This episode reviews two articles "Traumatic Encephalopathy Syndrome in the Late Effects of Traumatic Brain Injury (LETBI) Study Cohort" and "Dementia Risk Due to Traumatic Brain Injury in Subtypes of Dementia in the Welsh Population," both investigate the long-term consequences of traumatic brain injury (TBI). The first study aims to operationalize and test the applicability of traumatic encephalopathy syndrome (TES) diagnostic criteria in individuals with TBI, exploring whether core clinical features of TES are prevalent regardless of repetitive head impact (RHI) exposure. Simultaneously, the second study assesses the association between TBI and the overall risk of dementia, as well as its specific subtypes, using extensive electronic health records to understand how TBI impacts neurodegenerative vulnerability.

This original investigation published in JAMA Neurology concerning the association between influenza, oseltamivir treatment, and serious neuropsychiatric events in children and adolescents. The study, conducted retrospectively using data from Tennessee Medicaid, aimed to determine if oseltamivir, a common antiviral, is linked to these events or if the influenza infection itself is the primary factor. The findings indicate that while influenza infection increases the risk of neuropsychiatric events, oseltamivir treatment was associated with a reduced risk of these complications compared to untreated influenza. This research supports the use of oseltamivir for preventing influenza-related neurological and psychiatric issues in the pediatric population.

This article published in 2025 by Huw Green and Jon Stone, focuses on health anxiety within neurological settings. It explains health anxiety as a distinct, treatable psychological disorder characterized by excessive worry about illness and compulsive "safety behaviors" like seeking reassurance. The authors distinguish health anxiety from normal health concerns and functional neurological disorders, emphasizing that reassurance is often counterproductive. The article also offers practical suggestions for neurologists on how to accurately diagnose and educate patients about health anxiety, facilitating successful referrals for psychological treatment, particularly cognitive behavioral therapy (CBT).

Laser interstitial thermal therapy (LITT) is an increasingly standard surgical tool for ablating epileptic foci, and the Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) registry, representing the largest prospective multicenter cohort, aimed to describe seizure outcomes, procedural outcomes, and safety data for LITT in mesial temporal lobe epilepsy (MTLE). LITT was found to be well tolerated and effective for drug-resistant MTLE, showing clinically meaningful seizure outcomes and quality of life (QOL) improvements. At two-year follow-up, 58.4% of patients achieved Engel 1 outcomes (seizure-free or non-disabling auras) and 57.2% achieved International League Against Epilepsy (ILAE) 1/2 outcomes (seizure-free or rare seizures), which are comparable to anterior temporal lobectomy (ATL) and significantly better than medical management (18.5 odds ratio for Engel 1 outcome). The procedure demonstrated significant QOL improvements at nearly all assessed time points, affecting domains like seizure worry, medication effects, and social functioning, with outcomes similar to ATL for seizure-free patients. Procedurally, LITT is considered expedient, with a median hospital stay of 1.3 days (compared to 3 days for resection), a low 90-day readmission rate of 7.7%, and minimal mean discharge head pain of 2.1 on a 0-10 scale. Adverse events occurred in 16.5% of patients, mostly mild and transient, with permanent deficits observed in 5.5% of patients, which is lower than reported for ATL. The study also noted a decrease in postoperative intensive care unit (ICU) admissions over time, suggesting increased familiarity with the procedure, and highlighted that the 14 pediatric patients in the cohort had similar outcomes to adults. Overall, these findings strongly support LITT as a safe, effective, and minimally invasive treatment option for drug-resistant MTLE.

This paper investigates the heterogeneity of autoantibodies in patients with myasthenia gravis (MG), focusing on their diverse pathogenic properties and temporal fluctuations. The researchers utilized advanced cell-based assays to analyze serum samples, revealing that different immunoglobulin isotypes (IgG, IgM, IgA) and IgG subclasses contribute to the disease through varying mechanisms like complement activation, receptor internalization, and acetylcholine binding site blocking. The findings suggest that a comprehensive understanding of each patient's unique autoantibody profile could lead to more personalized and effective therapeutic strategies for MG.

