The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: Defining a consensus terminology

There is a need for consistent definition of human immunodeficiency virus (HIV)-associated cases of progressive multifocal leukoencephalopathy (PML), especially following the profound disease changes that have resulted from the use of highly active antiretroviral therapy (HAART). According to the criteria used for diagnosis, PML cases should be either referred to as “histology-confirmed,” with evidence of JC virus (JCV) infection in brain, “laboratory-confirmed,” with detection of JCV DNA in cerebrospinal fluid (CSF), or “possible,” in the presence of typical clinical and radiological picture, but no demonstration of JCV infection. Disease outcome should be defined by the evidence or lack of evidence of disease activity, rather than using survival or other variables. Disease activity should be based on clinical (scored neurological examination), radiological (magnetic resonance imaging), and virological (JCV DNA levels in CSF) indicators, to be assessed regularly, e.g., every 3 months until evidence of disease arrest or death. Furthermore, parallel assessments of other HIV-associated manifestations, including CD4+ cell counts and viral load, are required. A standard patient classification would be helpful for clinical management of PML patients, for their inclusion in clinical studies, and also will increase our current knowledge of PML and its evolution in relation with HAART.     

Inflammatory reaction in progressive multifocal leukoencephalopathy: Harmful or beneficial?

Progressive multifocal leukoencephalopathy (PML) occurs in patients with profound immunosuppression. Although lesions are usually devoid of lymphoplasmocytic infiltrates, inflammatory forms of PML have been described, in both human immunodeficiency virus (HIV)-seropositive (HIV+) and-seronegative (HIV?) patients. In addition, PML has been shown to develop in HIV+ patients shortly after introduction of highly active antiretroviral therapy (HAART), despite a recovery of the immune system. Therefore, one could postulate that PML might arise in the context of an immune reconstitution syndrome. To examine the clinical and neuroradiological characteristics of inflammatory forms of PML, the authors performed a retrospective analysis of the patients seen at their institution since 1996 as well as a review of the literature. Of 39 HIV+ and HIV?PML patients, 5 (13%) presented with an inflammatory form of this disease. Two HIV+ patients developed PML soon after the onset of HAART, concomitant to immune recovery, as demonstrated by a decrease of HIV viral load (VL) and an increase of CD4+ T-cell count. Three patients (2 HIV+ and 1 HIV?) had signs of inflammation in the central nervous system (CNS) characterized by contrast-enhancing lesions on neuroimaging studies, and/or inflammatory infiltrates on brain biopsy. The presence of JC virus-specific cytotoxic T lymphocytes was demonstrated in 4/4 patients tested and the outcome was favorable in 3 of them. In agreement with previously published case reports, the data indicate that inflammatory reactions in PML are not infrequent, and that they are generally associated with a favorable prognosis. Therefore clinicians should not disregard the diagnosis of PML in presence of contrast-enhancing brain lesions, and should use caution before treating these immunosuppressed individuals with steroids.     

Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Cognitive Impairment and Psychiatric Morbidity in HIV+ Zambians with New-Onset Seizure

A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.