Current Opinion in Neurology最新文献

Purpose of review: To review the current practices and evidence for the diagnostic accuracy and the benefits of presurgical evaluation.

Recent findings: Preoperative evaluation of patients with drug-resistant focal epilepsies and subsequent epilepsy surgery leads to a significant proportion of seizure-free patients. Even those who are not completely seizure free postoperatively often experience improved quality of life with better social integration. Systematic reviews and meta-analysis on the diagnostic accuracy are available for Video-electroencephalographic (EEG) monitoring, magnetic resonance imaging (MRI), electric and magnetic source imaging, and functional MRI for lateralization of language and memory. There are currently no evidence-based international guidelines for presurgical evaluation and epilepsy surgery.

Summary: Presurgical evaluation is a complex multidisciplinary and multiprofessional clinical pathway. We rely on limited consensus-based recommendations regarding the required staffing or methodological expertise in epilepsy centers.

Purpose of review: To review recent advances in the field of seizure detection in ambulatory patients with epilepsy.

Recent findings: Recent studies have shown that wrist or arm wearable sensors, using 3D-accelerometry, electrodermal activity or photoplethysmography, in isolation or in combination, can reliably detect focal-to-bilateral and generalized tonic-clonic seizures (GTCS), with a sensitivity over 90%, and false alarm rates varying from 0.1 to 1.2 per day. A headband EEG has also demonstrated a high sensitivity for detecting and help monitoring generalized absence seizures. In contrast, no appropriate solution is yet available to detect focal seizures, though some promising findings were reported using ECG-based heart rate variability biomarkers and subcutaneous EEG.

Summary: Several FDA and/or EU-certified solutions are available to detect GTCS and trigger an alarm with acceptable rates of false alarms. However, data are still missing regarding the impact of such intervention on patients' safety. Noninvasive solutions to reliably detect focal seizures in ambulatory patients, based on either EEG or non-EEG biosignals, remain to be developed. To this end, a number of challenges need to be addressed, including the performance, but also the transparency and interpretability of machine learning algorithms.

Purpose of review: All human beings undergo a lifelong cumulative exposure to potentially preventable adverse factors such as toxins, infections, traumatisms, and cardiovascular risk factors, collectively termed exposome. The interplay between the individual's genetics and exposome is thought to have a large impact in health outcomes such as cancer and cardiovascular disease. Likewise, a growing body of evidence is supporting the idea that preventable factors explain a sizable proportion of Alzheimer's disease and related dementia (ADRD) cases.

Recent findings: Here, we will review the most recent epidemiological, experimental preclinical, and interventional clinical studies examining some of these potentially modifiable risk factors for ADRD. We will focus on new evidence regarding cardiovascular risk factors, air pollution, viral and other infectious agents, traumatic brain injury, and hearing loss.

Summary: While greater and higher quality epidemiological and experimental evidence is needed to unequivocally confirm their causal link with ADRD and/or unravel the underlying mechanisms, these modifiable risk factors may represent a window of opportunity to reduce ADRD incidence and prevalence at the population level via health screenings, and education and health policies.

Purpose of review: Genetics studies provide important insights into Alzheimer disease (AD) etiology and mechanisms. Critical advances have been made recently, mainly thanks to the access to novel techniques and larger studies.

Recent findings: In monogenic AD, progress has been made with a better understanding of the mechanisms associated with pathogenic variants and the input of clinical studies in presymptomatic individuals. In complex AD, increasing sample sizes in both DNA chip-based (genome-wide association studies, GWAS) and exome/genome sequencing case-control studies unveiled novel common and rare risk factors, while the understanding of their combined effect starts to suggest the existence of rare families with oligogenic inheritance of early-onset, nonmonogenic, AD.

Summary: Most genetic risk factors with a known consequence designate the aggregation of the Aβ peptide as a core etiological factor in complex AD thus confirming that the research based on monogenic AD - where the amyloid cascade seems more straightforward - is relevant to complex AD as well. Novel mechanistic insights and risk factor studies unveiling novel factors and attempting to combine the effect of common and rare variants will offer promising perspectives for future AD prevention, at least regarding early-onset AD, and probably in case of later onset as well.

