Abstract
Background and Purpose
There are an estimated 1.5 million children living with HIV (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is the occurrence of seizure, for which imaging is helpful but is not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure.
Methods
In this prospective cohort study, participants were recruited at the University Teaching Hospital (UTH) in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Either CT or MRI, or both, were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool which quantifies brain imaging findings. Age-dependent neuropsychological assessments were administered.
Results
19/39 (49%) children had a brain MRI, 16/39 (41%) had CT and 4/39 (10%) had both. Mean age was 6.8 years (SD = 4.8). Children with advanced HIV disease had higher odds of atrophy (OR 7.2 95% CI 1.1 to 48.3). Focal abnormalities were less likely in children receiving ART (OR 0.22 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2 95% CI 0.03 to 0.9).
Conclusion
Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.
Introduction:
The introduction of combination antiretroviral therapy (ART) has transformed the human immunodeficiency virus (HIV) epidemic from a fatal condition to a chronic, manageable illness for those able to commence timely treatment and maintain reasonable adherence (1). However, in regions with limited resources like Sub-Saharan Africa, HIV infection continues to be a leading cause of disease and disability (2). Of the estimated 39 million people living with HIV worldwide in 2022, 1.5 million were children, most residing in sub-Saharan Africa and the majority of whom were infected through mother-to-child transmission (3). HIV can lead to neurological disease and seizures in children (4), and one common hospital presentation of children living with HIV (CLHIV) is the occurrence of a first-time seizure (2). Diagnosing and treating seizures in children with HIV can be challenging in areas with limited resources. Routine brain imaging is not commonly performed for seizure workup in this population, mainly due to the scarcity of imaging resources (5). In comparison, imaging is a routine part of workup for HIV-positive patients with first time seizures in high-income countries (HIC), as it provides valuable insight into seizure etiology and the effects of HIV on the brain, thus directing treatment and long-term interventions.
Neuroimaging may help to identify risk factors for seizures and predict clinical outcomes (6). Previous studies on neuroimaging in HIV-infected adults or children on various ART regimens have revealed basal ganglia calcification, cortical atrophy, white matter abnormalities, and focal mass lesions (7, 8). Imaging studies of HIV infected children have consistently revealed lower brain volumes and poor white matter integrity. Other findings in children living with HIV include cortical atrophy, involvement of the basal ganglia, and damage to the corpus callosum (8). In one study, children with HIV encephalopathy were found to have calcification of the basal ganglia, dilation of the lateral ventricles, and white matter involvement (9). A number of these imaging studies correlate these structural abnormalities with cognitive function and behavioral abnormalities but with mixed results due to the variety of outside factors involved including limited expertise for quantifying behavioral and cognitive deficits in children in African settings and a lack of well-validated, assessment tools that are relevant across cultures and languages (6).
Among CLHIV in Africa, there are complex risk factors for seizures including antenatal injuries, opportunistic infections (OI) associated with HIV, drug toxicity including ART, and metabolic obscurations (10, 11). Identifying the etiology for new onset seizure in a child living with HIV could aid clinicians in treating the underlying seizure etiology and in estimating the risk for subsequent epilepsy which is critical to the decision regarding whether to initiate antiseizure medications (ASMs). This is especially important since drug-drug interactions occur between ART and enzyme-inducing ASMs, which are the only readily available ASM in this region. Interactions may substantially reduce the effectiveness of either or both medication and/or increase drug toxicity (12). Furthermore, there is a chronic shortage of ASMs in sub-Saharan Africa, underscoring the challenges of initiating long-term ASM therapy (13, 14).
In addition to seizures, children born to HIV-infected mothers are at increased risk of developmental delays including cognitive and motor dysfunction (15). Timely interventions can improve outcomes among children living with HIV with neuro-disabilities (16). Therefore, evaluation of risk factors for neurodevelopmental impairments/delays can facilitate prognostication in this vulnerable population.
