Journal of Neurology最新文献

Diabetic neuropathy (DN) is one of the most common and debilitating chronic complications of diabetes mellitus. It typically presents as a distal symmetric polyneuropathy (DSP), which is characterized by symmetric involvement of the distal extremities, manifesting as numbness, pain, paresthesia, and sensory loss. In addition to peripheral sensory involvement, patients may also experience autonomic neuropathy and focal nerve injuries. Persistent hyperglycemia can impair the structure and function of the nervous system through multiple interrelated mechanisms. Prolonged elevation of blood glucose levels induces non-enzymatic glycation reactions, leading to the excessive accumulation of advanced glycation end products (AGEs). These AGEs bind to their receptor RAGE, triggering a cascade of downstream signaling pathways, including ROS/NF-κB, JAK/STAT, and PKC, that promote oxidative stress and chronic inflammation. In addition, hyperglycemia exacerbates neural injury and impedes repair by disrupting microvascular integrity, altering immune cell function, disturbing ionic homeostasis within nerves, and inducing Schwann cells (SCs) apoptosis along with impaired production of neurotrophic factors. Currently, a variety of pharmacological agents are available for the treatment of DN, including gabapentin, pregabalin, methylcobalamin, α-lipoic acid, and aldose reductase inhibitors, either as monotherapy or in combination. These treatments can partially alleviate neurological dysfunction and neuropathic pain. This review summarizes the key mechanisms by which hyperglycemia induces nerve injury and highlights recent advances in pharmacological interventions. The aim is to provide a theoretical framework and therapeutic perspective to support both mechanistic research and clinical management of DN.

Background: Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disease caused by galactocerebrosidase deficiency. Juvenile phenotypes-onset between ages 3 and 16-account for up to 25% of cases. Hematopoietic stem cell transplantation (HSCT) is the only available treatment, yet only eight juvenile-onset cases treated with HSCT have been reported, with heterogeneously collected data. We aim to comprehensively evaluate long-term neurological outcomes post-HSCT in juvenile GLD.

Methods: We conducted a retrospective study of all juvenile GLD patients treated with HSCT and followed at our Institution. We assessed survival, neurological status, disability (modified Rankin Scale), cognitive outcomes, GALC activity, serial MRIs (Loes score), evoked potentials (internal scoring system), and nerve conduction studies at pre-HSCT, first post-HSCT visit, and last follow-up.

Results: Six biochemically and genetically confirmed juvenile GLD cases were included. Four were symptomatic at diagnosis; two were pre-symptomatic. All survived to last follow-up (range 9 years, 2 months-19 years, and 8 months). Four achieved near-normal cognitive, motor, and functional status. Two symptomatic patients-with extensive pre-HSCT white matter disease and specific pre-HSCT clinical features (epilepsy and cognitive impairment)-had suboptimal outcomes. Loes scores stabilized/improved in four patients; GALC enzyme activity normalized in all. Electrophysiological measures mostly remained stable.

Conclusions: HSCT significantly impacts the natural history of juvenile GLD, resulting in largely optimal long-term outcomes, preserved quality of life, and minimal disability. Standardized pre-transplant assessments are critical. High pre-HSCT Loes scores, epilepsy, and cognitive impairment could be prognostic indicators, highlighting the importance of early intervention based on comprehensive instrumental evaluations.

Background: Orthostatic tremor (OT) is a rare, heterogenous disorder, recently sub-classified into primary OT (isolated 13-18 Hz tremor), OT-plus (OT with additional neurological features) and pseudo-OT (OT with frequencies < 13 Hz). However, to our knowledge no study to date has compared clinical characteristics between all three subgroups.

Objectives: We aim to further define and compare the clinical characteristics of the three different OT subgroups, utilising one of the largest described single centre cohorts to date.

Methods: A retrospective analysis was undertaken of clinical records from 74 OT patients at Charing Cross Hospital between 1999 and 2023, enabling categorisation into subgroups. Clinical characteristics, including treatment efficacy and overall disability, were subsequently described and compared between subgroups.

Results: 61 primary OT, 5 OT-plus and 8 pseudo-OT patients were identified. Baseline demographics were comparable between subgroups. Logistic regression suggested age of onset (OR = 1.02, p = 0.229), symptom duration (OR = 1.05, p = 0.083), tremor frequency (OR = 1.02, p = 0.826) and subgroup (OT-plus (OR = 1.86, p = 0.565) and pseudo-OT (OR = 1.41, p = 0.683)) were not significant predictors of disability. Treatment response varied between subgroup, with primary OT and pseudo-OT patients more frequently reporting symptomatic improvement with clonazepam, gabapentin and/or alprazolam than OT-plus patients.

