Neurology最新文献

Background and objectives: Social determinants of health (SDOH) affect patient health outcomes, but the impact on patients with pediatric-onset multiple sclerosis (POMS) has not been well studied. Study objectives were to (1) describe the frequency of adverse SDOH, (2) evaluate social hardships as a potential barrier to the initiation of disease-modifying therapy (DMT), and (3) explore the association between adverse SDOH and disease outcomes in POMS, as well as study attrition.

Methods: This was a retrospective multicenter observational study conducted through the United States Network of Pediatric MS Centers database. Participants were patients diagnosed with POMS (excluding primary progressive MS). The primary outcome was time to initiation of DMT. Secondary outcomes included most recent Expanded Disability Status Scale (EDSS) score, steroid treatment for the first event, time to second event, and study attrition. Demographic variables and clinical outcomes were compared between patients with and without hardships (maternal education of high school or less, public insurance/no insurance, or single/no-income household). Multivariable regression models were used to assess the impact of social hardship on study outcomes.

Results: There were 996 total participants (69% female, mean age at symptom onset and EDSS score [±SD] were 14.2 ± 3 and 1.2 ± 1.1, respectively). Of 768 patients with complete demographic information, 66% reported a hardship. Hardship was associated with younger age at symptom onset and diagnosis. While there was no difference in time to DMT initiation, patients with hardship were more likely to receive steroids for the first event (odds ratio [OR] 1.66, 95% CI 1.21-2.26, p = 0.002). Lack of private insurance was associated with increased risk of study attrition (OR 1.85, 95% CI 1.14-3.00, p = 0.012) and higher EDSS score (β = 0.15, 95% CI 0.01, 0.28). Living in a no-income household (vs dual-income) was associated with a shorter time to second event (hazard ratio 1.33, 95% CI 1.02-1.74, p = 0.034).

Discussion: The experience of hardships is common and associated with younger age at symptom onset and diagnosis, as well as shorter time to second event. Lack of private insurance is associated with study attrition and a higher EDSS score despite no difference in time to initiating DMT. There may be differences in early disease pathophysiology related to social hardship, and future studies are needed to better understand this complex relationship.

Background and objectives: Clinical diagnosis of multiple system atrophy (MSA) is challenging. In 2022, new diagnostic criteria for MSA were proposed. We hypothesized that the positive predictive value (PPV) of clinical diagnosis of MSA improved because of advanced diagnostic tools, including brain MRI. This study aimed to understand temporal changes in PPV of MSA.

Methods: We conducted a retrospective analysis of patients clinically diagnosed with MSA whose brains were examined in the Mayo Clinic brain bank from 2008 to 2022. PPV was compared between 2 periods (2008-2017 and 2018-2022) and successively with a 4-year moving average. PPV for each clinical subtype (parkinsonism type [MSA-P] and cerebellar type [MSA-C]) was assessed.

Results: This study included 321 patients (136 women, age at death 68 ± 9 years) with a clinical diagnosis of MSA. Among them, 225 were pathologically confirmed as MSA, resulting in an overall PPV of 70%. The remaining 30% had alternative pathologic diagnoses including Lewy body disease (18%), progressive supranuclear palsy (4%), cerebrovascular disease (1%), corticobasal degeneration (1%), and others (6%). PPV improved from 63% in 2008-2017 to 78% in 2018-2022 (odds ratio [OR] 2.0 [1.2-3.5], p = 0.005). Linear analysis also demonstrated increased PPV over time (r = 0.66 [0.14-0.89], p = 0.02). Brain MRI scans were more frequently performed in 2018-2022 compared with 2008-2017 (91% vs 80%; OR 2.4 [1.2-5.0], p = 0.012). PPV was higher in patients with brain MRI compared with those without (73% vs 52%; OR 2.5 [1.3-4.9], p = 0.0057). PPV for MSA-C was similar in both groups (87% in 2008-2017 and 93% in 2018-2022), while that for MSA-P improved from 59% in 2008-2017 to 72% in 2018-2022 (OR 1.8 [1.0-3.2], p = 0.04).

Discussion: This study demonstrates an improvement in the PPV of MSA in recent years, potentially attributed to the increased use of brain MRI. Nevertheless, it also highlights that it remains difficult to make a correct diagnosis for some patients based on their clinical presentation. These findings provide a baseline for future clinicopathologic research on MSA.

