Current Neurology and Neuroscience Reports最新文献

Purpose of review: Huntington's disease (HD) is an autosomal-dominant disorder caused by a pathological expansion of a trinucleotide repeat (CAG) on exon 1 of the huntingtin (HTT) gene. HD is characterized by the presence of chorea, alongside other hyperkinesia, parkinsonism and a combination of cognitive and behavioural features. Currently, there are no disease-modifying therapies (DMTs) for HD, and the only intervention(s) with approved indication target the treatment of chorea. This article reviews recent research on the clinical development of DMTs and newly developed tools that enhance clinical trial design towards a successful DMT in the future.

Recent findings: HD is living in an era of target-specific drug development with emphasis on the mechanisms related to mutant Huntingtin (HTT) protein. Examples include antisense oligonucleotides (ASO), splicing modifiers and microRNA molecules that aim to reduce the levels of mutant HTT protein. After initial negative results with ASO molecules Tominersen and WVE-120101/ WVE-120102, the therapeutic landscape continues to expand, with various trials currently under development to document proof-of-concept and safety/tolerability. Immune-targeted therapies have also been evaluated in early-phase clinical trials, with promising preliminary findings. The possibility of quantifying mHTT in CSF, along with the development of an integrated biological staging system in HD are important innovations applicable to clinical trial design that enhance the drug development process. Although a future in HD with DMTs remains a hope for those living with HD, care partners and care providers, the therapeutic landscape is promising, with various drug development programs underway following a targeted approach supported by disease-specific biomarkers and staging frameworks.

In this paper, we analyse the different advances in artificial intelligence (AI) approaches in multiple sclerosis (MS). AI applications in MS range across investigation of disease pathogenesis, diagnosis, treatment, and prognosis. A subset of AI, Machine learning (ML) models analyse various data sources, including magnetic resonance imaging (MRI), genetic, and clinical data, to distinguish MS from other conditions, predict disease progression, and personalize treatment strategies. Additionally, AI models have been extensively applied to lesion segmentation, identification of biomarkers, and prediction of outcomes, disease monitoring, and management. Despite the big promises of AI solutions, model interpretability and transparency remain critical for gaining clinician and patient trust in these methods. The future of AI in MS holds potential for open data initiatives that could feed ML models and increasing generalizability, the implementation of federated learning solutions for training the models addressing data sharing issues, and generative AI approaches to address challenges in model interpretability, and transparency. In conclusion, AI presents an opportunity to advance our understanding and management of MS. AI promises to aid clinicians in MS diagnosis and prognosis improving patient outcomes and quality of life, however ensuring the interpretability and transparency of AI-generated results is going to be key for facilitating the integration of AI into clinical practice.

Purpose of review: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a distinct neuroinflammatory condition characterized by attacks of optic neuritis, transverse myelitis, and other demyelinating events. Though it can mimic multiple sclerosis and neuromyelitis optica spectrum disorder, distinct clinical and radiologic features which can discriminate these conditions are now recognized. This review highlights recent advances in our understanding of clinical manifestations, diagnosis, and treatment of MOGAD.

Recent findings: Studies have identified subtleties of common clinical attacks and identified more rare phenotypes, including cerebral cortical encephalitis, which have broadened our understanding of the clinicoradiologic spectrum of MOGAD and culminated in the recent publication of proposed diagnostic criteria with a familiar construction to those diagnosing other neuroinflammatory conditions. These criteria, in combination with advances in antibody testing, should simultaneously lead to wider recognition and reduced incidence of misdiagnosis. In addition, recent observational studies have raised new questions about when to treat MOGAD chronically, and with which agent. MOGAD pathophysiology informs some of the relatively unique clinical and radiologic features which have come to define this condition, and similarly has implications for diagnosis and management. Further prospective studies and the first clinical trials of therapeutic options will answer several remaining questions about the peculiarities of this condition.

Purpose of review: To review replicated and highlight novel studies of sleep in children and adults with episodic and chronic migraine.

Recent findings: Attack-related sleep symptoms are most common in the prodrome and may represent early activation of the hypothalamus rather than migraine triggers. Interictally, patients with migraine report poor sleep quality and high rates of insomnia symptoms. Cognitive behavioral therapy for insomnia in adults and adolescents with chronic migraine and comorbid insomnia results in significant improvement on their headache burden. Thus far, objective studies report that migraine per se is a not associated with sleep apnea. At the present time, there is minimal evidence that migraine is under circadian influence. The current body of evidence suggests that the insomnia symptoms and poor sleep quality commonly reported by patients with migraine are not attack-related but occur interictally and are a marker of worsening disease. The development of clinical guidelines to approach sleep symptoms and expansion of CBT-I trials in those with episodic migraine would be clinically valuable.

Purpose of the review: To briefly review the latest updates in management in giant cell arteritis, an autoimmune vasculitis affecting the medium to large vessels.

Recent findings: Here, we review the known and newer trends in management of giant cell arteritis. While high dose glucocorticoids remain the mainstay of therapy, immunosuppressive medications are increasingly utilized to reduce the burden and risk of long-term glucocorticoid use. Published guidelines by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) suggest early use of steroid-sparing immunosuppressive medications in patients with recently diagnosed or relapsing giant cell arteritis. Immunosuppressive medications include oral small molecules such as methotrexate and leflunomide and biologics, including the recently Federal Drug Administration (FDA) approved tocilizumab. Glucocorticoids remain the cornerstone of management for newly diagnosed disease but with the increasing use of medications such as IL-6 inhibitors, patients are decreasing steroid use within weeks, thereby limiting risks associated with long-term steroid use.

