NEURO

No abstract available from Current Opinion in Neurology - Current Issue https://ift.tt/2H5D6V7

No abstract available from Current Opinion in Neurology - Current Issue https://ift.tt/2tJuOdI

Purpose of review Recent publications point to an increasingly important role of variants in genes encoding GABAA receptor subunits associated with both common and rare forms of epilepsies. The aim of this review is to give an overview of the current clinical phenotypes, genetic findings and pathophysiological mechanisms related to GABAA receptor variants. Recent findings Early work showed that inherited variants in GABRG2 and GABRA1 cause relatively mild forms of monogenic epilepsies in large families. More recent studies have revealed that de novo variants in several GABAA receptor genes cause severe developmental and epileptic encephalopathies, inherited variants cause remarkably variable phenotypes within the same pedigrees ranging from asymptomatic carriers to developmental and epileptic encephalopathies, and variants in all GABAA receptor genes are enriched in common forms of epilepsy, namely rolandic epilepsy and genetic generalized epilepsy. Analyses from cellular expression sy

Purpose of review There has been rapid progress in defining novel causative gene variants responsible for a large spectrum of human epilepsy syndromes and subtypes. Of particular interest is the discovery that somatic mutations, for example, noninherited mutations occurring in neuroglial progenitor cells during embryonic brain development, are highly linked to malformations of cortical development (MCD) such as focal cortical dysplasia (FCD) type II and hemimegalencephaly. Recent findings Somatic gene variants have been identified in genes encoding regulatory proteins within the mechanistic target of rapamycin (mTOR) signaling cascade and have thus comprised the group classified as mTORopathies. FCD II and hemimegalencephaly often result from mutations in identical genes suggesting that these are spectrum disorders. An exciting recent development has been the identification of somatic mutations causing both FCD Ia and nonlesional neocortical epilepsy. Summary Defining somatic gene muta

Purpose of review There is need for automated seizure detection using mobile or wearable devices, for objective seizure documentation and decreasing morbidity and mortality associated with seizures. Due to technological development, a high number of articles have addressed non-electroencephalography (EEG)-based seizure detection. However, the quality of study-design and reporting is extremely heterogeneous. We aimed at giving the reader a clear picture on the current state of seizure detection, describing the level of evidence behind the various devices. Recent findings Fifteen studies of phase-2 or above, demonstrated that non-EEG-based devices detected generalized tonic–clonic seizures (GTCS) with high sensitivity (≥90%) and low false alarm rate (FAR) (down to 0.2/day). We found limited evidence for detection of motor seizures other than GTCS, mostly from subgroups in larger studies, targeting GTCS. There is little evidence for non-EEG-based detection of nonmotor seizures: sensitivit

Purpose of review The current review updates our knowledge regarding sudden unexpected death in epilepsy patient (SUDEP) risks, risk factors, and investigations of putative biomarkers based on suspected mechanisms of SUDEP. Recent findings The overall incidence of SUDEP in adults with epilepsy is 1.2/1000 patient-years, with surprisingly comparable figures in children in recently published population-based studies. This risk was found to decrease over time in several cohorts at a rate of −7% per year, for unknown reasons. Well established risk factors include frequency of generalized tonic–clonic seizures, while adding antiepileptic treatment, nocturnal supervision and use of nocturnal listening device appear to be protective. In contrast, recent data failed to demonstrate the predictive value of heart rate variability, periictal cardiorespiratory dysfunction, and postictal generalized electroencephalography suppression. Preliminary findings suggest that brainstem and thalamic atrophy

