The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children.</p> <p>Methods</p> <p>Children, aged between three months and five years, with acute uncomplicated <it>Plasmodium falciparum </it>malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28.</p> <p>Results</p> <p>From December 1994 to July 1997, 91 children with uncomplicated <it>P. falciparum</it>, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033).</p> <p>Conclusion</p> <p>In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.</p

Neurological status of low-risk Vietnamese newborns: a comparison with a British newborn cohort.

A shortened version of the Dubowitz newborn neurological examination, recently reassessed in rural Thailand, was applied to a group of 58 Vietnamese newborns. The aim was to establish the neurological status of newborns in this population for use in further studies and to compare with groups previously studied. Compared to the original British cohort, the Vietnamese newborns showed significantly lower scores in 10 of 25 items, including several related to truncal tone. Evidence was sought of thiamine and long-chain fatty acid deficiency as a possible cause for these findings, but no correlation was found between the neurological status and the maternal or infant blood levels of these nutritional indicators. The findings suggest that the neurological status of low-risk Vietnamese newborns appears to lie between that of British newborns and those ethnic minority Karen newborns in refugee camps on the Thai-Burmese border tested previously. Although no specific nutritional cause has been identified in the study, the findings may still reflect sub-optimal intake of some important nutrients

Neurological Status of Low-risk Vietnamese Newborns: A Comparison with a British Newborn Cohort

A shortened version of the Dubowitz newborn neurological examination, recently re-assessed in rural Thailand, was applied to a group of 58 Vietnamese newborns. The aim was to establish the neurological status of newborns in this population for use in further studies and to compare with groups previously studied. Compared to the original British cohort, the Vietnamese newborns showed significantly lower scores in 10 of 25 items, including several related to truncal tone. Evidence was sought of thiamine and long-chain fatty acid deficiency as a possible cause for these findings, but no correlation was found between the neurological status and the maternal or infant blood levels of these nutritional indicators. The findings suggest that the neurological status of low-risk Vietnamese newborns appears to lie between that of British newborns and those ethnic minority Karen newborns in refugee camps on the Thai-Burmese border tested previously. Although no specific nutritional cause has been identified in the study, the findings may still reflect sub-optimal intake of some important nutrients

Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from welldesigned clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population

Application of a scorable neurologic examination in healthy term infants aged 3 to 8 months

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Neurological examination in healthy term infants aged 3-10 weeks

The neurodevelopmental progress of newborn term infants is checked routinely at around 6 weeks of postnatal age. The maturation of neurological signs in this age range however has not been systematically studied and normative data are not available. The aim of this study was to document any changes in posture, tone, reflexes, behaviour and movements in low-risk full-term infants between 3 and 10 weeks of postnatal age.We performed a structured neurological examination previously standardised in full-term newborns in the first 48 h after birth. In the current study, a total of 76 examinations were performed between 3 and 10 weeks of age in low-risk full-term infants.The results of the examinations were divided according to postnatal age. In most items, the scores changed with time, with a definite shift in their distribution occurring around 6 weeks. At this age, a reduction in flexor tone of the limbs was observed, together with an increase in active neck tone. Visual orientation in contrast had already improved by 3 weeks when all infants were able to follow a target in a full circle compared to newborns that are often only able to follow a target in an arc.Our results suggest that 6 weeks post-term birth is an important milestone for changes in neurological signs, particularly those related to muscle tone and posture, probably reflecting maturation of the nervous system. These findings provide important guidelines for the interpretation of the neurological examination performed at this age

Risk factors for neonatal arterial ischemic stroke: The importance of the intrapartum period

Objective To investigate risk factors for neonatal arterial ischemic stroke (NAIS), and compare them with those present in term controls and infants with hypoxic-ischemic encephalopathy (HIE). Study design Antepartum and intrapartum data were collected at presentation from 79 infants with NAIS and compared with 239 controls and 405 infants with HIE. The relationships between risk factors and NAIS were explored using univariable and multivariable regression. Results Compared with controls, infants with NAIS more frequently had a family history of seizures/neurologic diseases, primiparous mothers, and male sex. Mothers of infants with NAIS experienced more intrapartum complications: prolonged rupture of membranes (21% vs 2%), fever (14% vs 3%), thick meconium (25% vs 7%), prolonged second stage (31% vs 13%), tight nuchal cord (15% vs 6%), and abnorm8al cardiotocography (67% vs 21%). Male sex (OR 2.8), family history of seizures (OR 6.5) or neurologic diseases (OR 4.9), and ≥1 (OR 5.8) and ≥2 (OR 21.8) intrapartum complications were independently associated with NAIS. Infants with NAIS and HIE experienced similar rates though different patterns of intrapartum complications. Maternal fever, prolonged rupture of membranes, prolonged second stage, tight nuchal cord, and failed ventouse delivery were more common in NAIS; thick meconium, sentinel events, and shoulder dystocia were more frequent in HIE. Abnormal cardiotocography occurred in 67% of NAIS and 77.5% of infants with HIE. One infant with NAIS and no infant with HIE was delivered by elective cesarean (10% of controls). Conclusions NAIS is multifactorial in origin and shares risk factors in common with HIE. Intrapartum events may play a more significant role in the pathogenesis of NAIS than previously recognized

Neurologic examination of preterm infants at term age: Comparison with term infants

Objectives: The aim was to establish the range of neurologie findings in preterm infants reaching term age, their relation to gestational age at birth, and the possible differences with healthy term newborns tested during the first days of life. Study design: The Dubowitz neonatal neurologie examination was performed at term age in 157 low-risk preterm infants born between 25 and 34 weeks' gestation who had cranial ultrasonograms that were normal or showed minor abnormalities. Infants were subdivided in 3 groups according to their gestational age at birth. Results: Within the preterm cohort, the range of scores for the 3 gestational age subgroups was different from each other for 21 of the 34 items, although the median scores were different only in 10 of the 34 items. The range of scores and their median in preterm infants however was wider than that found in term infants. Preterm infants examined at term were also more hyperexcitable and tended to have less flexor tone in the limbs and less extensor tone in the neck in the sitting posture. Conclusions: The distribution of scores provides useful guidelines when a preterm infant is examined at term