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November 18, 1988, Vol 260, No. 19 >
ARTICLE | November 18, 1988

Diabetic Neuropathy: Title and subTitle BreakStructural Analysis of Nerve Hydration by Magnetic Resonance Spectroscopy FREE

Richard H. Griffey, PhD; R. Philip Eaton, MD; Randy R. Sibbitt, MD; Wilmer L. Sibbitt, Jr, MD; Joseph M. Bicknell, MD
[+] Author Affiliations

Reprint requests to the Department of Medicine, University of New Mexico School of Medicine, UNMH 7-South, Albuquerque, NM 87131 (Dr Eaton).


JAMA. 1988;260(19):2872-2878. doi:10.1001/jama.1988.03410190120034
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References

The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated with aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.

(JAMA 1988;260:2872-2878)

REFERENCES

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Thomas PK, Brown MJ:  Diabetic polyneuropathy , in Dyck PJ, Thomas PK, Asbury AK, et al (eds): Diabetic Neuropathy . Philadelphia, WB Saunders Co, 1987;, pp 56-65.
2 +
Rollo J: Cases of Diabetes Mellitus , ed 2. London, Dilly, 1978;.
3 +
Brown MJ, Martin JR, Asbury AK:  Painful diabetic neuropathy: A morphometric study . Arch Neurol 1976;;33:164.
4 +
Green DA, Brown MJ, Braunstein SN, et al:  Comparison of clinical course and sequential electrophysiological tests in diabetics with symptomatic polyneuropathy and its implications for clinical trials . Diabetes 1981;;30:139-147.
5 +
Powell HC:  Pathology of diabetic neuropathy: New observations, new hypotheses . Lab Invest 1983;;49:515-518.
6 +
Jacobsen J:  Peripheral nerves in early experimental diabetes: Expansion of the endoneurial space as a cause of increased water content . Diabetologia 1978;;14:113-119.
7 +
Gabbay KH, Snider JJ:  Nerve conduction defect in galactose-fed rats . Diabetes 1972;;21:295-300.
8 +
Gabbay KH:  The sorbitol pathway and the complications of diabetes . N Engl J Med 1973;;288:831-836.
9 +
Clements RA:  Diabetic neuropathy: New concepts of its etiology . Diabetes 1979;;28:604-611.
10 +
Low PA, Dyck PJ, Schmelzer JD:  Chronic elevation of endoneurial fluid pressure is associated with low-grade fiber pathology . Muscle Nerve 1982;;5:162-165.
11 +
Myers RR, Powell HC:  Galactose neuropathy: Impact of chronic endoneurial edema on nerve blood flow . Ann Neurol 1984;;16:587-594.
12 +
Tuck RR, Schmelzer JD, Low PA:  Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy . Brain 1984;;107:935-950.
13 +
Cameron NE, Leonard MB, Ross IS, et al:  The effects of sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocin-diabetic rat . Diabetologia 1986;; 29:168-174.
14 +
Griffey RH, Eaton RP, Gasparovic C, et al:  Galactose neuropathy: Structural changes evaluated by nuclear magnetic resonance spectroscopy . Diabetes 1987;;36:776-778.
15 +
Dyck PJ, Sherman WR, Hallcher LM, et al:  Human diabetic endoneurial sorbitol, fructose, and myoinositol related to sural nerve morphometry . Ann Neurol 1980;;8:590-596.
16 +
Odusote K, Ohwovoriole A, Roberts O:  Electrophysiologic quantification of distal polyneuropathy in diabetes . Neurology 1985;;35:1432-1437.
17 +
Braddom RI, Johnson EW:  Standardization of H reflex and diagnostic use in S1 radiculopathy . Arch Phys Med Rehabil 1974;;55:161-166.
18 +
Electromyography and Clinical Neurophysiology Laboratory: A Manual of Techniques in Motor and Sensory Clinical Neurophysiology . Rochester, Minn, Mayo Clinic, 1986;.
19 +
