MEDICAL AND NEUROLOGICAL COMPLICATIONS AMONG STROKE PATIENTS ADMITTED FOR INPATIENT CARE IN ADDIS ABABA, ETHIOPIA.

BACKGROUND AND PURPOSE: Medical and neurologic complications of acute stroke adversely impact patient outcome and in some cases can be preventable. There is scarcity of data in the African medical setup and none to date in our country to our knowledge. The current study aims to describe types and frequencies of neuro-medical complications occurring in hospitalized patients after an acute stroke and to identify risk factors for development of these complications and the role of these factors on mortality. METHODS: A total of 71 patients with acute stroke (excluding Sub-arachnoid Hemorrhage) who were admitted to three hospitals in Addis Ababa from June 2008 to March 2009 were included in the study. These patients were prospectively followed until their discharge or death to look for the nature and frequency of neuro-medical complications. Basic demographic data, stroke related medical information, pre-existing medical conditions, admission laboratory and imaging findings were recorded. All events were documented for each patient using pre-defined medical complication using a data collection format. Descriptive and analytic statistical tests were performed to measure associations between risk and outcome factors. RESULTS: Stroke-complications were detected in 71.8% (51/71) of the study participants and the most frequent complication was aspiration pneumonia which occurred in 33.8% (24/71). Miscellaneous complications such as sepsis, hypokalemia exposure keratitis were detected in 25% (17/71) of stroke patients. Complications were more common in patients with severe neurologic deficit as measured by Glasgow coma scale (GSC) and old age. GCS < 12 and age > 40 years were both significantly associated with developments of complications after stroke (p < 0.05). A total of 17 (23%) patients died during their in-patient stay. GCS < 12 was significantly associated with mortality related to stroke in the admitted patients (p = 0.0002) while there was no association between old age and mortality. CONCLUSIONS: Complications after stroke are common and are major factors contributing to mortality. Being aware of the types of common complications and associated risk factors helps the clinical team involved in the care of stroke patients to make preparations and plans for the best possible care and to take preventive measures that will save a lot of lives with best possible use of meager resources available such as educating the population to avoid oral feeding for patients with altered mental state and physicians to evaluate gag reflex bedside swallowing test and proper positioning of patients to avoid aspiration pneumonia. GSC measurement at admission is an important predictor of complications and death following stroke.

Chronic meningitis in immunocompromised adult Ethiopians visiting Tikur Anbessa Teaching Hospital and Ye'huleshet Clinic from 2003-2004.

BACKGROUND: Chronic meningitis is inflammation of the meninges where signs and symptoms develop and last for at least four weeks without alleviation. Little is known about the current etiology and incidence of the disease in adults living in developing countries. OBJECTIVE: The objective of this study was to elucidate the most common etiologies of chronic meningitis in adult Ethiopian patients and give an aid in the empiric therapy. METHODOLOGY: A total of 53 adult patients (median age 32 years) having chronic meningitis and who were admitted at Tikur Anbessa Teaching Hospital and Ye'huleshet Clinic, Addis Ababa, Ethiopia were recruited between 2003 and 2004. Of the 53 patients, bacteriological, molecular and immunological investigations were done for 52 of the study participants to detect Cryptococcus neoformans, Mycobacterium tuberculosis, Toxoplasma gondii, Brucella and Neisseria meningitides infections. RESULTS: Forty eight of the participants were HIV positive and 15% (8/52) of the CSF were positive with Cryptococcal latex antigen detection test; in addition, M. tuberculosis DNA was detected using PCR from CSF ofpatients infew of the patients. Multiple infections were observed in studyparticipants with < 0.1 to 1 CD4 to CD8 ratio. CONCLUSION: Chronic meningitis mostly occurred in HIV infected patients, where most of the infections were attributed to Cryptococcus neoformans whereas M. tuberculosis appeared secondary.

Factors Associated with EEG Slowing in Individuals with Parkinson's Disease.

