APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

BACKGROUND: Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. OBJECTIVE: To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. METHODS: We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. RESULTS: Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P < 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P = 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P = 0.000). CONCLUSION: The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.

Negative screening for 12 rare LRRK2 pathogenic variants in a cohort of Nigerians with Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). More than 300 rare LRRK2 variants have been described, with approximately 17 having confirmed or probable pathogenic role in PD. The distribution differs across ethnic groups, but no PD-related LRRK2 pathogenic variant has been described in persons of Black African ancestry within or outside Africa. We previously reported the absence of LRRK2 p.Gly2019Ser mutation in 126 PD and 55 controls from Nigeria. Using Kompetitive Allele Specific Polymerase Chain Reaction, we screened a new cohort of 92 Nigerians with PD and 210 ethnically matched controls for 12 rare LRRK2 variants shown to be pathogenic in other ethnic populations, including p.Gly2019Ser, p.Arg1441His, p.Gly2385Arg, p.Ala419Val, p.Arg1628Pro, p.Pro755Leu, p.Ile2020Thr, and Tyr1699Cys. All were absent in PD and controls, endorsing our previous findings and confirming that rare LRRK2 pathogenic variants reported in Caucasians, Asians, and persons of mixed ancestry are absent in West Africans. Future studies applying next generation sequencing are necessary to explore novel LRRK2 variants indigenous to Black Africans.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

A Nationwide Survey of Parkinson's Disease Medicines Availability and Affordability in Nigeria.

BACKGROUND AND OBJECTIVES: Limited access to medicines can impact negatively on outcomes in people with Parkinson's disease (PD). The study objectives were to determine the availability and assess the affordability of antiparkinsonian medications in pharmacies across Nigeria. METHODS: This was a cross-sectional nationwide study utilizing the World Health Organization/Health Action Initiative methodology. Strategically selected private- and public-sector pharmacies in the six geopolitical zones of Nigeria were surveyed for availability of medicines for management of early and advanced PD. The nine categories were: levodopa/peripheral decarboxylase inhibitors, dopamine receptor agonists, monoamine oxidase type B inhibitors, anticholinergics, catechol-o-methyl transferase inhibitors, atypical antipsychotics, antidepressants, antidementia drugs, and miscellaneous (e.g., drugs for orthostatism, urinary incontinence, and sleep disturbance). Unaffordability was defined as paying more than 1 days' wages (>N600 or > US$1.67) for a standard 30-day supply. RESULTS: One hundred twenty-three pharmacies were surveyed (62 private [50.4%] and 61 public sector [49.6%]; range of 15-25 pharmacies in each geopolitical zone). Private exceeded public-sector availability across all nine categories of PD medicines (P < 0.05). The most available medicines were dopamine receptor agonists (68.3%; predominantly ergot-derived bromocriptine), anticholinergics (56.1%; mainly trihexyphenidyl), and l-dopa formulations (48%; mainly 250/25 l-dopa/carbidopa). Only two medications (trihexyphenidyl tablets and biperiden injection) were affordable. The average number of day's minimum wages for a 30-day supply of PD medicines was 41.3 days (range, 1-371). CONCLUSIONS: PD medicines access is limited in Nigeria. Strategies, including engagement of stakeholders to consider interventions to improve and prioritize PD medicines access, are urgently warranted.

Glucose and lipid assessment in patients with acute stroke.

BACKGROUND: Stroke is a major health issue in Nigeria and it is also a common cause of emergency admissions. Stroke often results in increased morbidity, mortality and reduced quality of life in people thus affected. The risk factors for stroke include metabolic abnormalities such as dyslipidaemia and diabetes mellitus (DM). The stress of an acute stroke may present with hyperglycaemia and in persons without a prior history of DM, may be a pointer to stress hyperglycaemia or undiagnosed DM. METHODOLOGY: This was a cross sectional study carried out over a period of one year in a teaching hospital in Lagos, Nigeria. Patients with acute stroke admitted to the hospital within three days of the episode of stroke and who met other inclusion criteria for the Study were consecutively recruited. Clinically relevant data was documented and biochemical assessments were carried out within three days of hospitalization. Tests for lipid profile, glycosylated haemoglobin(HbA1c), and blood glucose at presentation were carried out. The presence of past history of DM, undiagnosed DM, stress hyperglycaemia and abnormal lipid profile were noted. Students t test and Chi square were the statistical tests employed. RESULTS: A total of 137 persons with stroke were recruited of which 107 (76%) met the defining criteria for ischaemic stroke. The mean age and age range of the Study subjects were 62.2 (11.7) and 26-89 years respectively. The Study subjects were classified according to their glycaemic status into the following categories viz; stress hyperglycaemia, euglycaemia, DM and previously undiagnosed DM. Stress hyperglycaemia occurred commonly in the fifth decade of life and its incidence was comparable between those with cerebral and haemorrhagic stroke. The commonly occurring lipid abnormalities were elevated LDL-C and low HDL. CONCLUSIONS: The detection of abnormal metabolic milieu is a window of opportunity for aggressive management in persons with stroke as this will improve outcome. Routine screening for hyperglycaemia in persons with stroke using glycosylated haemoglobin tests and blood glucose may uncover previously undiagnosed DM.

