Neurocognitive and Motor Deficits in HIV-Infected Ugandan Children With High CD4 Cell Counts

Ruel, Theodore; Boivin, Michael J.; Boal, Hannah E.; Bangirana, Paul; Charlebois, Edwin D.; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey, Grant; Achan, Jane; Akello, Carolyne; Kamya, Moses R.; Wong, Joseph K.

doi:10.1093/cid/cir1037

Cited by 136 publications

(150 citation statements)

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“…The BOT-2 has proven adaptable and useful in characterizing the specific aspects of motor impairment associated with HIV in Ugandan children. 18,19 …”

Section: Bot-2mentioning

confidence: 99%

Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava

2013

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT:Konzo is an irreversible sudden-onset upper-motor neuron disorder affecting children dependent on bitter cassava for food. The neuroepidemiology of konzo is well characterized. Children subsisting on poorly processed bitter cassava without adequate dietary sulfur-based amino acids are especially at risk. WHAT THIS STUDY ADDS:We found a pervasive subclinical neurocognitive effect in children with konzo. This study provides the first evidence we are aware of that a motor proficiency examination can effectively characterize konzo severity. abstract BACKGROUND: Konzo is an irreversible upper-motor neuron disorder affecting children dependent on bitter cassava for food. Although the neuroepidemiology of konzo is well characterized, we report the first neuropsychological findings.METHOD: Children with konzo in the Democratic Republic of Congo (mean age 8.7 years) were compared with children without konzo (mean age 9.1 years) on the Kaufman Assessment Battery for Children, second edition (KABC-II), and the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2). Both groups were also compared with normative KABC measures from earlier studies in a nearby nonkonzo region. RESULTS:Using a Kruskal-Wallis test, children with konzo did worse on the KABC-II simultaneous processing (visual-spatial analysis) (K [1] = 8.78, P = .003) and mental processing index (MPI) (K [1] = 4.56, P = .03) than children without konzo. Both konzo and nonkonzo groups had poorer KABC sequential processing (memory) and MPI relative to the normative group from a nonkonzo region (K [2] = 75.55, P , .001). Children with konzo were lower on BOT-2 total (K [1] = 83.26, P , .001). KABC-II MPI and BOT-2 total were predictive of konzo status in a binary logistic regression model: odds ratio = 1.41, P , .013; 95% confidence interval 1.13-1.69. CONCLUSIONS:Motor proficiency is dramatically affected, and both children with and without konzo have impaired neurocognition compared with control children from a nonoutbreak area. This may evidence a subclinical neurocognitive form of the disease, extending the human burden of konzo with dramatic public health implications.

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“…The BOT-2 has proven adaptable and useful in characterizing the specific aspects of motor impairment associated with HIV in Ugandan children. 18,19 …”

Section: Bot-2mentioning

confidence: 99%

Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava

2013

PEDIATRICS

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“…We speculate that suppression of viral replication by ART relieves neurocognitive deficits in both groups of children to near normal levels, effectively eliminating subtype‐specific differences. We had previously observed that high HIV viral load was associated with neurocognitive impairment in Ugandan children who were not on ART 5. In that same cohort, children infected with subtype A who had poorer neurocognitive outcomes also had higher HIV viral load than subtype D‐infected children 8.…”

