The purpose of the study was to develop a culture-informed measure of developmental outcome and to apply it to detect differences in developmental level between children with cerebral malaria enrolled in a clinical trial to control seizures during the acute phase of the illness. The instrument was administered to a sample of 180 children, three and 12 months after discharge from hospital. The measure demonstrated high internal consistency, good inter-observer reliability, age sensitivity and strong relations with parental report of child functioning. No association was found between performance, or change in performance, with the prophylactic regime administered. The results suggested that the use of Phenobarbital in controlling provoked seizures has no observable effect on cognitive function.

/pdf/assessing-developmental-outcomes-in-children-from-kilifi-iqjzryvzg6.pdf

Assessing developmental outcomes in children from Kilifi, Kenya, following prophylaxis for seizures in cerebral malaria.

Bacterial infections of the central nervous system (CNS) in the newborn are common and are of major clinical importance. By far the most frequent of these infections is neonatal bacterial meningitis. Other bacterial processes include primary intracranial infections (e.g., epidural and subdural empyema and brain abscess) and disorders in which involvement of the CNS is secondary to extraneural infection (e.g., neonatal tetanus). Systemic candidiasis, a disseminated fungal infection, is also part of this chapter. The emphasis will be on the neuropathological, clinical, and neuroimaging features.

Bacterial and Fungal Intracranial Infections

Certain minerals and trace elements are essential for the development of healthy nervous system. Altered serum levels of these elements may lead to the development of various diseases including epilepsy. The present study was designed to evaluate the association of serum calcium, magnesium, zinc and copper in the development of genetic generalized epilepsy [GGE; erstwhile known as idiopathic generalized epilepsy (IGE)] as well as idiopathic intractable epilepsy (IIE), in which seizures persist despite treatment with at least two or three antiepileptic drugs tolerated at reasonable dosage. 200 GGE patients and equal number of healthy controls were recruited for study with their written informed consent. The patients were further divided into responders and non-responders based on their response to antiepileptic drugs. Copper and zinc levels were assayed by atomic absorption spectrophotometer whereas calcium and magnesium were analyzed by Human Star 600 fully automated biochemistry analyzer. The patients with GGE had significant low levels of calcium, magnesium and zinc (1.85 ± 0.33, 0.69 ± 0.13 mmol/L and 11.33 ± 3.32 µmol/L respectively) and the corresponding values for controls were 2.27 ± 0.22, 0.89 ± 0.15, 12.71 ± 3.24 (p < 0.05). Significant high levels of copper were found in patients as compared to controls (26.69 ± 8.79 µmol/L; 16.64 ± 3.64) (p < 0.05). Significantly decreased levels of zinc were noted in non-responders (10.38 ± 2.99) compared to responders (12.62 ± 3.30) (p < 0.05). No significant difference was observed in serum calcium, magnesium and copper levels between responders and non-responders. In conclusion, low levels of calcium, magnesium, zinc and high levels of copper were found to be associated with GGE. Further, the patients with IIE were also found to have low levels of zinc.

Association of Serum Trace Elements and Minerals with Genetic Generalized Epilepsy and Idiopathic Intractable Epilepsy

Background Cerebral oedema occurs with cerebral malaria, and some clinicians think osmotic diuretics, such as mannitol or urea, may improve outcomes. Objectives To compare mannitol or urea to placebo or no diuretic for treating children or adults with cerebral malaria. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register (Issue 4, 2010), CENTRAL (The Cochrane Library Issue 12, 2010), MEDLINE (1966 to November 2010), EMBASE (1974 to November 2010), LILACS (1982 to November 2010), and the reference lists of articles. We contacted relevant organizations and researchers. Selection criteria Randomized or quasi-randomized controlled trials comparing mannitol or urea to placebo or no treatment in children and adults with cerebral malaria. Primary outcomes were death, life-threatenining sequelae and major neurological sequelae at six months. Data collection and analysis Two authors applied the inclusion criteria, assessed risk of bias, and extracted data independently. Main results One trial met the inclusion criteria, comparing mannitol 20% to saline placebo in 156 Ugandan children. Allocation was concealed. No difference in mortality, time to regain consciousness, or neurological sequelae were detected. Authors' conclusions There are insufficient data to know what the effects of osmotic diuretics are in children with cerebral malaria. Larger, multicentre trials are needed.

Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria.

SUMMARY Purpose: In view of a putative role of oxidative stress in the pathophysiology of seizures, this study addressed the interactions between N-acetylcysteine (NAC), a potent antioxidant and two antiepileptic drugs sodium valproate (SVP) and phenytoin (PHT) on experimental seizures in mice. Methods: The interaction was studied at three fixed ratio combinations (i.e., 1:1, 1:3, and 3:1) in the mouse maximal electroshock (MES) test using isobolographic analysis. Markers of oxidative stress (reduced glutathione [GSH] and malondialdehyde [MDA]) were estimated in the cortex of mice pretreated with either of these drugs alone or their 3:1 ratio combinations at the experimentally determined ED50 values (ED50 exp values). The grip strength and spontaneous alternation behavior (SAB) were also assessed. In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and calcium levels were estimated. Results: We found an anticonvulsant action of NAC in the MES test. Further, the ED50 exp values for the combinations of PHT and NAC did not differ from the theoretically calculated ED50 values indicating additive effects. In case of SVP and NAC, however, the ED50 exp values were lower than the theoretically calculated ED50 values. The interaction of SVP with NAC at the fixed ratios of 1:3 and 3:1 was found to be synergistic. No significant changes were observed in the grip strength, SAB, cortical GSH and MDA levels, serum AST, ALT, ALP, or calcium levels. Conclusion: Our results thus hold promise for the use of NAC as an adjunct to PHT and SVP therapy.