Materials & Methods:
Setting
This study took place at the University Teaching Hospital’s (UTH) Children’s Hospital in Lusaka, Zambia from April 2016 to June 2019. Potential patients were identified in the Emergency Department, Pediatric Intensive Care Unit, and the General Inpatient Service. Both magnetic resonance imaging (MRI) and computed tomography (CT) were undertaken at the Cancer Diseases Hospital (CDH) adjacent to UTH. Head CT images were acquired on a Siemens CT2007YS CT scanner and MRIs on a Siemens Magnetom Essenza 1.5T MRI scanner (Siemens, Munich, Germany).
Study Design
This was a prospective cohort study of CLHIV who had experienced new onset seizure with the outcome of interest being seizure recurrence during follow up. Consent for enrollment was sought from the parents or guardians of CLHIV presenting with new onset seizures to UTH between April 2016 and April 2019. Eligibility criteria included age 1-month to 17 years and no prior history of seizure except febrile seizures.
Study Procedures and Data Collection
At enrollment, clinical and demographic characteristics including HIV disease history, ART exposure (pre- or post-natal), index seizure semiology, history of OIs, cerebrovascular events, head injury and socioeconomic status were obtained. Blood samples were collected for HIV viral loads, CD4 counts, CD4 percent, and serum cryptococcal antigen. If CSF was obtained, extensive cerebrospinal fluid (CSF) studies including polymerase chain reaction (PCR) investigations for common viral OIs as well as GeneXpert and culture for tuberculosis were conducted. Index seizure etiology and death etiology were independently assigned by two reviewers (CB, GB) and adjudicated by a third, if needed.
If brain imaging was requested by the clinician caring for the child, research resources supported the associated cost and studies were obtained during the inpatient stay or shortly after discharge. Sedation was provided by an anesthetist, when needed. CT protocols included: 1.5 mm contiguous axial imaging from the foramen magnum through the vertex for 3D reconstruction with 4 mm oblique axial imaging pre- and post-contrast. AltaVista 300 was used for CT contrast. MRI protocols included sagittal T1, axial T2, T2-FLAIR, diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADC), T1 pre-and post-contrast as well as coronal T2 imaging. When ordered, the MRI contrast agent Magnevist was administered by hand injection. Both CT and MRI findings were interpreted and coded using a REDCap-based data collection program, NeuroInterp (17) adapted for pediatric HIV pathologies, which codes dichotomous and ordinal values for specific, fairly comprehensive anatomic findings with an option for open text, if needed. Findings captured include but are not limited to: the presence of cortical abnormalities, presence of white matter abnormalities, the extent of white matter involvement, deep structure abnormalities, and posterior fossa abnormalities. Other radiographic findings captured include the presence of mass effect, abnormal fluid collections, intracranial bleeds, and calcifications. Brain volume was denoted on a scale of 1 to 8 with 3 being normal (18). Two neuroradiologists (SK, MJP) interpreted both the clinical and research images. They were provided with age and gender and were aware of the patient HIV status and presenting symptoms but were blinded to other acute clinical and outcomes information. The NeuroInterp codebook has been provided as a supplementary appendix.
After discharge to allow for recovery from the acute seizure event, age-dependent neuropsychological assessments were administered: the Malawi Developmental Assessment Tool (MDAT) (19) was administered on children aged 6 years or younger and the Universal Non-Verbal Intelligence Tool (UNIT) and finger tapping tests in the Developmental NEuroPSYchological Assessment (NEPSY) (20) were administered to children age 6 and older. Follow-ups were conducted quarterly to capture recurrent seizures. Study participants were followed for a minimum of one year. Death outcomes were obtained through clinical and hospital records and contact with family members. When family members were interviewed after the death of the participant, a verbal autopsy was administered which included questions regarding recurrent seizures and any seizures around the time of death. The primary outcomes of interest were recurrent seizure and developmental delays with severe impairments, but mortality was an important competing outcome. Risk factors evaluated included those readily ascertained in resource-limited settings. They included World Health Organization (WHO) HIV Clinical Stage I/II versus advanced stage III/IV, Centre for Disease Control (CDC) Stage 1–3, presence of absence of ART on presentation, index seizure severity—brief, multiple, or status epilepticus. Outcomes evaluated include recurrent seizures, neurocognitive impairment, death.
