Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral demyelinating infectious disease of the central nervous system (CNS) which is rare & fetal, initially described in 1958 in patients with lymphoproliferative and myeloproliferative diseases [1, 2]. PML, at first named with respect to its pathological characteristics as a white matter progressive demyelinating multifocal disease, which can now be thought of as the classical form of this disease.
The causative agent of the disease is the John Cunningham polyomavirus (JCV) reactivation, which almost always occurs in the context of a major suppression of cell-mediated immunity. JCV is a dsDNA ubiquitous human pathogen which the main routs of its transmission are both inhalation and ingestion of contaminated water causing primary infection that is presumably asymptomatic; thereafter the second phase would be a variable long period of latent infection in the body, most recognized in the kidneys, bone marrow, spleen and B lymphocytes. The third or final stage is reactivation and homogenous dissemination of virus into the CNS when cellular immunity is impaired. Of note, cellular immunity suppression is a potent risk factor for PML occurrence rather than humoral immunity impairment [3]. In the brain, where astrocytes and oligodendrocytes support JCV replication, the virus makes a lytic destruction and demyelination.
High prevalence (about 86%) JCV antibody has found in adults after an initial asymptomatic exposure to JCV in childhood [4]. Reactivation of JCV occurs in immunocompromised patients with HIV/HTLV1 and hematologic malignancies, organ transplantation, or individuals being treated with immunosuppressive or immunomodulatory therapies (e.g. monoclonal antibodies such as natalizumab).
There are few population based studies of PML epidemiology; most reports have looked at incidence in specific populations of patients at risk (eg, autoimmune disorders, HIV infection, malignancy, organ transplantation…). Malignancy is the most common predisposing condition among PML cases [5].
There is various clinical presenting symptoms for the disease: usually it begins with focal or multifocal neurological deficits that progress in a sub-acute course leading to serious disabilities or even death. Sometimes acute onset of symptoms may represent other neurological diagnosis like stroke. Previous studies has shown higher cerebral rather than brain stem involvement at a ratio of 10:1. [6]. There are few case reports of completely asymptomatic course of the disease in the literature [7]. In brain MRI imaging of these patients multifocal and mostly asymmetric lesions are seen in periventricular and subcortical regions which some of them may have minimal mass effect or enhancement.
As over time more data about the disease and its predisposing underlying factors has discovered, its diagnosis and management have changed to some extent. Underlying immunosuppression state is the main factor determining the prognosis, treatment course and immune reconstruction inflammatory syndrome (PML-IRIS) occurrence possibility.
Early detection of PML especially in asymptomatic phase is associated with a more acceptable outcome and survival rate; although the disease is devastating anyway with a significant risk of long term mortality & morbidity. There is no confirmed therapy for PML at the time of reporting this case, and the treatment is mainly consists of supportive care.
Here we are reporting a clinical case of PML in a patient with B-CLL in remission, previously treated with Chlorambucil that complicated later in disease course with Covid-19 and mucormycosis. Just few cases of PML following Chlorambucil treatment has described in the literature. Another challenging issue in our patient was his early manifestations just after Covid-19 vaccination making its diagnosis more difficult.