BACKGROUND: A plethora of scientific studies has shown diffuse slowing on electroencephalograph (EEG) study is a frequent occurrence in Parkinson's disease (PD) patients, compared to the healthy controls. Little is known about EEG slowing and PD in the sub-Saharan Africa, especially in Ethiopia. The objective of this study was to assess factors associated with EEG slowing in individuals with Parkinson's disease. METHOD: A cross-sectional observational study was conducted in 40 PD patients at Yehuleshet Specialty Clinic, Addis Ababa, Ethiopia. Both descriptive and analytical statistics were used to analyze the data. RESULTS: Total of 40 patients with PD was included in the present survey. The median age was 66 (IQR: 52.5 - 72.5 years) and young onset PD accounted 20%. Males accounted for twothird of the participants. Diffuse EEG slowing was observed in 52.5% (n=21) of participants. Majority (85%) were on levodopa treatment. Hypovitaminosis D was observed in 93.1% of the study participants. White matter hyperintensity (WMH) and global brain atrophy were seen in 47.5% and 27.5% respectively. Even though statistically not significant, PD patients with EEG slowing, reported more forgetfulness and had WMH on their brain MRI, compared to those with normal EEG. Age was associated with diffuse EEG slowing when adjusted for forgetfulness and WMH (Adjusted OR 1.18 95% CI (1.01 - 1.37) p=0.03). CONCLUSION: The present study indicates high prevalence of diffuse EEG slowing in PD patients. Age was associated with diffuse EEG slowing. Higher proportion of patients with EEG slowing reported forgetfulness and hypovitaminosis D compared to those with normal EEG recordings.

Millard-Gubler Syndrome Associated with Cerebellar Ataxia in a Patient with Isolated Paramedian Pontine Infarction - A Rarely Observed Combination with a Benign Prognosis: A Case Report.

Isolated pontine infarction accounts for 7% of all ischemic strokes. Millard-Gubler syndrome is a clinical syndrome which occurs following lesions involving the ventral portion of the caudal pons, resulting in classic clinical features such as ipsilateral abducens and facial nerve palsy and contralateral hemiparesis. We report the case of a 55-year-old male patient having presented to the Yehuleshet Specialty Clinic 6 years back with sudden-onset dysarthria and appendicular ataxia of 10 days duration. He reported having right hemibody weakness and blurred vision, which have significantly improved since then. He had a history of smoking of 30 pack-years. However, he quit smoking 8 years ago. There was no history of prior stroke, transient ischemic attack, diabetes, hypertension, head trauma, or dyslipidemia. On examination, he had horizontal left gaze palsy with horizontal nystagmus suggesting left-sided 6th cranial nerve palsy. He had mild left-sided facial palsy causing dysarthric speech. Right upper limb dysmetria was observed during examination; otherwise, motor, sensory, fundus, and gait examination results were normal. He had low serum vitamin D. Brain magnetic resonance imaging examination showed a 25 × 10 mm segmental lesion in the left median pons involving the basis pontis and tegmentum section. The lesion had T2 and T1 abnormal prolongation with no diffusion restriction, suggesting a subacute pontine infarct. The patient was managed with aspirin 325 mg, atorvastatin 80 mg, physical therapy, and vitamin D supplementation, and advised on behavioral risk factors. Six years after his isolated pontine infarction, the patient is fully recovered from dysarthria, facial palsy, hemiparesis, right-sided appendicular ataxia, and horizontal nystagmus, and the follow-up brain MRI showed radiological evidence of chronic paramedian pontine perforator infarction. Millard-Gubler syndrome may present with cerebellar ataxia if the paramedian pontine infarction area slightly extends laterally, affecting the middle cerebellar peduncles. Isolated pontine infarction may have a good prognosis if diagnosed and managed early.

Patterns of lumbar myelographic findings in patients with LBP a 5 years retrospective study at Yehuleshet Higher Clinic, Addis Ababa, Ethiopia.

