Current Treatment Options in Neurology最新文献

Purposeof review: Autonomic disorders disrupt homeostasis and cause symptoms such as orthostatic hypotension, urinary urgency, bladder overfilling, sexual dysfunction, constipation, and gastroparesis. Pathophysiologic mechanisms include neurodegeneration, autoimmunity, toxic exposure, medication-induced, and an array of others. Despite the lack of disease-modifying treatments for the most common etiologies, there is a plethora of therapeutic options available to treat the manifestations of dysautonomia. Here we review established and recent therapeutic strategies available for dysautonomia. We also provide a general schema to approach the management of this class of disorders in the clinical setting.

Recent findings: New emerging neuromodulatory devices are showing promise in treating dysautonomic orthostatic hypotension (spinal cord stimulators), urinary dysfunction (tibial and sacral nerve stimulators), sexual dysfunction (percutaneous perineal and sacral nerve stimulation), constipation (sacral anterior root stimulation), and gastroparesis (gastric electrical stimulation). However, most of these approaches are either experimental or not yet widely implemented. Recent medications are often more effective and/or better tolerated than older ones. These include droxidopa for orthostatic hypotension, β-3-adrenergic agonists for spastic bladder, and prucalopride, elobixibat and linaclotide for constipation.

Summary: Autonomic disorders manifest with symptoms of homeostatic dysfunction. A wide variety of central and peripheral nervous system disorders cause dysautonomia. While the treatment of each specific disorder varies based on etiology, strategies overlap to manage dysautonomia. Treatments are divided into non-pharmacological, pharmacological, and neuromodulatory strategies. Here, we focus on the most common issues encountered in clinical practice and propose a stepwise approach to manage common symptoms that frequently integrates all three strategies.

Primary progressive aphasia(PPA) is a rare neurodegenerative condition and variant presentation of Alzheimer's disease or Frontotemporal Dementia. It is characterized by progressive decline isolated to language functions. PPA provides a model for understanding the anatomy of language, where each cortical language center corresponds to distinct PPA subtypes. Understanding this anatomy and its corresponding PPA subtypes helps clinicians choose testing, interpret imaging, and tailor treatment. These subtypes are termed agrammatic/nonfluent, semantic, and logopenic PPA. Each subtype is probabilistically associated with three proteinopathies: the amyloid and tau of Alzheimer's disease and frontotemporal lobar degeneration due to Tau or TDP-43. We will discuss when biomarker testing is indicated and the nuances of choosing among the increasing array of biomarker tests to improve diagnostic certainty. While medical treatment is limited, there are increasing pharmacologic options for treating Alzheimer's disease. Non-pharmacologic strategies can also be tailored to the patient's specific subtype and caregivers' needs.

Purpose of review: Multiple sclerosis (MS) is a complex neurodegenerative disease characterized by inflammation, demyelination, and neurodegeneration. Significant hypoxia exists in brain of people with MS (pwMS), likely contributing to inflammatory, neurodegenerative, and vascular impairments. In this review, we explore the concept of a negative feedback loop between hypoxia and inflammation, discussing its potential role in disease progression based on evidence of hypoxia, and its implications for therapeutic targets.

Recent findings: In the experimental autoimmune encephalomyelitis (EAE) model, hypoxia has been detected in gray matter (GM) using histological stains, susceptibility MRI and implanted oxygen sensitive probes. In pwMS, hypoxia has been quantified using near-infrared spectroscopy (NIRS) to measure cortical tissue oxygen saturation (StO₂), as well as through blood-based biomarkers such as Glucose Transporter-1 (GLUT-1). We outline the potential for the hypoxia-inflammation cycle to drive tissue damage even in the absence of plaques. Inflammation can drive hypoxia through blood-brain barrier (BBB) disruption and edema, mitochondrial dysfunction, oxidative stress, vessel blockage and vascular abnormalities. The hypoxia can, in turn, drive more inflammation.

Summary: The hypoxia-inflammation cycle could exacerbate neuroinflammation and disease progression. We explore therapeutic approaches that target this cycle, providing information about potential treatments in MS. There are many therapeutic approaches that could block this cycle, including inhibiting hypoxia-inducible factor 1-α (HIF-1α), blocking cell adhesion or using vasodilators or oxygen, which could reduce either inflammation or hypoxia. This review highlights the potential significance of the hypoxia-inflammation pathway in MS and suggests strategies to break the cycle. Such treatments could improve quality of life or reduce rates of progression.