Kjos BO, Ehman RL, Brant-Zawadzki M, et al:  Reproducibility of relaxation times and spin density calculated from routine MR imaging sequences . Am J Radiol 1985;;144:1165-1170.
20 +
Dixon WT:  Separate magnetic resonance images of water and fat using phase modulation . Radiology 1984;;153:189.
21 +
Young RJ, Ewing DJ, Clark BF:  Chronic and remitting painful diabetic polyneuropathy: Correlations with subsequent changes in neurophysiology . Diabetes Care 1988;;11:34-40.
22 +
Graf RJ, Halter JB, Halar E, et al:  Nerve conduction abnormalities in untreated maturity-onset diabetes: Relation to levels of fasting plasma glucose and glycosylated hemoglobin . Ann Intern Med 1979;;90:298-303.
23 +
Jolesz FA, Polak JF, Ruenzel PW, et al:  Wallerian degeneration demonstrated by magnetic resonance: Spectroscopic measurements on peripheral nerve . Radiology 1984;;152:85-87.
24 +
Dyck PJ, Karnes JL, O'Brien P, et al:  The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia . Ann Neurol 1986;; 19:440-449.
25 +
Johnson PC, Doll SC, Cromey DW:  Pathogenesis of diabetic neuropathy . Ann Neurol 1986;; 19:450-457.
26 +
Nukada H, Dyck PJ:  Microsphere embolization of nerve capillaries and fiber degeneration . Am J Pathol 1984;;115:275-287.
27 +
Dyck PJ, Hansen S, Karnes J, et al:  Capillary number and percentage closed in human diabetic sural nerve . Proc Natl Acad Sci USA 1985;;82:2513-2517.
28 +
Yasuda H, Dyck PJ:  Abnormalities of endoneurial micro vessels and sural nerve pathology in diabetic neuropathy . Neurology 1987;;37:20-28.
29 +
Fagerberg SE:  Diabetic neuropathy, a clinical and histological study on the significance of vascular affections . Acta Med Scand 1959;;164( (suppl 345) ):1-70.
30 +
Powell HC, Rosoff J, Myers RR:  Microangiopathy in human diabetic neuropathy . Acta Neuropathol 1985;;68:295-305.
31 +
Newrick PG, Wilson AJ, Jakubowski J, et al:  Sural nerve oxygen tension in diabetes . Br Med J 1986;;293:1053-1054.
32 +
Ohi T, Poduslo JF, Dyck PJ:  Increased endoneurial albumin in diabetic polyneuropathy . Neurology 1985;;35:1790-1791.
33 +
Brownlee M, Vlassara H, Cerami A:  Trapped immunoglobulins on peripheral nerve myelin from patients with diabetes mellitus . Diabetes 1986;; 35:999-1003.
34 +
Graham AR, Johnson PC:  Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy . Ann Neurol 1985;;17:450-454.
35 +
Sutherland NH, Pollock M:  Endoneurial ATPase activity in Tangier disease and other peripheral neuropathies . Muscle Nerve 1984;;7:447-453.
36 +
Das PK, Bray GM, Aguayo AJ, et al:  Diminished ouabain-sensitive NA-K ATPase activity in sciatic nerves of rats with streptozotocin-induced diabetes . Exp Neurol 1976;;53:285-288.
37 +
Eaton RP:  The collagen hydration hypothesis: A new paradigm for the secondary complications of diabetes mellitus . J Chronic Dis 1986;;39:763-766.
38 +
Mizisin AP, Powell HC, Myers RR:  Edema and increased endoneurial sodium in galactose neuropathy reversed with an aldose reductase inhibitor . J Neurol Sci 1986;;74:35-43.
39 +
Ward JI, Baker RWR, David B:  Effectof blood sugar control on the accumulation of sorbitol and fructose in nervous tissue . Diabetes 1972;;21:1173-1178.
40 +
Hale PJ, Nattrass M, Silverman SH, et al:  Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients . Diabetologia 1987;;30:464-467.
41 +
Jedziniak JA, Chylack LT Jr, Cheng HM, et al:  The sorbitol pathway in the human lens: Aldose reductase and polyol dehydrogenase . Invest Ophthal Vis Res 1981;;20:314-326.
42 +
Lucarelli P, Sacchi R, Corbon RM, et al:  Genetic polymorphisms in juvenile onset diabetes . Hum Hered 1978;;28:89-95.

