Journal of Neurology最新文献

Background: Gradual worsening in relapsing-remitting MS (RRMS) may precede the formal transition to secondary progressive MS (SPMS). We aimed to quantify self-reported gradual worsening, assess concordance with clinically recorded subtype, and identify baseline predictors of discordance.

Methods: We included 1640 participants with incident RRMS from a population-based study (2005-2019). A 2021 follow-up survey captured patient-reported gradual worsening. Clinical data, including Expanded Disability Status Scale (EDSS) scores and SPMS classification, were obtained from the Swedish MS registry. Discordance with clinically recorded subtype was modeled using logistic regression stratified by subtype. Time to EDSS 3 and EDSS 4 were summarized with Kaplan-Meier estimates within subtype by self-reported worsening, and secondary Cox proportional hazards models were fitted stratified by subtype with self-reported worsening as the exposure.

Results: Among participants classified as RRMS, 24% reported gradual worsening, while 23% of those classified as SPMS did not. Kaplan-Meier curves showed clear within-subtype separation by self-reported worsening, consistent with higher hazards of reaching EDSS 3 and EDSS 4 among those reporting worsening. In RRMS, older age and higher baseline EDSS were associated with self-reported gradual worsening despite RRMS classification. In SPMS, self-reported worsening preceded clinical classification by 4.1 years.

Conclusions: Patient-reported gradual worsening aligns with disability accumulation and may help identify progression earlier than subtype reclassification, supporting integration of structured patient reports into routine monitoring.

The diagnostic approach to subjects with early-onset dementia (EOD) is often challenging due to the broader range of possible etiologies as compared to late-onset dementia cases. Pathogenic variants in CSF1R gene have been increasingly reported in subjects with EOD, mostly clinically mimicking behavioral variant of frontotemporal dementia (bvFTD). Here we screened for variants in CSF1R gene in a large cohort of dementia patients consecutively referred for genetic analysis to an Italian tertiary center between 2005 and 2024 (n = 2163). Sequence of CSF1R gene was determined with next-generation sequencing through either a dedicated panel or whole-exome sequencing. Pathogenic variants or variants of uncertain significance with higher evidence of pathogenicity were found in four participants (one female); three of these were not previously reported. Clinical data were collected, including brain magnetic resonance imaging and neuropsychological assessment. Cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) protein were measured. A family history of dementia was present in one subject. Mean age at onset was 51.5. Seizures were the presenting symptom in two cases and later appeared in other two. Two subjects presented with behavioral disturbances, resembling early bvFTD. Neuropsychological assessment revealed executive and language impairment in most cases. Anterior-predominant atrophy, symmetric white-matter involvement, and serpentine calcifications were the most common imaging abnormalities. High CSF NfL levels were found in all cases, with two of them showing markedly elevated values. CSF1R-related disease should be considered in EOD subjects, especially those presenting with executive/language deficits, seizures, white matter involvement, and markedly elevated CSF NfL levels.

Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS).

Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18-39 years), transition onset (40-49 years), LOMS (50-59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions.

Results: Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93).

Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

Aims: Rivaroxaban has been approved for the primary prevention of stroke with non-valvular atrial fibrillation caused by one or more risk factors. However, the optimal antithrombotic therapy for secondary prevention of stroke in atrial fibrillation (AF) with ischemic stroke/transient ischemic attack (TIA) had been uncertain. We compared the safety and efficacy of novel oral anticoagulants. (NOACs) and Warfarin in treating AF with ischemic stroke.

Methods: Seven databases were searched from inception up to December 2024 for studies comparing NOACs and Warfarin in AF with ischemic stroke. 7 randomized controlled trials (RCTs) and 9 cohort studies with 128,808 patients were included. A random-effects model or fix effects model was used.

Results: Pooled results showed that the NOACs are superior to Warfarin in the prevention of stroke or systemic embolism (RR 0.90, 95%CI [0.82,1.0], P = 0.04) and all-cause mortality (RR 0.83, 95%CI [0.76,0.92], P = 0.0003). As well as NOACs has lower risk in total bleeding (RR 0.79, 95%CI [0.76,0.83], P < 0.00001), fatal bleeding (RR0.64, 95% CI [0.54,0.76], P < 0.00001), hemorrhagic stroke (RR0.50, 95%CI [0.43,0.58], P < 0.00001), and intracranial bleeding (RR 0.49, 95%CI [0.36,0.65], P < 0.00001) than Warfarin.

