Hypertension Trends and White Matter Brain Injury in the Offspring Framingham Heart Study Cohort.

BACKGROUND: Hypertension is the most potent stroke risk factor and is also related to cerebral small vessel disease. We studied the relation between mid-to-late-life hypertension trends and cerebral white matter injury in community-dwelling individuals from the FHS (Framingham Heart Study). METHODS: FHS Offspring cohort participants with available mid-life and late-life blood pressure measurements and brain magnetic resonance imaging were included. Multiple regression analyses were used to relate hypertension trends (normotension-normotension [reference], normotension-hypertension, and hypertension-hypertension) to white matter injury metrics on diffusion tensor imaging (free water, fractional anisotropy, and peak skeletonized mean diffusivity) and Fluid Attenuated Inversion Recovery (white matter hyperintensity volume) by different blood pressure cutoffs (130/80, 140/90, and 150/90 mm Hg). RESULTS: We included 1018 participants (mean age 47.3±7.4 years at mid-life and 73.2±7.3 at late-life). At the 140/90 mm Hg cutoff, the hypertension-hypertension trend was associated with higher free water (ß, 0.16 [95% CI, 0.03-0.30]; P=0.021) and peak skeletonized mean diffusivity (ß, 0.15 [95% CI, 0.01-0.29]; P=0.033). At a 130/80 mm Hg cutoff, the hypertension-hypertension trend had significantly higher free water (ß, 0.16 [95% CI, 0.01-0.30]; P=0.035); and the normotension-hypertension (ß, 0.24 [95% CI, 0.03-0.44]; P=0.027) and hypertension-hypertension (ß, 0.22 [95% CI, 0.04-0.41]; P=0.022) trends had significantly increased white matter hyperintensity volume. Exploratory stratified analysis showed effect modifications by APOE ɛ4 allele and age. CONCLUSIONS: Mid-to-late-life hypertension exposure is significantly associated with microstructural and to a lesser extent, visible white matter injury; the effects are observed at both conventional and lower blood pressure cutoffs and are associated with longer duration of hypertension.

Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study.

BACKGROUND: Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification. OBJECTIVE: To relate PVS burden according to brain topography and plasma NfL. METHODS: Framingham Heart Study (FHS) participants with brain MRI and NfL measurements were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) using validated methods and categorized based on counts. A mixed region variable representing high burden PVS in either BG or CSO was assessed. Multivariable linear regression analyses were used to relate PVS burden to log-transformed NfL levels in models adjusted for age, sex, FHS cohort, time between MRI and clinic exam, and image view (model 1), vascular risk factors (model 2), and white matter hyperintensity volume, covert brain infarcts, and cerebral microbleeds (model 3). RESULTS: Among 1,457 participants (68.1±8.5 years, 45% males), NfL levels increased with higher PVS burden. Multivariable analysis showed an association of high PVS burden strictly in BG with NfL (ß= 0.117, 95% CI 0.014-0.221; p = 0.027), but attenuated in model 3. The associations were mainly in participants≥65 years (ß= 0.122, 95% CI 0.015-0.229, p = 0.026), women (ß= 0.156, 95% CI 0.024-0.288, p = 0.021), and APOE ɛ4 non-carriers (ß= 0.140, 95% CI 0.017-0.263, p = 0.026). CONCLUSIONS: The association of strictly BG high PVS burden with NfL suggests a role for PVS as markers of neuroaxonal injury, but our results are hypothesis generating and require further replication.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

Inflammatory biomarkers and MRI visible perivascular spaces: The Framingham Heart Study.

We studied the association between inflammatory biomarkers and magnetic resonance imaging (MRI) visible perivascular spaces (PVS) in Framingham Heart Study participants free of stroke and dementia. PVS in the basal ganglia (BG) and centrum semiovale (CSO) were rated with validated methods and categorized based on counts. A mixed score of high PVS burden in neither, one or both regions was also evaluated. We related biomarkers representing various inflammatory mechanisms to PVS burden using multivariable ordinal logistic regression analysis accounting for vascular risk factors and other MRI markers of cerebral small vessel disease. Among 3604 participants (mean age 58±13 years, 47% males), significant associations were observed for intercellular adhesion molecule1, fibrinogen, osteoprotegerin, and P-selectin in relation to BG PVS, P-selectin for CSO PVS, and tumor necrosis factor receptor 2, osteoprotegerin and cluster of differentiation 40 ligand for mixed topography PVS. Therefore, inflammation may have a role in the pathogenesis of cerebral small vessel disease and perivascular drainage dysfunction represented by PVS, with different and shared inflammatory biomarkers depending on PVS topography.