BACKGROUND: Low back pain (LBP) is usually defined as pain, muscle tension, or stiffness localized below the costal margin and above the inferior gluteal folds, with or without leg pain (sciatica). LBP is a common health problem and the imaging of which need carful clinical diagnostic triage. Most of us will experience at least one episode of LBP during our life. Despite its burden to the health facilities, more than 90% have no identifiable organic cause so their diagnosis is based on exclusion of other specific pathologies. OBJECTIVE: The study asses level of association of LBP and lumbar Myelographic findings in a higher clinic in Addis Ababa and provide baseline information of patterns of lumbar myelographic disease. PATIENTS AND METHODS: This is a retrospective record review of patients with LBP for whom lumbar myelography was done at Yehuleshet Higher Clinic. Data were collected from the clinics record, both hard and soft copy records were used a total of 1688 patients who had lumbar myelography study done for a complaint of LBP in the years from 2002-2008 are included in the study. RESULTS: Among the study subjects 895 (53%) were males and 793 (47%) were females. Mean age was 42.41 +/- 13.22. 1073 (63.6%) had abnormal myelographic findings and the rest 615 (36.4%) had normal lumbar myelography. The commonest abnormality is disc prolapse 36.7% with L4-L5 and L5-S1 being the commonest sites. CONCLUSION: Even if lumbar myelography showed abnormal findings in 63.6% a significant number of the studies (36.4%) were normal indicating lack of optimal clinical triage. Overall in countries like ours, where the recommended primary imaging modality, i.e., MRI is inaccessible and expensive, the value of myelography is unquestionable. RECOMMENDATION: But because of the invasive nature of the examination which also uses radiation, a diagnostic clinical triage should be taken first before subjecting patients to Myelographic procedures. Further studies to assess the positive predictive value of myelography with surgical confirmation are recommended.

Vitamin D Levels in Patients Presenting with Non-Specific Neuromuscular Pain and Fatigue in Ethiopia.

BACKGROUND: Vitamin D is an important micronutrient impacting multiple physiologic functions including calcium, phosphorus and bone metabolism. Various studies demonstrate low vitamin D levels in non-specific neuromuscular pain disorders and chronic-fatigue-syndromes. This observation was supported by significant improvement of these disorders following Vitamin D supplementation. Several studies demonstrate low serum vitamin D levels in healthy adult Ethiopians despite availability of abundant sunlight. METHOD: Retrospective medical records review of 62 patients presented to Yehuleshet Specialty Clinic between March 2014-August 2015 with non-specific neuromuscular pain and fatigue. Serum vitamin D levels were obtained at initial clinic visit. RESULTS: The mean (±SD) age was 51.5 ±15.5 years. Two-third (69.4%) of the participants were female. The majority (56.5%) presented with mixed symptoms, including generalized body ache, paresthesia, neck and back pain, while 45.2% reported fatigue. Fifteen (24.2%) participants were on antiepileptic drugs. All patients had initial serum vitamin D levels < 30 ng/ml, among these 62.9% demonstrated severe deficiency (< 12 ng/ml). Thirty (48.4%) participants reported symptomatic improvement after treatment with standard doses of vitamin D and calcium. Age > 50 years, being housewife, use of antiepileptic medications (AEDs), and higher serum parathyroid hormone are associated with severe vitamin D deficiency. CONCLUSION: This study demonstrated high prevalence of vitamin D deficiency among patients with non-specific neuromuscular pain and fatigue. Vitamin D replacement resulted in significant clinical improvement. It is important to screen vitamin D in individuals with limited sunlight exposure and patients on AEDs when presenting with neuromuscular pain and fatigue.

Symptomatic Giant Virchow-Robin Spaces: A Rare Cause of Spastic Quadriparesis in 43-Year-old Ethiopian Patient: A Case Report.

