PMID- 35891671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220729
IS  - 2632-1297 (Electronic)
IS  - 2632-1297 (Linking)
VI  - 4
IP  - 4
DP  - 2022
TI  - Predictors of progression from a first demyelinating event to clinically definite 
      multiple sclerosis.
PG  - fcac181
LID - 10.1093/braincomms/fcac181 [doi]
LID - fcac181
AB  - Understanding the predictors of progression from a first to a second 
      demyelinating event (and formerly, a diagnosis of clinically definite multiple 
      sclerosis) is important clinically. Previous studies have focused on predictors 
      within a single domain, e.g. radiological, lacking prospective data across 
      multiple domains. We tested a comprehensive set of personal, environmental, 
      neurological, MRI and genetic characteristics, considered together, as predictors 
      of progression from a first demyelinating event to clinically definite multiple 
      sclerosis. Participants were aged 18-59 years and had a first demyelinating event 
      during the study recruitment period (1 November 2003-31 December 2006) for the 
      Ausimmune Study (n = 216) and had follow-up data to 2-3 years post-initial 
      interview. Detailed baseline data were available on a broad range of demographic 
      and environmental factors, MRI, and genetic and viral studies. Follow-up data 
      included confirmation of clinically definite multiple sclerosis (or not) and 
      changes in environmental exposures during the follow-up period. We used 
      multivariable logistic regression and Cox proportional hazards regression 
      modelling to test predictors of, and time to, conversion to clinically definite 
      multiple sclerosis. On review, one participant had an undiagnosed event prior to 
      study recruitment and was excluded (n = 215). Data on progression to clinically 
      definite multiple sclerosis were available for 91.2% (n = 196); 77% were 
      diagnosed as clinically definite multiple sclerosis at follow-up. Mean (standard 
      deviation) duration of follow-up was 2.7 (0.7) years. The set of predictors 
      retained in the best predictive model for progression from a first demyelinating 
      event to clinically definite multiple sclerosis were as follows: younger age at 
      first demyelinating event [adjusted odds ratio (aOR) = 0.92, 95% confidence 
      interval (CI) = 0.87-0.97, per additional year of age); being a smoker at 
      baseline (versus not) (aOR = 2.55, 95% CI 0.85-7.69); lower sun exposure at age 
      6-18 years (aOR = 0.86, 95% CI 0.74-1.00, per 100 kJ/m(2) increment in 
      ultraviolet radiation dose), presence (versus absence) of infratentorial lesions 
      on baseline magnetic resonance imaging (aOR = 7.41, 95% CI 2.08-26.41); and 
      single nucleotide polymorphisms in human leukocyte antigen (HLA)-B (rs2523393, 
      aOR = 0.25, 95% CI 0.09-0.68, for any G versus A:A), TNFRSF1A (rs1800693, 
      aOR = 5.82, 95% CI 2.10-16.12, for any C versus T:T), and a vitamin D-binding 
      protein gene (rs7041, aOR = 3.76, 95% CI 1.41-9.99, for any A versus C:C). The 
      final model explained 36% of the variance. Predictors of more rapid progression 
      to clinically definite multiple sclerosis (Cox proportional hazards regression) 
      were similar. Genetic and magnetic resonance imaging characteristics as well as 
      demographic and environmental factors predicted progression, and more rapid 
      progression, from a first demyelinating event to a second event and clinically 
      definite multiple sclerosis.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Guarantors of Brain.
FAU - Chapman, Caron
AU  - Chapman C
AD  - Barwon Health, PO Box 281, Geelong, VIC 3220, Australia.
FAU - Lucas, Robyn M
AU  - Lucas RM
AUID- ORCID: 0000-0003-2736-3541
AD  - National Centre for Epidemiology and Population Health, The Australian National 
      University, Cnr Mills and Eggleston Roads, Canberra 2601, Australia.
FAU - Ponsonby, Anne-Louise
AU  - Ponsonby AL
AUID- ORCID: 0000-0002-6581-3657
AD  - The Florey Institute of Neuroscience and Mental Health, 30 Royal Pde, Parkville, 
      VIC 3052, Australia.
FAU - Taylor, Bruce
AU  - Taylor B
AD  - Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool St, 
      Hobart, Australia.
CN  - Ausimmune Investigator Group
LA  - eng
PT  - Journal Article
DEP - 20220709
PL  - England
TA  - Brain Commun
JT  - Brain communications
JID - 101755125
PMC - PMC9308470
OTO - NOTNLM
OT  - MRI
OT  - conversion
OT  - environment
OT  - genetics
OT  - multiple sclerosis
FIR - Chapman, Caron
IR  - Chapman C
FIR - Coulthard, Alan
IR  - Coulthard A
FIR - Dear, Keith
IR  - Dear K
FIR - Dwyer, Terry
IR  - Dwyer T
FIR - Kilpatrick, Trevor
IR  - Kilpatrick T
FIR - Lucas, Robyn
IR  - Lucas R
FIR - McMichael, Tony
IR  - McMichael T
FIR - Pender, Michael
IR  - Pender M
FIR - Ponsonby, Anne-Louise
IR  - Ponsonby AL
FIR - Taylor, Bruce
IR  - Taylor B
FIR - Valery, Patricia C
IR  - Valery PC
FIR - van der Mei, Ingrid
IR  - van der Mei I
FIR - Williams, David
IR  - Williams D
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/09
CRDT- 2022/07/27 02:12
PHST- 2022/01/10 00:00 [received]
PHST- 2022/04/07 00:00 [revised]
PHST- 2022/07/08 00:00 [accepted]
PHST- 2022/07/27 02:12 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/09 00:00 [pmc-release]
AID - fcac181 [pii]
AID - 10.1093/braincomms/fcac181 [doi]
PST - epublish
SO  - Brain Commun. 2022 Jul 9;4(4):fcac181. doi: 10.1093/braincomms/fcac181. 
      eCollection 2022.