An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa.

BACKGROUND: Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent; however, recent work has shown the existence of a unique Htt haplotype in South-Africa specific to indigenous Africans. OBJECTIVE: We aimed to investigate the CAG trinucleotide repeats expansion in the Htt gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa. METHODS: We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the mHtt gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region. RESULTS: HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the mHTT; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the mHTT; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD-bar three who were juvenile onset of <21 years-were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54-16 kya ago: Nilo-Sahara and Niger-Congo. CONCLUSION: This is the first study examining HD in multiple sites in sub-Saharan Africa. We demonstrated that HD is found in multiple ethnic groups residing in five sub-Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio-economic impact, and genetic origins need further exploration and reappraisal.

MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset.

INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort.

Neuroimaging findings in DYT1 dystonia and the pathophysiological implication: A systematic review.

BACKGROUND: Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear. OBJECTIVES: This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques. METHODS: A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211). RESULTS: All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers. CONCLUSIONS: Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.

MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson's disease risk and age at onset.

Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking. Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans. Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration. Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.

Telemedicine ready or not? A cross-sectional assessment of telemedicine maturity of federally funded tertiary health institutions in Nigeria.

Introduction and objective: Telemedicine has reinforced its position as a means for the continuity of healthcare services and a cost-effective approach to improving health equity as demonstrated during the COVID-19 pandemic. The preparedness of health systems for telemedicine is an indicator of the scalability of their services, especially during catastrophes. We aimed to assess the maturity and preparedness of federally funded tertiary health institutions in Nigeria, to deploy telemedicine as such data are currently lacking and are required to drive improvements in health services delivery. Methods: We conducted a cross-sectional survey of thirty randomly selected federally funded tertiary health institutions in Nigeria using the Pan American Health Organization's tool for assessing the maturity level of health institutions to implement telemedicine between 17 September 2020 and 1 September 2021. Descriptive statistics were used for overall maturity levels and non-parametric tests to compare scores for overall maturity and specific Pan American Health Organization domains per region. The level of significance was set at p-value <0.05. Results: The response rate was 77.4% (24 of 30 randomly polled federally funded tertiary health institutions responded). Overall, the median telemedicine maturity level was 2.0 (1.75) indicating a beginner level. No significant inter-zonal difference in the median overall maturity level (p = 0.87). The median maturity levels for telemedicine readiness in specific domains were organizational readiness - 2.0 (2.0), processes 1.0 (1.0), digital environment 2.0 (3.0), human resources 2.0 (1.0), regulatory issues - 1.5 (1.0) and expertise 2.0 (2.0); mostly at beginner level, with no inter-zonal differences. Most participating institutions had no initiatives in place for domains of processes and regulatory issues. Conclusions: The current telemedicine maturity level of federally funded tertiary health institutions in Nigeria is at the beginner level. This behoves policy-makers to advance the implementation and deployment of telemedicine nationwide as part of digital quality healthcare, to improve health equity and to ensure continuity of healthcare services in the event of another pandemic.

Management of rare movement diseases in different world regions.

To evaluate the management of rare movement disorders (RMD) at the international level and identify care needs to be addressed, the Rare Movement Disorders Study Group of the International Parkinson and Movement Disorders Society (MDS) has conducted an exploratory survey. We sent an online survey to experts in Africa, Asia, Oceania and American continents following the classification of the MDS Regional Sections: Africa, Asia and Oceania (A&O), and Pan-America. We did not include Europe as the European Reference Network for Rare Neurological Diseases recently performed a similar care needs survey across European countries. We obtained responses from experts from 20 African, 26 A&O and 19 Pan-American countries. According to the respondents, only 55% of African countries had movement disorders experts, while these were present in 96% of A&O and 91% of Pan-American. Access to care for patients with RMD was stated difficult in 70% of African, 54% of A&O, and 65% of Pan-American countries. Africa was the region with greatest difficulties in accessing diagnostic tests. However, in Pan-America and A&O, large inequalities were observed between countries with quite variable access to therapeutic options such as deep brain stimulation. The survey results reflect wide variability in the management of RMD and provide evidence that a worldwide care-focused network is highly warranted. Scientific and medical organisations should raise awareness of deficits in managing RMD and care disparities among regions. The goals should be to facilitate the training of professionals, establish improvement strategies, and increase support and budgeting for these diseases.

Post-Vaccination Pharyngeal-Cervical-Brachial Variant of Guillain-Barré Syndrome.

The pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome (GBS) is very rare. It is characterized by weakness of the upper extremities associated with bulbar symptoms and facial diplegia. Documented cases were post-infectious, a post-vaccination occurrence has not been documented in the available literature. Even rarer is the occurrence of any variant of GBS following the mumps measles rubella (MMR) vaccine. The neurophysiological hallmark of PCB variant of GBS is a combination of myelinopathy and axonopathy, hence, its consideration as a subtype of the acute motor axonal neuropathy (AMAN) variant. It should be suspected in any case of acute-onset flaccid symmetrical weakness of the upper extremities, as early diagnosis and treatment are key to preventing fatal bulbar weakness. Here we report a case of a middle-aged man, who presented with features of PCB a fortnight after being vaccinated for MMR.

