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)