Neurology最新文献

Objectives: Several treatments have been approved for the prevention of attacks in AQP4-IgG+ neuromyelitis optica spectrum disorder (NMOSD). However, because of the rarity of the disease, little is known concerning how to switch from one treatment to another in case of lack of effectiveness or side effects. In this article, we report a severe attack in a patient with NMOSD after switching from eculizumab to satralizumab.

Methods: A 44-year-old woman with NMOSD was treated with azathioprine and then rituximab, without optimal control of the disease. Eculizumab was initiated with clinical efficacy. Two years later, after the onset of rheumatoid arthritis and because of difficult venous access, a switch to satralizumab was proposed.

Results: After switching, a severe attack occurred 11 weeks after the last eculizumab infusion. Severe tetraplegia was related to a new extensive cervical lesion associated with a tumefactive lesion of the corpus callosum. The patient was treated with 10 infusions of methylprednisolone and 10 plasma exchanges. Eculizumab was reintroduced 20 days after symptom onset. Three months later, mild improvement was observed.

Discussion: In clinical practice, in case of intolerance or side effects, anticomplement therapy should be switched to another NMOSD treatment with caution because of a high risk of relapse.

Classification of evidence: This case report provides Class IV evidence that eculizumab should be stopped with caution and switched to another treatment immediately. This is a single observational study without controls.

Background and objectives: Rheumatoid arthritis (RA) has been linked to an increased risk of dementia, yet little is known about how RA affects the progression of cognitive impairment and the risk of mortality in people with dementia. We aimed to investigate whether RA is linked to an accelerated cognitive decline and a higher risk of all-cause mortality in patients with dementia.

Methods: We conducted a propensity score-matched register-based cohort study based on the Swedish Registry for Cognitive/Dementia Disorders-SveDem. Patients diagnosed with dementia and registered in SveDem between May 1, 2007, and October 16, 2018, were included. The main outcome for the study was cognitive decline, measured by Mini-Mental State Examination (MMSE) score changes over years. The secondary outcome was all-cause death. We used mixed-effects models to examine the association between RA and cognitive decline, and Cox proportional hazards models to investigate the risk of all-cause mortality. We also conducted subgroup analyses to explore the potential effects of sociodemographic, baseline MMSE, comorbidities, and the use of dementia medications on the association between RA and outcomes.

Results: We included 1,685 dementia patients with RA (mean [SD] age, 79.9 [6.7] years; 73.4% were women) and 5,055 dementia patients with non-RA (80.1 [7.5] years; 73.1% were women). The median follow-up was 2.9 years (interquartile range, 1.5-4.6 years) for non-RA and 2.6 years (interquartile range, 1.4-4.2 years) for RA. In total, 111,266 MMSE measurements were available for analysis. Compared with non-RA patients, patients with RA presented faster cognitive decline (β = -0.24 points/y; 95% CI -0.38 to -0.10) and an increased risk of death (hazard ratio 1.15; 95% CI 1.06-1.24). In subgroup analysis, significant interactions were observed between RA and baseline MMSE scores as well as living conditions regarding cognitive decline (p for interaction <0.05).

Discussion: We identified a worse cognitive function and an increased mortality risk in dementia patients with RA compared with non-RA. However, we lacked information on the duration of RA before the onset of dementia and on disease activity, which could influence our findings. Further studies are needed to validate these results in comparable populations.

Background and objectives: In the field of stroke epidemiology, one of the major advances in the recently implemented International Classification of Diseases, 11th revision (ICD-11) relates to the definition of ischemic stroke, which now includes events shorter than 24 hours when ischemia can be proven on brain imaging. However, data are scarce to ascertain the incidence of strokes of short duration with tissue evidence of ischemia. In this study, we determined the incidence, 30-day case fatality, and mortality rate of stroke in the Geneva population using the new ICD-11 criteria, taking advantage of the organization of stroke service in the area.

Methods: In this population-based observational cohort study, we used data from the Swiss Stroke Registry, supplemented by hospital records, outpatient medical files, and autopsy, to identify residents of the canton of Geneva, Switzerland, meeting the ICD-11 criteria for first-ever stroke, including ischemic strokes, nontraumatic intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH), from January 1, 2018, to December 31, 2019.

Results: We identified 1,186 first-ever strokes (75.8 years [interquartile range 63.4-84.5]; 571 women [48.1%]). MRI was performed in 90.9% of patients with ischemic strokes. The annual incidence of first-ever stroke, age-adjusted to the European Standard Population, was 127.0/100,000 (95% CI 119.8-134.3) (107.3 [100.7-114.0] for ischemic stroke, 13.2 [10.9-15.5] for ICH, and 6.0 [4.4-7.5] for SAH [3.1 {2.0-4.2} for aneurysmal SAH]). Overall, the 30-day case fatality was higher in ICH (32.5% [95% CI 19.7-38.8], compared with SAH (17.2% [6.6-27.9] and ischemic strokes 10.8% [8.4-12.4]). The incidence of ischemic stroke was 107.3 (100.7-114.0) according to ICD-11 and 90.4 (84.3-96.5) according to ICD-10 (excluding patients with radiologic infarct and symptoms lasting <24 hours). Compared with ICD-10, ICD-11 increased the number of ischemic stroke cases by 18.3%. Patients with ischemic strokes identified with ICD-11 but not under ICD-10 (i.e., patients with symptoms lasting <24 hours and a brain lesion) were younger and presented with a lower National Institutes of Health Stroke Scale (NIHSS) score on admission compared with those identified by ICD-10 and ICD-11.

