Impact of a free medication intervention on seizure recurrence and anxious and depressive symptoms in people living with epilepsy in the Republic of Guinea.

BACKGROUND AND OBJECTIVE: Of ~5 million people living with epilepsy (PLWE) in Sub-Saharan Africa, roughly one-third experience depression and over one third experience anxiety. In Guinea, these issues may be compounded by fewer available resources, such as appropriate anti-seizure medications (ASMs). We aim to quantify seizure frequency, anxiety and depression in PLWE in Guinea, before and after a free ASM intervention and neurologist's consultation. METHODS: Guinean participants >12 years old with ≥2 unprovoked seizure were prospectively recruited. As part of a broader interview, participants reported prior 30-day seizure frequency and screened for depression (PHQ-9) (range 0-27 points) and anxiety (GAD-7) (range 0-21 points) with re-evaluation at 90 days. RESULTS: Of 148 participants enrolled (mean age = 27.3 years, range 12-72; 45% female), 62% were currently taking ASMs. For the 30 days pre-enrolment, average seizure frequency was 3.2 (95%CI 2.3, 4.2); 28% of participants were seizure-free. ASM regimens were modified for 95% of participants, mostly initiating levetiracetam (n = 115, 80% of modifications). 90-day study retention was 76% (n = 113) among whom 87% reported full adherence to the ASM. After 90 days, the average seizure frequency over the prior 30 days was 1.5 (95%CI 0.5, 2.6), significantly lower than at baseline (p = 0.002). 66% were seizure-free. At baseline, average PHQ-9 score was 21.2 (95%CI [20.2, 22.2]), indicating severe depressive symptoms. Average GAD-7 score was 16.5 [15.6, 17.4], indicating severe anxious symptoms. At 90-days, average PHQ-9 score was 17.5[16.4, 18.5] and significantly lower than baseline (p < 0.001). Average GAD-7 score was 14.4 [13.6, 15.3] and significantly lower than baseline (p = 0.002). Seizure frequency was not correlated with PHQ-9 nor GAD-7 scores at baseline but was at 90 days for both PHQ-9 (r = 0.24, p = 0.01) and GAD-7 (r = 0.22, p = 0.02) scores. The prevalence of suicidal ideation dropped from 67% to 47% of participants (p = 0.004). DISCUSSION: ASM management has dual importance for PLWE in resource-limited settings, improving both seizure control and mental health.

Neurological Care of Refugees and Other Forcibly Displaced Persons.

There are more than 100 million forcibly displaced persons (FDPs) in the world today, including a high number of people who experience neurologic symptoms and presentations. This review summarizes the conceptual frameworks for understanding neurological health risks and conditions across the migration journey (premigration, migration journey, and postmigration) and life span, including special attention to pediatric FDPs. The interaction with psychiatric illness is discussed, as well as the available published data on neurologic presentations in FDPs in the medical literature. A social determinant of health lens is used to provide ways in which forcible displacement can influence brain health and neurological outcomes. Priorities and future needs for the neurological care of refugees and other FDPs are suggested.

A quality of care assessment for women of childbearing potential with epilepsy in Bhutan: An observational study.

