Current Neurology and Neuroscience Reports最新文献

Purpose of review: Postoperative delirium (POD) is a common complication that has important implications for surgical patients, often leading to both short- and long-term cognitive deficits, worse outcomes, and increased healthcare costs. Given these implications, there may be a benefit in reducing the incidence of POD. Pharmacologic interventions may have the potential to reduce the risk of a patient developing POD.

Recent findings: Recently studied therapies include dexmedetomidine, propofol, haloperidol, ketamine, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, acetaminophen, melatonin/ramelteon, corticosteroids, midazolam, physostigmine, and neostigmine. In addition, the implementation of regional anesthesia and reduction of overall anesthetic depth have been examined. Of these therapies, dexmedetomidine has been studied the most and has the most supporting evidence for prevention of POD, but current studies lack clarity on optimal dosing and timing of dexmedetomidine administration. Acetaminophen, corticosteroids, and melatonin/ramelteon are other plausible medications that have potential for reducing POD incidence, but they all require further investigation. Reduction of anesthetic depth and regional anesthetics are options for anesthetic management that show promise but still lack enough supporting evidence in recent literature to receive a strong recommendation. Future research should focus on identifying optimal strategies for the implementation of the pharmacological options listed, including doses and timing of administration. Attention should be given to dexmedetomidine given its promise demonstrated by recent literature.

Purpose of review: To evaluate the role of sedation vacations in optimizing patient outcomes and enhancing the quality of care in neurological intensive care units (ICUs). We discuss the importance of sedation management in neurocritical care, considering recent research findings and clinical guidelines.

Recent findings: Recent studies have highlighted the significance of sedation interruption protocols in improving patient outcomes in the ICU setting. Evidence suggests that daily sedation interruptions can reduce the duration of mechanical ventilation, ICU length of stay, and mortality rates. However, the implementation of these protocols requires careful consideration of patient-specific factors and a multidisciplinary approach. Sedation vacations play a critical role in neurocritical care by reducing mechanical ventilation duration, ICU stay length, and mortality rates. Despite the benefits, the presence of complications must be addressed to avoid adverse outcomes. Continued research is necessary to refine these strategies and improve guideline quality, ensuring safe and effective sedation management in critically ill neurological patients.

Purpose of review: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive form of lymphoma that can involve the brain, spinal cord, leptomeninges and eyes. PCNSL prognosis continues to be poor, with 5-year survival rates of 30-40%. Therapeutic options are especially limited for relapsed/refractory (r/r) PCNSL. In recent years, studies shed light on the pathogenesis and oncogenic pathways driving PCNSL, leading to the development of novel therapeutics. In this review, we discuss the evidence supporting these novel agents and present ongoing clinical studies.

Recent findings: Key oncogenic drivers of PCNSL include activation of the NFkB pathway, cell cycle dysregulation, somatic hypermutation and immune evasion, leading to the investigation of targeted therapeutics and immunotherapeutics to inhibit these pathways. Such approaches include BTK inhibitors, mTOR/PI3K inhibitors, immunomodulatory agents (IMIDs), immune checkpoint inhibitors and CD19-based CAR T-cells. The therapeutic repertoire for PCNSL is rapidly evolving, and a multi-modality approach including intensive chemotherapy regimens and novel therapies will likely be utilized in the future.

Purpose of review: To describe different pitfalls in the diagnosis of primary cluster headaches (CHs) with the guidance of seven case vignettes.

Recent findings: The question of whether primary CHs and migraines are totally different entities has been long debated. Autonomic features can be detected in as many as 60% of migraine patients. Although some genetic similarities have been found, CACNA1A mutations have not been detected among CH patients with hemimotor aura in contrast to hemiplegic migraine. Recently, functional MRI studies have shown that the left thalamic network was the most discriminative MRI feature in distinguishing migraine from CH patients. Compared to migraine, CH patients showed decreased functional interaction between the left thalamus and cortical areas mediating interception and sensory integration. However, clinically the most significant feature had been the restlessness and agitation seen during headache attacks patients with CHs. This feature is also important in distinguishing cluster patients from other patients having other trigeminal autonomic cephalalgias except for a subset of patients with hemicrania continua. CH is an important member of the group of headache disorders characterized by their association with one or more autonomic features in the trigeminal nerve distribution and termed Trigeminal Autonomic Cephalalgias (TACs). Although CH is a relatively rare condition, judged by the distress it generally causes to the affected individual, early diagnosis and institution of appropriate therapy seem mandatory. Correct diagnosis of CHs needs avoidance of pitfalls. Such pitfalls generally include differentiation from migraine, differentiation from other side locked headache disorders, from other trigeminal autonomic cephalalgias (TACs), and lastly, recognition of rare presentations of cluster-like manifestations with hemiplegic aura and simulating trigeminal and glossopharyngeal neuralgias. Differentiation between primary and symptomatic CHs related to sellar pathologies and systemic medical conditions is of equal importance. In the present review such issues are discussed with the assistance of seven case vignettes.

Purpose of review: Migraine affects a large portion of the world's population. Migraine encompasses a broad range of symptoms, with broad reaching ramifications in the form of Health-Related Quality of Life (HRQoL) factors. In our review we sought to understand the aspects encompassing the burden of disease on both an individual and population level. Furthermore, we reviewed the development and incorporation of Patient Reported Outcome Measures (PROM), questionnaires that assess HRQoL in real time, in how they have been incorporated in clinical research up to now and how they can be utilized in clinical practice moving forward.