Valosin-Containing Protein (VCP) myopathy, also known as Multisystem Proteinopathy (MSP1) or Inclusion Body Myopathy associated with Paget disease of bone and Frontotemporal Dementia (IBMPFD), is a complex, progressive, autosomal dominant adult-onset disorder caused by mutations in the VCP gene. The VCP protein, also called p97, is a highly conserved ATPase crucial for maintaining cellular protein homeostasis (proteostasis) through mechanisms like the ubiquitin-proteasome system (UPS) and autophagy, as well as other functions like membrane fusion and genomic integrity. Pathogenic mutations in VCP disrupt these processes, leading to the accumulation of ubiquitin-positive protein aggregates, a hallmark feature. The disease presents with significant clinical heterogeneity, even within families, commonly affecting muscle (Inclusion Body Myopathy), bone (Paget disease of bone), and brain (Frontotemporal Dementia), and can also be associated with amyotrophic lateral sclerosis (ALS) or other neurological phenotypes like peripheral neuropathy and parkinsonism. Muscle biopsies, a key diagnostic tool, consistently show features such as muscle fiber atrophy (87.5% of cases), rimmed vacuoles (72.3%), endomysial fibrosis (58.0%), and protein aggregates (51.8%), often staining positive for p62 and VCP. Notably, degenerative niches, focal areas of muscle degeneration with atrophic fibers embedded in fibrotic and fatty tissue, were observed in over 30% of biopsies and are proposed as starting points for disease progression. These histopathologic findings are generally consistent across different clinical phenotypes and VCP genetic variants, despite variations in VCP's ATPase activity, though some discrepancies between clinical, neurophysiological, and biopsy findings can occur. Currently, there is no cure, with treatment focusing on symptomatic management and supportive care. However, research is actively exploring targeted therapies, including VCP inhibitors like CB-5083, which show promise in preclinical studies by addressing the overactivity of mutant VCP.

This comprehensive report from the American Academy of Neurology, in collaboration with the American Congress of Rehabilitation Medicine and the National Institute on Disability, Independent Living, and Rehabilitation Research, provides updated guidelines for managing prolonged disorders of consciousness (DoC) in both adults and children. It outlines diagnostic accuracy improvements, including the use of standardized assessments and multimodal evaluations, while emphasizing the importance of serial assessments due to fluctuating patient states. The document offers detailed prognostic recommendations, especially concerning traumatic versus non-traumatic injuries, and stresses the need for early family counseling regarding long-term care and disability. Finally, it addresses treatment approaches, notably recommending amantadine for specific adult DoC cases, and advises caution regarding unvalidated therapies.

This article presents a multicenter cohort study examining the influence of comorbidities on outcomes and infectious complications in patients with autoimmune encephalitis (AE). The study analyzed data from 308 adult patients with common AE variants, identifying various preexisting conditions (PECs) and secondary diagnoses. Key findings indicate that psychiatric PECs are an independent risk factor for unfavorable outcomes, while severe infections during hospitalization, though common, were not associated with worse long-term results. The authors emphasize the need for integrated care and incorporating comorbidities into prognostic models for AE patients.

This systematic review and individual participant data meta-analysis of randomized controlled trials focuses on the optimal timing for initiating direct oral anticoagulants (DOACs) in patients who have experienced an acute ischemic stroke alongside atrial fibrillation. The study, known as CATALYST, analyzes data from four major trials (TIMING, ELAN, OPTIMAS, and START) to determine if starting DOACs early (within 4 days) significantly reduces the risk of recurrent stroke or hemorrhage. The findings suggest that early DOAC initiation is beneficial in reducing a composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke within 30 days without increasing the risk of bleeding complications. This robust analysis aims to inform clinical practice by providing clearer guidance on anticoagulation timing.

This single-center retrospective cohort study investigates small vessel predominant primary CNS vasculitis (sv-PCNSV), a rare autoimmune disorder affecting brain and spinal cord blood vessels. Researchers analyzed data from 26 patients with biopsy-proven sv-PCNSV to understand their clinical features and the effectiveness of different treatments. The study compared an early intensive treatment (EIT) group receiving cyclophosphamide within three months of immunosuppression with an escalation treatment (ESC) group given initial glucocorticoids. Findings indicate that EIT was associated with a significantly shorter time to remission (5 months vs. 19 months), highlighting the importance of timely and aggressive treatment for this condition. While all patients in the EIT group achieved remission, 78.6% did in the ESC group, suggesting a benefit from early cyclophosphamide.

This review article from Neurology Neuroimmunology & Neuroinflammation, centers on the growing significance of neurofilament light chain (NfL) assays in managing multiple sclerosis (MS). It explains how NfL levels in blood can indicate neuroaxonal damage, offering a less invasive method than traditional MRI for predicting disease progression and monitoring treatment effectiveness in MS patients. While highlighting the potential of NfL as a prognostic and monitoring biomarker, the article also addresses current challenges in its widespread clinical application, such as the need for standardized measurements and established reference ranges, as well as the influence of confounding factors like age and other health conditions. The authors ultimately suggest that NfL, especially when combined with other biomarkers, holds promise for personalizing MS treatment and improving patient outcomes.

This research article explores the potential link between nucleoside reverse transcriptase inhibitors (NRTIs), medications used for HIV and hepatitis B, and a reduced risk of Alzheimer's disease (AD). The authors hypothesize that NRTIs' ability to inhibit inflammasome activation, a process implicated in AD, contributes to this protective effect. Through a retrospective analysis of two extensive health insurance databases—the United States Veterans Health Administration and MarketScan—the study found a significantly lower incidence of AD in individuals exposed to NRTIs. The findings suggest a rationale for further clinical trials to investigate inflammasome inhibitors, like NRTIs or their less toxic derivatives, as potential treatments for AD.

