Journal of the Neurological Sciences最新文献

Parkinson's Disease (PD) is a progressive neurodegenerative condition, which is highly heterogeneous upon diagnosis. Brain extracellular matrix (ECM) accounts for 10-20 % of the total brain volume and is responsible for the physical organization of neuronal and glia cells. Blood-based biomarkers quantifying ECM fragments holds the potential as diagnostic and prognostic biomarkers. Here we evaluated the serum ECM biomarkers C1M, C4M, TUM, SPARC-M and BGM in healthy donors and patients diagnosed with PD. The biomarkers were able to separate between healthy donors and PD patients with an AUC up to 0.926. These pathologically relevant biomarkers could be used as biomarkers in clinical management.

Introduction: Cognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD subtypes with varying cognitive trajectories. This study aimed to identify early PD subtypes based on patterns of gray matter atrophy in brain regions associated with cognition and assess their distinct patterns of cognitive change over time. Recognizing PD primarily as a movement disorder, we also evaluated their motor symptoms.

Methods: We analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (M_GMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models.

Results: Two PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher M_GMV in frontal (p < 0.001) and subcortical (p < 0.001) regions, indicating atrophy. At 48 months, subtype 1 had poorer global cognitive performance than subtype 2 (p = 0.005) and faster progression of postural instability and gait disturbance (p = 0.04).

Conclusions: PD subtypes identified early by distinct frontal and subcortical atrophy patterns exhibited divergent trajectories of cognitive decline and worsening motor symptoms over time, underscoring the neuroanatomical heterogeneity that drives clinical variability in PD.

Background and objectives: Magnetic resonance imaging (MRI) and neurohistopathology are important correlates for evaluation of disease progression in multiple sclerosis (MS). Here we used experimental autoimmune encephalomyelitis (EAE) as an animal model of MS to determine the correlation between clinical EAE severity, MRI and histopathological parameters.

Methods: N = 11 female C57BL/6J mice were immunized with human myelin oligodendrocyte glycoprotein 1-125, while N = 9 remained non-immunized. Mice were scanned longitudinally over a period of 13 weeks using a 11.7 Tesla (T) Bruker BioSpec® preclinical MRI instrument, and regional volume changes of the lumbar spinal cord were analyzed using Voxel-Guided Morphometry (VGM). Following the final in vivo T1-weighted MRI scan, the lumbar spinal cord of each mouse was subjected to an ex vivo MRI scan using T1-, T2*- and diffusion tensor imaging (DTI)-weighted sequences. Tissue sections were then stained for immune cell infiltration, demyelination, astrogliosis, and axonal damage using hematoxylin-eosin staining and immunohistochemistry.

Results: While in vivo MRI VGM detected an overall increase in volume over time, no differences were observed between EAE animals and controls. Ex vivo MRI showed a generalized atrophy of the spinal cord, which was pronounced in the anterolateral tract. The most striking correlation was observed between EAE score, white matter atrophy in ex vivo T1-weighted scans and histological parameters.

Discussion: The data demonstrate that ex vivo MRI is a valuable tool to assess white matter atrophy in EAE, which was shown to be directly linked to the severity of EAE and spinal cord histopathology.

Introduction: Atrial fibrillation (AF) and large artery atherosclerotic diseases are major causes of ischemic stroke and their coexistence increases the risk of stroke and mortality. Research on antithrombotic strategies for AF patients with symptomatic large artery atherosclerosis is limited. This study aims to report a single center's experience regarding the antithrombotic regimens prescribed for this population and the association with stroke recurrence and hemorrhagic events.

Methodology: This retrospective cohort study included AF patients admitted to the Medical University of South Carolina with stroke due to symptomatic intracranial (sICAS) or extracranial atherosclerosis (sECAS). Patients were grouped based on prescribed antithrombotic regimens and compared according to their outcomes.

Results: Of 1,924 ischemic stroke patients with AF, 114 (6%) met the inclusion criteria. At discharge, the majority of patients were prescribed anticoagulants alone (sAC) or combined with a single antiplatelet (sAC + sAP) 26% and 34% respectively. Stroke recurrence was highest during the first 90-days after index stroke (11%). Patients on combination sAC + sAP had fewer recurrent strokes in the first 90-days compared to sAC (5.5% vs. 22.2%,p = 0.056) without significant increase in symptomatic hemorrhagic events (5.5% vs. 3.7%, p = 0.6). However the hemorrhagic risk significantly increased with prolonged therapy beyond 90-days (18% vs. 0%,p = <0.02). Early deaths were also high with 37% of total deaths occurring within 90-days after index stroke.

Conclusion: In this cohort, AF patients with stroke due to sICAS or sECAS had early stroke recurrence and mortality. While combination AC + sAP may reduce short-term stroke recurrence they may increase the hemorrhagic risk in the long-term.

