Abstract: When rare neurologic diseases become topics of editorials in
journals such as Nature Neuroscience,1 the New England Journal of
Medicine,2 and Neurology®, 3 there is usually something more of general
interest than the rare disease itself. Such is the case for progressive
multifocal leukoencephalopathy (PML), the JC virus-induced demyelinating
disease that was once relegated for discussion to the back of the
textbook, whether in microbiology or neurology. Not any longer.
Incidence and publication of cases of PML have risen more than 50-fold
within the last decade. Renewed recognition of PML started in
the
mid-1980s, when it was recognized as an AIDS-defining illness in 1%-3%
of all HIV-1-infected persons, still true in the era of combined
antiretroviral therapy.4 PML is reported in patients with underlying
neoplastic diseases, organ transplants, and rheumatic diseases, but by
2004, PML dramatically entered the mainstream as a serious adverse event
associated with a promising monoclonal antibody therapy, natalizumab,
for treatment of relapsing-remitting multiple sclerosis (MS). Nature
itself showed that demyelinating diseases of substantially different
etiologies and pathologies can occur in the same brain, and remarkably
enough in some cases, not with a fatal outcome. In 2006, the estimated
occurrence of PML in natalizumab-treated patients with MS, with an
average treatment of 17 months, was 1 per 1,000.5 With more than 115,000
patients globally treated with natalizumab for longer periods of time,
that estimate is 1 per 330.6 In patients who test positive for
antibodies to JCV, have a clinical history of immune suppressive
treatment before natalizumab, and have received more than 24 doses, the
number of PML cases is 1 per 90. CLICK: http://www.ncbi.nlm.nih.gov/pubmed/23925759