Guta Zenebe

Neurologic services in the nations of Africa

Objective: To define the current state of neurologic health care services in the nations of Africa. Methods: A survey on neurologic services was prepared in English, French, and Portuguese and sent to representatives of 53 of 53 African nations. Representatives for each country were identified first through the Pan African Association of Neurologic Sciences, followed by the World Federation of Neurology and the World Health Organization (WHO). If these representatives did not return survey results, contacts were attempted through officials in the embassies in Washington, DC, or Addis Ababa, Ethiopia, or local ministries of health. Results: Surveys were received from representatives of 38 (71.7%) of the 53 African nations. Data from the WHO were added for 12 nations, resulting in information on 50 (94.3%) of the 53 nations. The nations were divided into four categories according to the number of neurologists per nation. Group A (>10 neurologists/country) included 11 nations, averaging 711,856 population per neurologist. Group B (5 to 10 neurologists/country) included five nations, averaging 1,612,039 population per neurologist. Group C (1 to 4 neurologists/country) included 23 nations, averaging 5,099,908 population per neurologist. Group D included 12 nations with a total population of 25,939,273 that reported having no neurologists. The level of training, presence of local training programs, ancillary equipment, and practice setting options decreased progressively from Group A to Group D. Conclusions: The population/neurologist ratio in all African nations far exceeds that of the United States and other developed nations. Neurologic services in the African nations range from no formal care at all to established neurologic care with residency training and ancillary equipment.

Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of “fitness” for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.

Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes

BackgroundAlthough it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited.ResultsWe report here the results of the first whole genome resequencing-based analysis identifying genes that likely modulate high altitude adaptation in native Ethiopians residing at 3,500 m above sea level on Bale Plateau or Chennek field in Ethiopia. Using cross-population tests of selection, we identify regions with a significant loss of diversity, indicative of a selective sweep. We focus on a 208 kbp gene-rich region on chromosome 19, which is significant in both of the Ethiopian subpopulations sampled. This region contains eight protein-coding genes and spans 135 SNPs. To elucidate its potential role in hypoxia tolerance, we experimentally tested whether individual genes from the region affect hypoxia tolerance in Drosophila. Three genes significantly impact survival rates in low oxygen: cic, an ortholog of human CIC, Hsl, an ortholog of human LIPE, and Paf-AHα, an ortholog of human PAFAH1B3.ConclusionsOur study reveals evolutionarily conserved genes that modulate hypoxia tolerance. In addition, we show that many of our results would likely be unattainable using data from exome sequencing or microarray studies. This highlights the importance of whole genome sequencing for investigating adaptation by natural selection.

Neurological evaluation of untreated human immunodeficiency virus infected adults in Ethiopia

Human immunodeficiency virus (HIV) has been implicated in neurological complications in developed countries. Developing countries have different viral clades and potentially different genetic and social risks for these complications. Baseline neurological performance measures associated with HIV infection have rarely been available from developing countries. The authors carried our a cross-sectional neurological evaluation of a cohort of community-dwelling treatment-naïve HIV-infected patients and similar control subjects from the same communities in Ethiopia. Blinded evaluation using standardized structured questionnaires and a neurological examination was performed by neurologists and treating physicians trained by an HIV neurology specialist. Quantitative performance measures for cognitive and motor function were employed. Data were analyzed with descriptive statistical methods, standard contingency table methods, and nonparametric methods. HIV-positive and control groups were similar by age, gender, and job site. Participants included 73 HIV-positive and 87 HIV-negative controls. Fingertapping speed in the dominant hand was more poorly performed in HIV positives than negatives (P = .01) and was significantly associated with HIV viral load levels (P = .03). Other quantitative neuropsychiatric tests including timed gait, grooved peg-board, task learning, and animal naming did not show significant differences between the two groups. The overall prevalence of central nervous system (CNS) and/or peripheral nervous system (PNS) disease did not significantly differ in the two populations. HIV patients had slowed fingertapping speed correlating with viral load. Other measures of CNS and/or peripheral nervous performance did not differ from controls. The unanticipated minor evidence of HIV-associated neurocognitive and peripheral nerve deficits in this untreated HIV-positive population invite further investigation.

Status epilepticus : Clinical presentation, cause, outcome, and predictors of death in 119 Ethiopian patients

Purpose: Status epilepticus (SE) is a common neurological emergency with high morbidity and mortality. There is no study that has been conducted among Ethiopian patients with SE. The purpose of this study was to analyze clinical presentation, causes, complications, outcomes, and predictors of mortality.

