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Diabetic Neuropathy? Why Diabetic Neuropathy? • Diabetes is the most common cause of Diabetic Neuropathy peripheral neuropathy in the western countries • There are 20.8 million Americans with Bakri Elsheikh, MD diabetes mellitus The Ohio State University Medical Center • Nearly one third are undiagnosed • There are 54 million Americans who have pre-diabetes American Diabetes Association - http://www.diabetes.org Diabetic Neuropathy Talk Outline Why Diabetic Neuropathy? • Why diabetic neuropathy? • What is diabetic neuropathy ? • Diabetic neuropathy is a major contributory factor • How common is diabetic neuropathy in the pathogenesis of • Who gets diabetic neuropathy? foot ulceration and • How to recognize the different types? Charcot joints • How to evaluate diabetic neuropathy? • How does hyperglycemia causes peripheral • 15% of diabetics develop neuropathy? foot ulcer during life time • How to treat it? • What is the future prospective? 1 What is Diabetic The Rochester Diabetic Neuropathy? Neuropathy Study Neuropathy type Type 1 Type 2 • A simple definition of DN for clinical Any neuropathy 66% 59% practice is Distal neuropathy 54% (15%) 45% (13%) “ The presence of symptoms and/or signs of CTS 33% (11%) 35% (6%) peripheral nerve dysfunction in people with Autonomic 7% 5% diabetes after exclusion of other causes” Ulnar neuropathy 2% 2% Boulton AJM et al. Diabet Med 1998 LSRPN 1% 1% • About 10%of diabetic patients had neurologic deficits attributable to non-diabetic causes Dyck PJ et al. Neurology 1993 How common is Staging Severity of diabetic neuropathy? Diabetic Neuropathy • N0: No objective evidence of DN • A prospective study of 4400 patients found • N1: Asymptomatic polyneuropathy 8% had neuropathy at the time of N1a: No symptoms, no signs, abnormal diagnosis, and 50% after 25 years test N1b: No symptoms, abnormal signs, Pirart J. Diabetes Care 1978 abnormal test • A landmark study of 380 diabetic subjects • N2: Symptomatic neuropathy were evaluated for development and N2a: Symptoms, signs and test abnormality distribution of neuropathy N2b: N2a plus significant ankle dorsiflexor weakness Dyck PJ et al. Neurology 1993 • N3: Disabling neuropathy 2 The Rochester Diabetic Neuropathy Study Risk factors for DPN N2b 1% N2a 12% • Duration of diabetes N1 39% • The degree of hyperglycemia N2a 9% N1 32% N2b 6% • The presence of other microvascular N0 55% N0 46% complications is a marker for the presence of neuropathy rather than a risk factor per se Type 1 Type 2 Dyck PJ et al. Diabetes Care 1992; Adler AI et al. Diabetes care 1997; Van de Poll-Franse L et al. Diabet Med 2002 The Rochester Diabetic Diabetic Neuropathy Neuropathy Study Classification Symmetric Asymmetric N2b N2a N2b N2b Diabetic distal N2a Cranial neuropathies N2a polyneuropathy N0 N1 N0 Diabetic Mononeuropathies autonomic neuropathy N0 N1 N1 Polyneuropathy with Radiculoplexus glucose impairment neuropathies Diabetic truncal Diabetic cachectic radiculoneuropathy < 10 years >10 - <20 years > 20 years neuropathy CIDP in diabetes Dyck PJ et al. Neurology 1993 3 Diabetic Distal Symmetric Polyneuropathy • Symptoms begin with sensory disturbance usually in the toes Symmetric Diabetic and feet • With time, as symptoms progress to involve the calves, the hands Neuropathies may be affected • eventually may develop a “tear drop” pattern of loss over the anterior trunk • In patients with hand symptoms early in the course, entrapment neuropathy is the likely cause Diabetic Distal Symmetric Diabetic Distal Symmetric Polyneuropathy Polyneuropathy • The most common form of diabetic Clinical examination tools: neuropathy • Pin prick test using • It is a length dependent, distal process a disposable pin • Light touch using • It is very slowly progressive a cotton wisp • It is rarely disabling • Vibration test using • Sensory symptoms predominate 128Hz tuning fork • Ankle reflex using a • Painful symptoms are present in about 10% reflex hammer of the patients • Pressure perception using • Motor symptoms are usually minimal 10 g monofilament may be used to assess the risk of ulceration 4 Diabetic Autonomic Polyneuropathy with Neuropathy Glucose Impairment • Usually accompanies mixed neuropathies • Usually correlates with severity of somatic neuropathy • The neuropathy associated with IGT is • Occasionally, occurs out of proportion to milder than the neuropathy associated with underlying neuropathy newly diagnosed diabetes mellitus • May involve cardiovascular, genitourinary, • Small fiber involvement may be the earliest gastrointestinal, and/or thermoregulatory systems detectable sign of neuropathy • Common symptoms are orthostatic dizziness, Sumner CJ et al. Neurology 2003 erectile dysfunction, nausea, vomiting, bloating, abdominal pain, constipation or diarrhea, anhydrosis and