title: Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To define patterns of spread through the order of lower motor neuron involvement (first, second or third order), relationships between interval or sites of affected areas from onset to involvement of a second region, and prognosis, including 5 year survival, normal preservation of motor function at onset of respiratory symptoms and cumulative occurrence of each region and direction of spread.
  
  
  METHODS
  150 patients with sporadic amyotrophic lateral sclerosis (ALS) underwent follow-up at 3 month intervals until the appearance of respiratory symptoms. Symptom appearances were determined using the revised version of the ALS Functional Rating Scale.
  
  
  RESULTS
  Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3&emsp14;months from onset) survived >5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (p<0.001) although no significant difference in survival was seen between groups with and without bulbar symptoms (p=0.51). In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%.
  
  
  CONCLUSIONS
  The interval between onset and involvement of the second region is an important predictor of survival. The data support the contiguous anatomical propagation of lower motor neuron involvement in sporadic ALS.
authors.affiliation: Division of Neurology, First Department of Internal Medicine, Osaka Medical College, Takatsukishi, Osaka, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Fujimura-Kiyono
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Kimura
authors.forename: Simon
authors.initials: S
authors.lastname: Ishida
authors.forename: Hideto
authors.initials: H
authors.lastname: Nakajima
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sugino
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome