Acta neurologica Belgica最新文献

Background: This research aimed to examine the causal connections between multiple sclerosis (MS) and a range of sex hormone-related traits, such as bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), testosterone, and estradiol (E2).

Methods: A bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) was conducted to investigate the relationship between sex hormone-related traits and MS. Moreover, the Inverse-variance weighted (IVW) method was employed as the primary analysis approach.

Results: The MR analysis, using the IVW method, found a significant correlation between genetically determined SHBG levels and MS (OR = 1.634, 95% CI: 1.029-2.599, p = 0.038). Similarly, the reverse MR analysis suggested a causal link between MS and SHBG (OR = 1.005, 95% CI: 1.001-1.009, P = 0.003). However, no association was observed between MS risk and E2, testosterone, or BT levels.

Conclusion: Our MR analysis demonstrated that genetically predicted higher SHBG may be positively correlated with the risk of MS. Moreover, the role of SHBG in MS could be further investigated.

Objective

This study aimed to investigate the potential association between polymorphisms in monocyte chemoattractant protein-1 (MCP-1), chemokine receptor type 2 (CCR2), type 5 (CCR5), regulated on activation, normal T cell expressed, and secreted (RANTES) and susceptibility to Parkinson’s disease (PD).

Methods

The MEDLINE, EMBASE, and Web of Science databases were searched for relevant articles, and a meta-analysis was conducted to assess the associations between the MCP-1 -2518 G/A, CCR2 V64I, CCR5-Δ32, RANTES − 405 G/A, -28 G/A polymorphisms and the risk of PD.

Results

Six studies with 1,416 patients with PD and 1,715 controls that met the inclusion criteria were identified. Meta-analysis of all study participants demonstrated no association between PD and the MCP-1 -2518 G allele (odds ratio [OR] = 1.089, 95% confidence interval [CI] = 0.980–1.211, p = 0.114). Stratification by ethnicity indicated no association between the MCP-1 -2518 G allele and PD in the European and Asian populations. Meta-analysis demonstrated no association between PD and the MCP-1-2518 A/G polymorphism in recessive and dominant models and homozygote contrast. However, meta-analysis revealed a significant association between the risk of PD and the CCR2-V64I AA + GG genotype in all study participants (OR = 0.418, 95% CI = 0.232–0.753, p = 0.004). Stratification based on ethnicity validated this association between the CCR2-V64I AA + GG genotype and PD in the Asian population (OR = 0.460, 95% CI = 0.243–0.870, p = 0.017), but not in European populations. Analysis using the homozygous contrast model revealed the same pattern for the CCR2-V64I AA + GG genotype. Meta-analysis revealed no association between the CCR5-Δ32 allele and the risk of PD (OR = 0.972, 95% CI = 0.377–2.501, p = 0.952). Moreover, the meta-analysis demonstrated no allelic association between RANTES − 405 G/A and − 28 G/A polymorphisms and the risk of PD.

Conclusions

Our meta-analysis showed that the CCR2 V64I polymorphism is associated with PD, especially in Asian populations.

Background

Erenumab is a monoclonal antibody specifically targeting the CGRP-receptor. Several studies showed efficacy and safety in patients with migraine. Less is known regarding dosage increase, especially in a difficult to treat patients. The aim of the study is to evaluate the increased dosage under real world conditions with particular focus on 70 mg non-responders.

Methods

In a retrospective analysis, patients treated in tertiary headache centers (Halle or Jena, Germany) receiving 70 mg erenumab for at least 3 months with a dosage increase to 140 mg were analyzed. Data were evaluated regarding headache days, intake of acute medication, previous prophylaxis, and medication overuse. Baseline and all treatment intervals were determined as three-month periods.

Results

Datasets of 52 migraine patients (90.4% women) aged between 22 and 78 years (mean 50.4 years, SD 12.1 years) were analyzed. At baseline (mean headache-days 15.67 ± 6.37) 51.9% met criteria for chronic migraine and 56% were currently overusing acute medication. While therapy with 70 mg showed significant improvement in headache days and 50% response, further improvement was not achieved for therapy escalation to 140 mg. The same applies to the secondary endpoints and covers the entire study population as well as the subgroups of chronic and episodic migraine. The 50% response of the 70 mg non-responders for escalation was only 5.14%.

Conclusions

In this difficult-to-treat patient cohort we reconfirmed the effectiveness of erenumab, but could not detect any additional benefit for a dosage escalation from 70 mg to 140 mg erenumab.

Parkinson’s disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson’s disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson’s disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.

Background: Multiple sclerosis (MS) is commonly associated with work difficulties. This study aimed to examine the relationship between work difficulties and physical disability, cognitive and social cognitive impairment, and subcortical gray matter (scGM) atrophy in pwMS.

