A rare midbrain infarction presenting with plus-minus lid syndrome with ataxia: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present the case of a patient with midbrain infarction with an unusual clinical presentation, where clinical diagnosis and anatomical localization were valuable tools in deciding treatment.</p> <p>Case presentation</p> <p>Our patient was a 59-year-old, right-handed Caucasian man with hypertension who presented to our facility with acute diplopia that persisted until he developed complete right-sided ptosis. He also had difficulty walking and coordinating movements of his upper extremities bilaterally, but this was worse on his left side.</p> <p>Conclusions</p> <p>Plus-minus lid syndrome with ataxia is a rare presentation of midbrain infarction with a unique localization and anatomical description. This case highlights the importance of clinical skills for making a diagnosis in the absence of imaging to confirm the findings.</p

Ipsilesional Mu Rhythm Desynchronization and Changes in Motor Behavior Following Post Stroke BCI Intervention for Motor Rehabilitation

Loss of motor function is a common deficit following stroke insult and often manifests as persistent upper extremity (UE) disability which can affect a survivor’s ability to participate in activities of daily living. Recent research suggests the use of brain–computer interface (BCI) devices might improve UE function in stroke survivors at various times since stroke. This randomized crossover-controlled trial examines whether intervention with this BCI device design attenuates the effects of hemiparesis, encourages reorganization of motor related brain signals (EEG measured sensorimotor rhythm desynchronization), and improves movement, as measured by the Action Research Arm Test (ARAT). A sample of 21 stroke survivors, presenting with varied times since stroke and levels of UE impairment, received a maximum of 18–30 h of intervention with a novel electroencephalogram-based BCI-driven functional electrical stimulator (EEG-BCI-FES) device. Driven by spectral power recordings from contralateral EEG electrodes during cued attempted grasping of the hand, the user’s input to the EEG-BCI-FES device modulates horizontal movement of a virtual cursor and also facilitates concurrent stimulation of the impaired UE. Outcome measures of function and capacity were assessed at baseline, mid-therapy, and at completion of therapy while EEG was recorded only during intervention sessions. A significant increase in r-squared values [reflecting Mu rhythm (8–12 Hz) desynchronization as the result of attempted movements of the impaired hand] presented post-therapy compared to baseline. These findings suggest that intervention corresponds with greater desynchronization of Mu rhythm in the ipsilesional hemisphere during attempted movements of the impaired hand and this change is related to changes in behavior as a result of the intervention. BCI intervention may be an effective way of addressing the recovery of a stroke impaired UE and studying neuromechanical coupling with motor outputs.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02098265

Behavioral Outcomes Following Brain–Computer Interface Intervention for Upper Extremity Rehabilitation in Stroke: A Randomized Controlled Trial

Stroke is a leading cause of persistent upper extremity (UE) motor disability in adults. Brain–computer interface (BCI) intervention has demonstrated potential as a motor rehabilitation strategy for stroke survivors. This sub-analysis of ongoing clinical trial (NCT02098265) examines rehabilitative efficacy of this BCI design and seeks to identify stroke participant characteristics associated with behavioral improvement. Stroke participants (n = 21) with UE impairment were assessed using Action Research Arm Test (ARAT) and measures of function. Nine participants completed three assessments during the experimental BCI intervention period and at 1-month follow-up. Twelve other participants first completed three assessments over a parallel time-matched control period and then crossed over into the BCI intervention condition 1-month later. Participants who realized positive change (≥1 point) in total ARAT performance of the stroke affected UE between the first and third assessments of the intervention period were dichotomized as “responders” (&lt;1 = “non-responders”) and similarly analyzed. Of the 14 participants with room for ARAT improvement, 64% (9/14) showed some positive change at completion and approximately 43% (6/14) of the participants had changes of minimal detectable change (MDC = 3 pts) or minimally clinical important difference (MCID = 5.7 points). Participants with room for improvement in the primary outcome measure made significant mean gains in ARATtotal score at completion (ΔARATtotal = 2, p = 0.028) and 1-month follow-up (ΔARATtotal = 3.4, p = 0.0010), controlling for severity, gender, chronicity, and concordance. Secondary outcome measures, SISmobility, SISadl, SISstrength, and 9HPTaffected, also showed significant improvement over time during intervention. Participants in intervention through follow-up showed a significantly increased improvement rate in SISstrength compared to controls (p = 0.0117), controlling for severity, chronicity, gender, as well as the individual effects of time and intervention type. Participants who best responded to BCI intervention, as evaluated by ARAT score improvement, showed significantly increased outcome values through completion and follow-up for SISmobility (p = 0.0002, p = 0.002) and SISstrength (p = 0.04995, p = 0.0483). These findings may suggest possible secondary outcome measure patterns indicative of increased improvement resulting from this BCI intervention regimen as well as demonstrating primary efficacy of this BCI design for treatment of UE impairment in stroke survivors.Clinical Trial Registration:ClinicalTrials.gov, NCT02098265

