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Research paper
Spreading of amyotrophic lateral sclerosis lesions—multifocal hits and local propagation?
  1. Teruhiko Sekiguchi1,
  2. Tadashi Kanouchi2,
  3. Kazumoto Shibuya3,
  4. Yu-ichi Noto4,
  5. Yohsuke Yagi5,
  6. Akira Inaba6,
  7. Keisuke Abe7,
  8. Sonoko Misawa3,
  9. Satoshi Orimo6,
  10. Takayoshi Kobayashi7,
  11. Tomoyuki Kamata5,
  12. Masanori Nakagawa4,
  13. Satoshi Kuwabara3,
  14. Hidehiro Mizusawa1,
  15. Takanori Yokota1
  1. 1Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
  2. 2Clinical Laboratory, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan
  3. 3Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  4. 4Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  5. 5Department of Neurology, Musashino Red Cross Hospital, Tokyo, Japan
  6. 6Department of Neurology, Kanto Central Hospital, Tokyo, Japan
  7. 7Department of Neurology, Nakano General Hospital, Tokyo, Japan
  1. Correspondence to Dr Takanori Yokota, Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8519, Japan; tak-yokota.nuro{at}tmd.ac.jp

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.

  • Motor Neuron Disease
  • ALS
  • EMG
  • Neurophysiology
  • Clinical Neurology

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