Ultrastructural studies of the dying-back process 1. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication

Herbert H. Schaumburg, Henryk M. Wiśniewski, Peter S. Spencer

Research output: Contribution to journalArticlepeer-review

217 Scopus citations


The spatio-temporal pattern of distal peripheral nerve, sensory and motor nerve terminal, degeneration in experimental acrylamidc neuropathy has been examined. Tissue was sampled from limbs of cats throughout various stages of intoxication (e.g. 7-32 days of 10 mg/kg/day and up to 294 days of 3 mg/kg/ day of acrylamidc) and examined by light and electron microscopy. Nerve terminals of a few Pacinian corpuscles in hindfoot and forefoot tocpads displayed the first abnormalities, before the onset of clinical signs; filopod axon processes were lost, axolcmmas disappeared and axoplosm was phagocytosed by inner core cells. egeneration of adjacent primary annulospiral endings of muscle spindles in hindfoot muscle began shortly after the first changes in Pacinian corpuscle axons. Later, juxtaposed secondary muscle spindle endings and motor nerve terminals, supplying nearby extrafusal muscle fibers, began to degenerate. These sensory and motor nerve terminals accumulated neurofilaments, became swollen and disappeared. Contemporaneous with the early degenerative changes in some nerve terminals, scattered preterminal nodes, and their paranodes, displayed focal axonal accumulations of neurofilaments, mitochondria and dense bodies. These organelle conglomerations were associated with focal axonal swelling and paranodal retraction of myelin. This axonal change appeared to spread along intcrnodes and to lead to fiber degeneration with the formation of ovoids which were later replaced by bands of Bungncr. Fiber degeneration proceeded proximally as intoxication progressed. Above the proximal limit of fiber breakdown, axons displayed progressively fewer abnormalities in the form of adaxonal Schwann cell ingrowths and swollen paranodal regions. The cardinal conclusions of this study of acrylamidc neuropathy are: 1- some distal sensory nerve endings (Pacinian corpuscle and annulospiral terminals) in the hindfeet begin to degenerate before adjacent motor nerve terminals supplying extrafusal muscles, and 2- the distal tips of the largest and longest axons are not most vulnerable, although there is a propensity for long and large axons to dieback first. In view of these observations, the etiology of the dying-back process requires re-xamination.

Original languageEnglish (US)
Pages (from-to)260-284
Number of pages25
JournalJournal of Neuropathology and Experimental Neurology
Issue number2
StatePublished - Apr 1974

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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