Authors: Haya Al-Taweel, Andrew Matta, Logan Moore, Marcus Chacon
Categories: Case Report, Acute ischemic stroke, Epstein–Barr virus, Viral infections, Case report
Source: Journal of Medical Case Reports
Authors: Haya Al-Taweel, Andrew Matta, Logan Moore, Marcus Chacon
Ischemic strokes are a leading cause of disability. While traditional risk factors including hypertension and diabetes are common, younger adults may experience strokes from less typical causes, such as infections. This case report presents an acute ischemic stroke in a young adult linked to Epstein–Barr virus infection, emphasizing the potential role of viral infections in stroke risk.
This is a case of a 36-year-old African-American female who presented with sudden-onset right-sided weakness and aphasia. Computed tomography angiography revealed a left middle cerebral artery occlusion; patient received thrombolysis therapy and endovascular thrombectomy. A comprehensive workup excluded other stroke risk factors such as hypercoagulability and cardio-embolism. Blood tests showed an acute Epstein–Barr virus infection, which was treated with supportive care. Patient received rehabilitation and secondary stroke prevention treatment, resulting in full recovery.
This case contributes to growing evidence suggesting that viral infections, including Epstein–Barr virus infection, may be an underrecognized risk factor for ischemic stroke in young adults. It highlights the importance of considering viral causes in the differential diagnosis of ischemic strokes, particularly in patients without traditional stroke risk factors, and suggests that future research should explore viral-induced vascular injury as a potential stroke mechanism.
Stroke is one of the most common adverse health events and causes of long-term disability [1]. Various risk factors exist for acute ischemic stroke (AIS), including modifiable (hypertension, high lipid profile, smoking) and nonmodifiable (age, family history, genetics) [2]. In the younger population of 18–50 years, traditional risk factors such as atherosclerosis contribute to about one-third of ischemic strokes, but other seen etiologies include migraine, pregnancy, the postpartum period, illicit drug use, oral contraceptives, and hypercoagulable states [3]. Owing to the wide variety of potential etiologies, a thorough investigation of possible underlying causes is recommended.
Specifically, various viruses have been linked to an increasing incidence of ischemic strokes. Often, infections are peripheral without central nervous system (CNS) invasion, yet they are found to correlate with increased stroke incidence within days of symptom onset. Some proposed mechanisms leading to this phenomenon include immune activation and associated hypercoagulability or endothelial dysfunction, which may lead to vascular injury. The current literature suggests that viral infections may increase the risk of ischemic stroke in young adults. However, there is currently insufficient data to fully understand these associations and the underlying pathophysiology. In this paper, we present a case report of an acute ischemic stroke in a relatively young adult who was found to have an underlying Epstein–Barr virus (EBV) infection during the stroke workup. This case report aims to highlight the potential association between Epstein–Barr virus infection and acute ischemic stroke in young adults, emphasizing the need for further research into viral-induced vascular injury as a potential stroke mechanism.
A 36-year-old African-American female presented to the emergency department with sudden onset right hemiparesis, numbness, dysarthria, and aphasia, with National Institutes of Health (NIH) stroke scale of 10. Pertinent past medical history was significant for class III obesity and hepatic steatosis with family history of vascular risk factors.
Evaluation in the emergency department with computed tomography (CT) angiogram of the head showed a partially occlusive filling defect in the left middle cerebral artery’s (MCA) superior division of M2 segment, with favorable mismatch findings on CT perfusion (Fig. 1). Patient was appropriately given intravenous tenecteplase (TNK) and referred for emergent endovascular thrombectomy, achieving complete reperfusion (Fig. 2). Symptoms continued to improve throughout the hospitalization. Aspirin and atorvastatin were started for secondary stroke prevention. Comprehensive diagnostic testing was pursued to determine stroke etiology. Antiphospholipid antibodies (aPL) testing showed negative anti-cardiolipin and beta-2-glycoprotein labs. Lupus anticoagulant (LA) was initially abnormally positive and was negative on repeat testing 6 weeks later.Fig. 1A–C. Computed tomography angiogram of the head showing a partially occlusive filling defect in the M2 segment of the left middle cerebral artery’s superior division in the (a) coronal and (b) sagittal views with use of maximum intensity projections technique. (c) Computed tomography perfusion imaging demonstrating elevated time-to-maximum (Tmax) greater than 6 seconds with corresponding decreased cerebral blood flow less than 30% of 7 mL in the superior distribution of the left middle cerebral artery territory, indicative of core infarctFig. 2A–B Conventional cerebral angiography showing M4 segment occlusion of the left middle cerebral artery in sagittal view of (a) pre- and (b) post-thrombectomy, achieving complete reperfusion with thrombolysis in cerebral infarction score of 3
