The Pathology of Diabetic Neuropathy
Published 1 January 2004
P. K. Thomas
Citations248
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TL;DR
The chapter attempts to describe the expected diversed underlying pathological alterations in patients with diabetes mellitus and to relate the changes to the clinical syndromes.
Abstract
Abstract The chapter attempts to describe the expected diversed underlying pathological alterations in patients with diabetes mellitus and to relate the changes to the clinical syndromes.
Keywords
MedicineNeuroscience
Annals of NeurologyHuman diabetic endoneurial sorbitol, fructose, and <i>myo</i>‐inositol related to sural nerve morphometry
511 Citations1980P. James B. Dyck, William R. Sherman +6 more
A comparison of scored symptoms and signs and clinical neurophysiological studies against morphometric and teased fiber studies of sural nerve demonstrated that the former three provide sensitive and reliable measures of severity of neuropathy that can be used for controlled clinical trials of diabetic neuropathy.
Journal of Neurology Neurosurgery & PsychiatryNerve biopsy and conduction studies in diabetic neuropathy.
360 Citations1977F. Behse, Fritz Buchthal +1 more
Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy.
BrainOCULOMOTOR PALSY IN DIABETES MELLITUS: A CLINICO-PATHOLOGICAL STUDY
353 Citations1970Arthur K. Asbury, HORATIO ALDREDGE +2 more
Journal of Neurology Neurosurgery & PsychiatryThe natural history of acute painful neuropathy in diabetes mellitus.
341 Citations1983A. G. Archer, Peter Watkins +3 more
It is concluded that acute painful diabetic neuropathy is a distinct syndrome, occurring in insulin or noninsulin dependent patients of any duration, and unrelated to other diabetic complications.
NeurologyMicrovasculitis and ischemia in diabetic lumbosacral radiculoplexus neuropathy
331 Citations1999P. James B. Dyck, Jane E. Norell +1 more
Annals of NeurologyFiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy
299 Citations1986P. James B. Dyck, Alfred C. Lais +3 more
It is concluded that there is increasing evidence that microvascular pathological abnormality and ischemia may be involved in the pathogenesis of human diabetic polyneuropathy.
Annals of NeurologyPathogenesis of diabetic neuropathy
295 Citations1986Peter C. Johnson, Susan C. Doll +1 more
It is concluded that beyond the possible metabolic abnormalities involved in the genesis of diabetic polyneuropathy, focal fascicular lesions, likely due to diabetic microangiopathy, are also important in the development of diabetic neuropathy.
New England Journal of MedicineRegeneration and Repair of Myelinated Fibers in Sural-Nerve Biopsy Specimens from Patients with Diabetic Neuropathy Treated with Sorbinil
294 Citations1988Anders A. F. Sima, Vera Bril +5 more
It is concluded that sorbinil, as a metabolic intervention targeted against a specific biochemical consequence of hyperglycemia, can improve the neuropathologic lesions of diabetic neuropathy.
DiabetologiaMicroangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy
293 Citations1989Rayaz A. Malik, P. G. Newrick +7 more
All measures of nerve capillary pathology correlated significantly with neurophysiological and neuropathological measures of neuropathic severity and there was no significant correlation between the duration of diabetes and HbA1 levels with capillaryPathology or with neuropathy severity.
Annals of NeurologyNerve biopsy findings in different patterns of proximal diabetic neuropathy
264 Citations1994Gérard Saïd, Catherine Goulon‐Goeau +2 more
It is shown that axonal and demyelinative lesions similar to those found in diabetic DSSP are present in proximal nerves in mild forms of proximal diabetic neuropathy; while nerve ischemia, inflammatory infiltration, and vasculitis are encountered in the most severe forms of distal symmetrical sensory polyneuropathy.
BrainPROGRESSIVE CENTRIPETAL DEGENERATION OF AXONS IN SMALL FIBRE DIABETIC POLYNEUROPATHY
252 Citations1983G. Saïd, G. Slama +1 more
A clinicopathological study is presented of 5 patients with a pseudosyringomyelic dissociation of sensory loss and severe autonomic disturbances related to diabetic polyneuropathy, finding that observations are consistent with a progressive centripetal degeneration of axons in predominantly sensory diabetic polyNEuropathy.
Annals of NeurologyThe spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia
252 Citations1986P. James B. Dyck, Jeannine L. Karnes +4 more
Even in cases with mild polyneuropathy, fiber loss, a decrrease in the median diameter, and an increase in the variability of density among frames and among fascicles began in proximal nerve and extended to distal levels.
Annals of Internal MedicinePathology of Autonomic Neuropathy in Diabetes Mellitus
250 Citations1980L. W. Duchen, A. ANJORIN +2 more
There may be several different pathogenetic mechanisms involved in the development of autonomic neuropathy in diabetes, and inflammatory changes in the autonomic ganglia in all cases were studied postmortem.