Section: Discussionmentioning

confidence: 81%

Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy

et al. 2017

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IntroductionInfection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype‐specific differences are also observed among children receiving ART.Materials and MethodsChildren were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)‐ or non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐ based ART (NCT00978068). Age at initiation of ART ranged from six months to six years. HIV subtype was determined by PCR amplification and population sequencing of the pol region derived from peripheral blood mononuclear cell DNA, followed by application of the REGA and Recombinant Identification Programme algorithms. General cognition was assessed using the Kaufman Assessment Battery for Children (Second Edition), attention using the Test of Variables of Attention, and motor skills using the Bruininks‐Oseretsky Test of Motor Proficiency (Second Edition). Home environment was assessed using the Home Observation for the Measurement of the Environment (HOME). Age‐adjusted test z‐scores were entered into a regression model that adjusted for sex, socio‐economic status score, HOME score, years of schooling, and ART treatment type.ResultsOne hundred and five children were tested; median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was 867.7 cells/mm3 (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to 4.23). Seventy‐eight children had HIV subtype A and 27 had subtype D; the groups had comparable home and socio‐economic status, except that there were more males among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There were no differences between the subtypes in general cognition (estimated mean difference: 0.20; 95% CI: −0.11 to 0.50); p = 0.21), attention (−0.18, 95% CI: −0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: −0.84 to 4.04, p = 0.20).ConclusionsOur results imply that ART may diminish the neurocognitive disadvantage seen in treatment‐naïve HIV‐infected children with subtype A.

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“…The KABC-II maintained its factor structure with Ugandan cerebral malaria survivors 23 and is sensitive to clinical biomarkers of disease status in Ugandan children with HIV. 9,24 The primary outcome variables were the global scores of Sequential Processing (memory), Simultaneous Processing (visual-spatial analysis), Learning (immediate and delayed memory), Planning (executive reasoning), and Knowledge (crystallized intelligence). These (except for Knowledge) are combined into a total mental processing index (MPI).…”

Section: Assessments For Neuropsychological Outcomesmentioning

confidence: 99%

“…28 This test takes about 23 min to administer and is designed to minimize cultural differences, and has been used in Uganda to assess cognitive factors associated with pediatric HIV. 9,24 The TOVA rapidly presents simple geometric stimuli (i. Captain's Log performance measures. The Captain's Log internal evaluator (CLIE) measures of session performance were used to gauge fidelity of training during a training session.…”

Section: Assessments For Neuropsychological Outcomesmentioning

confidence: 99%

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV

Boivin

Nakasujja

Sikorskii

et al. 2016

AIDS Research and Human Retroviruses

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Objectives: Clinically stable children with HIV can have neuromotor, attention, memory, visual-spatial, and executive function impairments. We evaluated neuropsychological and behavioral benefits of computerized cognitive rehabilitation training (CCRT) in Ugandan HIV children. Design: One hundred fifty-nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77 boys, 82 girls; M = 8.9, SD = 1.86 years) were randomized to one of three treatment arms over a 2-month period. Methods: The CCRT arm received 24 one-hour sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed for games targeting working memory, attention, and visual-spatial analysis. These games progressed in difficulty as the child's performance improved. The second arm was a ''limited CCRT'' with the same games rotated randomly from simple to moderate levels of training. The third arm was a passive control group receiving no training. All children were assessed at enrollment, 2 months (immediately following CCRT), and 3 months after CCRT completion. Results: The CCRT group had significantly greater gains through 3 months of follow-up compared to passive controls on overall Kaufman Assessment Battery for Children-second edition (KABC-II) mental processing index ( p < .01), planning ( p = .04), and knowledge ( p = .03). The limited CCRT group performed better than controls on learning ( p = .05). Both CCRT arms had significant improvements on CogState Groton maze learning ( p < .01); although not on CogState attention/memory, TOVA/impulsivity, or behavior rating inventory for executive function and child behavior checklist (psychiatric behavior/symptom problems) ratings by caregiver. Conclusions: CCRT intervention can be effective for neurocognitive rehabilitation in children with HIV in lowresource settings, especially in children who are clinically stable on ARV treatment.

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Neurocognitive and Motor Deficits in HIV-Infected Ugandan Children With High CD4 Cell Counts

Abstract: Significant motor and cognitive deficits were found in HIV-infected ART-naive Ugandan children with CD4 cell counts of ∼350 cells/μL and percentages of >15%. Study of whether early initiation of ART could prevent or reverse such deficits is needed.

Cited by 136 publications

References 35 publications

Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava

Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava

Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV

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