/pdf/pharmacological-and-biochemical-analysis-of-interactions-17elwcce8h.pdf

Pharmacological and Biochemical Analysis of Interactions between N-Acetylcysteine and Some Antiepileptic Drugs on Experimental Seizures in Mice

BACKGROUND Magnesium and calcium have been found to have increasing roles in the patho-physiology of epilepsy. Hypomagnesaemia and hypocalcaemia cause hyper-exitability of neurons and have been associated strongly with seizures in adults and children. OBJECTIVES To determine if hypomagnesaemia or hypocalcaemia is present in Nigerian children with epilepsy and to determine the relationship between serum magnesium and calcium levels and frequency and control of epilepsy. DESIGN A prospective case control study at the Lagos University Teaching Hospital. PATIENTS AND METHODS 45 children with epilepsy and 45 controls were recruited from the paediatric neurology unit of the Lagos University Teaching Hospital. Serum magnesium and calcium were measured by spectrophotometric methods. RESULTS Serum magnesium and calcium was significantly lower in the patients compared to the controls; Magnesium - 0.98 (0.0005) Vs 1.2 (0.04) mmol/L, p< 0.0001 and Calcium - 2.29 (0.04) Vs 2.3 (0.02) mmol/L, p<0.05 respectively. No significant differences were noted in the plasma phosphorus and albumin concentrations. CONCLUSION Magnesium and calcium levels are lower in the epileptic children compared to the controls during the seizure-free periods. More studies are needed to evaluate these electrolytes during seizures and the effect of the different anticonvulsant drugs on these electrolytes.

Plasma magnesium and calcium levels in children with epilepsy in lagos.

Although tetanus is a well-recognised, well-described, preventable and eradicable infection, it continues to ravage the lives of children in developing countries, especially among neonates. A cross-sectional review of cases of neonatal tetanus seen in LUTH was carried out retrospectively. Thirty-nine (39) cases were studied, comprising 26 (63.4%) males and 15 (36.6%) females, giving a male: female ratio of 1.6:1. Case fatality rate was 10.3%, thirty-five (89.7%) cases survived, of which nine (23.8%) survived with complications. Clinical factors that influence outcome were: a short interval between onset and presentation (p = 0.03), low tetanus score below 6.0 (p = 0.002), hyperpyrexia (p = 0.0001), heart failure (p = 0.035), cyanosis (p = 0.008) and crepitations (p = 0.003). Although several management factors were associated with mortality, these failed to meet statistical significance (p > 0.05). In this study, clinical factors, including presentation interval, were the principal determinants of outcome. The need for intensification and sustenance of preventive measures, early recognition and presentation, prompt treatment as well as improved care are emphasised. We recommend periodic audit of patient clinical data towards improving quality of care.

Clinical and management factors related to outcome in neonatal tetanus.

UNLABELLED Cerebral malaria is one of the most lethal forms of malaria. Given that malaria is a constantly evolving disease, it is therefore necessary to document patterns of presentation even in the same centre over a period of time. OBJECTIVE To document the prevalence and pattern of cerebral malaria in children. DESIGN Cross-sectional descriptive study of children with cerebral malaria attending the emergency room of the Lagos University Teaching Hospital. Age, sex, month at which diagnosis was made, associated clinical features, condition at discharge and mortality were assessed. RESULTS Cerebral malaria was documented in 107/3309 (3.2%) children. There was an equal male:female ratio. Cerebral malaria occurred most frequently between July and September and in children between 2 and 2.9 years. A total of 79/107 (73.8) recovered fully at discharge, 9/107 (8.4%) recovered with some neurological sequelae while 19/107 (17.8%) died. Coma score on admission was significantly lower among those who died compared with those who survived (p = 0.001). Clinical signs observed in these children were seizures-88/107 (82.2%), pallor-75/107 (70.1%), jaundice-55/107 (51.4%) and hepato-splenomegaly-18 (16.8%). However, decerebrate posturing was the only clinical sign associated with a fatal outcome OR, 11.47 (p = 0.009). CONCLUSION This study shows that cerebral malaria still remains a problem of the under fives with unacceptably high mortality. The clinical significance of decerebrate posture as an indicator of mortality would require further evaluation.

Pattern of cerebral malaria in children at the Lagos University Teaching Hospital.

UNLABELLED Cerebral malaria, one of the severe forms of malaria, carries a very high fatality rate even when managed in the best of centres. This underpins the need for a medical audit to review patient management steps or procedures to improve the standard of patient care of children with cerebral malaria in the Lagos University Teaching Hospital. METHODS A retrospective audit of records of children with cerebral malaria who presented in the emergency room of the Lagos University Teaching Hospital in the last five years. Relevant clinical and patient management information of survivors were extracted from the records and analysed. RESULTS The records show that critical information useful in the management of these children was lacking in 50 - 60% of the records reviewed. The appropriate anti-malarial drug (intravenous quinine) in adequate doses was used in 54(94.7% ) of cases. A total of 12 patients (21.1% ) still had either mannitol or dexamethasone given to them. Blood transfusion was ordered in 60% of the children despite severe anaemia being present in only 30% of them. CONCLUSION This study highlights the sub-optimal level of knowledge and practice among doctors and the need for retraining of medical staff in maintaining proper records. The authors recommend the use of patient management guidelines.

Management of children with cerebral malaria in Lagos - a medical audit.

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Plasma magnesium and calcium levels in children with epilepsy in lagos.

Clinical and management factors related to outcome in neonatal tetanus.

Pattern of cerebral malaria in children at the Lagos University Teaching Hospital.

Management of children with cerebral malaria in Lagos - a medical audit.