Epstein-Barr virus encephalitis in an immunocompetent elderly patient: A case report

Abstract

We report a case of severe Epstein-Barr virus (EBV) encephalitis in a 79-year-old immunocompetent patient. The patient initially presented without overt infectious manifestations, complaining solely of weakness in both lower limbs for one week. Physical examination revealed tremors in the upper limbs and tachypnea. Symptoms progressed rapidly after admission, with the subsequent development of headache and fever. Based on the clinical presentation, viral encephalitis was suspected. Cerebrospinal fluid analysis via next-generation sequencing (NGS) confirmed the diagnosis of EBV encephalitis. Despite treatment with ganciclovir, the patient's condition deteriorated, leading to respiratory arrest that required tracheal intubation and mechanical ventilation. The patient’s status improved significantly following a combination therapy of intravenous immunoglobulin and steroid pulse therapy, ultimately achieving clinical recovery and successful discharge. This case highlights that EBV encephalitis can occur in immunocompetent elderly individuals, and early-stage symptoms may be atypical. When conventional antiviral therapy proves ineffective, immunoglobulins and corticosteroids should be considered as therapeutic options.

Introduction

Epstein-Barr virus (EBV) is a common human herpes virus belonging to the Herpesvirus family, premarily affecting the lympoid system [1]. In adults, risk factors for EBV infection include organ transplantation, human immunodeficiency virus infection, and the use of immunosuppressant drugs, etc. The central nervous system can be involved, manifesting as EBV encephalitis [2], [3], [4]. EBV encephalitis often leads to significant neurological symptoms with variable severity, and outcomes can range from complete recovery to death. Herein, we report a case of EBV encephalitis in an immunocompetent elderly patient who presented with atypical early manifestations and experienced rapid, severe progression, yet ultimately achieved a favorable outcome .

Case presentation (Table 1)

Table 1.

Therapeutic timeline.

Day of admission	Interventions	CSF findings	Clinical status
1	Admission to hospital, correction of the internal environment disturbances, symptomatic treatment	-	Bilateral lower limb weakness for 1 week, bilateral upper limb tremors 2 days, PE: tremors in both upper limbs, mild tachypnea
4	-	-	transient headache
7	Antiviral therapy	Pressure: 226 mmH2O, Leukocyte: 71 × 106/L, Protein: 968 mg/L	Fever, worsening tremors in upper limbs and tachypnea
10	IVIG pulse therapy	-	Cheyne-Stokes respiration, bilateral Babinski signs positive
11	Endotracheal intubation, transfered to ICU for mechanical ventilation, continued antiviral and IVIG therapy	-	Respiratory arrest
16	Completed 5-day IVIG course	Pressure: 195 mmH₂O, Leukocyte: 1 × 10⁶/L, Protein: 850 mg/L, NGS: EBV (289 sequences)	Mechanical ventilation
18	Extubated, continued antiviral therapy	-	Tachypneic pontaneous breathing, yet maintained normal oxygen saturation levels
20	Transferred back to general ward, continued antiviral therapy	-	Mild euphoria, reduced sleep, amnesia for the ICU period
29	Initiated 5-day intravenous, methylprednisolone (500 mg), followed by a tapering dose	Pressure: 200 mmH2O, Leukocyte: 49 × 109/L, Protein: 774 mg/L, NGS: EBV (169 sequences)	Irritability, hallucinations
43	Oral steroids	Pressure: 195 mmH2O, Leukocyte: 20 × 106/L, Protein: 317 mg/L, NGS: EBV (29 sequences)	Marked clinical improvement
48	Discharged from hospital, continued oral steroids	-	Mild hallucinations and tachypnea persisted
2 months after discharge	Glucocorticoid therapy discontinued	-	Complete resolution of hallucinations and tachypnea, exertional intolerance
6 months after discharge			Could participate in mountain hiking
10 months after discharge	-	-	Fully recovery

Abbreviations: PE, physical examination; IVIG, Intravenous immunoglobulin; NGS, next-generation sequencing; EBV, Epstein-Barr virus.

A 79-year-old male patient was admitted to the Neurology Department of Anhui No.2 Provincial People’s Hospital due to bilateral lower limb weakness for one week, followed by bilateral upper limb tremors for two days. He was afebrile. One week before the onset of symptoms, he had experienced cough and diarrhea. The patient's past medical history includes hypertension and benign prostatic hyperplasia.