BACKGROUND & OBJECTIVE: In lower-middle income countries such as Bhutan, the treatment gap for epilepsy is over 50% as compared to a treatment gap of less than 10% in high-income countries. We aim to analyze the quality of epilepsy care for women of childbearing potential in Bhutan using the Quality Indicators in Epilepsy Treatment (QUIET) tool, and to assess the usefulness of the tool's section for women with active epilepsy (WWE) in the Bhutanese setting. METHODS: A prospective convenience cohort was enrolled in Thimphu, Paro, Punakha, and Wangdue, Kingdom of Bhutan, in 2022. Bhutanese women of childbearing potential at the time of enrollment (18-44 years old) were evaluated for the diagnosis of active epilepsy and underwent a structured survey-based interview with Bhutanese staff. Participants were surveyed on their epilepsy, pregnancy, and antiseizure medicine (ASM) histories. The clinical history and quality of epilepsy care of adult WWE were assessed using a section of the QUIET tool for women, an instrument originally developed by the U.S. Department of Veterans Affairs to analyze the quality of epilepsy care for American adults. RESULTS: There were 82 Bhutanese WWE of childbearing potential, with mean age of 30.6 years at enrollment (range 18-44, standard deviation (SD) 6.6) and mean age of 20.3 years at epilepsy diagnosis (range 3-40, SD 8.0)). 39 % (n = 32) had a high school or above level of education, and 42 % (n = 34) were employed. 35 % (n = 29) reported a seizure within the prior week, and 88 % (n = 72) reported a seizure within the prior year. 49 % (n = 40) of participants experienced > 100 lifetime seizures. All but one participant took antiseizure medications (ASMs). At enrollment, participants presently took no (n = 1), one (n = 3), two (n = 37), three (n = 25), four (n = 11), or over five (n = 5) ASMs. The most common ASMs taken were levetiracetam (n = 40), phenytoin (n = 27), carbamazepine (n = 23), phenobarbital (n = 22), and sodium valproate (n = 20). 61 % of all WWE took folic acid. Of the 40 previously pregnant WWE, eight (20 %) took folic acid during any time of their pregnancy. 35 % (n = 29) used betel nut (doma, quid) and 53 % (n = 21) of pregnant WWE used betel nut during pregnancy. CONCLUSIONS: Based on data about WWE participants' ASM, supplement, and substance use, our study identified the high use of first generation ASMs (including valproate), frequently in polytherapy, and betel nut use as treatment gaps in women of childbearing potential age with active epilepsy in Bhutan. To address these gaps for locations such as Bhutan, we propose modifications to the QUIET tool's "Chronic Epilepsy Care for Women" section.

Rectifying global inequities in neuromyelitis optica diagnosis and treatment.

The standard of care for patients with neuromyelitis optica (NMO) has become highly unequal globally. Sufficient data have been published to demonstrate that NMO is a disabling-and at times, fatal-disease needing preventive immunosuppressive treatment. Since 2019, there are multiple regulatory authority-approved disease-modifying therapies (DMTs) for aquaporin-4 antibody seropositive NMO for patients. Reframing the picture of NMO globally is now needed. When considered as a disease of high mortality when left untreated, parallel programs to those for cancer, HIV/AIDS, or tuberculosis can be considered. Nine collective goals for rectifying global inequities in NMO diagnosis and treatment are proposed.

Clinically relevant increases in serum neurofilament light chain and glial fibrillary acidic protein in patients with Susac syndrome.

BACKGROUND AND PURPOSE: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. METHODS: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. RESULTS: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). CONCLUSION: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.

Epilepsy diagnosis using a clinical decision tool and artificially intelligent electroencephalography.

OBJECTIVE: To construct a tool for non-experts to calculate the probability of epilepsy based on easily obtained clinical information combined with an artificial intelligence readout of the electroencephalogram (AI-EEG). MATERIALS AND METHODS: We performed a chart review of 205 consecutive patients aged 18 years or older who underwent routine EEG. We created a point system to calculate the pre-EEG probability of epilepsy in a pilot study cohort. We also computed a post-test probability based on AI-EEG results. RESULTS: One hundred and four (50.7%) patients were female, the mean age was 46 years, and 110 (53.7%) were diagnosed with epilepsy. Findings favoring epilepsy included developmental delay (12.6% vs 1.1%), prior neurological injury (51.4% vs 30.9%), childhood febrile seizures (4.6% vs 0.0%), postictal confusion (43.6% vs 20.0%), and witnessed convulsions (63.6% vs 21.1%); findings favoring alternative diagnoses were lightheadedness (3.6% vs 15.8%) or onset after prolonged sitting or standing (0.9% vs 7.4%). The final point system included 6 predictors: Presyncope (-3 points), cardiac history (-1), convulsion or forced head turn (+3), neurological disease history (+2), multiple prior spells (+1), postictal confusion (+2). Total scores of ≤1 point predicted <5% probability of epilepsy, while cumulative scores ≥7 predicted >95%. The model showed excellent discrimination (AUROC: 0.86). A positive AI-EEG substantially increases the probability of epilepsy. The impact is greatest when the pre-EEG probability is near 30%. SIGNIFICANCE: A decision tool using a small number of historical clinical features accurately predicts the probability of epilepsy. In indeterminate cases, AI-assisted EEG helps resolve uncertainty. This tool holds promise for use by healthcare workers without specialty epilepsy training if validated in an independent cohort.

