PMID- 21832229
OWN - NLM
STAT- MEDLINE
DCOM- 20111102
LR  - 20220408
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 77
IP  - 11
DP  - 2011 Sep 13
TI  - Immune reconstitution inflammatory syndrome in natalizumab-associated PML.
PG  - 1061-7
LID - 10.1212/WNL.0b013e31822e55e7 [doi]
AB  - OBJECTIVE: To study the outcome of patients with multiple sclerosis (MS) and with 
      natalizumab-associated progressive multifocal leukoencephalopathy (PML) and 
      immune reconstitution inflammatory syndrome (IRIS). METHODS: MedWatch reports 
      from Biogen-Idec (manufacturer of natalizumab, Tysabri((R))) were reviewed which 
      comprised all 42 cases of natalizumab-related PML cases since its reintroduction 
      until March 2010. RESULTS: All except 2 patients with natalizumab-related PML 
      were managed by discontinuation of natalizumab and 
      plasmapheresis/immunoadsorption (PLEX/IA). Seventeen patients had contrast 
      enhancement of PML lesions on neuroimaging at the time of diagnosis before 
      withdrawal/removal of natalizumab (early-PML-IRIS) and 23 patients developed 
      contrast enhancement only after withdrawal/removal of natalizumab 
      (late-PML-IRIS). All patients developed IRIS. IRIS was defined as worsening of 
      neurologic deficits during the immune reconstitution following discontinuation of 
      natalizumab, corroborated by inflammatory changes on neuroimaging. Following 
      PLEX/IA, JC viral load in CSF increased by >10 fold in those with early-PML-IRIS 
      but <2 fold in late-PML-IRIS. IRIS developed earlier and was more severe in 
      early-PML-IRIS (p < 0.05). At the last follow-up, all patients had worse EDSS 
      scores but this was higher in patients with early-PML-IRIS compared to those with 
      late-PML-IRIS (p > 0.05). Mortality was comparable between the 2 groups, 29.4 +/- 
      11% vs 21.7 +/- 8.8%. Corticosteroid therapy during IRIS was associated with better 
      Expanded Disability Status Scale outcome, p < 0.05. CONCLUSION: Early immunologic 
      rebound in natalizumab-associated PML has worse survival and neurologic outcome. 
      PLEX/IA may accelerate IRIS and its impact on the final outcome is unclear. 
      Corticosteroid therapy provides a modest benefit and needs to be systemically 
      studied in a controlled manner in the management of natalizumab-associated 
      PML-IRIS.
FAU - Tan, I L
AU  - Tan IL
AD  - Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
FAU - McArthur, J C
AU  - McArthur JC
FAU - Clifford, D B
AU  - Clifford DB
FAU - Major, E O
AU  - Major EO
FAU - Nath, A
AU  - Nath A
LA  - eng
GR  - 1P30MH075673/MH/NIMH NIH HHS/United States
GR  - R01NS056884/NS/NINDS NIH HHS/United States
GR  - UL1RR025005/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110810
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
SB  - IM
CIN - Neurology. 2011 Sep 13;77(11):1033-4. PMID: 21832217
CIN - Neurology. 2012 Jan 3;78(1):73; author response 73. PMID: 22201114
CIN - Neurology. 2012 Jan 31;78(5):371; author reply 371. PMID: 22291067
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*chemically 
      induced/*diagnosis/therapy
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically 
      induced/*diagnosis/therapy
MH  - Male
MH  - Middle Aged
MH  - Natalizumab
MH  - Plasmapheresis/methods
MH  - Retrospective Studies
PMC - PMC3174071
EDAT- 2011/08/13 06:00
MHDA- 2011/11/04 06:00
PMCR- 2012/09/13
CRDT- 2011/08/12 06:00
PHST- 2011/08/12 06:00 [entrez]
PHST- 2011/08/13 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2012/09/13 00:00 [pmc-release]
AID - WNL.0b013e31822e55e7 [pii]
AID - WNL202978 [pii]
AID - 10.1212/WNL.0b013e31822e55e7 [doi]
PST - ppublish
SO  - Neurology. 2011 Sep 13;77(11):1061-7. doi: 10.1212/WNL.0b013e31822e55e7. Epub 
      2011 Aug 10.