Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy

Selvarajah, Dinesh; Wilkinson, Iain D.; Emery, Celia; Harris, Nigel; Shaw, Pamela J.; Witte, Daniel R.; Griffiths, Paul D.; Tesfaye, Solomon

doi:10.2337/dc06-0650

Cited by 154 publications

(97 citation statements)

References 37 publications

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“…Images are presented according to neurologic convention, with right hemisphere structures shown on the right. However, evidence is now emerging that the impact of this disorder may be more generalized than previously thought, involving the spinal cord and thalamus (8,10,35). It seems logical therefore to investigate whether other areas of the brain may also be affected by the neuropathic process.…”

Section: Discussionmentioning

confidence: 97%

“…However, the relevance to the pathogenesis of neuropathy depends on whether there are changes in the brain of patients with early (subclinical) neuropathy. We have previously demonstrated that spinal cord atrophy appears to occur early in the neuropathic process, which, if also observed in the brain, would suggest that extensive and perhaps even irreversible damage may have occurred (8). Indeed, with this in mind, it is not surprising that, so far, the variety of therapeutic options attempted in subjects with DPN have been unsuccessful.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, we reported that this reduction in spinal cord volume was found early in the neuropathic process in DPN, even in patients with subclinical DPN (8). The fact that this appears to occur early in the neuropathic process in DPN is worrying as this may indicate irreversible damage.…”

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confidence: 95%

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Magnetic Resonance Neuroimaging Study of Brain Structural Differences in Diabetic Peripheral Neuropathy

et al. 2014

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OBJECTIVEDiabetic peripheral neuropathy (DPN) has hitherto been considered a disease of the peripheral nervous system only, with central nervous system (CNS) involvement largely overlooked. The aim of this study was to investigate any differences in brain structure in subjects with DPN. RESEARCH DESIGN AND METHODSThirty-six subjects with type 1 diabetes (No DPN [n = 18], Painful DPN [n = 9], Painless DPN [n = 9]) underwent neurophysiological assessment to quantify the severity of DPN. All subjects, including 18 healthy volunteers (HVs), underwent volumetric brain magnetic resonance imaging at 3 Tesla. RESULTSAdjusted peripheral gray matter volume was statistically significantly lower in subjects with painless and painful DPN (mean 599.6 mL [SEM 9.8 mL] and 585.4 mL [10.0 mL], respectively) compared with those with No DPN (626.5 mL [5.7 mL]) and HVs (639.9 mL [7.2 mL]; ANCOVA, P = 0.001). The difference in adjusted peripheral gray matter volume between subjects with No DPN and HVs and those with Painful DPN and Painless DPN was not statistically significant (P = 0.16 and 0.30, respectively). Voxel-based morphometry analyses revealed greater localized volume loss in the primary somatosensory cortex, supramarginal gyrus, and cingulate cortex (corrected P < 0.05) in DPN subjects. CONCLUSIONSThis is the first study to focus on structural changes in the brain associated with DPN. Our findings suggest increased peripheral gray matter volume loss, localized to regions involved with somatosensory perception in subjects with DPN. This may have important implications for the long-term prognosis of DPN.Diabetic peripheral neuropathy (DPN) is a common, debilitating, and distressing complication that develops in up to 30-50% of patients with diabetes (1). A painless distal symmetrical sensorimotor neuropathy, which increases the risk of foot ulceration and subsequent amputation, develops in most patients. In a significant proportion of patients, a chronic painful condition also develops, which can result in considerable disability and suffering. Although various vascular and metabolic factors (2) have been implicated, a complete understanding of the pathogenesis of DPN remains elusive (3,4). DPN has hitherto been considered a disease of the peripheral

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Magnetic Resonance Neuroimaging Study of Brain Structural Differences in Diabetic Peripheral Neuropathy

et al. 2014

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“…An important approach is the use of combination treatments; a recent trial showed that use of morphine and gabapentin together is superior to either alone in individuals with neuropathic pain, with gabapentin similar to placebo, although combination treatment was associated with an increased frequency of side effects, including constipation, dry mouth, and sedation (42). For many patients, Tesfaye suggested, "the remedy is worse than the disease," so that we need to better understand the pathogenesis of pain in neuropathy and distinguish peripheral from central pain, with a potentially important contributory factor being spinal cord abnormality (43), which his group has found to occur early in the development of diabetic neuropathy (44). Magnetic resonance imagining sprectroscopy shows abnormality of the thalamus, which acts as a gateway for pain, to occur in individuals with painful neuropathy.…”

Section: Diabetic Neuropathymentioning

confidence: 99%

Diabetic Retinopathy and Diabetic Neuropathy

Bloomgarden

2007

Diabetes Care

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“…27 Furthermore, a larger prospective study reported significantly lower mean spinal cord area in clinically asymptomatic diabetic patients with subclinical neuropathy compared to those without neurophysiological abnormalities. 28 Marked abnormalities in somatosensory-evoked potentials within the spinal cord may be present in patients with severe painful diabetic neuropathy and nearly normal peripheral sensory nerve conduction study. 29 These findings suggest that spinal cord involvement may be considered as an early manifestation in the course of neuropathy.…”

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confidence: 99%