COVID-19 vaccine hesitancy in multiple sclerosis: A cross-sectional survey.

BACKGROUND: Vaccine willingness among people living with multiple sclerosis (PwMS) requires assessment following the approval of the first COVID-19 vaccines, since there remains uncertainty on multiple aspects of COVID-19 vaccination in immunosuppressed patients. OBJECTIVE: To understand COVID-19 and influenza vaccine willingness and its associations among PwMS, following the approval of the first two mRNA COVID-19 vaccines. METHODS: A survey was distributed to PwMS via an online platform from December 2020 to February 2021. Logistic regression models were constructed to determine the relationship between (1) COVID-19 and (2) influenza vaccination willingness with demographic and clinical characteristics. RESULTS: Of 701 responding PwMS, 76.6% were COVID-19 vaccine willing. COVID-19 vaccine willingness was significantly associated with influenza vaccine willingness (p < 0.001). In multivariable models, older age increased the odds of COVID-19 and influenza vaccine willingness (odds ratios (ORs) > 1) and other race decreased the odds of COVID-19 and influenza vaccine willingness (ORs < 1); higher functional disability decreased the odds of COVID-19 vaccine willingness (OR = 0.88, 95% confidence interval = 0.80-0.96). Prevalent vaccine-related concerns include safety (n = 244) and efficacy (n = 122). CONCLUSION: Our findings identify demographic and clinical factors as well as concerns influencing vaccine hesitancy in PwMS. These results may inform effective public health interventions to improve vaccine acceptability in this at-risk group.

Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study.

Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received emergency use authorization for the acute treatment of COVID-19. We are not aware of published data on their use in immunosuppressed people with multiple sclerosis (pwMS). We report 23 pwMS (mean age = 49 years, ocrelizumab (n = 19), fingolimod (n = 2), vaccinated with at least an initial series (n = 19)) who received mAb for acute COVID-19. Following mAb receipt, approximately half recovered in <7 days (48%). There were no adverse events or deaths. Use of mAb for pwMS treated with fingolimod or ocrelizumab was not observed to be harmful and is likely helpful for treatment of acute COVID-19.

Efficacy of Fluoxetine for Post-Ischemic Stroke Depression in Tanzania.

OBJECTIVE: Post-stroke fluoxetine trials are primarily conducted in high-income countries. We characterize post-ischemic stroke depression in fluoxetine-treated and -untreated study participants in urban Tanzania. METHODS: Adults (>18 years old) within 14 days of CT-confirmed acute ischemic stroke onset were enrolled at Muhimbili National Hospital, Tanzania. The fluoxetine-treated group took 20mg fluoxetine daily for 90 days in a phase II trial and were compared to fluoxetine-untreated historical controls. The primary outcome was depression at 90 days, measured by the Patient Health Questionnaire-9 (PHQ-9). PHQ-9 scores were compared between fluoxetine-treated and -untreated groups. A score >=9 points was considered to reflect depression. A multivariable linear regression model assessed associations with post-stroke PHQ-9 scores. RESULTS: Of the fluoxetine-treated (n=27) and -untreated (n=32) participants, the average age was 56.8 years old (39% women, 100% Black/African). The average presentation NIHSS score was 12.1 points and modified Rankin Scale (mRS) score was 3.5. The average mRS score at 90-day follow-up was 2.3. There was no significant difference between 90-day PHQ-9 scores in the fluoxetine-treated (mean=4.1 points, standard deviation=3.2; 11% depression) and untreated (mean=4.4, standard deviation=4.8; 19% depression) groups, p=.69. In the multivariable analysis, older age (ß=0.08, p=.03) and higher NIHSS score (ß=0.15, p=.04), but neither fluoxetine (ß=0.57, p=.59) nor sex (ß=-0.51, p=.63), were significantly associated with more depressive symptoms. CONCLUSIONS: Our findings parallel results from trials from higher income settings that fluoxetine does not significantly improve post-ischemic stroke depression, although our sample size was small. More work is needed to depict the longitudinal nature and treatment of post-stroke depression in Sub-Saharan Africa.

