title: Spreading of amyotrophic lateral sclerosis lesions--multifocal hits and local propagation?
abstract: OBJECTIVE
  To investigate whether or not the lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation in the rostrocaudal direction along the spinal cord, as has been hypothesised (the 'single seed and simple propagation' hypothesis).
  
  
  METHODS
  Subjects included 36 patients with sporadic ALS and initial symptoms in the bulbar, respiratory or upper limb regions. Abnormal spontaneous activities in needle electromyography (nEMG)-that is, fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation potentials (FPs)-were compared among the unilateral muscles innervated by different spinal segments, especially between the T10 and L5 paraspinal muscles, and between the vastus medialis and biceps femoris. Axon length and the proportion of muscle fibre types, which are both related to motoneuronal vulnerability in ALS, are similar in the paired muscles.
  
  
  RESULTS
  Fourteen of 36 patients showed a non-contiguous distribution of nEMG abnormalities from the onset site, with skipping of intermediate segments. In eight of them, the non-contiguous pattern was evident between paired muscles with the same motoneuronal vulnerability. The non-contiguously affected lumbosacral lesions involved motoneuron columns horizontally or radially proximate to one another, appearing to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs, were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5, suggesting that 2nd hits occur at L5 and then spread to other lumbosacral segments.
  
  
  CONCLUSIONS
  In sporadic ALS, the distribution of lower motoneuron involvement cannot be explained by the 'single seed and simple propagation' hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis instead.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, , Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Sekiguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kanouchi
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Shibuya
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Noto
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Yagi
authors.forename: Akira
authors.initials: A
authors.lastname: Inaba
authors.forename: Keisuke
authors.initials: K
authors.lastname: Abe
authors.forename: Sonoko
authors.initials: S
authors.lastname: Misawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Orimo
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kamata
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwabara
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology
keywords: ALS; Clinical Neurology; EMG; Motor Neuron Disease; Neurophysiology