Recent findings: It has been shown that there is much heterogeneity within the field in PROM development processes as well as their utilization in episodic migraine (EM) clinical trials. Furthermore, they are inconsistently used in clinical practice. Among the most commonly used PROMs, the MSQv2.1 is among the most valid and reliable. Beyond that, it also shows promise to help in guidance of clinical management of migraine.

Purpose of review: This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing and recovery.

Recent findings: The immune response is now considered a key element in the pathophysiology of TBI, with consequences far beyond the acute phase after injury. A delicate equilibrium is crucial for a healthy recovery. When this equilibrium is disrupted, chronic inflammation and immune imbalance can lead to detrimental effects on survival and disability. Globally, traumatic brain injury (TBI) imposes a substantial burden in terms of both years of life lost and years lived with disability. Although its epidemiology exhibits dynamic trends over time and across regions, TBI disproportionally affects the younger populations, posing psychosocial and financial challenge for communities and families. Following the initial trauma, the primary injury is succeeded by an inflammatory response, primarily orchestrated by the innate immune system. The inflammasome plays a pivotal role during this stage, catalyzing both programmed cell death pathways and the up-regulation of inflammatory cytokines and transcription factors. These events trigger the activation and differentiation of microglia, thereby intensifying the inflammatory response to a systemic level and facilitating the migration of immune cells and edema. This inflammatory response, initially originated in the brain, is monitored by our autonomic nervous system. Through the vagus nerve and adrenergic and cholinergic receptors in various peripheral lymphoid organs and immune cells, bidirectional communication and regulation between the immune and nervous systems is established.

Purpose of review: The identification of isocitrate dehydrogenase (IDH) mutations has led to a transformation in our understanding of gliomas and has paved the way to a new era of targeted therapy. In this article, we review the classification of IDH-mutant glioma, standard of care treatment options, clinical evidence for mutant IDH (mIDH) inhibitors, and practical implications of the recent landmark INDIGO trial.

Recent findings: In the phase 3 randomized placebo-controlled INDIGO trial, mIDH1/2 inhibitor vorasidenib increased progression-free survival among non-enhancing grade 2 IDH-mutant gliomas following surgery. This marks the first positive randomized trial of targeted therapy in IDH-mutant glioma, and led to the US Food and Drug Administration's approval of vorasidenib in August 2024 for grade 2 IDH-mutant glioma. Vorasidenib is a well-tolerated treatment that can benefit a subset of patients with IDH-mutant glioma. Targeting mIDH also remains a promising strategy for select groups of patients excluded from the INDIGO trial. Ongoing and future studies, including with new agents and with combination therapy approaches, may expand the benefit and unlock the potential of mIDH inhibitors.

Purpose of review: This review seeks to examine the prevalence, pathophysiology, diagnostic challenges, and treatment strategies for movement disorders in patients with systemic lupus erythematosus (SLE).

Recent findings: In recent years, the spectrum and number of autoimmune movement disorders has rapidly expanded with the identification of neuronal and paraneoplastic antibodies which should be considered in the differential for patients with acute to subacute development of a movement disorder. The identification of SLE in a patient with a new onset movement disorder may lead to earlier treatment with immune therapies especially if other systemic manifestations are present. Current treatment for SLE-associated movement disorders involves co-management with rheumatology and is based on expert clinical opinion on symptomatic management. Further understanding of the contributing pathophysiology may lead to advancements in therapeutic approaches.

Purpose of review: Stroke incidence and outcomes are disproportionately unfavorable among Indigenous populations in Western colonized countries. These inequities are often attributed to poor health literacy. This paper summarizes recent evidence on the topic of Indigenous health literacy, describes current gaps, and proposes priorities for future work/research.

Recent findings: Traditionally, much focus has been placed on improving health literacy for Indigenous Peoples as a key intervention to address Indigenous stroke and other health disparities. Recent literature, however, challenges this approach as it risks stigmatization and marginalization and portrays the deficiencies as sitting with Indigenous people. Increasingly, an emphasis is placed on the need for health literacy approaches to be culturally responsive for the populations of interest, for institutions to provide high quality culturally relevant stroke care, and for providers to upskill in cultural safety to better meet the needs of Indigenous patient populations. Very little evidence exists to indicate that stroke care providers are meeting these needs. To close the health gap and improve stroke care for Indigenous Peoples, the focus needs to shift from promoting health literacy among Indigenous Peoples to providing high quality culturally relevant health care. More research into this topic and monitoring of progress over time is needed.

Purpose of review: This review examines the role of different viral infections in epileptogenesis, with a focus on Herpesviruses such as Human Herpesvirus 6 (HHV-6) and Epstein Barr Virus (EBV), Flaviviruses, Picornaviruses, Human Immunodeficiency Virus (HIV), Influenzavirus and Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2).

Recent findings: A growing literature on animal models, such as the paradigmatic Theiler's murine encephalomyelitis virus (TMEV) model, and clinical investigations in patients with epilepsy have started to elucidate cellular mechanisms implicated in seizure initiation and development of epilepsy following viral infections. A central role of neuroinflammation has emerged, with evidence of activation of the innate and adaptive immunity, dysregulation of microglial and astrocytic activity and production of multiple cytokines and other inflammatory mediators. Several chronic downstream effects result in increased blood-brain barrier permeability, direct neuronal damage, and modifications of ion channels ultimately leading to altered neuronal excitability and seizure generation. Key findings underscore the complex interplay between initial viral infection, neuroinflammation, and later development of epilepsy. Further research is needed to elucidate these mechanisms and develop targeted interventions.