The central neurotoxicity of the excitatory amino acid neurotransmitter glutamate has been postulated to participate in the pathogenesis of the neuronal cell loss associated with several neurological disease states, but the complexity of the intact nervous system has impeded detailed analysis of the phenomenon. In the present study, glutamate neurotoxicity was studied with novel precision in dissociated cell cultures prepared from the fetal mouse neocortex. Brief exposure to glutamate was found to produce morphological changes in mature cortical neurons beginning as quickly as 90 sec after exposure, followed by widespread neuronal degeneration over the next hours. Quantitative dose- toxicity study suggested an ED50 of 50–100 microM for a 5 min exposure to glutamate. Immature cortical neurons and glia were not injured by such exposures to glutamate. Uptake processes probably do not limit GNT in culture, as the uptake inhibitor dihydrokainate did not potentiate GNT. Possibly reflecting the lack of uptake limitation, glutamate was found to be actually more potent than kainate as a neurotoxin in these cultures, a dramatic reversal of the in vivo potency rank order. Some neurons regularly survived brief glutamate exposure; these possibly glutamate-resistant neurons had electrophysiologic properties, including chemosensitivity to glutamate, that were grossly similar to those of the original population.
Background Physical activity volume (PAV) has been linked to a wide range of health outcomes; however, its association with incident nervous system diseases remains incompletely understood. This study explored their relationship using data from UK Biobank. Methods A retrospective cohort study was conducted involving 278,306 participants from the UK Biobank. PAV was quantified as metabolic equivalent of task (MET) minutes per week, derived from self-reported physical activity levels, and categorized into three groups. Incident cases of nervous system diseases were identified through ICD-10 codes obtained from hospital inpatient records, death registries, and self-reports. Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for a series of covariates. Restricted cubic splines were applied to assess potential non-linear associations. Results Women and individuals aged 60 years or older exhibited higher incidence rates of nervous system diseases. After multivariable adjustment, higher PAV was significantly associated with a lower risk of overall nervous system diseases (HR < 1). A non-linear dose–response relationship was observed, with the lowest risk occurring at a PAV level of 1,356 MET-min/week. Subgroup analyses indicated that elevated PAV conferred protective effects against several specific conditions. Conversely, higher PAV was associated with an increased risk of meningitis. Conclusion Increased levels of physical activity are associated with a reduced risk of numerous nervous system diseases, with optimal protection observed at approximately 1,356 MET-min/week. These findings support the promotion of moderate-to-vigorous physical activity as a preventive strategy for neurological disorders, particularly among high-risk populations.
Emma Larsson, Emma Larsson, Ellen Iacobaeus
et al.
BackgroundSurgery is a common exposure. Multiple sclerosis (MS) is a chronic neuroinflammatory demyelinating disease of the central nervous system and a systemic inflammatory activation caused by surgery may result in exacerbation of the disease. It is unknown how surgical procedures affect morbidity and mortality rates in MS.ObjectivesThis study aimed to investigate morbidity associated with surgical interventions in MS patients by assessing disease burden before and after surgery. Non-MS patients were used as controls, allowing for comparisons of disease burden and mortality between the two groups.MethodsThe cohort study analyzed data from the Swedish Perioperative Register, including 3,022 MS patients among over 1.5 million surgeries performed between January 2019 and March 2023. Disease burden was measured as the number of pre-specified ICD-codes before and after surgery.ResultsWe demonstrated that MS patients exhibited a higher mean number of diagnoses before and after surgery compared to controls. Specifically, the number of diagnoses peaked in the first month post-surgery but returned to baseline within three to 4 months. Notably, there were no significant differences in 30-day or 365-day mortality rates between MS and non-MS patients, highlighting the relative safety of surgical interventions for persons with MS.ConclusionThe findings suggest that surgery is generally safe for patients with MS, indicating that MS should not preclude necessary surgical interventions. Nevertheless, tailored preoperative assessments and postoperative care strategies are essential to address the unique health challenges encountered by MS patients, ensuring optimal surgical outcomes and monitoring for potential complications.
Carolin Luisa Hoehne, Aysenur Sahin, Lucas Hendrik Overeem
et al.