Encephalitis and meningitis in Western Africa: a scoping review of pathogens.

OBJECTIVE: To give an overview of the recently reported literature on the aetiologies of meningitis and encephalitis in western sub-Saharan Africa. METHODS: We conducted a scoping review following PRISMA guidance on published meningitis and encephalitis cases in the 16 countries of the United Nations-defined western sub-Saharan African region as identified in cohort studies, case series, and case reports, published 01/01/2000-08/01/2020, and available in four databases in August 2020 with an abstract in English, French or Italian. RESULTS: There were 38 distinct pathogens identified from 91 cohort studies' data and 48 case reports or case series' data. In cohort-level data, the majority of cases were caused by Neisseria meningitidis (71.5%), Streptococcus pneumoniae (17.6%) and Haemophilus influenzae (7.3%). In case report- and case series-level data, 40.5% of patients were <18 years old, 28.6% were female, and 28.6% were known to be immunocompromised. The case fatality rate was 39.3%. The most commonly reported pathogens among immunocompetent patients were Salmonella species (13 cases) and Ebola virus (9 cases), and the most commonly reported pathogen among immunocompromised patients was Cryptococcus neoformans (18 cases). Most cohort cases (52.3%) derived from Niger followed by Burkina Faso (28.6%). Most cases from single reports or series were reported from Nigeria (21.4%), Mali (20.2%) and Burkina Faso (19.0%). CONCLUSIONS: Given the small number of pathogens reported, our findings underscore the need to better screen, diagnose and monitor populations in western sub-Saharan Africa for additional CNS pathogens, including those posing significant outbreak risks.

Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.

Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.

Socioeconomic associations of poorly controlled epilepsy in the Republic of Guinea: cross-sectional study.

OBJECTIVE: To explore the socioeconomic factors associated with epilepsy in the Republic of Guinea. METHODS: People living with epilepsy (PLWE) were prospectively recruited at Ignace Deen Hospital, Conakry, in 2018. An instrument exploring household assets as a measure of wealth was designed and administered. Multivariate logistic regression models with fixed effects were fitted to assess the associations of sociodemographic and microeconomic factors with self-reported frequency of seizures in the prior month and regular intake of antiseizure medications (ASMs). Participants were stratified by age group: children (<13 years), adolescents (13-21) and adults (>21). RESULTS: A total of 285 participants (mean age 19.5 years; 129 females; 106 children, 72 adolescents, 107 adults, median household size 8) had an average of 4.2 seizures in the prior month. 64% were regularly taking ASMs. Direct costs of epilepsy were similar across income strata, averaging 60 USD/month in the lowest and 75 USD/month in the highest wealth quintiles (P = 0.42). The poorest PLWE were more likely to spend their money on traditional treatments (average 35USD/month) than on medical consultations (average 11 USD/month) (P = 0.01), whereas the wealthiest participants were not. Higher seizure frequency was associated with a lower household education level in adolescents and children (P = 0.028; P = 0.026) and with being male (P = 0.009) in children. Adolescents in higher-educated households were more likely to take ASMs (P = 0.004). Boys were more likely to regularly take ASMs than girls (P = 0.047). CONCLUSIONS: Targeted programming for children and adolescents in the households with the lowest education and for girls would help improve epilepsy care in Guinea.

