Stroke services in MENA: What is there and what is needed.

OBJECTIVES: Stroke represents a health care challenge to most parts of the world including the Middle East and North Africa (MENA) region. The MENA represents 6% of the world population with an age-standardized stroke rate of 87.7 (78.2-97.6) per 100,000 population. This number is subject to increase given that the cause of morbidity has recently shifted from infectious diseases to non-communicable diseases. Thus, in the coming years, treatment of stroke will pose a major burden on MENA countries which mostly lie in the low to middle income economies. Accordingly, we need to study the state of MENA stroke services in order to recognize and further inform policy makers about any gaps that need to be bridged in this domain. METHODS AND RESULTS: Stroke specialists representing 16 countries filled an online survey that included: screening for risk factors, acute management, diagnostics, medications, post-discharge services, and stroke registries. Results showed that 11 countries screen for risk factors, 16 have neuroimaging studies, 15 provide intravenous thrombolysis (IVT), 13 mechanical thrombectomy (MT) while medications for secondary prevention are available in all countries. However, stroke units are not equally available and even absent in 4 countries, and despite the availability of IVT yet, the rate of administration is still low in 6 countries (<5%), and ranges from 5-20% in 7 countries. Stroke registries and training still need to be implemented in most countries. CONCLUSION: Although imaging, revascularization therapies and medications for secondary prevention are available in most MENA countries, yet the rate of revascularization is low, so is the number of stroke units insufficient in some countries. Additionally, registries and structured training are still defective. Further field studies are required for more accurate determination of the status of stroke services in the MENA region.

PLA2G6-associated late-onset parkinsonism in a Sudanese family.

INTRODUCTION: The phospholipase A2 group VI gene (PLA2G6) encodes an enzyme that catalyzes the hydrolytic release of fatty acids from phospholipids. Four neurological disorders with infantile, juvenile, or early adult-onset are associated with PLA2G6 genetic alterations, namely infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia-parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). Few studies in Africa reported PLA2G6-associated disorders and none with parkinsonism of late adult onset. MATERIAL AND METHODS: The patients were clinically assessed following UK Brain Bank diagnostic criteria and International Parkinson and Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Brain MRI without contrast was performed. Genetic testing was done using a custom-made Twist panel, screening 34 known genes, 27 risk factors, and 8 candidate genes associated with parkinsonism. Filtered variants were PCR-amplified and validated using Sanger sequencing and also tested in additional family members to study their segregation. RESULT: Two siblings born to consanguineous parents developed parkinsonism at the age of 58 and 60 years, respectively. MRI showed an enlarged right hippocampus in patient 2, but no overt abnormalities indicative of INAD or iron deposits. We found two heterozygous variants in PLA2G6, an in-frame deletion NM_003560:c.2070_2072del (p.Val691del) and a missense variant NM_003560:c.956C>T (p.Thr319Met). Both variants were classified as pathogenic. CONCLUSION: This is the first case in which PLA2G6 is associated with late-onset parkinsonism. Functional analysis is needed to confirm the dual effect of both variants on the structure and function of iPLA2ß.

Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan.

PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homozygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co-segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic heterogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.

Methylation of alpha-synuclein in a Sudanese cohort.

BACKGROUND: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan. MATERIALS AND METHODS: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCAintron1 was performed as described earlier. RESULTS: Of the fourteen analyzed CpGs of SNCAintron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P-values improved, when sporadic cases were excluded from the analysis. CONCLUSION: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCAintron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering.

Practical needs and considerations for refugees and other forcibly displaced persons with neurological disorders: Recommendations using a modified Delphi approach.

Background: There are >70 million forcibly displaced people worldwide, including refugees, internally displaced persons, and asylum seekers. While the health needs of forcibly displaced people have been characterized in the literature, more still needs to be done globally to translate this knowledge into effective policies and actions, particularly in neurology. Methods: In 2020, a global network of published experts on neurological disease and refugees was convened. Nine physician experts from nine countries (2 low, 1 lower-middle income, 5 upper-middle, 1 high income) with experience treating displaced people originating from 18 countries participated in three survey and two discussion rounds in accordance with the Delphi method. Results: A consensus list of priority interventions for treating neurological conditions in displaced people was created, agnostic to cost considerations, with the ten highest ranking tests or treatments ranked as: computerized tomography scans, magnetic resonance imaging scans, levetiracetam, acetylsalicylic acid, carbamazepine, paracetamol, sodium valproate, basic blood tests, steroids and anti-tuberculous medication. The most important contextual considerations (100% consensus) were all economic and political, including the economic status of the displaced person's country of origin, the host country, and the stage in the asylum seeking process. The annual cost to purchase the ten priority neurological interventions for the entire displaced population was estimated to be 220 million USD for medications and 4.2 billion USD for imaging and tests. Conclusions: A need for neuroimaging and anti-seizure medications for forcibly displaced people was emphasized. These recommendations could guide future research and investment in neurological care for forcibly displaced people.