Statistical Analyses
Univariate logistic regressions were completed to evaluate the association between imaging findings and clinical characteristics at enrollment, using dichotomized variables (ART usage, EFV usage, seizure severity, WHO stage, Center for Disease Control (CDC) stage at enrollment). Imaging findings were also associated with outcomes data, including presence of recurrent seizures, neurocognitive impairment, and death. Variables were dichotomized into categorical variables for the purposes of statistical modeling. No adjustments were made for multiple testing. A p-value of <0.05 was considered significant. Analyses were conducted using STATA, (STATA Corporation, College Station, Texas) version 12.
Standard Protocol Approvals, Registrations, and Patient Consents
The University of Rochester’s Institutional Review Board, Michigan State University’s Biomedical Institutional Review Board and the University of Zambia’s Biomedical Research Ethics Committee provided ethical review and approval for the study. Written, informed consent from the parents or the proxy was required. Children were assented before study closure, when appropriate.
Results:
The cohort included 49 children and 39/49 (80%) were neuroimaged. In 6 of the 39 children who had imaging, HIV was diagnosed at the index admission. Children who died during the index admission, many of whom died within a couple of days of enrollment, were less likely to be imaged (OR = 0.17, 95% CI 0.04 – 0.77). Of the 39 children who received neuroimaging: 19 (49%) had a brain MRI, 16 (41%) had a head CT and 4 (10%) had both.1 11/39 died during admission. All others completed neurocognitive assessments during follow up. Among those with imaging, mean age at enrolment was 6.8 years (SD = 4.8). Eighteen (46%) children were female, 28 (72%) had advanced HIV disease (WHO Clinical Stage III or IV) and 18 (46%) were not receiving ART. During follow-up, 13 (33%) experienced at least one seizure recurrence and 15 (38%) died. Demographic and clinical data for the children who underwent neuroimaging are presented in Table 1.
Table 1:
Demographic and Clinical Characteristics of Children Living with HIV Presenting with First Time Seizure, Who Received Imaging (n=39)
| CHARACTERISTIC | |
|---|---|
|
| |
| Demographic | |
|
| |
| Age (years), mean | 6.8 (4.8) |
|
| |
| Female Sex (n, %) | 18 (46) |
|
| |
| Clinical | |
|
| |
| History of opportunistic infection, n (%) | 11 (28) |
|
| |
| Pre-existing CNS insult2, n (%) | 5 (13) |
|
| |
| Index Seizure Severity, n (%) | |
|
| |
| Brief, single | 10 (26) |
|
| |
| Multiple, prolonged | 15 (38) |
|
| |
| Status Epilepticus | 14 (36) |
|
| |
| Clinical WHO Stage, n (%) | |
| WHO Stage I/II | 11 (28) |
| WHO Stage III/IV | 28 (72) |
|
| |
| Admitted on cART, n (%) | 21 (54) |
| EFV use (n=21, %) | 7 (33) |
|
| |
| CDC HIV Disease Category, n (%) (n = 30) | |
| Stage 1 | 8 (27) |
| Stage 2 | 7 (23) |
| Stage 3 | 15 (50) |
|
| |
| Seizure etiology, n (%) | |
| CNS OI | 22 (56) |
| Toxic/Metabolic | 5 (13) |
| TBI (all non-accidental trauma) | 2 (5) |
| CVA, Old infarct | 2 (5) |
| CVA, Acute/subacute infarct | 3 (8) |
| Other3 | 3 (8) |
| Unknown, no cause identified | 2 (5) |
Pre-enrollment history of traumatic brain injury, severe malaria, stroke, meningitis/encephalitis
One each-febrile seizure, neurocysticercosis, sinus infection with para-meningeal foci
Structural abnormalities were identified on brain imaging in 33 (85%) children--26 (67%) exhibited focal abnormalities, 19 (49%) had diffuse cerebral atrophy, 15 (38%) had subcortical white matter abnormalities and 8 (21%) had leptomeningeal enhancement. More than one finding was possible per patient. Specific imaging findings are delineated in Table 2. Illustrative images are presented in Figure 1.
