Sural nerve pathology in diabetic patients with minimal but progressive neuropathy.
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.
Malik
R A
RA
Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. Rayaz.a.malik@man.ac.uk
Tesfaye
S
S
Newrick
P G
PG
Walker
D
D
Rajbhandari
S M
SM
Siddique
I
I
Sharma
A K
AK
Boulton
A J M
AJ
King
R H M
RH
Thomas
P K
PK
Ward
J D
JD
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
Acta Neuropathol. 2001 Apr;101(4):367-74
11355308
N Engl J Med. 1988 Sep 1;319(9):542-8
3136330
Br Med J (Clin Res Ed). 1986 Oct 25;293(6554):1053-4
3094772
N Engl J Med. 1992 May 7;326(19):1257-63
1560802
Diabetologia. 1994 Sep;37(9):847-54
7806013
Electromyogr Clin Neurophysiol. 2002 Jan-Feb;42(1):3-6
11851006
Diabetologia. 2003 May;46(5):683-8
12739016
Diabetes. 2003 Oct;52(10):2615-22
14514647
Clin Sci (Lond). 2002 Sep;103(3):311-21
12193157
Nature. 2000 Apr 13;404(6779):787-90
10783895
Diabet Med. 2002 May;19(5):377-84
12027925
Muscle Nerve. 1978 Sep-Oct;1(5):375-87
233736
Ann N Y Acad Sci. 2002 Apr;959:368-83
11976211
Brain. 1991 Apr;114 ( Pt 2):867-92
2043955
J Neurol Neurosurg Psychiatry. 1992 Jul;55(7):557-61
1640230
J Clin Invest. 1988 Feb;81(2):349-64
3339124
Biochem Biophys Res Commun. 2004 Jul 16;320(1):241-8
15207727
Diabetes. 1990 Aug;39(8):909-13
2373263
Diabetes. 1990 Aug;39(8):898-908
2373262
Diabetes. 1986 Feb;35(2):192-7
3002887
Diabetologia. 1989 Feb;32(2):92-102
2721843
J Neuropathol Exp Neurol. 2002 Oct;61(10):872-84
12387453
J Anat. 1999 Oct;195 ( Pt 3):419-27
10580857
Neurology. 1981 Sep;31(9):1087-91
7022260
Diabetologia. 1998 Nov;41(11):1253-62
9833930
Ann Neurol. 1995 Apr;37(4):498-504
7717686
J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1420-4
3236020
Diabetes Care. 1999 Sep;22(9):1479-86
10480512
Diabetologia. 1990 Oct;33(10):611-8
2257998
Int Rev Neurobiol. 2002;50:229-55
12198812
Int Rev Neurobiol. 2002;50:293-321
12198814
Ann Neurol. 1994 Sep;36(3):408-15
8080248
J Neuropathol Exp Neurol. 1997 Mar;56(3):255-62
9056539
Diabetes Care. 2004 Jun;27(6):1458-86
15161806
N Engl J Med. 1995 Jul 13;333(2):89-94
7777034
Neurology. 2003 Jan 14;60(1):108-11
12525727
Diabetes. 2004 Jun;53(6):1556-63
15161761
Acta Neuropathol. 1994;88(6):571-8
7879605
Acta Neuropathol. 1996 Dec;92(6):614-20
8960320
Ann Intern Med. 1995 Apr 15;122(8):561-8
7887548