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.