Different patterns of presentation and evolution of Non-Determined Leucoencephalopathy (NDLE) in HIV positive subjects.

Background: The introduction of highly active antiretroviral therapy (HAART) has significantly modified the pattern of HIV-related neurological diseases and the occurrence of opportunistic infections of the central nervous system (CNS). Among leucoencephalopathies, more and more cases have been reported where no viral agent was involved, being classified as NDLE. Methods: In our prospective study were enrolled HIV positive patients of the HIV Clinic in Pavia from May 2003 to June 2005, either asymptomatic but on HAART for at least 7 years or with neurological symptoms, possibly related to the presence of NDLE, regardless the duration of the infection. A neurological examination and a brain MRI were performed in eligible subjects. Patients presenting white matter lesions at the MRI underwent spinal puncture at baseline ad every six months. CSF was tested for JCV, CMV, HSV-1, HSV-2, EBV, VZV using PCR. NDLE was diagnosed in presence of lesions of white matter without the detection of any infectious cause. Results: 105 subjects were enrolled in the study, 26 of these being symptomatic. Fifteen patients had a positive MRI (2 neurotoxoplasmosis, 1 cryptococcal meningitis, 1lymphoma, Eleven cases of NDLE were identified, M/F ratio 5/6, median age: 41.3 years old, the median CD4 cells count at diagnosis was 324 cells/microl. Nine patients were classified as C3 according to CDC classification, one was B2 and one was A1. Plasma HIV RNA was undetectable in 9 patients, one patient was naïve and one was in stop therapy. The MRI lesions were hyperintense in T2 and isointense in T1, there was no perilesional oedema and gadolinium enhancement. The lesions had a heterogeneous distribution, the majority of them were multiple and involved more then one site. During the follow up (median: 20 months) 2 patients had a CNF positive for JCV virus and diagnosed with progressive multifocal leucoencephalopathy (PML). Only one of the nine subjects currently on follow up had a clinical progression of the neurological disease, the others are stable. Conclusions: In our study, 11/26 HIV positive patients with neurological symptoms presented white matter lesions, 9 of them being currently followed for NDLE. At the moment we can’t exclude the possibility of further detection of other PML cases in our NDLE group of patients