Table 2:
Neuroimaging Findings in Children Living with HIV Presenting with New onset seizure4
| Image Finding | Prevalence, n (%) |
|---|---|
|
| |
| Brain Volume | |
| Atrophic | 19 (49) |
| Normal | 17 (44) |
| Edematous5 | 3 (7) |
|
| |
| Focal abnormality | 26 (67) |
|
| |
| Subcortical white matter abnormality | 15 (38) |
|
| |
| Cortical abnormality | 10 (26) |
|
| |
| Intracerebral hemorrhage | 1 (2.5) |
|
| |
| Subdural fluid | 8 (21) |
|
| |
| Vascular event, n (%) | |
| Acute/subacute | 3 (8) |
| Chronic/old | 2 (5) |
|
| |
| Leptomeningeal enhancement | 8 (21) |
|
| |
| Cerebritis | 2 (5) |
Inclusion in one category does not exclude the presence of other findings.
All of the findings were obtained during the index admission.
Figure 1.
Sagittal T1 and axial T2 images of a child with cerebral atrophy (a & b). Axial T2 FLAIR image of a child with right parietal venous infarct (c). Axial CT image of a child with multifocal infarcts (d).
Associations between imaging findings and the acute clinical and long-term outcomes are detailed in Table 3. In terms of clinical characteristics at the time of enrolment, children with advanced HIV disease had higher odds of atrophy by both WHO (OR 7.2 95% CI 1.1 to 48.3) and CDC (OR 8.3 95% CI 1.2 to 59.3) staging. Focal abnormalities were less likely in children receiving ART (OR 0.22 95% CI 0.05 to 1.0), but more common if the ART regimen included those on EFV (OR 10.8 95% CI 1.0 to 117.0) albeit with very wide confidence intervals. Imaging abnormalities were not predictive of recurrent seizures or death, but children with neurocognitive impairment, based upon evaluations completed after recovery from the index seizure, were more likely to have atrophy (OR 8.4 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2 95% CI 0.03 to 0.9).
Table 3:
Imaging Findings—Associations with Enrollment Characteristics and Outcomes
| Image Findings | Enrollment characteristics | |
|---|---|---|
|
| ||
| Atrophy | cART at enrollment | OR 2.1 (95% CI 0.6 to 7.6) |
| EFV use | OR 0.2 (95% CI 0.02 to 1.2) | |
| Seizure z severity (1=single, brief) | ||
| Multiple, prolonged | OR 0.6 (95% CI 0.1 to 3.0) | |
| Status Epilepticus | OR 0.5 (95% CI 0.1 to 2.6) | |
| WHO stage (1= Stage I) | ||
| WHO Stage II | OR 3.0 (95% CI 0.2to 43.7) | |
| WHO Stage III | OR 15.0 (95% CI 0.4 to 576.7) | |
| WHO Stage IV | OR 7.2 (95% CI 1.1 to 48.3) | |
| CDC stage (1=Stage 1) | ||
| Stage 2 | OR 1.2 (95% CI 0.1 to 11.9) | |
| Stage 3 | OR 8.3 (95% CI 1.2 to 59.3) | |
|
| ||
| Focal structural abnormality | cART at enrollment | OR 0.22 (95% CI 0.05 to 1.0) |