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis

Background: The Diabetes Prevention Program (DPP) study showed that weight loss in high-risk adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States. Methods and Findings: In this systematic review and meta-analysis, we pooled data from studies in the United States implementing DPP lifestyle modification programs (focused on modest [5%–7%] weight loss through ≥150 min of moderate physical activity per week and restriction of fat intake) in clinical, community, and online settings. We reported aggregated pre- and post-intervention weight and cardiometabolic risk factor changes (fasting blood glucose [FBG], glycosylated hemoglobin [HbA1c], systolic or diastolic blood pressure [SBP/DBP], total [TC] or HDL-cholesterol). We searched the MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov databases from January 1, 2003, to May 1, 2016. Two reviewers independently evaluated article eligibility and extracted data on study designs, populations enrolled, intervention program characteristics (duration, number of core and maintenance sessions), and outcomes. We used a random effects model to calculate summary estimates for each outcome and associated 95% confidence intervals (CI). To examine sources of heterogeneity, results were stratified according to the presence of maintenance sessions, risk level of participants (prediabetes or other), and intervention delivery personnel (lay or professional). Forty-four studies that enrolled 8,995 participants met eligibility criteria. Participants had an average age of 50.8 years and body mass index (BMI) of 34.8 kg/m2, and 25.2% were male. On average, study follow-up was 9.3 mo (median 12.0) with a range of 1.5 to 36 months; programs offered a mean of 12.6 sessions, with mean participant attendance of 11.0 core sessions. Sixty percent of programs offered some form of post-core maintenance (either email or in person). Mean absolute changes observed were: weight -3.77 kg (95% CI: -4.55; -2.99), HbA1c -0.21% (-0.29; -0.13), FBG -2.40 mg/dL (-3.59; -1.21), SBP -4.29 mmHg (-5.73, -2.84), DBP -2.56 mmHg (-3.40, 1.71), HDL +0.85 mg/dL (-0.10, 1.60), and TC -5.34 mg/dL (-9.72, -0.97). Programs with a maintenance component achieved greater reductions in weight (additional -1.66kg) and FBG (additional -3.14 mg/dl). Findings are subject to incomplete reporting and heterogeneity of studies included, and confounding because most included studies used pre-post study designs. Conclusions: DPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective

Hypercapnic evaluation of vascular reactivity in healthy aging and acute stroke via functional MRI

Functional MRI (fMRI) is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR), which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a breath-hold fMRI task to evaluate CVR across gray matter in a group of acute stroke patients (<10 days from stroke; N = 22) to address this question. These estimates were compared with those from both age-matched (N = 22) and younger (N = 22) healthy controls. As expected, young controls had the greatest mean CVR, as indicated by magnitude and extent of fMRI activation; however, stroke patients did not differ from age-matched controls. Moreover, the ipsilesional and contralesional hemispheres of stroke patients did not differ with respect to any of these measures. These findings suggest that fMRI remains a valid tool within the first few days of a stroke, particularly for group fMRI studies in which findings are compared with healthy subjects of similar age. However, given the relatively high variability in CVR observed in our stroke sample, caution is warranted when interpreting fMRI data from individual patients or a small cohort. We conclude that a breath-hold task can be a useful addition to functional imaging protocols for stroke patients

Brain-Computer Interface Therapy after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers

Background. Brain-computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective. This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods. Stroke patients (n=19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results. No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p<0.05 corrected. Conclusions. These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke

Dose-response relationships using brain-computer interface technology impact stroke rehabilitation

Brain-computer interfaces (BCI) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n=16, 11M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p<0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p<0.05) or trending (0.05<p<0.1) negative correlations with LI changes, while therapy frequency did not affect LI. Reductions in LI were then associated (p<0.05) with increased SIS Activities of Daily Living scores and improved 9-HPT performance. Therefore, some behavioral changes may be reflected by brain changes sensitive to differences in BCI therapy administration, while others such as SIS strength may be directly responsive to BCI therapy administration. Data preliminarily suggest that when using BCI in stroke rehabilitation, therapy frequency may be less important than dose and intensity