JCV GCN in a natalizumab-treated MS patient is associated with mutations of the VP1 capsid gene
- 19 August 2014
- journal article
- case report
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 83 (8), 727-732
- https://doi.org/10.1212/wnl.0000000000000713
Abstract
Objective: To describe the clinical, neuroimaging, immunologic, and virologic characteristics of JC virus–associated granule cell neuronopathy (JCV GCN) in a natalizumab-treated patient with multiple sclerosis (MS) who developed immune reconstitution inflammatory syndrome (IRIS) after natalizumab withdrawal. Methods: We obtained longitudinal clinical data as well as MRI and proton magnetic resonance spectroscopy from this patient with MS. We measured JCV-specific cellular immune response in his peripheral blood by intracellular cytokine staining and sequenced a fragment of JCV VP1 capsid gene detected in his CSF. We contrast our findings with the first recently reported case. Results: This patient presented with worsening cerebellar symptoms and progressive cerebellar atrophy without new MS lesions on MRI after 63 months of natalizumab monotherapy. JCV DNA was detected in his CSF by PCR and harbored novel GCN-type mutations in the VP1 gene. He developed IRIS upon discontinuation of natalizumab and plasma exchange, which manifested itself by a worsening of clinical symptoms and contrast enhancement in the cerebellum on MRI. Treatment with corticosteroids resulted in resolution of IRIS, as demonstrated by proton magnetic resonance spectroscopy. The patient had a strong JCV-specific T-cell response in his peripheral blood and remains alive after 15 months from onset of symptoms, although with significant disability. He did not have MS relapse on glatiramer acetate. Conclusions: JCV GCN should be considered in patients on natalizumab presenting with progressive cerebellar symptoms and cerebellar atrophy, and is associated with mutations in the JCV VP1 gene. Natalizumab withdrawal may be complicated by JCV GCN IRIS, and require treatment with corticosteroids.Keywords
This publication has 12 references indexed in Scilit:
- Maraviroc and JC Virus–Associated Immune Reconstitution Inflammatory SyndromeNew England Journal of Medicine, 2014
- JC virus granule cell neuronopathy and GCN–IRIS under natalizumab treatmentAnnals of Neurology, 2013
- Progressive Multifocal Leukoencephalopathy: Why Gray and White MatterAnnual Review Of Pathology-Mechanisms Of Disease, 2013
- Metabolic profile of PML lesions in patients with and without IRISNeurology, 2012
- JC virus granule cell neuronopathy is associated with VP1 C terminus mutantsJournal of General Virology, 2012
- Role of CD4 + and CD8 + T-Cell Responses against JC Virus in the Outcome of Patients with Progressive Multifocal Leukoencephalopathy (PML) and PML with Immune Reconstitution Inflammatory SyndromeJournal of Virology, 2011
- Is maraviroc beneficial in paradoxical progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome management?AIDS, 2009
- A granule cell neuron-associated JC virus variant has a unique deletion in the VP1 geneJournal of General Virology, 2006
- Acute disseminated encephalomyelitis: an MRI/MRS longitudinal studyPediatric Neurology, 2004
- Magnetic resonance spectroscopy of multiple sclerosis: in-vivo detection of myelin breakdown productsThe Lancet, 1993