What's Current?

Finding sheds light on what may kill neurons after stroke

Medical News Today - 4 hours 37 min ago
Discovery paves the way for a highly specific drug target for strokes and brain injuries.
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Salts in the brain control our sleep-wake cycle

Medical News Today - 4 hours 37 min ago
Danish research is behind a new epoch-making discovery, which may prove decisive to future brain research. The level of salts in the brain plays a critical role in whether we are asleep or awake.
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Brain signals between seizures may explain memory problems in patients with epilepsy

Medical News Today - Tue, 04/26/2016 - 11:00
Study suggests how future devices might prevent cognitive deficits. Between seizures and continually, brain cells in epileptic patients send signals that make "empty memories," perhaps explaining...
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Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a

Epilepsia - Tue, 04/26/2016 - 00:30
Summary

More than 1,200 mutations in neuronal voltage-gated sodium channel (VGSC) genes have been identified in patients with several epilepsy syndromes. A common feature of genetic epilepsies is variable expressivity among individuals with the same mutation. The Scn2aQ54 transgenic mouse model has a mutation in Scn2a that results in spontaneous epilepsy. Scn2aQ54 phenotype severity varies depending on the genetic strain background, making it a useful model for identifying and characterizing epilepsy modifier genes. Scn2aQ54 mice on the [C57BL/6JxSJL/J]F1 background exhibit earlier seizure onset, elevated spontaneous seizure frequency, and decreased survival compared to Scn2aQ54 mice congenic on the C57BL/6J strain. Genetic mapping and RNA-Seq analysis identified Cacna1g as a candidate modifier gene at the Moe1 locus, which influences Scn2aQ54 phenotype severity. In this study, we evaluated the modifier potential of Cacna1g, encoding the Cav3.1 voltage-gated calcium channel, by testing whether transgenic alteration of Cacna1g expression modifies severity of the Scn2aQ54 seizure phenotype. Scn2aQ54 mice exhibited increased spontaneous seizure frequency with elevated Cacna1g expression and decreased seizure frequency with decreased Cacna1g expression. These results provide support for Cacna1g as an epilepsy modifier gene and suggest that modulation of Cav3.1 may be an effective therapeutic strategy.

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EEG desynchronization during phasic REM sleep suppresses interictal epileptic activity in humans

Epilepsia - Tue, 04/26/2016 - 00:25
Summary Objective

Rapid eye movement (REM) sleep has a suppressing effect on epileptic activity. This effect might be directly related to neuronal desynchronization mediated by cholinergic neurotransmission. We investigated whether interictal epileptiform discharges (IEDs) and high frequency oscillations—a biomarker of the epileptogenic zone—are evenly distributed across phasic and tonic REM sleep. We hypothesized that IEDs are more suppressed during phasic REM sleep because of additional cholinergic drive.

Methods

Twelve patients underwent polysomnography during long-term combined scalp-intracerebral electroencephalography (EEG) recording. After sleep staging in the scalp EEG, we identified segments of REM sleep with rapid eye movements (phasic REM) and segments of REM sleep without rapid eye movements (tonic REM). In the intracerebral EEG, we computed the power in frequencies <30 Hz and from 30 to 500 Hz, and marked IEDs, ripples (>80 Hz) and fast ripples (>250 Hz). We grouped the intracerebral channels into channels in the seizure-onset zone (SOZ), the exclusively irritative zone (EIZ), and the normal zone (NoZ).

Results

Power in frequencies <30 Hz was lower during phasic than tonic REM sleep (p < 0.001), most likely reflecting increased desynchronization. IEDs, ripples and fast ripples, were less frequent during phasic than tonic REM sleep (phasic REM sleep: 39% of spikes, 35% of ripples, 18% of fast ripples, tonic REM sleep: 61% of spikes, 65% of ripples, 82% of fast ripples; p < 0.001). In contrast to ripples in the epileptogenic zone, physiologic ripples were more abundant during phasic REM sleep (phasic REM sleep: 73% in NoZ, 30% in EIZ, 28% in SOZ, tonic REM sleep: 27% in NoZ, 70% in EIZ, 72% in SOZ; p < 0.001).