| EFV use | OR 10.8 (95% CI 1.0 to 117.0) | |
| Seizure severity (1=single, brief) | ||
| Multiple, prolonged | OR 1.6 (95% CI 0.2 to 13.9) | |
| Status Epilepticus | OR 0.1 (95% CI 0.0 to 0.90) | |
| WHO stage (1=Stage I) | ||
| WHO Stage II | OR 0.3 (95% CI 0.0 to 4.9) | |
| WHO Stage III | OR 0.6 (95% CI 0.0 to 23.1) | |
| WHO Stage IV | OR 0.3 (95% CI 0.0 to 1.9) | |
| CDC stage (1=Stage 1) | ||
| Stage 2 | OR 0.4 (95% CI 0.0 to 4.0) | |
| Stage 3 | OR 0.5 (95% CI 0.1 to 3.4) | |
|
| ||
| Subcortical white matter abnormality | cART at enrollment | OR 0.4 (95% CI 0.1 to 1.5) |
| EFV use | OR 1.0 (95% CI 0.1 to 7.5) | |
| Seizure severity (1=single, brief) | ||
| Multiple, prolonged | OR 2.3 (95%CI 0.4 to 11.5) | |
| Status Epilepticus | OR 0.3 (95% CI 0.0 to 1.8) | |
| WHO stage (1=Stage I) | ||
| WHO Stage II | OR 0.6 (95% CI 0.1 to 6.7) | |
| WHO Stage III | OR 0.3 (95% CI 0.01 to 10.6) | |
| WHO Stage IV | OR 0.6 (95% CI 0.1 to 2.7) | |
| CDC stage (1=Stage 1) | ||
| Stage 2 | OR 0.5 (95% CI 0.03 to 7.1) | |
| Stage 3 | OR 2.0 (95% CI 0.3 to 13.4) | |
|
| ||
| Leptomeningeal enhancement | cART at enrollment | OR 1.2 (95% CI 0.2 to 6.1) |
| EFV use | OR 2.4 (95% CI 0.3 to 22.1) | |
| Seizure severity (1=single, brief) | ||
| Multiple, prolonged | OR 4.5 (95% CI 0.4 to 46.2) | |
| Status Epilepticus | OR 0.7 (95% CI 0.03 to 12.6) | |
| WHO stage (1=Stage I) | ||
| WHO Stage 2 | OR 0.6 (95% CI 0.1 to 6.7) | |
| WHO Stage 3 | OR 0.3 (95% CI 0.0 to 10.6) | |
| WHO Stage 4 | OR 0.1 (95% CI 0.0 to 0.6) | |
| CDC stage (1=Stage 1) | ||
| Stage 2 | OR 0.7 (95% CI 0.1 to 5.9) | |
| Stage 3 | OR 0.1 (95% CI 0.0 to 1.4) | |
|
| ||
| Imaging Finding | Outcomes | |
|
| ||
| Atrophy | Recurrent seizure(s) | OR 1.4 (95% CI 0.4 to 5.2) |
| Neurocognitive impairment | OR 8.4 (95% CI 1.3 to 55.4) | |
| Death | OR 1.4 (95% CI 0.4 to 4.9) | |
|
| ||
| Focal structural abnormality | Recurrent seizure(s) | OR 0.4 (95% CI 0.1 to 1.7) |
| Neurocognitive impairment | OR 0.2 (95% CI 0.03 to 0.90) | |
| Death | OR 1.7 (95% CI 0.4 to 6.8) | |
|
| ||
| Subcortical white matter abnormality | Recurrent seizure(s) | OR 0.4 (95% CI 0.1 to 1.6) |
| Neurocognitive impairment | OR 0.4 (95% CI 0.1 to 2.6) | |
| Death | OR 1.8 (95% CI 0.5 to 6.6) | |
|
| ||
| CVA (any age infarct) | Recurrent seizure(s) | OR 2.0 (95% CI 0.3 to 13.6) |
| Death | OR 0.3 (95% CI 0.03 to 2.4) | |
|
| ||
| Leptomeningeal abnormality | Recurrent seizure(s) | OR 0.3 (95% CI 0.03 to 2.6) |
| Neurocognitive impairment | OR 0.6 (95% CI 0.05 to 6.6) | |
| Death | OR 0.6 (95% CI 0.1 to 3.5) | |
Bolded categories represent results with P value p<0.05.
