We retrospectively collected information for 324 consecutively hospitalized adults with stroke on the neurology service at the University Teaching Hospital in Lusaka, Zambia, between October 2018 and March 2019. Stroke characteristics were then compared by biological sex.
Female participants constituted 62% (n = 200) of the cohort, were older (61 ± 19 vs 57 ± 16 years, p = 0.06), had fewer hemorrhagic stroke than male participants (22% vs 37%, p = 0.001), and had higher rates of hypertension (84% vs 74%, p = 0.04), diabetes (19% vs 13%, p = 0.04), heart disease (38% vs 27%, p = 0.04), and history of stroke (26% vs 14%, p = 0.01). Male participants had higher rates of alcohol (33% vs 4%, p < 0.001) and tobacco (19% vs 2%, p < 0.001) use. Female participants were less likely to have neuroimaging completed during their hospitalization (82% vs 94%, p = 0.002) and had higher 90 days postdischarge mortality (28% vs 10%, p = 0.002) independent of age and stroke subtype (OR 2.48, 95% CI 1.1–5.58, p = 0.03).
Female participants in this Zambian stroke cohort had a higher prevalence of vascular risk factors but were less likely to have neuroimaging completed. Postdischarge mortality was markedly higher among female participants even after adjusting for age and stroke subtype. Our data highlight the need for future studies of social and socioeconomic factors that may influence stroke-related outcomes.
Based on the patient's nerve conduction studies, he was diagnosed with a specific immune-mediated neuromuscular disorder. He was started on intravenous immunoglobulin, but within days of the first infusions experienced a rare and potentially life-threatening complication. He received appropriate treatment and was started on alternative immunotherapy, after which his symptoms improved.
Our case exemplifies the features of a specific subtype of a more common immune-mediated neuromuscular diagnosis with unique elements of history, examination, and nerve conduction studies that required interpretation in the clinical context. We also discuss a rare side effect of a commonly used immunotherapy and its risk factors and comment on the likelihood that this diagnosis may be related to a preceding COVID-19 vaccine booster.
We identified 6 studies, including 1,723 participants (mean age: 71 years, 51% women; 53% treated with IVT at a PSC). The mean onset-to-groin puncture time did not differ between the 2 groups (mean difference: –20 minutes, 95% CI –115.89 to 76.04). Patients receiving IVT before transfer had higher odds of 3-month reduced disability (common OR = 1.98, 95% CI 1.17–3.35), excellent (OR = 1.70, 95% CI 1.28–2.26), and good (OR = 1.62.95% CI 1.15–2.29) functional outcomes, with no increased sICH (OR = 0.87, 95% CI 0.54–1.39) or mortality (OR = 0.55, 95% CI 0.37–0.83) risks. In the adjusted analyses, patients receiving IVT at a PSC had higher odds of excellent functional outcome (aOR = 1.32, 95% CI 1.00–1.74) and a lower probability for mortality (aOR = 0.50, 95% CI 0.27–0.93).
Patients with LVO receiving IVT at a PSC before an EVT transfer have a higher likelihood of excellent functional recovery and lower odds of mortality, with no increase in sICH and onset-to-groin puncture times, compared with those transferred for EVT without previously receiving IVT.
Participants enrolled 2003–2007 in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who were stroke free at baseline were followed for incident stroke. Associations of traditional stroke risk factors with incident stroke were assessed using (1) proportional hazards analysis based on the baseline age of the participant and (2) Poisson regression analysis assessing associations based on the changing age of the participant during their follow-up (age at exposure). In each analysis, age strata were selected to have a similar number of strokes in each stratum, specifically 45–64, 65–73, and 74+ years for the proportional hazards analysis and 45–69, 70–79, and 80+ years for Poisson regression.
A total of 1,405 ischemic stroke events occurred among 28,235 participants over a median follow-up of 11.3 years, with a total of 276,074 person-years exposure. For both analytic approaches, the magnitude of the association with stroke was significantly less at older ages for diabetes (hazard or relative risk decreasing from 2.0 in younger strata to 1.3 in older strata), heart disease (from 2.0 to 1.3), and hypertension defined at a threshold of 140/90 mm Hg (from 1.80 to 1.50); however, there was no age-related difference in the magnitude of the association for smoking, atrial fibrillation, or left ventricular hypertrophy.
Hypertension and diabetes are 2 of the more important risk factors for stroke; however, their association with stroke risk appears substantially less at older ages. That the magnitude of the association for smoking, atrial fibrillation, and left ventricular hypertrophy does not decrease with age suggests their relative importance in determining stroke risk likely increases with age.
To understand the role of premature (defined as ≤ 60 years) cardiovascular disease (CVD) in brain health earlier in life, we examined the associations of premature CVD with midlife cognition and white matter health.
We studied a prospective cohort in the Coronary Artery Risk Development in Young Adults study, who were 18–30 years at baseline (1985–1986) and followed up to 30 years when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI measures of white matter hyperintensity (WMH) and white matter integrity. A premature CVD event was adjudicated based on medical records of coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the associations of nonfatal premature CVD with cognitive performance (z-standardized), cognitive decline, and MRI measures.
