Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts

Long referral and diagnostic delays can impact both the opportunity for early therapeutic intervention and estimates of MS incidence and prevalence. We investigated factors associated with diagnostic or referral delays within two geographically distinct MS Canadian cohorts and the association between referral delay and disability at first clinic visit. Adult-onset MS patients were selected from the population-based British Columbian MS (BCMS) (n=5705) and the clinic-based Hôpital Notre-Dame, Quebec (CHUM) (n=1489) databases. Referral delay (BCMS) and diagnostic delay (CHUM) were examined by sex, onset age, disease course (primary progressive (PPMS) vs. relapsing at onset), onset symptoms (BCMS only) and year of first clinic visit/diagnosis. Cohorts were analyzed separately by stratified analyses and multivariable linear modeling. The relationship between referral delay and initial disability was examined by multiple ordinal regression in the BCMS cohort. Younger at onset patients or those with PPMS exhibited significantly longer delays (p<0.001). Delays decreased over the 20+ year period, but reductions varied by clinical course, onset age and sex. Long referral delays were associated with greater disability at first clinic visit (p<0.001). If early intervention at mild disability levels is warranted in MS, then the extended delays to medical recognition for young adult-onset and PPMS patients must be addressed.

[1]  R. Marrie,et al.  Comorbidity delays diagnosis and increases disability at diagnosis in MS , 2009, Neurology.

[2]  J. Frederiksen,et al.  Optic neuritis as onset manifestation of multiple sclerosis , 1999, Neurology.

[3]  G. Rosati,et al.  Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk , 2001, Acta neurologica Scandinavica.

[4]  R. Marrie,et al.  Changes in the ascertainment of multiple sclerosis , 2005, Neurology.

[5]  N Koch-Henriksen,et al.  The Danish Multiple Sclerosis Registry: a 50-year follow-up , 1999, Multiple sclerosis.

[6]  David H. Miller,et al.  Primary-progressive multiple sclerosis , 2007, The Lancet Neurology.

[7]  E. Celius,et al.  Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25‐year period , 2001, European journal of neurology.

[8]  L. Weiner,et al.  Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial , 2003, Multiple sclerosis.

[9]  H. Kölmel,et al.  Incidence of Multiple Sclerosis in the Urban Area of Erfurt, Thuringia, Germany , 2008, Neuroepidemiology.

[10]  J. Wolinsky.  The diagnosis of primary progressive multiple sclerosis , 2003, Journal of the Neurological Sciences.

[11]  D. B. Williams,et al.  Progressive increase in incidence and prevalence of multiple sclerosis in Newcastle, Australia: a 35-year study , 2003, Journal of the Neurological Sciences.

[12]  K. Hyllested,et al.  Incidence of multiple sclerosis in Denmark 1948-1982: a descriptive nationwide study. , 1992, Neuroepidemiology.

[13]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[14]  C. Poser,et al.  The epidemiology of multiple sclerosis: the Iceland model onset-adjusted prevalence rate and other methodological considerations , 1992, Journal of the Neurological Sciences.

[15]  N Keiding,et al.  Reporting delay and corrected incidence of multiple sclerosis. , 1999, Statistics in medicine.

[16]  T. Riise,et al.  Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern. , 1991, Neuroepidemiology.

[17]  W. Valdar,et al.  Sex ratio of multiple sclerosis in Canada: a longitudinal study , 2006, The Lancet Neurology.

[18]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[19]  Ludwig Kappos,et al.  Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study , 2007, The Lancet.

[20]  M. Hakama,et al.  Survival of multiple sclerosis in Finland between 1964 and 1993 , 2002, Multiple sclerosis.

[21]  J. Aarseth,et al.  Multiple sclerosis in Nord‐Trøndelag County, Norway: a prevalence and incidence study , 2003, Acta neurologica Scandinavica.

[22]  M. Hakama,et al.  Multiple sclerosis in Finland: incidence trends and differences in relapsing remitting and primary progressive disease courses , 2003, Journal of neurology, neurosurgery, and psychiatry.

[23]  J. Kurtzke.  A New Scale for Evaluating Disability in Multiple Sclerosis , 1955, Neurology.

[24]  J. Baskerville,et al.  The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. , 1999, Brain : a journal of neurology.

[25]  J H Simon,et al.  Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. , 2000, The New England journal of medicine.

[26]  F. Guillemin,et al.  Increasing incidence of multiple sclerosis among women in Lorraine, Eastern France , 2007, Multiple sclerosis.

[27]  F. Patti,et al.  Prevalence and incidence of multiple sclerosis in Catania, Sicily , 2001, Neurology.

[28]  D. Paty,et al.  Disability progression in multiple sclerosis is slower than previously reported , 2006, Neurology.

[29]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[30]  D. Goodin.  IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event , 2006, Neurology.

[31]  T. Riise,et al.  Increasing Incidence of Multiple Sclerosis in the Province of Sassari, Northern Sardinia , 2005, Neuroepidemiology.

[32]  F. Barkhof,et al.  Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis. , 2006, Archives of neurology.

[33]  G. McDonnell,et al.  Clinical study of primary progressive multiple sclerosis in Northern Ireland, UK , 1998, Journal of neurology, neurosurgery, and psychiatry.

[34]  M. Hernán,et al.  Temporal trends in the incidence of multiple sclerosis , 2008, Neurology.

[35]  T. Riise,et al.  Incidence of multiple sclerosis in Møre and Romsdal, Norway from 1950 to 1991. An age-period-cohort analysis. , 1996, Brain : a journal of neurology.

[36]  W. Pryse-Phillips,et al.  Incidence and Prevalence of Multiple Sclerosis in Newfoundland and Labrador , 2005, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[37]  B. Weinshenker,et al.  Not every patient with multiple sclerosis should be treated at time of diagnosis. , 2006, Archives of neurology.

[38]  Marco Rovaris,et al.  Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study , 2001, The Lancet.

[39]  I. Yee,et al.  Incidence and prevalence of multiple sclerosis in Saskatoon, Saskatchewan , 2007, Neurology.