Purpose of review Precise localization of the epileptogenic zone is imperative for the success of resective surgery of drug-resistant epileptic patients. To decrease the number of surgical failures, clinical research has been focusing on finding new biomarkers. For the past decades, high-frequency oscillations (HFOs, 80–500 Hz) have ousted interictal spikes – the classical interictal marker – from the research spotlight. Many studies have claimed that HFOs were more linked to epileptogenicity than spikes. This present review aims at refining this statement in light of recent studies. Recent findings Analysis based on single-patient characteristics has not been able to determine which of HFOs or spikes were better marker of epileptogenic tissues. Physiological HFOs are one of the main obstacles to translate HFOs to clinical practice as separating them from pathological HFOs remains a challenge. Fast ripples (a subgroup of HFOs, 250–500 Hz) which are mostly pathological are not found in

Purpose of review To review the history, pharmacology, and clinical science of cannabidiol (CBD) in the treatment of epilepsy. Recent findings Phase III randomized controlled trials and prospective open label trials have provided efficacy and safety data for the use of CBD in pediatric onset severe epilepsies. The product that was studied in the vast majority of these published trials, Epidiolex (>99% of CBD and <0.10% Δ9-tetrahydrocannabinol (THC); GW pharmaceuticals, Cambridge, UK), has now been FDA approved based on this published data. Summary Identification of CBD, Δ9-THC, and the endocannabinoid system in the mid-20th century has led to advancement of cannabis-based therapies for epilepsy. Based on clinical trial data, Epidiolex is the first CBD medication approved by a national regulatory agency (US Food and Drug Administration for Dravet and Lennox Gastaut syndrome; European Medicines Agency for Lennox Gastaut syndrome). Approval of CBD as a treatment for these rare and s

Purpose of review Behavioral intervention describes multiple modalities of treatments which are of increasing interest in epilepsy. This review addresses recent behavioral clinical trials in epilepsy including cognitive behavioral therapy (CBT), mindfulness, progressive muscle relaxation (PMR), and self-management. Results and conclusions from updated Cochrane reviews and the recent International League Against Epilepsy Psychology task force are presented. Recent findings Two recent large randomized controlled trials (mindfulness and progressive muscle relaxation) reported improved seizure frequency with behavioral treatments. In both studies, participants in both the active and the attentional control arms showed significant seizure reduction, whereas quality of life and stress reduction were better noted in the active arms. Additional behavioral modalities have reported improved seizure control including yoga, bio/neurofeedback, and music therapy. Significant improvements in multiple

Purpose of review MRI-guided stereotactic laser interstitial thermal therapy (LiTT) has been utilized in the surgical treatment of discrete, small epileptogenic lesions. This review summarizes the current literature and addresses the clinical application of this technique. Recent findings LiTT has the potential to reduce the morbidity and discomfort of epilepsy surgery. Review of data from retrospective, uncontrolled studies suggests that LiTT may offer benefit when treating drug-resistant epilepsy because of mesial temporal sclerosis, hypothalamic hamartoma, cavernous hemangioma, and small cortical dysplasias and malformations. It is now being offered as initial therapy in place of anterior temporal lobectomy in many centers, and a prospective study is underway to compare it with historical temporal lobectomy reports. Summary LiTT appears promising and has potential for reduced morbidity and improved tolerability compared with open surgery. Studies must be done to compare efficacy and

Purpose of review We review data on the comparative teratogenicity of antiepileptic drugs (AEDs), focusing on major congenital malformations (MCMs), intrauterine growth restriction, impaired cognitive development, and behavioral adverse effects following prenatal exposure. Recent findings Prospective registries and meta-analyses have better defined the risk of MCMs in offspring exposed to individual AEDs at different dose levels. Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent. Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits. In a population-based study, the risk of AED-induced autistic traits was attenuated by periconceptional folate supplementation. Summary The risk of adverse fetal effects differs in relation to th

No abstract available from Current Opinion in Neurology - Current Issue https://ift.tt/2H7LQtU