Purpose of review: Over the past decade, it has become clear that brain somatic mosaicism is an important contributor to many focal epilepsies. The number of cases and the range of underlying pathologies with somatic mosaicism are rapidly increasing. This growth in somatic variant discovery is revealing dysfunction in distinct molecular pathways in different focal epilepsies.

Recent findings: We briefly summarize the current diagnostic yield of pathogenic somatic variants across all types of focal epilepsy where somatic mosaicism has been implicated and outline the specific molecular pathways affected by these variants. We will highlight the recent findings that have increased diagnostic yields such as the discovery of pathogenic somatic variants in novel genes, and new techniques that allow the discovery of somatic variants at much lower variant allele fractions.

Summary: A major focus will be on the emerging evidence that somatic mosaicism may contribute to some of the more common focal epilepsies such as temporal lobe epilepsy with hippocampal sclerosis, which could lead to it being re-conceptualized as a genetic disorder.

Purpose of review: Multiple complex medical decisions are necessary in the course of a chronic disease like epilepsy. Predictive tools to assist physicians and patients in navigating this complexity have emerged as a necessity and are summarized in this review.

Recent findings: Nomograms and online risk calculators are user-friendly and offer individualized predictions for outcomes ranging from safety of antiseizure medication withdrawal (accuracy 65-73%) to seizure-freedom, naming, mood, and language outcomes of resective epilepsy surgery (accuracy 72-81%). Improving their predictive performance is limited by the nomograms' inability to ingest complex data inputs. Conversely, machine learning offers the potential of multimodal and expansive model inputs achieving human-expert level accuracy in automated scalp electroencephalogram (EEG) interpretation but lagging in predictive performance or requiring validation for other applications.

Summary: Good to excellent predictive models are now available to guide medical and surgical epilepsy decision-making with nomograms offering individualized predictions and user-friendly tools, and machine learning approaches offering the potential of improved performance. Future research is necessary to bridge the two approaches for optimal translation to clinical care.

Purpose of review: To review recent progress in preventing epileptogenesis in patients with epilepsy.

Recent findings: The recent success of epilepsy prevention and disease modification in tuberous sclerosis using simple EEG biomarkers to guide treatment initiation, and the identification of biomarkers to enrich the targeted patient population has made clinical trials of epilepsy prevention after acquired central nervous system (CNS) insults such as traumatic brain injury, stroke or infection both feasible and timely. Two such trials are currently on-going to prevent poststroke epilepsy.

Summary: No disease-modifying or preventive treatments exist for epilepsy, and their development remains a major unmet need.. We have entered though the era of change in the treatment of epilepsy from symptomatic only to disease prevention. In this review, we summarize developments and review opportunities, challenges, and potential solutions to develop preventive treatment for acquired epilepsies in humans. The 'Holy Grail' of epilepsy is within our reach.

Purpose of review: To explore the differential diagnosis of posterior fossa transient ischemic attacks (TIA) associated with vertigo and/or imbalance.To review the contribution of cerebral small vessel (SVD) disease to balance dysfunction and dizziness in the elderly.

Main findings: TIAs involving vestibular structures that mediate the vestibulo-ocular and vestibulospinal reflexes remain a diagnostic challenge because they overlap with causes of benign episodic vertigo. Here, we summarize the results of multidisciplinary specialty efforts to improve timely recognition and intervention of peripheral and central vestibular ischemia. More papers confirm that SVD is a major cause of gait disability, falls and cognitive disorder in the elderly. Recent work shows that early stages of SVD may also be responsible for dizziness in the elderly. The predominant location of the white matter changes, in the frontal deep white matter and genu of the corpus callosum, explains the association between cognitive and balance dysfunction in SVD related symptoms.

Summary: The evaluation of patients with intermittent vascular vertigo represent a major diagnostic challenge, recent reviews explore the ideal design approach for a multidisciplinary study to increase early recognition and intervention. Hemispheric white matter microvascular ischemia has been the subject of research progress - advanced stages are known to cause gait disorder and dementia but early stages are associated with "idiopathic" dizziness in the elderly.