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.

High acceptability, convenience and reduced carbon emissions of tele-neurology outpatient services at a regional referral centre in Kenya.

Background: There is severe shortage of neurologists in sub-Saharan Africa. Tele-neurology consultations (TNC) can bridge this service gap, but there is very little published evidence on TNC in our setting, which we addressed through our study. Methods: We prospectively enrolled patients at our neurology outpatients from October 2020 to October 2021. We administered a post-TNC questionnaire which captured satisfaction/acceptability using Likert scales. A sub-group of participants who also did in-person consultations (IPC) were additionally administered post-IPC questionnaires. Statistical comparisons were made using the paired student t-test, and descriptive data expressed as median (inter-quartile range). Results: From 219 enrolled patients, 66.7% participants responded: 74.0% had both IPC and TNC; 63.0% were female; age was 40.9 (30.6-55.2) years; and 2.7% were from neighbouring countries. The commonest presentations were headache (30.8%), seizures (26.0%) and neurodegenerative disorders (15.1%). For TNC, >90% found it: (i) as comfortable as IPC (p = 0.35); (ii) didn't violate their privacy; (iii) saved time [3.0 (2.0-4.0) hours], travel [11.0 (7.2-21.1) km] and cost [$9.09 (4.55-18.18)]; and (iv) addressed their concerns satisfactorily such that they would use TNC again. Conversely, 15.1% didn't agree with TNC being as effective as IPC, and felt the neurologist did not satisfactorily identify all of their health problems (p = 0.03). In total, our TNC service saved our patients $6167, 1143 h, and 25,506 km of travel, translating to 3.5 t (equivalent to 21 newly-planted trees) of carbon dioxide emissions. Conclusions: Our study demonstrates that TNC is an acceptable, efficient, effective, and environmentally-sustainable care delivery model.

A Case Report of Concurrent Cryptococcal and Tuberculous Meningitis in an Immunosuppressed Renal Transplant Patient.

Infections after renal transplant are a common cause of morbidity and are commonly due to Cytomegalovirus (CMV), Cryptococcus, Mycobacterium tuberculosis, and Aspergillus. Concurrent infections with both cryptococcal and tuberculous aetiologies are rare within the central nervous system (CNS). We present a case of a 67-year-old male patient who presented with three weeks of headaches, confusion, unsteady gait, and seizures. He had type 2 diabetes mellitus and hypertension. He had a kidney transplant three years prior and was on three immunosuppressive agents. He was HIV-negative. He was evaluated and found to have cryptococcal meningitis and received appropriate treatment with liposomal amphotericin B, flucytosine, and serial lumbar punctures. He also had treatment for CMV viremia with valganciclovir. Three weeks later, after an initial good clinical response, he deteriorated with worsening confusion and persistent seizures. We re-evaluated him and found him to have brain imaging suggestive of tuberculosis. We started him on anti-tuberculous medication, and he improved significantly and was alert and seizure free at discharge home one month later. This case highlights that concurrent CNS infections with cryptococcus and tuberculosis do occur especially in patients who are severely immunosuppressed such as after a renal transplant. Failure to improve while on treatment for one CNS opportunistic infection should prompt one to investigate for other concurrent causes.

Clinical Characteristics of Peripheral Neuropathy in Kenyan Patients with HIV Infection Compared with Patients with Concurrent HIV Infection and Diabetes Mellitus.

