An Unusual Case of CMV/EBV Ventriculoencephalitis with Evolution to Primary Central Nervous System Lymphoma in HIV-Positive Patient

Case Reports in Infectious Diseases, Jul 2018

Epstein–Barr virus (EBV) is a well-known cause of different types of malignancies particularly Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s lymphomas, and non-Hodgkin’s lymphomas including primary central nervous system lymphoma (PCNSL). A higher tendency of malignant transformation associated with EBV has been noticed in immunocompromised patients, such as human immunodeficiency virus (HIV) infected patients. The rapid and effective immune reconstitution is crucial to prevent PCNSL in HIV-positive patients. We present a clinical case of a young patient diagnosed with HIV infection and medicated with antiretroviral therapy (ART) with poor immunological recovery. After two weeks, he developed ventriculoencephalitis, observed in the cranial magnetic resonance imaging (MRI), caused by cytomegalovirus (CMV) and EBV, both with high serum viral load, rapidly evolving to PCNSL. With this unusual clinical case, the authors want to draw attention to the importance of rapid immunological reconstitution in preventing the progression of EBV infection to PCNSL, as well as encouraging the confirmation of the usefulness of early combination of chemotherapy and antiviral therapy, in order to reach a more effective treatment of this herpesvirus infection and associated malignancies.

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An Unusual Case of CMV/EBV Ventriculoencephalitis with Evolution to Primary Central Nervous System Lymphoma in HIV-Positive Patient

An Unusual Case of CMV/EBV Ventriculoencephalitis with Evolution to Primary Central Nervous System Lymphoma in HIV-Positive Patient Gisela Borges 0 Diana Neves Maria de Jesus Silva 0 Ine?s Pintado Maury 1 Aida Pereira 1 Peter Olumese 0 Internal Medicine Department, Hospital Pulido Valente , Lisbon , Portugal 1 Infectious Diseases Department, Hospital Santa Maria , Lisbon , Portugal Epstein-Barr virus (EBV) is a well-known cause of different types of malignancies particularly Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphomas, and non-Hodgkin's lymphomas including primary central nervous system lymphoma (PCNSL). A higher tendency of malignant transformation associated with EBV has been noticed in immunocompromised patients, such as human immunodeficiency virus (HIV) infected patients. (e rapid and effective immune reconstitution is crucial to prevent PCNSL in HIV-positive patients. We present a clinical case of a young patient diagnosed with HIV infection and medicated with antiretroviral therapy (ART) with poor immunological recovery. After two weeks, he developed ventriculoencephalitis, observed in the cranial magnetic resonance imaging (MRI), caused by cytomegalovirus (CMV) and EBV, both with high serum viral load, rapidly evolving to PCNSL. With this unusual clinical case, the authors want to draw attention to the importance of rapid immunological reconstitution in preventing the progression of EBV infection to PCNSL, as well as encouraging the confirmation of the usefulness of early combination of chemotherapy and antiviral therapy, in order to reach a more effective treatment of this herpesvirus infection and associated malignancies. 1. Introduction HIV infected patients, especially with low CD4+ T cell count, are more susceptible to severe central nervous system (CNS) infections. Several studies have shown that EBV DNA detection in cerebrospinal fluid (CSF) is a good PCNSL marker in this group of patients [ 1 ]. Nonetheless, focal brain lesion stereotactic biopsy is the gold standard procedure to establish the final diagnosis. A prompt HIV infection diagnosis and a highly active antiretroviral therapy (HAART) initiation are essential measures to achieve an immunological recovery and consequently prevent EBV infection and its progression to PCNSL [ 2 ]. (e association between antiviral therapies with specific viral acting chemotherapy (rituximab) may be a more effective therapy against EBV replication and associated PCNSL. (e prognosis of patients with EBV associated PCNSL is poor. (e average life expectancy varies between two and twelve months after diagnosis [ 3 ]. We present a clinical case of a 31-year-old man diagnosed with HIV-1 infection, with CD4 T cell count of 35 cells/mm3 (4%) and HIV RNA 305349 copies/mL (log10 5.48) having initiated ART with abacavir/lamivudine and nevirapine. Around two weeks after starting ART, the patient is admitted due to a sudden cognitive impairment (anhedonia and memory loss) with progression to gait change and imbalance. (e cranial computerized tomography (CT) scan showed no lesions but the cranial MRI revealed ventriculoencephalitis (Figure 1). (e cerebrospinal fluid (CSF) had 38 nucleated cells/mm3, 175 mg/dL proteins and 37 mg/dL glucose (glycaemia 82 mg/dL). (e CSF CMV and EBV viral load were 189000 (log10 5.28) and 799 (log10 2.90) copies/mL with negative CSF neurotropic microorganism serologies and molecular identification (HSV 1/2, VZV, Cryptococcus, Brucella, Treponema pallidum, Borrelia burgdorferi, JC virus, Mycobacterium tuberculosis, and Toxoplasma gondii). (e final considered diagnostic was mainly CMV-related ventriculoencephalitis and ganciclovir was started. Nevertheless, the patient started left conjugate horizontal gaze palsy with abducting horizontal saccadic (or jerk-type) nystagmus of the right eye as well as a slight anisocoria with left eye miosis. (ese changes were enclosed in the one-anda-half syndrome and left-sided Horner's syndrome. (e patient also presented a grade II-III paresis of the right lower limb. (e cranial CT scan (performed fifteen days later) revealed a dubious right linear protuberancial hypodensity without signs of intracranial hypertension. Cranial MRI was repeated one month later revealing improvement of the ventriculitis signs but a larger hippocampus and left mesial temporal region involvement with a discrete increase of the lateral ventricles dimensions. Due to these clinical and imagiological changes and because we could not exclude tuberculosis infection, classic first-line tuberculostatic therapy was empirically started (stopped after excluding this infection) and foscarnet was added to ganciclovir (until a negative CMV viral load was achieved). At this point, the hypotheses of limbic encephalitis, epileptic activity or paraneoplastic encephalitis could not be excluded. (e lumbar puncture was repeated and CSF antineuronal antibodies, HHV-8, and other neurotropic microorganisms were nega (...truncated)


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Gisela Borges, Diana Neves, Inês Pintado Maury, Aida Pereira, Maria de Jesus Silva. An Unusual Case of CMV/EBV Ventriculoencephalitis with Evolution to Primary Central Nervous System Lymphoma in HIV-Positive Patient, Case Reports in Infectious Diseases, 2018, 2018, DOI: 10.1155/2018/7683797