Chapter 8. Neuro-infectious Disease
A 57-year-old man with acquired immunodeficiency syndrome (AIDS) and hepatitis C presents with worsening weakness. He complains of several weeks of left-arm and bilateral leg weakness, as well as worsening gait instability for which he has started using a cane. He provides vague explanation about the timing of the symptoms but admits to difficulty with short-term memory. On further questioning, he admits to being noncompliant with the antiretroviral therapy. On initial laboratory values include the following:
WBC: 3.00 × 103/μL
RBC: 2.66 × 106/μL
Hb: 7.9 g/dL
PLT: 109 × 103/μL
CD4: 198 cells/mm3
MRI of the brain was obtained as part of his diagnostic workup (Figure 8-1).
Figure 8-1 T2-weighted magnetic resonance imaging (MRI) of the brain.
In order to noninvasively confirm this patient's most likely diagnosis, which of the following is the most appropriate test to send?
(A) JC virus detection in circulating lymphocytes
(B) JC virus detection in cerebrospinal fluid (CSF) polymerase chain reaction (PCR) amplification
(C) Herpesvirus PCR amplification in CSF
(D) Human immunodeficiency virus (HIV) RNA viral load
(E) JC virus detection in circulating B cells
(B) The man in the vignette has evidence of progressive multifocal leukoencephalopathy (PML). PML is a demyelinating disease caused by a JC virus infection. The JC virus invades white matter oligodendrocytes causing focal myelin loss. Contrary to what the name may suggest, the clinical presentation may be focal or multifocal. The term “multifocal” refers to the multifocal microscopic lesions found in pathological samples.
PML is considered an opportunistic infection. AIDS is the most common mechanism of immunosuppression leading to PML, with an increased risk when the CD4 count is less than or equal to 200 cells/mm3. It is estimated that PML complicates 1% to 4% of AIDS cases. PML is also associated with lymphoreticular malignancies (such as chronic lymphocytic leukemia and Hodgkin and non-Hodgkin lymphoma) and treatment with immunosuppressant drugs (such as prednisone, methotrexate, cyclophosphamide, cyclosporine, rituximab, leflunomide, and mycophenolate mofetil).
Although some authors have detected JC virus in lymphocytes, (A) and some suggest B cells (D) have a role in carrying the virus to the CNS, PCR amplification–aided detection of the JC virus in CSF has become the noninvasive standard of diagnosis and is accepted as a surrogate marker of histologic proof, as brain biopsy has drawbacks in clinical practice. (Viscidi, 711–715; Chen et al, 1067–1074; Yousry, 924–933; Aksamit, 178–185)
Viscidi RP, Khanna N, Tan CS, et al. John Cunningham virus antibody ...