We report the first in-vivo case of BKV-associated meningoencephalitis in an AIDS patient who showed clinical improvement and regression of brain lesions while on HAART.
BKV infection is generally a benign condition in immunocompetent patients, and the causative agent of "polyomavirus associated nephropathy" and hemorrhagic cystitis in immunocompromised individuals [12, 14]. However, there is a growing body of evidence demonstrating its neurotropism [14–16]. Among AIDS patients, only 3 cases of BKV- meningoencephalitis have been described, and all of them reported post-mortem [9–12].
Initially, the morphology of the lesions and the cytochemical profile of the CSF samples led us to empirically diagnose the patient with cerebral toxoplasmosis and herpes simplex encephalitis afterwards. However, the lack of response to treatment and the presence of BKV DNA in CSF samples and brain tissue led us to reclassify the patient as with BKV meningoencephalitis.
Compared to the other 3 cases reported, the presence of BKV DNA in the CSF is a common denominator of true neurological disease. As previously described, the detection of BKV genome in brain samples is unspecific, as it is normally present in 3%–6% of HIV-1 infected patient, even without neurological symptoms . Our patient's histopathological description is identical to the ones previously reported, showing diffuse areas of increased signal [9, 11]. Progressive multifocal leukoencephalopathy was ruled out because of the normal morphology of oligodendrocytes. In terms of the radiological changes, our case is similar to the previous ones, showing areas of increased signal intensity of the periventricular white matter (MRI) . Other descriptions include increased meningeal contrast enhancement along with increased meningeal thickness (MRI) , and marked internal hydrocephalus and periventricular lucencies (CT scan) . None of the previous reports showed features suggesting immune reconstitution inflammatory syndrome (IRIS).
Our main limitation to conclude that BKV is the causative agent of the neurological disorders is the lack of demonstration of the virus in the brain tissue sample, either by immunohistochemistry or by in-situ hybridization. Tissue samples extracted by stereotactic surgery are limited, and most of the times insufficient to run all diagnostic tests. These limitations were not faced in other reported cases, as all of these were done post-mortem.
Another important difference is the lack of renal/systemic involvement in our patient, when compared to the other cases previously reported. Our patient' renal work up included serial urianalysis and renal function tests that remained normal throughout the course of the disease (creatinine 0.8 mg/dl, BUN of 16 mg/dl, in April, 2004, creatinine of 0.9 mg/dl, BUN of 28 mg/dl in October, 2004,). As an outpatient his renal function has continued in the normal ranges (creatinine of 0.9 mg/dl, BUN of 40 mg/dl, May 2007). The containment of the disease was possibly related to a partial effect of HAART, similar to what has been reported for other AIDS-associated neurological complications in the post-HAART era, opening a broader spectrum of AIDS-associated neurocognitive disorders .
In this case, the change of atazanavir-ritonavir for efavirenz might have helped to reactivate the immune system, improving the symptoms and morphology of the lesions associated with BKV meningoencephalitis. The rationale of this change was based upon our previous experience and the results of an unpublished work describing the benefits of protease inhibitors in the restoration of the CD4 count when compared to non-nucleoside analogs (Riddler SA, Haubrich R, DiRienzo G, et al. A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection: ACTG 5142. Program and abstracts of the XVI International AIDS Conference; August 13–18, 2006; Toronto, Canada. Abstract THLB0204). Unfortunately, the restoration of the immune system is not innocuous, and as previously described, deleterious effects are found in the context of polyomavirus infection, introduction of HAART, and a rising CD4+ count . Immune reconstitution inflammatory syndrome (IRIS), as the latter phenomenon is known, affects 15% to 45% of patients receiving HAART. CNS involvement hás been reported to occur in the presence of tuberculosis (33%), cryptococcosis (4.2%–15.9%), JC vírus (unknown frequency); being manifested radiologically as the extension or worsening of a previous condition or by the apparison of lesions that are enhanced by contrast, with or without involvement of the meninges and sometimes accompanied by hydrocephalus . In our patient, the newly developed cerebral lesions and the headaches spontaneously resolved.
In conclusion, our report demonstrates that BKV might be the causative agent of meningoencephalitis in AIDS patients, and that this virus must be investigated in higher frequencies in HIV-1 positive patients with neurological manifestations now that its neurotropism has been better documented. In our patient, a previously reported life-threatening and disseminated disease progressed to a mild and focalized neurological condition in the presence of HAART.