Multifocal Motor Neuropathy: Pathologic Alterations at the Site of Conduction Block

Bruce V. Taylor, P. James B Dyck, JaNean Engelstad, Gregory Gruener, Ian Grant, Peter J Dyck

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm of arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number2
StatePublished - Feb 2004

Fingerprint

Regeneration
Demyelinating Diseases
Myelin Sheath
Ranvier's Nodes
Onions
Muscular Atrophy
Antibodies
Muscle Weakness
Forearm
Arm
Pathology
Biopsy

Keywords

  • Axonal degeneration
  • Multifocal motor neuropathy
  • Nerve fiber degeneration
  • Regenerating nerve clusters

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Multifocal Motor Neuropathy : Pathologic Alterations at the Site of Conduction Block. / Taylor, Bruce V.; Dyck, P. James B; Engelstad, JaNean; Gruener, Gregory; Grant, Ian; Dyck, Peter J.

In: Journal of Neuropathology and Experimental Neurology, Vol. 63, No. 2, 02.2004, p. 129-137.

Research output: Contribution to journalArticle

Taylor, Bruce V. ; Dyck, P. James B ; Engelstad, JaNean ; Gruener, Gregory ; Grant, Ian ; Dyck, Peter J. / Multifocal Motor Neuropathy : Pathologic Alterations at the Site of Conduction Block. In: Journal of Neuropathology and Experimental Neurology. 2004 ; Vol. 63, No. 2. pp. 129-137.
@article{f35870caa17a4f83846bdbc9acef9ea2,
title = "Multifocal Motor Neuropathy: Pathologic Alterations at the Site of Conduction Block",
abstract = "The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm of arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).",
keywords = "Axonal degeneration, Multifocal motor neuropathy, Nerve fiber degeneration, Regenerating nerve clusters",
author = "Taylor, {Bruce V.} and Dyck, {P. James B} and JaNean Engelstad and Gregory Gruener and Ian Grant and Dyck, {Peter J}",
year = "2004",
month = "2",
language = "English (US)",
volume = "63",
pages = "129--137",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Multifocal Motor Neuropathy

T2 - Pathologic Alterations at the Site of Conduction Block

AU - Taylor, Bruce V.

AU - Dyck, P. James B

AU - Engelstad, JaNean

AU - Gruener, Gregory

AU - Grant, Ian

AU - Dyck, Peter J

PY - 2004/2

Y1 - 2004/2

N2 - The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm of arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).

AB - The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm of arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).

KW - Axonal degeneration

KW - Multifocal motor neuropathy

KW - Nerve fiber degeneration

KW - Regenerating nerve clusters

UR - http://www.scopus.com/inward/record.url?scp=0842309733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842309733&partnerID=8YFLogxK

M3 - Article

C2 - 14989599

AN - SCOPUS:0842309733

VL - 63

SP - 129

EP - 137

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 2

ER -