David Levy, MD, FRCP
Mononeuropathies and other focal syndromes
Carpal tunnel syndrome (median nerve)
Carpal tunnel syndrome is very common (remember the association with primary hypothyroidism, especially in type 1 diabetes) and may present with atypical symptoms, as it is often superimposed on diabetic polyneuropathy. Consider it in any patient presenting with pain or ache in the forearm or hand, especially at night; classical presentation with pain and numbness in the thumb, index and middle fingers is relatively uncommon. Request median nerve conduction studies and refer for decompression. The surgical outcomes are either as good as or rather worse than in non-diabetic individuals. The clinical impression is that symptom relief is often less satisfactory; this may reflect other components in the diabetic hand as well as coexistent polyneuropathy. Ulnar neuropathy is also associated with diabetes, entrapment occurring at the elbow or in the forearm; pain and numbness may occur in the ring and little fingers….
The diabetic hand
In long-standing (usually type 1) diabetes the hands are affected not only by polyneuropathy and median/ulnar mononeuropathies, but by three significant connective tissue complications.
- Cheiroarthropathy (generalized connective tissue thickening/limited joint mobility) affecting the small joints of the hand, resulting in minor reduction in mobility and inability to closely oppose the palms of the hands (prayer sign).
- Dupuytren’s contracture: up to four times more common in diabetes.
- Tenosynovitis/trigger fingers: increased about 10-fold in diabetes .
In its advanced state, the hand is stiff, slightly painful, immobile and weak. All but the cheiroarthropathy can be managed, but an expert hand surgeon is needed to identify the most usefully treatable components. It is worth mentioning the threefold increased risk of adhesive capsulitis of the shoulder in diabetes, again particularly in type 1 diabetes. It also persists longer, can be bilateral and is more resistant to standard treatments.
Foot drop, caused by a common peroneal nerve mononeuropathy, is uncommon. Meralgia paresthetica (lateral femoral cutaneous nerve, L2–L3) presents with sensory symptoms, usually burning or numbness in the anterolateral thigh, sometimes aggravated by standing or walking, with a variable hypoesthetic area on examination. It may be due to compression at the inguinal ligament, and is probably more common in people with diabetes. Nerve conduction studies can help, and local steroid injection preceded by confirmatory nerve block has been reported to be useful. Usually no specific treatment is needed, and reassurance about the self-limiting nature of the condition is sufficient; however, there is an important distinction to be made from proximal motor neuropathy. The current fashion for wearing jeans low-slung over the hips may be contributory.
Proximal motor neuropathy
Also known as diabetic amyotrophy or diabetic neuropathic cachexia, it is uncommon, and the impression is that it is becoming less frequent. It is probably a lumbosacral plexopathy, rather than a femoral mononeuropathy. It usually occurs in men in their fifties or sixties, often with long-standing type 2 diabetes, taking oral hypoglycemic agents. It has a subacute onset with symmetrical thigh weakness and wasting, and there is always pain that is deep, burning and aching and, like other neuropathic pain, worse at night. Profound weight loss of more than 20 kg and anorexia are common, usually leading to a presumptive malignant diagnosis, which must be excluded with routine laboratory tests including prostate-specific antigen plus chest and lumbar and thoracic spine radiographs. Blood glucose and HbA1c may be unexpectedly low, on account of the anorexia. Insulin treatment aborts the weight loss. The natural his- tory is of slow spontaneous improvement over about 18 months.
Focal diabetic muscle infarction
Focal myonecrosis usually occurs in the vastus muscles of the thigh, very rarely in the abdominal and upper limb muscles, and presents with acute thigh pain not associated with trauma. There is sometimes a palpable and tender mass and erythema; consider infection first. It usually occurs in poorly controlled diabetes with advanced microvascular complications. MRI will demonstrate the infarction and associated muscle oedema. It resolves with conservative treatment and analgesia.
An unusual mononeuropathy involving one or more intercostal nerves that presents with acute onset of pain in a dermatomal distribution. Cutaneous hyperesthesia is characteristic. It is very occasionally associated with herniation of the intercostal or abdominal muscles. Osteoporotic or malignant spinal collapse would be the usual primary diagnoses; shingles would become obvious. Spontaneous recovery occurs over several months.