Conclusion: In the secondary prevention with AF related to ischemic stroke, NOACs showed potential advantages over Warfarin in the incidence of stroke or systemic embolism, all-cause mortality, total bleeding, fatal bleeding, hemorrhagic stroke, and intracranial bleeding.

Background: Only a few longitudinal studies, with follow-up duration up to 3.6 years, have assessed the substrates of relapses and disability in aquaporin-4 (AQP4) IgG-positive neuromyelitis optica spectrum disorders (NMOSD), primarily focusing on clinical and conventional MRI variables.

Objective: We evaluated the association of clinical and MRI measures, including a comprehensive multimodal advanced MRI protocol, with key long-term clinical outcomes in AQP4 IgG-positive NMOSD patients over a median follow-up of 8.5 years (interquartile range [IQR] = 3.5; 13.3).

Methods: Forty-six NMOSD patients and 77 healthy controls underwent 3T brain MRI. In patients, neurological evaluations were collected at baseline and every six months. Time to first relapse and 6-month confirmed disability worsening (6m-CDW) were recorded. Lesion volume and topography, global and regional brain volumes, normal-appearing white matter and gray matter fractional anisotropy and mean diffusivity, choroid plexus volume, enlarged perivascular spaces number and glymphatic system function were assessed.

Results: During the follow-up, 30% patients experienced at least one clinical relapse, while 22% had 6m-CDW. Higher number of previous attacks (hazard ratio [HR] = 1.17, 95%-confidence interval [CI] = 1.04; 1.32) and presence of anterior optic pathway lesions (HR = 4.92, 95%-CI = 1.12; 21.852) were risk factors independently associated with a shorter time to a first clinical relapse; lower thalamic volume was marginally associated (HR = 0.93, 95%-CI = 0.87; 1.00). Presence of cervical cord lesions (HR = 3.93, 95%-CI = 1.16; 13.31) and lower normalized cortical volume (HR = 0.94, 95%-CI = 0.89;0.99) were risk factors independently associated with a shorter time to 6m-CDW; higher number of previous attacks contributed marginally (HR = 1.19, 95% = 0.99; 1.43). High efficacy treatments (HETs) delayed time to first relapse and 6m-CDW.

Conclusions: Previous attacks, optic nerve/spinal cord involvement, cortical/thalamic atrophy and the use of HETs associate with long-term outcomes in NMOSD.

Background and objectives: Age at onset is a key determinant of disease course in the general Parkinson's disease (PD) population, but its influence among GBA-PD remains undetermined. This study investigates whether age at onset affects cognitive decline in GBA-PD patients and compares symptoms between GBA-PD and nonGBA-PD groups, stratified by age of onset.

Methods: In this multicentric cross-sectional study, PD patients were stratified into early onset (< 50 years), intermediate onset (50-60 years), and late onset (> 60 years). Demographic-clinical data and scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT), and Beck Depression Inventory (BDI-II) were compared using ANCOVA. The effects of age of onset, GBA1 status, and their interaction were investigated. External validation on cognition was performed using data from the PPMI cohort.

Results: We analyzed 80 GBA-PD and 236 nonGBA-PD patients. Among GBA-PD, late-onset patients exhibited worse axial scores (p = 0.037), while early-onset had more severe motor complications (p = 0.007) and dysautonomia (p = 0.012). Age of onset and GBA1 status did not influence MoCA scores. Conversely, GBA1 status independently affected MDS-UPDRS parts I and II (p < 0.001 and p = 0.019, respectively) and BDI-II scores (p = 0.002). Analysis on the external dataset (PPMI) showed late-onset PD had lower MoCA scores (p < 0.001) and confirmed GBA1 status did not influence cognition.

Discussion: In the first decade of PD, cognitive decline is mainly age and duration dependent, irrespective of GBA1 genotype. Early onset does not increase cognitive risk in GBA-PD, supporting its relevance for counseling and treatment planning.