Archives of NeurologyPainful Diabetic Neuropathy
242 Citations1976Mark J. Brown
Three diabetic patients whose neuropathy was characterized by pain, hypesthesia, and autonomic dysfunction, with preservation of epicritic sensation and muscle-stretch reflexes were investigated, suggesting small-fiber involvement.
Journal of Clinical InvestigationHistopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy.
219 Citations1988Anders A. F. Sima, Virgil Nathaniel +3 more
The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.
Proceedings of the National Academy of SciencesCapillary number and percentage closed in human diabetic sural nerve.
217 Citations1985P. James B. Dyck, S Hansen +5 more
The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls, and this percentage increased with the severity of neuropathy.
BMJMedial arterial calcification and diabetic neuropathy.
212 Citations1982Michael Edmonds, Nancy Morrison +2 more
Medial arterial calcification was much more common and extensive in the patients with neuropathy, occurring in the feet in 15 and in the hands in eight compared with in four and none of the controls respectively.
BrainSURAL NERVE MORPHOMETRY IN DIABETIC AUTONOMIC AND PAINFUL SENSORY NEUROPATHY
191 Citations1991J. Llewelyn, S. G. Gilbey +4 more
No correlation between the occurrence of pain and active degeneration of myelinated fibres or with regenerative activity either in myelination or unmyelinated axons was detectable.
A M A Archives of Neurology & PsychiatryDiabetic Ophthalmoplegia
183 Citations1957P Dreyfus
The ophthalmoplegia is often seen in patients who have had mild diabetes of long standing, frequently complicated by retinopathy, nephropathy, peripheral neuropathy, and lenticular opacities.
Archives of NeurologyIschemic Mononeuropathy Multiplex Associated With Diabetes Mellitus
181 Citations1968Martin Raff, Virgilio Sangalang +1 more
Diabetic mononeuropathy multiplex tends to affect elderly patients with mild, or undiscovered, diabetes, and has an acute or subacute onset with a tendency to recover over a period of months, and usually causes a painful, asymmetrical, often proximal disorder.
Journal of NeurocytologyUltrastructural studies of the dying-back process II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axons
181 Citations1974Peter S. Spencer, P. K. Thomas
The sequestration and phagocytosis of unusual and abnormal axoplasmic organelles by Schwann and oligodendroglial cells is described, maximally developed in situations where there is centripetal axonal degeneration such as occurs in dying-back toxic disease and in the proximal stump of an amputated nerve.
Journal of the Neurological SciencesChronic inflammatory demyelinating polyneuropathy (CIDP) in diabetics
145 Citations1996John Stewart, Roger McKelvey +3 more
Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neuropathy predominantly affecting the legs that met clinical and electrophysiological criteria for chronic inflammatory demyelinating polyneuropathy (CIDP).
BrainPATHOLOGICAL OBSERVATIONS ON SIX CASES OF DIABETIC NEUROPATHY
131 Citations1964David S. Greenbaum, PM Richardson +2 more
BrainTHE PATHOGENESIS OF SURAL NERVE CHANGES IN DIABETES MELLITUS
130 Citations1969J.S. Chopra, L. J. Hurwitz +1 more
Acta NeuropathologicaMicroangiopathy in human diabetic neuropathy
126 Citations1985Henry C. Powell, J. Rosoff +1 more
These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.
Acta NeuropathologicaAcute painful diabetic neuropathy precipitated by strict glycaemic control
122 Citations1986J. Llewelyn, P. K. Thomas +3 more
The suggestion is made that adequate diabetic control promoted regeneration and that the pain may have been related to the ectopic generation of impulses in regenerating axon sprouts.
GastroenterologyThere are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis
120 Citations1988Mark M. Yoshida, Michael D. Schuffler +1 more
There were no abnormalities in the numbers or appearance of neurons or axons in the myenteric plexus of the stomach of diabetics, with or without gastroparesis, and no morphologic abnormalities of the gastric wall or abdominal vagus were identified in diabetic gastropareis.
PubMedPrednisone-responsive hereditary motor and sensory neuropathy.
120 Citations1982Dyck Pj, Swanson Cj +3 more
Neurologic improvement with use of prednisone, in some cases on several occasions, was demonstrated in seven patients who had a chronic progressive polyradiculoneuropathy with nerve conduction velocity and electromyographic findings consistent with segmental demyelination and axonal degeneration and increases protein concentration in the cerebrospinal fluid.
Journal of NeurologyEpineurial microvasculitis in proximal diabetic neuropathy
118 Citations1998J. Llewelyn, P. K. Thomas +1 more
The present observations confirm the view that secondary vasculitic or other inflammatory reactions may contribute to some forms of diabetic neuropathy.