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1 +
Thomas PK, Brown MJ:  Diabetic polyneuropathy , in Dyck PJ, Thomas PK, Asbury AK, et al (eds): Diabetic Neuropathy . Philadelphia, WB Saunders Co, 1987;, pp 56-65.
2 +
Rollo J: Cases of Diabetes Mellitus , ed 2. London, Dilly, 1978;.
3 +
Brown MJ, Martin JR, Asbury AK:  Painful diabetic neuropathy: A morphometric study . Arch Neurol 1976;;33:164.
4 +
Green DA, Brown MJ, Braunstein SN, et al:  Comparison of clinical course and sequential electrophysiological tests in diabetics with symptomatic polyneuropathy and its implications for clinical trials . Diabetes 1981;;30:139-147.
5 +
Powell HC:  Pathology of diabetic neuropathy: New observations, new hypotheses . Lab Invest 1983;;49:515-518.
6 +
Jacobsen J:  Peripheral nerves in early experimental diabetes: Expansion of the endoneurial space as a cause of increased water content . Diabetologia 1978;;14:113-119.
7 +
Gabbay KH, Snider JJ:  Nerve conduction defect in galactose-fed rats . Diabetes 1972;;21:295-300.
8 +
Gabbay KH:  The sorbitol pathway and the complications of diabetes . N Engl J Med 1973;;288:831-836.
9 +
Clements RA:  Diabetic neuropathy: New concepts of its etiology . Diabetes 1979;;28:604-611.
10 +
Low PA, Dyck PJ, Schmelzer JD:  Chronic elevation of endoneurial fluid pressure is associated with low-grade fiber pathology . Muscle Nerve 1982;;5:162-165.
11 +
Myers RR, Powell HC:  Galactose neuropathy: Impact of chronic endoneurial edema on nerve blood flow . Ann Neurol 1984;;16:587-594.
12 +
Tuck RR, Schmelzer JD, Low PA:  Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy . Brain 1984;;107:935-950.
13 +
Cameron NE, Leonard MB, Ross IS, et al:  The effects of sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocin-diabetic rat . Diabetologia 1986;; 29:168-174.
14 +
Griffey RH, Eaton RP, Gasparovic C, et al:  Galactose neuropathy: Structural changes evaluated by nuclear magnetic resonance spectroscopy . Diabetes 1987;;36:776-778.
15 +
Dyck PJ, Sherman WR, Hallcher LM, et al:  Human diabetic endoneurial sorbitol, fructose, and myoinositol related to sural nerve morphometry . Ann Neurol 1980;;8:590-596.
16 +
Odusote K, Ohwovoriole A, Roberts O:  Electrophysiologic quantification of distal polyneuropathy in diabetes . Neurology 1985;;35:1432-1437.
17 +
Braddom RI, Johnson EW:  Standardization of H reflex and diagnostic use in S1 radiculopathy . Arch Phys Med Rehabil 1974;;55:161-166.
18 +
Electromyography and Clinical Neurophysiology Laboratory: A Manual of Techniques in Motor and Sensory Clinical Neurophysiology . Rochester, Minn, Mayo Clinic, 1986;.
19 +
Kjos BO, Ehman RL, Brant-Zawadzki M, et al:  Reproducibility of relaxation times and spin density calculated from routine MR imaging sequences . Am J Radiol 1985;;144:1165-1170.
20 +
Dixon WT:  Separate magnetic resonance images of water and fat using phase modulation . Radiology 1984;;153:189.
21 +
Young RJ, Ewing DJ, Clark BF:  Chronic and remitting painful diabetic polyneuropathy: Correlations with subsequent changes in neurophysiology . Diabetes Care 1988;;11:34-40.
22 +
