Journal of Neurology最新文献

Introduction: Weight loss can cause or exacerbate peripheral nerve disorders, including peripheral neuropathy and entrapments. Novel antihyperglycaemic agents, including glucagon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors, may cause weight loss in addition to their effects on glucose levels.

Methods: Retrospective cohort review from 2020 to 2024 of adult patients undergoing electrodiagnostic evaluation for suspected peripheral nerve dysfunction. Cases were included if there was clinical and/or electrodiagnostic confirmation of peripheral nerve disorder with temporal association (onset < 12 months) to use of GLP1R agonists, SGLT2 inhibitors, or dipeptidyl peptidase-4 inhibitors.

Results: Five cases are described (78 M with femoral and fibular neuropathy, 58 F with fibular neuropathy, 85 M with fibular neuropathy, 48 M with median nerve entrapments and sensory peripheral neuropathy, 45 M with median and ulnar nerve entrapments and sensory peripheral neuropathy) all temporally associated with weight loss and use of GLP1R agonists or SGLT2 inhibitors.

Discussion: Neuropathy may develop following rapid weight loss or normalization of hyperglycaemia during treatment with GLP1R agonists or SGLT2 inhibitors. The underlying pathogenesis is unclear, but is unlikely due to direct effect of these medications on peripheral nerves. Caution is recommended and further work to establish safe targets for HbA1c and weight loss is needed.

Background: Serum neurofilament light chain (sNfL) is an established biomarker of disease activity and progression in persons with multiple sclerosis (PwMS), with studies showing elevated sNfL levels during relapses and positive associations with disability scores.

Objective:  To assess sNfL levels in PwMS receiving different disease-modifying therapies (DMTs), with a particular focus on extended-interval dosing (EID) regimens in real-world clinical practice.

Methods: In this two-center cross-sectional study, 172 PwMS without relapses in the preceding three months were included (University Hospital Cologne, n = 125; University Hospital Mainz, n = 47). Patients were categorized into the following groups: (1) low-efficacy DMT (leDMT; n = 8), (2) natalizumab standard-interval dosing (SID; every 4 weeks; n = 7), (3) natalizumab EID (every 6-8 weeks; n = 53), (4) ofatumumab (n = 17), (5) ocrelizumab SID (every 6 months; n = 48), (6) ocrelizumab EID (every 9 months; n = 17), and (7) no DMT (n = 19). sNfL levels were measured once in a cross-sectional design using an electrochemiluminescence immunoassay.

Results:  No significant differences in sNfL levels were observed across DMT subgroups in the ANCOVA analysis after adjusting for age and the presence of new T2 lesions on the most recent cranial MRI. However, PwMS receiving DMTs showed lower sNfL levels compared with untreated patients. Notably EID of ocrelizumab (every 9 months; 1.56 pg/mL, 95% CI 1.26-1.85) and natalizumab (every 8 weeks; 1.46 pg/mL, 95% CI 1.29-1.64) was not associated with higher sNfL levels compared to standard interval dosing (SID) of ocrelizumab (1.45 pg/mL, 95% CI 1.27-1.63) or natalizumab (1.13 pg/mL, 95% CI 0.68-1.58).

Conclusion:  EID regimens were not associated with increased sNfL levels, suggesting that they may effectively limit neuroaxonal damage. Larger studies that assess the added value sNfL monitoring for safely personalizing treatment intervals in PwMS with initially active disease are needed.

Purpose: Autoimmune encephalitis (AE) refers to a group of rare autoimmune diseases affecting the central nervous system. New research shows that it can trigger neurodegenerative changes, especially brain atrophy. This atrophy has multiple causes, which worsen the prognosis. Thus, future studies need to focus on the early identification of AE patients at risk of brain atrophy and early interventions to prevent this complication. This review covers epidemiology, risk factors, clinical symptoms, pathophysiological mechanisms, and immunosuppressive therapy and summarizes current progress in understanding AE-related brain atrophy.