Abstract Introduction In clinical practice, switching between preventive treatments is common in patients with chronic migraine when efficacy is insufficient or tolerability is poor. With the advent of more targeted therapies, such as onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies, treatment options have expanded, yet evidence to guide sequencing decisions remains limited. The aim of this study was to investigate the real-world effectiveness of switching between onabotulinumtoxinA and erenumab and vice versa in patients with chronic migraine who showed inadequate response to their initial preventive treatment. Methods This retrospective real-world study included patients with chronic migraine treated at the Headache Center, Charité—Universitätsmedizin Berlin between October 2022 and December 2024. Eligible patients had received both onabotulinumtoxinA and erenumab in sequence, switching as a result of insufficient efficacy or tolerability. A very good response was defined as a ≥ 50% reduction in monthly headache days in the third month after the switch. Results Out of 632 screened patients, 78 met the inclusion criteria (84.6% female; mean age 43 ± 14 years). Of these, 54 switched from onabotulinumtoxinA to erenumab, and 24 from erenumab to onabotulinumtoxinA. A very good response was observed in 14 patients (17.9%): 10/54 (18.5%) after switching to erenumab and 4/24 (16.7%) after switching to onabotulinumtoxinA. Conclusion Sequential preventive treatment with onabotulinumtoxinA and erenumab resulted in a very good response in about one-fifth of patients. Although both treatments target the CGRP pathway, their distinct mechanisms of action may still provide benefit when switching therapies after initial failure.
Wolfgang H. Oertel, Martin T. Henrich, Elisabeth Sittig
et al.
Abstract Background Multiple system atrophy (MSA) is a rare, rapidly progressive alpha-synucleinopathy characterized by autonomic dysfunction, parkinsonism and marked cerebellar ataxia, with very limited treatment options. N-acetyl-DL-leucine (ADLL) (Tanganil™), a racemic derivative of leucine is usually well tolerated and has shown promise in improving cerebellar symptoms and reducing REM sleep behavior disorder (RBD), a common non-motor dream-sleep disorder feature of alpha-synucleinopathy. Given this dual potential, we treated three patients with advanced-stage MSA under compassionate use rules. Case presentations Three patients with advanced-stage MSA and severe cerebellar symptoms—two of whom also had moderate RBD—were treated with ADLL (TanganilTM), titrated to 5g/day over 10 days. While both patients with RBD reported self-assessed decrease of RBD symptoms within 2–3 weeks on the full dosage (approximately four weeks after treatment initiation), all three patients had major worsening of gait and balance during the same period, leading to sudden falls and overall health decline. These adverse events prompted early discontinuation of therapy. Gait improved within two weeks after discontinuation of therapy in two patients. In parallel, the RBD phenotype reoccurred. In the third, who had very advanced MSA and concurrent infections, gait only slowly improved over time and it remains unclear whether his worsening of truncal ataxia was attributable to ADLL (TanganilTM), or whether it was related to his concurrent infections with slow recovery. Conclusions While ADLL improved RBD, it was poorly tolerated in these three patients with advanced-stage MSA of predominantly cerebellar type. Further studies are needed to evaluate its safety and efficacy in different, preferably early, stages of MSA.
The diagnosis of multiple sclerosis (MS) is through clinical assessment and supported by investigations. There is no single accurate and reliable diagnostic test. MS is a disease of young adults with a female predominance. There are characteristic clinical presentations based on the areas of the central nervous system involved, for example optic nerve, brainstem and spinal cord. The main pattern of MS at onset is relapsing-remitting with clinical attacks of neurological dysfunction lasting at least 24 hours. The differential diagnosis includes other inflammatory central nervous system disorders. Magnetic resonance imaging of the brain and lumbar puncture are the key investigations. New diagnostic criteria have been developed to allow an earlier diagnosis and thus access to effective disease modifying treatments.
Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.
