children’s Hospital and Ohio State University in Columbus performed a four-year chart review of all children who received long-term monitoring in one centre to characterise staring.

“The two goals were a) assess how often [a long-term monitoring] admission captured a staring spell that was diagnosed as a seizure and b) determine if any baseline factors predicted this particular positive result,” the researchers wrote.

Long-term monitoring was able to capture only 29 staring spells in all 276 patients who were referred for monitoring, and diagnose it as seizures. This is just a little more than 10% of all cases. Importantly, the researchers were able to predict whether or not staring spells would be diagnosed as seizures before the long-term monitoring. This was thanks to the scoring system they developed based on the following criteria: most recent EEG results, parental reports of the duration, frequency, and breakability of the staring events. Factors such as the mental status of the children following seizures, the presence or absence of automatisms, previous neurological and psychiatric diagnoses and medications, and family history of epilepsy were also considered.

The score of a child was calculated as follows: − 3 points if the previous EEG was normal, − 1 point if the child took any drugs for a psychiatric condition, + 1 point if the child took an antiepileptic drug (AED) for epilepsy, and + 1 point if the spells lasted less than one minute. If the total score was zero or less, staring spells were rarely diagnosed (in less than 5% of cases) during long-term monitoring.

“Our scoring system shows how consideration of prior EEG findings, medication history, and staring spell duration can help prioritise patients for [long-term monitoring admission] to evaluate if staring spells are epileptic seizures,” the authors concluded.

They added that the scoring system can only be an addition to clinical judgment on when children should be referred for long-term monitoring, and cannot replace it. It is important to note that factors predicting the outcome of the prediction may be different from one patient group to the other and across different centres. Therefore a comprehensive approach should be adopted when evaluating patients before admission to long-term monitoring. Further research in more than one centre is needed to evaluate the validity of the scoring system proposed in the present study.

The study was published in the journal Epilepsy and Behavior.

Author: Dr Özge Özkaya

 

Categories: What's Current?

MRI-guided laser surgery proving effective for some epilepsy patients

Science Daily - Tue, 02/21/2017 - 22:27
The MRI-guided laser ablation method is far less invasive and time-consuming than conventional surgery and has produced good results for people with medial temporal lobe epilepsy, report investigators.
Categories: What's Current?

Anti-epilepsy medicine taken by pregnant women does not harm the child's overall health

Science Daily - Tue, 02/21/2017 - 12:08
Previous studies have shown that anti-epilepsy medicine may lead to congenital malformations in the fetus and that the use of anti-epilepsy medicine during pregnancy affects the development of the brain among the children. There is still a lack of knowledge in the area about the general health of children who are exposed to anti-epilepsy medicine in fetal life. But this new study is generally reassuring for women who need to take anti-epilepsy medicine during their pregnancy.
Categories: What's Current?

A randomized controlled trial of lacosamide versus sodium valproate in status epilepticus

Epilepsia - Sat, 02/18/2017 - 04:15
Summary Objective

To compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)–resistant status epilepticus (SE).

Methods

Patients with LOR-resistant SE were randomized to intravenous LCM 400 mg at a rate of 60 mg/kg/min or SVA 30 mg/kg at a rate of 100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and magnetic resonance imaging (MRI) findings were noted. Primary outcome was seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission, in hospital death and severe adverse events (SAEs).

Results

Sixty-six patients were included, and their median age was 40 (range 18–90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs. 69.7%; p = 0.79). Twenty-four hour seizure freedom was higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%), but this difference was not statistically significant. Death (10 vs. 12) and composite side effects (4 vs. 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (one patient), and SVA with liver dysfunction (six patients).

Significance

In LOR-resistant SE patients, both LCM and SVA have comparable efficacy and safety. SVA resulted in slightly better 24 h seizure remission.

Categories: What's Current?

Some Forms of Epilepsy Could Be Autoimmune in Nature, Suggests Study Linking Parasitic Infection and Nodding Syndrome

Epilepsy Research - Fri, 02/17/2017 - 04:15

Some forms of epilepsy such as nodding syndrome, could be autoimmune in nature according to a study published in the journal Science Translational Medicine.

“The findings … suggest that therapies targeting the immune system may be effective treatments against this disorder and possibly other forms of epilepsy,” said the senior author of the study Dr Avindra Nath who is also the clinical director of the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), in a press release.

Nodding syndrome is a form of childhood epilepsy seen in certain areas of East Africa. It is characterised by head nodding, seizures, severe impairment in thinking ability and restricted growth.