Among 3,146 participants, the mean age (57% women and 48% Black) was 55.1 ± 3.6 years, with 5% (n = 147) having premature CVD. Adjusting for demographics, education, literacy, income, depressive symptoms, physical activity, diet, and APOE, premature CVD was associated with lower cognition in 4 of 5 domains: global cognition (–0.22, 95% CI –0.37 to –0.08), verbal memory (–0.28, 95% CI –0.44 to –0.12), processing speed (–0.46, 95% CI –0.62 to –0.31), and executive function (–0.38, 95% CI –0.55 to –0.22). Premature CVD was associated with greater WMH (total, temporal, and parietal lobes) and higher white matter mean diffusivity (total and temporal lobes) after adjustment for covariates. These associations remained significant after adjusting for cardiovascular risk factors (CVRFs) and excluding those with stroke/TIA. Premature CVD was also associated with accelerated cognitive decline over 5 years (adjusted OR 3.07, 95% CI 1.65–5.71).
Premature CVD is associated with worse midlife cognition and white matter health, which is not entirely driven by stroke/TIA and even independent of CVRFs. Preventing CVD in early adulthood may delay the onset of cognitive decline and promote brain health over the life course.
We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989–2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight.
The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy migraine (11%) was associated with higher risks of preterm delivery (RR = 1.17; 95% CI = 1.05–1.30), gestational hypertension (RR = 1.28; 95% CI = 1.11–1.48), and preeclampsia (RR = 1.40; 95% CI = 1.19–1.65) compared with no migraine. Migraine was not associated with low birthweight (RR = 0.99; 95% CI = 0.85–1.16) or GDM (RR = 1.05; 95% CI = 0.91–1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22–1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04–1.61; p-heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2x/week RR = 1.24; 95% CI = 1.11–1.38; ≥2x/week RR = 0.55; 95% CI = 0.35–0.86; p-interaction < 0.01) and preeclampsia (<2x/week RR = 1.48; 95% CI = 1.25–1.75; ≥2x/week RR = 1.10; 95% CI = 0.62–1.96; p-interaction = 0.39); however, power for these stratified analyses was limited.
Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine.
Participants were followed for an average of 10 years in one of the 2 longitudinal clinical pathologic studies of aging. Global cognition was assessed using a composite score derived from 19 neuropsychological tests' scores. Postmortem pathologic assessment included examination of 3 AD (amyloid-β and tau tangles determined by immunohistochemistry, and a global AD pathology score derived from diffuse and neurotic plaques and neurofibrillary tangle count) and 8 non-AD pathology indices. ER molecular genomic variants included genotyping and examining ER DNA methylation and RNA expression in brain regions including the dorsolateral prefrontal cortex (DLPFC) that are major players in cognition and often have AD pathology.
The mean age of women (N = 1711) at baseline was 78.0 (SD = 7.7) years. In women, GPER1 molecular variants had the most consistent associations with AD traits. GPER1 DNA methylation was associated with cognitive decline, tau tangle density, and global AD pathology score. GPER1 RNA expression in DLPFC was related to cognitive decline and tau tangle density. Other associations included associations of ER2 and ER1 sequence variants and DNA methylation with cognition. RNA expressions in DLPFC of genes involved in signaling mechanisms of activated ERs were also associated with cognitive decline and tau tangle density in women. In men (N = 651, average age at baseline: 77.4 [SD = 7.3]), there were less robust associations between ER molecular genomic variants and AD cognitive and pathologic traits. No consistent association was seen between ER molecular genomic variations and non-AD pathologies in either of the sexes.
ER DNA methylation and RNA expression, and to some extent ER polymorphisms, were associated with AD cognitive and pathologic traits in women, and to a lesser extent in men.
Of 1,435 patients in the original cohort, 90 patients received ASM triple therapy after second-line ASM treatment failure due to uncontrolled seizures. LEV + VPA + CLB was prescribed to 48% (43/90) and other ASM triple therapy to 52% (47/90) of patients. The cumulative incidence of treatment failure for any reason of LEV + VPA + CLB did not statistically significantly differ from that of other ASM triple therapy combinations (12 months: 47% [95% CI 31%–62%] vs 42% [95% CI 27%–56%], p = 0.892). No statistically significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95% CI 4%–25%] vs 18% [95% CI 8%–30%], p = 0.445), adverse effects (12 months: 22% [95% CI 11%–36%] vs 15% [95% CI 7%–27%], p = 0.446), or recurrent seizures (1 month: 65% [95% CI 48%–78%] vs 63% [95% CI 47%–75%], p = 0.911) were found.
LEV + VPA + CLB might show equivalent effectiveness compared with other ASM triple therapy combinations in patients with glioma.
This study provides Class III evidence that for patients with glioma with refractory epilepsy on triple therapy ASMs, LEV + VPA + CLB demonstrated similar effectiveness and tolerability compared with other ASM triple therapy combinations.
PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Francaise de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected.
Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5–23.7), and the median progression-free survival was 5.9 months (range 1.6–10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0–1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02–0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05–7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32–12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D–E) (HR 0.38, 95% CI 0.07–1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118–1.05; p = 0.06) was at the limit of significance.
Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.
This study suggests an overall favorable prognosis for slowly recovering athletes and provides data for athletes and medical teams to consider in calibrating RTP expectations and making decisions about medical disqualification vs ongoing engagement in their sport.
