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Magnetic Resonance Imaging of the Central Nervous System in Diabetic Neuropathy

  • Microvascular Complications-Neuropathy (D Ziegler, Section Editor)
  • Published:
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Abstract

Diabetic ‘peripheral’ neuropathy (DPN) is one of the common sequelae to the development of both type-1 and type-2 diabetes mellitus. Neuropathy has a major negative impact on quality of life. Abnormalities in both peripheral vasculature and nerve function are well documented and, in addition, evidence is emerging regarding changes within the central nervous system (CNS) that are concomitant with the presence of DPN. The often-resistant nature of DPN to medical treatment highlights the need to understand the role of the CNS in neuropathic symptomatology and progression, as this may modulate therapeutic approaches. Advanced neuroimaging techniques, especially those that can provide quantitative measures of structure and function, can provide objective markers of CNS status. With that comes great potential for not only furthering our understanding of involvement of the CNS in neuropathic etiology but also most importantly aiding the development of new and more effective, targeted, analgesic interventions.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Tesfaye S. Advances in the management of painful diabetic neuropathy. Curr Opin Support Palliat Care. 2009;3:136–43.

    Article  PubMed  Google Scholar 

  2. Daousi C, MacFarlane IA, Woodward A, et al. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004;21:976–82.

    Article  PubMed  CAS  Google Scholar 

  3. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29:1518–22.

    Article  PubMed  Google Scholar 

  4. Gore M, Brandenburg N, Dukes, et al. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptoms Manage. 2005;30:374–85.

    Article  Google Scholar 

  5. Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain. 2006;22:681–5.

    Article  PubMed  Google Scholar 

  6. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000;47(2):123–8.

    Article  PubMed  CAS  Google Scholar 

  7. Gore M, Brandenburg N, Hoffman DL, et al. Burden of illness in painful diabetic peripheral neuropathy: the patients’ perspectives. J Pain. 2006;7(12):982–900.

    Google Scholar 

  8. Quattrini C, Tesfaye S. Understanding the impact of painful diabetic neuropathy. Diabetes Metab Res Rev. 2003;19:S2–8.

    Article  PubMed  Google Scholar 

  9. Jensen T, Baconja MM, Jimenez H, Tesfaye S, Valensi P, Ziegler. Management of diabetic neuropathic pain. Diab Vas Dis Res. 2006;3:108–19.

    Article  Google Scholar 

  10. Tesfaye S, Vileikyte L, Rayman G, et al on behalf of the Toronto Expert Panel on diabetic neuropathy painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011. [Epub ahead of print].

  11. Lukic IK, Humpert PM, Nawroth PP, Bierhaus A. The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy. Ann N Y Acad Sci. 2008;1126:76–80.

    Article  PubMed  CAS  Google Scholar 

  12. Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics. 2009;6:638–47.

    Article  PubMed  CAS  Google Scholar 

  13. Vincent AM, Callaghan BC, Smith AL, Feldman EL. Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nat Rev Neurol. 2011;7:573–83.

    Article  PubMed  CAS  Google Scholar 

  14. Said G, Slama G, Selva J. Progressive centripital degeneration of axons in small-fiber type diabetic polyneuropathy. A clinical and pathological study. Brain. 1983;106:791.

    Article  PubMed  Google Scholar 

  15. Malik RA, Newrick PG, Sharma AK, et al. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia. 1989;32:92–102.

    Article  PubMed  CAS  Google Scholar 

  16. Tesfaye S, Malik R, Ward JD. Vascular factors in diabetic neuropathy. Diabetologia. 1994;37:847–54.

    Article  PubMed  CAS  Google Scholar 

  17. Malik RA, Tesfaye S, Thompson SD, et al. Endoneurial localisation of microvascular damage in human diabetic neuropathy. Diabetologia. 1993;36:454–9.

    Article  PubMed  CAS  Google Scholar 

  18. Malik RA, Tesfaye S, Thompson SD, et al. Transperineurial capillary abnormalities in the sural nerve of patients with diabetic neuropathy. Microvasc Res. 1994;48:236–45.

    Article  PubMed  CAS  Google Scholar 

  19. Giannini C, Dyck PJ. Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus. Ann Neurol. 1994;36:408–15.

    Article  PubMed  CAS  Google Scholar 

  20. Ferguson SC, Blane A, Perros P, McCrimmon RJ, Best JJ, Wardlaw J, et al. Cognitive ability and brain structure in type 1 diabetes: relation to microangiopathy and preceding severe hypoglycemia. Diabetes. 2003;52:149–56.