BACKGROUND: Virchow-Robin Spaces (VRS) are perivascular spaces that surround small arteries and arterioles. These normal anatomical structures are thought to be involved in the drainage of interstitial fluid and also to play an immunomodulatory role by hosting macrophages. Rarely, it becomes giant and symptomatic resulting in mass effect on adjacent neuronal structures and ventricular system causing different neurological disorders. CASE PRESENTATION: We report a 43-year-old, Ethiopian woman who presented with progressive weakness of all her extremity over the period of seven years. She had associated speech difficulty, visual blurring and pseudo-bulbar affect. Neurologic examination revealed spastic quadriparesis with increased deep tendon reflexes and up going plantar bilaterally. She had horizontal nystagmus, dysarthria and reduced bilateral visual acuity, otherwise normal cognition and cranial nerves examination. Brain MRI showed T1 hypointense, T2 hyperintense and non-enhancing multiple cystic lesions of different size, mainly in bilateral basal ganglia area with mass effect on adjacent internal capsule and lateral ventricles. Considering her clinical presentation and typical radiological features, diagnosis of symptomatic dilated Virchow-Robin spaces was made, and the patient was treated symptomatically. CONCLUSION: Commonly, dilation of Virchow-Robin spaces are not symptomatic, but giant Virchow-Robin spaces, as in our patient may result in spastic quadriparesis, causing great disability on the patient. Thus, we recommend considering symptomatic Virchow-Robin spaces as a potential differential diagnosis of progressive quadriparesis, as early neurosurgical intervention may reduce the neurological complications, such as spastic quadriparesis.

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 (P(ET)o(2)) was decreased from 100 mm Hg to 50 mm Hg with end-tidal carbon dioxide (P(ET)co(2)) clamped at the subject's resting level. P(ET)co(2) was then manipulated by voluntary hyper- and hypoventilation, with P(ET)o(2) clamped at 100 mm Hg (normoxia) and 50 mm Hg (hypoxia). RESULTS: During spontaneous breathing, P(ET)co(2) 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 P(ET)co(2) were greater in Ethiopians than Peruvians, particularly at high altitude. This, coupled with their high P(ET)co(2) levels, would lead to high cerebral blood flows, and may be advantageous for altitude living.

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 (P(ET)co2), 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 P(ET)co2 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.

Central nervous system toxoplasmosis in adult Ethiopians.

OBJECTIVES: Toxoplasmosis is identified as one of the major central nervous system (CNS) opportunistic infections in AIDS patients. Sero-epidemiological surveys done among Ethiopian patients indicated a very high prevalence rate. This study was conducted to describe the clinical course of the disease in Ethiopians with AIDS. PATIENTS AND METHODS: Three hundred and twenty three patients with AIDS and CNS Toxoplasmosis that were consecutively admitted and treated with Sulfadoxine Pyrimethamine (SP) at the Tikur Anbessa Specialized Referral Hospital were reviewed. The diagnosis CNS Toxoplasmosis was made based on clinical features or neuroradiologic findings and response to treatment. In over 80% of the cases the dose of Pyrimethamine used was 100 mgs for two days and then 25 mgs daily PO. RESULTS: The male to female ratio was one to one. The median age was 34 years (range 18 - 75). The most common presenting symptoms were headache 293 (91%), fever 269 (83%), and abnormal level of consciousness in 201 (62%) of the cases. Focal neuralgic deficits were seen in 203 (63%) of the cases. The diagnosis of CNS toxoplasmosis was based on clinical features and response to treatment in 186 (58%) of the cases and on CT scan findings and clinical response in 54 (17%) of the cases. Among the 248 (78%) of the cases that had responded favorably to SP, 53% had improvement on the 7th day, while the rest had improvement on the 14th day of treatment. Major treatment related adverse reactions, which required changing treatment, were seen in 68 (20%) of the cases. Among patients who survived the first episode of toxoplasmosis, the median follow up was for 29 days (range 15-1800). CONCLUSION: Toxoplasmosis had been the most AIDS defining event in the study group and clinical response to empiric treatment was essentially diagnostic. In our study group the outcome seen with SP as compared to the standard recommended treatment yielded comparable results. Tolerance to treatment was better and the adverse effects warranting change in treatment were fewer despite that only few patients received folinic acid supplements. We recommend a well-designed prospective study to establish the efficacy and optimal dose of SP in the treatment of CNS toxoplasmosis.

Ramsay Hunt syndrome.

Ramsay Hunt Syndrome was described in a 58 years old woman from Addis Ababa. The woman presented with vesicular eruptions in the right ear which was followed by weakness of the same side of face & otalgia. The objective of this case report is to address herpes zoster & its complications with the treatment modalities & an uncommon clinical entity, Ramsay hunt syndrome.

