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1.  Co-morbidity of epilepsy in Tanzanian children: a community-based case-control study 
Purpose
To define the prevalence and associations of co-morbidity and school attendance in older children with epilepsy (CWE) from a rural district of Tanzania by conducting a community-based case-control study.
Methods
Children aged 6 -14 years old with active epilepsy (at least two unprovoked seizures in the last five years) were identified in a cross-sectional survey in Tanzania. Co-morbidities were assessed and cases were compared with age-matched controls.
Results
Co-morbidity was very common amongst cases (95/112, 85%), with 62/112 (55%) having multiple co-morbidities. Co-morbidities consisted of cognitive impairment (72/112, 64%), behaviour disorder 68/112 (61%), motor difficulties 29/112 (26%), burns and other previous injuries (29/112, 26%). These complications were significantly more common in cases than in controls (Odds Ratio 14.8, 95%CI 7.6–28.6, p<0.001). Co-morbidity in CWE was associated with structural cause, abnormal electroencephalogram and early onset seizures. Cognitive impairment was very common in CWE (64%) and was not associated with Phenobarbital use but was associated with motor difficulties, early onset and recurrent seizures. Poor school attendance was found in 56/112 (50%) of CWE, but not in the controls: it was associated with the presence of multiple co-morbidities, especially with motor difficulties in CWE.
Conclusion
Children with epilepsy in a rural area of sub-Saharan Africa had a high level of co-morbidity. Cognitive impairment and poor school attendance were very common. These associated difficulties in CWE in the region need to be addressed to reduce the negative impact of epilepsy on these children.
doi:10.1016/j.seizure.2011.10.011
PMCID: PMC3672980  PMID: 22130004
epilepsy; Africa; children; co-morbidity; cognitive impairment; education
2.  Death within 8 years after childhood convulsive status epilepticus: a population-based study 
Brain  2011;134(10):2819-2827.
The risk of long-term mortality and its predictors following convulsive status epilepticus in childhood are uncertain. We report mortality within 8 years after an episode of convulsive status epilepticus, and investigate its predictors from a paediatric, prospective, population-based study from north London, UK. In the current study, we followed-up a cohort previously ascertained during a surveillance study of convulsive status epilepticus in childhood. After determining the survival status of the cohort members, we defined cause of death as that listed on their death certificates. We estimated a standardized mortality ratio to compare mortality in our cohort with that expected in the reference population. Multivariable Cox regression analysis was used to investigate any association between the clinical and demographic factors at the time of status epilepticus and subsequent risk of death. The overall case fatality was 11% (95% confidence interval 7.5–16.2%); seven children died within 30 days of their episode of convulsive status epilepticus and 16 during follow-up. The overall mortality in our cohort was 46 times greater than expected in the reference population, and was predominantly due to higher mortality in children who had pre-existing clinically significant neurological impairments when they had their acute episode of convulsive status epilepticus. Children without prior neurological impairment who survived their acute episode of convulsive status epilepticus were not at a significantly increased risk of death during follow-up. There were no deaths in children following prolonged febrile convulsions and idiopathic convulsive status epilepticus. A quarter of deaths during follow-up were associated with intractable seizures/convulsive status epilepticus, and the rest died as a complication of their underlying medical condition. On regression analysis, presence of clinically significant neurological impairments prior to convulsive status epilepticus was the only independent risk factor for mortality. In conclusion, there is a high risk of death within 8 years following childhood convulsive status epilepticus but most deaths are not seizure related. Presence of pre-existing clinically significant neurological impairments at the time of convulsive status epilepticus is the main risk factor for mortality within 8 years after the acute episode. The attributable role of convulsive status epilepticus on mortality remains uncertain, but appears less than is generally perceived.
doi:10.1093/brain/awr239
PMCID: PMC3187542  PMID: 21914715
status epilepticus; childhood; death; standardized mortality ratio; neurological impairment
3.  Co-morbidity of epilepsy in Tanzanian children: A community-based case–control study 
Seizure  2012;21(3):169-174.
Purpose
To define the prevalence and associations of co-morbidity and school attendance in older children with epilepsy (CWE) from a rural district of Tanzania by conducting a community-based case–control study.
Methods
Children aged 6–14 years old with active epilepsy (at least two unprovoked seizures in the last five years) were identified in a cross-sectional survey in Tanzania. Co-morbidities were assessed and cases were compared with age-matched controls.