INTRODUCTION: Persons living with human immunodeficiency virus (HIV) are living longer and at risk of non-communicable diseases, including diabetes mellitus (DM). Both HIV and DM place patients at risk of peripheral neuropathy (PN). Our aim was to demonstrate the prevalence and characteristics of PN in our population of patients with HIV infection compared with concomitant HIV and DM. METHODS: A prospective cross-sectional study was performed at the Aga Khan Hospital in Nairobi, Kenya. Data were collected on demographics and characteristics of DM and HIV. Symptoms and signs of PN were evaluated by Neuropathy Symptom Score, Neuropathy Disability Score, and 10 g monofilament testing. RESULTS: Two groups were recruited, each consisting of 68 patients: (1) HIV only, (2) HIV and DM. The median age of patients was 51 years (IQR 42.8-58.6) and 55% were male. Median duration for HIV was 10 years (IQR 5-12) with a median CD4 count of 524 cells/mm3 (IQR 369-731). Median duration for DM was 1 year with a median glycosylated hemoglobin of 6.7% (IQR 6.6-7.6). Sixty-nine percent of patients with HIV had suppressed viral loads, and 9 patients (6.6%) had a history neurotoxic antiretroviral therapy use. PN was detected in 11 (16%) HIV-only patients, and in 17 (25%) participants who had both HIV and DM (Fisher exact test chi-square = 0.4). Univariate analysis demonstrated older age, high body mass index, and long duration of HIV were associated with an OR of 1.07 (95% CI 1.02-1.11), 1.21 (95% CI 0.46-3.11), and 1.07 (95% CI 0.99-1.15) in the overall group, respectively. CONCLUSION: Our study demonstrates a higher but non-significant prevalence of PN in patients with both HIV and DM when compared to HIV alone. HIV disease control had no association with PN presence.

Prevalence of Epilepsy, Human Cysticercosis, and Porcine Cysticercosis in Western Kenya.

Cysticercosis is the leading cause of acquired epilepsy worldwide and has been shown to be highly prevalent in pig populations in western Kenya. We conducted a community-based door-to-door survey in a region of western Kenya with a high proportion of pig-keeping households. Persons with epilepsy (PWE) were determined using a screening questionnaire followed by a neurologist evaluation. Cysticercosis serum apDia antigen ELISAs and Western blot for LLGP and rT24h antigen were performed on all PWE and 2% of screen-negative patients. All PWE or people with positive apDia underwent contrast-enhanced brain computed tomography (CT). Of a sample of 810 village residents, 660 (81%) were present in the homestead, of whom 648 (98%) participated. Of these, 17 were confirmed to have lifetime epilepsy, an estimated crude prevalence of 2.6%. No humans with (N = 17) or without (N = 12) epilepsy had serological evidence of cysticercosis infection. Fourteen PWE and one individual with borderline positive apDia antigen ELISA underwent brain CT; none had radiographic findings consistent with neurocysticercosis. Nearly 30% of households kept pigs, with 69% always tethered in both wet and dry seasons. More than 8% (6/72) of pigs had palpable lingual cysts; these pigs all originated from homesteads with latrines, one-third of which were free-ranging at least some of the time. Epilepsy prevalence in our study was greater than the national prevalence, but we found no individuals with epilepsy attributable to cysticercosis. Additional studies are required to identify causes of epilepsy, human and porcine cysticercosis, the role of spatial clustering, and protective factors like host-pathogen immunity.

Takayasu arteritis: A rare cause of chronic headache.

Chronic headache can be a presenting manifestation of Takayasu arteritis, although patients usually have other characteristic features. A thorough clinical assessment remains key in the evaluation of chronic headache.

Safe Thrombolysis During Pregnancy for Recurrent Acute Ischaemic Stroke Due to Concomitant Isolated Left Ventricular Non-Compaction and Bilateral Foetal Posterior Communicating Arteries.

Isolated left ventricular non-compaction (ILVNC) is a rare congenital cardiomyopathy and is associated with arrhythmias, heart failure and thromboembolism including ischaemic stroke. Pregnancy is a relative contraindication to thrombolysis for acute ischaemic stroke, although case reports suggest the treatment can be given in selected cases. We report a case of recurrent cryptogenic strokes in a 36-year-old female who was thrombolysed with good outcome at 37 weeks' gestation and was eventually found to have ILVNC as the cause. She had a predilection to recurrent posterior circulatory strokes due to foetal posterior communicating arteries. To our knowledge this is the first case report of safe thrombolysis for acute ischaemic stroke in pregnancy caused by ILVNC.