Discussion: The new ICD-11 clinicoradiologic definition of ischemic stroke increased the number of ischemic stroke cases by 18.3% in our Western European population. Future studies will evaluate the impact of ICD-11 on the human, organizational, and economic needs allocated to the management of the disease.

Background and objectives: Migraine is a multifaceted primary headache disorder. In neuroimaging of migraine, fMRI has been used to elucidate pathophysiology or monitor treatment effects. The current literature, however, is highly heterogeneous regarding reported variables and methodologies. This begets a lack of comparability and complicates synthesis of results across studies. We developed a framework for standardized reporting of fMRI studies in migraine.

Methods: Experts on fMRI in migraine were identified from the literature and subjected to structured questionnaires in 2 iterations of 3 rounds according to the DELPHI method. A total of 157 statements across 17 reporting domains were rated on 5-point Likert scales (strong support to strong opposition). The first iteration covered demographic data, migraine-specific factors, medication, scan timing, healthy controls (HCs), participant sampling/recruiting, standardized forms, study preregistration, region of interest (ROI) analyses, validation data sets, data sharing, preprocessing documentation, and analysis software. The second iteration of the questionnaire covered scanner-related factors, sequence-related factors, physiology monitoring, and stimulation-related factors. Items showing strong consensus/consensus (≥90%/≥75% of participants indicating scores 4 or 5) were included as standard reporting items.

Results: All 3 rounds of the first/second iteration were completed by 29 and 26 researchers (age 46 ± 11 years; 38% female/age 46 ± 12 years; 44% female) from 23 and 21 institutions. Across both iterations, strong consensus and consensus was achieved for 34 (3 scanner-related factors, 9 sequence-related factors, 1 stimulation-related factor, 2 demographic factors, 7 migraine-specific factors, 2 medication-factors, 2 scan timing factors, 4 HC factors, 1 preregistration factor, 1 analysis software factor, and 2 ROI analyses factors) and 33 (1 scanner-related factors, 4 sequence related factors, 1 factor related to physiology monitoring, 1 stimulation-related factor, 3 demographic factors, 6 migraine-specific factors, 4 medication factors, 3 HC factors, 2 sampling factors, 1 standardized form, 1 preregistration factor, 1 data sharing factor, 2 analysis software factors, and 3 ROI analyses factors) items, respectively. From these, a checklist covering 63 items from 14 reporting domains was created.

Discussion: We present an expert-based framework for reporting standards in fMRI studies of migraine, which can be used for future studies to homogenize cohort characterization, fMRI acquisitions, and analysis protocols.

Background and objectives: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible neurologic disorder that remains poorly understood. Accurate differential diagnosis of iNPH and Alzheimer disease (AD) is complicated by overlapping clinical manifestations. Beyond neuroimaging, there are currently no biomarkers available for iNPH leading to frequent misdiagnosis, and proteomic studies into iNPH have been limited by low sample sizes and inadequate analytical depth. In this study, we report the results of a large-scale proteomic analysis of CSF from patients with iNPH to elucidate pathogenesis and identify potential disease biomarkers.

Methods: CSF samples were collected through lumbar puncture during diagnostic visits to the Mass General Brigham neurology clinic. Samples were analyzed using mass spectrometry. Differential expression of proteins was studied using linear regression models. Results were integrated with publicly available single-nucleus transcriptomic data to explore potential cellular origins. Biological process enrichment was analyzed using gene-set enrichment analyses. To identify potential diagnostic biomarkers, decision tree-based machine learning algorithms were applied.

Results: Participants were classified as cognitively unimpaired (N = 53, mean age: 66.5 years, 58.5% female), AD (N = 124, mean age: 71.2 years, 46.0% female), or iNPH (N = 44, mean age: 74.6 years, 34.1% female) based on clinical diagnosis and AD biomarker status. Gene Ontology analyses indicated upregulation of the immune system and coagulation processes and downregulation of neuronal signaling processes in iNPH. Differential expression analysis showed a general downregulation of proteins in iNPH. Integration of differentially expressed proteins with transcriptomic data indicated that changes likely originated from neuronal, endothelial, and glial origins. Using machine learning algorithms, a panel of 12 markers with high diagnostic potential for iNPH were identified, which were not all detected using univariate linear regression models. These markers spanned the various molecular processes found to be affected in iNPH, such as LTBP2, neuronal pentraxin receptor (NPTXR), and coagulation factor 5.

Discussion: Leveraging the etiologic insights from a typical neurologic clinical cohort, our results indicate that processes of immune response, coagulation, and neuronal signaling are affected in iNPH. We highlight specific markers of potential diagnostic interest. Together, our findings provide novel insights into the pathophysiology of iNPH and may facilitate improved diagnosis of this poorly understood disorder.