Characteristics and outcomes of stroke at Tikur Anbessa Teaching Hospital, Ethiopia.

Hospital studies have shown that stroke is an important cause of hospital morbidity and mortality in Ethiopia. The aim of this study is to determine the pattern, risk factors and determinants of mortality in patients with clinical diagnosis of stroke. It is a cross sectional study of all patients admitted with a clinical diagnosis of stroke between September 2000 and August 2001 to the Addis Ababa University Teaching Hospital. A total of 128 patients with mean age of 53.2 and M: F ratios of 1.5:1 were admitted The hospital burden of stroke appears to have increased significantly over the past three decades. Hemorrhagic stroke was the most common cause of stroke accounting for 57% of all patients and 59.2% among those who had CT scan. The number of patients with stroke increased linearly until age group 55-64, with peak incidence in the age group 55-64 years accounting for a third of all admissions. Hypertension was the most frequent risk factor identified followed by cardiac disease, 65.6% and 22.7% respectively. The majority of hypertensive patients were either on no form of treatment (28.9%) or erratic and irregular treatments (38.3%). Valvular heart disease (VHD) accounted for 40% of all heart diseases, and almost half of these also had atrial fibrillation of which none were on treatment. The overall mortality was 44.5%. Altered mental state and non focal neurologic deficits were the only independent predictors of mortality, odds ratio (95% CI), 5.7 (2.8-11.6) P = 0.001 and 5.5 (1.6-19.2) P=0.008 respectively. Treatment of hypertension and educating health-care professionals and the public on strategies of primary and secondary prevention remains the most important tool to prevent stroke in Ethiopia. Intensive care and inpatient facilities at referral hospitals have to be improved to curb the high mortality.

Guillain-Barré syndrome in Ethiopian patients.

This is a ten years retrospective study conducted to assess the clinical profile and outcome of Guillain-Barré Syndrome (GBS) in Ethiopian patients. The medical records of all patients admitted with the diagnosis of GBS to the Department of Internal Medicine, Tikur Anbessa University Hospital, Addis Ababa, Ethiopia during the period September 1992 to September 2001 were reviewed. During the ten-year review period ninety-five patients were admitted with the diagnosis of GBS, of which eighty-one met the National Institute of Neurological and Communicative Disorders and Stroke diagnostic criteria. The mean age (SD) of patients was 34.4 +/- 14.4 years. The male to female ratio was 1.25:1. History of antecedent event such as upper respiratory tract infection, diarrhea and vaccination was obtained in 47/81 (58.1%) of patients. The majority of the patients 62 (78.5%), presented with an ascending areflexic quadriparesis while 10 (12.7%) presented with a descending type of arefilexic quadriparesis, but in 6 (7.4%) of the patients the weakness was confined to the lower extremities (i.e. Paraparetic variant). Signs of autonomic involvement were seen in 25/81 (30.9%). Cytoalbzuminological dissociation in the cerebrospinal fluid was demonstrated in 62.3%. EMG was done in 47 patients The commonest electrophysiologic abnormality encountered was demyelinating picture in 26 (55.3%) followed by mixed and axonal in 12 (25.5%) and 9 (19.1%) respectively). Nineteen (70.3% of 27 GBS patients for whom serology for HIV was done were seropositive. The clinical findings were similar in both groups, except for a higher frequency of CSF pleocytosis, need for ventilatory support and mortality among HIV-positive patients. The overall mortality was 25.9%. This study highlights the importance of GBS as a cause of peripheral nerve disease in our setup. The higher mortality rate observed in this study appeared to be related mainly to the lack of adequate intensive carefacility and highlights the need to improve these services. Further-more, the finding of high frequency of seropositivity among GBS patients in this study underlines the need for further prospective research on the association and clinical course of GBS and HIV, particularly in Africa where HIV/AIDS has become an important public health problem.

How accurate is Siriraj stroke score among Ethiopians? A brief communication.