The National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, most of whom experienced augmented symptoms from dopamine agonists. Information on opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors was collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention was provided by the study staff to local providers.
Registry participants (n = 448) with 2-year longitudinal data available were mostly White, female, older than 60 years, and, at Registry entry, had been on opioids for a median of 1–3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD = 43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2 years was 0 MME (interquartile range = 0–10). While 41.1% of participants increased their dose during the follow-up period (median increase = 10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME, respectively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of nonopioid RLS treatment medications, at least mild insomnia at baseline, a history of depression, male sex, younger than 45 years, and opioid use for comorbid pain.
Low-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 years of follow-up in most of the participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and nonopioid RLS medications and opioid use for a non-RLS condition. Continued longitudinal observations will provide insight into the long-term safety and efficacy of opioid treatment of severe, augmented RLS.
This study provides Class IV evidence that opioid doses increase in roughly 40% of patients, in most by small amounts, over a 2-year period when prescribed for adult refractory restless leg syndrome.
Extracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared with 3 other non-COVID surgical epilepsy brain tissues.
We demonstrate the presence of viral nucleocapsid protein in extracellular vesicles and microvascular disease in the brain of a patient undergoing epilepsy surgery shortly after SARS-CoV-2 infection. Endothelial cell activation was indicated by increased levels of platelet endothelial cell adhesion molecule-1 and was associated with fibrinogen leakage and immune cell infiltration in the biopsy tissue as compared with control non-COVID surgical epilepsy brain tissues.
Despite the lack of evidence of viral replication within the brain, the presence of the nucleocapsid protein was associated with disease-specific endothelial cell activation, fibrinogen leakage, and immune cell infiltration.
The impact of neurologic deficits on the EQ-5D in patients with ischemic stroke is mostly due to limb paresis, while the EQ-5D is less sensitive to other nonmotor deficits such as hemianopia, aphasia, and neglect. This may lead to overestimation of quality of life and, consequently, underestimation of the (cost-)effectiveness of treatments and interventions.
ClinicalTrials.gov. Unique identifier: NCT00359424.
The 55 included patients had a median admission Glasgow Coma Scale score of 14 (interquartile range [IQR] 9–15), an intracerebral hemorrhage (ICH) score of 1 (IQR 1–2), and a hematoma volume of 8.6 mL (IQR 3.4–13.8 mL). Receiver operating curve analysis found the sST2 level to be predictive of poor outcome with an area under the curve of 0.763 (95% CI 0.632–0.894) and Youden optimum cut point of 61.8 ng/mL (p < 0.001). sST2 remained an independent predictor after adjustment for ICH score (adjusted odds ratio 2.53, 95% CI 1.03–6.19, p = 0.042). Measurement of PHE found those patients with high sST2 to have greater edema volume over time (β = 1.07, 95% CI 0.51–1.63, p < 0.001). High sST2 was associated with a shift toward an innate peripheral immune response (monocytes and natural killer cells; 68.6% ± 5.1% vs 47.5% ± 4.0%; p = 0.003).
Our findings demonstrate that elevated sST2 links the peripheral innate immune response to PHE volume and outcome after IPH. This knowledge is relevant to future studies that seek to identify patients with IPH at highest risk for immune-mediated injury or limit injury through targeted interventions.
Between April 2017 and March 2019, we randomized 736 participants. Because only 9 participants just had tension-type headache, our main analyses were on the 727 participants with migraine. Of them, 376 were allocated to the self-management intervention and 351 to usual care. Data from 586 (81%) participants were analyzed for primary outcome. There was no between-group difference in HIT-6 (adjusted mean difference = –0.3, 95% CI –1.23 to 0.67) or headache days (0.9, 95% CI –0.29 to 2.05) at 12 months. The Chronic Headache Education and Self-management Study intervention generated incremental adjusted costs of £268 (95% CI, £176–£377) (USD383 [95% CI USD252–USD539]) and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI –0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained.
These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management program for people living with chronic migraine or chronic tension–type headache with episodic migraine.
Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 doi.org/10.1186/ISRCTN79708100. The first enrollment was April 24, 2017.
This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache-related quality of life in people with chronic migraine.
Our findings do not support migraine as a causal risk factor of MS. Several genetic variants, particularly in the MHC, may account for some of the overlap. It seems likely that migraine within the context of MS is because of MS. Identifying what increases the risk of migraine within MS might lead to an improved treatment and quality of life.
Children younger than 16 years with a DEE or ID+E were ascertained using EEG records from 2000 to 2016 in the Wellington region of New Zealand. Epilepsy syndromes were diagnosed on medical record and EEG review. Point prevalence and cumulative incidence for children with epilepsy and developmental impairment, DEE and ID+E were calculated. Cumulative incidence for each epilepsy syndrome was calculated.