Significance

Phasic REM sleep has an enhanced suppressive effect on IEDs, corroborating the role of EEG desynchronization in the suppression of interictal epileptic activity. In contrast, physiologic ripples were increased during phasic REM sleep, possibly reflecting REM-related memory consolidation and dreaming.

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Brain signals between seizures may explain memory problems in patients with epilepsy

Science Daily - Mon, 04/25/2016 - 14:23
Brain cells in epileptic patients send signals that make 'empty memories,' perhaps explaining the learning problems faced by up to 40 percent of patients.
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Commanding, between-seizure brain signals may explain memory problems in patients with epilepsy

Medical News Today - Mon, 04/25/2016 - 11:00
Between seizures and continually, brain cells in epileptic patients send signals that make "empty memories," perhaps explaining the learning problems faced by up to 40 percent of patients.
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Anti–tumor necrosis factor alpha therapy (adalimumab) in Rasmussen's encephalitis: An open pilot study

Epilepsia - Sat, 04/23/2016 - 00:10
Summary Objective

Rasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug-resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology.

Methods

We report an open-label study evaluating the efficacy and the safety of anti-TNF-α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects.

Results

Adalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow-up was for a median period of 18 months (range 9–54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated.

Significance

Our study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results.

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New neurodevelopmental syndrome identified

Medical News Today - Fri, 04/22/2016 - 08:00
A multicenter research team led by Columbia University Medical Center (CUMC) has discovered a new neurodevelopmental syndrome and the genetic mutations that cause it.
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Novartis drug Afinitor significantly reduces seizures in Phase III study of patients with tuberous sclerosis complex

Medical News Today - Fri, 04/22/2016 - 07:00
Everolimus is the first adjunctive therapy shown in a prospective randomized Phase III study to achieve clinically significant seizure control in TSC patients1.
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Once-daily eslicarbazepine equals twice-daily carbamazepine for controlling partial-onset seizures

Clinical Neurology News - Thu, 04/21/2016 - 15:55

VANCOUVER – Once-daily eslicarbazepine may offer a more convenient option for controlling newly diagnosed partial-onset seizures, suggest findings of a phase III trial reported at the annual meeting...

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Researchers discover moving, electrically 'silent' source initiates brain waves

Medical News Today - Thu, 04/21/2016 - 05:00
Finding may help in understanding memory formation, treating epilepsy. Brain waves that spread through the hippocampus are initiated by a method not seen before--a possible step toward...
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Extrastriate visual cortex in idiopathic occipital epilepsies: The contribution of retinotopic areas to spike generation

Epilepsia - Wed, 04/20/2016 - 00:36
Summary Objectives

To provide insight into the pathophysiology of idiopathic childhood occipital epilepsies (ICOEs), by mapping the contribution of retinotopic visual areas to the generation and sustainment of epileptic activity.

Methods

Thirteen patients affected by ICOEs (mean age = 10.9 years) underwent a video electroencephalography–functional magnetic resonance imaging (EEG-fMRI) study. A flexible-related fMRI analysis was applied to estimate the shape of the blood oxygen level–dependent (BOLD) response in each patient. Second-level analysis was performed using the interictal EEG discharge (IED)–specific response shape for the ICOE group. The resulting fMRI t-maps were warped to the Population-Average, Landmark- and Surface-based (PALS)-B12 atlas in Caret. For localization purposes, functional results were plotted and compared against 19 retinotopic areas for each hemisphere. A correlation analysis was performed between the hemodynamic maps and electroclinical variables.