Purpose of review Knowledge on primary progressive aphasia (PPA) has expanded rapidly in the past few decades. Clinical characteristics, neuroimaging correlates, and neuropathological features of PPA are better delineated. This facilitates scientific studies on the disease pathophysiology and allows speech and language therapy to be more precisely targeted. This review article begins with a summary of the current understanding of PPA and discusses how PPA can serve as a model to promote scientific discovery in neurodegenerative diseases. Recent findings Studies on the different variants of PPA have demonstrated the high compatibility between clinical presentations and neuroimaging features, and in turn, enhances the understanding of speech and language neuroanatomy. In addition to the traditional approach of lesion-based or voxel-based mapping, scientists have also adopted functional connectivity and network topology approaches that permits a more multidimensional understanding of neur

Purpose of review This study, taking the example of Alzheimer's and Parkinson's diseases, presents the experimental and human data that support the hypothesis that Aβ, tau, and α-synuclein may seed and propagate the pathology and consider the potential clinical consequences. Recent findings Aβ aggregates transmit Aβ pathology to experimental animals. Interhuman transmission of Aβ pathology has also been observed in iatrogenic Creutzfeldt–Jakob disease, or after dural graft. Tau aggregates also transmit the pathology to mice when injected in the brain and propagates along neuronal pathways. Evidence of interhuman transmission is weak. Finally α-synuclein aggregates, when injected in specific areas of the brain may recapitulate Lewy pathology of Parkinson's disease but there is currently no hint of human to human transmission. Summary Since the first evidence that at least Aβ pathology of Alzheimer's disease could be transmitted to the animal, data have accumulated indica

Purpose of review Over the last year, research into the immunological and inflammatory signatures of frontotemporal lobar degeneration (FTLD) has accelerated greatly. Herein, we highlight recently proposed roles of brain-resident microglia as well as peripheral myeloid cells in frontotemporal dementia (FTD)-spectrum disorders. Recent findings Recent unbiased genetic, transcriptomic, and proteomic surveys using human data confirm significantly altered immune-function genes as well as transcript and protein modules associated with inflammatory and immune function. Beyond human studies, novel animal models indicate important roles for both microglia and monocytes, and central involvement of genes such as Trem2, Apoe, and Tbk1. Summary The importance of neuroinflammatory activity in FTD pathophysiology is unambiguous, but whether this activity is primarily beneficial or detrimental remains unclear, with variable results reported for distinct disease paradigms. Going forward, it will be cru

Purpose of review The purpose of this review is to provide an update on comorbidities in neurodegenerative conditions. The term comorbidity is used here to distinguish cases with overlapping pathogenic mechanisms, which includes combinations of neurodegenerative proteinopathies from cases with multimorbidity, which is defined as concomitant brain and systemic disorders with different pathogenic mechanisms. Recent findings Comorbid proteinopathies are more frequent in both sporadic and hereditary neurodegenerative diseases than previously assumed. The most frequent additional proteinopathies are related to Alzheimer's disease, Lewy body disorder, and limbic predominant transactive response DNA-binding protein 43 proteinopathy, however, different forms of tau pathologies are also increasingly recognized. In addition to ageing, synergistic interaction of proteins, common disease pathways, and the influence of genetic variations are discussed as possible pathogenic players. Summary Com

Purpose of review Alzheimer's disease is a progressive neurodegenerative disease without effective pharmacological treatment. Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are increasingly being investigated for their potential to ameliorate the symptoms of Alzheimer's disease and related dementias (ADRD). Recent findings A comprehensive literature review for primary research reports that investigated the ability of TMS/tES to improve cognition in ADRD patients yielded a total of 20 reports since 2016. Eight studies used repetitive TMS and 12 used transcranial direct current stimulation, the most common form of tES. Eight of the studies combined NIBS with cognitive training. Promising results should encourage continued investigation, however there is currently insufficient evidence to support widespread adoption of NIBS-based clinical treatments for ADRD. Summary NIBS re

No abstract available from Neurology Today - Current Issue https://ift.tt/2T9KAgm

No abstract available from Neurology Today - Current Issue https://ift.tt/2IrdLHG

No abstract available from Neurology Today - Current Issue https://ift.tt/2T76qRt