About 40% of oculomotor nerve palsies (cranial nerves III, IV and VI) occur in people with diabetes. Lateral rectus (VI) palsy and painful III nerve palsy with pupillary sparing are common, especially in type 1 diabetes. They are probably due to focal microvascular thrombosis in a capillary supplying the peripheral course of the nerve. They do not require brain MRI unless there are atypical features, for example pupillary involvement, other neurological symptoms or signs, or more than one episode.
Asymptomatic autonomic neuropathy is very common, especially if sensitive diagnostic methods are used to detect it, but only a small proportion of patients develop significant symptoms beyond erectile dysfunction. Impairment of cardiovascular reflexes is probably irreversible, but requires vigilance during anesthesia (see Chapter 3), and in long-term follow-up in ACCORD was associated with a 1.5- to 2.0-fold increased risk of all-cause and cardiovascular death. Gastrointestinal symptoms and postural hypotension are rare but can be debilitating. Treatment options for advanced autonomic neuropathy are limited, but the associated unstable blood glucose control in type 1 diabetes is an indication for considering pancreas or islet transplantation. Intensive multimodal intervention in microalbuminuric type 2 patients (glycemia, blood pressure, lipids and lifestyle) significantly reduced the risk of progression to autonomic neuropathy in the Steno-2 study. Glycemic control alone is not the important factor here: intensive glycemic control in ACCORD did not reduce mortality .
Cardiovascular autonomic reflexes (Table 10.2)
These are the only tests routinely available for the diagnosis of early autonomic neuropathy. Because there are no clear treatment options, they are required only when there is a clinical problem, for example establishing the cause of gastrointestinal symptoms or in preoperative assessment. The simplest test of vagal function is heart rate variation (sinus arrhythmia) with standardized deep breathing (5 s inspiration, 5 s expiration). It requires only a single-lead ECG rhythm strip. Decrease in systolic blood pressure after standing will detect orthostatic hypotension and is presumptive evidence of sympathetic neuropathy (other causes having been excluded). The other tests of vagal function (heart rate response to Valsalva manoeuvre and the lying/standing ratio) are too complicated for occasional use.
Management of autonomic neuropathy syndromes
Symptomatic postural hypotension
Uncommon, and correlates poorly with measured blood pressure fall, but can be disabling. It is usually worse in the morning. As a late complication it is often associated with nephropathy, posing the difficult balance of valuable renal protection with angiotensin blockade and the resulting postural symptoms, especially with ACE inhibitors. These patients also often have recumbent hypertension, demonstrable on ambulatory blood pressure testing, adding to the difficulties of management. Very careful adjustment of antihypertensive agents is needed, minimizing the use of diuretics, vasodilators and tricyclics. Short-acting agents (e.g. captopril) can be valuable for use during the night. Mechanical devices and graduated compression stockings and similar aids are of little practical value. Other, unlicensed, treatments can be considered, but use with great care and with specialist input.
- Fludrocortisone (British National Formulary, section 6.3.1): valuable, but hypertension, especially nocturnal, is a major problem. Start at a low dose (e.g. 50 µg daily) with frequent monitoring of blood pressure and electrolytes.
- DDAVP (desmopressin) (British National Formulary, section 6.5.2) is of anecdotal value, for example 0.1 mL of nasal solution or one dose of nasal spray (each 10 µg) at bedtime. Hyponatremia is a risk; monitor electrolytes frequently.
ESAs have been occasionally used in people with very severe postural symptoms (there seems to be a link between autonomic neuropathy and anemia, even in the absence of nephropathy). Discuss in detail with the nephrology team.
- Freeman R. Not all neuropathy in diabetes is of diabetic etiology: differential diagnosis of diabetic neuropathy. Curr Diab Rep 2009;9:423–31. PMID: 19954686.
- Boulton AJ, Meneses P, Ennis WJ. Diabetic foot ulcers: a framework for prevention and care. Wound Repair Regen 1999;7:7–16. PMID: 10231501.
- Bloom S, Till S, Sonksen P, Smith S. Use of a biothesiometer to measure individual vibration thresholds and their variation in 519 non-diabetic subjects. Br Med J 1984;288:1793–5. PMID: 6428547.