Discussion
Despite programs for the prevention of vertical HIV transmission, early ART initiation via ‘test and treat’ policies, and widespread availability of ART, most children living with HIV who presented to this tertiary care center in Zambia’s capital city with new onset seizure had advanced HIV disease and 85% had brain abnormalities evident on imaging. This is similar to an earlier cohort of urban Zambian adults (21) which found that 70% of HIV infected adults with new onset seizure had advanced disease and demonstrated similar rates of imaging abnormalities. All of the children in our cohort were born to HIV infected mothers and believed to have acquired HIV via mother-to-child-transmission (MTCT). In this urban pediatric cohort, 33% had at least on subsequent seizure during follow-up. Approximately half (54%) of the cohort was admitted on ART. In those with ART and first-time seizure, focal structural abnormalities were less likely to have been present on imaging, OR 0.22 (95% CI 0.05 to 1.0) suggesting that ART are protective against HIV-mediated focal structural brain injury, usually OIs. There was a surprisingly higher risk of focal abnormalities in those on EFV therapy, which warrants further investigation. We suspect that having the “double hit” of a focal brain lesion plus being on EFV, which lowers the seizure threshold, likely explains this finding. However, as EFV is being removed from ART armamentarium, this issue will become less relevant.
Brain atrophy was associated with advanced HIV disease and predicted severe neurocognitive impairment (OR 8.4 95% CI 1.27 – 55.9). Previous studies on neuroimaging and neurocognitive disabilities in HIV-positive children have identified various imaging abnormalities in children with HIV, with the most consistent finding being that of diffuse brain volume loss (22, 23). Our findings show a significant correlation between presence of brain atrophy and neurocognitive disability. Within the literature, the majority of studies examining neuroimaging in children with HIV included those on ART (6, 22, 24). Our cohort consisted of both ART and non-ART subjects with an approximate 50% split, and there was no statistically significant difference in presence or absence of atrophy in those with or without ART treatment. Multiple studies have shown that presence of ART is associated with milder severity of long-term HAND (HIV-associated neurocognitive disease), and one would expect that within our cohort those who were admitted on ART would be less likely to show neurologic impairment. However, in this urban, mostly impoverished cohort, ART initiation and adherence is not always consistent, with the high likelihood of ART non-adherence. No formal ART adherence assessment was undertaken beyond ascertaining if they were on ART at the time of the index seizure. Therefore, our results should be viewed through that context.
The use of neuroimaging in the setting of seizures and HIV may serve as an adjunct to the standard workup currently in practice in most LMIC, where access to timely imaging studies is often limited. As more centers in LMIC become equipped with imaging technology, staff, and radiologists, imaging will soon be incorporated in the diagnosis and management of both communicable and noncommunicable diseases. Understanding the most common imaging findings in HIV will greatly aid in diagnosis, as well as selection of appropriate treatment and prognosis. Our data indicates that brain imaging is particularly useful in those with HIV and seizure with the vast majority (85%) demonstrating a structural abnormality. Furthermore, 33% of our cohort exhibited at least one subsequent seizure, and although our results did not show a statistically significant association between imaging and subsequent seizure, this association warrants further investigation, with potential to facilitate management decisions such as starting ASM regimen in the appropriate population.