Serum ferritin levels in adults with sickle cell disease in Lagos, Nigeria.

BACKGROUND: Serum ferritin is considered to be one of the most important tools in the measurement of iron balance in steady-state sickle cell disease. Increased gastrointestinal absorption of iron has been reported in sickle cell disease because of the associated chronic hemolysis, and it is also thought that repeated red cell transfusion consequent to chronic hemolysis and anemia causes excessive iron levels. The aim of this study was to determine overall and gender-specific mean ferritin levels in patients with steady-state sickle cell disease in order to establish the prevalence of iron deficiency and overload. METHODS: This was a cross-sectional study in homozygous patients with sickle cell disease attending the sickle cell clinic at Lagos State University Teaching Hospital, Ikeja. A 5 mL blood sample was collected in plain bottles from consenting participants during steady-state periods. The serum was separated and analyzed for ferritin by enzyme-linked immunosorbent assay. Another 5 mL sample was collected for a full blood count, done on the same day of collection, to determine red blood cell indices, ie, mean cell volume, mean cell hemoglobin concentration, and mean corpuscular hemoglobin concentration. The Pearson Chi-square test was used for statistical analysis. The differences were considered to be statistically significant when P was <0.05. RESULTS: In total, 103 patients were recruited for this study and comprised 58 women (56.40%) and 45 men (43.70%). The overall mean ferritin concentration was 93.72 ± 92.24 ng/mL. The mean ferritin concentration in the women was 92.00 ± 88.07 ng/mL and in men was 96.41 ± 99.80 ng/mL. Only eight (7.76%) of the 103 patients had a serum ferritin level < 15 ng/mL, while two subjects (1.94%) had a serum a ferritin level > 300 ng/mL. Ninety-three subjects (90.29%) had serum ferritin within the normal reference range of 15-300 ng/mL. CONCLUSION: In this study, 90% of subjects with sickle cell disease had normal iron stores; serum ferritin was higher in men than in women, and iron deficiency was more common than overload in the disease.

Improving case fatality rate of adult tetanus in urban Nigeria: focus on better facilities of care.

Tetanus is a life threatening preventable infection with a high mortality. Our aim was to determine the current case fatality rate at our centre in a retrospective case review of patients aged > 10 years who had been hospitalized with tetanus between August 2006 and July 2011. We show the intrahospital case fatality rate. Data are based on 176 cases for which we had sufficient information. There was a preponderance of males (3.09:1); 167 (95%) had generalized tetanus and nine (5%) had localized tetanus. The overall case fatality rate was 56.2% and was higher in males (64.4%) than females (27.9%; P = 0.0001). In a multivariate analysis, older age (P = 0.000), male gender (P = 0.005) and a longer duration of admission (P = 0.004) were significant determinants of outcome. The case fatality rate of tetanus has declined at our centre from 70% between January 2004 and March 2006 to 56.2% currently. Improved facilities are required in order to significantly reduce adverse outcome from tetanus.

Seroprevalence of hepatitis B e antigen (HBe antigen) and B core antibodies (IgG anti-HBcore and IgM anti-HBcore) among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria.

BACKGROUND: Hepatitis B virus (HBV) is a common cause of liver disease throughout the world. HBV is transmitted through blood and other body fluids, including semen and saliva. Chronic replication of HBV virons is characterized by persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and occasionally with anti-HBs. AIM: To determine the prevalence of HBeAg, IgG anti-HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters are reflective of transmissibility and active hepatitis B infection. A cross sectional study was carried out at the blood donor clinics of Lagos State University Teaching Hospital Ikeja and Lagos University Teaching Hospital Idiaraba. A total of 267 donors were recruited to determine HBe antigen, IgG and IgM anti-HBcore antibodies amongst hepatitis BsAg positive donors. Five milliliters of blood was collected from those who tested positive to HBsAg screen during donation. The sera were subjected to enzyme linked immunosorbent assay (ELISA). Pearson chi-squared test was used for the analytical assessment. FINDINGS: A total number of 267 HBsAg positive blood donors were studied. A seroprevalence of 8.2% (22 of 267) HBeAg was obtained, 4 of 267 (1.5%) were indeterminate while 241 (90.3%) tested negative. Only 27 out of 267 donors (10.1%) tested positive to IgM anti-HBcore, 234(87.6%) tested negative, while 6(2.2%) were indeterminate. A higher percentage of 60.7% (162 of 267) tested positive to IgG anti-HBcore, while 39.3% (105 of 267) tested negative. CONCLUSION: There is a low seroprevalence rate of HBeAg-positive chronic hepatitis and relatively high IgG anti-HBcore and IgM anti-HBcore rates in South West Nigeria.