Riboflavin transporter deficiency (RTD), previously referred to as Brown-Vialetto-Van Laere syndrome, is caused by pathogenic variants in the SLC52A1, SLC52A2, or SLC52A3 genes, resulting in RTD types 1, 2, and 3, respectively. Researchers estimate an occurrence of approximately 1 in 1,000,000. There is only one case of type 1 described in medical literature. Type 2 is characterized by muscle weakness in the arms and neck, vision loss, hearing impairment, and sensory ataxia. In type 3, vocal cord paralysis is more common and muscle weakness is more generalized. In 2018, we described a case of a 6-year-old girl with RTD type 2 who made remarkable visual recovery after initiation of treatment with oral riboflavin and coenzyme Q10 supplementation. The patient's younger brother began the same treatment regimen after genetic testing confirmed that he carried the same genetic variant. In this report, we update the visual and neurologic status in these siblings 5 years after our initial report and 7.5 years after initiation of riboflavin treatment.

Background and objectives: Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT.

Methods: We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean).

Results: Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system.

Discussion: All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous.

Trial registration information: ClinicalTrials.gov (NCT01422616).

Background and objectives: Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease.

Methods: Retrospective examination of data from the prospective Genetic Frontotemporal Initiative (GENFI) cohort study that recruits individuals who carry or were at risk of carrying a pathogenic variant causing FTD. GENFI participants underwent a standardized clinical and neuropsychological assessment, MRI, and a blood sample test yearly. We generated an asymmetry index for brain MRI to characterize brain asymmetry in participants with or at risk of FTD-GRN. Depending on the side of the asymmetry, we classified symptomatic GRN patients as right-GRN or left-GRN and compared their clinical features and disease progression. We generated generalized additive models to study how the asymmetry index evolves in carriers and noncarriers and compare its models with others created with volumetric values and plasma neurofilament light chain.

Results: A total of 399 participants (mean age 49.7 years, 59% female) were included (63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers). Symptomatic carriers showed higher brain asymmetry (11.6) than noncarriers (1.0, p < 0.001) and presymptomatic carriers (1.0, p < 0.001), making it possible to classify most of them as right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN showed more disease severity at baseline (β = 6.9, 95% CI 2.4-11.0, p = 0.003) but a lower deterioration by year (β = -1.5, 95% CI -2.7 to -0.31, p = 0.015) than patients with left-GRN. Brain asymmetry could be found in GRN carriers 10.4 years before the onset of the symptoms (standard difference 0.85, CI 0.01-1.68).

Discussion: FTD-GRN affects the brain hemispheres asymmetrically and causes 2 anatomical asymmetry patterns depending on the side of the disease onset. We demonstrated that these 2 anatomical asymmetry patterns present different symptoms, severity at the time of the first visit, and different disease courses. Our results also suggest brain asymmetry as a possible biomarker of conversion in GRN carriers.

Background and objectives: In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes.

Methods: Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543). We acquired 3T brain MRI at baseline and 1 year. At baseline, we measured cerebrovascular reactivity to 6% inhaled CO₂ in subcortical gray matter, normal-appearing white matter, and white matter hyperintensities (WMH). At baseline and 1 year, we quantified SVD MRI features, incident infarcts, assessed stroke severity (NIH Stroke Scale), recurrent stroke, functional outcome (modified Rankin Scale), and cognition (Montreal Cognitive Assessment). We performed linear and logistic regressions adjusted for age, sex, and vascular risk factors, reporting the regression coefficients and odds ratios with 95% CIs.

Results: We recruited 208 patients of whom 163 (mean age and SD: 65.8 ± 11.2 years, 32% female) had adequate baseline CVR and completed the follow-up structural MRI. The median increase in WMH volume was 0.32 mL with (Q1, Q3) = (-0.48, 1.78) mL; 29% had a recurrent stroke or incident infarct on MRI. At 1 year, patients with lower baseline cerebrovascular reactivity in normal-appearing tissues had increased WMH (regression coefficient: B = -1.14 [-2.13, -0.14] log₁₀ (%ICV) per %/mm Hg) and perivascular space volumes (B = -1.90 [-3.21, -0.60] log₁₀ (%ROIV) per %/mm Hg), with a similar trend in WMH. CVR was not associated with clinical outcomes at 1 year.

Discussion: Lower baseline cerebrovascular reactivity predicted an increase in WMH and perivascular space volumes after 1 year. CVR should be considered in SVD future research and intervention studies.