Graf RJ, Halter JB, Halar E, et al:  Nerve conduction abnormalities in untreated maturity-onset diabetes: Relation to levels of fasting plasma glucose and glycosylated hemoglobin . Ann Intern Med 1979;;90:298-303.
23 +
Jolesz FA, Polak JF, Ruenzel PW, et al:  Wallerian degeneration demonstrated by magnetic resonance: Spectroscopic measurements on peripheral nerve . Radiology 1984;;152:85-87.
24 +
Dyck PJ, Karnes JL, O'Brien P, et al:  The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia . Ann Neurol 1986;; 19:440-449.
25 +
Johnson PC, Doll SC, Cromey DW:  Pathogenesis of diabetic neuropathy . Ann Neurol 1986;; 19:450-457.
26 +
Nukada H, Dyck PJ:  Microsphere embolization of nerve capillaries and fiber degeneration . Am J Pathol 1984;;115:275-287.
27 +
Dyck PJ, Hansen S, Karnes J, et al:  Capillary number and percentage closed in human diabetic sural nerve . Proc Natl Acad Sci USA 1985;;82:2513-2517.
28 +
Yasuda H, Dyck PJ:  Abnormalities of endoneurial micro vessels and sural nerve pathology in diabetic neuropathy . Neurology 1987;;37:20-28.
29 +
Fagerberg SE:  Diabetic neuropathy, a clinical and histological study on the significance of vascular affections . Acta Med Scand 1959;;164( (suppl 345) ):1-70.
30 +
Powell HC, Rosoff J, Myers RR:  Microangiopathy in human diabetic neuropathy . Acta Neuropathol 1985;;68:295-305.
31 +
Newrick PG, Wilson AJ, Jakubowski J, et al:  Sural nerve oxygen tension in diabetes . Br Med J 1986;;293:1053-1054.
32 +
Ohi T, Poduslo JF, Dyck PJ:  Increased endoneurial albumin in diabetic polyneuropathy . Neurology 1985;;35:1790-1791.
33 +
Brownlee M, Vlassara H, Cerami A:  Trapped immunoglobulins on peripheral nerve myelin from patients with diabetes mellitus . Diabetes 1986;; 35:999-1003.
34 +
Graham AR, Johnson PC:  Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy . Ann Neurol 1985;;17:450-454.
35 +
Sutherland NH, Pollock M:  Endoneurial ATPase activity in Tangier disease and other peripheral neuropathies . Muscle Nerve 1984;;7:447-453.
36 +
Das PK, Bray GM, Aguayo AJ, et al:  Diminished ouabain-sensitive NA-K ATPase activity in sciatic nerves of rats with streptozotocin-induced diabetes . Exp Neurol 1976;;53:285-288.
37 +
Eaton RP:  The collagen hydration hypothesis: A new paradigm for the secondary complications of diabetes mellitus . J Chronic Dis 1986;;39:763-766.
38 +
Mizisin AP, Powell HC, Myers RR:  Edema and increased endoneurial sodium in galactose neuropathy reversed with an aldose reductase inhibitor . J Neurol Sci 1986;;74:35-43.
39 +
Ward JI, Baker RWR, David B:  Effectof blood sugar control on the accumulation of sorbitol and fructose in nervous tissue . Diabetes 1972;;21:1173-1178.
40 +
Hale PJ, Nattrass M, Silverman SH, et al:  Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients . Diabetologia 1987;;30:464-467.
41 +
Jedziniak JA, Chylack LT Jr, Cheng HM, et al:  The sorbitol pathway in the human lens: Aldose reductase and polyol dehydrogenase . Invest Ophthal Vis Res 1981;;20:314-326.
42 +
Lucarelli P, Sacchi R, Corbon RM, et al:  Genetic polymorphisms in juvenile onset diabetes . Hum Hered 1978;;28:89-95.

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