Latest findings: AE patients with brain atrophy often have anti-N-Methyl-D-Aspartate Receptor (NMDAR), anti-Leucine-Rich Glioma-Inactivated 1 (LGI1), anti-glutamic acid decarboxylase 65 kDa Isoform (GAD65) antibodies, and other antibodies in serum and cerebrospinal fluid; however, seronegative patients may also have atrophy. The temporal lobe, cerebellum, and brainstem most often show reduced volume, causing ataxia, memory decline, and cognitive and motor impairments. The risk factors include patient age, antibody types, and early cognitive impairments as non-modifiable factors. Timely treatment, the duration of status epilepticus, cumulative disease burden, nutritional status, and concomitant medications are modifiable risk factors. The mechanisms of AE-related brain atrophy include metabolic disturbances and immune-mediated pathology. Glucocorticoids and intravenous immunoglobulin (IVIG) may reduce atrophy but do not restore brain volume. Some novel treatments are under investigation; however, no current clinical trials specifically target brain atrophy. Previous research has facilitated the understanding of the clinical presentation, mechanisms, and treatment of brain atrophy. Some studies suggest that children with AE can also experience brain atrophy, and subsequent follow-ups revealed brain dysplasia. However, the data primarily originate from studies with small-sized adult samples, and studies concerning children are lacking. Large-sample, multi-age stratified cohort studies are needed to explore early identification using neuroimaging biomarkers, new mechanisms, and novel therapeutic approaches to improve patient prognosis.

Progressive supranuclear palsy (PSP) is a rare and debilitating four-repeat (4R) tauopathy, characterized by motor dysfunction, cognitive decline, and oculomotor abnormalities, yet it lacks reliable biomarkers for early diagnosis, disease stratification, and prognosis. This review critically examines recent advancements in human biomarker research for PSP across multiple domains, including fluid specimen assays, i.e., blood and cerebrospinal fluid (CSF) assays, molecular profiling, and neuroimaging, with the aim of identifying markers that facilitate differential diagnosis, monitor disease progression, and support subtype classification. By synthesizing the findings of studies published, this article highlights the established biomarkers and emerging biomarkers from novel analytical methods and in vivo technologies and their potential utility for clinical trials. Emerging potential biomarkers considered include exosomal α-synuclein and tau aggregates, circulating molecular biomarkers, and relevant biomarkers from magnetic resonance spectroscopy (MRS), diffusion tensor imaging, neuromelanin MRI (NM-MRI), and functional MRI (fMRI) methods. Furthermore, the heterogeneous clinical presentations clearly reflect variable anatomical and molecular pathology in PSP and indicate that relying solely on clinical classification risks misdiagnosis, delayed treatment, and inappropriate management. A biologically grounded biotyping framework, which includes multimodal data integration and artificial intelligence, can resolve this heterogeneity by aligning observable phenotypes with underlying pathophysiology. To move beyond purely clinical classifications, this review proposes a conceptual biotyping framework to categorize PSP based on underlying biological processes, such as neurodegeneration, tau pathology, and neuroinflammation. This framework aims to guide future biomarker validation efforts, facilitate patient stratification in clinical trials, and accelerate the transition toward precision medicine approaches in PSP.

Background: Functional dystonia (FD) is one of the most common presentations among patients with functional movement disorders (FMDs). However, FD affecting neck muscles has not been well studied, even though cervical dystonia (CD) is one of the most common movement disorders.

Methods: We aimed to assess the clinical features and correlations of functional CD. Additionally, we compared the clinical features with 120 consecutive patients with non-functional CD and determined the diagnostic accuracy of contrasting variables.

Results: We studied 72 consecutive patients with FD (n = 57, 79.2% were females), of whom 34 (47.2%) were identified with functional CD. The latter group had greater severity of FMDs determined by the Simplified Functional Movement Disorders Rating Scale (S-FMDRS) and a more common functional speech disorder compared with patients with FD without CD (P ≤ 0.001, for both variables). Compared to patients with non-functional CD, those with functional CD were younger, had more common retrocollis, anterior head shift, greater severity of dystonic postures, more frequent changing pattern of dystonia, more common dystonia in other body parts, lack of typical alleviating maneuvers (AM) and less frequent neck pain (P < 0.05, for all comparisons). Lack of AM had the highest sensitivity (0.97) and change in dystonia pattern had the highest specificity for the diagnosis of functional CD (0.98).

Conclusions: Functional CD represented 47.2% of patients with FD. Greater severity of FMDs and comorbid functional speech disorders were more common in patients with functional CD. Several clinical features distinguished functional to non-functional CD.

