Search

Background and purpose: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. Methods: We performed further exploratory in‐depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. Results: Placebo‐treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS‐R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65–0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS‐R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. Conclusions: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12–18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future. [ABSTRACT FROM AUTHOR]

Burundi has one of the highest prevalence of stunting in the world. This study aimed to identify determinants of stunting among children under age five in Burundi. A total of 4993 children with anthropometric measurements from the 2016–2017 Burundi Demographic and Health Survey were included in the study. Stunting was assessed from the height‐for‐age Z‐scores (HAZ). Logistic regression models were analyzed to identify demographic, maternal, child‐related, and structural variables that influence stunting. In total, 56.9% of children under age five were stunted, of those 31.0% moderately and 25.9% severely. Multivariable logistic regression indicated that older children, male children (adjusted OR (aOR) = 1.41, 95% CI 1.24–1.61), and children who were perceived as small (aOR = 2.00, 95% CI 1.55–2.59) or very small at birth (aOR = 2.37, 95% CI 1.57–3.59) were significantly more likely to be stunted. Moreover, children of single mothers, with lower levels of education, who were underweight at the time of the survey (aOR = 1.95, 95% CI 1.42–2.68), who had short stature (aOR = 3.76, 95% CI 2.50–5.66) or who conceived more than four children (aOR = 1.22, 95% CI 1.05–1.42) were more commonly stunted. Stunting was more prevalent in rural areas (aOR = 2.53, 95% CI 1.72–3.73) and in households with no access to improved types of toilet facilities (aOR = 1.27, 95% CI 1.10–1.45). The results of this study show that the prevalence of stunting in children under age five in Burundi is alarmingly high and underscores the urgent need for decisive and determined action. [ABSTRACT FROM AUTHOR]

Objective: Taenia solium (T. solium) neurocysticercosis (NCC) affects the central nervous system and is associated with 30% of acquired epilepsy in some endemic areas. Epilepsy is a stigmatizing disease in many societies and people with epilepsy (PWE) and their families experience discrimination. This study aimed to explore the knowledge, perceptions, and experiences of epilepsy among PWE and their caregivers attending mental health clinics. Methods: In T. solium endemic areas of Tanzania, PWE and their caregivers attending mental health clinics were identified and their informed consent was sought prior to study participation. In‐depth interviews were conducted in Swahili language and analyzed thematically. The coding was undertaken by two independent researchers using NVivo (Version 12, QSR International). Results: Thirty‐eight participants were interviewed. Three themes were identified during the analysis, namely, knowledge about epilepsy; perception of epilepsy; and experience with epilepsy among PWE and their caregivers. Participants commonly defined epilepsy as a "falling disease," perceived to be caused by witchcraft, and were unaware of the association between T. solium and epilepsy. Stigmatization of epilepsy was reported as a problem. Reported treatment patterns after the initial onset of epilepsy varied widely; however, patients usually began treatment with traditional healing methods, and only later opted for biomedical treatment. Patients had generally poor adherence to antiseizure medication, which could be caused by inadequate knowledge or irregular supply. Significance: Level of knowledge about epilepsy was low, and NCC was not mentioned as a cause of epilepsy among participants. Epilepsy was generally perceived to be the result of witchcraft, evil spirits, or curses. Health education is needed, including an explanation of the model of T. solium transmission and the insistence on hygiene measures. This could reduce the number of new infections with T. solium, improve access to prompt biomedical treatment, and improve the lives of PWE. [ABSTRACT FROM AUTHOR]

Objective: To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S. Methods: We used publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021 and June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post‐vaccination neurological event rates were compared between vaccine types and to age‐matched baseline incidence rates in the U.S. and rates of neurological events following COVID. Results: Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0‐3) from inoculation. Guillain‐Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer‐BioNtech (BNT162b2) or Moderna (mRNA‐1,273; 0.15% vs 0.03% vs 0.03% of doses, respectively, p < 0.0001). The observed‐to‐expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5‐fold higher than background rates. However, the rate of neurological events after acute SARS‐CoV‐2 infection was up to 617‐fold higher than after COVID vaccination. Interpretation: Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS‐CoV‐2 infection are up to 617‐fold higher than after COVID vaccination. ANN NEUROL 2022;91:756–771 [ABSTRACT FROM AUTHOR]