Clinical profile of parkinsonism and Parkinson's disease in Lagos, Southwestern Nigeria.

BACKGROUND: Current data on the pattern of parkinsonism and Parkinson's disease in Nigerians are sparse.This database was designed to document the clinical profile of PD in Nigerians, and compare this to prior observations. METHODS: A database of patients presenting to the Neurology out-patients clinic of the Lagos University Teaching Hospital was established in October 1996. Demographic and clinical data at presentation (disease stage using Hoehn and Yahr scale; 'off' state severity on the Unified Parkinson's disease Rating Scale) were documented for patients diagnosed with parkinsonism between October 1996 and December 2006. Cases were classified as Parkinson's disease or secondary parkinsonism (in the presence of criteria suggestive of a secondary aetiology). RESULTS: The hospital frequency of parkinsonism (over a 2-year period, and relative to other neurologic disorders) was 1.47% (i.e. 20/1360). Of the 124 patients with parkinsonism, 98 (79.0%) had PD, while 26 (21.0%) had secondary parkinsonism. Mean age (SD) at onset of PD (61.5 (10.0) years) was slightly higher than for secondary parkinsonism (57.5 (14.0) years) (P = 0.10). There was a male preponderance in PD (3.3 to 1) and secondary parkinsonism (2.7 to 1), while a positive family history of parkinsonism was present in only 1.02% (1/98) of PD. There was a modestly significant difference in age at onset (SD) of PD in men (60.3 (10.4)) compared to women (65.2 (7.9)) (T = 2.08; P = 0.04). The frequency of young onset PD (< or = 50 years) was 16.3% (16/98). The mean time interval from onset of motor symptoms to diagnosis of PD was 24.6 +/- 26.1 months with majority presenting at a median 12 months from onset. On the H&Y scale, severity of PD at presentation was a median 2.0 (range 1 to 4). PD disease subtype was tremor-dominant in 31 (31.6%), mixed 54 (55.1%) and akinetic-rigid 14 (14.3%). Hypertension was present as a co-morbidity in 20 (20.4%), and diabetes in 6 (6.12%). CONCLUSIONS: The clinical profile of PD in Nigerians is similar to that in other populations, but is characterized by delayed presentation as has been reported in other developing countries. Young-onset disease occurs but may be less commonly encountered, and frequency of a positive family history is lower than in western populations.

The clinical spectrum of neurological manifestations in HIV/AIDS patients on HAART at the Lagos University Teaching Hospital, Lagos, Nigeria.

BACKGROUND: The human immunodeficiency virus (HIV) is primarily neurotrophic and lymphotrophic. Diverse neurologic sequealae have been documented with variations based on disease severity, but geographic variation may determine the distribution of these neurological complications. OBJECTIVE: This study was designed to evaluate the current status of neurologic manifestations of HIV/AIDS as seen at our tertiary referral centre in Lagos, Nigeria. METHODS: Consecutively presenting persons with HIV/ AIDS receiving HAART, who were seen between August 2004 and March 2006 at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, were recruited into the study. RESULTS: Two hundred and fifty consecutively presenting HIV sero-positive patients were seen. There were 102 males (40.8%) and 148 females (59.2%) with a mean age of 37.4 years. 86 (34.4%) had clinically evident neurological disease, including neurocognitive dysfunction in 65 (53%), distal sensory neuropathy in 41 (16.4%), meningitis in 16 (6.4%), myopathy in 13 (5.2%), myelopathy in 6 (2.4%) and cerebrovascular disease in 5 (2%). The mean CD4 count (cells/mm3) of patients with neurological disease, 201.1 +/- 124.8 was significantly lower than that of patients without neurological disease 253.5 +/-149.2 (P = 0.001). CONCLUSION: Clinically evident neurological disease occurs in about 1/3rd of patients with HIV/AIDS on HAART at our tertiary centre, and predominantly affects patients with more advanced disease stages evidenced by lower CD4 count.