Undiagnosed 33-Year-Old Filipino Male HIV Case Presenting Initially as Stroke in the Young: A Case Report

Introduction

The central nervous system (CNS) is the first part of the body to be affected by the human immunodeficiency virus (HIV). Any neurological manifestations may be brought on by opportunistic infections, neoplasia, the immune and metabolic response to HIV, iatrogenic causes, co-risk factors, or they may be caused by HIV itself.[1,2]

In a clinical series, up to 70% of HIV-infected patients eventually develop neurological manifestations.[3] Stroke-like clinical presentation is unusual, occurring in 1% of cases, with cerebral hemorrhage constituting 32% of the cases. Only 4% to 29% present as ischemic infarction.[4]

The condition known as cerebral small vessel disease (CSVD) may be a major cause of HIV-associated neurocognitive disorders. It is believed that one of the primary causes of vascular cognitive impairment is CSVD, which refers to a series of disease processes that damage the tiny blood arteries of the brain. CSVD has a variety of effects on the brain, including ischemia and hemorrhagic damage.[5,6] In addition to the known atherosclerotic mechanisms affecting the older population, older HIV+ individuals are also exposed to HIV proteins, host immune activation products and combination antiretroviral therapy (cART), which can affect the neurovascular unit (endothelial cells, pericytes, astrocytes, neurons and microglia). Interestingly, CSVD has been associated with markers secreted by myeloid cells.[7,8]

Case Presentation

A 33-year-old male presented with recurrent transient focal neurologic deficits. In January 2022, he developed sudden-onset dysarthria associated with left-sided body weakness and facial asymmetry, which completely resolved. Four months later, he experienced a similar episode with spontaneous resolution within 15-30 minutes. One month thereafter, he again developed acute-onset numbness and weakness of the left upper and lower extremities with associated left facial asymmetry; symptoms resolved approximately one hour after onset.

Within the same month, he was noted to have facial rash, right foot dragging and right facial asymmetry. In June 2022, he developed acute-onset numbness of the left upper and lower extremities, inability to grasp with the left hand, left facial weakness and dysarthria lasting approximately one hour. This episode was accompanied by persistent hiccups and dysphagia to liquids. Owing to the persistence of symptoms, the patient sought medical consultation and was subsequently admitted.

The patient had no comorbidities. He was an 18-pack years of smoking, occasional alcoholic beverage drinker and denies illicit drug use. The patient’s mother had diabetes mellitus and hyperthyroidism, hypertension in both parents and stroke in both maternal grandparents. He had multiple sexual partners of both genders, approximately 10 sexual partners, protected and unprotected. Unintentional weight loss was noted.

Upon hospitalization, vital signs were normal. The patient was conscious, coherent and not in cardiorespiratory distress with a malar rash on the face (Figure 1), oral thrush and mouth ulcers. Neurological examination was unremarkable. The patient has an ABCD score of 3 composed of unilateral weakness: 2 and a duration of 10-59 minutes: 1.

Figure 1. Malar rash on the face

The patient was assessed as having a recurrent transient ischemic attack, an ABCD score of 3, ruling out autoimmune disorder, probably systemic lupus erythematosus, and to consider as an immunocompromised host. He was immediately given Aspirin 80 mg/tab one tablet once a day and was referred to the infectious and rheumatology services.

Laboratories and ancillaries were done and showed normal results. Neuroimaging of cranial magnetic resonance imaging with angiography and contrast enhancement was done (Figure 2), which showed progressive patchy non-enhancing signal abnormalities involving the basal ganglia and corona radiata bilaterally. These demonstrate mild restricted diffusion on diffusion-weighted imaging, consistent with some degree of ischemia. Magnetic arteriogram of the brain demonstrates multiple contour irregularities involving the right middle cerebral artery, the posterior cerebral arteries and the right vertebral artery. There was right vertebral artery congenital hypoplasia versus severe atherosclerotic disease.

Figure 2: Cranial magnetic resonance imaging with angiography and contrast-enhancement

The ANA assay was positive with a nucleolar pattern and anti-dsDNA was 69.66 which was negative. The ANA assay was not significantly high, hence systemic lupus erythematosus was ruled out. The transesophageal echocardiogram showed an ejection fraction of 64% with good wall motion. There was no intra-arterial and intraventricular shunt and intracardiac thrombus. The anti-Smith and anti-RNP were weakly positive, which was unlikely to be a connective tissue disease.

The cerebrospinal fluid (CSF) analysis and CSF bacterial and viral panel assays were unremarkable. The Enzyme-Linked Immunosorbent Assay (ELISA) screening test for HIV showed a positive result and the CD4 count was 33. Antiretroviral therapy and AIDS prophylaxis were started. He was discharged improved and on regular antiretroviral therapy.