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.

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.

Pattern and determinants of self-reported enacted stigma among rural dwellers living with epilepsy attending a tertiary health facility in Enugu State Nigeria.

PURPOSE: Epilepsy related stigma is a barrier to recovery and has been linked to a broad range of psychosocial consequences and has the potential to influence the provision of care to people with epilepsy. Understanding the determinants of enacted stigma in epilepsy is relevant in the understanding of the burden of epilepsy in Nigeria. METHOD: Using a semi-structured questionnaire, a cross-sectional descriptive study was conducted among rural dwellers receiving treatment for epilepsy in a tertiary referral specialist hospital in Enugu, south east Nigeria. RESULTS: The participants consisted of 108 patients, 63% of whom were males. Most patients 99(91.7%) reported experiencing stigma in the past. The commonest forms of enacted stigma were being regarded as having 'spiritual attack' 88(81.5%) and restraining from interacting with others 49(45.4%). Most individuals who received nonorthodox treatment 55(55.6%) experienced stigma. Severely stigmatized individuals were more likely to be females. Age of onset of epilepsy, use of non-orthodox treatment, seizures occurrence in public places and the presence of physical injuries positively correlated with enacted stigma. CONCLUSIONS: The burden of epilepsy related enacted stigma is high among rural dwellers attending a tertiary medical outpatient clinic in Enugu, southeast Nigeria.

Prevalence of active convulsive epilepsy in an urban slum in Enugu South East Nigeria.

PURPOSE: To determine the prevalence of active convulsive epilepsy and treatment gap in two Urban slums in Enugu South East Nigeria. METHODS: A 3 phase cross-sectional descriptive study was done to survey individuals ≥ 15 years in 2 slums in Enugu, South East Nigeria. RESULTS: The prevalence of epilepsy was 6.0 (95% CI: 5.9-6.0) per 1000 (men 4.4/1000, 95% CI: 2.3-6.4, women 7.8/1000, 95% CI: 4.9-10.4), p=0.06. The peak age of active convulsive epilepsy was 40-44 years (11.2 per 1000) with two smaller peaks at 25-29 and ≥ 50 years. The age and sex adjusted prevalence using WHO standard population and 2006 Nigerian census population were 5.9 per 1000 (95% CI: 4.0-7.9) and 5.4 per 1000 (95% CI: 3.4-7.4). CONCLUSION: The prevalence of epilepsy is high in urban slums in Enugu. Nationwide studies should be done to find out the true prevalence in the country.

Headache prevalence and its characterization amongst hospital workers in Enugu, South East Nigeria.

BACKGROUND: Headaches are probably the commonest neurological complaint worldwide. Amongst workers it contributes significantly to loss of productive time and work efficiency. It is an important cause of disability and reduced quality of life. The prevalence and pattern amongst health workers in Africa has not been extensively studied. OBJECTIVE: This epidemiological sampling-based preliminary study examined the frequency and pattern of headache in a population of health workers of a tertiary hospital in Enugu, South East Nigeria. METHODS: Study participants, recruited by balloting, completed a self-administered questionnaire to screen for headache and its associations (defined as headache unrelated to fever and experienced within 6 months prior to the date the questionnaire was administered). Data analysis was by SPSS version 16. Ethical approval was obtained from the Hospital Ethical Review Committee. RESULTS: One hundred and thirty-three workers aged 18 - 70 years, were evaluated (males 53.4%, n=71 and females 46.6%, n=62). Headache was experienced by 88% of workers with primary headaches constituting more than 70% of cases. Females were more affected in both instances. Primary and secondary headaches occurred more in younger and older workers respectively and the association was significant (P <0.05). Headaches were not a significant cause of disability and loss of productivity. CONCLUSION: Headaches are very prevalent in hospital workers in Enugu, Nigeria. In older workers screening for underlying causes is indicated. Disability, work absenteeism and loss of productive time are minimal despite the high headache prevalence.

Knowledge, attitude and practice of epilepsy among community residents in Enugu, South East Nigeria.