Objective: Global action for epilepsy requires information on the cost of epilepsy, which is currently unknown for most countries and regions of the world. To address this knowledge gap, the International League Against Epilepsy Commission on Epidemiology formed the Global Cost of Epilepsy Task Force. Methods: We completed a systematic search of the epilepsy cost‐of‐illness literature and identified studies that provided a comprehensive set of direct health care and/or indirect costs, followed standard methods of case identification and cost estimation, and used data on a representative population or subpopulation of people with epilepsy. Country‐specific costs per person with epilepsy were extracted and adjusted to generate an average cost per person in 2019 US dollars. For countries with no cost data, estimates were imputed based on average costs per person of similar income countries with data. Per person costs for each country were then applied to data on the prevalence of epilepsy from the Global Burden of Disease collaboration adjusted for the treatment gap. Results: One hundred one cost‐of‐illness studies were included in the direct health care cost database, 74 from North America or Western Europe. Thirteen studies were used in the indirect cost database, eight from North America or Western Europe. The average annual cost per person with epilepsy in 2019 ranged from $204 in low‐income countries to $11 432 in high‐income countries based on this highly skewed database. The total cost of epilepsy, applying per person costs to the estimated 52.51 million people in the world with epilepsy and adjusting for the treatment gap, was $119.27 billion. Significance: Based on a summary and extrapolations of this limited database, the global cost of epilepsy is substantial and highly concentrated in countries with well‐developed health care systems, higher wages and income, limited treatment gaps, and a relatively small percentage of the epilepsy population. [ABSTRACT FROM AUTHOR]

Objective: Neurocysticercosis (NCC), caused by the pork tapeworm Taenia solium, is a major cause of acquired epilepsy in endemic regions. The Republic of Uganda, one of the great‐lakes nations in East Africa, has undergone major strives of political instability in the past century, impeding control of T. solium and other foodborne diseases. Building on data on the epidemiology of NCC, we aimed to assess the health and economic impact of NCC‐associated epilepsy and headache in Uganda. Methods: We used DisMod II to generate an internally consistent, complete and age‐stratified set of epidemiological parameters for NCC epilepsy, and subsequently modelled the NCC headache incidence from the NCC epilepsy incidence. The health impact of both conditions was quantified in terms of Disability‐Adjusted Life Years (DALYs), while the economic impact was quantified as the cost of illness associated with direct healthcare costs, patient costs and productivity losses. For both assessments, we adopted an incidence perspective and used 2010 as reference year. Uncertainty was propagated using 100,000 Monte Carlo simulations. Results: In 2010, NCC was estimated to cause more than 9000 (CI: 7685–11,071) new cases of epilepsy and nearly 1500 new cases of headache, eventually leading to nearly 3000 deaths. Overall, it was estimated that NCC led to more than 170,000 DALYs (5.2 per 1000 person years; 16 per incident case) and an economic loss of more than USD 75 million (8000 per incident case). Non‐fatal health outcomes were the largest contributors to the overall health impact, while productivity losses dominated the NCC cost of illness. Conclusions: NCC imposes a substantial burden on public health and the economy in Uganda with poor attention given to this public health problem. Increased awareness among governments, international agencies, and general public, as well as targeted intervention studies using a One Health approach are needed to reduce the significant burden of NCC in Uganda. [ABSTRACT FROM AUTHOR]

Objectives: Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have a high disease burden and are prevalent in overlapping low‐ and middle‐income areas. Yet, treatment guidance for people living with HIV/AIDS (PLWH/A) co‐infected with NCC is currently lacking. This study aims to scope the available literature on HIV/AIDS and NCC co‐infection, focusing on epidemiology, clinical characteristics, diagnostics and treatment outcomes. Methods: The scoping literature review methodological framework, and the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines were followed. A total of 16,969 records identified through database searching, and 45 additional records from other sources were reduced to 52 included studies after a standardised selection process. Results: Two experimental studies, ten observational studies, 23 case series/case reports and 17 reviews or letters were identified. Observational studies demonstrated similar NCC seroprevalence in PLWH/A and their HIV‐negative counterparts. Of 29 PLWH/A and NCC co‐infection, 17 (59%) suffered from epileptic seizures, 15 (52%) from headaches and 15 (52%) had focal neurological deficits. Eighteen (62%) had viable vesicular cysts, and six (21%) had calcified cysts. Fifteen (52%) were treated with albendazole, of which 11 (73%) responded well to treatment. Five individuals potentially demonstrated an immune‐reconstitution inflammatory syndrome after commencing antiretroviral therapy, although this was in the absence of immunological and neuroimaging confirmation. Conclusions: There is a paucity of evidence to guide treatment of PLWH/A and NCC co‐infection. There is a pressing need for high‐quality studies in this patient group to appropriately inform diagnostic and management guidelines for HIV‐positive patients with NCC. [ABSTRACT FROM AUTHOR]