Discussion

In HIV patients, cerebrovascular illness is prevalent, occurring in as many as 1.9% of people.[9] In people with acquired immunodeficiency, in particular, there have been reports of a rise in the syndrome (AIDS). The stroke risk is for both ischemic and hemorrhagic types, including more strokes occurring from ischemic causes. The pathology is unclear how HIV affects the risk of ischemic stroke, with several hypothesized processes, including cardio embolism, Highly Active Antiretroviral Therapy (HAART) related coagulopathy, opportunistic infections, primary vasculitis of the arteries and accelerated atherosclerosis of the nervous system in the brain.[10]

Neurological complications of HIV infection are common since HIV can cross the blood-brain barrier early, thus entering the nervous system at all levels of the neuraxis (brain, meninges, spinal cord, nerve and muscle). The presence of vasculopathy and extent of cerebral infarction were not associated with viral load.[9,10]

CSVD in HIV infected individuals is likely a multifactorial disease where there is convergence of traditional vascular risk factors and HIV-mediated chronic inflammation. In this patient, conventional vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and advanced age were absent, with cigarette smoking as the only traditional risk factor identified. The presence of advanced HIV infection with severe immunosuppression (CD4 count of 33) suggests that HIV-mediated inflammation and vasculopathy likely played a significant role in the development of recurrent ischemic events.

HIV infection is associated with persistent immune activation and systemic inflammation, resulting in endothelial dysfunction, HIV-associated vasculopathy and a prothrombotic state that predisposes to cerebral small vessel ischemia, even in the absence of traditional vascular risk factors. In the setting of advanced immunosuppression, as demonstrated in this case, these pathogenic mechanisms may lead to multifocal arterial irregularities and recurrent transient ischemic attacks involving predominantly penetrating cerebral vessels.[11]

CSVD and HIV infection may also have a synergistic effect on brain function and increase the risk of cognitive impairment in this vulnerable population. In the cART era, individuals living with HIV infection have significantly increased life expectancy; however, quality of life may be reduced with significant rates of CSVD.[12]

In conclusion, this case report suggests that cerebral infarcts in HIV-infected patients are not common in the absence of cerebral opportunistic infection, lymphoma, non-HIV infection, or embolic sources. A confirmed co-existence of HIV-associated vasculopathy and CSVD may present with a stroke or transient ischemic attack, potentially treatable causes. These results suggest that optimizing vascular health in people living with HIV who are on stable antiretroviral therapy and virologically suppressed may be a useful route to improve brain health and protect against decline.

Ethical Considerations

This study complies with the ethical principles set out in relevant guidelines as specified in the certificate of agreement and compliance in this research, as well as the National Ethical Guidelines 2017 edition.

Informed Consent Process

A clearly written informed consent form was obtained, understood and signed by the legally acceptable representative, securing their consent for presentation, publication of the case, taking of photographs and videos, including other diagnostic results and images. The primary investigator, not the primary physician of the patient, obtained consent.

Vulnerability

The subject in this research was a patient of the secondary investigator of this research. Nevertheless, vulnerability was reduced with the primary investigator obtaining consent from the legally acceptable representative. The decision maker should be a legally acceptable representative, should be of sound mind, have appropriate judgment and without hindrance to any cognitive skills which may be possible in cases with recurrent ischemic attack or any seizure disorders. Any first-degree relative or spouse, in this case, may act as the legally acceptable representative for participation in this case report.

Privacy and Confidentiality

The patient’s confidentiality is protected by removing patient identifiers in the case report, with full compliance to the Data Privacy Act and its implementing rules and regulations. The raw data collected in this study will be stored up to five years only.

Acknowledgements

None

Authors’ Contributions

Conceptualization - SKI and JAC and MRMB; Data curation - SKI and JAC and MRMB; Formal analysis - Not applicable; Funding acquisition - Not applicable; Investigation - SKI and JAC and MRMB; Methodology - Not applicable; Project administration - Not applicable; Resources - SKI and JAC and MRMB; Software - Not applicable; Supervision - SKI and JAC and MRMB; Validation - SKI and JAC and MRMB; Visualization - SKI and JAC and MRMB; Roles/Writing - original draft - SKI and JAC and MRMB; Writing - review and editing SKI and JAC and MRMB. All the authors have read and approved the manuscript.

SKI - Samantha Karla Inoncillo, JAC - Joseree Ann Catindig, MRMB - Ma. Rhona M Bergantin

Funding

None

Data Availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declaration of Generative AI and AI-assisted Technologies

None

Declaration of Interests

None of the authors has any conflict of interest to disclose. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Consent for Publication

The consent for publication of collected data is secured as part of informed consent of the participant. It was reassured to the participant that all data will be anonymized and that privacy will be upheld.