The cohort comprised 235 children (58% male) with developmental impairment and epilepsy, including 152 (65%) with DEE and 83 (35%) with ID+E. The median age of seizure onset was 15.4 months (range day 1–15 years). The median follow-up from seizure onset was 7.9 years (range 0–18.2 years). Point prevalence for the broad group of children with epilepsy and developmental impairment was 175/100,000 children (95% CI 149–203; DEE 112 and ID+E 63/100,000 children). Cumulative incidence for DEE was 169/100,000 children (95% CI 144–199) and that for ID+E was 125/100,000 children (95% CI 95.4–165). Cumulative incidence per 100,000 children was as follows: infantile epileptic spasms syndrome 58.2 (95% CI 45.0–75.3), epilepsy with myoclonic-atonic seizures 16.4 (95% CI 9.69–27.7), Lennox-Gastaut syndrome 13.2 (95% CI 4.1–41.9), and Dravet syndrome 5.1 (95% CI 2.1–12.2). Fifty/152 (33%) of children with DEE and 70/83 (84%) with ID+E could not be diagnosed with a known epilepsy syndrome.
Epilepsy and developmental impairment before the age of 16 years occurs in 1 in 340 children, with 1 in 590 having a DEE and 1 in 800 having ID+E. These individuals require significant health and community resources; therefore, these data will inform complex health service and education planning. Epidemiologic studies have focused on early childhood–onset DEEs. These do not fully reflect the burden of these disorders because 27% of DEEs and 70% of ID+E begin later, with seizure onset after the age of 3 years. Understanding the cumulative incidence of specific syndromes together with the broad group of DEEs is essential for the planning of therapeutic trials. Given trials focus on specific syndromes, there is a risk that effective therapies will not be developed for one-third of children with DEE.
A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5–33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea.
The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies.
The clinical trial registry of India: CTRI/2015/07/006048.
This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.
We studied 9,595 women and 5,795 men from 2 prospective cohort studies of community-dwelling elders followed up to 20 years. In individuals without prevalent PD, we estimated the associations of incident PD diagnosis with rates of change in cognition and function before and after diagnosis compared with healthy older adults using multivariate mixed-effects models.
Over follow-up, 297 individuals developed incident PD. Interactions between the terms in our model and sex were statistically significant for the 3 outcomes (p < 0.001 for all), so we stratified results by sex. Compared with older men without PD, men who developed PD exhibited faster decline in global cognition (0.04 SD more annual change, p < 0.001), executive function (0.05 SD more annual change, p < 0.001), and functional status (0.06 SD more annual change, p < 0.001) in the prediagnostic period. Women who developed PD compared with women without PD displayed faster decline in executive function (0.02 SD more annual change, p = 0.006) and functional status in the prediagnostic period (0.07 SD more annual change, p < 0.001).
Individuals with incident PD exhibit cognitive and functional decline during the prediagnostic phase that exceeds rates associated with normal aging. Better understanding heterogeneity in prodromal PD is essential to enable earlier diagnosis and identify impactful nonmotor symptoms in all subgroups.
Unilateral magnetic resonance–guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of patients with PD treated with unilateral FUS-STN.
We conducted a prospective open-label study of patients with asymmetrical PD who underwent unilateral FUS-STN. All patients were evaluated up to 36 months after treatment. The primary outcome was the difference from baseline to 36 months after FUS-STN in the score of the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor part (III) for the treated hemibody in the off-medication state. The safety outcome included all adverse events occurring during follow-up. Secondary outcomes were the change in the MDS-UPDRS III score on-medication; subscores of rigidity, bradykinesia, tremor, and axial features; total MDS-UPDRS III; and the MDS-UPDRS part IV. Functional disability and quality of life were assessed using the MDS-UPDRS II and the PDQ39, respectively. Patient impression of change and satisfaction with the treatment were self-assessed. The Wilcoxon signed-rank test with subsequent Bonferroni's correction was used for data analysis.
Thirty-two patients with PD were evaluated at 36 months after treatment. The mean (±SD) age at baseline was 56.0 ± 10.1 years, with a mean disease duration of 6.8 ± 2.8 years. The MDS-UPDRS III score for the treated hemibody off-medication was improved by 52.3% from baseline to 3 years (score reduction from 19.0 ± 3.2 to 8.9 ± 3.3, 95% CI 8.7 to 11.6, p < 0.001), and all specific motor features were improved from baseline. No disabling or delayed adverse events were reported. The total MDS-UPDRS III off-medication score was 22.9% lower at 3 years than before treatment (36.8 ± 7.4 vs 27.4 ± 6.2, 95% CI 6.0 to 11.5, p < 0.001). The MDS-UPDRS II, IV, and PDQ39 scores and levodopa dose were equivalent to those at baseline.
The benefit of unilateral FUS-STN on PD motor features is sustained in the long term. FUS-STN contributes to better clinical control over several years of evolution. NCT02912871/03454425.
This study provides Class IV evidence on the utility of focused ultrasound unilateral subthalamotomy in the treatment of people with Parkinson disease.
Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003 to 2018. Patients with IBM were included if they met at least one of the following criteria: Griggs possible, European Neuromuscular Centre 2011 probable, or Lloyd-Greenberg data-derived criteria for IBM. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in patients with IBM. Thus, linear and logistic regressions were used to adjust for potential confounding variables. The evolution of creatine kinase and muscle strength was studied using multilevel linear regression models. Nonmodifiable risk factors (sex, race, disease duration, and age at the onset of first symptoms) were used as adjusting covariates for the regression analyses.
Among the 335 patients meeting the inclusion criteria for IBM, 64% were male with an average age of disease onset of 58.7 years and delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all 3 pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared with non-Black patients. Female patients had stronger finger flexors and knee extensors compared with their male counterparts. Younger age (<50 years) at onset was not associated with increased weakness.