Results
Co-morbidity was very common amongst cases (95/112, 85%), with 62/112 (55%) having multiple co-morbidities. Co-morbidities consisted of cognitive impairment (72/112, 64%), behaviour disorder 68/112 (61%), motor difficulties 29/112 (26%), burns and other previous injuries (29/112, 26%). These complications were significantly more common in cases than in controls (odds ratio 14.8, 95%CI 7.6–28.6, p < 0.001). Co-morbidity in CWE was associated with structural cause, abnormal electroencephalogram and early onset seizures. Cognitive impairment was very common in CWE (64%) and was not associated with Phenobarbital use but was associated with motor difficulties, early onset and recurrent seizures. Poor school attendance was found in 56/112 (50%) of CWE, but not in the controls: it was associated with the presence of multiple co-morbidities, especially with motor difficulties in CWE.
Conclusion
Children with epilepsy in a rural area of sub-Saharan Africa had a high level of co-morbidity. Cognitive impairment and poor school attendance were very common. These associated difficulties in CWE in the region need to be addressed to reduce the negative impact of epilepsy on these children.
doi:10.1016/j.seizure.2011.10.011
PMCID: PMC3672980  PMID: 22130004
Epilepsy; Africa; Children; Co-morbidity; Cognitive impairment; Education
4.  Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis 
PLoS ONE  2010;5(11):e14001.
Background
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.
Methods
We recruited 133 children, aged 3–156 months, who presented to a district hospital on the Kenyan coast with acute seizures and frequency-matched these to children of similar ages but without seizures. We defined iron deficiency according to the presence of malarial infection and evidence of inflammation. In patients with malaria, we defined iron deficiency as plasma ferritin<30µg/ml if plasma C-reactive protein (CRP) was<50mg/ml or ferritin<273µg/ml if CRP≥50mg/ml, and in those without malaria, as ferritin<12µg/ml if CRP<10mg/ml or ferritin<30µg/ml if CRP≥10mg/ml. In addition, we performed a meta-analysis of case-control studies published in English between January 1966 and December 2009 and available through PUBMED that have examined the relationship between iron deficiency and febrile seizures in children.
Results
In our Kenyan case control study, cases and controls were similar, except more cases reported past seizures. Malaria was associated with two-thirds of all seizures. Eighty one (30.5%) children had iron deficiency. Iron deficiency was neither associated with an increased risk of acute seizures (45/133[33.8%] cases were iron deficient compared to 36/133[27.1%] controls, p = 0.230) nor status epilepticus and it did not affect seizure semiology. Similar results were obtained when children with malaria, known to cause acute symptomatic seizures in addition to febrile seizures were excluded. However, in a meta-analysis that combined all eight case-control studies that have examined the association between iron deficiency and acute/febrile seizures to-date, iron deficiency, described in 310/1,018(30.5%) cases and in 230/1,049(21.9%) controls, was associated with a significantly increased risk of seizures, weighted OR 1.79(95%CI 1.03–3.09).
Conclusions
Iron deficiency is not associated with an increased risk of all acute seizures in children but of febrile seizures. Further studies should examine mechanisms involved and the implications for public health.
doi:10.1371/journal.pone.0014001
PMCID: PMC2982825  PMID: 21103365
5.  Atypical brain response to novelty in rural African children with a history of severe falciparum malaria 
Plasmodium falciparum is the most common parasitic infection of the central nervous system causing neuro-cognitive deficits in 5–26% of paediatric cases. The burden cannot be reliably estimated because of lack of sensitive, culture-fair and robust assessments in rural settings. Auditory and visual brain event related potentials (ERPs) are used to compare novelty processing in children exposed to severe malaria with community controls. Fifty children previously admitted and discharged from Kilifi District Hospital with severe falciparum malaria were selected and compared with 77 unexposed agematched children. The results showed that up to 14% of children exposed to severe malaria had significantly different responses to novelty compared to unexposed children. Children exposed to severe malaria had smaller P3a amplitudes to novelty in both auditory [F (3, 119) = 4.545, p = 0.005] and visual [F (3, 119) = 6.708, p < 0.001] paradigms compared to unexposed children. In the auditory domain the differences in processing of novelty were not related to early component processing. The percentage of children with severe malaria showing impaired performance using ERPs is within the range previously reported using neuropsychological tests. The overall pattern suggests that severe malaria affects prefrontal and temporal cortices normally activated by stimulus novelty.
doi:10.1016/j.jns.2010.05.018
PMCID: PMC2923746  PMID: 20566207
Severe falciparum malaria; Event-related potentials; Cognitive; Children
7.  Chromosome 15 in floppy infants 
Archives of Disease in Childhood  1981;56(11):882-885.