OBJECTIF: Explorer les facteurs socioéconomiques associés à l'épilepsie en République de Guinée. MÉTHODES: Des personnes vivant avec l'épilepsie (PVE) ont été recrutées prospectivement à l'hôpital Ignace Deen, à Conakry, en 2018. Un outil explorant les actifs des ménages en tant que mesure de la richesse a été conçu et administré. Des modèles de régression logistique multivariée avec des effets fixes ont été ajustés pour évaluer les associations de facteurs sociodémographiques et microéconomiques avec la fréquence autodéclarée des crises au cours du mois précédent et la prise régulière de médicaments antiépileptiques (MAE). Les participants ont été stratifiés par groupe d'âge: enfants (<13 ans), adolescents (13-21) et adultes (> 21). RÉSULTATS: 285 participants (âge moyen 19,5 ans; 129 femmes; 106 enfants, 72 adolescents, 107 adultes, taille médiane du ménage 8) ont eu en moyenne 4,2 crises au cours du mois précédent. 64% prenaient régulièrement des MAE. Les coûts directs de l'épilepsie étaient similaires dans toutes les strates de revenus, atteignant en moyenne 60 USD/mois dans les quintiles de richesse les plus bas et 75 USD/mois dans les quintiles de richesse les plus élevés (p = 0,42). Les PVE les plus pauvres étaient plus susceptibles de dépenser leur argent pour des traitements traditionnels (35 USD/mois en moyenne) que pour des consultations médicales (11 USD/mois en moyenne) (p = 0,01), contrairement aux participants les plus riches. Une fréquence de crises plus élevée était associée à un niveau d'éducation du ménage plus faible chez les adolescents et les enfants (p = 0,028; p = 0,026) et au fait d'être de sexe masculin (p = 0,009) chez les enfants. Les adolescents des ménages avec un niveau d'éducation plus élevé étaient plus susceptibles de prendre des MAE (p = 0,004). Les garçons étaient plus susceptibles de prendre régulièrement des MAE que les filles (p = 0,047). CONCLUSIONS: Des programmes ciblés pour les enfants et les adolescents dans les ménages les moins scolarisés et pour les filles aideraient à améliorer les soins de l'épilepsie en Guinée.

Depression, sleep quality, and social isolation among people with epilepsy in Bhutan: A cross-sectional study.

PURPOSE: The aim of this study was to analyze the possible contributions of seizure burden, sleep quality, and social integration to depression among people with epilepsy (PWE) in Bhutan. METHODS: Bhutan is a lower-middle-income country in Southeast Asia with a public healthcare system without neurologists. People with epilepsy were prospectively recruited from psychiatrist-run epilepsy clinics at the National Referral Hospital in the capital city of Thimphu. Adult participants with epilepsy were interviewed for clinical history, sleep quality using the Pittsburgh Sleep Quality Index, social networks using the Berkman-Syme Social Network Index, and depressive symptoms using the Patient Health Questionnaire - 9 (PHQ-9). A multivariable regression model was built to assess the relationship between depression as an outcome and the possible contributors of sleep quality, sex, and seizure in the prior month. RESULTS: Out of 80 participants (39 women, mean age: 29.4 years old, range: 18-56 years, 58 [73%] with a seizure in the previous month), 33% had poor sleep quality, 68% were socially isolated, 30% had a mild depressive symptom burden or more, and 18% reported suicidal ideation at the time of their interview. Women had a higher average PHQ-9 score versus men, which showed a trend towards statistical significance (5.6 versus 3.3 PHQ-9 points, p = 0.07), and on average met criteria for mild depression. Social integration was not significantly associated with sleep quality and had no relationship with depressive burden. There was a small positive correlation between poorer sleep quality and depressive symptoms which showed a trend towards statistical significance (r = 0.21, p = 0.06). In a multivariable regression, poor sleep quality was associated with higher depressive symptom burden, adjusting for participant sex and having a seizure in the previous month (p = 0.01). CONCLUSIONS: Our exploratory study disentangles the multilayered psychosocial burden of disease experienced by PWE in Bhutan, a lower-middle-income country with access to antiseizure medications and psychiatrists but not expert epilepsy services or human resources. Further investigation into the interrelationships among social isolation, poor sleep quality, depression, and seizure burden could identify preventable and remediable constituents of this burden.