Relationship Between Obesity and Severity of Carpal Tunnel Syndrome in Tanzania.

Background: Carpal tunnel syndrome (CTS) is the most common focal mononeuropathy in the general population, and obesity is one of its established independent risk factors The prevalence of obesity in CTS patients and its association with CTS severity are yet to be fully studied among Tanzanians. In this study, we determined the frequency of obesity in patients with CTS and its relationship with the electrophysiological severity of CTS in a Tanzanian private tertiary level hospital. Methods: This is a retrospective observational and analytical study of patients referred for electrodiagnostic (EDX) evaluation of suspected CTS at the clinical neurophysiology laboratory of the Aga Khan Hospital, Dar es Salaam, Tanzania. All EDX studies done for CTS indications between August 1, 2017, and December 31, 2019, were reviewed. The frequency of CTS patients with obesity (body mass index >30 kg/m2) and overweight (25.0-29.9 kg/m2) was determined. Next, we explored the relationship between obesity and the electrophysiologic severity of CTS. Results: One-hundred nine hands were studied. The prevalence of obesity was 50.5% and overweight was 31.2%. Females were significantly more obese than males (P = 0.001). Many of the EDX parameters that defined CTS, including prolonged median nerve sensory and distal motor latencies as well as sensory conduction velocity, were significantly more abnormal in the obese when compared to the nonobese patients. On univariate analysis, severe CTS (stage 5) was commoner among nonobese patients (P = 0.031), while moderate CTS (stage3) was more prevalent among obese patients (P < 0.001). Multivariate regression analysis, however, revealed no effect of obesity on CTS severity (P = 0.490). Conclusion: Obesity and overweight are prevalent among this cohort with CTS, but did not predict severe CTS. The use of other indices of adiposity may show a trend.

COVID-19 and Teleneurology in Sub-Saharan Africa: Leveraging the Current Exigency.

Africa has over 1.3 billion inhabitants, with over 60% of this population residing in rural areas that have poor access to medical experts. Despite having a ridiculously huge, underserved population, very few African countries currently have any form of sustained and organized telemedicine practice, and even fewer have dedicated tele-neurology services. The ongoing COVID-19 pandemic has proved to be one of the most significant disruptors of vital sectors of human endeavor in modern times. In the healthcare sector, there is an increasing advocacy to deliver non-urgent care via telemedicine. This paper examined the current state of tele-neurology practice and infrastructural preparedness in sub-Saharan Africa. Currently, there is over 70% mobile phone penetration in most of the countries and virtually all of them have mobile internet services of different technologies and generations. Although the needed infrastructure is increasingly available, it should be improved upon. We have proposed the access, costs, ethics, and support (ACES) model as a bespoke, holistic strategy for the successful implementation and advancement of tele-neurology in sub-Saharan Africa.

Genomic Literacy and Awareness of Ethical Guidance for Genomic Research in Sub-Saharan Africa: How Prepared Are Biomedical Researchers?

Achieving the objectives of rolling out genomic research programs in sub-Saharan Africa depends on how prepared indigenous biomedical researchers are for this type of research. We explored the level of preparedness of biomedical researchers in a sub-Saharan African country using in-depth interviews to obtain data on their understanding of genomics and genomic research and assess their awareness of the scope of the country's code of health research ethics. Thirty biomedical researchers were interviewed. Only eight were familiar with concepts of genomics, a form of "genomic health literacy." The majority were not aware of the country's code of research ethics. This study showed that generally biomedical researchers were not genomic health literate, unaware of the code and its limitations as a source of ethical guidance for the conduct of genomic research. These findings underscore the need for educational training in genomics and creating awareness of ethical oversight for genomic research in sub-Saharan Africa.

EMG indications and findings in a sub-Saharan African neurorehabilitation center.

OBJECTIVE: This study aims to assess the frequency and indication for electrodiagnostic referrals as well as to summarize the findings from the procedure at a neurorehabilitation center in Ibadan, Nigeria. METHODS: This is a retrospective cross-sectional study. Data from referrals to Blossom Medical Centre/World Federation for Neurorehabilitation (BMC/WFNR) center, Ibadan, Nigeria, from April 2014 to December 2016 were collated and analyzed. RESULTS: Sixty referrals were received during the period of evaluation. Neurologists referred most of the patients (47; 71.7%). Disorders of the peripheral nerves were the most frequent reasons for electromyography (EMG), and they were the most common electrodiagnosis with better classified into axonal and demyelinating types. The overall congruence between the suspected diagnosis and final diagnosis was 58.3%. Requests by neurologists were significantly more appropriate than those by other specialists (p value = 0.02). CONCLUSION: Polyneuropathy, entrapment neuropathy, and disorders of the motor nerve root and plexus were the most common reasons for electrodiagnostic requests, and the majority of the referrals were from neurologists. SIGNIFICANCE: EMG has changed the approach towards the diagnosis and management of neuromuscular disorders in Nigeria. It is hoped that with more neurophysiology education in this environment, neurophysiological practice will become widely available.