Cardioembolic workup with a transthoracic echocardiogram (TTE) was normal without right atrial enlargement. A transesophageal echocardiogram (TEE) was done, revealing a small patent foramen ovale (PFO), prompting an ultrasound Doppler of the bilateral lower extremities, which were negative for a venous thromboembolism (VTE). Patient was also later referred for an outpatient cardiac catheterization procedure after discharge, which showed no evidence of a PFO. A magnetic resonance (MR) venogram of the abdomen and pelvis was obtained to further evaluate for other sources of VTE, which revealed multiple splenic infarcts but no vein thrombosis. Initially, a cardioembolic process was assumed to be the source of the splenic infarcts, as with the stroke, though no definitive source was found. CT imaging of the chest, abdomen, and pelvis was done to evaluate for malignancy as a source of hypercoagulability, which showed a new finding of pelvic and inguinal lymphadenopathy (LAD), but no masses were identified. Infectious and inflammatory laboratory testing was done, showing leukocytosis (highest of 16.7 K/uL) with lymphocyte predominance that later normalized. Lab testing also revealed marked elevations of inflammatory markers with C-reactive protein (5.9 mg/L; normal 0.0–0.8), erythrocyte sedimentation rate (51 mm/hour; normal 0–20), and ferritin (856 ng/mL; normal 15–200), and a negative urine toxicology screen. Patient also developed a fever (highest of 101.1 F), and empiric antibiotics were administered, later discontinued with evidence of negative blood cultures.
Patient was found to have mild rising transaminitis during the hospital stay, which were initially normal (aspartate aminotransferase (AST): 49 → 102 → 168 → 170; ALT: 47 → 124 → 162 → 177; normal 5–34 U/L; 0–55 U/L, respectively). The atorvastatin initiated during hospitalization was considered the contributor and was discontinued. Hepatology was consulted for further investigation. A right upper quadrant Doppler ultrasound was normal. Hepatology workup revealed a markedly elevated EBV quantitative polymerase chain reaction (PCR) of 20,417 IU/mL (normal no detection). Subsequent testing 6 weeks later with serologies revealed positive EBV immunoglobulin G (IgG) antibody and negative immunoglobulin M (IgM) antibody (initial serologic testing with IgG and IgM was not completed during hospitalization). In addition, an inguinal lymph node biopsy was obtained given findings of pelvic and inguinal LAD. Biopsy revealed EBV-positive lymphoid proliferation, consistent with reactive EBV lymphadenitis. These findings raised the possibility of viral association with a hypercoagulable and thromboembolic state, which could have resulted in ischemic stroke and splenic infarcts. No cerebrospinal fluid (CSF) testing done during hospitalization. Upon discharge, patient received an extended cardiac monitor for 11 days as part of stroke workup, which showed sinus rhythm without atrial fibrillation or flutter. Patient was then discharged and followed in clinic several weeks later and found to be in stable condition with overall improved symptoms and full recovery (Fig. 3).Fig. 3Timeline figure with summary of hospitalization
In our patient, the evidence of EBV-positive lymphoid proliferation raised the question of a potential association between viral infections and AIS, especially given the patient’s young age and absence of other major risk factors for ischemic stroke. Herpesvirus infections are among the pathogens implicated in stroke risk, especially in the pediatric and younger adult population. Some of these viruses contribute to risk of ischemic stroke through the proposed mechanisms of endothelial dysfunction, impaired vascular reactivity, induction of proinflammatory cytokines, and T-cell-mediated inflammatory responses [4]. Of the herpesvirus family, varicella zoster virus (VZV) and herpes simplex virus (HSV) were found in some studies to affect the vessel walls of small and large cerebral arteries directly, leading to vascular injury and brain pathologies associated with ischemic strokes [4, 5]. Although no precise mechanism for EBV has been shown, a number of processes have been proposed. These include activation of platelets and the coagulation cascade, tissue factor exposure, and endothelial damage resulting in disruption of the vascular lining [6, 10]. Concurrently, proinflammatory cytokines such tumor necrosis factor (TNF)-α, interleukin (IL)−1β, and IL-6 are released as a result of immune activation. These cytokines increase the production of tissue factors, inhibit anticoagulant pathways, and enhance endothelial activity [6]. In addition, a transient prothrombotic state can be created through secondary antiphospholipid antibody (APS) syndrome by inducing the production of antiphospholipid antibodies, likely as a result of molecular mimicry [7]. It is thought that EBV infects B lymphocytes, leading to polyclonal B-cell activation and autoantibody production where EBV antigens resemble host phospholipid-binding proteins [7, 8]. While still theoretical, these pathways collectively offer a biologically plausible framework that connects EBV infection to ischemic stroke and hypercoagulability.
