European Journal of Neurology最新文献

Background and purpose: The aim was to investigate the causal relationships of inflammatory cytokines and serum metabolites in cerebral small vessel disease (CSVD).

Methods: Bidirectional Mendelian randomization was first conducted to screen inflammatory cytokines and serum metabolites that were associated with imaging features of CSVD, including white matter hyperintensities, recent small subcortical infarcts, cortical cerebral microinfarcts, cerebral microbleeds, lacunes and enlarged perivascular spaces. Sensitivity analyses were performed to evaluate the robustness and pleiotropy of these results. Subsequently, inflammatory cytokines and serum metabolites that were associated with CSVD were subjected to functional enrichment. Finally, mediation analysis was employed to investigate whether inflammatory cytokines or serum metabolites acted as an intermediary for the other in their causal relationship with CSVD.

Results: Of the inflammatory cytokines, five were risk factors (e.g., tumour-necrosis-factor-related apoptosis-inducing ligand) and five (e.g., fibroblast growth factor 19) were protective factors for CSVD. Eleven serum metabolites that increased CSVD risk and 13 metabolites that decreased CSVD risk were also identified. The majority of these markers of CSVD susceptibility were lipid metabolites. Natural killer cell receptor sub-type 2B4 was determined to act as a mediating factor of an unidentified metabolite for the enlargement of perivascular spaces.

Conclusion: Several inflammatory cytokines and serum metabolites had causal relationships with imaging features of CSVD. A natural killer cell receptor mediated in part the promotional effect of a metabolite on perivascular space enlargement.

Background and purpose: Our objective was to define phenotypes of non-lesional late-onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months.

Methods: In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment.

Results: The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure-free) and cognitive performance was stabilized or even improved.

Conclusion: This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se.

Introduction: Cognitive decline is prevalent in maintenance hemodialysis patients. The blood-brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium-related biomarkers and steeper cognitive decline in this population.

Methods: Cognitive function was assessed using the Portuguese-adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini-Mental State Examination (MMSE). Endothelium-related biomarkers included syndecan-1, ICAM-1, VCAM-1 and angiopoietin-2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline.

Results: A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow-up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of -0.39 (95% CI -0.27 to -0.51) and -0.51 (95% CI -0.27 to -0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan-1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan-1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07-0.33) SD from baseline. Syndecan-1 was associated with a steeper decline in MMSE score (β 0.54, 95% CI 0.28-0.81) and executive function (β 0.17, 95% CI 0.02-0.32). Syndecan-1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64-0.83).

Conclusion: Our findings highlight the potential of syndecan-1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients.

Background and purpose: This study evaluated associations of brain amyloid with 2-year objective and subjective cognitive measures in a trial-ready older general population at risk for dementia.

Methods: Forty-eight participants in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability underwent ¹¹C-Pittsburgh compound B (PiB) positron emission tomography (PET) scans and assessment of cognition (modified Neuropsychological Test Battery [NTB]) and subjective memory complaints (Prospective and Retrospective Memory Questionnaire).

Results: Mean age was 71.4 ± 5.06 years, and 20 participants (42%) had positive baseline PiB-PET scans. Amyloid positivity was associated with lower NTB executive function at baseline and less favorable 2-year NTB total score and memory trajectories, but not with other objective or subjective cognitive measures. Overall, there was little cognitive decline during 2 years.

Conclusions: Amyloid accumulation may affect objective but not necessarily subjective cognition from a very early at-risk stage, although substantial decline likely requires >2 years to occur.

Background and purpose: The purpose was to perform a nationwide epidemiological study of Guillain-Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the coronavirus disease 2019 (COVID-19) years.

Methods: This was an observational study collecting all GBS diagnoses from the National Epidemiological Surveillance Network collected by the Ministry of Health. Patients discharged with GBS as the main diagnosis and admitted during 2018-2021 were included. Data on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were obtained from the National Epidemiology Centre.

Results: In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, the elderly population and in the winter season. Eleven per cent of GBS patients needed ventilatory support. GBS and SARS-CoV-2 incidences did not correlate with one another (r = -0.29, p = 0.36). GBS incidence decreased during 2020 and during the COVID-19 lockdown period in comparison to the same months of 2018-2019.

Conclusions: The incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID-19-associated GBS in Spain, a significant drop of GBS incidence during the SARS-CoV-2 pandemic was detected, probably due to prevention measures.

Background and purpose: HER-MES was the first head-to-head study of erenumab against topiramate (standard of care). This post hoc analysis of the HER-MES study evaluated the effect of erenumab versus topiramate on patient-reported outcomes at week 24.

Methods: Adult patients with episodic or chronic migraine (n = 777) were randomized (1:1) to monthly subcutaneous erenumab (n = 389) or daily oral topiramate (n = 388). Migraine-related disability, as measured by the Headache Impact Test 6 (HIT-6) and Short Form 36 Health Survey version 2 (SF-36v2), was analysed in the entire study cohort and true completers.

Results: In the erenumab group (vs. topiramate), significant improvements were reported in Headache Impact Test 6 total scores (composite populations, -10.88 vs. -7.72; true completers, -11.92 vs. -10.61) and a higher proportion of patients achieved a ≥5-point reduction from baseline with erenumab (composite populations, 72.2% vs. 53.9%; true completers, 79.64% vs. 71.43%). The adjusted mean change from baseline in the SF-36v2 score was greater with erenumab for both physical component summary (composite population, 5.48 vs. 3.63; true completers, 5.95 vs. 5.23) and mental component summary (composite populations, 1.00 vs. -1.18; true completers, 1.74 vs. -0.33). A higher proportion of patients on erenumab versus topiramate had a ≥5-point improvement in SF-36v2 for the physical component summary (composite populations, 47.7% vs. 37.4%; true completers, 52.1% vs. 48.9%) and mental component summary (composite populations, 25.3% vs. 16.8%; true completers, 27.3% vs. 17.7%).

Conclusions: This post hoc analysis demonstrated that patients treated with erenumab had significant improvements in headache impact and quality of life as measured by patient-reported outcomes versus patients treated with topiramate.

Background and purpose: Acetylcholine receptor antibody (AChR-Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR-Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell-based assay (F-CBA) in RIA-AChR-Ab positive subjects without MG symptoms, to assess whether F-CBA could show a higher specificity compared to RIA in detecting pathogenic Abs.

Methods: We reviewed medical records of patients referred to our MG outpatient clinic because of RIA-AChR-Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR-Abs were tested by RIA in the whole cohort. Serum samples from RIA-positive asymptomatic subjects were retested by F-CBA.

Results: Of 605 subjects who tested RIA-AChR-Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA-AChR-Ab positive although they had never had MG symptoms; in four of these subjects AChR-Abs were not detected by F-CBA, whereas the remaining two (both non-MG thymoma cases) were positive also by F-CBA.

Conclusions: RIA false positivity for AChR-Ab is very rare. Previous literature has demonstrated that F-CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F-CBA may be more specific than RIA for MG diagnosis.