Three children with Prader-Willi syndrome and chromosome abnormalities affecting chromosome 15 are described and the literature is reviewed. The usefulness of chromosome analysis in the investigation of the floppy infant is illustrated by two of the cases described. Twenty-three other children with similar clinical features had normal chromosomes.
PMCID: PMC1627383  PMID: 7305434
8.  Epilepsy in Tanzanian children: Association with perinatal events and other risk factors 
Epilepsia  2012;53(4):752-760.
Purpose
To define the prevalence and risk factors for epilepsy in children in a rural district of Tanzania by conducting a community-based case–control study.
Methods
Children aged 6–14 years with active epilepsy (at least two unprovoked seizures in the last 5 years) were identified in a cross-sectional survey in Tanzania. Cases were compared with age-matched controls.
Key Findings
Overall 112 children with epilepsy (CWE) were identified; the unadjusted prevalence of epilepsy was 2.91 per 1,000 (95% confidence interval [95% CI] 2.4–3.5). The main seizure types were focal motor with secondary generalization in 73 (65.2%) of 112 and generalized convulsive seizures in 19 (16.9%) of 112. Adverse perinatal events were present in 16 (14%) of 112 cases but in no controls. In multivariate analysis, epilepsy was associated with number of parents who were resident at home (odds ratio [OR] 6.2 for none vs. both resident, 95% CI 1.5–25.5), history of adverse perinatal events (OR 14.9, 95% CI 1.4–151.3), family history of afebrile seizures (OR 5.7, 95% CI 1.0–27.5), and poor scholastic attainment (OR 8.6, 95% CI 4.0–18.4). Electroencephalography (EEG) and computed tomography (CT) scans were abnormal in 44 (44%) of 101 and 26 (29%) of 90 cases, respectively. Overall, 98 (88%) of 112 cases had focal features on assessment.
Significance
In this study from sub-Saharan Africa, CWE predominantly had focal features that support the suggestion that most epilepsy in this region has a symptomatic etiology. Adverse perinatal events were strongly associated with epilepsy. Genetic and social factors may also be important. Epilepsy may be preventable in a significant proportion of children with better antenatal and perinatal care.
doi:10.1111/j.1528-1167.2011.03395.x
PMCID: PMC3467761  PMID: 22308971
Epilepsy; Africa; Children; Etiology; Adverse perinatal events; Prevalence
9.  Seizures in 204 comatose children: incidence and outcome 
Intensive Care Medicine  2012;38(5):853-862.
Purpose
Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain.
Methods
cEEG (one to three channels) was performed for a median 42 h (range 2–630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state).
Results
Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36 %, 95 % confidence interval, 95 % CI, 32–41 %) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46 %) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95 % CI 1.012–1.042; p < 0.0005), Adelaide coma score (aOR 0.813, 95 % CI 0.700–0.943; p = 0.006), and EEG grade on admission (excess slow with >3 % fast, aOR 5.43, 95 % CI 1.90–15.6; excess slow with <3 % fast, aOR 8.71, 95 % CI 2.58–29.4; low amplitude, 10th centile <9 µV, aOR 3.78, 95 % CI 1.23–11.7; and burst suppression, aOR 10.68, 95 % CI 2.31–49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95 % CI 1.18–4.81). Unfavourable outcome (29/111 survivors; 26 %) was independently predicted by the presence of ES (aOR 15.4, 95 % CI 4.7–49.7) and PIM (aOR 1.036, 95 % CI 1.013–1.059).
Conclusion
Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool.
doi:10.1007/s00134-012-2529-9
PMCID: PMC3338329  PMID: 22491938
Seizures; Status epilepticus; Coma; Child; Outcome; Medicine & Public Health; Pain Medicine; Emergency Medicine; Intensive / Critical Care Medicine; Pneumology/Respiratory System; Pediatrics; Anesthesiology
10.  Haptoglobin HP2-2 genotype, α-thalassaemia and acute seizures in children living in a malaria-endemic area 
Epilepsy Research  2008;81(2-3):114-118.
Summary
Polymorphisms of the haptoglobin (HP) gene and deletions in α-globin gene (α-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with α-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African α-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3–156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p = 0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p = 0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in α-globin gene (p = 0.403). Among cases, HP2-2 polymorphism and deletions in α-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in α-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.
doi:10.1016/j.eplepsyres.2008.04.021
PMCID: PMC2670977  PMID: 18554871
Haptoglobin genotypes; α-Thalassaemia; Acute seizures and children

Results 1-10 (10)