hyperhidrosis. Vinik AI et al. Diabetes Care 2003 Polyneuropathy with Diabetic Neuropathic Glucose Impairment Cachexia • Rare entity • Acute painful neuropathy • Prospective study of 107 patients with • Associated with rapid, profound weight loss idiopathic neuropathy found 13 of 107 had diabetes and 36 had IGT • Occurs in the setting of poor glucose control • Hypersensitivity and painful dyesthesias over the Singleton JR et al. Diabetes Care 2001 limbs and trunk • Minimal sensory impairment • Normal to near normal strength • Prognosis is good Ellenberg M Diabetes 1974; Jackson CE et al. J Neurol Neurosurg Psychiatry 1998 5 Chronic Inflammatory Demyelinating Diabetic Polyradiculoneuropathy (CIPD) in Diabetes Mononeuropathies • Diabetics are more susceptible to • The possibility of increased incidence in compression neuropathies diabetic patients is raised • Median neuropathy at the wrist (carpal • It is a gradually progressive disorder tunnel syndrome) • It is usually painless with proximal and • Ulnar neuropathy at the elbow distal arm and leg weakness • Common peroneal neuropathy at the fibular • Diagnosis is problematic head Cornblath DR et al. Ann Neurol 1987 • Lateral femoral cutaneous neuropathy Gordon KC et al. Muscle Nerve 2002 (Meralgia paresthetica) Stevens JC et al. Neurology 1988; Dyck PJ et al. neurology 1993 Cranial Neuropathies • Acute in onset • Can be accompanied by severe pain Asymmetric Diabetic • Usually occurs after the age of 50 Neuropathies • CN III is the most common 9 Retroorbital pain 9 Diplopia, 20 to partial ophthalmoplegia 9 Pupil sparing Asbury AK et al. Brain 1970; Smith BE et al. Ann Neurol 1992 6 Lumbosacral Cranial Neuropathies Radiculoplexopathy • CN IV and VI may also be affected • Presents with: • Thought to be ischemic in nature 9 Severe pain in the back, hip, +/or thigh • Self limiting with symptoms resolving over 9 Followed by proximal > distal leg months to a year weakness 9 Weight loss 9 Minimal sensory features 9 Onset usually unilateral; may progress to other leg Asbury AK et al. Brain 1970; Smith BE et al. Ann Neurol 1992 Lumbosacral Lumbosacral Radiculoplexopathy Radiculoplexopathy • Also known as diabetic amyotrophy, Bruns-Garland syndrome, or proximal • Clinical examination: diabetic neuropathy 9Atrophy of the thigh • It affects older patients, usually after the age of 50, with Type 2 DM 9Patellar reflex abnormal (Achilles’ reflex +/-) • Glucose control is not a clear factor o • May be the presenting sign of diabetes (1/3) 9Strength difficult to assess 2 pain Barhon RJ et al. Arch Neurol 1991 7 Diabetic Truncal Radiculoneuropathy Red Flags • Acute or subacute pain in one or more thoracic • Rapidly progressive symptoms dermatomes “Shingles without the rash” • Asymmetry • Pain is stabbing or burning in nature • Significant weakness • Usually asymmetric • Occurs after age 50 • Severe loss of position sense • Often diagnosed after fruitless and expensive • The presence of any of the above is an abdominal evaluation and exploratory surgeries alert to look for other etiologies • EMG useful Stewart JD. Ann Neurol 1989 What else should we know about diabetic Diabetic Peripheral neuropathy? Neuropathies: • Peripheral nerve involvement can present Part II in a number of distinct syndromes Miriam L. Freimer, M.D. • Patient with diabetes mellitus can develop Ohio State University several types of peripheral nerve disorder at the same time Dept. of Neurology Director, Electromyography Lab • Not all peripheral neuropathies occurring in patients with diabetes mellitus are due to March 2008 the diabetes 8 Diabetic Neuropathy Talk Outline Diagnostic Testing • Why diabetic neuropathy? • Nerve conduction studies and • What is diabetic neuropathy ? electromyography are used to define the characteristics of the neuropathy (e.g. axonal, • How common is diabetic neuropathy demyelinating) and the extent of neuropathy • Who gets diabetic neuropathy? (e.g. distal length dependent; • How to recognize the different types? mononeuropathy; radiculopathy) • How to evaluate diabetic neuropathy? • Autonomic testing (tilt table, R-R variation) is usually reserved for patients with symptoms • How does hyperglycemia causes peripheral referable to the ANS (e.g. syncope or near neuropathy? syncope). Less useful for other autonomic • How to treat it? symptoms (GI, GU) • What is the future prospective? Diagnostic Testing Diagnostic Testing • Quantitative Blood Work: sudomotor testing • Fasting plasma glucose and hemoglobin A1c - (QSART) screening tools and are useful for following glycemic control • Small fiber • Two-hour glucose tolerance test - May be more neuropathy sensitive in borderline cases • Screening labs to rule out other etiologies – BUN, • Helpful in Cr, ANA, immunoelectropheresis and documenting extent
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