Acta neurologica Belgica最新文献

Background: Functional Cognitive Disorder (FCD) is defined by persistent subjective cognitive complaints that are inconsistent with objective performance on neuropsychological testing. One leading hypothesis suggests that FCD may involve a dissociation between different forms of metacognition, particularly between global and local self-monitoring mechanisms.

Objective: To quantitatively synthesize the evidence for global and local metacognitive performance in individuals with FCD through meta-analysis.

Methods: We conducted a systematic review and meta-analysis of studies measuring metacognitive performance in FCD, including comparisons with healthy controls and mild cognitive impairment (MCI). Global metacognition was assessed using self-appraisal metrics, while local metacognition was measured using trial-by-trial confidence accuracy tools such as meta-d'/d'. Effect sizes (Cohen's d) were calculated and pooled using random-effects models.

Results: Three studies were included in the global metacognition analysis, revealing a large pooled effect size indicating impaired global metacognition in FCD (Cohen's d = - 1.07). One study assessed local metacognition and showed no impairment (Cohen's d = 0.00). This supports the proposed dissociation, with preserved local but disrupted global self-monitoring.

Conclusion: Our findings provide meta-analytic evidence for a substantial deficit in global metacognitive insight in individuals with FCD, while local metacognitive abilities remain relatively intact. These results offer a mechanistic explanation for the discrepancy between subjective complaints and objective test performance in FCD. Interventions targeting global metacognitive appraisal may enhance clinical outcomes. Given the very small number of eligible studies, these findings should be interpreted cautiously and viewed as preliminary.

Objective: Diagnosing prolonged disorders of consciousness (DoC) remains a significant challenge in neurorehabilitation. Heart rate variability (HRV), a noninvasive measure of cardiac autonomic regulation, has been increasingly recognized as relevant to the mechanisms underlying consciousness. However, long-term HRV data in DoC patients remain scarce. This study aimed to investigate the relationship between long-term HRV metrics and the severity of consciousness impairment in patients with prolonged DoC.

Methods: In this cross-sectional study, 49 patients with prolonged DoC were enrolled. Each participant underwent five assessments using the Coma Recovery Scale-Revised (CRS-R) and one 24-hour electrocardiographic (ECG) monitoring session within one week of enrollment. Based on their highest CRS-R subscale scores, patients were categorized into three groups: unresponsive wakefulness syndrome (UWS, n = 17), minimally conscious state (MCS, n = 19), and emergence from MCS (EMCS, n = 13). HRV time-domain and frequency-domain indices were extracted from the 24-hour ECG recordings. Differences in HRV metrics among the consciousness groups were analyzed, and correlations between HRV parameters and CRS-R scores were examined.

Results: Significant differences in HRV metrics were observed among the three consciousness groups (P < 0.05), including both time-domain indices (SDNN, SDANN, SDNN Index) and frequency-domain indices (HF, LF, VLF, ULF, and Total power). Furthermore, these HRV indices were significantly correlated with CRS-R scores (P < 0.05), indicating a strong association between autonomic function and the level of consciousness.

Conclusion: Long-term HRV monitoring reveals significantly greater heart rate variability in EMCS patients compared to those in UWS and MCS, highlighting its potential utility as a supplementary biomarker for assessing consciousness in patients with prolonged DoC.

Background and objectives: In stroke thrombi, neutrophil extracellular traps (NETs) have been hypothesized to promote thrombogenic processes that enhance stability and decrease amenability to thrombolysis and endovascular removal. Here, we examined the relationship between NET enrichment and clot structure and mechanical properties.

Methods: Platelet-rich plasma and red blood cells (RBCs) were isolated from human blood and mixed with concentrated white blood cells to produce no-RBC and high-RBC clot analogs (0% and 40%, respectively). Lipopolysaccharide (LPS) was added at 3 different concentrations to enrich clots with varying amounts of NETs. Clots were analyzed mechanically using a uniaxial stretch tester. Clots were also imaged by microCT, and histology was used to investigate biologic structure and composition, as well as NET enrichment. Statistical analysis was completed to assess stiffness, radiomic, and histological features among clots of various NET enrichment. Clustering was performed on radiomic and histological image features to identify feature signatures unique to NET-enriched clots, and correlation was performed to identify radiomics and histomics related to NET enrichment.

