PML diagnostic criteria
Consensus statement from the AAN Neuroinfectious Disease Section
Abstract
Objective:
To establish criteria for the diagnosis of progressive multifocal leukoencephalopathy (PML).
Methods:
We reviewed available literature to identify various diagnostic criteria employed. Several search strategies employing the terms “progressive multifocal leukoencephalopathy” with or without “JC virus” were performed with PubMed, SCOPUS, and EMBASE search engines. The articles were reviewed by a committee of individuals with expertise in the disorder in order to determine the most useful applicable criteria.
Results:
A consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of PML. Two separate pathways, histopathologic and clinical, for PML diagnosis are proposed. Diagnostic classification includes certain, probable, possible, and not PML.
Conclusion:
Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.
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Information & Authors
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© 2013 American Academy of Neurology.
Publication History
Received: September 26, 2012
Accepted: December 26, 2012
Published online: April 8, 2013
Published in print: April 9, 2013
Disclosure
J. Berger serves on Data Safety Boards for Millennium and Amgen; has served on scientific advisory boards or as a consultant for Amgen, Bayer, BiogenIdec, Eisai, Genzyme, GlaxoSmithKline, Genentech, Novartis, and Pfizer; has received speaking fees from CMSC, AAN, Bayer, and BiogenIdec; and receives research support from the PML Consortium. A. Aksamit reports no disclosures. D. Clifford is funded by NIH grants U10 NS077384, MH22005, AI25903, and the Alzheimer Association. He serves on Data Safety Boards for Biogen, GSK, Millennium, Genzyme, Genentech, and Pfizer; has been a consultant to Amgen, Brinker, Biddle, Reath (PML Consortium), Genentech, Genzyme, Bristol-Myers Squibb, Millennium, Biogen Idec, and Pfizer; has received research support from Biogen Idec, NeurogesX, Tibotec, and Pfizer; and has received speaking fees from University of Kentucky and CMSC/ACTRIMS and ECTRIMS. L. Davis reports no disclosures. I. Koralnik is funded by NIH grants R56-NS041198, R01-NS047029, R01-NS074995, and K24-NS060950; has received a research grant from Biogen Idec and the National MS Society; served on scientific advisory boards for Hoffmann La-Roche, GlaxoSmithKline, and Merck Serono; received consulting fees from Bristol-Myers Squibb, Ono Pharmaceuticals, Merck Serono, Hoffmann La Roche, GlaxoSmithKline, Perseid Therapeutics, Vertex Pharmaceutical, and Johnson & Johnson; and receives royalties from Up-To-Date for topics on the management of HIV and CNS mass lesions and on PML. J. Sejvar, R. Bartt, E. Major, and A. Nath report no disclosures. Go to Neurology.org for full disclosures.
Study Funding
No targeted funding reported.
Authors
Author Contributions
All the authors are members of the PML Guidelines Committee and contributed to the study concept and design. Dr. Berger drafted the first and final versions of the manuscript. Drs. Aksamit, Clifford, Davis, Koralnik, Sejvar, Bartt, Major, and Nath provided critical revisions of the manuscript.
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