HSV-2 Encephalitis: A Rare Stroke Culprit You Need to Know About
"Unmasking the unexpected link between herpes simplex virus-2 and ischemic stroke, and why prompt diagnosis is crucial."
Herpes simplex virus-2 (HSV-2) encephalitis (HSE) is an uncommon condition in adults. Typically, HSV-2 infections of the central nervous system (CNS) have been linked to hemorrhagic or ischemic strokes, or just ischemic strokes, but these occurrences are rare.
Here, we report a unique case: HSV-2 encephalitis presenting as an ischemic stroke initially, followed by a transient ischemic attack (TIA), all without any bleeding in the brain. This unusual presentation underscores the complexities of diagnosing neurological conditions.
The patient, a 68-year-old Hispanic woman with a history of systemic lupus erythematosus on immunosuppressants, hypertension, depression, and migraines, initially complained of a three-week-long mild headache. This was followed by acute left-sided numbness, occurring alongside acute kidney injury and a urinary tract infection. She also experienced brief episodes of visual and auditory hallucinations at night, which doctors initially attributed to metabolic imbalances due to her kidney issues and infection. Importantly, she showed no signs of encephalopathy during her hospital stay and had a non-focal neurological examination upon admission.
Rare but Serious Complications
A 2016 review reported that stroke-like presentations occurred in 25% of the reviewed cases of HSV encephalitis, while HSV encephalitis in a typical location occurred in 10%. Evidence of cerebral vasculitis appeared in 63% of cases and was confined to large vessels. Reported mortality differed by complication: 21% for hemorrhage and 0% for infarction in that review. Other reports describe recurrent ischemic strokes followed by bilateral intracerebral hemorrhages and persistent neurologic sequelae among survivors.
Recognizing an Unusual Stroke Cause
A stroke-journal report concludes that ischemic stroke, although infrequent, can complicate herpes simplex meningitis or encephalitis. It recommends including HSV central nervous system infection in the differential diagnosis, particularly for young patients with ischemic stroke of unknown etiology. The available material emphasizes recognition of this infectious cause rather than presenting a definitive diagnostic method. A related literature record describes the report's objective as documenting an ischemic stroke after HSV-2 encephalitis and reviewing prior cases.
An Emerging Clinical Link
The relationship between HSV encephalitis and ischemic stroke has been developed through case reports and literature reviews rather than a single defining discovery. These reports have drawn attention to the possibility that an encephalitic illness may also present with stroke-like features. The historical record remains limited, so the timing and importance of individual milestones should be interpreted cautiously.
The Diagnostic Journey: Uncovering HSV-2's Role in Stroke
Initial MRI scans revealed three distinct areas of acute ischemia, affecting the right anterior inferior insula and two regions in the right frontal cortex. Further investigations, including MRA of the head and neck, transesophageal echocardiogram, 24-hour Holter monitoring, and a hypercoagulable panel, did not reveal any vascular abnormalities or other common stroke causes.
- Significantly elevated protein levels (255 mg/dl).
- Normal glucose levels (45 mg/dl).
- Elevated white blood cell count (649 mm³ with 100% lymphocytes).
- Presence of red blood cells (91/mm³).
- Positive PCR for HSV type 2; negative for HSV type 1.
- Negative results for EBV, VZV, CMV, VDRL, and TB in CSF.
Recurrent Stroke With HSV-2 Vasculitis
A 2021 case report described HSV-2 encephalitis in a patient with antisynthetase syndrome receiving potent combined immunosuppressive treatment. The course was complicated by central nervous system vasculitis and multiple recurrent ischemic strokes. A separate report, dated July 27, 2026, likewise described severe HSV-2 encephalitis with vasculitis and recurrent strokes in a patient with antisynthetase syndrome. Together, these reports highlight recurrent ischemia as a documented complication in an immunosuppressed clinical setting.
Limits of the Evidence
The available evidence is largely based on individual case reports and small literature reviews, which limits how broadly their findings can be applied. Similar neurologic presentations may not establish HSV-2 as the cause without adequate clinical evaluation. The rarity of the complication also makes precise estimates of risk and treatment effectiveness uncertain.
A Distinct but Overlapping Presentation
HSV-2 encephalitis can overlap clinically with stroke because both may produce focal neurologic deficits and acute deterioration. At the same time, an encephalitic process may involve vasculitis and recurrent ischemic events rather than a single isolated infarct. Direct comparisons with other stroke causes cannot be made reliably from the supplied source material, so the comparison remains descriptive rather than quantitative.
Key Takeaways: Why Early Detection Matters
While most ischemic strokes are managed with antiplatelets (or anticoagulants) and vascular risk factor management, this case highlights the critical need to consider less common etiologies that require alternative treatment approaches. A high degree of suspicion is essential.
Keeping HSV-2 in the Differential
The central clinical lesson from the cited stroke-journal report is that HSV-2 encephalitis can be complicated by ischemic stroke. Its authors described a patient with this complication and reviewed the available literature. This supports considering HSV central nervous system infection when a stroke occurs in an unusual clinical context, particularly when the presentation does not fit common causes.
Earlier Recognition and Better Treatment
A review in the Journal of Neuroinfectious Diseases identifies pathogenesis, diagnosis, treatment, prognosis, and current research trends as important areas in herpes encephalitis. The supplied article on HSV-2 encephalitis similarly emphasizes considering infections in stroke etiology and the need for timely diagnosis and treatment. Future work can therefore focus on recognizing stroke presentations of HSV infection earlier and clarifying how best to manage them. The available sources do not establish a specific new therapy or diagnostic technology.
Misleading Initial Presentations
A reported case of cerebral HSV-2 vasculitis was initially masked by a thalamic hemorrhage. The patient subsequently developed an encephalitic syndrome and multifocal ischemic stroke. This sequence illustrates how changing neurologic findings can obscure the underlying infectious and vascular process. It also underscores the challenge of maintaining a broad differential diagnosis when hemorrhagic and ischemic features occur in the same illness.
Potential for Lasting Disability
The cited case report describes an ischemic stroke as a complication of HSV-2 encephalitis. This combination can add an abrupt focal neurologic injury to an already serious encephalitic illness. The source's purpose was to document the complication and review the literature, rather than quantify long-term outcomes. Its practical human impact is the possibility of substantial neurologic illness when infection and stroke occur together.
In this particular case, the lumbar puncture and CSF analysis were pivotal in diagnosing HSV-2-related stroke, prompting the initiation of antiviral treatment. This underscores the importance of performing a lumbar puncture in cases of ischemic stroke with unclear etiology, especially when CNS infection is suspected.
The patient's history of chronic immunosuppression likely predisposed her to an indolent viral infection. While the exact mechanism of ischemic stroke in HSV-2 infection remains unknown, it is hypothesized that, similar to varicella-zoster virus vasculopathy, HSV-2 can cause viral invasion and vessel wall inflammation, potentially leading to vessel occlusion or secondary thrombosis. Further research is needed to confirm this hypothesis.