Pattern of myelinated fibre loss in the sural nerve in neuropathy related to Type 1 (insulin-dependent) diabetes

Diabetologia, Mar 1988

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 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.

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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)


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J. G. Llewelyn, P. K. Thomas, S. G. Gilbey, P. J. Watkins, J. R. Muddle. Pattern of myelinated fibre loss in the sural nerve in neuropathy related to Type 1 (insulin-dependent) diabetes, Diabetologia, 1988, pp. 162-167, Volume 31, Issue 3, DOI: 10.1007/BF00276850