There are a few limitations of our study. This cohort was comprised largely of urban, mostly impoverished children who reside within the vicinity of the hospital, a sample that may not be representative of all children living with HIV who experience new onset seizure in Zambia. A disproportionate number of our cohort had advanced HIV disease (72% with WHO stage II/III), which may suggest that neuroimaging and neurocognitive outcomes of our study may have contained an element of selection bias. However, within our larger work (10) which included children from more routine, primary care settings without access to neuroimaging we found similar levels of severe HIV disease suggesting that most children presenting with HIV and new onset seizure will have advanced disease. In the overall cohort of 49 children, only 39 underwent imaging. Precise reasons for non-imaging could not be captured as the decision to image (or not) was determined by the clinicians caring for the child. The research study enrolment did not mandate imaging but simply provided resources to support imaging if the clinicians requested it. Nonetheless, our data suggests that early demise was one driving factor (Table 4). Imaging facilities at UTH are all located on the adult hospital campus so imaging necessitates ambulance transport. Many children underwent CT rather than MRI studies and CT is less sensitive for more subtle structural abnormalities, particularly for determining presence of leptomeningeal enhancement or presence or focal cortical abnormalities, which may have underestimated the imaging abnormalities reported.
Table 4:
Comparison of children who did vs. did not undergo imaging (n = 49)
| Characteristics | Among Imaged (n=39) | Among not imaged (n=10) | |
|---|---|---|---|
|
| |||
| Age (mean years) | 6.8 | 7.1 | p=0.87 |
|
| |||
| Seizure severity | p=0.93 | ||
| Brief, single | 10 (26) | 3 (30) | |
| Multiple, prolonged | 15 (38) | 4 (40) | |
| Status epilepticus | 14 (36) | 3 (30) | |
|
| |||
| Death during index admission | 11 (28) | 7 (70) | OR 0.17 (0.04–0.77) |
Conclusion:
Brain imaging abnormalities were a common finding in urban Zambian CLHIV who presented with new onset seizure. Presence of ART was associated with lower likelihood of focal structural abnormalities. The most prevalent imaging abnormality was presence of brain atrophy, which was linked to severe neurocognitive impairment.
Supplementary Material
Funding
This work was funded by the United States National Institute of Health’s (US NIH) National Institute of Neurological Disorders and Stroke R01NS094037 and K23NS117310. The content is solely the responsibility of the authors and does not necessarily represent that of the US NIH.
Footnotes
Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Declarations of Interest: None
Where both CT and MRI were obtained, analysis based upon the MRI data are presented here
Pediatric Neurology https://www.elsevier.com/journals/pediatric-neurology/0887-8994/guide-forauthors as Original Article
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
References
- 1.Haeuser E, Serfes AL, Cork MA, Yang M, Abbastabar H, Abhilash ES, et al. Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018. BMC Med. 2022;20(1):488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Burman RJ, Wilmshurst JM, Gebauer S, Weise L, Walker KG, Donald KA. Seizures in Children with HIV infection in South Africa: A retrospective case control study. Seizure. 2019;65:159–65. [DOI] [PubMed] [Google Scholar]
- 3.UNAIDS. UNAIDS Data 20202020. Available from: https://www.unaids.org/sites/default/files/media_asset/2020_aids-data-book_en.pdf.