Objective: This study aimed to investigate the influence of different obesity-metabolic syndrome (MetS) statuses on mild cognitive impairment (MCI) and to explore the modifying roles of related factors.

Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015) and a real-world cohort (RWC). Binary logistic regression and restricted cubic spline models were used to examine the associations between obesity, MetS, and MCI, adjusting for covariates. In the RWC, the effects of obesity-metabolic phenotypes on cognitive function were further explored using structural magnetic resonance imaging (MRI) to evaluate brain atrophy.

Results: A total of 6079 participants from CHARLS and 522 from the RWC were included. Each additional MetS component increased the risk of MCI in females aged < 60 and 60-70 years. Low high-density lipoprotein (HDL) levels in older males negatively affected cognition, and elevated fasting glucose was significantly associated with poorer cognitive performance. Metabolically unhealthy non-obesity (MUNO) and metabolically unhealthy obesity (MUO) were associated with higher MCI risk both in males and females, while metabolically healthy obesity (MHO) in males aged 60-70 years was also linked to increased risk. RWC further revealed that MHO, MUNO, and MUO groups exhibited varying degrees of brain atrophy compared with healthy controls.

Conclusion: Findings from both cohorts suggest that obesity and metabolic health jointly influence cognitive impairment risk. Structural MRI results highlight that metabolic dysregulation may exacerbate obesity-related neurodegeneration.

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe complication of anti-CD19 CAR T-cell therapy. Nevertheless, its neuroradiological characterization remains insufficiently defined, as most available evidence stems from retrospective cohorts, heterogeneous imaging protocols, or studies limited to pediatric populations.

Methods: We conducted a prospective, monocentric study including adult patients with B-cell lymphoproliferative disorders undergoing anti-CD19 CAR T-cell therapy. All patients underwent a standardized neurological and neuroradiological protocol, with brain MRI performed at screening (15-20 days before CAR T-cell infusion), 60 days, and 12 months after infusion, as well as urgently in the event of ICANS. Brain MRI records were reviewed by a panel of expert neuroradiologists.

Results: Of 154 treated patients, 112 were included. ICANS occurred in 34 patients (30.4%); 27 underwent urgent MRI, which showed abnormalities in 11 cases (40.7%). Two distinct radiological patterns emerged. The central variant pattern-characterized by symmetric involvement of thalami, hippocampi, brainstem, and variably the geniculate bodies or corpus callosum-was associated with severe ICANS and acute clinical deterioration, including two cases with diffuse centrum semiovale edema and intracranial hypertension. This pattern resolved in most cases on follow-up imaging. The stroke-like pattern consisted of focal cortico-subcortical white matter lesions, often DWI-restricted, appearing in both ICANS and asymptomatic patients, typically in subacute phases. These lesions persisted as non-enhancing FLAIR abnormalities at follow-up.

Conclusions: Serial brain MRI enabled identification of two specific ICANS-related imaging signatures with distinct temporal and radiological characteristics. While overall MRI sensitivity for ICANS remains low, pattern recognition improves diagnostic specificity, supports clinicians in the differential diagnosis, and provides insights into underling pathophysiology.

The Short-Term Memory Conjunctive Binding (STMCB) test assesses the ability to maintain integrated shape-colour associations in memory. It has been applied to detect Alzheimer's disease (AD) across the continuum, from preclinical stages and subjective cognitive decline (SCD) to dementia. The objective of the present study was to examine whether the STMCB test can differentiate individuals at very early stages of AD from controls. The sample included 67 participants with normal performance on standard neuropsychological tests. Participants were classified as controls or as having SCD based on self-reported memory complaints. Twenty-three controls and 44 individuals with SCD completed the STMCB test. All individuals also underwent a comprehensive neuropsychological evaluation, amyloid ([¹¹C]PIB) and FDG-PET scans. No significant group differences were observed in STMCB test performance between the groups. Furthermore, the STMCB test did not distinguish between amyloid-negative controls and SCD participants with amyloid pathology. These findings suggest that binding deficits may emerge later in the AD continuum, particularly when tau deposition or neurodegeneration is present.