Knowledge of electromyography (EMG) among Sub-saharan African patients - a pilot survey

Background: Electromyography (EMG) is one of the common diagnostic procedure in neurology but still scarce in sub-Saharan Africa. Objective: This cross-sectional study evaluated the knowledge of EMG among patients undergoing this procedure, considering the type, quality and reliability of the information they have. Methodology: Consecutive patients who underwent EMG for the first time between 2014 and 2016, at the WFNR/Blossom Medical Centre Ibadan, Nigeria were interviewed prior to their test. Data on patient's demography, type of referring physicians were collated. Knowledge of EMG was also assessed. A patient was considered "informed" if she/he knew, at least, that the EMG is a test that uses an electric current or a needle, that it may be painful or cause discomfort, and that it is used to study the function of muscles and nerves. Descriptive and inferential statistics were performed to know the determinants of EMG knowledge. Result: 55 patients. 32 males and 23 females (mean ages 48.69± 18.32 and 43.30±14.88 respectively) were interviewed. Twenty-three (41.8%) patients were adjudged informed about the nature of EMG while 32 (58.2%) were uninformed about the procedure. Twenty one (38.2%) were informed about the procedure by their doctors while 4 (7.3%) got information from friends and relatives and 4 (7.3%) from the internet. Level of education was associated with being informed (p=0.039) Multivariate logistic regression analysis revealed no significant predictor or EMG knowledge. Conclusion: Knowledge of EMG is poor and could be improved upon. More patient education needs to be done to prepare the patients, and allay their fears about the procedure

The clinical syndrome of dystonia with anarthria/aphonia.

OBJECTIVES: In dystonia the formulation of a clinical syndrome is paramount to refine the list of etiologies. We here describe the rare association of dystonia with anarthria/aphonia, by examining a large cohort of patients, to provide a narrow field of underlying conditions and a practical algorithmic approach to reach diagnosis. METHODS: We retrospectively reviewed cases, which were evaluated between 2005 and 2014, to identify those with dystonia combined with marked anarthria and/or aphonia. We reviewed demographic information, clinical characteristics, as well as clinico-genetic investigations. We evaluated video material where available. RESULTS: From 860 cases with dystonia as the predominant motor feature, we identified 32 cases (3.7%) with anarthria/aphonia. Age at neurological symptom onset was variable, but the majority of cases (n = 20) developed symptoms within their first eight years of life. A conclusive diagnosis was reached in 27 cases. Monoamine neurotransmitter disorders, neurodegeneration with brain iron accumulation syndromes, hypomyelination with atrophy of the basal ganglia and cerebellum, and syndromes with inborn errors of metabolism were the most common diagnoses. Brain MRI was crucial for reaching a diagnosis by examining the structural integrity of the basal ganglia, the cerebral cortex, brain myelination and whether there was abnormal metal deposition. Pathophysiological mechanisms underlying anarthria/aphonia included dystonia, corticobulbar involvement, apraxia and abnormalities of brain development. CONCLUSIONS: The spectrum of conditions that may present with the syndrome of dystonia with anarthria/aphonia is broad. Various causes may account for the profound speech disturbance. A practical brain MRI-based algorithm is provided to aid the diagnostic procedure.

Task-shifting training improves stroke knowledge among Nigerian non-neurologist health workers.

BACKGROUND: The increasing stroke burden in sub-Saharan Africa far outstrips the availability of skilled human resource to provide timely and efficient acute, rehabilitative and preventive services. The objective of this study was to examine the impact of a short-term task-shifting stroke training program on the stroke knowledge of a cohort of Nigerian non-neurologist health workers (NNHWs). METHODS: Utilizing a quasi-experimental design, NNHWs drawn from 53 local government areas of Ogun and Oyo states participated in an intensive, multicomponent one-day stroke workshop. Stroke knowledge was evaluated before and after the training using a self-administered questionnaire. RESULTS: Out of a total of 210 NNHWs who participated in the session, 116 (55.2%) completed the pre-workshop questionnaire survey of stroke knowledge while 191 (91.0%) completed the post-workshop questionnaire survey. There were no statistically significant differences in the distribution of the age, gender and professional categories of the two groups. The participants' knowledge was significantly increased at the end of the training about stroke risk factors (p<0.001), stroke symptoms (p<0.001) and how stroke develops (p=0.009). The proportion of respondents who understood the FAST mnemonic increased from 10.3% before the training to 90.6% at the end of the training (p<0.001). The professional category of participants was associated with knowledge gain about swallowing test and thrombolysis. CONCLUSION: Our data support the effectiveness of stroke-specific task-shifting training for non-neurologist health workers in a low resource setting. Interim studies with intermediate outcomes are needed to show that improved knowledge results in better care despite resource limitation. Randomized controlled trials will be useful to confirm findings and translate knowledge improvement into practical intervention.