    Article  PubMed  CAS  Google Scholar 

  21. Manschot SM, Brands AM, van der Grond J, et al. Utrecht Diabetic Encephalopathy Study Group. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes. 2006;55:1106–13.

    Article  PubMed  CAS  Google Scholar 

  22. Reske-Neilsen E, Lundbaek K, Rafaelsen OJ. Pathological changes in the central and peripheral nervous system of young long-term diabetics: II. Spinal cord and peripheral nerve. Diabetologia. 1968;4:34–43.

    Article  Google Scholar 

  23. Slager UT. Diabetic myelopathy. Arch Pathol Lab Med. 1978;102:467–9.

    PubMed  CAS  Google Scholar 

  24. Lauterbur PC. Image formation by induced local interactions: examples employing NMR. Nature. 1973;242:190–1.

    Article  CAS  Google Scholar 

  25. Wilkinson ID, Paley MNJ. Magnetic resonance imaging: basic principles, Chapter 4. In: Grainger A, Adam D, editors. Diagnostic radiology: a textbook of medical imaging. 5th ed. Churchill Livingstone; 2007. Philadelphia, USA.

  26. Ogawa S, Tank DW, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A. 1992;89:5951–5.

    Article  PubMed  CAS  Google Scholar 

  27. Boguslawska R, Romanowski CAJ, Wilkinson ID, et al. Introduction to functional magnetic resonance imaging. Med Sci Monit. 1999;5:1179–86.

    Google Scholar 

  28. Wilkinson ID. Perfusion and diffusion imaging in chronic carotid disease, Chapter 19. In: Gillard, Waldman, Barker, editors. Clinical MR neuroimaging: physiological and functional techniques. Cambridge University Press; Cambridge, UK, 2010.

  29. Wilkinson ID, Paley M, Chong WK, et al. Proton spectroscopy in HIV infection: relaxation times of cerebral metabolites. Magn Reson Imaging. 1994;12:951–7.

    Article  PubMed  CAS  Google Scholar 

  30. Wilkinson ID, Lunn S, Miszkiel KA, et al. Proton MRS and quantitative MRI assessment of the short-term neurological response to anti-retroviral therapy in AIDS. J Neurol Neurosurg Psychiatry. 1997;63:477–82.

    Article  PubMed  CAS  Google Scholar 

  31. Puts NA, Edden RA. In vivo magnetic resonance spectroscopy of GABA: a methodological review. Prog Nucl Magn Reson Spectrosc. 2012;60:29–41.

    Article  PubMed  CAS  Google Scholar 

  32. Jones DK, editor. Diffusion MRI: theory, methods, and applications. Oxford University Press; Oxford, UK, 2010.

  33. Eaton S, Harris ND, Rajbhandari SM, et al. Spinal cord involvement in diabetic peripheral neuropathy. Lancet. 2001;358:35–6.

    Article  PubMed  CAS  Google Scholar 

  34. Selvarajah D, Wilkinson ID, Emery CJ, et al. Early involvement of the spinal cord in diabetic peripheral neuropathy. Diabetes Care. 2006;29:2664–9.

    Article  PubMed  Google Scholar 

  35. Suzuki C, Ozaki I, Taosaki M, et al. Peripheral and central conduction abnormalities in diabetes mellitus. Neurology. 2000;54:1932–7.

    Article  PubMed  CAS  Google Scholar 

  36. Wilkinson ID, Selvarajah D, Hutton M, Griffiths PD, Gandhi R, Tesfaye S. Imaging of the cortico-spinal tracts in diabetic neuropathy using diffusion tensor magnetic resonance. Diabetes. 2009;58 (Supp 1): A214.

  37. McCormick DA, Bal T. Sensory gating mechanisms of the thalamus. Curr Opin Neurobiol. 1994;4:550–6.

    Article  PubMed  CAS  Google Scholar 

  38. Selvarajah D, Wilkinson ID, Emery CJ, Shaw PJ, Griffiths PD, Gandhi R, et al. Thalamic neuronal dysfunction and chronic sensorimotor distal symmetrical polyneuropathy in patients with type 1 diabetes mellitus. Diabetologia. 2008;51:2088–92.

