PMID- 22710964
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20201229
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 71
IP  - 7
DP  - 2012 Jul
TI  - Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with 
      natalizumab.
PG  - 604-17
LID - 10.1097/NEN.0b013e31825caf2c [doi]
AB  - The use of natalizumab to treat multiple sclerosis (MS) has been associated with 
      the development of progressive multifocal leukoencephalopathy (PML), with 242 PML 
      cases reported as of May 3, 2012. Fortunately, rapid withdrawal of the drug and 
      administration of plasma exchange has allowed survival in many of these patients, 
      but a new problem, immune reconstitution inflammatory syndrome (IRIS), has 
      emerged after drug withdrawal. This report provides an update on PML in 
      natalizumab-treated patients and reviews what is currently known about PML-IRIS 
      in this setting; autopsy findings from a well-studied patient are illustrated. 
      This patient with relapsing-remitting MS had been treated for 4 years with 
      natalizumab, with discontinuation of drug after diagnosis of PML by cerebrospinal 
      fluid polymerase chain reaction testing. Disease was manifested by severe 
      paraparesis and expressive aphasia, which progressed before and after the 
      diagnosis of PML. Immune reconstitution inflammatory syndrome was diagnosed, 
      comfort care was instituted, but demise did not occur until 9 months later. 
      Autopsy showed ongoing severe PML-IRIS, with massive cavitary brain lesions 
      containing abundant perivascular and parenchymal CD8-positive T-cell infiltrates. 
      Bone marrow and spleen, but not brain, contained monoclonal T-cell populations by 
      polymerase chain reaction-based gene rearrangement studies, indicating 
      overstimulation of peripheral T cells; T-cell lymphoma was not identified by 
      morphological or immunohistochemical criteria.
FAU - Kleinschmidt-DeMasters, B K
AU  - Kleinschmidt-DeMasters BK
AD  - Department of Pathology University of Colorado Anschutz Medical Campus, 12631 E. 
      17th Avenue Mail Stop C307, Aurora, CO 80045, USA. bk.demasters@ucdenver.edu
FAU - Miravalle, Augusto
AU  - Miravalle A
FAU - Schowinsky, Jeffrey
AU  - Schowinsky J
FAU - Corboy, John
AU  - Corboy J
FAU - Vollmer, Timothy
AU  - Vollmer T
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Review
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Brain/pathology
MH  - CD8-Positive T-Lymphocytes/pathology
MH  - Female
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*chemically induced/diagnosis
MH  - Immunologic Factors/*adverse effects
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically induced/diagnosis
MH  - Magnetic Resonance Imaging/methods
MH  - Multiple Sclerosis/drug therapy
MH  - Natalizumab
EDAT- 2012/06/20 06:00
MHDA- 2012/09/05 06:00
CRDT- 2012/06/20 06:00
PHST- 2012/06/20 06:00 [entrez]
PHST- 2012/06/20 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
AID - 10.1097/NEN.0b013e31825caf2c [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2012 Jul;71(7):604-17. doi: 
      10.1097/NEN.0b013e31825caf2c.