ObjectiveThis study aimed to investigate the association between the risk of suicidal behaviors and student-supervisor relationships and subjective family socioeconomic status (SFSS) in medical graduate students, and to propose preventive strategies to reduce the suicidal risk among medical graduate students.Materials and methodsA total of 1,310 validated questionnaires were collected from medical graduate students, which included demographic information, study programs, the Suicidal Behaviors Questionnaire-Revised (SBQ-R) questionnaire, the Leader-Member Exchange 7 (LMX-7) questionnaire, and SFSS by MacArthur Scale. Multiple regression analysis was employed to examine the associations between variables and adjust for confounders. A moderation analysis, containing simple slope analysis and Johnson-Neyman interval plots were used to analyze the moderating effect of the SFSS in the association of SBQ-R and LMX-7 scores.ResultsA total of 88 participants (6.7%) were at risk of suicidal behaviors. In the high-quality student-supervisor relationship group (LMX-7 score ≥ 25), SFSS was significantly higher than in the low- and moderate-quality relationship group (p=0.002). The median SBQ-R score and proportion of suicide risk was significantly lower (p<0.001) in the high-quality student-supervisor relationship group. Multiple regression analysis indicated LMX-7 scores (β=-0.098, 95% CI [-0.118, -0.077], p<0.001) and SFSS (β=-0.073, 95% CI [-0.127, -0.019], p=0.008) were significantly negatively associated with SBQ-R, whereas the interaction term of SFSS with LMX-7 (β=0.018, 95% CI [0.007, 0.029], p=0.001) showed a significant positive association with SBQ-R. The Johnson-Neyman interval showed a significant association between LMX-7 and SBQ-R scores only when SFSS was less than 7.82 (p<0.05).ConclusionThe risk of suicidal behaviors was associated with student-supervisor relationships and SFSS among medical graduate students. Poor relationships with supervisor were associated with an elevated risk of suicidality, and SFSS moderated this association. Educators should pay increased attention to the suicidal risk of medical graduate students with poor supervisor relationships, especially those from families with low SFSS, and provide timely preventive strategies.
Mohamed A. Al‐Shamrani, Hussain Bin Amir, Fawaz F. Alotaibi
et al.
Background In acute ischemic stroke caused by large‐vessel occlusion, tissue viability is dependent on the blood supply from leptomeningeal collaterals until reperfusion is achieved. Rapid and accurate evaluation of baseline collateral status is a key marker of eligibility for endovascular therapy but can be challenging to interpret using source images of the computed tomography angiography (SI‐CTA). Our objective was to assess whether the use of thick maximum‐intensity projection computed tomography angiography (MIP‐CTA) improves interrater agreement for evaluation of baseline collaterals status between stroke trainees and an expert stroke neurologist. Methods An expert stroke neurologist and 2 stroke trainees independently reviewed images from 40 brain CTA scans with anterior circulation large‐vessel occlusion and assessed collateral status using the Tan collateral scoring system using SI‐CTA in the first reading and then using MIP‐CTA in the second reading. We calculated interrater agreement and recorded the total time needed in each reading. Results Interrater agreement was fair between the 2 stroke fellows and stroke expert when using SI‐CTA (κ=0.45 with 52.5% agreement). After using MIP‐CTA, interrater agreement improved to moderate (κ=0.69 with 70% agreement). The median reading time was 1.89 minutes per scan using SI‐CTA and 1.00 minute per scan using MIP‐CTA (P<0.0001). Conclusions We show that using MIP‐CTA, when compared with SI‐CTA, shortens interpretation time and improves interrater agreement between stroke trainees and a stroke imaging expert for the evaluation of baseline collaterals in patients presenting with anterior circulation large‐vessel occlusion.
Neurology. Diseases of the nervous system, Diseases of the circulatory (Cardiovascular) system
C. Santoyo-Medina, I. Elorriaga Mínguez, I. Galán Cartañá
et al.