Prevalence, severity, and associations of depression in people with epilepsy in Guinea: A single-center study.

BACKGROUND AND OBJECTIVE: Depression has long been recognized as a comorbidity of epilepsy in high-income countries, ranging from 17 to 49% of people with epilepsy (PWE). Of the limited studies from sub-Saharan Africa (SSA), where most people have uncontrolled seizures, an even higher prevalence of depression is reported among PWE at times exceeding 80%. We sought to assess the prevalence and severity of depression and its associated factors among PWE in Guinea, a sub-Saharan West African country where most PWE have poorly controlled seizures. METHODS: People with epilepsy from the community, age 16 years old and above, were consecutively recruited into a convenience cohort at the Ignace Deen Hospital in the capital city, Conakry, in summer 2018 as part of a larger study characterizing PWE in Guinea. Each participant was evaluated by a team of Guinean physicians and a U.S.-based neurologist to confirm the diagnosis of epilepsy. Inperson interviews were performed to measure demographic, clinical, socioeconomic, and related variables. Depression was measured via the Patient Health Questionniare-9 in the language of the participant's preference with a cutoff of 5 or more points being categorized as depressed. Regression analyses were performed to measure the associations between explanatory variables with the outcome of depression. RESULT: Of 140 PWE (age range: 16-66 years old; 64 female; 64% taking an antiseizure medication including 28% carbamazepine, 16% phenobarbital, and 14% valproic acid; duration of epilepsy: 11 years; 71% with one or more seizures in the past month; 17% never treated with an antiseizure medication; 90% with loss of consciousness during seizures; 10% without formal education; 31% with university level education; 62% using tap water; 48% with a serious seizure-related injury), the point prevalence of depression was 66% (95% confidence interval [CI]: 58%-74%): 43% of PWE had mild depression, 19% moderate, 4% moderate to severe, and 0.1% severe. In a multivariate analysis, the occurrence of a seizure in the past month (odds ratio: 3.03, 95% CI: 2.63-3.48, p = 0.01) was associated with depression, while gender, self-perceived stigma score, serious injuries, and the number of antiseizure medications taken were not statistically significantly associated (p > 0.05). Twenty-five percent of all participants endorsed thoughts of self-harm or suicidality. CONCLUSION: Two-thirds of PWE in Guinea had depression in this single-institution convenience cohort. The presence of a seizure in the last month was the factor most associated with depression and is modifiable in many PWE. The high prevalance of depression suggests that screening and addressing depressive symptoms should be incorporated into routine epilepsy care in Guinea.

Relapsing remitting multiple sclerosis in progressive external ophthalmoplegia: A report of two cases.

Evidence from genetic and pathologic studies suggests that mitochondrial dysfunction occurs in multiple sclerosis (MS). Furthermore, cases of MS have been reported in patients with mitochondrial disease. The phenotypic range of mitochondrial illness associating with MS is not yet well defined. In this report, we highlight two cases of patients with confirmed genetic mutations responsible for progressive external ophthalmoplegia who independently meet McDonald criteria for MS. Better characterization of the range of mitochondrial disease associated with MS may improve our understanding of MS disease pathophysiology.

Cognitive Function and Impairment in Older, Rural South African Adults: Evidence from "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in Rural South Africa".

BACKGROUND/AIMS: We aimed to estimate the prevalence of cognitive impairment, and the sociodemographic and comorbid predictors of cognitive function among older, rural South African adults. METHODS: Data were from a population-based study of 5,059 adults aged ≥40 years in rural South Africa in 2015. Cognitive impairment was defined as scoring ≤1.5 SDs below the mean composite time orientation and memory score, or requiring a proxy interview with "fair" or "poor" proxy-reported memory. Multiple linear regression estimated the sociodemographic and comorbid predictors of cognitive score, with multiplicative statistical interactions between each of age and sex with education. RESULTS: Cognitive impairment increased with age, from 2% of those aged 40-44 (11/516) to 24% of those aged ≥75 years (214/899). The independent predictors of lower cognitive score were being older, female, unmarried, not working, having low education, low household wealth, and a history of cardiovascular conditions. Education modified the negative associations between female sex, older age, and cognitive function score. CONCLUSIONS: The prevalence of cognitive impairment increased with age and is comparable to rates of dementia reported in other sub-Saharan African countries. Age and sex differences in cognitive function scores were minimized as education increased, potentially reflecting the power of even poor-quality education to improve cognitive reserve.