PURPOSE: The understanding of the opinions of the Nigerian public about epilepsy and its treatment is relevant to the reduction of the large treatment gap that exists in management of the condition. The major aim of this study was to determine the knowledge and attitudes of urban dwellers to epilepsy and its treatment and to identify the gaps in knowledge that could pose as barriers in the treatment and care of epilepsy patients within the community. METHOD: This cross-sectional and descriptive study was carried out in one of the districts of Enugu metropolis, Nigeria. Data collection was by means of a semi-structured validated questionnaire. RESULTS: The mean score in knowledge was low, 48.1±18.8%; higher in females (50.6±18.6%, p=0.03 and those who had witnessed seizures in the past 49.7±18.8, p<0.01. On attitudes, 61.8% of the respondents accepted that it is right if sufferers married but most (93.2%) would not marry them and 87.2% would not allow them to have children or make a new acquaintance by working or playing with them (72.8%). There were no significant differences in the attitude scores of respondents with different levels of education. CONCLUSION: The level of knowledge of epilepsy in among urban dwellers in SE Nigeria is low and fraught with misconceptions and gaps. There were no significant differences in the attitude scores of respondents with different levels of education. There is a need for a multi-faceted educational interventions directed at improving the awareness and understanding of the condition by all segments of the society.

Frequency and risk factors for distal sensory polyneuropathy in HIV infection in a developing country.

Distal sensory polyneuropathy is a source of morbidity in HIV infection. This study aims to determine the frequency and effect of demographic and clinical variables on distal sensory polyneuropathy, among HIV-positive participants in south-east Nigeria. The study involved highly active antiretroviral therapy (HAART)-naive, patients on HAART and HIV-negative matched controls conducted at the University of Nigeria Teaching Hospital, Enugu south-east Nigeria. Distal sensory polyneuropathy was diagnosed with clinical evaluation and the use of Bio Thesiometer, 10 g monofilament and ankle reflex. There were 100 participants in each of the groups, comprising 109 (36.3%) men and 191 (63.7%) women, with median age of 35 years. About 42.5% (85/200) of the HIV-positive participants (37 drug naive and 48 on HAART) had distal sensory polyneuropathy. None in the control group had distal sensory polyneuropathy. Age (p = 0.02), height (p = 0.002), low haemoglobin (p = 0.03) and mean duration on HAART (p = 0.006) were significantly associated with distal sensory polyneuropathy, while gender (p = 0.497), body mass index (p = 0.657) and CD4 count (p = 0.482) did not affect distal sensory polyneuropathy. Low haemoglobin, height, and duration on HAART were independent risk factors for distal sensory polyneuropathy. Addressing correctable causes of anaemia, and alternatives to neurotoxic HAART may minimize the risk of distal sensory polyneuropathy.

Ischaemic stroke in hyperthyroidism without cardiac arrhythmia. A case report from south east Nigeria.

BACKGROUND: The relationship between hyperthyroidism and stroke is well established in the setting of atrial fibrillation. However there is limited literature for ischaemic stroke occuring in hyperthyroidism without cardiac arrhythmia. No such case had been described in South East Nigeria. METHOD: This report highlights a case of ischaemic lacunar infarction in an elderly Nigerian woman with reemergent thyrotoxicosis, without atrial fibrillation. RESULT: A 75- year old retired female teacher presented with a painless goiter of 3 years duration and right sided hemiplegia of 2 months duration. She had sub-total thyroidectomy 32 years ago for thyrotoxicosis with subsequent good outcome and had been managed for diabetes mellitus for 13 years with good glycaemic control. She was not a known hypertensive. She was thyrotoxic on examination with a large non-tender goiter. There was sinus tachycardia. She had a right sided facial nerve palsy and ipsilateral spastic hemiplegia. Sensations were spared. Results of investigations confirmed hyperthyroidism while brain CT scan was unremarkable except for cerebral atrophy. She had no other associated risk factor associated with hyperthyroidism. Within two weeks of admission she was stabilized on anti-thyroid and anti-diabetic medications, her motor functions significantly recovered and she was independent. She was discharged to be followed up at the out-patients' clinic. CONCLUSION: Ischaemic stroke may present in hyperthyroid patients without atrial fibrillation. This possibility needs to be entertained despite the absence of cardiac arrhythmia or other well established factors for cardioembolic stroke. There is a need for more studies on this relationship.

Frequency and pattern of headache among medical students at Enugu, South East Nigeria.

OBJECTIVE: To ascertain frequency and pattern of primary headaches among young Nigerians as represented by medical students in the University of Nigeria, Enugu Campus, South East Nigeria. METHODS: This was a cross-sectional descriptive interview-based study using structured headache questionnaire. Consent was obtained and the results interpreted following the guidelines of the International Headache Society. RESULTS: The one year Frequency of headache of any type was 88.3% (86.7% in males and 90.4% in females). The Frequency for migraine, tension-type headache and chronic daily headache was 18.1% (males 16.3%, females 20.5% with male: female ratio = 1:1.3), 36.8% and 17% respectively. CONCLUSION: There is a high Frequency of headache of several types--migraine, tension type headache and chronic daily headache--among medical students. Migraine was 1.3 times commoner in females than in males.