PMID- 20298967
OWN - NLM
STAT- MEDLINE
DCOM- 20100412
LR  - 20220408
IS  - 1474-4465 (Electronic)
IS  - 1474-4422 (Linking)
VI  - 9
IP  - 4
DP  - 2010 Apr
TI  - Natalizumab-associated progressive multifocal leukoencephalopathy in patients 
      with multiple sclerosis: lessons from 28 cases.
PG  - 438-46
LID - 10.1016/S1474-4422(10)70028-4 [doi]
AB  - BACKGROUND: Treatment of multiple sclerosis with natalizumab is complicated by 
      rare occurrence of progressive multifocal leukoencephalopathy (PML). Between 
      July, 2006, and November, 2009, there were 28 cases of confirmed PML in patients 
      with multiple sclerosis treated with natalizumab. Assessment of these clinical 
      cases will help to inform future therapeutic judgments and improve the outcomes 
      for patients. RECENT DEVELOPMENTS: The risk of PML increases with duration of 
      exposure to natalizumab over the first 3 years of treatment. No new cases 
      occurred during the first two years of natalizumab marketing but, by the end of 
      November, 2009, 28 cases had been confirmed, of which eight were fatal. The 
      median treatment duration to onset of symptoms was 25 months (range 6-80 months). 
      The presenting symptoms most commonly included changes in cognition, personality, 
      and motor performance, but several cases had seizures as the first clinical 
      event. Although PML has developed in patients without any previous use of 
      disease-modifying therapies for multiple sclerosis, previous therapy with 
      immunosuppressants might increase risk. Clinical diagnosis by use of MRI and 
      detection of JC virus in the CSF was established in all but one case. Management 
      of PML has routinely used plasma exchange (PLEX) or immunoabsorption to hasten 
      clearance of natalizumab and shorten the period in which natalizumab remains 
      active (usually several months). Exacerbation of symptoms and enlargement of 
      lesions on MRI have occurred within a few days to a few weeks after PLEX, 
      indicative of immune reconstitution inflammatory syndrome (IRIS). This syndrome 
      seems to be more common and more severe in patients with natalizumab-associated 
      PML than it is in patients with HIV-associated PML. WHERE NEXT?: Diagnosis of 
      natalizumab-associated PML requires optimised clinical vigilance, reliable and 
      sensitive PCR testing of the JC virus, and broadened criteria for recognition of 
      PML lesions by use of MRI, including contrast enhancement. Optimising the 
      management of IRIS reactions will be needed to improve outcomes. Predictive 
      markers for patients at risk for PML must be sought. It is crucial to monitor the 
      risk incurred during use of natalizumab beyond 3 years.
CI  - 2010 Elsevier Ltd. All rights reserved.
FAU - Clifford, David B
AU  - Clifford DB
AD  - Department of Neurology, Washington University in St Louis, Saint Louis, MO 
      63110, USA. cliffordd@neuro.wustl.edu
FAU - De Luca, Andrea
AU  - De Luca A
FAU - Simpson, David M
AU  - Simpson DM
FAU - Arendt, Gabriele
AU  - Arendt G
FAU - Giovannoni, Gavin
AU  - Giovannoni G
FAU - Nath, Avindra
AU  - Nath A
LA  - eng
GR  - U01 NS032228/NS/NINDS NIH HHS/United States
GR  - R01NS055628/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - England
TA  - Lancet Neurol
JT  - The Lancet. Neurology
JID - 101139309
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
SB  - IM
EIN - Lancet Neurol. 2010 May;9(5):463. DeLuca, Andrea [corrected to De Luca, Andrea]
CIN - Lancet Neurol. 2010 Jun;9(6):564; author reply 564-5. PMID: 20494319
MH  - Antibodies, Monoclonal/*adverse effects/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Humans
MH  - Immunologic Factors/*adverse effects/therapeutic use
MH  - Leukoencephalopathy, Progressive 
      Multifocal/diagnosis/epidemiology/*etiology/therapy
MH  - Multiple Sclerosis/*drug therapy
MH  - Natalizumab
RF  - 30
EDAT- 2010/03/20 06:00
MHDA- 2010/04/13 06:00
CRDT- 2010/03/20 06:00
PHST- 2010/03/20 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2010/04/13 06:00 [medline]
AID - S1474-4422(10)70028-4 [pii]
AID - 10.1016/S1474-4422(10)70028-4 [doi]
PST - ppublish
SO  - Lancet Neurol. 2010 Apr;9(4):438-46. doi: 10.1016/S1474-4422(10)70028-4.