White matter hyperintensities (WMHs) have been associated with neurological complications including cognitive impairment. WMHs have been often described in HIV positive subjects and they have been linked to neurocognitive impairment, cerebrospinal fluid (CSF) residual viral replication and biomarkers of monocyte activation. Aim of this study was to grade WMHs in HIV-positive individuals using a simple visual scale and to explore their severity with clinical, neurocognitive and biomarker characteristics. Brain MRIs were retrospectively evaluated by two reviewers who rated WMHs following the "age-related white matter changes (ARWMC)" scale. 107 adult HIV-positive patients receiving lumbar punctures for clinical reasons were included. 70 patients (66.6%) were diagnosed with WMHs. Average WMH scores were higher in treated [7 (1-11)] vs. naïve individuals [3 (0-6)] (p = 0.008). Higher WHMs scores were observed in patients with chronic renal impairment along with chronic hepatitis (naïve) and longer HIV duration (treated participants). No consistent associations between plasma, CSF biomarkers and WMHs scores were found. 45 patients underwent full neurocognitive tests and WMHs scores were non-significantly higher in patients diagnosed with HAND [6.5 (0.5-8.3) vs. 1.5 (0-7), p = 0.165]; screening (IHDS and FAB), visuo-spatial (Corsi's) and auditory-verbal memory (disillabic words repetition) tests scored worse in patients with higher WMHs. In our population of HIV-positive patients with low CD4 nadir and partial CD4 cell recovery the burden of WMHs was associated with the duration of HIV infection and with commonly observed comorbidities (such as renal and hepatic impairment). Given the association with worse neurocognition, further studies on tailored interventions are needed.

Cytomegalovirus (CMV) central nervous system involvement is uncommon and hardly diagnosed because it can mimic many different conditions. We here present a case of an HIV-positive patient with neurological signs and symptoms (headache, asthenia, confusion, hallucinations, ataxia) with concurrent opportunistic diseases (neurotoxoplasmosis, disseminated Kaposi's sarcoma, disseminated CMV infection). CMV CNS involvement was not initially considered given the observed multiple comorbidities: antiviral treatment duration was probably not adequate given the end-organ disease. Concomitantly, plasma CMV DNA was undetectable while cerebrospinal fluid viral load was 31,340 copies/ml. Ganciclovir treatment followed by oral valganciclovir maintenance was associated with the slow disappearance of symptoms, the improvement of MRI images and the persistent undetectability of CMV DNA. The case here reported highlights the challenges of diagnosing CMV encephalitis in HIV-positive patients (with several cerebral comorbidities), the incomplete knowledge of the appropriate treatment for such a disease and the possibility of CMV replication in the cerebrospinal fluid despite undetectable plasma CMV DNA.Cytomegalovirus (CMV) is a ubiquitous virus that infects almost all human beings at some time in their lives and anti-CMV antibodies are usually found in the majority of healthy adults (40 to 100%) [1]. Even if CMV infection is usually asymptomatic or pauci-symptomatic in immune competent hosts, serious complications have been constantly described in newborns and in patients affected by immune deficiencies [2]. In HIV-positive patients with extremely low numbers of CD4 + T lymphocytes, serious end-organ CMV infections have been reported (retinitis, colitis and, although debated, pneumonias). Central nervous system (CNS) involvement is rare (less than 1% of CMV infections) but aggressive (with approximately 100% mortality if untreated) neurological presentation can be polymorphic and brain imaging may mimic other CNS opportunistic diseases [3]; therefore, timely and appropriate diagnosis may significantly impact patients' outcomes. We here describe a case of CMV encephalitis presenting concomitantly with other CNS opportunistic infections and with a slow response to antiviral treatment.We report the case of a 42-year-old patient of subSaharan African origin. After a two-week history of fever and headache he was admitted to the neurology ward and HIV-positivity was discovered. HIV RNA (336,135 copies/ml) and CD4 + T lymphocyte cell count (22/mm 3 , 1%, CD4/CD8 ratio 0.0) were consistent with very late presentation. Cranial CT scan showed two hypodense lesions (left cerebellar hemisphere and left temporal cortex); brain magnetic resonance revealed T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensity in left basal ganglia, temporo-occipital areas and left cerebellum as well as multiple diffuse contrast-enhanced cortical and subcortical lesions. Cerebrospinal fluid (CSF) analysis showed 8 cells/ml (lympho-monocytes), reduced g...

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.