DiabetesImpotence and Diabetes: Histological Studies of the Autonomic Nervous Fibers of the Corpora Cavernosa in Impotent Diabetic Males
115 Citations1974Isaac Faerman, Leticia Glocer +3 more
This first study of the autonomic nervous system in the corpora cavernosa of impotent diabetics lends strong support to the idea that their sexual impotence is due to a neurological lesion of the nerve fibers that control erection.
Diabetic MedicineThe Relationship Between Sural Nerve Morphometric Findings and Measures of Peripheral Nerve Function in Mild Diabetic Neuropathy
109 Citations1991Aristidis Veves, Rayaz A. Malik +5 more
It is concluded that conventional electrophysiological tests in the lower limb are reliable surrogate measures for structural abnormalities in early diabetic neuropathy.
DiabetologiaClinical and histological studies in diabetic neuropathy
109 Citations1976W R Timperley, J. D. Ward +3 more
Fibrin deposition within small vessels could well play a part in damaging the diabetic nerve and a disturbance of the balance between deposition and removal by fibrinolysis could explain phasic variation in the symptoms of neuropathy.
Journal of Neurology Neurosurgery & PsychiatryDiabetic gastroparesis from autonomic neuropathy: surgical considerations and changes in vagus nerve morphology.
104 Citations1984Rebecca Guy, J L Dawson +5 more
The severity of the abnormalities supports the view that diabetic gastroparesis is related to vagal denervation, and electron microscopic studies of the vagus nerve in one of the cases showed a severe reduction in the density of unmyelinated axons.
BrainTHE SYMPATHETIC NERVOUS SYSTEM IN ALCOHOLIC NEUROPATHY
85 Citations1975Phillip A. Low, John Walsh +2 more
Tests of autonomic function were performed on 12 subjects with alcoholic neuropathy and the absence of significant disturbance of blood pressure control correlates well with the presence of pathology in the greater splanchnic nerve.
Journal of the Neurological SciencesMultifocal fiber loss in proximal sciatic nerve in symmetric distal diabetic neuropathy
84 Citations1982K. Sugimura, P. James B. Dyck
The findings suggest that multifocal lesions at upper levels of sciatic nerve can summate distally to produce a symmetric diabetic neuropathy.
Neuropathology and Applied NeurobiologyTHE PATHOLOGY OF ULNAR NERVE COMPRESSION IN MAN
84 Citations1975D. Neary, Rosemary A. Eames
It is suggested that the presence of many regeneration clusters in otherwise apparently normal transverse sections of nerves taken from sites where entrapment may occur indicates that underlying abnormalities will be seen in single teased nerve fibres and early compression neuropathy is present.
Journal of Neurology Neurosurgery & PsychiatryNeuropathology of the oesophagus in diabetes mellitus
79 Citations1974Bruce A. Smith
Abnormalities of the innervation of the oesophagus have been shown in 18 out of 20 unselected diabetics without clinical dysphagia or neuropathy and it is probable that, as in the peripheral nerves, the major changes are in the Schwann cells, although here the affected fibres are unmyelinated.
The Tohoku Journal of Experimental MedicineUltrastructural Pathology of Peripheral Nerves in Patients with Diabetic Neuropathy
79 Citations1979Soroku Yagihashi, Muneo Matsunaga
The results indicated that the peripheral nerve lesions in human diabetics were mainly due to metabolic impairment of nerve fibers, accompanying dysmetabolism of Schwann cells and diabetic microangiopathy, and that these changes proceeded independently.
Neuropathology and Applied NeurobiologyDIABETIC NEUROPATHY: ABNORMALITIES OF SCHWANN CELL AND PERINEURIAL BASAL LAMINAE. IMPLICATIONS FOR DIABETIC VASCULOPATHY
78 Citations1989R. H. M. King, J. Llewelyn +3 more
During Wallerian degeneration, the Schwann cell basal laminal ensheathment around myelinated nerve fibres remains after the removal of myelin and axonal debris, forming a corrugated tube within which Schwanncell proliferation takes place.
DiabetesAutonomic Nervous System and Diabetes: Histological and Histochemical Study of the Autonomic Nerve Fibers of the Urinary Bladder in Diabetic Patients
74 Citations1973Isaac Faerman, Leticia Glocer +5 more
The findings lead to the hypothesis that diabetic neuropathy injures the biochemical phase of the myelin sheath in the first stage and the nerve fibers later, as well as the anatomic or histochemical lesions.
Proceedings of the National Academy of SciencesIncrease in albumin, IgG, and IgM blood-nerve barrier indices in human diabetic neuropathy.