In hospitals where emergency neuroimaging is not available, the use of stroke scores has been proposed to distinguish ischemic from hemorrhagic stroke. The aim of this case study is to evaluate the accuracy of SSS among Ethiopian patients and was conducted in the Addis Ababa University teaching Hospital. Between September 1, 2000 and August 31, 2001. A total of 128 patients were admitted with a clinical diagnosis of stroke. 49(38.3%) had a CT scan result that was done within 24 to 72 hours of admission. CT revealed cerebral infarction in 20 (40.8%) patients and hemorrhagic stroke including subarachnoid hemorrhage in 29 (59.2%) patients. SSS was calculated and its sensitivity to diagnose hemorrhage and infarction was 77% and 61.5% respectively with an overall accuracy of 69.2% (Table 1) Its positive predictive values were 67% and 72.7% for hemorrhage and infarction respectively. The study has shown that bedside clinical examination does not always help in distinguishing between cerebral infarction and intracranial hemorrhage.

Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes.

BACKGROUND: Although 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. RESULTS: We 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. CONCLUSIONS: Our 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.

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.

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. METHODS: In this retrospective study, patients aged >or=13 year with SE were included. Medical records were reviewed and demographic and clinical data were collected. RESULTS: Records of 119 patients were analyzed; preexisting epilepsy was found in 38.7%. Primarily generalized and focal with secondarily generalized (FWSG) seizures were identified in 60.5% and 36%, respectively. Simple partial SE occurred in 3.4%. Central nervous system (CNS) infection was the most common cause of SE in the whole group as well as in those with new onset seizure. Antiepileptic drug withdrawal (AEDW) was the main cause in those with preexisting seizure. One or more complications were detected in 61%. Intravenous diazepam and oral phenytoin were given to 95% and 97.5%, respectively. Case fatality was 20.2%; poor outcome occurred in 24%. Predictors of mortality were FWSG type, acute symptomatic etiology, stroke, systemic infection, and HIV/AIDS and its CNS complications. Idiopathic and SE due to AEDW were associated with good prognosis. CONCLUSIONS: CNS infection was the most common cause of SE in the whole group and AEDW was the major cause in patients with preexisting epilepsy. Parenteral anticonvulsants, emergency measurement of serum AED level, and electroencephalography for urgent diagnosis and monitoring were unavailable. Mortality was related to underlying etiologies especially HIV/AIDS and its CNS complications.

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.

Autonomic regulation during orthostatic stress in highlanders: comparison with sea-level residents.

This report is a comparison of orthostatic tolerance and autonomic function in three groups of high-altitude dwellers: Andeans with and without chronic mountain sickness (CMS) and healthy Ethiopians. Results are compared with those from healthy sea-level residents. The aim was to determine whether different high-altitude populations adapted differently to the prevailing hypobaric hypoxia. Orthostatic tolerance was assessed using a test involving head-up tilt (HUT) and graded lower body suction. This was performed at the subjects' resident altitude. Blood pressure (Portapres) and R-R interval (ECG) were recorded during the test, and spectral and cross-spectral analyses of heart period and systolic blood pressure time series were performed using data obtained both while supine and during HUT. The transfer function gain in the low-frequency range (LF, approximately 0.1 Hz) at the point of maximal coherence was used as a measure of cardiac baroreflex sensitivity (BRS). As previously reported, Peruvians displayed an unusually good orthostatic tolerance, while Ethiopians showed an orthostatic tolerance comparable to that of healthy sea-level residents. There were no significant differences between groups in the supine values of the spectral analysis results. Head-up tilt induced the expected changes in Ethiopians (an increase in the LF components and a decrease in the respiratory components) but not in Andeans. Cross-spectral analysis showed abnormal results from all groups of high-altitude dwellers. These results indicate that Ethiopians, but not Peruvians, behave similarly to sea-level residents in terms of orthostatic tolerance and autonomic responses to orthostatic stress, as assessed from spectral analyses, and this indicates good adaptation to their environment. However, in all the high-altitude groups the results of cross-spectral analysis were atypical, suggesting some degree of impairment in baroreflex function.