Collet-Sicard syndrome due to concurrent extramedullary intracranial plasmacytoma and jugular venous sinus thrombosis in multiple myeloma.

In a patient with Collet-Sicard syndrome and multiple myeloma, both extramedullary plasmacytomas and internal jugular vein-sigmoid sinus thrombosis should be considered as they can coexist.

Multiple sclerosis in Kenya: Demographic and clinical characteristics of a registry cohort.

BACKGROUND: Multiple Sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. There is limited literature regarding the burden of MS in sub-Saharan Africa (SSA). OBJECTIVE: To describe the demographic and clinical characteristics of patients with MS (PwMS) presenting to a tertiary referral hospital in Nairobi. METHODS: We conducted a retrospective descriptive study for PwMS presenting to Aga Khan University Hospital, Nairobi from 2008-2018. RESULTS: 99 cases met the diagnostic criteria for MS with a male to female ratio of 1:4. Majority (68.7%) of PwMS were indigenous Africans with a mean age of onset of 30.7 years. Mean duration from symptom onset to first neuro-imaging was 5.04 years. Only 33% of patients had sensory symptoms at onset whereas 54.5% had vitamin D deficiency/insufficiency. Majority (79.5%) had relapsing remitting MS (RRMS) and 56.6% were initiated on disease modifying therapy (DMT). Only 21.2% of patients on DMT were non-compliant. Patients with RRMS were more likely to be initiated on DMT at our hospital (p < 0.001). CONCLUSION: Clinical characteristics of these patients largely resemble those of other SSA cohorts and African American patients. There was a delay between symptom onset and neuroimaging. There were also issues with DMT compliance.

Fatal Autoimmune Anti-NMDA-Receptor Encephalitis with Poor Prognostication Score in a Young Kenyan Female.

Auto-immune N-methyl-D-aspartate receptor encephalitis (NMDARE) is a relatively recently described cause of acute encephalopathy with very few reports from sub-Saharan Africa (SSA). We report a case of NMDARE in a young Kenyan female who was transferred to our facility with headaches, insomnia, behaviour changes and latterly pathognomonic orofacial dyskinesias. We comprehensively ruled out infectious and other inflammatory/auto-immune causes. She was diagnosed with NMDARE by positive antibody testing in serum and cerebrospinal fluid and changes on brain magnetic resonance imaging. She was immunosuppressed with high-dose steroids, intravenous immunoglobulins, plasma exchange and rituximab, and showed signs of neurological improvement clinically and radiologically. Unfortunately, she succumbed to septic shock from prolonged intensive care. This is the first report of NMDARE in an indigenous patient from the eastern SSA. The majority (>80%) of patients are either left with mild disability or make a full recovery after NMDARE, but some factors - which comprise the NMDARE One-Year Functional Status (NEOS) prognostication score - can adversely affect outcome, as was the case in our patient.

Cases of neuromyelitis optica spectrum disorder from the East Africa region, highlighting challenges in diagnostics and healthcare access.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an auto-immune disease of the central nervous system (CNS) associated with the IgG-antibody against aquaporin-4 (AQP4-IgG). There is little published epidemiology of NMOSD from sub-Saharan Africa (SSA). METHODS: We retrospectively collated NMOSD cases admitted to our tertiary regional neurology centre. RESULTS: We identified 11 cases (10 female, average age 30 years). 64% (7/11) were seropositive for AQP4-IgG, measured using indirect immunofluorescence. The remaining cases could either not afford tests, or had pathognomonic radiological features. 57% (4/7) of seropositive cases had concurrent/recent CNS infection. All patients were treated with high-dose intravenous methylprednisolone (IVMP), and 36% (4/11) also had plasma exchange. Only 55% (6/11) of the patients were seen by a neurologist at presentation: they had less relapses (1.3 vs 2.4), less diagnostic delay (2.3 vs 7.4 months), and were less disabled at the end of our review period. 10 cases were immunosuppressed long-term: 60% on mycophenolate, 30% azathioprine, and one on rituximab. CONCLUSION: Our study is the largest case series of NMOSD from the East Africa region. Patients faced challenges of access to appropriate and affordable testing, and timely availability of a neurologist at onset, which had impacts on their functional outcomes. The majority of the seropositive cases had recent/concurrent CNS infections, suggesting triggered auto-immunity.