Methods: Thirty-three employees with MS underwent assessments with Multiple Sclerosis Work Difficulties Questionnaire-23 MSWDQ-23. Physical disability was measured using EDSS, Timed 25-Foot Walk (T25FW), 2-Minute Walking Test (2-MWT), the Nine-Hole Peg test (N-HPT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Cognitive functions were evaluated with Brief International Cognitive Assessment in MS (BICAMS), social cognition with Facial Emotion Identification (FEI), Reading the Mind in the Eyes Test (RMET), and Empathy Quotient (EQ). Anxiety and depression were assessed using Hospital Anxiety and Depression Scale (HADS). The association between variables was analysed using Spearman's correlation coefficient. GM volumes were calculated from 3T MRI data using Freesurfer, their potential relationship with work difficulties were evaluated through a linear regression model.

Results: MSWDQ-23 was strongly correlated with T25FW and MSWS-12 (p < 0.01), moderately correlated with EDSS, 2MWT, HAD, BICAMS, and EQ (p < 0.05). According to the linear regression model the decrease in volumes of total GM and scGM, bilateral Thalamus, bilateral Hippocampus, left Putamen, and right Caudate related with the severity of work difficulties (R²=0.815, p = 0.25).

Conclusion: This study provides valuable insights into the multifaceted nature of work difficulties experienced by pwMS. It suggests that not only physical disability but also other factors, such as mood, cognition, empathy, and cortical and subcortical gray matter atrophy may contribute to work difficulties among pwMS.

Purpose: Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020.

Methods: This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved.

Conclusion: Our study in a large cohort of MS patients confirmed that PLEX is effective.

Objectives: This study explored the characteristics of muscle stiffness of lower gastrocnemius in resting and exercise states in patients with postural instability gait difficulty (PIGD) and tremor dominant (TD) Parkinson's disease patients using shear wave elastography (SWE).

Data and methods: 75 PD patients from the Department of Parkinson's Disease Center in the Hospital from September 2021 to December 2022 were prospectively included, including 44 patients with PIGD and 31 with TD. In the same period, 40 healthy subjects matching gender and age were included as the control group. SWE was used to detect Young's modulus of both sides (right and left, R- and L-) of the lateral head of the gastrocnemius in resting (YM1) and exerciser states (YM2) in all participants and the absolute difference Young's modulus between resting and exercise state (ΔYM) was calculated.

Results: R-YM2 and R-ΔYM were the highest in the normal controls, followed by the TD group, and lowest in the PIGD group. There were no differences in L-YM2 and L-ΔYM between the PIGD group and the TD group (all p > 0.05), but they were lower than those in the normal control group (all p < 0.05). In addition, R-YM2 and R-ΔYM were negatively correlated with disease duration and UPDRS III scores in the PIGD group (all p < 0.05). R-ΔYM has the highest value in the differential diagnosis of PIGD and TD patients. The area under the receiver operating characteristic curve (ROC) curve is 0.812 (95%CI, 0.730-0.893), and the diagnostic threshold is 120.5 Kpa with a sensitivity of 63.6%, a specificity of 90.1%, a positive predictive of 80%, and a negative predictive value of 80%.

Conclusion: Shear wave elastography is a sensitive ultrasound method for evaluating muscle strength in patients with PIGD and TD. It also provides a new biological indicator to distinguish between different phenotypes of patients with PD.

Background: Given the evolving application and promising outcomes of direct oral anticoagulants (DOACs) in various thromboembolic conditions, we aimed to compare the efficacy and safety of DOACs with warfarin in the post-acute treatment of cerebral venous sinus thrombosis (CVST) using clinical and radiological parameters.

Methods: A total of 140 CVST patients were enrolled, with 95 receiving warfarin and 45 receiving DOACs as post-acute treatment. Clinical and imaging parameters of the patients in follow-up visits were investigated, including the last modified Rankin Scale (mRS), venous thromboembolic events, CVST recurrence, mortality rate, recanalization status, and hemorrhagic events, to compare the efficacy and safety of treatment between the two groups.

Results: At baseline, patients' assessments using two prognostic scores, ISCVT-RS and IN-REvASC, revealed that there was no statistically significant difference in the distribution of prognostic risk categories between the warfarin and DOACs groups. Following acute therapy, patients in the warfarin and DOACs groups were followed up for the median of 359 and 325 days, respectively. Analysis to compare the efficacy of warfarin and DOACs revealed no significant difference in last mRS scores, CVST recurrence rate, venous thromboembolic events, and recanalization status between the two groups. Additionally, there was no statistically significant difference in the risk of hemorrhagic events between warfarin and DOACs groups.

Conclusion: Our findings show that DOACs have comparable safety and efficacy in the post-acute treatment of CVST patients; however, large-scale randomized controlled trials are required to validate our findings.