Purpose of review: Mobile stroke units (MSU) have established a new, evidence-based treatment in prehospital stroke care, endorsed by current international guidelines and can facilitate pre-hospital research efforts. In addition, other novel pre-hospital modalities beyond the MSU are emerging. In this review, we will summarize existing evidence and outline future trajectories of prehospital stroke care & research on and off MSUs.

Recent findings: The proof of MSUs' positive effect on patient outcomes is leading to their increased adoption in emergency medical services of many countries. Nevertheless, prehospital stroke care worldwide largely consists of regular ambulances. Advancements in portable technology for detecting neurocardiovascular diseases, telemedicine, AI and large-scale ultra-early biobanking have the potential to transform prehospital stroke care also beyond the MSU concept. The increasing implementation of telemedicine in emergency medical services is demonstrating beneficial effects in the pre-hospital setting. In synergy with telemedicine the exponential growth of AI-technology is already changing and will likely further transform pre-hospital stroke care in the future. Other promising areas include the development and validation of miniaturized portable devices for the pre-hospital detection of acute stroke. MSUs are enabling large-scale screening for ultra-early blood-based biomarkers, facilitating the differentiation between ischemia, hemorrhage, and stroke mimics. The development of suitable point-of-care tests for such biomarkers holds the potential to advance pre-hospital stroke care outside the MSU-concept. A multimodal approach of AI-supported telemedicine, portable devices and blood-based biomarkers appears to be an increasingly realistic scenario for improving prehospital stroke care in regular ambulances in the future.

Purpose of review: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus.

Recent findings: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures. Primary outcomes included those related to short-term burdens of seizures and the benefits of acute treatments to reduce short-term burdens. Of the 1332 articles identified through PubMed and 17 through other sources, 27 had relevant outcomes and were included in the qualitative synthesis. Seizure emergencies negatively affected short-term quality of life and the ability to conduct normal daily living activities and were associated with physical (injury) and financial (emergency transport, hospitalization) burdens. The use of acute treatment was associated with a rapid return (≤ 1 h) to normal function/self for both patients and caregivers and potentially lower healthcare utilization and costs. Seizure action plans may improve knowledge and comfort with seizure care, empowering patients and caregivers. The short-term burden of seizures can create a substantial negative impact on patients and caregivers. Acute treatments may reduce the short-term burdens of seizures in addition to their well-described role to reduce seizure activity and the risk for status epilepticus.

Purpose of review: Idiopathic intracranial hypertension (IIH) typically affects women of childbearing age, is associated with recent weight gain, and can result in debilitating headache as well as papilledema that can cause vision loss. There have been advances in the medical and surgical treatment of affected patients with IIH that can improve outcomes and tolerability of therapy.

Recent findings: Medical treatment with agents that lower intracranial pressure through pathways other than carbonic anhydrase inhibition are being developed, and medically-directed weight loss as well as bariatric surgery now may be considered as primary therapy. New surgical options including venous sinus stenting have shown efficacy even with cases of severe vision loss. Our treatment options for IIH patients are becoming more diverse, and individualized treatment decisions are now possible to address specific components of the patient's disease manifestations and to lead to IIH remission.

Purpose of review: When compared to ischaemic stroke, there have been limited advances in acute management of intracerebral haemorrhage. Blood pressure control in the acute period is an intervention commonly implemented and recommended in guidelines, as elevated systolic blood pressure is common and associated with haematoma expansion, poor functional outcomes, and mortality. This review addresses the uncertainty around the optimal blood pressure intervention, specifically timing and length of intervention, intensity of blood pressure reduction and agent used.

Recent findings: Recent pivotal trials have shown that acute blood pressure intervention, to a systolic target of 140mmHg, does appear to be beneficial in ICH, particularly when bundled with other therapies such as neurosurgery in selected cases, access to critical care units, blood glucose control, temperature management and reversal of coagulopathy. Systolic blood pressure should be lowered acutely in intracerebral haemorrhage to a target of approximately 140mmHg, and that this intervention is generally safe in the ICH population.

Purpose of review: This review article critically evaluates the latest advances in the surgical treatment of headache disorders.

Recent findings: Studies have demonstrated the effectiveness of innovative screening tools, such as doppler ultrasound, pain drawings, magnetic resonance neurography, and nerve blocks to help identify candidates for surgery. Machine learning has emerged as a powerful tool to predict surgical outcomes. In addition, advances in surgical techniques, including minimally invasive incisions, fat injections, and novel strategies to treat injured nerves (neuromas) have demonstrated promising results. Lastly, improved patient-reported outcome measures are evolving to provide a framework for comparison of conservative and invasive treatment outcomes. Despite these developments, challenges persist, particularly related to appropriate patient selection, insurance coverage, delays in diagnosis and surgical treatment, and the absence of standardized measures to assess and compare treatment impact. Collaboration between medical/procedural and surgical specialties is required to overcome these obstacles.