There is an accumulating volume of research into neurological manifestations of COVID-19. However, inconsistent study designs, inadequate controls, poorly-validated tests, and differing settings, interventions, and cultural norms weaken study quality, comparability, and thus the understanding of the spectrum, burden and pathophysiology of these complications. Therefore, a global COVID-19 Neuro Research Coalition, together with the WHO, has reviewed reports of COVID-19 neurological complications and harmonised clinical measures for future research. This will facilitate well-designed studies using precise, consistent case definitions of SARS-CoV2 infection and neurological complications, with standardised forms for pooled data analyses that non-specialists can use, including in low-income settings. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Objective: To analyse the cumulative incidence of febrile seizures, to evaluate the accuracy of our screening questionnaire and to describe clinical characteristics of children with febrile seizure in an urban population in Tanzania.Methods: A large random cluster sampled population was screened for a febrile seizure history as part of a larger epilepsy study using a standardised questionnaire in a two-stage door-to-door survey in Tanzania. A subset of screen positive participants was further examined for confirmation of diagnosis and evaluation of clinical characteristics.Results: Overall, 49 697 people were screened for a febrile seizure history of whom 184 (0.4%) screened positive. Women more commonly screened positive than men (112 [0.4%] vs. 72 [0.3%]). There was no marked difference between age groups or education. The positive predictive value of the screening tool was 37% (95% CI 24-51%) but its accuracy varied with the age of interviewed individuals. Cumulative incidence rates were estimated between 1.1% and 2.0% after adjusting for the inaccuracy of the screening tool. Most febrile seizures occurred before the age of two (65%) and most children had more than one episode (80%). A large proportion of children had complex febrile seizure (65%), often caused by malaria or respiratory infections.Conclusions: The community-based cumulative incidence of a febrile seizure history in an urban Tanzanian population was similar to rates reported from other rural populations after adjusting for the inaccuracy of our screening tool. Based on the integrated nature of the febrile seizure questionnaire, screening positivity rates may have been too low. This has implications for the design of future studies. The majority of cases had complex febrile seizures often associated with malaria. This has implications for clinical case management. [ABSTRACT FROM AUTHOR]

Objective: Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival.Methods: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date.Results: Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44.Interpretation: The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216. [ABSTRACT FROM AUTHOR]

Objectives Nodding syndrome ( NS), a new epilepsy disorder of sub-Saharan Africa, has only recently been classified. In a study conducted in southern Tanzania in 2005, 62 patients with NS were analyzed in great detail. The present study, a follow-up investigation, was conducted to evaluate the progression of NS over time and to obtain serial electroencephalography ( EEG) data. Methods Of the 62 NS patients, 53 (85.5%), the majority of whom were currently on some form of antiepileptic treatment, could be reevaluated in 2009 with a standardized questionnaire. A subset of these patients (25/53) underwent EEG investigation. Results In patients with 'head nodding ( HN) only' in 2005, 10 (43.5%) of 23 remained with the same diagnosis, whereas 5 (21.7%) of 23 had developed ' HN plus' (i.e., HN and generalized tonic-clonic seizures). Six patients (26.1%) had seizures other than HN only, and two patients (8.7%) had fully recovered. In the ' HN plus' group of 2005, 9 (30.0%) of 30 patients remained ' HN plus,' and 15 patients (50.0%) had seizures other than HN only. Four patients (13.3%) reverted to ' HN only,' and two patients (6.7%) stopped all seizures. In 11 (44.0%) of 25 patients, electroencephalography ( EEG) showed generalized slowing. Six (54.6%) of these 11 abnormal EEG studies further showed generalized epileptiform discharges: (1) ictal electroencephalographic pattern with generalized 2.5 Hz spike and waves in two patients and (2) interictal bursts of 1.5-2 Hz spike and waves in four patients. Significance This follow-up study confirms that HN represents an epilepsy disorder, possibly of the atypical absence type with dynamic development over time. [ABSTRACT FROM AUTHOR]