The cause of the condition remained a mystery until now. The present study suggests that the condition might be caused by an immune response triggered by a parasitic worm called Onchocerca volvulus, which then attacks the body’s own nervous system.

For the study, Dr Nath and colleagues compared blood samples from children with nodding syndrome and children without, who all lived in the same village in Uganda. They found antibodies in the blood of children with nodding syndrome, which recognised proteins from the parasitic worm as well as a protein called leiomodin-1. Leiomodin-1 antibodies were also present in the fluid covering the brain and the spinal chord of the children with nodding syndrome.

Leiomodin-1 is highly expressed in human nerve cells grown in the laboratory and is also found in certain areas of the mouse brain. These areas of the brains are the counterparts of the areas in the children’s brain that were affected by nodding syndrome.

When the researchers treated normal nerve cells grown in the laboratory with serum from nodding syndrome patients, they saw that the nerve cells died suggesting that the serum of the children contains a factor that was toxic for nerve cells. In order to test whether this factor could be leiomodin-1 antibodies, the researchers treated the nerve cells with the antibody directly and obtained the same results: the nerve cells died. And when they treated the nerve cells with serum from which the leiomodin-1 antibodies had been removed, the nerve cells survived

The researchers concluded that nodding syndrome may be an auto-immune epileptic disorders triggered by infection with a parasitic worm. The antibodies that the body produces to fight off the parasite wrongly recognise a protein found in the nerve cells and attacks them.

According to the authors, more research is needed to better understand the role of leiomodin-1 in healthy people and people with epilepsy.

Author: Dr Özge Özkaya

What is Nodding Syndrome?  This information is from the WHO website
Nodding syndrome (NS) is a neurological condition with unknown etiology. It was first documented in the United Republic of Tanzania (URT) in the 1960s, then later in the Republic of South Sudan in the 1990s and in northern Uganda in 2007. Typically, NS affects children between the ages of 5 and 15 years old, causing progressive cognitive dysfunction, neurological deterioration, stunted growth and a characteristic nodding of the head. Despite numerous and extensive investigations in all three countries, very little is known about the cause of the disease.

To date, Nodding Syndrome is known to occur in the southern region of the United Republic of Tanzania (URT) (Mahenge mountains, Ulanga District), South Sudan (Western Equatoria State, Eastern Equatoria State, Central Equatoria State, and Lakes State) and northern Uganda (Pader, Kitgum and Lamwo districts, with new cases starting to present in Gulu, Amuru, Oyam and Lira districts).

Jilek et al (1962) first described several children with attacks of “head nodding” in Mahenge, a region in URT. The current burden of NS in URT is unknown but observations during case control studies in 2005 and 2009 in the Mahenge region do not suggest a notable increase in the number of cases relative to those detected in the late 1950s and early 1960s.

Samaritan Purse, a local NGO, described observations of head nodding among several children in southern Sudan in the Lui and Amadi villages of East Mundri County in the mid-1990s. A physician from Samaritan Purse reported the outbreak to WHO in 1997. The 2001-2002 investigations by WHO and partners estimated the prevalence of NS at 4.6% among a small population in Western Equatoria State, which appeared to have the highest burden of the illness. By 2003, an estimated 300 cases had been reported from this region. The Ministry of Health of South Sudan estimates the current burden of NS at between six and seven thousand cases, but no systematic large-scale prevalence study has been conducted. The Mundri region in the northeast of Western Equatoria is the presumed epicentre for the disease.

In 2008 and 2009, an illness consistent with NS was reported from Kitgum and Pader Districts in northern Uganda. As of February 2012, Uganda has reported over 3 000 cases of NS from the three districts of Kitgum, Lamwo and Pader. A community survey is underway in Uganda to determine the real burden of NS in the affected districts. Kaiser et al (2009) referred to a phenomenon of head nodding observed in the Kabarole District in Western Uganda as possibly constituting a feature of an epileptic syndrome caused by Onchocerca volvulus (O. volvulus).

The prevalence of both onchocerciasis and epilepsy in the areas affected by NS is high. The affected populations are impoverished and experience regular and prolonged periods of severe food shortages. In South Sudan and in northern Uganda, affected populations have a history of internal displacement and living in internally displaced persons (IDPs) camps.

Familial clustering has been observed in some families with NS patients, with more than one sibling with NS and/or siblings or relatives with other forms of epilepsy.

The age of onset in the vast majority of cases ranges between 5 and 15 years old, but cases have been reported in children as young as 2 years old and in adults up to 32 years old. There is no observed significant difference in the proportion of males to females among the affected, nor is there an observed seasonal variation.

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