Physical examination demonstrated tremors in both upper limbs, particularly during voluntary movement or posture maintenance. Muscle strength was normal. Additionally, mild tachypnea was observed, which could not be explained by the patient's current cardiopulmonary status. No other significant abnormalities were noted during the physical examination.

The patient’s clinical features were non-special, giving the impression that they may be caused by a systemic disease. Laboratory tests revealed hyponatremia and hypokalemia. After comprehensive evaluation of the patient’s history, physical examination, and auxiliary test results, drug-related, metabolic, psychogenic, and peripheral neuropathic causes were sequentially ruled out. The white blood cell count and C-reactive protein levels were within normal ranges upon hospital admission. Although electrolyte imbalances were appropriately corrected, the patient’s symptoms failed to resolve following treatment.

The patient’s hospital course was marked by a transient headache on day 4, which resolved without intervention. On day 7, he developed fever accompanied by worsening bilateral upper limb tremors and tachypnea. A repeat complete blood count revealed a monocyte count of 0.94 × 10⁹/L and lymphocyte count of 1.08 × 10⁹/L. Subsequent lumbar puncture demonstrated a cerebrospinal fluid (CSF) opening pressure of 226 mmH2O, a leukocyte count of 71 × 10⁶/L, and a protein level of 968 mg/L. Based on these findings, viral encephalitis was suspected, and intravenous ganciclovir was initiated Autoimmune encephalitis and paraneoplastic syndrome antibody panels were sent and later returned negative. No significant abnormalities were detected on non-contrast MRI of the brain (including T1, T2, FLAIR, and DWI sequences) or on post-contrast imagin By day 10, his respiratory pattern evolved into Cheyne-Stokes respiration, and neurological examination revealed positive bilateral Babinski signs. Repeat blood tests showed normalized white blood cell count. Intravenous immunoglobulin (IVIG) pulse therapy was added to the treatment regimen. Despite these interventions, the patient deteriorated rapidly, progressing to respiratory arrest by the following morning. After endotracheal intubation, the patient was transferred to the intensive care unit (ICU).

The patient experienced loss of consciousness following respiratory arrest. After admission to the ICU, mechanical ventilation was initiated with subsequent improvement in gas exchange and regained consciousness. Antiviral therapy combined with IVIG pulse therapy was continued. Following completion of 5-day IVIG therapy, a repeat lumbar puncture revealed a CSF pressure of 195 mmH₂O, a leukocyte count of 1 × 10⁶/L, and a protein level of 850 mg/L. CSF next-generation sequencing (NGS) detected EBV with a viral load of 289 sequences. On day 18, the patient continued to exhibit tachypneic spontaneous breathing, yet maintained normal oxygen saturation levels. After 9 consecutive days of intensive care management with stabilized condition, the patient was transferred back to the general ward.

After returning to the general ward, the patient exhibited mild euphoria and reduced sleep, with no recall of the intensive care period. On day 29, his clinical course was marked by the emergence of irritability and hallucinations. A repeat contrast-enhanced MRI of the brain (T1, T2, FLAIR) showed no interval change. Another lumbar puncture revealed a CSF pressure of 200 mmH2O, 49 × 10⁶/L white blood cells, a CSF protein level of 774 mg/L, and an EBV load of 169 sequences via CSF NGS. Given the fluctuating clinical condition, the patient received 500 mg methylprednisolone intravenous pulse therapy for 5 days followed by gradual tapering of corticosteroids. Clinical symptoms gradually improved. By day 43, lumbar puncture confirmed a response to therapy, showing a CSF cell count of 20 × 10⁶/L, normalization of protein, and a decreased EBV load (29 sequence counts on NGS). The patient achieved sustained stability and was successfully discharged after a 48-day hospitalization.

Upon discharge, mild hallucinations and shortness of breath were still noted. During the subsequent outpatient follow-up, his condition improved steadily. The hallucinations and dyspnea at rest had completely resolved within two months, while exertional intolerance remained. A significant milestone was observed at six months, when the patient could participate in mountain hiking. He achieved a full recovery to his pre-morbid health status by the tenth month after discharge.

Discussion

We report a case of EBV encephalitis occurring in an immunocompetent elderly. According to previous case reports, EBV encephalitis has been documented across all age groups, ranging from 8-month-old infants to 82-year-old elderly individuals [2], [5]. While EBV encephalitis typically occurs in immunocompromised or immunodeficient patients, it is rarely observed in immunocompetent populations. In recent years, however, there have been increasing reports of EBV encephalitis diagnoses in immunocompetent individuals, though the overall number of cases remains limited. The patient presented in this case report represents another instance of an immunocompetent elderly individual with this condition.