Background: According to the literature, patients with multiple sclerosis (MS) are less active and show higher levels of sedentary behaviour than the general population of the same age range. This study aims to explore the impact of the COVID-19 pandemic on levels of physical activity in these patients. Methods: An online survey was launched between May and June 2021, aimed at patients with MS in Spain, regarding their physical activity habits (performance, intensity, and activities carried out) prior to and during the COVID-19 pandemic. Results: A total of 230 patients responded to the survey, of whom 69.6% were women, 52.6% were between 45 and 64 years old, and 41.3% had moderate disability (Patient-Determined Disease Steps score 3–5). A total of 82.2% of the respondents reported being physically active before the pandemic, decreasing to 75.9% during the pandemic [P=.057 (McNemar test)]. Activities at sports centres decreased and exercise at home, as well as walking, increased. A total of 61.7% reported not using any technology during physical activity practise before the pandemic. For 63.9% of respondents, the preferred format after the pandemic was the mixed format combining in-person and remote physical activity. Conclusions: Physical activity levels decreased during the COVID-19 pandemic among patients with MS. Although SARS-CoV-2 is currently in an endemic phase, this experience should be helpful for the development and implementation of interventions to facilitate physical activity among patients with MS. Resumen: Introducción: Según la literatura, las personas con esclerosis múltiple (PcEM) son menos activas y muestran niveles más altos de sedentarismo que la población de su mismo rango de edad. El objetivo de este estudio es conocer cuál fue el impacto de la pandemia por COVID-19 en el nivel de actividad física (AF) de las PcEM. Métodos: Estudio mediante una encuesta online lanzada entre mayo y junio del 2021, dirigida a PcEM en territorio español, sobre los hábitos de AF (rendimiento, intensidad y actividades realizadas) previos y durante la pandemia por COVID-19. Resultados: Un total de 230 PcEM contestaron la encuesta, de los cuales un 69.6% eran mujeres, un 52,6% tenían entre 45 y 64 años y un 41,3% una discapacidad moderada (PDSS 3–5). Antes de la pandemia, el 82,2% de los encuestados referían ser físicamente activos, reduciéndose a un 75,9% durante la pandemia (McNemar; p = .057). Disminuyeron las actividades en centros deportivos y se incrementaron las desarrolladas en el domicilio, así como caminar como ejercicio. Un 61,7% refería no utilizar tecnología durante la práctica de AF antes de la pandemia. El formato de preferencia tras la pandemia para el 63,9% fue el formato mixto combinando AF presencial y remota. Conclusiones: La AF disminuyó durante la pandemia por COVID-19 entre las PcEM. Aunque actualmente se encuentra en una fase endémica, esta experiencia debería ser un impulso para el desarrollo y aplicación de intervenciones que faciliten su práctica entre las PcEM.
Even though severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed to principally affect the respiratory system, neurological involvements have already been reported in some published work. We have reviewed original articles, case reports, and existing open-source data-sets to delineate the spectrum of neurological disorders potentially observed in SARS-CoV-2 positive cases. Neurological involvement in coronavirus disease 2019 (COVID-19) corresponds to three situations: (a) neurological manifestations of viral infection, (b) post-infective neurological complications, and (c) infection in patients with neurological co-morbidity. Neurological manifestations can further be subdivided into the central nervous system (headache, dizziness, alteration of the sensorium, ataxia encephalitis, stroke, and seizures) and peripheral nervous system (skeletal muscle injury and peripheral nerve involvement including hyposmia and hypogeusia) symptomatology. Post-infective neurological complications include demyelinating conditions. Reduced mobility and dementia as co-morbidities may predispose a patient to have a viral infection. It is concluded that the pandemic of COVID-19 presents for a neurologist some unique challenges. We observe that SARS-CoV-2 may have various neurological manifestations and in many cases, neurological features may precede typical respiratory symptoms.
Heather D. Ots, Jovanna A. Tracz, Katherine Vinokuroff
et al.
Immune-inflammatory conditions in the central nervous system (CNS) rely on molecular and cellular interactions which are homeostatically maintained to protect neural tissue from harm. The CD40–CD40L interaction upregulates key proinflammatory molecules, a function best understood in the context of infection, during which B-cells are activated via CD40 signaling to produce antibodies. However, the role of CD40 in neurological disease of non-infectious etiology is unclear. We review the role of CD40–CD40L in traumatic brain injury, Alzheimer’s Disease, Parkinson’s Disease, stroke, epilepsy, nerve injury, multiple sclerosis, ALS, myasthenia gravis and brain tumors. We also highlight therapeutic advancements targeting the CD40 system to either attenuate the neuroinflammatory response or leverage the downstream effects of CD40 signaling for direct tumor cell lysis.