Our study demonstrates that female and Black patients have distinct clinical phenotypes and trajectories within the overarching IBM clinical phenotype. These subgroups may have different responses to therapies, which may influence the design of future clinical trials in IBM.
Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)–associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG–positive neuromyelitis optica spectrum disorder (AQP4+NMOSD).
We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD.
We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance.
Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.
In the current issue of Neurology®, Fourier et al.1 published one of the most comprehensive studies of sex differences in cluster headache; they confirmed previous epidemiologic suspicions, provided new insights, and raised important questions into sex hormones and the influence of genetic factors. The authors surveyed 874 participants who were diagnosed with cluster headache by neurologists using the criteria of the International Classification of Headache Disorders (ICHD)–3.2 Approximately half were personally assessed by study authors, while the other half were identified through International Classification of Diseases 10 (ICD10) codes and had their charts reviewed by a study neurologist applying ICHD-3 criteria. Participants then completed a questionnaire that included demographics, headache features, and treatments. This questionnaire provided information on prevalence (higher in male participants), incidence (peaks between 20- and 29-year-olds), family aggregation (more common in female participants), and burden of disease (worse in female participants).
In a 2-decade prospective population-based study from Sweden, Dr. Glans and colleagues investigated the association between adherence to conventional dietary recommendations or to a modified Mediterranean diet and subsequent risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or accumulation of AD-related β-amyloid pathology in the CSF, among 28,025 participants. They concluded that these dietary habits were not significantly associated with a reduced risk for developing all-cause dementia, AD dementia, VaD, or AD pathology. In response, Dr. Kawada cites a previous study that found significant interactions between dietary patterns and APOE-4 status in relation to incident dementia, with a healthy dietary pattern being associated with lower dementia incidence in 4 noncarriers and a Western dietary pattern associated with higher dementia incidence in 4 carriers. Dr. Kawada argues that studies examining the long-term effect of dietary patterns on incident dementia should consider the contribution of genetic factors. In another response, Dr. Hoffman notes that the researchers' use of a modified Mediterranean diet score does not explicitly measure for extra virgin olive oil (EVOO), which may be an important component for maintaining cognitive health, citing epidemiologic and animal studies in this regard. He contends that it is important to consider the role of EVOO as part of a Mediterranean diet for cognitive health to better inform the implementation of this diet in non-Mediterranean countries. Responding to these comments, the authors note that they did not find any significant interaction effects between conventional dietary recommendations or a modified Mediterranean diet and APOE-4 status with respect to subsequent dementia but do not comment about the role of extra virgin olive oil. Overall, this exchange highlights enduring uncertainties about the role of specific dietary factors in mitigating the long-term risk of dementia.
Glans et al.1 investigated the association between dietary habits and subsequent development of all-cause dementia, Alzheimer disease, vascular dementia, or increased CSF Aβ42. The adjusted hazard ratio (HR) of a conventional diet and a modified Mediterranean diet for dementia-related indicators did not become significant. Regarding the lack of association by the follow-up over a 20-year period, I present information regarding the significance of genetic interaction with dietary habits.
Study participants were identified by screening medical records from 2014 to 2020, requested from hospitals and neurology clinics in Sweden for the ICD-10 code G44.0 for cluster headache. Each study participant answered a detailed questionnaire on clinical information and lifestyle, and all variables were compared with regard to sex.
A total of 874 study participants with a verified cluster headache diagnosis were included. Of the participants, 575 (66%) were male and 299 (34%) were female, and biological sex matched self-reported sex for all. Female participants were to a greater extent diagnosed with the chronic cluster headache subtype compared with male participants (18% vs 9%, p = 0.0002). In line with this observation, female participants report longer bouts than male participants (p = 0.003) and used prophylactic treatment more often (60% vs 48%, p = 0.0005). Regarding associated symptoms, female participants experienced ptosis (61% vs 47%, p = 0.0002) and restlessness (54% vs 46%, p = 0.02) more frequently compared with male participants. More female than male study participants had a positive family history of cluster headache (15% vs 7%, p = 0.0002). In addition, female participants reported diurnal rhythmicity of their attacks more often than male participants (74% vs 63%, p = 0.002). Alcohol as a trigger occurred more frequently in male participants (54% vs 48%, p = 0.01), whereas lack of sleep triggering an attack was more common in female participants (31% vs 20%, p = 0.001).
With this in-depth analysis of a well-characterized cluster headache population, we could demonstrate that there are significant differences between male and female participants with cluster headache, which should be regarded at the time of diagnosis and when choosing treatment options. The data suggest that female patients generally may be more gravely affected by cluster headache than male patients.
Blood and CSF samples were obtained from prospectively enrolled patients with acute SCI through days 1–4 postinjury, and the concentration of NF-L and GFAP was quantified using Simoa technology. Neurologic assessments defined the ASIA Impairment Scale (AIS) grade and motor score (MS) at presentation and 6 months postinjury.