Objective.- One goal of the campaign 'Lifting the burden: The global campaign against headache' is to highlight existing evidence about headache worldwide. In this context, the aim of our study was to report the migraine-related headache burden in northern Tanzania. Methods.- From December 2003 until June 2004 a community-based door-to-door survey was undertaken in northern Tanzania, using multistage cluster sampling. Based on the criteria of the International Headache Society, 7412 individuals were enrolled in this survey. Results.- Migraine patients' average annual attack frequency was 18.4 (n = 308, standard deviation [SD] ± 47.4) with a mean duration of 16.4 hours (SD ± 20.6). The average headache intensity per patient was 2.65 (SD ± 0.59) with a calculated loss of 6.59 (SD ± 26.7) working days per year. Extrapolation of data to the investigated population (n = 7412) resulted in annual migraine burden of 281.0 migraine days per 1000 inhabitants. Conclusions.- To our knowledge, this study reports for the first time the burden that arises from migraine headache in a rural population of sub-Sahara Africa (SSA). As the presented migraine-related burden is considerable, we hope that our data will increase the awareness among local decision makers in allocating resources for treatment and research on headache. [ABSTRACT FROM AUTHOR]

The main aim of this door-to-door-study was to determine the prevalence, incidence, and clinical characteristics of epilepsy in northern Tanzania. A total of 7,399 people were screened with a standardized questionnaire using “multistage random sampling.” The prevalence rate of epilepsy was 11.2/1,000 [95% confidence interval (CI) 8.9–13.9/1,000] and the age-adjusted prevalence rate was 13.2/1,000. The prevalence of active epilepsy was 8.7/1,000 (95% CI 6.7–11/1,000). There was a preponderance of women. The average retrospective incidence including the last 5 years was 81.1/100,000 (95% CI 65–101/100,000). Fifty-four percent (45 of 83) of the people with epilepsy had generalized seizures without any identifiable cause; 71% (59 of 83) of the epilepsy patients had not visited health institutions prior to the study and 76% (63 of 83) had never received treatment. Our study shows that the prevalence and incidence of epilepsy in northern Tanzania are higher compared to developed countries and that the majority of people with epilepsy do not access treatment. [ABSTRACT FROM AUTHOR]

In the 1960s in Tanzania, L. Jilek-Aall observed a seizure disorder characterized by head nodding (HN). Decades later, “nodding disease,” reminiscent of what was seen in Tanzania, was reported from Sudan. To date this seizure disorder has not been classified and possible causes still remain obscure. In a prospective study in southern Tanzania, we evaluated 62 patients with HN. Selected patients underwent blood (n = 51) and cerebrospinal fluid (CSF) (n = 48) analyses. Others were chosen for MRI (n = 12) and EEG (n = 10). Seizure type was classified as “head nodding only” and “head nodding plus,” the latter being combined with other types of seizure (n =34). During HN, consciousness was impaired in 11 patients (17.7%) and supportive signs of epileptic seizures were described by 15 (24.2%) patients. Precipitating factors were confirmed by 11 (17.7%) patients. Fifty-six (90.3%) patients had at least one relative with epilepsy. EEG confirmed interictal epileptic activity in two patients and unspecific changes in four patients. MRI showed hippocampus pathologies (n = 5) and gliotic changes (n = 5). Skin polymerase chain reaction (PCR) positivity for Onchocerca volvulus was significantly associated with lesions on MRI. However, PCR of the CSF was negative in all cases. We present a comprehensive clinical description of the “HN syndrome,” possibly a new epilepsy disorder in sub-Saharan Africa. MRI lesions and their association with positive skin PCR for O. volvulus despite negative PCR of the CSF is intriguing and deserves attention. Furthermore, the high prevalence of hippocampus sclerosis and familial clustering of epilepsy may point toward other potential pathogenetic mechanisms. [ABSTRACT FROM AUTHOR]