Pattern of myelinated fibre loss in the sural nerve in neuropathy related to Type 1 (insulin-dependent) diabetes
Pattern of myelinated fibre loss in the sural nerve in neuropathy related to Type 1 (insulin-dependent) diabetes
J. G. Llewelyn 1
R K. Thomas 1
S. G. Gilbey 0
R J.Watkins 0
J. R. Muddle 1
0 Diabetic Department, King's College Hospital , London, U K
1 Department of Neurological Science, Royal Free Hospital School of Medicine
Summary. Sural nerve biopsies were obtained from 17 diabetic patients with neuropathy. All patients except three had both a symmetric distal sensory and autonomic polyneuropathy related to Type 1 (insulin-dependent) diabetes mellitus; 3 patients had a purely sensory polyneuropathy. Mean age was 34.5 years (range 18-53 years). The biopsies were compared with specimens from an age-matched control series. Myelinated fibre loss in the diabetic nerves was found to be nonuniform. Although patchy fibre loss has been considered to favour a vascular basis, an identical pattern of nonuniform
Diabetic neuropathy; hereditary motor and sensory neuropathy; sural nerve
-
9 Spfinger-Verlag 1988
The central question relating to diabetic neuropathy is
its cause. One view has been that the focal and
multifocal neuropathies that are encountered, particularly in
the older diabetic patient, are likely to have a vascular
basis. Some focal neuropathies may be related to an
abnormal susceptibility to injury from compression.
The commoner sensory and autonomic
polyneuropathy has been considered more probably to result from
metabolic factors [
1
]. Recently, increasing evidence has
been amassed suggesting that ischaemia is also
important in the causation of diffuse polyneuropathies. In
patients with a distal sensorimotor polyneuropathy,
postmortem examination showed that the symmetric
deficit was produced as a result of multifocal lesions
[
2
]. Sural nerve biopsies have shown that the number
of 'closed' capillaries is greater in patients with
diabetic neuropathy than in nerves from age-matched control
subjects and is positively correlated with the severity of
the neuropathy [
3
]. In biopsies from 36 patients, the
pattern of nerve fibre loss was both multifocal and
diffuse [
4, 5
], the former pattern again suggesting a
vascular basis. In another postmortem study, multifocal
lesions in the lumbosacral trunks and the tibial nerve,
but not in the sural nerve, were observed to be more
numerous in 16 patients with diabetic neuropathy than
in nondiabetic subjects [6]. Finally, intraluminal
vascular changes have been recorded in cases of diabetic
neuropathy [
7, 8
].
loss was observed in a series of sural nerve biopsies from
patients with Type I hereditary motor and sensory neuropathy, a
subgroup within the spectrum of peroneal muscular atrophy,
mainly of autosomal dominant inheritance, and a condition
in which a vascular causation can be discounted. Possible
reasons for nonuniform fibre loss other than vascular disease
are discussed.
Most of these studies, however, have been
performed on older patients. Mean age in the autopsied
series reported by Johnson et al. [
6
] was 64 years. In
the nerve biopsy study by Dyck et al. [
5
], median age
was 52 years in men with Type 1 (insulin-dependent)
diabetes (only 3 women were included); it was 56 years
for men and 55 years for women with Type 2
(non-insulin-dependent) diabetes. In the present investigation,
observations were therefore performed on a series of
younger patients with diabetic neuropathy. All had
Type I diabetes and were less than 54 years of age. The
pattern of myelinated fibre loss in the sural nerve was
assessed in comparison with the findings in
agematched control subjects without neuropathy and in
sural nerve biopsies from patients with Type I
hereditary motor and sensory neuropathy, a condition in
which a vascular basis has not been proposed.
Subjects and methods
All diabetic patients (5 male, 12 female; mean age 34.5 years, range
18-53 years) had clinical and electrophysiological evidence of a
distal symmetric, predominantly sensory polyneuropathy; 14 of the
17 patients had significant autonomic dysfunction either clinically or
on formal testing. The clinical and biochemical data at, or near the
time of, nerve biopsy are given in Table 1. Only 2 patients had
clinical evidence of peripheral vascular disease. Case 8 had absent foot
pulses but no symptoms of vascular insufficiency. Case 11 had
typical claudication and subsequent rest pain that led to amputation.
There was no evidence of focal cranial, thoracoabdominal or limb
neuropathy in any of the cases. All patients were on highly purified
bovine or porcine insulin. Sural nerve fascicular biopsies were
obtained with informed consent and had the approval of the Ethics
Committee at King's College Hospital.
Total sural nerve biopsies were obtained from six organ donor
cases (3 male, 3 female; mean age 38.3 years, range 21-48 years) at
the time of organ donation before circulatory arrest with the
permission of next of kin and the approval of the Ethics Committee at the
Royal Free Hospit (...truncated)