One hundred eighteen patients with acute SCI (78 AIS A, 20 AIS B, and 20 AIS C) were enrolled, with 113 (96%) completing 6-month follow-up. NF-L and GFAP levels were strongly associated between paired serum and CSF specimens, were both increased with injury severity, and distinguished among baseline AIS grades. Serum NF-L and GFAP were significantly (p = 0.02 to <0.0001) higher in AIS A patients who did not improve at 6 months, predicting AIS grade conversion with a sensitivity and specificity (95% CI) of 76% (61, 87) and 77% (55, 92) using NF-L and 72% (57, 84) and 77% (55, 92) using GFAP at 72 hours, respectively. Independent of clinical baseline assessment, a serum NF-L threshold of 170 pg/mL at 72 hours predicted those patients who would be classified as motor complete (AIS A/B) compared with motor incomplete (AIS C/D) at 6 months with a sensitivity of 87% (76, 94) and specificity of 84% (69, 94); a serum GFAP threshold of 13,180 pg/mL at 72 hours yielded a sensitivity of 90% (80, 96) and specificity of 84% (69, 94).
The potential for NF-L and GFAP to classify injury severity and predict outcome after acute SCI will be useful for patient stratification and prognostication in clinical trials and inform communication of prognosis.
This study provides Class I evidence that higher serum NF-L and GFAP are associated with worse neurological outcome after acute SCI.
Registered on ClinicalTrials.gov: NCT00135278 (March 2006) and NCT01279811 (January 2012).
Through a multinational collaborative, we studied a cohort of neonates with encephalopathy associated with biallelic pathogenic variants in BRAT1 for whom detailed clinical, neurophysiologic, and neuroimaging information was available from the onset of symptoms. Neuropathologic changes were also analyzed.
We included 19 neonates. Most neonates were born at term (16/19) from nonconsanguineous parents. 15/19 (79%) were admitted soon after birth to a neonatal intensive care unit, exhibiting multifocal myoclonus, both spontaneous and exacerbated by stimulation. 7/19 (37%) had arthrogryposis at birth, and all except 1 progressively developed hypertonia in the first week of life. Multifocal myoclonus, which was present in all but 1 infant, was the most prominent manifestation and did not show any EEG correlate in 16/19 (84%). Video-EEG at onset was unremarkable in 14/19 (74%) infants, and 6 (33%) had initially been misdiagnosed with hyperekplexia. Multifocal seizures were observed at a median age of 14 days (range: 1–29). During the first months of life, all infants developed progressive encephalopathy, acquired microcephaly, prolonged bouts of apnea, and bradycardia, leading to cardiac arrest and death at a median age of 3.5 months (range: 20 days to 30 months). Only 7 infants (37%) received a definite diagnosis before death, at a median age of 34 days (range: 25–126), and almost two-thirds (12/19, 63%) were diagnosed 8 days to 12 years postmortem (median: 6.5 years). Neuropathology examination, performed in 3 patients, revealed severely delayed myelination and diffuse astrogliosis, sparing the upper cortical layers.
BRAT1 encephalopathy is a neonatal-onset, rapidly progressive neurologic disorder. Neonates are often misdiagnosed as having hyperekplexia, and many die undiagnosed. The key phenotypic features are multifocal myoclonus, an organized EEG, progressive, persistent, and diffuse hypertonia, and an evolution into refractory multifocal seizures, prolonged bouts of apnea, bradycardia, and early death. Early recognition of BRAT1 encephalopathy allows for prompt workup, appropriate management, and genetic counseling.
Participants completed validated self-report questionnaires of driving behaviors (assessing lapses, errors, violations, and attentional issues) and 2 computer-based measures of hazard perception skill (both known to be associated with crash risk).
We compared 43 patients who experience dissociative attacks or functional motor symptoms and 43 healthy controls. Patients with FND self-reported significantly more driving lapses and driving errors compared with healthy controls. However, there were no significant between-group differences in self-reports of ordinary violations, aggressive violations, or attention-related errors. Participants in the FND group and healthy controls exhibited a similar performance on a response time hazard perception test (6.27 vs 5.51 seconds, p = 0.245). However, participants with FND remarkably outperformed the controls in the number of plausible predictions they made in a verbal response hazard prediction test (1.55 vs 1.18 predictions per clip, p = 0.006).
Our findings suggest that the ability of drivers with FND to predict traffic hazards in between attacks or flares is not worse than that of healthy individuals, with the possibility that it might even be better under some circumstances. Further studies with various populations are needed to replicate our findings.
In the external validation set of 1,379 cases, the algorithm identified 136 of 137 SAH cases correctly (sensitivity 99.3% and specificity 63.2%). Of the 49,064 axial head CT slices, the algorithm identified and localized SAH in 1845 of 2,110 slices with SAH (sensitivity 87.4% and specificity 95.3%). Of 519 consecutive emergency head CT scans imaged in September 2021, the algorithm identified all 8 SAH cases correctly (sensitivity 100.0% and specificity 75.3%). The slice-level (27,167 axial slices in total) sensitivity and specificity were 87.3% and 98.8%, respectively, as the algorithm identified and localized SAH in 58 of 77 slices with SAH. The performance of the algorithm can be tested on through a web service.
We show that the shared algorithm identifies SAH cases with a high sensitivity and that the slice-level specificity is high. In addition to openly sharing a high-performing deep learning algorithm, our work presents infrequently used approaches in designing, training, testing, and reporting deep learning algorithms developed for medical imaging diagnostics.
