A comparison of the clinical presentation of HIV infected children with spastic diplegia to HIV uninfected children with spastic diplegia in a South African setting

Abstract

Background Globally, an estimated 36.7 (34-39.8) million people were living with HIV in December 2015. Sub-Saharan Africa accounts for 69% of the people living with HIV worldwide as well as 90% of all the children infected with the virus (UNAIDS [1]). The prevalence of children under the age of fifteen living with HIV in South Africa has decreased from 300,000 in 2012 to 240,000 in 2015 as a result of an increasing access to antiretroviral therapy (ART). According to 2015 statistics, 73% of the infected children in South Africa are receiving ART (UNAIDS [1]). Early invasion of the central nervous system (CNS) by the virus affects the developing foetal and infant brain. This, results in the most common primary HIV-related CNS complication: HIV encephalopathy (HIVE) [2-4]. Children who develop HIVE usually present within the first two years of life [4] and have significant delays in motor, cognitive and language development [4-7]. One of the residual impairments of HIVE is diplegia [3,8,9]. Langerak et al. [3] assessed children with spastic diplegia as a result of HIVE in order to present a first description of gait and physical status. Their results showed two distinct patterns of gait which could not be classified in the typical spastic diplegic CP gait that was described by Rodda et al. [10]. Children with diplegia as a result of CP or HIV encephalopathy have different pathogenesis but present with similar motor deficits. There are limited studies which have investigated and compared the clinical presentation of children presenting with spastic diplegia as a result of HIVE in comparison to HIV uninfected children with diplegia. With the advent of HAART, HIV-infected children are surviving, but with this comes an increase in co-morbid complications that are not life-threatening but still have an adverse effect on activity and participation. Aim The aim of this study was to determine if there are similarities and/or differences with regards to function, tone and strength between children with spastic diplegia as a result of CP and HIV encephalopathy. Methods Ethical clearance was approved (clearance number M140936) by the Human Research and Ethics Committee (Medical) of the University of Witwatersrand. Permission to conduct research was granted by clinical sites. Written informed consent and assent (for children over the age of six) was obtained from the participant and his or her primary caregiver. Participants between the ages of four to sixteen years with known HIV status were included if they presented with spastic diplegia, GMFCS level I-lV and were able to understand a two-step instruction. Children were excluded if they had botulinum toxin injections less than six months or orthopaedic surgery less than one year previously. Results A total of 31 HIV uninfected and 33 HIV-infected participants were assessed. There was a predominance of males (80.6%) in the HIV uninfected group while there was a more even gender distribution in the HIV-infected group (boys =51.5%; girls =48.5%). The two groups were well matched for age when comparing HIV infected to uninfected participants. However, in the functional group the HIV infected participants were significantly younger (p=.01) than their uninfected counterparts. Participants were well matched for age, GMFCS level, weight and height. For the purposes of crude analyses GMFCS I and II were grouped together (functional group), while levels III and IV were grouped as the non-functional group. The functional group was able to walk either independently or with assistance while the non-functional group was predominantly wheelchair bound. Pearsons Chi2 test showed no significant difference between the HIV infected and uninfected groups for GMFCS level (p=.2). With regard to the HIV-infected participants, ART initiation was most frequent between 6 weeks and 1 year of age (62.6%). Early ART initiation from birth to 6 weeks was only observed in 15.6% of the participants. There were no significant differences between groups with regard to GMFM scores. There is a trend for the HIVinfected participants to perform better in the functional group and this is most noticeable in Dimension E (walking, running and jumping) where there is a difference in scores of 6.3%. FMS scores for the groups showed no significant differences at 5m (p=.18), 50m (p=.14) and 500m (p=.08) (results not displayed). Similarly there were no significant differences between the participants in the functional and non-functional groups. The majority of participants in the functional group were able to walk independently at 5, 50 and 500 m. There was an increase in the use of an assistive device like a crutch or stick as the distance increased. In the non-functional group, the majority of participants in both groups crawled at 5 m and used wheelchairs at 50 and 500 m. There were no significant differences in tone when comparing HIV-infected to uninfected participants in both the functional and non-functional groups. Significantly lower right hip adductor tone (p=.03) was found in the non-functional HIV-infected children. Overall, both the functional HIV infected and uninfected groups presented predominantly with mild tone. However, the frequency of mild tone accounted for more than 50% of the tone across all muscle groups in the HIV-infected participants. The prevalence of severe tone in this group was less than 10% and only prevalent in the hamstrings (5.9%) and gastrocnemius (8.9%) muscle groups. The HIV uninfected participants had mild tone which increased in frequency from proximal to distal. However, almost one third of this group (27.2%) had severe tone in the hamstrings. In the non-functional group, the HIV-infected participants had a predominance of mild tone distally and moderate tone proximally. The greatest frequency of severe tone was observed in the hamstrings (28.2%). The HIV uninfected participants had a greater frequency of severe tone proximally in the hip adductors (55%) and hamstrings (42.5%) while the frequency of mild tone was more prevalent in the distal muscle groups. It can be said that the severity of tone decreased from proximal to distal in this group. For muscle strength, there were no significant differences between the groups except, that the HIV-infected participants have significantly stronger ankle plantarflexors (p=.05) on the right. The following trends were observed. In the functional group, the HIV uninfected participants tended to be stronger in all muscle groups except right and left ankle plantar flexion. In the non-functional groups there was a tendency for the HIV-infected participants to be stronger in all muscle groups except right knee extension and left hip abduction (results not displayed). A moderate significant correlation (r=0.35-0.48) (p