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 [Citation1]). 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 [Citation1]).
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) [Citation2–4]. Children who develop HIVE usually present within the first two years of life [Citation4] and have significant delays in motor, cognitive and language development [Citation4–7].
One of the residual impairments of HIVE is diplegia [Citation3,Citation8,Citation9]. Langerak et al. [Citation3] 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. [Citation10].
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 HIV-infected 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 < .05) between strength and viral load was found in six muscle groups suggesting that viral load may have an impact on muscle strength in children with HIV.
In summary, there was a trend for the HIV-infected functional participants to be weaker and have milder tone from proximal to distal compared to their HIV uninfected counterparts while the non-functional HIV-infected participants tended to be stronger but also have mild rather than severe tone from proximal to distal compared to their HIV uninfected counterparts.
Conclusions
Diplegia is a common presentation in children with HIV encephalopathy. HIV-infected and uninfected children with diplegia may present similarly but subtle clinical differences are present. HIV-infected participants who are classified GMFCS I and II performed clinically better in terms of function. In conclusion, the HIV-infected group presented similarly to the HIV uninfected group. However, the HIV-infected participants tended to be more functional and have less severe tone but were weaker.
Implications of the study
The information obtained from this study will help clinicians better understand the clinical picture of spastic diplegia as a result of HIV. This will guide us in making more informed, evidence-based decisions with regard to rehabilitation, neurological and orthopaedic management as well and it will begin to fill some of the gaps that are evident in this field and will form the base upon which future research can be conducted.
Further research is required to compare functional and non-functional groups with larger sample sizes to determine if there are significant differences between the groups. Further research is also required in the adolescent HIV group to determine the natural progression of HIV-infected adolescents with diplegia.
As the authors, we acknowledge that this study is currently being reviewed by the journal Vulnerable Children and Youth studies for publication of a full article.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
- UNAIDS. AIDS Epidemic update – Global report 2015 [cited June 2016]. Available from: http://www.unaids.org/en/resources/factsheet
- Whitehead N, Potterton J, Coovadia A. The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care: Psychol Socio-Med Aspects AIDS/HIV. 2014;26(4):497–504.
- Langerak NG, Du Toit J, Burger M, et al. Spastic diplegia in children with HIV encephalopathy: first description of gait and physical status. Developm Med Child Neurol. 2014;56(7):686–694.
- Hilburn N, Potterton J, Stewart A. Paediatric HIV encephalopathy in sub-Saharan Africa. Phys Ther Rev. 2010;15:410–417.
- Baillieu N, Potterton J. The extent of delay of language, motor, and cognitive development in HIV-positive infants. J Neurol Phys Therapy: JNPT. 2008;32(3):118–121.
- Donald KA, Samia P, Kakooza-Mwesige A. Pediatric cerebral palsy in Africa: A systematic review. Semin Pediatr Neurol. 2014a;21(1):30–35.
- Donald KA, Hoare J, Eley B, et al. Neurologic complications of pediatric human immunodeficiency virus: Implications for clinical practice and management challenges in the African setting. Semin Pediatr Neurol. 2014b;21(1):3–11.
- Donald KA, Walker KG, Kilborn T, et al. HIV Encephalopathy: pediatric case series description and insights from the clinic coalface. AIDS Res Ther. 2015;12(1):2.
- Govender R, Eley B, Walker K, et al. Neurologic and neurobehavioral sequelae in children with human immunodeficiency virus (HIV-1) infection. J Child Neurol. 2011;26(11):1355–1364.
- Rodda JM, Graham KH, Carson I, et al. Sagittal gait patterns in spastic diplegia. J Bone Joint Surg. (British volume). 2004;86(2):251–258.