This study provides Class III evidence that a deep learning algorithm correctly identifies the presence of subarachnoid hemorrhage on CT scan.
We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses.
Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14–2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90–60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03–12.44; p < 0.001) compared with the non-cSS group.
Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.
We conducted a serial cross-sectional study using the 2007–2019 National Inpatient Sample. Primary AIS admissions in adults (aged 18 years or older) with and without complications were identified using International Classification of Diseases codes. We quantified the age/sex-specific prevalence of complications and used negative binomial regression models to evaluate trends over time.
Of 5,751,601 weighted admissions, 51.4% were women. 25.1% had at least 1 complication. UTI (11.8%), ARF (10.1%), pneumonia (3.2%), and AMI (2.5%) were the most common complications, while sepsis (1.7%), GIB (1.1%), DVT (1.2%), and PE (0.5%) were the least prevalent. Marked disparity in complication risk existed by age/sex (UTI: men 18–39 years 2.1%; women 80 years or older 22.5%). Prevalence of UTI (12.9%–9.7%) and pneumonia (3.8%–2.7%) declined, but that of ARF increased by 3-fold (4.8%–14%) over the period 2007–2019 (all p < 0.001). AMI (1.9%–3.1%), DVT (1.0%–1.4%), and PE (0.3%–0.8%) prevalence also increased (p < 0.001), but that of sepsis and GIB remained unchanged over time. After multivariable adjustment, risk of all complications increased with increasing NIH Stroke Scale (pneumonia: prevalence rate ratio [PRR] 1.03, 95% CI 1.03–1.04, for each unit increase), but IV thrombolysis was associated with a reduced risk of all complications (pneumonia: PRR 0.80, 85% CI 0.73–0.88; AMI: PRR 0.85, 95% CI 0.78–0.92; and DVT PRR 0.87, 95% CI 0.78–0.98). Mechanical thrombectomy was associated with a reduced risk of UTI, sepsis, and ARF, but DVT and PE were more prevalent in MT hospitalizations compared with those without. All complications except UTI were associated with an increased risk of in-hospital mortality (sepsis: PRR 1.97, 95% CI 1.78–2.19).
Infectious complications declined, but noninfectious complications increased after AIS admissions in the United States in the last decade. Utilization of IV thrombolysis is associated with a reduced risk of all complications.
We conducted an observational cohort study with data from patients with MS followed in the Observatoire Francais de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18–45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up).
We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [–0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93–1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate.
Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.
Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline.
The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9–12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84–0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80–0.89), but not in younger patients (HR 0.99, 95% CI 0.90–1.10).
In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population.
This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.
An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected.
One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%).
The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario.
In their multicenter randomized controlled clinical trial of patients with idiopathic intracranial hypertension (IIH), Mollan et al. sought to determine the amount of weight loss necessary to achieve physiologic remission (intracranial pressure [ICP] ≤25 cm CSF). The investigators not only found that greater weight loss was achieved with bariatric surgery over community weight management but patients who underwent surgery experienced greater and more rapid reduction in ICP. Furthermore, only patients in the surgical arm achieved a fall in ICP to ≤25 cm, which was associated with a mean weight loss of approximately 24% from their baseline weight. Dr. Ramsamy and colleagues highlight that surgery was not associated with statistically significant improvement in visual outcomes or headache, which are the most disabling symptoms of IIH. In response, Dr. Mollan and their coinvestigators note the study was powered to demonstrate a treatment effect for the primary outcome of ICP reduction (as a biomarker of disease remission), rather than for secondary outcomes regarding visual or other symptoms of IIH. That said, the investigators admit there remains no consensus definition for clinical remission in IIH. Dr. Brenner also comments on the potential adjuvant use of caffeine in weight loss for patients with IIH and the benefits of optic nerve sheath fenestration when vision loss occurs. The investigators cite their original manuscript (published in JAMA Neurology), which reported a rapid and significant fall in ICP within 2 weeks of bariatric surgery. It is possible that acute hormonal changes after surgery such as a rapid rise in gut neuropeptide glucagon-like peptide-1 may have played a larger role in ICP reduction than weight loss alone.
Eleven medical centers retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF using live cell-based assays. Comparisons were performed using parametric or nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression.
The cohort included 255 patients: 139 (55%) women and 132 (52%) children (i.e., <18-year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n = 14, 45%) and sensory symptoms (n = 13, 42%), and all but 4 (2 multiple sclerosis, 1 polyradiculoneuritis, and 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [IQR] 3.0–7.5 vs 3.0, IQR 2.0–6.8, p = 0.007) and presented more commonly with sensory (45.5% vs 24%, p = 0.002), motor (33.6% vs 19%, p = 0.021), and sphincter symptoms (26.9% vs 7.8%, p = 0.001) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008). Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up (p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0.
Paired serum and CSF MOG-Abs positivity are common in MOGAD and are associated with a more severe clinical presentation. CSF-only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus.
Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31–0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with –0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001).
The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy.
This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.
A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts.
In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.