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease: First Reported Case from East Africa.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare prion disease that causes rapidly progressive fatal neurodegeneration. The rarer Heidenhain variant of sCJD presents with visual symptoms and is rarely reported in the literature from sub-Saharan Africa. We report the case of a 57-year-old male with a three-week history of losing direction when driving home and visual hallucinations described as seeing rainbows. Magnetic resonance imaging (MRI) of the brain revealed unilateral parieto-occipital sulcal hyperintensities with restriction on diffusion-weighted imaging (DWI), and electroencephalography (EEG) showed right para-central slowing leading to an initial diagnosis of non-convulsive status epilepticus. He was treated with anti-epileptic medication but was re-admitted less than a month later with worsening spatial memory, aggression, ataxia, dysarthria, myoclonic jerks and a positive startle response, later developing generalised tonic-clonic seizures. Repeat MRI brain scan showed widespread posterior-predominant sulcal DWI restriction in a cortical ribboning pattern pathognomonic for sCJD. EEG showed diffuse slowing, and cerebrospinal fluid was analyzed for abnormal prion protein using real-time quaking-induced conversion but was inconclusive due to suboptimal sample collection. The patient fulfilled the diagnostic criteria for probable sCJD, Heidenhain variant; the family declined brain biopsy for definitive diagnosis. He was subsequently palliated at a local hospice where he died approximately three months after the onset of symptoms. Our case highlights the presence of a rare form of sCJD, and the diagnostic challenges faced in our resource-limited setting.

Determining the quality of life of children living with epilepsy in Kenya-A cross-sectional study using the CHEQOL-25 tool.

PURPOSE: Epilepsy is a chronic neurological disorder that is often diagnosed in childhood and may negatively impact physical, social and psychological abilities. Most tools measuring quality of life (QoL) rely on parent/caregiver feedback rather than the child's perspective. CHEQOL-25 is a QoL tool that documents both child and caregiver perspectives across five domains. The primary objective was to determine the QoL of children living with epilepsy (CWE) using the CHEQOL-25 tool in a Kenyan paediatric population. Other objectives were to describe the correlation between the caregivers' and children's' perspectives and describe factors affecting QoL. METHOD: We conducted a cross-sectional study across four sites in Nairobi. Quantitative data was collected using a self-administered CHEQOL-25 questionnaire. Caregivers and their children aged 7-15 years attending neurology clinics participated in the study. We used Kappa statistics to compare child and caregiver responses. RESULTS: A total of 354 participants were interviewed (177 children and 177 caregivers). A good QoL was reported by 60.5 % of children with a similar caregiver perception of 56.5 %. Caregivers with little education and male caregivers were associated with a poor QoL (p = 0.01); other socio-demographic factors had little impact on the measured QoL of CWE. Parent and child questionnaires correlated well in terms of response in terms of interpersonal (p = 0.001) and intrapersonal (p = 0.004) domains. CONCLUSION: This study demonstrated that a good quality of life was reported by the majority of CWE and their caregivers, although some factors such as a male caregiver gender and lower level of education were associated with poor QoL.

Phenytoin Toxicity Treatment with Haemodialysis in Epilepsy due to Glioblastoma Multiforme: Case Report and Review of the Literature.

Phenytoin is one of the most commonly used anticonvulsants in the developing world, but lack of monitoring and concurrent medications can easily lead to toxicity. We report the case of a 35-year-old female on phenytoin for symptomatic epilepsy due to previously treated glioblastoma multiforme, who presented with status epilepticus 1 week after being treated for a urinary tract infection. She was loaded with phenytoin and levetiracetam as per emergency protocol but had a persistently low level of consciousness, and her preloading phenytoin level result came back in the toxic range. She was managed conservatively, but after 4 days with no change she was dialyzed and her level of consciousness improved within 24 h, allowing for safe discharge home shortly after. Our case illustrates the option of haemodialysis in phenytoin-toxic patients who do not improve with conservative measures or who may need urgent reduction due to potentially fatal complications of phenytoin toxicity.