Results

The shape of the group-averaged hemodynamic response in ICOE patients showed an earlier time-to-peak and a more pronounced undershoot than the canonical hemodynamic response function (HRF). The random-effect analysis showed positive hemodynamic changes in the bilateral temporooccipital network. With regard to the retinotopic subdivision of the visual cortex, the primary visual area was consistently spared. Conversely, an extensive involvement of the occipitotemporal cortex, including the fusiform gyrus, and the occipitoparietal areas was observed. Moreover, a linear relationship was detected between the occipital spike-density and BOLD increases at the postcentral gyrus and temporooccipital cortex.

Significance

Our data indicate that both the ventral and dorsal visual pathways are involved in spike generation in ICOEs, to extents that vary between patients, and reinforce the concept of benign childhood seizure susceptibility syndrome as a substrate for ICOEs. Finally, these results underscore the need for appropriate neuropsychological testing in these children, aimed at revealing selective impairments in functions subserved by both visual pathways.

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Women with epilepsy conceive at normal rate

Clinical Neurology News - Tue, 04/19/2016 - 13:21

VANCOUVER – Women with epilepsy have fertility rates comparable with healthy women in the general population, according to results from the first prospective observational cohort study to make the...

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Toward quieting the brain - promising anti-seizure strategies

Medical News Today - Tue, 04/19/2016 - 12:00
Cluster Analysis of Cat Neural Networks Reveals Promising Anti-seizure Strategies.Chronic brain diseases such as epilepsy involve disturbances of the brain's electrical activity.
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Adenosine A1 receptor–mediated suppression of carbamazepine-resistant seizure-like events in human neocortical slices

Epilepsia - Mon, 04/18/2016 - 06:06
Summary Objective

The need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy (TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug-resistant seizure-like events (SLEs) in human temporal cortex slices.

Methods

Layer V/VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K+] and 50 μm bicuculline.

Results

Activating A1 receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A1 agonist, in slices insensitive to a high dose of carbamazepine (50 μm). Also in these cases the A1 agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A1 receptors.

Significance

Selective activation of A1 receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure-like activity is a feasible option for future studies investigating new antiepileptic drug (AED) candidates.

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Expanding the spectrum of cognitive outcomes after temporal lobe epilepsy surgery: A prospective study of theory of mind

Epilepsia - Mon, 04/18/2016 - 05:55
Summary Objective

Because temporal lobe epilepsy (TLE) can impair theory of mind (ToM), we examined the effects of anterior temporal lobectomy (ATL) by comparing the preoperative to postoperative ToM course with that of other cognitive functions characteristically impaired in TLE.

Methods

Eighty-five patients with left (n = 39) or right (n = 46) drug-resistant TLE and an age at epilepsy onset of >12 (n = 54) or ≤12 years (n = 31) were evaluated before and 1 year after surgery; 40 healthy controls were assessed at baseline. The participants' recognition and comprehension of faux pas (FPs) or correct rejection of nonexistent FPs was assessed using the Faux Pas task; and their language, memory, and planning were, respectively, assessed using the Boston Naming, Short Story, and Tower of London tests.

Results

Baseline ToM was impaired in the patients with left or right TLE in comparison with the controls, and significantly influenced by education and age at seizure onset, with more severe deficits being observed in those with less education and an age at onset of ≤12 years. After ATL, their recognition and comprehension of FPs was unchanged, whereas the rejection of nonexistent FPs improved in the patients with early seizure onset. Education, preoperative ToM, postoperative executive function, and fluid intelligence and the number of antiepileptic drugs predicted postoperative ToM. Postoperative naming and episodic memory were associated with ATL laterality and education, and planning was associated with age at seizure onset and chronological age.

Significance

After ATL, the components of ToM may be unchanged or slightly improved depending on cognitive reserve and age at seizure onset, thus suggesting that ATL does not further aggravate the deficits caused by TLE. Moreover, the course of ToM is distinct from that of other cognitive functions. These findings expand the spectrum of the cognitive phenotypes associated with TLE and ATL, and offer potential elements for individual prognoses.

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