The ethical and validity conundrum in epilepsy research in LMIC settings

In the last few decades, research in epilepsy has significantly improved understanding of risk factors and etiologies associated with epilepsy, promoting greater access to interventions and medications that have improved health-related outcomes for patients. However, these advances and benefits are not being felt evenly on a global scale due to significant inequalities in access to and utilization of research resources and expertise in Low-and Middle-Income Countries (LMICs). To promote effective research output, and advance evidence-based practices; the context, disease burden, and challenges that hinder good research need to be re-defined and addressed. This is key in facilitating implementation of coherent priorities and strategies in epilepsy research in LMICs; and in facilitating the conduct of scientifically and ethically valid research. This paper explores the capacity, ecosystem, and ethical issues that are at play and that need to be addressed to support better evidence generation and utilization in epilepsy care in LMICs

The ethical and validity conundrum in epilepsy research in LMIC settings

In the last few decades, research in epilepsy has significantly improved understanding of risk factors and etiologies associated with epilepsy, promoting greater access to interventions and medications that have improved health-related outcomes for patients. However, these advances and benefits are not being felt evenly on a global scale due to significant inequalities in access to and utilization of research resources and expertise in Low-and Middle-Income Countries (LMICs). To promote effective research output, and advance evidence-based practices; the context, disease burden, and challenges that hinder good research need to be re-defined and addressed. This is key in facilitating implementation of coherent priorities and strategies in epilepsy research in LMICs; and in facilitating the conduct of scientifically and ethically valid research. This paper explores the capacity, ecosystem, and ethical issues that are at play and that need to be addressed to support better evidence generation and utilization in epilepsy care in LMICs

Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis

OBJECTIVES: Recent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Secondary level health facility: Kilifi, Coast, Kenya. PARTICIPANTS: Children aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. EXCLUSION CRITERIA: delayed development, epilepsy and sickle cell disease. RESULTS: During the study period, 665 children (median age 32 (IQR 20-46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period. CONCLUSION: The decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies

The role for osmotic agents in children with acute encephalopathies: a systematic review

Background: Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy.Methods: We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death.Results: We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.Conclusion: HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation

The incidence, aetiology and outcome of acute seizures in children admitted to a rural Kenyan district hospital

<p>Abstract</p> <p>Background</p> <p>Acute seizures are a common cause of paediatric admissions to hospitals in resource poor countries and a risk factor for neurological and cognitive impairment and epilepsy. We determined the incidence, aetiological factors and the immediate outcome of seizures in a rural malaria endemic area in coastal Kenya.</p> <p>Methods</p> <p>We recruited all children with and without seizures, aged 0–13 years and admitted to Kilifi District hospital over 2 years from 1^stDecember 2004 to 30^thNovember 2006. Only incident admissions from a defined area were included. Patients with epilepsy were excluded. The population denominator, the number of children in the community on 30^thNovember 2005 (study midpoint), was modelled from a census data.</p> <p>Results</p> <p>Seizures were reported in 900/4,921(18.3%) incident admissions and at least 98 had status epilepticus. The incidence of acute seizures in children 0–13 years was 425 (95%CI 386, 466) per 100,000/year and was 879 (95%CI 795, 968) per 100,000/year in children <5 years. This incidence data may however be an underestimate of the true incidence in the community. Over 80% of the seizures were associated with infections. Neonatal infections (28/43 [65.1%]) and falciparum malaria (476/821 [58.0%]) were the main diseases associated with seizures in neonates and in children six months or older respectively. Falciparum malaria was also the main illness (56/98 [57.1%]) associated with status epilepticus. Other illnesses associated with seizures included pyogenic meningitis, respiratory tract infections and gastroenteritis. Twenty-eight children (3.1%) with seizures died and 11 surviving children (1.3%) had gross neurological deficits on discharge. Status epilepticus, focal seizures, coma, metabolic acidosis, bacteraemia, and pyogenic meningitis were independently associated with mortality; while status epilepticus, hypoxic ischaemic encephalopathy and pyogenic meningitis were independently associated with neurological deficits on discharge.</p> <p>Conclusion</p> <p>There is a high incidence of acute seizures in children living in this malaria endemic area of Kenya. The most important causes are diseases that are preventable with available public health programs.</p

Neonatal seizures in a rural Kenyan District Hospital: aetiology, Incidence and outcome of hospitalization

<p>Abstract</p> <p>Background</p> <p>Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya.</p> <p>Methods</p> <p>From 1^stJanuary 2003 to 31^stDecember 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data.</p> <p>Results</p> <p>Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, <it>P </it>= 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), <it>P </it>= 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge.</p> <p>Conclusion</p> <p>There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.</p

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area

Risk factors for seizure recurrence after initial withdrawal of anti-seizure medications in children with epilepsy at Aga Khan University Hospital, Nairobi, Kenya.

Objectives: We sought to determine risk factors associated with seizure recurrence following initial withdrawal of anti-seizure medications (ASM) among children with epilepsy. Methods: This was a retrospective observational study of children aged between 2 and 18 years with a diagnosis of epilepsy who underwent withdrawal of anti-seizure medication following remission of seizures. All eligible medical records between January 2011 and December 2019 were included. Demographic, clinical, imaging and electroencephalography data of all eligible patients were analyzed against seizure remission within 24 months after withdrawal of ASM, using appropriate parametric and non-parametric tests. Results: A total of 49 records of children who underwent withdrawal of ASM out of a total of 613 patients on follow up during the same period were included. The median age at ASM withdrawal was 70 months (IQR 52–112 months) and 14 (28.6%) were female. Thirteen patients (26.5%) had seizure recurrence within 24 months following withdrawal of ASM. Focal onset seizure type was associated with significant risk of seizure recurrence (OR 13.7; 95% CI 0.97, 193.54; P value = 0.011). Age at epilepsy diagnosis, abnormal EEG at initiation of treatment and at the time of de-escalation, abnormal MRI findings, first or second degree relative with epilepsy, history of developmental delay, seizure burden, use of 2 or more ASMs and duration of seizure-freedom before de-escalation of ASM were not associated with increased risk of relapse. Conclusion: Focal onset seizure type is associated with increased with risk of seizure recurrence in this cohort