Vascular cognitive impairment (VCI) stresses the vascular contributions to cognitive decline, ranging from mild to major forms. Except for symptomatic treatment for relevant vascular diseases, the other recommended strategy is to intervene in key vascular risk factors (VRFs) as early as possible. A considerable amount of previous research delineated the association of a specific factor with dementia, involving each risk factor discussed in the present review. However, due to the heterogeneity and complexity of VCI, managing a single factor is insufficient to reduce its incidence and prevalence. Ongoing studies suggest differences in the impact of various combinations of risk factors on dementia. Here in this review, we aimed to provide an updated overview of clinical evidence and implications of complex interactions among various risk factors of VCI, including common VRFs and modifiable dementia-related risk factors. Understating the effect of comorbid risk factors on VCI and underlying mechanisms of them during VCI progression is essential for identifying high-risk population and developing preventive strategies. Furthermore, we summarized common composite risk scores and models used for risk evaluation and prediction of VCI, involving conventional risk scores, subclinical vascular composites, and novel risk models driven by intelligent algorithms. Lastly, we discussed potential gaps and research directions on searching specific clinical risk profiles, constructing effective risk scores, and implementing targeted risk interventions.

Background: Myelin damage has recently been highlighted as a major causative factor of amyotrophic lateral sclerosis (ALS). Although myelin damage has been pathologically identified in ALS, it has not been clinically evaluated. This study aimed to quantify myelin volume using synthetic MRI to evaluate myelin damage in patients with ALS, and determine its association with clinical parameters.

Methods: We evaluated patients with ALS (n = 35) and individuals (n = 16) without intracranial disease using synthetic magnetic resonance imaging (MRI) and measured total myelin volume (TMV), myelin fraction (MYF), and myelin partial volume (V_MY) in the cerebral peduncle and the posterior limb of the internal capsule (PLIC). We also investigated factors associated with acquired quantitative values.

Results: The TMV was significantly lower in the patients with ALS than in the control group (P = 0.045). The TMV (r = 0.42, P = 0.013) and MYF (r = 0.34, P = 0.047) significantly correlated with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores in the patients, and MYF was independent of the traditional white matter lesion grading score. The V_MY of the PLIC was significantly lower in the ALS than the control group (P = 0.018), and the ALS group significantly correlated with ALSFRS-R scores (r = 0.36, P = 0.033).

Conclusions: Myelin damage can be quantified by synthetic MRI as reduced myelin volume, with the possibility of predicting prognoses in patients with ALS. Furthermore, myelin measurements in the PLIC might be a novel diagnostic marker for ALS.

Introduction: The FRED-X is a newer generation flow diverting stent (FDS) with surface modification that has demonstrated favorable efficacy in treating intracranial aneurysms. Our study provides an analysis of patients treated using FRED-X compared to FRED, PED Shield and PED.

Materials and methods: This was a retrospective single center study and a systematic review with network meta analysis of patients who underwent flow diversion using FRED-X, FRED, PED Shield or PED. Multivariate logistic regression was used to assess long-term outcomes of interest- angiographic occlusion, in-stent stenosis and functional outcome at 6- and 12-month follow up.

Results: 386 patients with 386 aneurysms were included. The average age of the cohort was 56.2 years, and 81 % was female. PED had significantly higher aneurysm occlusion rates compared to FRED-X at 6- and 12-months (OR: 3.03, 95 % CI: 1.36-6.62 and OR: 4.01, 95 % CI: 1.26-12.2), with higher odds of absent in-stent stenosis (OR: 9.03, 95 % CI: 3.63-23.3 and OR: 9.58, 95 % CI: 2.56-33.8) at 6- and 12-months, respectively. Rates of stroke, TIA, ICH and mortality were not significantly different across cohorts. All patients were functionally independent on follow-up. A network meta-analysis revealed no significant difference in occlusion rates among each of the included FDS.

Conclusion: Our study revealed comparable 12-month occlusion rates and in-stent stenosis between surface modified devices, FRED-X and PED Shield. In addition, angiographic results were comparable between FRED-X and the first generation FRED, however classic PED demonstrated higher rates of angiographic occlusion with lower in-stent stenosis.

Degeneration of the nigrostriatal system occurs in multiple system atrophy (MSA) and Parkinson's disease (PD) via distinct pathological mechanisms. Here, we investigated nigrostriatal degeneration in MSA and PD by combining a newly developed method for evaluating the regional accumulation of dopamine transporter single-photon emission computed tomography (DAT SPECT) and individual voxel-based morphometry adjusting covariates (iVAC). We recruited 17 MSA patients and 13 PD patients, and compared their clinical and imaging indices. All patients underwent DAT SPECT and head three-dimensional T1-weighted magnetic resonance imaging. We calculated the specific binding ratio (SBR) of the putamen and caudate separately using a region-based method, and evaluated the association between the SBR and iVAC Z-score. SBR values of the putamen and caudate were lower in the PD group than in the MSA group (p < 0.001 for both). The MSA and PD groups had lower SBR values in the putamen than in the caudate (p < 0.05 and p < 0.001, respectively). We found a negative correlation between the putamen SBR and iVAC Z-score in MSA (p < 0.001, r = -0.775), but such a correlation was not detected in PD. For the caudate, there was no correlation between the SBR and iVAC Z-score in MSA and PD. Our results indicate different mechanisms of reduced uptake of DATs in MSA and PD. The association between the striatal SBR and iVAC Z-score suggests parallel degeneration in the substantia nigra and striatum in MSA.