PMID- 25037207
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20220408
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 83
IP  - 8
DP  - 2014 Aug 19
TI  - JCV GCN in a natalizumab-treated MS patient is associated with mutations of the 
      VP1 capsid gene.
PG  - 727-32
LID - 10.1212/WNL.0000000000000713 [doi]
AB  - 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.
CI  - (c) 2014 American Academy of Neurology.
FAU - Agnihotri, Shruti P
AU  - Agnihotri SP
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Dang, Xin
AU  - Dang X
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Carter, Jonathan L
AU  - Carter JL
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Fife, Terry D
AU  - Fife TD
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Bord, Evelyn
AU  - Bord E
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Batson, Stephanie
AU  - Batson S
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ.
FAU - Koralnik, Igor J
AU  - Koralnik IJ
AD  - From the Division of Neurovirology, Department of Neurology (S.P.A., X.D., E.B., 
      S.B., I.J.K.), Center for Virology and Vaccine Research (S.P.A., X.D., E.B., 
      S.B., I.J.K.), and Department of Medicine (I.J.K.), Beth Israel Deaconess Medical 
      Center, Boston, MA; Department of Neurology (J.L.C., T.D.F.), University of 
      Arizona College of Medicine, Tucson; and Barrow Neurological Institute (T.D.F.), 
      Phoenix, AZ. ikoralni@bidmc.harvard.edu.
LA  - eng
GR  - R01 NS047029/NS/NINDS NIH HHS/United States
GR  - R01 NS074995/NS/NINDS NIH HHS/United States
GR  - R01-NS047029/NS/NINDS NIH HHS/United States
GR  - NS074995/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Capsid/*drug effects
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/chemically induced/genetics
MH  - JC Virus/*drug effects/immunology
MH  - Leukoencephalopathy, Progressive Multifocal/*drug therapy
MH  - Male
MH  - Multiple Sclerosis/diagnosis/*drug therapy
MH  - Mutation/genetics
MH  - Natalizumab
PMC - PMC4150135
EDAT- 2014/07/20 06:00
MHDA- 2014/12/23 06:00
PMCR- 2015/08/19
CRDT- 2014/07/20 06:00
PHST- 2014/07/20 06:00 [entrez]
PHST- 2014/07/20 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
PHST- 2015/08/19 00:00 [pmc-release]
AID - WNL.0000000000000713 [pii]
AID - NEUROLOGY2014571844 [pii]
AID - 10.1212/WNL.0000000000000713 [doi]
PST - ppublish
SO  - Neurology. 2014 Aug 19;83(8):727-32. doi: 10.1212/WNL.0000000000000713. Epub 2014 
      Jul 18.