The diagnosis of EBV encephalitis in this patient was established through NGS detection of EBV in CSF. During the disease course, the patient presented with headache, fever, and bilateral positive pathological signs, accompanied by corresponding CSF biochemical changes. These clinical manifestations and laboratory findings collectively suggested viral encephalitis. Subsequent identification of EBV in CSF via NGS confirmed the diagnosis of EBV encephalitis. Although the initial viral load detected was not particularly high, this is likely attributable to the timing of the first CSF EBV test after IVIG therapy, when the patient had already passed the peak severity of the illness. Notably, subsequent EBV loads paralleled clinical symptom progression, and repeated CSF-NGS examinations excluded other pathogens.

It should be acknowledged that our diagnostic process had limitations. First, EBV PCR testing was not performed during the diagnostic workup; its inclusion would have provided additional supportive evidence for the diagnosis. Additionally, repeated brain MRI scans (including non-contrast and contrast-enhanced sequences, and DWI upon admission) failed to reveal parenchymal abnormalities. Studies report that the rate of abnormal findings on brain MRI in patients with EBV encephalitis is approximately 60%, with diffusion restriction observed in about 24.4% of cases [6]. Although our MRI studies were negative, brain PET or SPECT might have provided supplementary information, potentially revealing focal metabolic abnormalities. These examinations were not performed as they are not routinely available at our institution.

The most prominent clinical manifestation in this case was abnormal respiration. In patients with various types of viral encephalitis, headache and fever are early and common clinical symptoms [2], [4]. Although this patient also developed headaches and fever during the disease course, the most notable clinical manifestation—first to appear and persisting throughout the entire clinical progression—was respiratory abnormalities. These respiratory changes could not be explained by the patient's existing cardiopulmonary function and was thus considered to be of central origin. We speculate that it may have resulted from early involvement of the brainstem respiratory centers. There have been reports of medullary, pontine, and midbrain involvement in EBV encephalitis, with brainstem lesions carrying a high mortality risk [7], [8]. This patient deteriorated rapidly within a short period, culminating in respiratory arrest. Timely intubation and mechanical ventilation support helped the patient survive the most critical phase. Upon reviewing previous literature on EBV-related encephalitis, we found that although respiratory abnormalities have been reported in some critically ill patients during disease progression, persistent respiratory manifestations serving as the primary clinical feature throughout the entire disease course are not commonly documented in existing case reports.

Currently, there is no standardized treatment protocol for EBV encephalitis. Acyclovir, ganciclovir, corticosteroids, and IVIG have all been documented in various case reports [2], [5], [9], [10], [11]. The therapeutic efficacy of the same medication varies among patients, with factors such as age, disease severity, comorbidities, and complications potentially influencing drug effectiveness [12]. When these conventional treatments prove ineffective, rituximab may be considered as an alternative option [9], [13]. In this case, the patient received a full course of ganciclovir at appropriate doses but showed no significant clinical improvement. Notably, the marked clinical improvements were observed following intravenous administration of IVIG and high-dose corticosteroids, suggesting that the pathogenesis of EBV encephalitis may involve not only direct viral damage to neurons but also immune-mediated mechanisms. This observation warrants further investigation to elucidate the underlying pathophysiological processes.

Conclusion

EBV encephalitis may occur in immunocompetent elderly individuals. Early-stage symptoms can be atypical, and definitive diagnosis relies on the detection of EBV through CSF-NGS. Regarding treatment, immunotherapy (including corticosteroids and IVIG) should be considered when antiviral therapy proves ineffective.

Abbreviations

EBV, Epstein-Barr virus; NGS, next-generation sequencing; CSF, cerebrospinal fluid; IVIG, Intravenous immunoglobulin; ICU, intensive care unit

Author statement

We hereby attest that the manuscript titled “Epstein-Barr virus Encephalitis in an Immunocompetent Elderly Patient: A Case Report” represents original work previously unpublished. Both authors have reviewed and approved the final version for submission to “IDCases”, including the mutually agreed authorship order. The corresponding author will provide data supporting this study's conclusions in accordance with institutional ethical requirements and upon reasonable request.

CRediT authorship contribution statement

Li Cao: Writing – review & editing, Writing – original draft, Data curation. Changchun Chen: Writing – review & editing.

Consent

Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This case report received approval from the Ethics Committee of Anhui No.2 Provincial People’s Hospital.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

For the manuscript "Epstein-Barr virus encephalitis in an immunocompetent elderly patient: a case report", 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.