Alzheimer's disease (AD) is a group of central nervous system degenerative diseases that affect cognitive function. During the diagnosis of AD, the levels of amyloid-β 42 (Aβ42) and amyloid-β 40 (Aβ40) in plasma, as well as their ratio Aβ42/Aβ40, have recently been recommended by the International Association for the Study of Aging and Alzheimer's Disease as biomarkers to assist in clinical decision-making. However, an increasing amount of research data indicates that the effectiveness of these biomarkers is influenced by various factors. The levels of Aβ42 and Aβ40 are not only related to the physiological state of the human body, but also closely associated with the collection and preservation of plasma samples, pre-analytical processing, different detection methodologies, and even the result analysis process. Moreover, the functional status of metabolic organs in the human body, different comorbidities, bacterial or viral infections, and other factors can all affect the true levels of Aβ42 and Aβ40. Therefore, to clearly and comprehensively understand the advantages and limitations of plasma Aβ42 and Aβ40 as diagnostic biomarkers for AD, this article focuses on reviewing and discussing the influencing factors when plasma Aβ42 and Aβ40 are applied to the diagnosis of AD, aiming to help clinicians make better use of these indicators to optimize their diagnostic value.

Introduction: Progression in Alzheimer's disease (AD) involves three main interrelated biological axes-tau deposition, neurodegeneration, and neuroinflammation-that jointly drive cognitive decline. Although several cerebrospinal fluid (CSF) and plasma biomarkers along these axes are well validated for diagnosis, their value for prognosis remains uncertain. We assessed how baseline markers of each axis predict cognitive trajectories in biomarker-confirmed AD.

Methods: We included 136 A + T + N + individuals (median follow-up = 24 months [IQR 12-24]; mean = 17.6 months [SD = 12.4]). Tau-deposition markers (CSF p-Tau181; plasma p-Tau181 and p-Tau217), neurodegeneration markers (CSF t-Tau; CSF and plasma neurofilament light chain, NfL) and a neuroinflammation marker (plasma glial fibrillary acidic protein, GFAP) were quantified using CLEIA, ELISA or Simoa, and stratified into tertiles. Participants were classified by age at onset, clinical phenotype, and APOE ε4 status. Cognition was assessed annually with a comprehensive neuropsychological battery. Linear mixed-effects models (MMRM) were used to test biomarker-cognition associations and interactions with clinical variables.

Results: Elevated CSF p-Tau181 and NfL levels were associated with greater decline in memory and executive function. Among plasma biomarkers, p-Tau217 and GFAP showed the strongest associations with widespread cognitive decline, particularly in language, visuospatial, and executive domains. These associations were independent of age at onset, clinical phenotype, and APOE ε4 status.

Discussion/conclusion: Our findings highlight the potential prognostic value of fluid biomarkers in AD, especially CSF p-Tau181 and NfL, and plasma p-Tau217 and GFAP. These results suggest promise for improving disease monitoring, although prognostic utility at the individual level remains uncertain.

Background: Guillain-Barré syndrome (GBS) is a life-threatening condition that has been associated with exposure to immune checkpoint inhibitors (ICIs); however, available data remain limited.

Methods: We conducted a retrospective, worldwide, observational analysis of individual case safety reports in VigiBase, the World Health Organization's pharmacovigilance database. To minimize competition bias, we excluded reports of vaccines and infectious associated with a known or potential risk of GBS. Subsequently, we searched for reports of GBS linked to ICI regimens, whether as monotherapy or dual immunotherapy, from the Food and Drug Administration (FDA) approval date of each agent until 12 February 2024. The primary endpoint of this study was to assess the association between GBS reporting and exposure to ICI regimens (either monotherapy or dual immunotherapy) using disproportionality analysis. This analysis was performed utilizing the Information Component (IC) and its 95% credibility interval lower boundary (IC₀₂₅).

Results: A total of 412 cases of GBS associated with ICIs were reported in VigiBase. The disproportionality analysis revealed a significant reporting signal between GBS and the anti-CTLA-4 and anti-PD-1 combination therapy (n = 102, IC₀₂₅ = 4.6), specifically with nivolumab and ipilimumab (n = 100, IC₀₂₅ = 4.6); anti-CTLA-4 monotherapy (n = 39, IC₀₂₅ = 3.6) with ipilimumab monotherapy (n = 39, IC₀₂₅ = 3.6); anti-PD-1 monotherapy (n = 217, IC₀₂₅ = 3.4), including pembrolizumab (n = 124, IC₀₂₅ = 3.5), nivolumab (n = 88, IC₀₂₅ = 3), and cemiplimab (n = 5, IC₀₂₅ = 1.2); and anti-PD-L1 monotherapy (n = 53, IC₀₂₅ = 3) with atezolizumab (n = 36, IC₀₂₅ = 3), durvalumab (n = 11, IC₀₂₅ = 1.8), and avelumab (n = 6, IC₀₂₅ = 1.1) in monotherapy. Among cases with available data (n = 123), the median time to onset was 68 days (interquartile range [IQR]: 24.5-119.5), with a shorter delay observed in patients receiving dual immunotherapy compared to those treated with monotherapy. Among the cases for which data was available (n = 242), data recovery or partial recovery was reported in 58.3% (n = 141/242), while a fatal outcome was reported in 9% (n = 21).