Purpose of review: Increased understanding of the pathophysiology of Alzheimer's disease (AD) has led to development of disease modifying therapies. The therapies primarily target measures of cognitive decline since AD has been thought of as a cognitive disorder. However, the non-cognitive symptoms seen in AD contribute to overall quality-of-life. This scoping review was undertaken to further our understanding of the non-cognitive features of AD.

Recent findings: The non-cognitive symptoms in AD range from changes in sensory perception, systemic changes, and neuropsychiatric manifestations. We targeted the following non-cognitive domains: vision, olfaction, GI, muscle, sleep, circadian rhythm, immune and behavioral symptoms as it relates to AD for this review. Non-cognitive features impact the ability of individuals to perform their activities of daily living, have safety implications and lead to increased caregiver burden. The review explores non-pharmacological and pharmacological measures targeted at the non-cognitive changes in AD.

Summary: Non-cognitive symptoms contribute to significant disease burden in Alzheimer's disease. It is important to screen for and provide supportive care for these symptoms to help improve clinical care. Incorporation of non-cognitive features of AD in clinical trials will help ascertain the true societal and economic impact of AD and that of potential therapeutics.

Opinion statement: Alzheimer's disease (AD) is primarily recognized as a disorder of cognition; however, non-cognitive symptoms significantly contribute to disease burden and clinical presentation. These manifestations particularly behavioral symptoms and systemic changes beyond the central nervous system impact patients' quality of life and increase caregiver stress. Often, such symptoms necessitate a transition from home-based care to more intensive settings, such as memory care facilities. As AD prevalence rises alongside an aging population, the shortage of dedicated memory care providers in community settings challenges access and quality of care. Improved awareness and early recognition of non-cognitive features among healthcare professionals can aid identification of modifiable systemic issues and allow timely behavioral management during clinical encounters. Treatment of these symptoms requires a multifaceted approach, incorporating pharmacological and non-pharmacological strategies. Non-pharmacological interventions, including tailored behavioral approaches and environmental modifications, can enhance quality of life for individuals with AD and reduce caregiver burden especially where specialized medical resources are limited.

Purpose of review

This review presents a critical appraisal of the current state of simulation-based education in neurocritical care, including a brief summary of its supporting conceptual frameworks and its emergence as a tool for quality improvement and patient safety. We discuss technological developments that will expand the uses of simulation within the field and/or lower entry costs.

Recent findings

Simulation-based educational interventions have improved learner performance in simulation-based assessments of interpretation of continuous electroencephalography ( as well as management of acute stroke and status epilepticus. Three recent studies demonstrate improved door-to-needle times for thrombolytics in acute ischemic stroke after simulation-based training, especially when such training focuses on interprofessional teamwork. Simulation can also be used to teach safety analysis and to identify patient safety threats.

Summary

Access to simulation and its application is growing in neurocritical care. More rigorous, multicenter studies are required to demonstrate translational outcomes for improved patient care.

Purpose of Review

This systematic scoping review examines evidence from the last five years on sleep interventions in cognitive healthy older adults and those with mild cognitive impairment.

Recent Findings

Sleep disturbance has been identified as a potential early, modifiable risk factor for dementia, making it crucial to investigate if these interventions also enhance cognitive function and neurodegenerative biomarkers.

Summary

Since 2019, research on sleep interventions in older adults with or without cognitive impairment has gradually expanded, especially on non-pharmacological treatments including CBT-I, exercise, and multi-modal interventions, which show promise but require further study to confirm cognitive benefits. Pharmacological interventions have primarily focused on melatonin and orexin antagonists, with long-term safety remaining a concern. Tailored, clinically effective interventions that consider the presence of Alzheimer’s disease biomarkers, such as amyloid, tau, cerebrovascular disease, or alpha-synuclein in key sleep-related circuits, are essential to developing feasible, cost-effective, and scalable treatments for older adults with or without cognitive impairment.

Purpose of Review

The aim is to elucidate the mechanisms of autoimmune dysregulation that contribute to the onset and course of Guillain–Barre Syndrome (GBS) and Myasthenia Gravis (MG), with an emphasis on the important role that the Epstein-Barr virus (EBV) plays as an exacerbator or trigger of these autoimmune reactions. It further explores diagnostic strategies and therapeutic approaches to improve patient outcomes.

Recent Findings

Recent researches have underscored the challenging nature of EBV due to its insidious behavior and persistent latency, which make it difficult to create successful preventive and therapeutic approaches. These discoveries have revealed how EBV's ability to induce host immune dysfunction can exacerbate or spark inflammatory processes, leading to its association with various autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. Moreover, this review will shed light on the intricate connections between EBV and autoimmune neuromuscular disorders like MG and GBS, emphasizing the urgent requirement for further investigation to devise effective strategies against EBV-related conditions.

