Progressive Multifocal Leukoencephalopathy: Opportunistic Infection in ART Era
Henry Ford Health System
Progressive Multifocal Leukoencephalopathy (PML) is a rare, progressive, fatal disease caused by reactivation of the JC polyomavirus. It is most often encountered in patients who are immunocompromised..more »
Progressive Multifocal Leukoencephalopathy (PML) is a rare, progressive, fatal disease caused by reactivation of the JC polyomavirus. It is most often encountered in patients who are immunocompromised by way of organ transplantation, hematopoietic stem cell transplant, or on certain immunologically suppressive drugs. Classically, PML has also been described in the HIV/AIDS population, although the incidence has become increasingly rare in the era of antiretroviral therapy (ART). Here, we present a case of a 31 year old gentleman with no previous comorbid conditions who presented to his local hospital with several weeks of progressive generalized muscle weakness, loss of appetite, weight loss and difficulty ambulating, suffering multiple falls at home. Physical examination revealed an underweight man in no acute cardiopulmonary distress with temporal wasting and reduced muscle bulk, with lethargy but intact mentation. Neurological examination revealed dysdiadokokinesia and dysmetria of the right upper extremity. Laboratory studies showed normal chemistries, with CBC disclosing pancytopenia and normal peripheral blood smear. MRI of the brain was done and showed a large lesion in the left cerebellar hemisphere. The lesion demonstrated low signal intensity on T1, high signal intensity on T2/FLAIR, no diffusion restriction or enhancement. Smaller lesions with similar signal characteristics were seen in the right thalamus, bilateral occipital lobes, right parietal lobe and left frontal lobe.Given the presence of white matter lesions with pancytopenia and a presentation consisting of weight loss and constitutional symptoms, HIV testing was done showing 4th generation antigen-antibody combination positivity with CD4 count of 35 and HIV viral load of 500,000 copies/ml. Extensive neurological workup was done with lumbar puncture showing normal opening pressure, elevated proteins, normal glucose, and negative CSF culture for bacteria, as well as for syphilis and enterovirus. With the finding of AIDS with white matter lesions in the MRI of the brain, CSF was sent for JC virus detection and was noted to be PCR positive. ART was started and HIV genotype was obtained. The patient continued to convalesce on the infectious disease floor while on ART. Eventually the patient was discharged to SAR to continue recovery. Unfortunately his disease had progressed to the point of the patient experiencing difficulty with activities of daily living and keeping up with nutritional needs. He succumbed to his illness within 8 weeks of presenting to medical attention.This case is illustrative of the textbook presentation of PML in HIV/AIDS. Evidence shows us that ART has decreased the incidence of PML reactivation to about 1.3 cases per 1000 person-years. When present, the illness is often progressive and fatal. Since the virus is asymptomatically acquired in childhood with antibodies positive in 86% of adults, it indicates the profound amount of immune suppression needed to reactivate and cause disease. Imaging findings are often classic with white matter streaking lesions diffusely in the cerebral cortex. Diagnostic testing, although only 70-90% sensitive, is 100% specific for PML when PCR positive for JC virus in CSF. Treatment includes correcting underlying immunodeficiency and discontinuation of offending drugs in the case of drug-induced PML. This case demonstrates that clinicians must be keenly aware of rare opportunistic infections in previously healthy individuals at risk for HIV acquisition and that organ-transplant recipients and those receiving immunomodulatory therapy are at particularly high risk of this progressive disease.
Henry Ford Hospital
Henry Ford Health System