Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Rayaz Malik, S. Tesfaye, P. G. Newrick, D. Walker, S. M. Rajbhandari, I. Siddique, A. K. Sharma, A. J M Boulton, R. H M King, P. K. Thomas, J. D. Ward

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

Original languageEnglish
Pages (from-to)578-585
Number of pages8
JournalDiabetologia
Volume48
Issue number3
DOIs
Publication statusPublished - Mar 2005
Externally publishedYes

Fingerprint

Sural Nerve
Diabetic Neuropathies
Schwann Cells
Demyelinating Diseases
Axons
Pathology
Biopsy
Autonomic Pathways
Electrophysiology
Peripheral Nerves
Nerve Fibers
Basement Membrane
Hyperplasia
Regeneration
Endothelial Cells
Cell Count

Keywords

  • Demyelination
  • Diabetes
  • Microangiopathy
  • Nerve fibres
  • Neuropathy
  • Schwann cell

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Malik, R., Tesfaye, S., Newrick, P. G., Walker, D., Rajbhandari, S. M., Siddique, I., ... Ward, J. D. (2005). Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia, 48(3), 578-585. https://doi.org/10.1007/s00125-004-1663-5

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. / Malik, Rayaz; Tesfaye, S.; Newrick, P. G.; Walker, D.; Rajbhandari, S. M.; Siddique, I.; Sharma, A. K.; Boulton, A. J M; King, R. H M; Thomas, P. K.; Ward, J. D.

In: Diabetologia, Vol. 48, No. 3, 03.2005, p. 578-585.

Research output: Contribution to journalArticle

Malik, R, Tesfaye, S, Newrick, PG, Walker, D, Rajbhandari, SM, Siddique, I, Sharma, AK, Boulton, AJM, King, RHM, Thomas, PK & Ward, JD 2005, 'Sural nerve pathology in diabetic patients with minimal but progressive neuropathy', Diabetologia, vol. 48, no. 3, pp. 578-585. https://doi.org/10.1007/s00125-004-1663-5
Malik R, Tesfaye S, Newrick PG, Walker D, Rajbhandari SM, Siddique I et al. Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia. 2005 Mar;48(3):578-585. https://doi.org/10.1007/s00125-004-1663-5
Malik, Rayaz ; Tesfaye, S. ; Newrick, P. G. ; Walker, D. ; Rajbhandari, S. M. ; Siddique, I. ; Sharma, A. K. ; Boulton, A. J M ; King, R. H M ; Thomas, P. K. ; Ward, J. D. / Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. In: Diabetologia. 2005 ; Vol. 48, No. 3. pp. 578-585.
@article{c973baf8873e4d1ea64da9d7f739764f,
title = "Sural nerve pathology in diabetic patients with minimal but progressive neuropathy",
abstract = "Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.",
keywords = "Demyelination, Diabetes, Microangiopathy, Nerve fibres, Neuropathy, Schwann cell",
author = "Rayaz Malik and S. Tesfaye and Newrick, {P. G.} and D. Walker and Rajbhandari, {S. M.} and I. Siddique and Sharma, {A. K.} and Boulton, {A. J M} and King, {R. H M} and Thomas, {P. K.} and Ward, {J. D.}",
year = "2005",
month = "3",
doi = "10.1007/s00125-004-1663-5",
language = "English",
volume = "48",
pages = "578--585",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

AU - Malik, Rayaz

AU - Tesfaye, S.

AU - Newrick, P. G.

AU - Walker, D.

AU - Rajbhandari, S. M.

AU - Siddique, I.

AU - Sharma, A. K.

AU - Boulton, A. J M

AU - King, R. H M

AU - Thomas, P. K.

AU - Ward, J. D.

PY - 2005/3

Y1 - 2005/3

N2 - Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

AB - Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

KW - Demyelination

KW - Diabetes

KW - Microangiopathy

KW - Nerve fibres

KW - Neuropathy

KW - Schwann cell

UR - http://www.scopus.com/inward/record.url?scp=20144389036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144389036&partnerID=8YFLogxK

U2 - 10.1007/s00125-004-1663-5

DO - 10.1007/s00125-004-1663-5

M3 - Article

VL - 48

SP - 578

EP - 585

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 3

ER -