Summary

MG and GBS, while both autoimmune illnesses affecting the neuromuscular system, differ greatly in their pathogenesis and clinical presentation. Viral infections, notably EBV, are vital in causing or aggravating these diseases. Understanding the link between EBV and autoimmune dysregulation could enhance diagnostic accuracy, therapeutic approaches, and preventive options, such as antiviral medications or vaccinations. Continued research and interdisciplinary collaboration are crucial to clarify how EBV affects MG and GBS, potentially leading to tailored treatments. Identifying precise biomarkers and pathways will improve clinical protocols, public health standards, and education on the EBV-autoimmunity relationship.

Introduction

Failed Back Surgery Syndrome (FBSS) presents a formidable challenge, marked by the persistence of chronic lower back pain and leg pain despite undergoing surgical interventions. Multicolumn spinal cord stimulation (m-SCS) has recently emerged as a promising therapeutic strategy for addressing the pain associated with FBSS. This meta-analysis aims to study the efficacy of m-SCS in mitigating chronic back and leg pain among patients with FBSS.

Methods

A comprehensive search of electronic databases (PubMed, Web of Science, Scopus, Cochrane Library) was conducted to identify relevant studies published up to October 25th, 2023. Inclusion criteria encompassed randomized controlled trials and cohort studies evaluating the outcomes of m-SCS in patients with FBSS. The primary outcome measured was the Visual Analog Scale (VAS) score for low back and leg pain at baseline, six months, and 12 months.

Results

A total of eight studies, including 271 patients, were analyzed. At six months, there was a statistically significant reduction in the VAS scores for low back pain (MD, 4.76; 95% CI, 3.78 to 5.74) and leg pain (MD, 4.41; 95% CI, 2.93 to 5.90) compared to baseline. Similarly, at 12 months, there was a statistically significant reduction in the VAS scores for low back pain (MD, 4.77; 95% CI, 4.34 to 5.20) and leg pain (MD, 2.78; 95% CI, 0.72 to 4.85) compared to baseline.

Conclusion

m-SCS effectively manages chronic back and leg pain in FBSS patients, providing sustained pain relief. Studies with more extended follow-up periods and qualitative analysis for the functional outcomes and overall improvement for the patients with FBSS are recommended.

Purpose of Review

About 30% of epilepsy cases have an underlying genetic etiology. Despite rapid progress with understanding the genetic underpinnings of epilepsy and with gene-specific treatments for epilepsy, many barriers for clinicians to send genetic testing remain. This review aims to provide clinicians with a practical approach to genetic testing for epilepsy.

Recent Findings

Incorporation of genetic counselors into neurology practices is a useful model for supporting providers to implement proper recommendations. Selecting the appropriate genetic test for epilepsy involves prioritizing patients’ informed consent and evaluating diagnostic yield, cost-effectiveness, and turnaround time following certain algorithms, with exome/genome sequencing as first-tier options, and multigene epilepsy panel as a more accessible alternate for resource-limited situations. Result interpretation should be conducted on a case-by-case basis, and should include interpretation of the results, changes in clinical management, inheritance risks, testing of family members, and discussion of additional testing if needed.

Summary

We provide a comparative assessment of the yield of genetic tests for epilepsy, with possible test outcomes and practical considerations for the clinical decision-making process. Continued research and integration of cutting-edge approaches will expand our understanding of genetics in epilepsy and improve clinical outcomes for individuals with epilepsy.

The relationship between epilepsy and autism spectrum disorder (ASD) is complex and multifaceted. The prevalence of ASD in children with epilepsy is notably high, particularly in those with developmental epileptic encephalopathies (DEEs). DEEs, characterized by co-occurring epileptic activity and developmental impairments, often overlap with ASD, further complicating clinical presentations of difficulties in motor skills, language, social interaction, and adaptive behavior. The co-occurrence may be attributable to shared pathophysiological mechanisms, common genes, pre- and peri-natal risk factors, and disruptions in neurotransmitter pathways, particularly the glutamatergic and GABAergic systems. The presence of ASD in epilepsy profoundly impacts treatment choices and necessitates a careful balance between seizure control and behavioral management. Effective management of epilepsy in individuals with ASD requires a comprehensive approach, including anti-seizure medications (ASMs) like valproate and levetiracetam, which may address both seizures and behavioral issues. EEG monitoring is crucial for accurate diagnosis, distinguishing between epileptic and ASD-related behaviors. This review carefully details the overlap and physiological underpinnings of both disorders and underscores the necessity of tailored therapeutic approaches to medical care, emphasizing a multidisciplinary strategy to optimize outcomes.