72 Citations1988Joseph F. Poduslo, Geoffry L. Curran +1 more
It is hypothesized that the observed increase in endoneurial concentration of these plasma proteins results from altered transport through the endothelial or perineurial barrier, which supports an underlying vascular mechanism in the development of diabetic polyneuropathy.
Proceedings of the National Academy of SciencesIncreased permeability across the blood-nerve barrier of albumin glycated in vitro and in vivo from patients with diabetic polyneuropathy.
68 Citations1992Joseph F. Poduslo, Geoffry L. Curran
It is hypothesized that the increased permeability of gALB and presumably other glycated serum components across the blood-nerve barrier, as well as the observed quantitative increase in ALB, IgG, and IgM in sural nerve biopsies from patients with diabetic polyneuropathy contribute to the development of diabetic polyNEuropathy over a prolonged period of time.
Acta NeuropathologicaThe extracellular matrix of peripheral nerve in diabetic polyneuropathy
65 Citations2000J. L. Bradley, R. H. M. King +2 more
There was increased endoneurial collagenisation both in the diabetic polyneuropathy cases and the disease controls, this predominantly involving types I and III.
DiabetologiaMorphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy
62 Citations1990J. Bradley, P. K. Thomas +4 more
Differences in the basal laminal zone between the diabetic and hereditary motor and sensory neuropathy cases suggesting that the reduplicated basal lamina was more persistent in the diabetic patients.
DiabetologiaPattern of myelinated fibre loss in the sural nerve in neuropathy related to Type 1 (insulin-dependent) diabetes
53 Citations1988J. Llewelyn, P. K. Thomas +3 more
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 and a condition in which a vascular causation can be discounted.
NeurologyIntima of epineurial arterioles is increased in diabetic polyneuropathy
41 Citations1988Jan K. Korthals, Maria A. Gieron +1 more
It is indicated that intima is increased in arterioles in diabetes, due primarily to proliferation of intimal cells, and may contribute to development of diabetic polyneuropathy.
NeurologySural nerve myelin thickness and axis cylinder caliber in human diabetes
38 Citations1981K. Sugimura, P. James B. Dyck
Microscopy Research and TechniqueNeuropathology of human sympathetic autonomic ganglia
36 Citations1996Robert E. Schmidt
The frequency of some pathologic lesions in control populations as a function of age or gender necessitates the careful selection of a relatively large, appropriately matched, control population for comparison with presumed disease‐induced ganglionic neuropathology, and emphasizes the importance of quantitative comparisons.
DiabetologiaAbnormal innervation of lower limb epineurial arterioles in human diabetes
36 Citations1981Nicola Grover‐Johnson, F.Gregory Baumann +3 more
It is demonstrated that the neuropathy associated with diabetes mellitus also involves the autonomic terminal innervation of some blood vessels, and this neuropathy selectively affects the vasomotor nerves closer than 7 μm to the media.
Acta NeuropathologicaEtude ultrastructurale du nerf périphérique chez 16 diabétiques sans neuropathie clinique. Comparaisons avec 16 neuropathies diabétiques et 16 neuropathies non diabétiques
30 Citations1974C Vital, Madeleine Blanc +4 more
The present communication described changes on nerve biopsies from 16 diabetics without neuropathy, except the fact that the ankle jerks were often decreased bilaterally, as it is often encountered in diabetes mellitus.
Neuropathology and Applied NeurobiologyPERINEURIAL CALCIFICATION
26 Citations1988R. H. M. King, J. Llewelyn +3 more
A study of the occurrence of extracellular deposits of calcium in the perineurium of the human sural nerve demonstrated that there is a higher incidence in abnormal nerves than in normal material and that nerves from cases of diabetic neuropathy showed the greatest incidence of calcification.
Acta NeuropathologicaCalcification of the perineurium
23 Citations1976Anders Paetau, Matti Haltia
Necropsy of a patient who died of uremia complicating juvenile diabetes revealed selective calcification of the perineurial sheaths in the sciatic nerves, which showed electron-dense, spicular deposits, which were composed mainly of finely crystallized hydroxyapatite.
Journal of the Neurological SciencesCalcium deposits in the perineurium and their relation to lipid accumulation
18 Citations1979J. Lis, F.G.I. Jennekens +1 more
Evidence indicates that calcification of the perineurium in sural nerves occurs in human adults and is related to nerve fibre breakdown and to the local presence of lipids in the perinaurium.
Journal of the Neurological SciencesLes neuropathies periphériques du diabète sucré
16 Citations1973C Vital, J.M. Vallat +3 more
Muscle & NerveMicroanalysis of perineural calcification in diabetic nephropathy
15 Citations1981Hannu Kalimo, Jouko Mäki +2 more
Three different microanalytical methods were used to identify calcium deposits in the sciatic nerve perineurium of a 33‐year‐old woman who died after developing nephropathy, retinopathy, and neuropathy as complications of diabetes.