title: Sural nerve pathology in diabetic patients with minimal but progressive neuropathy.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. Rayaz.a.malik@man.ac.uk
authors.forename: R A
authors.initials: RA
authors.lastname: Malik
authors.forename: S
authors.initials: S
authors.lastname: Tesfaye
authors.forename: P G
authors.initials: PG
authors.lastname: Newrick
authors.forename: D
authors.initials: D
authors.lastname: Walker
authors.forename: S M
authors.initials: SM
authors.lastname: Rajbhandari
authors.forename: I
authors.initials: I
authors.lastname: Siddique
authors.forename: A K
authors.initials: AK
authors.lastname: Sharma
authors.forename: A J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: R H M
authors.initials: RH
authors.lastname: King
authors.forename: P K
authors.initials: PK
authors.lastname: Thomas
authors.forename: J D
authors.initials: JD
authors.lastname: Ward
mesh_terms: D001369:Axons / Q000473:pathology; D001706:Biopsy; D003929:Diabetic Neuropathies / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008475:Median Nerve / Q000502:physiology; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D018579:Patient Selection; D013497:Sural Nerve / Q000473:pathology* / Q000503:physiopathology
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