- Dorresteijn JA, Kriegsman DM, Assendelft WJ, Valk GD. Patient education for preventing diabetic foot ulceration. Cochrane Database Syst Rev 2010;(5): CD001488. PMID: 20464718.
- Martin CL, Albers J, Herman WH et al. Neuropathy among the Diabetes Control and Complications Trial cohort 8 years after trial completion. Diabetes Care 2006;29:340–4. PMID: 16443884.
- Chaturvedi N, Abbott CA, Whalley A, Widdows P, Leggetter SY, Boulton AJ. Risk of diabetes-related amputation in South Asian vs. Europeans in the UK. Diabetic Med 2002;19:99–104. PMID: 11874424.
- Iversen MM, Tell GS, Riise T et al. History of foot ulcer increases mortality among individuals with diabetes: ten-year follow-up of the Nord-Trondelag Health Study, Norway. Diabetes Care 2009;32:2193–9. PMID: 19729524.
- Schaper NC. Diabetic foot ulcer classification system for research purposes: a progress report on criteria for including patients in research studies. Diabetes Metab Res Rev 2004;20(Suppl. 1):S90–S95. PMID:15150820.
- Lavery LA, Armstrong DG, Peters EJ, Lipsky BA. Probe-to-bone test for diagnosing diabetic foot osteomyelitis. Reliable or relic? Diabetes Care 2007;30: 270–4. PMID: 17259493.
- Malmstedt J, Leander K, Wahlberg E, Karlström L, Alfredsson L, Swedenborg J. Outcome after leg bypass surgery for critical limb ischemia is poor in patients with diabetes: a population-based cohort study. Diabetes Care 2008;31:887–92. PMID: 18268064.
- Bowling FL, Salgami EV, Boulton AJ. Larval therapy: a novel treatment in eliminating methicillin-resistant Staphylococcus aureus from diabetic foot ulcers. Diabetes Care 2007;30:370–1. PMID: 17259512,
- Löndahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care 2010;33:998–1003. PMID: 15106239. The results of this study support the findings of a Cochrane systematic review of 2004.
- Chantelau E. The perils of procrastination: effects of early vs. delayed detection and treatment of incipient Charcot fracture. Diabetic Med 2005;22:1707–12. PMID: 16401316.
- Basu S, Chryssikos T, Houseni M et al. Potential role of FDG PET in the setting of diabetic neuroosteoarthropathy: can it differentiate uncomplicated Charcot’s neuroarthropathy from osteomyelitis and soft-tissue infection? Nucl Med Commun 2007;28:465–72. PMID: 17460537.
- Steel JM, Young RJ, Lloyd GG, Clarke BF. Clinically apparent eating disorders in young diabetic women: associations with painful neuropathy and other complications. Br Med J 1987;294:859–62. PMID: 3105777.
- Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology 2003;60:927–34. PMID: 12654955.
- Smith LL, Burnet SP, McNeil JD. Musculoskeletal manifestations of diabetes mellitus. Br J Sports Med 2003;37:30–5. PMID: 12547740.
- Pop-Busui R, Evans GW, Gerstein HC et al. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial. Diabetes Care 2010;33:1578–84. PMID: 20215456.
- Grover SA, Lowensteyn I, Kaouache M et al. The prevalence of erectile dys- function in the primary care setting: importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006;166:213–19. PMID: 16432091.
- Gazzaruso C, Giordanetti S, DeAmici E et al. Relationship between erectile dysfunction and silent myocardial ischemia in apparently uncomplicated type 2 diabetic patients. Circulation 2004;110:22–6. PMID: 15210604.
- Scranton RE, Lawler E, Botteman M et al. Effect of treating erectile dysfunction on management of systolic hypertension. Am J Cardiol 2007;100:459–63. PMID: 17659929.
- Wu FC, Tajar A, Beynon JM et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363:123–35. PMID: 20554979.
- Corona G, Mannucci E, Petrone L et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res 2006;18:190–7. PMID: 16136189.
- Camilleri M. Diabetic gastroparesis. N Engl J Med 2007;356:820–9. PMID: 17314341.
- Ewing DJ et al. Diabetes Care. 1985;8:491–8.
For more information and to purchase this book, just follow this link:
David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK
This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)