https://orcid.org/0000-0003-4282-5759
This report presents a 41-year-old man with facial paralysis and ataxia post-kidney transplant. Cerebrospinal fluid (CSF) analysis revealed Epstein-Barr virus (EBV) infection with elevated proteins. EBV-specific antigen/antibody in CSF confirmed active infection. EBV infections post-transplant are linked to lymphoproliferative disorders but rarely neurological complications. For transplant recipients who present with central nervous system symptoms, the possibility of EBV encephalitis should be entertained regardless of the serum EBV load.
Case presentation
In the context of solid organ transplantation (SOT), patients are routinely administered immunosuppressive agents, rendering them highly vulnerable to opportunistic infections, particularly during the initial 1–12 months post-procedure. These infections are often attributed to a diverse array of pathogens, encompassing viruses, fungi, parasites and bacteria.1 Among the myriad of complications that can arise, respiratory infections and sepsis are the most frequently encountered, whereas central nervous system (CNS) infections, though less common, pose a substantial threat due to their association with poor prognostic outcomes and significant mortality rates among transplant recipients.2 Epstein-Barr virus (EBV), a ubiquitous virus that resides within most individuals’ bodies for life, primarily targets B lymphocytes and epithelial cells. It can precipitate various pathological conditions, such as infectious mononucleosis, hemophagocytic syndrome, B-cell lymphoma and nasopharyngeal carcinoma. In immunocompromised SOT patients, EBV can also lead to lymphoproliferative disorders.3 Current diagnostic strategies for EBV primarily involve detecting virus-specific antibodies and nucleic acids in peripheral blood. However, given the widespread prevalence of EBV infection, positive results must be interpreted in conjunction with clinical manifestations.
Notably, EBV encephalitis, though rare, is a critical contributor to infectious encephalitis. In some instances, patients may present with negative peripheral blood markers, posing a diagnostic challenge. Our study presents a case of an EBV encephalitis patient with a kidney transplant who exhibited negative results for peripheral blood EBV antibodies, thereby shedding light on the complexities of laboratory diagnostics for this condition.
A 41-year-old man with a kidney transplant for hypertension 17 years ago was admitted to the hospital due to right-sided facial paralysis and numbness for 1 month. Immunosuppression consisted of cyclosporine, mycophenolate mofetil and prednisone acetate. Neurological examination reveals an ataxic gait. Brain magnetic resonance imaging (MRI) revealed a ring-shaped enhancement lesion in the lower right pons, with surrounding edema in the medulla and cerebellum (Figure 1).
Brain MRI. Brain MRI showed patchy hyperintensities in the right side of pons on T2 (A, arrow), T2 FLAIR images (B, arrow), with ring-shaped enhancement on post-contrast T1 images (C and D, arrows).
Cerebrospinal fluid (CSF) analysis revealed pleocytosis (38/μl), elevated protein level (66 mg/dl) and normal glucose level (3.41 mmol/l). Bacterial and fungal smears, India ink staining, acid-fast staining, TB-DNA and herpes simplex virus Type 2 DNA were all negative in his CSF. Paraneoplastic antibodies in blood, autoimmune encephalitis antibodies in both blood and CSF, and demyelinating antibodies in blood were also negative.
The EBV serology tests revealed that the Epstein-Barr nuclear antigen (EBNA) result was within the gray zone, while viral capsid antigen (VCA) IgG was positive, the early antigen (EA), VCA-IgM and VCA-IgA, were all negative, suggesting a past infection. Additionally, the EBV nucleic acid load in serum was <50 copies/ml. Peripheral blood tests failed to demonstrate evidence of active EBV infection. Nevertheless, next-generation sequencing analysis identified high levels of EBV in the CSF, exceeding 104 copies/ml. EBV antibody in CSF testing showed that EBNA was again in the gray zone, VCA-IgG was positive, and both VCA-IgA and EA-IgA were also positive, indicating a recent infection in the patient (Table 1). There were no other signs of infection or malignancy. The patient was treated with intravenous acyclovir three times a week, resulting in symptomatic improvement.
Epstein-Barr virus special antibodies in cerebrospinal fluid and serum
| Item | CSF | Serum |
|---|---|---|
| EA-IgA(S/CO) | + | − |
| EA-IgG(RU/ml) | − | − |
| EBNA-IgG(RU/ml) | ± | ± |
| VCA-IgA(S/CO) | + | − |
| VCA-IgM(S/CO) | / | − |
| VCA-IgG(RU/ml) | + | + |
| Item | CSF | Serum |
|---|---|---|
| EA-IgA(S/CO) | + | − |
| EA-IgG(RU/ml) | − | − |
| EBNA-IgG(RU/ml) | ± | ± |
| VCA-IgA(S/CO) | + | − |
| VCA-IgM(S/CO) | / | − |
| VCA-IgG(RU/ml) | + | + |
EA: early antigen; EBNA: Epstein-Barr nuclear antigen; VCA: viral capsid antigen.
Epstein-Barr virus special antibodies in cerebrospinal fluid and serum
| Item | CSF | Serum |
|---|---|---|
| EA-IgA(S/CO) | + | − |
| EA-IgG(RU/ml) | − | − |
| EBNA-IgG(RU/ml) | ± | ± |
| VCA-IgA(S/CO) | + | − |
| VCA-IgM(S/CO) | / | − |
| VCA-IgG(RU/ml) | + | + |
| Item | CSF | Serum |
|---|---|---|
| EA-IgA(S/CO) | + | − |
| EA-IgG(RU/ml) | − | − |
| EBNA-IgG(RU/ml) | ± | ± |
| VCA-IgA(S/CO) | + | − |
| VCA-IgM(S/CO) | / | − |
| VCA-IgG(RU/ml) | + | + |
EA: early antigen; EBNA: Epstein-Barr nuclear antigen; VCA: viral capsid antigen.
In SOT recipients, EBV infection may originate from the donor organ. While CNS infections often manifest with systemic involvement, there are rare instances where patients may present with isolated EBV encephalitis. Symptoms can include increased intracranial pressure, headache, seizures and focal neurological deficits.4 SOT recipients are in a state of chronic immunosuppression, and the manifestations of EBV encephalitis are non-specific. MRI typically reveals involvement of multiple regions, commonly including the cerebellum, basal ganglia and frontal lobe. CSF cytology often shows lymphocytosis and increased protein levels, while blood EBV viral loads may not accurately reflect CNS involvement.3 These factors contribute to the diagnostic challenges, necessitating the exclusion of non-infectious conditions, autoimmune encephalitis and malignancies by physicians. Therefore, for transplant recipients who present with CNS symptoms, the possibility of EBV encephalitis should be entertained regardless of the serum EBV load. This underscores the importance of a comprehensive diagnostic workup that incorporates clinical presentation, neuroimaging and, when necessary, histopathological examination to ensure accurate diagnosis and timely intervention.
In conclusion, we report a rare case of CNS EBV infection post-solid organ transplant, providing valuable insights for a broad range of clinicians, including neurologists and neuroscientists.
Author contributions
Jianzhao Zhai (Formal analysis [equal], Writing—original draft [equal]), Huiyu Zhong (Formal analysis [equal], Writing—review & editing [equal]) and Minjin Wang (Conceptualization [equal], Supervision [equal], Writing—review & editing [equal])
Funding
No funds received.
Conflict of interest: None declared.
Statement of ethics
The study was approved by the Ethics Committee of West China Hospital of Sichuan University (ChiCTR1900027074). All patients or their relatives were informed of the study and signed written informed consent.