Results: LPS enriched clots with NETs in a dose-dependent manner, and NETs were associated with greater microstructural complexity. For fibrin-platelet rich clots (0% RBCs), NET enrichment produced a significant increase in mechanical stiffness as measured by Young's Modulus, as well as in breaking strength. For each percent composition, radiomic and histomic profiling clustered clot analogs well by NET-enrichment, with NET-enriched clots demonstrating radiomic and histological texture feature correlations distinct from clots without NETs.

Conclusion: NET enrichment produces mechanically stiffer stroke clot analogs with distinct microstructure, radiomic, and histological profiles.

X-linked adrenoleukodystrophy (X-ALD) is a rare, inherited peroxisomal disorder caused by pathogenic variants in the ABCD1 gene, which encodes an ATP-binding cassette transporter located on Xq28. These pathogenic variants result in defective peroxisomal beta-oxidation and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues, primarily affecting the adrenal cortex, myelin in the central nervous system, and Leydig cells. The estimated incidence is approximately 1 in 17,000 individuals (Kemp et al. 2016). Clinically, X-ALD is characterized by a broad phenotypic spectrum, including three main presentations: isolated adrenocortical insufficiency, adrenomyeloneuropathy (AMN), and cerebral X-ALD (Raymond et al. 1999). Considerable clinical overlap exists among these forms, and disease severity can vary. The cerebral form most commonly presents in childhood, between ages 4 and 8, whereas adult-onset cerebral X-ALD is rare, representing only about 1% of cases (Bezman et al., American Journal of Medical Genetics. 76(5):415-419, 1998). The parieto-occipital white matter is classically involved, while predominant frontal lobe lesions are unusual. Misdiagnosis is frequent, with rates up to 31%, particularly when cognitive and behavioral changes mimic frontotemporal dementia (Jiang et al., Acta Neurologica Belgica. 123(6):2259-2268, 2023). This report describes a 53-year-old man with an atypical adult-onset cerebral X-ALD presenting with frontal lobe involvement and rapid progression. The case underscores the importance of considering X-ALD in adults presenting with atypical cognitive decline and non-classical MRI patterns.

Background: Ocrelizumab, a CD20-targeting monoclonal antibody, is a novel disease-modifying therapy for relapsing-remitting multiple sclerosis (MS) and primary progressive multiple sclerosis. Despite established efficacy in reducing relapse rates and disease progression, its impact on patient-reported outcomes (PROs) such as health-related quality of life (HRQOL), depression, and fatigue remains understudied.

Methods: This single-arm observational study included 30 MS patients receiving ocrelizumab at a tertiary center in Tehran, Iran. Selected PROs were assessed at 0-, 6-, and 12-month time points using the Medical Outcomes Study Short Form-36 for HRQOL, the Beck Depression Inventory-II for depression severity, and the Fatigue Severity Scale for fatigue. Longitudinal changes were analyzed using linear mixed models. Linear regression models were used to explore associations between patient demographics, clinical characteristics, and PRO scores at baseline.

Results: At baseline, participants had impaired HRQOL across multiple domains. Over 12 months, significant improvements were observed in general health (P < .001), vitality (P = .032), and role-emotional (P = .012), along with increases in the mental (P = .026) and physical (P = .020) component summary scores. Depression severity decreased significantly (P = .029), but no significant changes were detected in fatigue levels (P = .818). Higher baseline EDSS was associated with lower physical functioning (P < .001) and general health (P = .023).

Conclusion: Ocrelizumab treatment was associated with improved physical and mental HRQOL and reduced depression severity in MS patients.

Objective: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions.

Methods: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships.

Results: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect).

Conclusion: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.