School status and its associations among children with epilepsy in the Republic of Guinea.

BACKGROUND: In low-income countries (LICs), there are multiple barriers for children with epilepsy (CWE) to attend school. We examined potentially modifiable associations with poor school performance in CWE in the West African Republic of Guinea. METHODS: Children with epilepsy of school age were recruited using public announcements and a clinical register of people with epilepsy at the Ignace Deen Hospital in Conakry in 2018. A team of Guinean and U.S. neurologists and neurologists-in-training interviewed each CWE and parent for his/her epilepsy history, household finances, educational attainment level, and perceived stigma using the Stigma Scale of Epilepsy (SSE). Each child was also tested using the Wechsler Nonverbal Scale of Ability (WNV). Low school performance was defined as either not attending school or being held back a grade level at least once. Potential predictors of low school performance were analyzed. FINDINGS: Of 128 CWE (mean age: 11.6 years, 48.4% female), 11.7% (n = 15) never attended school, 23.3% (n = 30) dropped out, and 64.8% (n = 83) were currently enrolled. Of CWE attending school, 46.9% (n = 39) were held back a grade level. Overall, 54 children were defined as low performers (LPs) (42%). ;Greater than 100 lifetime seizures (odds ratio (OR) = 8.81; 95% confidence interval (CI) = 2.51, 37.4; p = 0.001) and lower total WNV score (OR = 0.954; 95% CI = 0.926, 0.977; p < 0.001) were significantly associated with poor school performance in separate models, when controlling for potential confounders. Given the strong relationship between seizure freedom and school performance, we estimated that 38 additional CWE (33.6%) could become high performers (HPs) if all CWE were adequately treated to achieve the lifetime seizure category of <10 seizures and could be cognitively intact again. Models examining SSE and household wealth quintile were not significantly associated with school performance. CONCLUSIONS: Higher lifetime seizures and lower WNV score were significantly associated with low school performance in CWE in Guinea. In spite of our conservative definition of high school performance (attending without failing) and risk of referral bias at an academic center where patients were allowed to self-refer, we demonstrate that seizure control in this setting could increase the number of CWE who could attend and stay in school.

Opportunities for intervention: stroke treatments, disability and mortality in urban Tanzania.

OBJECTIVE: Given the high post-stroke mortality and disability and paucity of data on the quality of stroke care in Sub-Saharan Africa, we sought to characterize the implementation of stroke-focused treatments and 90-day outcomes of neuroimaging-confirmed stroke patients at the largest referral hospital in Tanzania. DESIGN: Prospective cohort study. SETTING: Muhimbili National Hospital (MNH) in Dar es Salaam, July 2016-March 2017. PARTICIPANTS: Adults with new-onset stroke (<14 days), confirmed by head CT, admitted to MNH. MAIN OUTCOMES MEASURES: Modified Rankin scale (mRS) and vital status. RESULTS: Of 149 subjects (mean age 57; 48% female; median NIH stroke scale (NIHSS) 19; 46% ischemic stroke; 54% hemorrhagic), implementation of treatments included: dysphagia screening (80%), deep venous thrombosis prophylaxis (0%), aspirin (83%), antihypertensives (89%) and statins (95%). There was limited ability to detect atrial fibrillation and carotid artery disease and no acute thrombolysis or thrombectomy. Of ischemic subjects, 19% died and 56% had severe disability (mRS 4-5) at discharge; 49% died by 90 days. Of hemorrhagic subjects, 33% died and 49% had severe disability at discharge; 50% died by 90 days. In a multivariable model, higher NIHSS score but not dysphagia, unconsciousness, or patient age was predictive of death by 90 days. CONCLUSIONS: The 90-day mortality of stroke presenting at MNH is 50%, much higher than in higher income settings. Although severe stroke presentations are a major factor, efforts to improve the quality of care and prevent complications of stroke are urgently needed. Acute stroke interventions with low number needed to treat represent challenging long-term goals.

