PMID- 22057786
OWN - NLM
STAT- MEDLINE
DCOM- 20120514
LR  - 20231105
IS  - 1432-0533 (Electronic)
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 123
IP  - 2
DP  - 2012 Feb
TI  - Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis 
      with natalizumab-associated progressive multifocal leukoencephalopathy.
PG  - 235-45
LID - 10.1007/s00401-011-0900-5 [doi]
AB  - Natalizumab is an approved medication for highly active multiple sclerosis (MS). 
      Progressive multifocal leukoencephalopathy (PML) may occur as a severe side 
      effect of this drug. Here, we describe pathological and radiological 
      characteristics of immune reconstitution inflammatory syndrome (IRIS), which 
      occurs in natalizumab-associated PML after the cessation of therapy, and we 
      differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS 
      patients with natalizumab-associated PML were analyzed and their histology 
      compared with non-MS PML. Histology showed an extensive CD8-dominated T cell 
      infiltrate and numerous macrophages within lesions, and in nondemyelinated white 
      and grey matter, in four out of five cases. Few or no virally infected cells were 
      found. This was indicative of IRIS as known from HIV patients with PML. 
      Outstandingly high numbers of plasma cells were present as compared to non-MS PML 
      and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions 
      with a band-like or speckled contrast enhancement either at the lesion edge or 
      within lesions. Only the fifth patient showed typical PML pathology, with low 
      inflammation and high numbers of virally infected cells. This patient showed a 
      similar interval between drug withdrawal and biopsy (3.5 months) to the rest of 
      the cohort (range 2.5-4 months). MRI could not differentiate between 
      PML-associated IRIS and ongoing PML. We describe in detail the histopathology of 
      IRIS in natalizumab-associated PML. PML-IRIS, ongoing PML infection, and MS 
      exacerbation may be impossible to discern clinically alone. MRI may provide some 
      clues for distinguishing different pathologies that can be differentiated 
      histologically. In our individual cases, biopsy helped to clarify diagnoses in 
      natalizumab-associated PML.
FAU - Metz, Imke
AU  - Metz I
AD  - Department of Neuropathology, University Medical Center, Georg August University 
      Gottingen, Germany. imetz@gwdg.de
FAU - Radue, Ernst-Wilhelm
AU  - Radue EW
FAU - Oterino, Agustin
AU  - Oterino A
FAU - Kumpfel, Tania
AU  - Kumpfel T
FAU - Wiendl, Heinz
AU  - Wiendl H
FAU - Schippling, Sven
AU  - Schippling S
FAU - Kuhle, Jens
AU  - Kuhle J
FAU - Sahraian, Mohammad Ali
AU  - Sahraian MA
FAU - Gray, Francoise
AU  - Gray F
FAU - Jakl, Veronika
AU  - Jakl V
FAU - Hausler, Darius
AU  - Hausler D
FAU - Bruck, Wolfgang
AU  - Bruck W
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111106
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Female
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*chemically 
      induced/immunology/*pathology
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically 
      induced/immunology/*pathology
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*drug therapy/immunology/*pathology
MH  - Natalizumab
MH  - Syndrome
PMC - PMC3259335
EDAT- 2011/11/08 06:00
MHDA- 2012/05/15 06:00
PMCR- 2011/11/06
CRDT- 2011/11/08 06:00
PHST- 2011/09/17 00:00 [received]
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/10/16 00:00 [revised]
PHST- 2011/11/08 06:00 [entrez]
PHST- 2011/11/08 06:00 [pubmed]
PHST- 2012/05/15 06:00 [medline]
PHST- 2011/11/06 00:00 [pmc-release]
AID - 900 [pii]
AID - 10.1007/s00401-011-0900-5 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2012 Feb;123(2):235-45. doi: 10.1007/s00401-011-0900-5. Epub 
      2011 Nov 6.