The burden of inpatient neurologic disease in two ethiopian hospitals

Objectives: To define the burden of inpatient neurologic disease seen in Ethiopian teaching hospitals. Methods: We reviewed records of all medical inpatients admitted over a 6-month period to two teaching hospitals, one with and one without neurologists. Results: Neurologic cases made up 18.0% and 24.7% of all medical admissions. The mortality rates were 21.8% and 34.7%. Noninfectious diseases were 36.7% and 31.7% of neurologic cases, but unknown etiologies made up 42.2% and 29.0% of all cases. Of total cases, only 42.9% and 24.1% had at least a high level of diagnostic certainty. Conclusions: Patients with neurologic disease make up a substantial minority of medical inpatients in Ethiopia. Noninfectious neurologic disease is at least as common as infectious neurologic disease. Reaching a well-defined final diagnosis occurs in only a minority of cases. Areas for improving the mortality rate include improving the barriers to diagnostic certainty and increasing treatment options for Ethiopian patients.

Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude

Background and Purpose— Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO. Methods— Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (PETco2), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor. Results— At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations. Ethiopians had higher PETco2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses. Conclusions— By our measure, high altitude–native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism.

Cerebrovascular Responses to Hypoxia and Hypocapnia in Ethiopian High Altitude Dwellers

Background and Purpose— Cerebrovascular responses to hypoxia and hypocapnia in Peruvian altitude dwellers are impaired. This could contribute to the high incidence of altitude-related illness in Andeans. Ethiopian high altitude dwellers may show a different pattern of adaptation to high altitude. We aimed to examine cerebral reactivity to hypoxia and hypocapnia in healthy Ethiopian high altitude dwellers. Responses were compared with our previous data from Peruvians. Methods— We studied 9 Ethiopian men at their permanent residence of 3622 m, and one day after descent to 794 m. We continuously recorded cerebral blood flow velocity (CBFV; transcranial Doppler). End-tidal oxygen (PETo2) was decreased from 100 mm Hg to 50 mm Hg with end-tidal carbon dioxide (PETco2) clamped at the subject’s resting level. PETco2 was then manipulated by voluntary hyper- and hypoventilation, with PETo2 clamped at 100 mm Hg (normoxia) and 50 mm Hg (hypoxia). Results— During spontaneous breathing, PETco2 increased after descent, from 38.2±1.0 mm Hg to 49.8±0.6 mm Hg (P<0.001). There was no significant response of CBFV to hypoxia at either high (−0.19±3.1%) or low (1.1±2.9%) altitudes. Cerebrovascular reactivity to normoxic hypocapnia at high and low altitudes was 3.92±0.5%.mm Hg−1 and 3.09±0.4%.mm Hg−1; reactivity to hypoxic hypocapnia was 4.83±0.7%.mm Hg−1 and 2.82±0.5%.mm Hg−1. Responses to hypoxic hypocapnia were significantly smaller at low altitude. Conclusions— The cerebral circulation of Ethiopian high altitude dwellers is insensitive to hypoxia, unlike Peruvian high altitude dwellers. Cerebrovascular responses to PETco2 were greater in Ethiopians than Peruvians, particularly at high altitude. This, coupled with their high PETco2 levels, would lead to high cerebral blood flows, and may be advantageous for altitude living.

Neurolathyrism: two Ethiopian case reports and review of the literature

Neurolathyrism is a toxic myelopathy caused by ingestion of the Lathyrus sativus grasspea. An irreversible acute to subacute spastic paraparesis or quadriparesis ensues. Despite public education, new cases of this preventable disease still occur. Two Ethiopian cases of neurolathyrism are reported to illustrate the disease, followed by a literature review. Two teenage male farmers from the same village developed irreversible spastic myelopathy following L. sativus ingestion. There was no sensory, sphincter or bulbar dysfunction. Likely causative factors identified were increased consumption of L. sativus prior to and following disease onset, heavy physical exertion and male gender, similar to those reported in the literature. Neurolathyrism is an entirely preventable neurotoxic myelopathy with permanent disability accrued. Treatment is symptomatic. Because of personal disability and subsequent socioeconomic effects, this disease warrants further public health measures to prevent occurrence. Education, avoidance of the grasspea and measures to reduce toxin burden are possible methods.

Frequency of movement disorders in an Ethiopian university practice

There is little information on the frequency of movement disorders seen by physicians in the continent of Africa. We performed a medical record review of all patients seen in a university‐based neurology clinic in Addis Ababa, Ethiopia, over 1 year to determine the frequency of movement disorders seen, disease characteristics, diagnostic evaluations, and treatment. A total of 15.1% of the neurological patients were seen for movement disorders. Of these, most were for parkinsonism (47.7%), followed by ataxia (16.5%), dystonia (8.3%), essential tremor (8.3%), chorea (7.3%), and miscellaneous (11.9%). Diagnostic evaluations were limited, but treatment was available, although expensive. In spite of the limitations, patients with movement disorders require and seek care in Ethiopia in proportions comparable to developed nations. This finding underlines the need for adequate training in movement disorders for physicians and neurologists in Africa.