    Article  PubMed  CAS  Google Scholar 

  39. Gandhi R, Selvarajah D, Emery CJ, Wilkinson ID, Tesfaye S. Neurochemical abnormalities within sensory pathways in the brain in diabetic neuropathy. Diabetologia. 2008;51(Supp 1):1–588.

    Google Scholar 

  40. Sorensen L, Siddall PJ, Trenell MI, Yue DK. Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. Diabetes Care. 2008;31:980–1.

    Article  PubMed  Google Scholar 

  41. Petrou M, Pop-Busui R, Foerster BR, Edden RA, et al. Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy. Acad Radiol. 2012;19:607–12.

    Article  PubMed  Google Scholar 

  42. •• Selvarajah D, Wilkinson ID, Gandhi R, Griffiths PD, Tesfaye S. Microvascular perfusion abnormalities of the thalamus in painful but not painless diabetic polyneuropathy: a clue to the pathogenesis of pain in type 1 diabetes. Diabetes Care. 2011;34:718–20. Data from this preliminary study implies increased blood supply to the thalamus in patients with painful diabetic neuropathy.

    Article  PubMed  Google Scholar 

  43. Paulson PE, Wiley JW, Morrow TJ. Concurrent activation of the somatosensory forebrain and deactivation of periacqueductal gray associated with diabetes-induced neuropathic pain. Exp Neurol. 2007;208:305–13.

    Article  PubMed  Google Scholar 

  44. Fischer TZ, Tan AM, Waxman SG. Thalamic neuron hyperexcitability and enlarged receptive fields in the STZ model of diabetic pain. Brain Res. 2009;1268:154–61.

    Article  PubMed  CAS  Google Scholar 

  45. Melzack R. From the gate to the neuromatrix. Pain. 1999;(Suppl 6):S121–6.

  46. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–8.

    Article  PubMed  Google Scholar 

  47. Bushnell MC, Duncan GH, Hofbauer RK, et al. Pain perception: is there a role for primary somatosensory cortex? Proc Natl Acad Sci U S A. 1999;96:7705–9.

    Article  PubMed  CAS  Google Scholar 

  48. Kanda M, Nagamine T, Ikeda A, et al. Primary somatosensory cortex is actively involved in pain processing in human. Brain Res. 2000;853:282–9.

    Article  PubMed  CAS  Google Scholar 

  49. Peyron R, García-Larrea L, Grégoire MC, et al. Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case. Pain. 2000;84:77–87.

    Article  PubMed  CAS  Google Scholar 

  50. Wilkinson ID, Gandhi RA, Hunter MD, et al. Functional MRI and response to pain in diabetic neuropathy. Diabet Med. 2007;24 Suppl 1:187.

    Google Scholar 

  51. Wilkinson ID, Gandhi R, Hunter MD, et al. A functional magnetic resonance imaging study demonstrating alterations in brain responses to acute pain stimulation in diabetic neuropathy. Diabetologia. 2007;50(Supp 1):1–538.

    Google Scholar 

  52. Tseng MT, Chiang MC, Chao CC, Tseng WY, Hsieh, ST. fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations. Hum Brain Mapp. 2012. [Epub ahead of print].

  53. • Manor B, Newton E, Abduljalil A, Novak V. The relationship between brain volume and walking outcomes in older adults with and without diabetic peripheral neuropathy. Diabetes Care. 2012;35:1907–12. In this study, patients’ walking disability is linked with the presence of intracranial brain atrophy.

    Article  PubMed  Google Scholar 

  54. •• Selvarajah D, Maxwell M, Davies J, et al. Diabetic neuropathy associated with increased cortical atrophy on brain MRI in patients with Type-1 Diabetes. Diabetic Med. 2013;30 Suppl 1:14. This work identifies atrophy of the somatosensory cortex in people with diabetic neuropathy.

    Google Scholar 

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Conflict of Interest

Iain D. Wilkinson declares that he has no conflict of interest.

Dinesh Selvarajah declares that he has no conflict of interest.

Marni Greig declares that he has no conflict of interest.

Pallai Shillo declares that he has no conflict of interest.

Elaine Boland declares that she has no conflict of interest.

Rajiv Gandhi declares that he has no conflict of interest.

Solomon Tesfaye declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Iain D. Wilkinson.

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Wilkinson, I.D., Selvarajah, D., Greig, M. et al. Magnetic Resonance Imaging of the Central Nervous System in Diabetic Neuropathy. Curr Diab Rep 13, 509–516 (2013). https://doi.org/10.1007/s11892-013-0394-8

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