Current Opinion in Neurology最新文献

Purpose of review: Advances in intravenous thrombolysis and endovascular thrombectomy have significantly reduced disability and improved outcomes associated with acute ischemic stroke.

Recent findings: An expansion of indications for reperfusion therapies in select groups of patients to permit treatment in an extended time window, with large ischemic core, and with simplified imaging protocols have enabled a broader group of patients access to disability-sparing therapy. Cerebroprotection has had renewed development in the era of acute reperfusion.

Summary: In this review, we highlight recent developments in stroke reperfusion research and related questions that are under study or remain unanswered.

Purpose of review: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.

Recent findings: Evidence from three clinical studies (RHODOS, RHODOS-OFU, and LEROS) suggest that idebenone should be started early and continued for at least 24 months. Treatment effect varies according to the stage of LHON and the underlying mutation. Favourable outcomes are associated with the m.11778G>A mutation and chronic eyes with the m.14484T>C mutation. Caution should be taken in subacute/dynamic eyes with the m.3460G>A mutation, due to possible clinical worsening with idebenone. Compared to eyes from an external natural history cohort, pooled data from four clinical studies (RESCUE, REVERSE, RESTORE and REFLECT) show that a single intravitreal injection of lenadogene nolparvovec can result in sustained bilateral visual improvement in m.11778G>A LHON patients aged ≥15 years when treated within 1 year of onset. Although the treatment effect is modest, the final visual acuity of treated patients (∼1.2 logMAR) significantly differs from the published natural history of LHON and the treatment benefit is more pronounced than the effect of idebenone alone in patients with the m.11778G>A mutation.

Summary: There is increasing evidence for the potential therapeutic benefit of idebenone and lenadogene nolparvovec gene therapy.

Purpose of review: This review explores the phenomenology, pathogenesis, and nosology of headaches associated with infections, an often-overlooked yet clinically significant symptom. With the increasing recognition of secondary headaches in infections, understanding their clinical patterns, mechanisms, and classifications is crucial for accurate diagnosis and management.

Recent findings: Headaches in infections are ubiquitous but vary in presentation, severity, and underlying mechanisms depending on the causative pathogen. Elevated intracranial pressure, meningeal irritation, and activation of the trigeminovascular system are key contributors to headache generation, which varies depending on each pathogen. Pathogen-specific predilection for one of these mechanisms may subtly alter the clinical phenotype of the headache, which can be used to guide management. Emerging evidence highlights postinfectious headache syndromes, particularly following bacterial meningitis and SARS-CoV-2 infection, underscoring the need for long-term follow-up in these patients.

Summary: The diverse presentations of infection-related headaches necessitate a systematic approach to evaluation and management. While the pathophysiology is complex and multifaceted, understanding these mechanisms aids in differentiating primary headaches from those secondary to infections.

Purpose of review: This scoping review summarizes key developments in the field of seizure forecasting.

Recent findings: Developments have been made along several modalities of seizure forecasting, including long term intracranial and subcutaneous encephalogram, wearable physiologic monitoring, and seizure diaries. However, clinical translation of these tools is limited by various factors. One is the lack of validation of these tools on an external dataset. Moreover, the widespread practice of comparing models to a chance forecaster may be inadequate. Instead, the model should be able to at least surpass a moving average forecaster, which serves as a 'napkin test' (i.e., can be computed on the back of a napkin). The impact of seizure frequency on model performance should also be accounted for when comparing performance across studies. Surprisingly, despite the potential for poor quality forecasts, some individuals with epilepsy still want access to imprecise forecasts and some even alter their behavior based upon them.

Summary: Promising advances have been made in the development of tools for seizure forecasting, but current tools have not yet overcome clinical translation hurdles. Future studies will need to address potentially dangerous patient behaviors as well as account for external validation, the napkin test, seizure frequency dependent metrics.

Purpose of review: This article discusses commonly encountered medical and neurological complications in patients with brain tumors and highlights recommendations for their management based on updated evidence.

Recent findings: Use of dexamethasone is correlated with worse prognosis in patients with glioblastoma, and in brain metastases, high doses may lead to increased side effects without additional clinical benefit. There are multiple antiseizure medications (ASM) to choose from and possible interactions and toxicity must be considered when choosing an agent. Additionally, there is growing interest in the use of AMPA receptor blockers as ASM in patients with brain tumors. Nonpharmacological strategies for the management of fatigue remain paramount. Cognitive decline is common after whole brain radiation (WBRT) and hippocampal-sparing WBRT results in superior cognitive outcomes. Venous thromboembolism is a common complication and there is growing evidence on the use of direct oral anticoagulants (DOACs) in this population.