Intravenous Thrombolysis for Stroke and Presumed Stroke in Human Immunodeficiency Virus-Infected Adults: A Retrospective, Multicenter US Study.

BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV) infection has been shown to increase both ischemic and hemorrhagic stroke risks, but there are limited data on the safety and outcomes of intravenous thrombolysis with tPA (tissue-type plasminogen activator) for acute ischemic stroke in HIV-infected patients. METHODS: A retrospective chart review of intravenous tPA-treated HIV patients who presented with acute stroke symptoms was performed in 7 large inner-city US academic centers (various search years between 2000 and 2017). We collected data on HIV, National Institutes of Health Stroke Scale score, ischemic stroke risk factors, opportunistic infections, intravenous drug abuse, neuroimaging findings, and modified Rankin Scale score at last follow-up. RESULTS: We identified 33 HIV-infected patients treated with intravenous tPA (mean age, 51 years; 24 men), 10 of whom were stroke mimics. Sixteen of 33 (48%) patients had an HIV viral load less than the limit of detection while 10 of 33 (30%) had a CD4 count <200/mm3. The median National Institutes of Health Stroke Scale score at presentation was 9, and mean time from symptom onset to tPA was 144 minutes (median, 159). The median modified Rankin Scale score for the 33-patient cohort was 1 and for the 23-patient actual stroke cohort was 2, measured at a median of 90 days poststroke symptom onset. Two patients had nonfatal hemorrhagic transformation (6%; 95% confidence interval, 1%-20%), both in the actual stroke group. Two patients had varicella zoster virus vasculitis of the central nervous system, 1 had meningovascular syphilis, and 7 other patients were actively using intravenous drugs (3 cocaine, 1 heroin, and 3 unspecified), none of whom had hemorrhagic transformation. CONCLUSIONS: Most HIV-infected patients treated with intravenous tPA for presumed and actual acute ischemic stroke had no complications, and we observed no fatalities. Stroke mimics were common, and thrombolysis seems safe in this group. We found no data to suggest an increased risk of intravenous tPA-related complications because of concomitant opportunistic infections or intravenous drug abuse.

The economic burden of epilepsy in Bhutan.

OBJECTIVE: To assess the economic impact of epilepsy in Bhutan, a lower-middle-income country with a universal health care system, but with limited access to neurological care. METHODS: A cross-sectional survey was conducted of patients with epilepsy at the Jigme Dorji Wangchuk National Referral Hospital from January to August 2016. Data were collected on clinical features, cost of care, impact of epilepsy on school or work and household economic status of participants and matched comparisons (a sibling or neighbour from a household without epilepsy). RESULTS: A total of 172 individuals were included in the study (130 adults and 42 children). One-third of adults and 20 (48%) children had seizures at least once per month. Mean direct out-of-pocket cost for epilepsy care was 6054 Bhutanese Ngultrum (BTN; 91 USD) per year, of which transportation formed the greatest portion (53%). Direct costs of epilepsy were an average of 3.2% of annual household income. Adults missed 6.8 (standard deviation [SD]: 9.0) days of work or school per year on average, and children missed 18.6 (SD: 34.7) days of school. Among adults, 23 (18%) abandoned employment or school because of epilepsy; seven children (18%) stopped school because of epilepsy. Households with a person with epilepsy had a lower monthly per-person income (6434 BTN) than comparison households without epilepsy (8892 BTN; P = 0.027). CONCLUSIONS: In Bhutan, despite universal health care services, households of people with epilepsy face a significant economic burden. With many adults and children unable to attend school or work, epilepsy causes a major disruption to individuals' livelihoods.