Rare variant in LAMA2 gene causing congenital muscular dystrophy in a Sudanese family. A case report.

Congenital muscular dystrophies (CMD) are a heterogeneous group of disorders caused by mutations in musculoskeletal proteins. The most common type of CMD in Europe is Merosin-deficient CMD caused by mutations in laminin-α2 protein. Very few studies reported pathogenic variants underlying these disorders especially from Africa. In this study we report a rare variant (p.Arg148Trp, rs752485547) in LAMA2 gene causing a mild form of Merosin-deficient CMD in a Sudanese family. The family consisted of two patients diagnosed clinically with congenital muscular dystrophy since childhood and five healthy siblings born to consanguineous parents. Whole exome sequencing was performed for the two patients and a healthy sibling. A rare missense variant (p.Arg148Trp, rs752485547) in LAMA2 gene was discovered and verified using Sanger sequencing. The segregation pattern was consistent with autosomal recessive inheritance. The pathogenicity of this variant was predicted using bioinformatics tools. More studies are needed to explore the whole spectrum of mutations in CMD in patients from Sudan and other parts of the world.

Neurology training in sub-Saharan Africa: A survey of people in training from 19 countries.

OBJECTIVE: To provide a comprehensive understanding of neurology training from the sub-Saharan African perspective. METHODS: A 40-question survey was distributed to attendees of the 7th annual sub-Saharan African neurology teaching course in Khartoum, Sudan (2015). Themes included the student body, faculty, curriculum, assessment and examinations, technology, and work hours and compensation. RESULTS: Of 19 responding countries, 10 had no formal neurology training programs; Burkina Faso, Cameroon, Republic of the Congo, and Mozambique had an adult neurology program; Ethiopia, Madagascar, Nigeria, Senegal, and South Africa had adult and pediatric neurology programs (training duration range = 3-6 years). There was a median of 2.5 full-time neurologists on the teaching faculty at the respondents' training institutions (neurologists on-faculty:in-country ratio = 0.48), with the lowest ratios in Sudan and Nigeria. Neurology was perceived to be a competitive specialty for entrance in 57% of countries, with 78% of respondents reporting a requisite entrance examination. Ninety-five percent had access to a personal smartphone, 62% used the Internet more than occasionally, and 60% had access to online neurology journals. The average number of weekly work hours was 51 (range = 40-75), and average monthly salary among those earning income was 1,191 USD (range = 285-3,560). Twenty percent of respondents reported paying for training. The most common barriers to neurology postgraduate education were few training programs and lack of training in neurodiagnostic tests. Among 17 reporting countries, there is an estimated average of 0.6 neurologists per million people. INTERPRETATION: Neurology training programs in sub-Saharan Africa are relatively limited in number and have several unmet needs including a small cadre of faculty and an opportunity to standardize curricula and financing of programs. Ann Neurol 2016;79:871-881.

Contribution of noncommunicable diseases to medical admissions of elderly adults in Africa: a prospective, cross-sectional study in Nigeria, Sudan, and Tanzania.

OBJECTIVES: To describe the nature of geriatric medical admissions to teaching hospitals in three countries in Africa (Nigeria, Sudan, Tanzania) and compare them with data from the United Kingdom. DESIGN: Cross-sectional cohort study. SETTING: Federal Medical Centre, Idi-Aba, Abeokuta, Nigeria; Soba University Hospital, Khartoum, Sudan; Kilimanjaro Christian Medical Centre, Moshi, Tanzania; and North Tyneside General Hospital, North Shields, United Kingdom. PARTICIPANTS: All people aged 60 and older urgently medically admitted from March 1 to August 31, 2012. MEASUREMENTS: Data were collected regarding age, sex, date of admission, length of stay, diagnoses, medication, date of discharge or death, and discharge destination. RESULTS: In Africa, noncommunicable diseases (NCDs) accounted for 81.0% (n=708) of admissions (n=874), and tuberculosis, malaria, and the human immunodeficiency virus and acquired immunodeficiency syndrome accounted for 4.6% (n=40). Cerebrovascular accident (n=224, 25.6%) was the most common reason for admission, followed by cardiac or circulatory dysfunction (n=150, 17.2%). Rates of hypertension were remarkably similar in the United Kingdom (45.8%) and Africa (40.2%). CONCLUSIONS: In the elderly population, the predicted increased burden of NCDs on health services in Africa appears to have occurred. Greater awareness and some reallocation of resources toward NCDs may be required if the burden of such diseases is to be reduced.

Acute mutism: a useful lesson.

Broca's aphasia may manifest as mutism in some patients. Mutism may be misinterpreted as part of a depressive illness in patients with a psychiatric history. We report on a patient presenting with acute mutism who had a history of amphetamine and cannabis abuse and was later found to have sustained an infarct of the dorsolateral frontal cortex. Recognition of this mode of presentation will aid early diagnosis and treatment.