Neuro-cognitive impairment following acquired central nervous system infections in childhood: A systematic review

ArticleinBrain Research Reviews 43(1):57-69 · October 2003with23 Reads
DOI: 10.1016/S0165-0173(03)00192-9 · Source: PubMed
Abstract
The morbid consequences of central nervous system (CNS) infections are often overlooked in the face of high mortality rates. However, neurological impairments not only affect the child's development and future prospects but also place an economic and social burden on communities and countries that often have few resources to deal with such problems. We conducted a systematic review to investigate the occurrence and pattern of persisting neurological impairment after common CNS infections. A comprehensive search of MEDLINE, EMBASE and PsycINFO databases, supplemented by hand-searches of key journals, resulted in forty-six eligible studies, five of which gave information on the spectrum of developmental domains. Despite the lack of comprehensive, methodologically-sound studies, the results show that postinfectious neurological impairment persists, most commonly in cognition and motor functions. Deficits include more subtle problems, which can be difficult to detect on gross neurological assessment but may still be deleterious to the child's social and educational functioning. Higher morbidity for similar mortality in acute bacterial meningitis compared with cerebral malaria in the epidemiological data may suggest future research directions for clinical research to devise more effective interventions.
    • "Cognitive deficits were reported following intraventricular injection of LPS, (Hauss-Wegrzyniak et al., 2000) which involves intraparenchymal damage, and with intraperitoneal injection, which is complicated by peripheral organ involvement and sepsis (Noble et al., 2007; Semmler et al., 2007; Sparkman et al., 2005a; Sparkman et al., 2005b). Our findings are similar to those reported in human brain inflammation, as it is well documented that meningitis and encephalitis in children and adults is accompanied by long lasting deficits in learning ability, memory, language, attention and executive function (Anderson et al., 1997; Carter et al., 2003; Hoogman et al., 2007) Those higher cognitive functions are intimately associated with areas such as the hippocampus, frontal, entorhinal and temporal cortices in both humans and rodents. Therefore, we have focused next on exploring the regional distribution of neuroinflammation in the same animals. "
    [Show abstract] [Hide abstract] ABSTRACT: Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke, and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons. Mice (n = 10/group) injected with endotoxin (LPS) or saline in the cisterna magna underwent neurobehavioral and cognitive testing followed by quantitative autoradiographic assessment of regional neuroinflammation with [3H]PK11195, an established marker of microgliosis. In parallel, cocultures of cortical and striatal neurons taken from embryonic day 19 rat embryos or postnatal day 1 mice expressing green fluorescent protein were exposed for 24 h to the proinflammatory cytokine TNFalpha, glutamate, or a combination of the two agents. LPS-treated mice exhibited significant deficits in memory and significant increases in specific PK11195 binding in cortical and hippocampal regions, but not in striatum. Cultured neurons of cortical origin showed significantly lower survival rate relative to striatal neurons in response to TNFalpha, glutamate, or a combination of the two agents. Furthermore, TNFalpha exerted neuroprotective rather than neurotoxic effects in the striatal but not in the cortical neurons. These results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component.
    Full-text · Article · Jul 2011
    • "Cerebral malaria accounts for 8.2% of these malaria cases with a mortality of 17% [6]. Despite its low prevalence, cerebral malaria is one of the major causes of neurodevelopmental difficulties [7,8] with several studies documenting cognitive and neurologic deficits in survivors, with 14% to 26% having cognitive deficits91011. There is however little evidence of behavioural problems resulting from cerebral malaria with only one study describing the behavioural problems [12]. "
    [Show abstract] [Hide abstract] ABSTRACT: No measure of childhood behaviour has been validated in Uganda despite the documented risks to behaviour. Cerebral malaria in children poses a great risk to their behaviour, however behavioural outcomes after cerebral malaria have not been described in children. This study examined the reliability of the Luganda version of the Child Behaviour Checklist (CBCL) and described the behavioural outcomes of cerebral malaria in Ugandan children. The CBCL was administered to parents of 64 children aged 7 to 16 years participating in a trial to improve cognitive functioning after cerebral malaria. These children were assigned to the treatment or control group. The CBCL parent ratings were completed for the children at baseline and nine weeks later. The CBCL was translated into Luganda, a local language, prior to its use. Baseline scores were used to calculate internal consistency using Cronbach Alpha. Correlations between the first and second scores of the control group were used to determine test-retest reliability. Multicultural norms for the CBCL were used to identify children with behavioural problems of clinical significance. The test-retest reliability and internal consistency of the Internalising scales were 0.64 and 0.66 respectively; 0.74 and 0.78 for the Externalising scale and 0.67 and 0.83 for Total Problems. Withdrawn/Depressed (15.6%), Thought Problems (12.5%), Aggressive Behaviour (9.4%) and Oppositional Defiant Behaviour (9.4%) were the commonly reported problems. The Luganda version of the CBCL is a fairly reliable measure of behavioural problems in Ugandan children. Depressive and thought problems are likely behavioural outcomes of cerebral malaria in children. Further work in children with psychiatric diagnoses is required to test its validity in a clinical setting.
    Full-text · Article · Dec 2009
    • "Cerebral malaria is the most severe form of malaria affecting 575,000 African children below five years of age of which 110,000 die [1]. Neuro-cognitive morbidity also presents a significant problem with more than 200,000 child survivors of cerebral malaria estimated to have long term cognitive impairment234. Retrospective studies show that cerebral malaria child survivors have cognitive deficits in several areas including language, memory, attention, visual spatial skills and somatosensory discrimination with some lasting up to nine years post illness5678. "
    [Show abstract] [Hide abstract] ABSTRACT: Our earlier studies on Ugandan children surviving cerebral malaria showed cognitive deficits mainly in attention and memory. We now present the first study in sub-Saharan Africa to investigate the feasibility and potential benefits of computerized cognitive rehabilitation training on neuropsychological and behavioral functioning of children surviving cerebral malaria. A randomized trial in which 65 children admitted 45 months earlier with cerebral malaria were recruited at Mulago Hospital, Kampala, Uganda. For 8 weeks, 32 of the children received weekly training sessions using Captain's Log cognitive training software and the other 33 were assigned to a nontreatment condition. Pre- and postintervention assessments were completed using CogState, a computerized neuropsychological battery, measuring visuomotor processing speed, working memory, learning, attention and psychomotor speed and the Child Behavior Checklist measuring internalizing problems, externalizing problems, and total problems. Preintervention scores were similar between both groups. Treatment effects were observed on visuospatial processing speed [group effect (standard error) 0.14 (0.03); p < .001], on a working memory and learning task [0.08 (0.02); p < .001], psychomotor speed [0.14 (0.07); p = .04], and on internalizing problems [-3.80 (1.56); p = .02] after controlling for age, sex, school grade, quality of the home environment, and weight for age z scores. Similar treatment effects were observed when no adjustments for the above covariates were made. Computerized cognitive training long after the cerebral malaria episode has immediate benefit on some neuropsychological and behavioral functions in African children. The long-term benefit of this intervention needs to be investigated.
    Full-text · Article · Sep 2009
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