Conclusions: We provide further insight into the clinical phenotypes of the OT subgroups and encourage future studies to validate these findings with larger sample sizes and establish reliable tools to measure OT severity to better assess disease progression and treatment response.

Background: Although many patients with Parkinson's disease (PD) report experiencing episodes of freezing of gait (FOG) at home under ON medication ("On-meds") conditions, objective and accurate diagnosis of different types of FOG events remains an extremely challenging task.

Methods: We conducted an observational, case-control study enrolling 75 consecutive PD patients, who were classified into "freezer" (n = 50) and "non-freezer" (n = 25) group, based on responses to the FOG Questionnaire and clinical confirmation. A modified timed up and go (TUG) protocol comprised one single‑task TUG (sTUG) and two dual‑task TUGs (cognitive, manual). Synchronized video and a single wearable sensor (Ambulosono) provided parallel capture for real‑time detection and subtyping of FOG.

Results: In the "freezers" group, 337 FOG episodes occurred during TUG testing, whereas none were recorded in the "non‑freezers" group (p < 0.01). The mean frequency was 2.25 FOG episodes per person per test. Compared with the sTUG test (74 FOG episodes), dual-task trials identified 263 FOG episodes, representing a 255% increase (p < 0.01). Trembling, shuffling and akinetic subtypes were identifiable on the device display (GMGI), with sensitivity 87.2% and specificity 89.5% versus video. Wearable data also localized subtypes by gait phase (initiation, turning, midway and ending).

Conclusions: "On-meds" FOGs can be objectively diagnosed among self-reported freezers using a dual task protocol during gait tests. Parallel video and wearable sensor recordings facilitate the real-time detection and subtyping of "On-meds" FOGs, which can substantially improve the current clinical practice.

Introduction: Hereditary spastic paraplegias (HSP) are rare inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. This study aimed to characterize an Austrian HSP cohort and prospectively assess disease progression using the Spastic Paraplegia Rating Scale (SPRS), addressing the knowledge gap regarding its longitudinal capabilities in a real-world setting.

Methods: Data from 126 patients were collected at the Center for Rare Movement Disorders Innsbruck. Baseline clinical data were available for 103 individuals. Follow-up extended up to 5 years (mean 2.3 ± 1.9). Disease severity was assessed with the SPRS, and longitudinal progression analyzed using generalized linear mixed models.

Results: The cohort (64.3% male, mean age 47.1 years) included 54.8% patients with complicated HSP. Genetic confirmation was achieved in 54.0%, with SPAST being the most frequent genotype (36.8%). Mean baseline SPRS was 18.2 points. SPRS scores increased significantly with disease duration, with an overall annual progression of 0.9 points (p < 0.001). Progression was faster in complicated versus pure HSP (1.3 vs. 0.6 points/year; p < 0.001). Most patients received symptomatic medication (69.8%) and neurorehabilitation (84.1%).

Conclusion: This study provides comprehensive real-world data on HSP from an Austrian cohort, including clinical, genetic, management, and imaging findings. We present the first prospective assessment of SPRS progression in a natural history cohort, revealing significant longitudinal change. Taken together, our findings may contribute to the design of future therapeutic trials in HSP.

Background: The central vein sign (CVS) is a promising imaging marker of multiple sclerosis (MS). We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of CVS-based rules in the differential diagnosis of MS and to identify the best cutoffs for these rules.

Methods: PubMed, Embase, and Scopus were systematically searched for available evidence. Data extracted were entered into Bayesian models recommended by the Cochrane network. Summary sensitivity and specificity of CVS-based diagnostic rules across different positivity thresholds were calculated. A meta-regression for the role of gadolinium-based MRI protocols was also performed.

Results: 3434 patients from 28 studies were included. Three CVS-based diagnostic rules were found: the first one considers the percentage of CVS + lesions (relative threshold method), the second one the presence of CVS in a given number of lesions selected in T2 sequences (select-n method), and the third one the presence of a given number of CVS + lesions in gradient-echo sequences (select-n* method). For relative threshold method, the best cutoff was 37.5% (sensitivity 97.3%, 95%CI 90.9-99.6%; specificity 90.4%, 95%CI 83.2-95.9%; Youden index 0.877); for select-n* method, 4 was the best threshold (sensitivity 87.1%, 95%CI 66.9-96.6%; specificity 88.2%, 95%CI 65.1-98.1%; Youden index 0.753). Use of gadolinium-based MRI protocols was irrelevant (for relative threshold method RDOR = 6.62, 95%CI 0.68-71.27; for select-n* method RDOR = 2.52, 95%CI 0.35-15.36).

Conclusions: Relative threshold and select-n* methods are good predictors of MS diagnosis. This synthesis should support the use of CVS in clinical practice and prompt further research.