In the literature, there have only been a handful of case reports that described a link between EBV and strokes in the younger population, and no major trials have investigated this association further. For instance, a case report of an EBV-induced ischemic stroke in a Caucasian 2-year-old female showed sampled cerebrospinal fluid with positive EBV PCR with increased IL-6 and IL-1β [8]. Another case report highlighted EBV’s ability to compromise the brain vasculature as it detailed an immunocompetent adult who developed encephalitis leading to brainstem hemorrhage through immune-mediated inflammation in the brainstem vessels [9]. Although this case does not report EBV-associated ischemic stroke, it signifies the ability of EBV-induced inflammatory response to contribute to intracranial disease and increased stroke risk. Infectious mononucleosis, a disease caused by EBV, was also reported to be complicated by an ischemic stroke in a 49-year-old male in a case report [10]. Similarly, the novel coronavirus was shown to be linked with large vessel strokes likely owing to severe neuro-inflammatory stress response related to the infection [11]. Beyond these cases described, a limited number of additional cases have also linked EBV to cerebrovascular events and neurological disease (Table 1).Table 1Reported cases of EBV-related neurological involvement and cerebral ischemic strokesAuthor/yearPatient demographicsStroke typeEBV diagnosis (method)Proposed mechanismGatto et al., 2021 [8]2-year-old Caucasian femaleIschemic strokeCSF PCRCytokine-mediated vascular injuryHuang et al., 2021 [9]59-year-old maleHemorrhagic strokeSerum PCR, CSF next-generation sequencing (NGS)Immune-mediated vascular inflammationChen et al., 2015 [10]49-year-old maleIschemic strokeSerum anti-EBV nuclear antigen, anti-EBV IgGHypercoagulability, vasculopathyRios et al., 2020 [13]31-year-old maleIschemic strokeSerum anti-EBV IgM and IgGProthrombotic state with transient antiphospholipid antibodiesMolka et al., 2025 [14]3.5-year-old femaleIschemic strokeSerum anti-EBV IgM and IgGImmune-mediated vascular inflammationLin et al., 2025 [15]10-year-old femaleIschemic strokeSerum anti-EBV IgGCytokine-mediated vascular injury
Overall, EBV-associated cerebrovascular events appear to be exceedingly rare, with only isolated cases documented to date. This underlines the importance of individual reports such as ours, while also highlighting the challenges in drawing definitive causal conclusions. Even though the exact mechanisms are still unclear, there is growing evidence that acute viral infections can temporarily increase the risk of ischemic stroke [12]. Influenza, coronavirus disease 19 (COVID-19), herpesviruses, and hepatitis C are among the acute and chronic viral infections that can make people more susceptible to stroke by impacting vascular function, triggering inflammation, and promoting thrombosis [12]. In addition, systemic effects of viral illness, such as alterations in coagulation pathways, blood pressure regulation, and lipid metabolism can create a permissive environment for cerebrovascular events.
In our patient, the relationship between the infection and stroke was not initially evident. On review, the combination of a transiently positive lupus anticoagulant and subsequently confirmed active EBV infection raised the possibility that EBV may have induced a temporary prothrombotic state, contributing to the development of both ischemic stroke and splenic infarcts. Nevertheless, although the temporal association is noteworthy, a causal relationship cannot be definitively determined, which represents a key limitation, and the findings should therefore be interpreted as preliminary and hypothesis-generating. Another limitation to note is the absence of serologic testing at the time of presentation, which prevents differentiation between a primary EBV infection and viral reactivation. Nonetheless, because the infection was considered active on the basis of laboratory findings and clinical infectious signs, it remains plausible that EBV could have been associated with the proposed stroke mechanism. EBV serology and/or PCR testing may be reasonable to consider in young patients presenting with stroke in the absence of conventional vascular risk factors, especially when accompanied by other signs of infection. Although such testing is not a part of the standard stroke evaluation, it may help identify otherwise unrecognized viral triggers in select cases. Acknowledging the limited available data on EBV-related ischemic strokes, additional studies are required to better delineate the underlying mechanisms and clarify the strength of this potential association.
This case report highlights the potential role of EBV and other viral infections in increasing the risk of acute ischemic stroke, particularly among young adults. In young patients without known risk factors and with presence of infectious signs, a viral etiology should be considered as part of the diagnostic workup. While several mechanisms have been proposed—such as immune-mediated vascular damage or increased coagulability—there is currently a lack of sufficient clinical data to definitively establish this association. This case emphasizes the need for further research to better understand the link between viral infections and ischemic stroke risk, a connection that could have important implications for clinical management.