title: Regional spread pattern predicts survival in patients with sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Sporadic amyotrophic lateral sclerosis (sALS) is a disease with a focal clinical onset and contiguous spread. We examined patterns of disease spread following symptoms onset in sALS and whether the pattern of spread predicted survival.
  
  
  METHODS
  Review of medical records (2003-2009) at London Ontario and Buenos Aires clinic cohorts retrieved 318 patients with sporadic sALS. According to patient self-report, we determined eight spread patterns: rostro-caudal, caudo-rostral, crossed, circular, superior interposed, middle interposed, inferior interposed and isolated. The variables studied were as follows: age, gender, sALS phenotypes, time from onset to diagnosis and time and direction of the spreading to the first region. Survival from symptoms onset was analysed by Kaplan-Meier, Tarone-Ware and Cox proportional hazards methods.
  
  
  RESULTS
  The direction of first spread was horizontal in 33%, rostral to caudal in 32% and caudal to rostral in 21%, whereas spread to remote regions was observed in 14% of patients. Survival curves and 3- and 5-year survival rates favoured patients with an isolated and caudo-rostral pattern of spread compared to patients progressing to distant regions without involvement in the intervening region, or 'superior and inferior interposed patterns' (Tarone-Ware P = 0.001, χ(2) = 0.002 and χ(2) = 0.006, respectively). Factors affecting survival were gender, time to diagnosis, flail arm phenotype and age at diagnosis.
  
  
  CONCLUSIONS
  We have provided evidence that not all spread in ALS is contiguous and that the nature of symptom progression influences survival. Patients with sALS with 'interposed patterns' had a worse prognosis, whereas patients with caudo-rostral pattern fared better than the rest.
authors.affiliation: Department of Neurology, Ramos Mejia Hospital. School of Medicine, Buenos Aires University, Buenos Aires, Argentina. gargiulo.gisella@ibyme.conicet.gov.ar
authors.forename: G M
authors.initials: GM
authors.lastname: Gargiulo-Monachelli
authors.forename: F
authors.initials: F
authors.lastname: Janota
authors.forename: M
authors.initials: M
authors.lastname: Bettini
authors.forename: C L
authors.initials: CL
authors.lastname: Shoesmith
authors.forename: M J
authors.initials: MJ
authors.lastname: Strong
authors.forename: R E P
authors.initials: RE
authors.lastname: Sica
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D057566:Self Report; D015996:Survival Rate; D055815:Young Adult