Conclusion: A significant reporting signal of GBS exists with the majority of ICI regimens employed in both monotherapy and dual immunotherapy.

Introduction: Health-related quality of life (HRQoL) in stroke survivors often remains impaired. Chronic vertigo and dizziness are common but frequently overlooked symptoms. We investigated their impact on HRQoL and characterized symptom patterns.

Patients and methods: Patients from a prospective stroke cohort study were assessed during hospitalization and followed up after three and twelve months. We evaluated functional outcomes using the modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS), and measured HRQoL with the Stroke Impact Scale (SIS). The relationship between vertigo and dizziness and the HRQoL measures was analyzed by multivariable-adjusted regression models. Subgroup analyses were performed for pre-existing and new vertigo or dizziness after stroke.

Results: Of 1785 patients enrolled (mean age 69 years; 42.7% female), 988 (55%) completed the 12 months follow-up. Here, 41% reported chronic vertigo or dizziness. These symptoms significantly impacted health-related quality of life across SIS domains, with strongest effects in participation (ß = -11.45 (new-onset)), mobility (ß = -10.26 (preexisting)), and memory (ß = -12.80 (unspecified)), independent of age, sex, stroke severity, and comorbidities. Patients with new-onset symptoms showed higher rehabilitation participation compared to asymptomatic patients (64.3% vs 48.3%, p = 0.001), despite similar stroke severity (mRS: median 2 [IQR 1-3] vs 2 [1-3], p = 0.137; NIHSS: median 2 [IQR 0-4] vs 1 [0-4], p = 0.951).

Discussion: Patient-reported vertigo and dizziness after acute stroke are common symptoms that impact HRQoL. Current poststroke care inadequately addresses these symptoms.

Conclusion: Early identification, systematic assessment, and targeted interventions are needed.

Background: Peripapillary retinal nerve fiber layer (pRNFL) thinning, detected by optical coherence tomography (OCT), is an early marker of neuroaxonal injury in multiple sclerosis (MS). Its prognostic value for long-term outcomes and responsiveness to disease-modifying therapies (DMTs) remains insufficiently explored, particularly in Asian populations. This study aimed to identify clinical and radiological correlates of pRNFL thickness, evaluate whether pRNFL thinning predicts disability and cognitive decline, and examine the effects of DMTs on retinal neurodegeneration in Chinese MS patients.

Methods: We analyzed 354 Chinese MS patients who underwent OCT, neurological assessments, and brain MRI. Multivariate regression identified determinants of baseline pRNFL thickness. Among 159 patients with follow-up longer than 12 months, logistic regression was used to assess whether baseline pRNFL thickness and annualized pRNFL thinning predicted disability or cognitive decline. Linear mixed-effects models were applied to evaluate longitudinal effects of DMT classes on pRNFL thinning.

Results: Median pRNFL thickness was 105.0 μm (range: 65.0-136.5). Thinner pRNFL was associated with longer disease duration (p < 0.001), optic neuritis (p = 0.019), longer 9-Hole Peg Test completion time (p = 0.025), and increased paramagnetic rim lesions (p = 0.002). Baseline pRNFL thickness did not predict EDSS progression or Symbol Digit Modalities Test (SDMT) decline. In contrast, faster annualized pRNFL thinning predicted SDMT worsening (OR = 1.29, p = 0.018), alongside fewer years of education (OR = 0.84, p = 0.033) and a secondary progressive MS phenotype (OR = 7.67, p = 0.006). No significant differences in pRNFL preservation were observed among DMT classes.

Conclusion: pRNFL thinning reflects disease severity and predicts cognitive decline in MS. Current DMTs provide limited retinal neuroprotection. These findings support the routine OCT-derived pRNFL monitoring and highlight the need for neuroprotective strategies in MS.