Summary: There is evolving evidence on the management of medical and neurological complications in patients with brain tumors. These complications, require early identification and multidisciplinary collaboration and expertise.

Purpose of review: Cognitive impairment is one of the most challenging non-motor symptoms of Parkinson's disease (PD) and may occur during all PD stages. There are no established pharmacological treatments for PD-related cognitive impairment, which may be improved by cognition-based interventions (i.e., cognitive stimulation, cognitive training, cognitive rehabilitation). Multimodal cognition-based interventions by adjunctive drugs, exercise, non-invasive brain stimulation and technologies may be effective in PD.

Recent findings: Exercise combined with cognitive training may enhance global, memory, visuospatial and executive functioning, transcranial direct current stimulation delivered alongside cognitive training may improve attention and executive functioning, and exergames, semi-immersive virtual reality (VR) and telerehabilitation plus non-immersive VR combined with cognitive training may ameliorate global and executive functioning in PD patients.

Summary: The evidence reviewed here, despite preliminary, is very encouraging and suggests strong rationale for combining pharmacological and non-pharmacological interventions with cognition-based treatments in PD. To overcome limitations of current studies, we propose some recommendations for future trials on drugs, exercise, non-invasive brain stimulation and technologies combined with cognition-based treatments for cognitive impairment in PD.

Purpose of review: While wearable robotics is expanding within clinical settings, particularly for neurological rehabilitation, there is still a lack of consensus on how to effectively assess the performance of these devices. This review focuses on the most common metrics, whose selection and design are crucial for optimizing treatment outcomes and potentially improve the standard care.

Recent findings: The literature reveals that while wearable robots are equipped with various embedded sensors, most studies still rely on traditional, nontechnological methods for assessment. Recent studies have shown that, although quantitative data from embedded sensors are available (e.g., kinematics), these are underutilized in favor of qualitative assessments. A trend toward integrating automatic assessments from the devices themselves is emerging, with a few notable studies pioneering this approach.

Summary: Our analysis suggests a critical need for developing standardized metrics that leverage the data from embedded sensors in wearable robots. This shift could enhance the accuracy of patient assessments and the effectiveness of rehabilitation strategies, ultimately leading to better patient outcomes in neurological rehabilitation.

Purpose of review: Current biological findings provide new insights into the genetics driving growth of low-grade gliomas in pediatric patients. This has provided new targets for novel therapies. The purpose of this paper is to review novel therapies for pediatric low-grade gliomas that have been published in the past 24 months.

Recent findings: Low-grade gliomas are often driven by mitogen activated protein kinase (MAPK) alterations either with BRAF V600E point mutations or BRAF fusions. Current advances have also highlighted novel fusions of fibroblast growth factor receptor (FGFR), myeloblastosis family of transcription factors (MYB), meningioma 1 tumor suppressor (MN1), neurotrophic receptor kinase family of receptors (NTRK), Kristen RAS (Rat Sarcoma Virus) oncogene homolog in mammals (KRAS), Receptor tyrosine kinase ROS proto oncogene 1 (ROS1), protein kinase C alpha (PRKCA), and platelet derive growth factor receptor (PDGFR) amplification. Novel therapies have been employed and are showing encouraging results in pediatric low-grade gliomas. Current trials are underway with newer generation pan RAF inhibitors and mitogen activated protein kinase - kinase (MEK) inhibitors. Other early phase clinical trials have provided safety data in pediatric patients targeting FGFR fusion, NTRK fusion, PDGFR amplification and ROS1 mutations.

Summary: Historical treatment options in pediatric low-grade gliomas have utilized surgery, radiation therapy and conventional chemotherapy. Recently greater insight into their biology has found that alterations in MAPK driven pathways are often the hallmark of tumorigenesis. Targeting these novel pathways has led to tumor control and shrinkage without the use of conventional chemotherapy. Caution should be taken however, since these treatment options are still novel, and we do not fully appreciate the long-term effects. Nonetheless a new era of targeted medicine is here.