Forty-three women and 43 men aged 60–93 years were recruited, 87% of whom had focal epilepsy, with an average frequency of 3.4 seizures per month. Multiple linear regression and zero-inflated negative binomial regression models showed that EFS and CFS scores were associated with decreased ASM tolerability, each point increase leading to 1.83 (95% CI: 0.67–4.30) and 2.49 (95% CI: 1.27–2.39) point increases on the LAEP scale, respectively. Neither the EFS and CFS scores nor grip strength were significantly associated with seizure frequency. The EFS was moderately correlated with depression, anxiety, quality of life, and functional disability, demonstrating the best construct validity among the 3 tested measures of frailty.
The EFS was significantly, both statistically and clinically, associated with ASM tolerability. It also showed multiple advantages in performance while assessing for frailty in older adults with epilepsy, when compared with the 2 other measures of frailty that we tested. Future studies must focus on what role the EFS during epilepsy diagnosis may play in ASM selection among older adults with epilepsy.
The Save ChildS retrospective cohort study (January 2000–December 2018) enrolled children (1 month–18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only.
Of 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4–7.5) perfusion+; 3.4 hours (IQR 2.5–6.5) perfusion-, p = 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5–2.0] vs 2.0 [1.5–3.0], p = 0.026) and modified Rankin Scale 1.0 [0–1] vs 2.0 [1.5–3.5], p = 0.048) in this small sample.
Automated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children.
In univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (odds ratio [OR] = 1.30; 95% CI: 1.10–1.54, p = 0.002). Genetic liability to short sleep, long sleep, and continuous sleep duration were not associated with poststroke functional outcome (all p > 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08–1.44, p = 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking, and alcohol consumption, the overall patterns between genetic liability to insomnia and poststroke outcome remained (all p < 0.05).
This MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context.
This cohort study retrospectively evaluated participants from the Predicting Outcomes of Language Rehabilitation in Aphasia clinical trial (NCT03416738), recruited through local advertisement in South Carolina (US). Primary inclusion criteria were left hemisphere stroke and chronic aphasia (≥12 months after stroke). Participants completed baseline behavioral testing including the Western Aphasia Battery–Revised (WAB-R), Philadelphia Naming Test (PNT), Pyramids and Palm Trees Test (PPTT), and Wechsler Adult Intelligence Scale Matrices subtest, before completing 6 weeks of language therapy. The PNT was repeated 1 month after therapy. We leveraged modern neuroimaging techniques to estimate brain age and computed a proportional difference between chronologic age and estimated brain age. Multiple linear regression models were used to evaluate the relationship between proportional brain age difference (PBAD) and behavior.
Participants (N = 93, 58 males and 35 females, average age = 61 years) had estimated brain ages ranging from 14 years younger to 23 years older than chronologic age. Advanced brain age predicted performance on semantic tasks (PPTT) and language tasks (WAB-R). For participants with advanced brain aging (n = 47), treatment gains (improvement on the PNT) were independently predicted by PBAD (T = –2.0474, p = 0.0468, 9% of variance explained).
Through the application of modern neuroimaging techniques, advanced brain aging was associated with aphasia severity and performance on semantic tasks. Notably, therapy outcome scores were also associated with PBAD, albeit only among participants with advanced brain aging. These findings corroborate the importance of brain age as a determinant of poststroke recovery and underscore the importance of personalized health factors in determining recovery trajectories, which should be considered during the planning or implementation of therapeutic interventions.
Adults aged 18–75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies.
From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device.
The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development.
ClinicalTrials.gov Identifier: NCT00912041.
This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.
This randomized, double-blind, placebo-controlled, phase 3 study investigated mirogabalin efficacy and safety for the treatment of CNeP in patients with traumatic SCI. Adult patients from 120 sites throughout Japan, Korea, and Taiwan were randomized (1:1) to receive placebo or mirogabalin (5 mg twice daily [BID] for 1 week, 10 mg BID for 1 week, and 10 or 15 mg BID for 12 weeks). Patients with moderate renal impairment received half the dosage. The primary efficacy endpoint was change from baseline in the weekly average daily pain score (ADPS) at week 14. The secondary endpoints included ADPS responder rates, the Short-Form McGill Pain Questionnaire (SF-MPQ), average daily sleep interference score (ADSIS), and Neuropathic Pain Symptom Inventory (NPSI). Adverse events were monitored for safety.
Each treatment group comprised 150 patients. Mirogabalin elicited a statistical and clinically relevant improvement in change from baseline in the weekly ADPS at week 14 (least-squares mean difference [95% CI] vs placebo –0.71 [–1.08 to –0.34], p = 0.0001). Responder rates at week 14 were higher for mirogabalin than those for placebo (odds ratio [95% CI] 1.91 [1.11–3.27] for the ≥30% responder rate; 2.52 [1.11–5.71] for the ≥50% responder rate). Statistical improvements (i.e., least-squares mean difference [95% CI] vs placebo) were also observed in the SF-MPQ (–2.4 [–3.8 to –1.1]), ADSIS –0.71 (–1.04 to –0.38), and NPSI –7.7 (–11.1 to –4.4) scores. Most treatment-emergent adverse events were mild; no serious adverse drug reactions were reported.
Mirogabalin elicited clinically relevant decreases in pain and was well tolerated, suggesting that mirogabalin is a promising treatment for patients with CNeP due to SCI.
This study provides Class I evidence that in adult patients with CNeP due to traumatic SCI, mirogabalin, 10 or 15 mg BID, effectively improves weekly ADPS at week 14.