- 4.Thompson PM, Jahanshad N. Novel Neuroimaging Methods to Understand How HIV Affects the Brain. Curr HIV/AIDS Rep. 2015;12(2):289–98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Potchen MJ, Kampondeni S, Birbeck GL, Hammond CA, Gonani A, Phiri KS, et al. Magnetic Resonance Imaging in Malawi: Contributions to Clinical Care, Medical Education and Biomedical Research. Malawi Med J. 2011;23(2):60–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ackermann C, Andronikou S, Laughton B, Kidd M, Dobbels E, Innes S, et al. White matter signal abnormalities in children with suspected HIV-related neurologic disease on early combination antiretroviral therapy. Pediatr Infect Dis J. 2014;33(8):e207–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Hoare J, Ransford GL, Phillips N, Amos T, Donald K, Stein DJ. Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents. Metab Brain Dis. 2014;29(2):221–9. [DOI] [PubMed] [Google Scholar]
- 8.George R, Andronikou S, du Plessis J, du Plessis A-M, Van Toorn R, Maydell A. Central nervous system manifestations of HIV infection in children. Pediatr Radiol. 2009;39(6):575–85. [DOI] [PubMed] [Google Scholar]
- 9.G Mariam A, Assefa G. Clinical and neuroimaging profile of HIV-1 encephalopathy in infancy and childhood in a sub-Saharan African country. Ethiop Med J. 2012;50(4):337–47. [PubMed] [Google Scholar]
- 10.Ravishankar M, Dallah I, Mathews M, Bositis CM, Mwenechanya M, Kalungwana-Mambwe L, et al. Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era. Epilepsia Open. 2022;7(2):315–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Siddiqi OK, Elafros MA, Bositis CM, Koralnik IJ, Theodore WH, Okulicz JF, et al. New-onset seizure in HIV-infected adult Zambians: A search for causes and consequences. Neurology. 2017;88(5):477–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Birbeck GL, French JA, Perucca E, Simpson DM, Fraimow H, George JM, et al. Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy. Neurology. 2012;78(2):139–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Birbeck GL. Epilepsy Care in Developing Countries: Part II of II. Epilepsy Curr. 2010;10(5):105–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Wilmshurst JM, Sperling MR Epilepsia. 2023;64:2011–2013. 10.1111/epi.17685. Equity in access to antiseizure medications: Who has the right to decide and what are the consequences of crisis decisions?. Epilepsia 2023;64:2011–3. [DOI] [PubMed] [Google Scholar]
- 15.Le Doare K, Bland R, Newell ML. Neurodevelopment in children born to HIV-infected mothers by infection and treatment status. Pediatrics. 2012;130(5):e1326–44. [DOI] [PubMed] [Google Scholar]
- 16.McHenry MS, McAteer CI, Oyungu E, Deathe AR, Vreeman RC. Interventions for developmental delays in children born to HIV-infected mothers: a systematic review. AIDS Care. 2019;31(3):275–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Potchen MJ, Kampondeni SD, Ibrahim K, Bonner J, Seydel KB, Taylor TE, Birbeck GL. NeuroInterp: a method for facilitating neuroimaging research on cerebral malaria. Neurology. 2013;81(6):585–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Kampondeni SD, Birbeck GL, Seydel KB, Beare NA, Glover SJ, Hammond CA, et al. Noninvasive measures of brain edema predict outcome in pediatric cerebral malaria. Surg Neurol Int. 2018;9:53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Gladstone M, Lancaster GA, Umar E, Nyirenda M, Kayira E, van den Broek NR, Smyth RL. The Malawi Developmental Assessment Tool (MDAT): the creation, validation, and reliability of a tool to assess child development in rural African settings. PLoS Med. 2010;7(5):e1000273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ahmad SA, Warriner EM. Review of the NEPSY: a developmental neuropsychological assessment. Clin Neuropsychol. 2001;15(2):240–9. [DOI] [PubMed] [Google Scholar]
- 21.Potchen MJ, Siddiqi OK, Elafros MA, Koralnik IJ, Theodore WH, Sikazwe I, et al. Neuroimaging abnormalities and seizure recurrence in a prospective cohort study of zambians with human immunodeficiency virus and first seizure. Neurol Int. 2014;6(4):5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Musielak KA, Fine JG. An Updated Systematic Review of Neuroimaging Studies of Children and Adolescents with Perinatally Acquired HIV. J Pediatr Neuropsychol. 2016;2(1):34–49. [Google Scholar]
- 23.Dean O, Buda A, Adams HR, Mwanza-Kabaghe S, Potchen MJ, Mbewe EG, et al. Brain Magnetic Resonance Imaging Findings Associated With Cognitive Impairment in Children and Adolescents With Human Immunodeficiency Virus in Zambia. Pediatr Neurol. 2020;102:28–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Ackermann C, van Toorn R, Andronikou S. Human immunodeficiency virus-related cerebral white matter disease in children. Pediatr Radiol. 2019;49(5):652–62. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.