This paper is a systematic review and meta-analysis published in the Journal of Stroke concerning lipoprotein(a) and its relationship to stroke outcomes. The authors investigated the association of elevated lipoprotein(a) levels with stroke recurrence and functional outcomes in patients who have experienced ischemic stroke or transient ischemic attack. The study synthesized data from multiple studies, comprising over 17,900 patients, to conclude that higher lipoprotein(a) levels are significantly linked to increased stroke recurrence and poorer functional recovery. The research highlights lipoprotein(a) as a potential biomarker and therapeutic target for preventing subsequent strokes.

This scientific study investigated the use of serum neurofilament light chain (sNFL), particularly when adjusted for age and BMI as z-scores (zNFL), as a biomarker for chronic inflammatory demyelinating polyneuropathy (CIDP). Analyzing a large cohort of patients with immune-mediated neuropathies, the researchers found that elevated zNFL correlated with increased disease severity in patients with typical CIDP, especially in the early stages of the illness. A zNFL score above 2 in the early phase of typical CIDP was associated with more severe motor dysfunction and a lack of response to initial standard treatments, suggesting that this biomarker could help identify patients needing more aggressive, early immunotherapy and potentially distinguish between typical and atypical forms of CIDP. The study concludes by recommending sNFL measurement with z-score analysis as a valuable tool for CIDP diagnosis, assessment of severity, and treatment guidance in clinical practice.

This is a research article from the New England Journal of Medicine detailing the findings of the SELECT-GCA clinical trial, which investigated a potential new treatment for giant-cell arteritis. The trial randomly assigned patients to receive either upadacitinib at different doses or a placebo, in combination with a glucocorticoid taper. The results indicated that a 15 mg dose of upadacitinib was more effective than placebo in achieving sustained remission and reducing glucocorticoid exposure. The study also reviewed the safety profile of upadacitinib in this patient population.

This comprehensive review focuses on validated techniques used by clinicians to assess functional motor weakness, also known as functional neurological symptom disorder, which is a common presentation in neurology. The article discusses the importance of employing specific, studied examination methods to distinguish functional weakness from objective neurological weakness, which arises from structural or electrophysiological causes. Several diagnostic signs are described, including Hoover's sign, give-way weakness, the abductor sign, the abduction finger sign, the spinal injuries center test, motor inconsistency, drift without pronation, paradoxical wrist flexion, and the elbow flex-ex sign, detailing their techniques, interpretation, and limitations based on existing research. The review emphasizes that interpreting these findings should occur within a full neurological examination, potentially using multiple techniques to improve diagnostic accuracy and patient care.

This paper serves as a comprehensive review of approaches for treating neuropsychiatric symptoms in Parkinson's disease (PD). It highlights that these non-motor symptoms are highly prevalent, significantly impair quality of life for both patients and caregivers, and often appear before motor symptoms. Despite recent advancements in diagnosis and management, treatment options, including both pharmacological and non-pharmacological therapies, remain limited due to the complex underlying brain changes in PD. The review summarizes current treatments for cognitive impairment, psychosis, depression, anxiety, apathy, and impulse control disorders, while also outlining ongoing research efforts to address the existing therapeutic gaps. Ultimately, the paper emphasizes that the treating neurologist's expertise is crucial for tailoring individualized treatment plans in this challenging context.

This multicenter cohort study investigated the effectiveness of rituximab in preventing relapses in adult patients diagnosed with anti-NMDAR antibody-mediated encephalitis. Researchers evaluated the impact of a single course of rituximab on the time to first relapse and explored the duration of its effect, specifically at six and twelve months following treatment. The findings suggest that a single rituximab course is associated with a reduced risk of relapse, with the protective effect lasting for approximately six months. These results highlight the potential benefit of rituximab in managing this condition and suggest optimal redosing intervals for select patients.

This episode combines two articles and discusses the importance of laboratory expertise in accurately diagnosing autoimmune neurological syndromes, particularly autoimmune encephalitis and paraneoplastic syndromes, which are often difficult to identify due to overlapping symptoms and low prevalence. The author reviews two companion studies evaluating commercially available tissue-based assays for detecting antibodies against intracellular and surface antigens. The studies reveal significant limitations in the sensitivity and specificity of these commercial tests when used as standalone screening tools, highlighting the risk of both false positives and false negatives. Ultimately, the piece emphasizes the need for multimodal testing, skilled interpretation of results, and interdisciplinary communication between clinicians and laboratory staff to ensure reliable diagnosis and improve patient outcomes.

This paper provides a comprehensive review of repeat expansion disorders, focusing on their significance in neurology. It explains how abnormal expansions of DNA repeats cause a wide range of neurological conditions, highlighting the diagnostic challenges and opportunities for management. The authors discuss the molecular characteristics of these disorders, including repeat size, location, and inheritance patterns, and detail the clinical features like anticipation and heterogeneity that can aid in diagnosis. Finally, the piece outlines the evolution and current state of genetic testing methods, emphasizing the increasing role of whole-genome sequencing and bioinformatics tools in detecting these complex genetic variations.