title: Concomitant granule cell neuronopathy in patients with natalizumab-associated PML.
abstract: Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients.
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. m.wijburg@vumc.nl.|Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. m.wijburg@vumc.nl.
authors.forename: Martijn T
authors.initials: MT
authors.lastname: Wijburg
authors.affiliation: Department of Neurology, Erasmus MC, University Medical Center Rotterdam, MS Center, Rotterdam, The Netherlands.
authors.forename: Dorine
authors.initials: D
authors.lastname: Siepman
authors.affiliation: Department of Neurology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
authors.forename: Jeroen J J
authors.initials: JJ
authors.lastname: van Eijk
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
mesh_terms: D000328:Adult; D000368:Aged; D002531:Cerebellum / Q000473:pathology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab / Q000009:adverse effects*; D009474:Neurons / Q000473:pathology*; D012189:Retrospective Studies
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Cerebellar atrophy; Granule cell neuronopathy; MRI; Multiple sclerosis; PML
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