Treatment of the unknown patient: insights from acute stroke.

When an unidentified patient who cannot communicate presents with symptoms and signs suggesting an acute stroke, the decision to thrombolyse is a particular challenge. In a time-pressured environment, clinicians need clear thought processes for diagnosis and treatment. Ethical considerations, diagnosis, identity and previous history, contraindications, time of symptom onset (EDICT) can help decision-making in this situation.

Neurologists can identify diagnostic linguistic features during routine seizure clinic interactions: results of a one-day teaching intervention.

The diagnostic distinction between epilepsy and psychogenic nonepileptic seizures (PNES) can be challenging. Previous studies have demonstrated that experts in conversation analysis can identify linguistic and interactional features in transcripts and recordings of interviews with patients that reliably distinguish between epilepsy and PNES. In this study, ten senior neurology trainees took part in a one-day intervention workshop about linguistic and interactional differences in the conversation behavior of patients with epilepsy and those with PNES. Participants were familiarized with a 12-item questionnaire designed to capture their conversational observations immediately after talking to a patient with seizures. After the intervention, 55 initial outpatient visits of patients referred to seizure clinics were video and audio recorded. All medical diagnoses were confirmed two years after initial presentation on the basis of a chart review (including MRI and EEG findings) by a fully trained epilepsy expert. Postvisit questionnaires relating to patients confirmed to have epilepsy (n=20) or PNES (n=13) were analyzed. Doctors' mean responses to 6 of the 12 questions about linguistic and interactional observations differed significantly between the groups with epilepsy and PNES. Receiver operating curve analysis showed that a summation scale based on items demonstrating significant between-group differences correctly classified 81.8% of patients as having epilepsy or PNES. This study shows that a brief Conversation Analytic teaching intervention can enable neurologists to identify linguistic and interactional features supporting the differentiation of epilepsy and PNES as they take their patients' history in routine seizure clinic consultations, potentially improving diagnostic accuracy.

Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 (G93A) mouse model of amyotrophic lateral sclerosis.

Astrocytes are key players in the progression of amyotrophic lateral sclerosis (ALS). Previously, gene expression profiling of astrocytes from the pre-symptomatic stage of the SOD1(G93A) model of ALS has revealed reduced lactate metabolism and altered trophic support. Here, we have performed microarray analysis of symptomatic and late-stage disease astrocytes isolated by laser capture microdissection (LCM) from the lumbar spinal cord of the SOD1(G93A) mouse to complete the picture of astrocyte behavior throughout the disease course. Astrocytes at symptomatic and late-stage disease show a distinct up-regulation of transcripts defining a reactive phenotype, such as those involved in the lysosome and phagocytic pathways. Functional analysis of hexosaminidase B enzyme activity in the spinal cord and of astrocyte phagocytic ability has demonstrated a significant increase in lysosomal enzyme activity and phagocytic activity in SOD1(G93A) vs. littermate controls, validating the findings of the microarray study. In addition to the increased reactivity seen at both stages, astrocytes from late-stage disease showed decreased expression of many transcripts involved in cholesterol homeostasis. Staining for the master regulator of cholesterol synthesis, SREBP2, has revealed an increased localization to the cytoplasm of astrocytes and motor neurons in late-stage SOD1(G93A) spinal cord, indicating that down-regulation of transcripts may be due to an excess of cholesterol in the CNS during late-stage disease possibly due to phagocytosis of neuronal debris. Our data reveal that SOD1(G93A) astrocytes are characterized more by a loss of supportive function than a toxic phenotype during ALS disease progression and future studies should focus upon restorative therapies.