Abstract
Abbreviations and Acronyms:
EMG (electromyography), IGT (impaired glucose tolerance), MGUS (monoclonal gammopathy of undetermined significance), NCS (nerve conduction study), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin abnormalities), SPEP (serum protein electrophoresis), SPIEP (serum protein immunofixation electrophoresis)- 1.Read the activity.
- 2.Complete the online CME Test and Evaluation. Participants must achieve a score of 80% on the CME Test. One retake is allowed.
Centers for Disease Control and Prevention. National Ambulatory Medical Care Survey factsheet: neurology. Centers for Disease Control and Prevention website. http://www.cdc.gov/nchs/data/ahcd/NAMCS_2010_factsheet_neurology.pdf. Accessed May 13, 2015.
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
Screening for Peripheral Neuropathy
- Boulton A.J.
- Armstrong D.G.
- Albert S.F.
- et al.
Evaluating Patients Presenting With Clinical Signs or Symptoms Suggesting Peripheral Neuropathy
Clinically Stratifying Patients With Peripheral Neuropathy
• Acute, subacute in onset • Rapidly progressive • Severe, functionally limiting | ![]() |
• Length independent (polyradiculoneuropathy) | |
• Multifocal | |
• Motor predominant | |
• Associated with severe dysautonomia |
Evaluation of Length-Dependent Peripheral Neuropathies
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Serologic Evaluation
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
|
Diabetic Neuropathy
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
- Dyck P.J.
- Kratz K.M.
- Karnes J.L.
- et al.
Impaired Glucose Tolerance
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Vitamin B12 Deficiency
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Dysproteinemias
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Other Laboratory Tests
Toxic Neuropathies
Hereditary Neuropathies
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Other Diagnostic Tests
Nerve Conduction Studies and Electromyography
Test of Small Nerve Fiber Function
- England J.D.
- Gronseth G.S.
- Franklin G.
- et al.
Nerve Biopsy
Symptomatic Management of Peripheral Neuropathy
- Bril V.
- England J.
- Franklin G.M.
- et al.
Agent | Dosing | Maximum dosage | Precautions | Common and notable adverse effects | Comorbid conditions treated | Comments |
---|---|---|---|---|---|---|
Tier 1 | ||||||
Anticonvulsants | ||||||
Gabapentin | 300 mg at bedtime, increase every 4-7 d by 300-mg increments initially to 3 times daily, then to goal of 1800 mg/d as necessary to 3600 mg/d | 3600 mg/ d (split TID) | Renal insufficiency (dosage adjust); risk of seizure if abruptly stopped | Sedation, dizziness, confusion, edema, tremor | Seizure disorder, sleep disturbance, chronic migraine, hot flashes | 100-mg increments available for slower titration; no notable drug interactions |
Pregabalin | 75 mg twice daily; after 4-7 d, increase by same dosage to goal of 300 mg/d as necessary to 600 mg/d | 600 mg/d (split BID) | Renal insufficiency (dosage adjust); risk of seizure if abruptly stopped; psychiatric disease or addiction history (euphoria risk) | Sedation, dizziness, confusion, edema, tremor, euphoria (Schedule V controlled substance) | Seizure disorder, sleep disturbance, fibromyalgia, central pain related to spinal cord injury, anxiety | Can split 3 times daily but better compliance with 2 times daily dosing with similar efficacy; 25- and 50-mg dosing available for slower titration; no notable drug interactions |
Antidepressants | ||||||
Amitriptyline, nortriptyline | 10-25 mg at bedtime, increase every 4-7 d to goal of 100 mg at bedtime | 150 mg/d | Risk of serotonin syndrome; caution if cardiac disease or dysrhythmia history | Sedation, dry mouth, orthostatic hypotension, confusion, weight gain, urinary retention, constipation, blurred vision | Depression, fibromyalgia, chronic migraine, sleep disturbance, irritable bowel syndrome | Goal dosing for pain usually inadequate for mood effect; higher dosages (∼100 mg/d) often necessary for neuropathic pain; secondary amine TCAs (nortriptyline, desipramine) have lower adverse effect profile than tertiary amine TCAs (amitriptyline) |
Duloxetine | 20-30 mg once daily, then increase weekly by same dosage to goal of 60 mg/d | 120 mg/d (split BID) | Risk of serotonin syndrome; increased bleeding risk (care with anticoagulants), withdrawal syndromes with abrupt discontinuation, caution with hepatic failure | Sedation, fatigue, nausea, hyperhidrosis, dizziness, modest hypertension | Depression, anxiety, fibromyalgia, chronic musculoskeletal pain, urinary incontinence | Dosing for neuropathic pain is adequate for treatment of depression/anxiety |
Supplements | ||||||
α-Lipoic acid | 600 mg once daily | 600 mg/d | Caution if tendency toward hypoglycemia | Nausea, rash, hypothyroidism | None | Generally well tolerated |
Acetyl-L-carnitine | 1000 mg 3 times per day | 3000 mg/d (split TID) | None | Nausea, bloating, agitation | None | Generally well-tolerated |
Topicals | ||||||
Lidocaine (5%) patch | Apply patch for 12 h | 3 patches per application | Avoid over broken skin | Localized skin irritation; no notable systemic toxicity | None | May cut patch to shape |
Capsaicin (8%) patch | Should be placed by medical staff trained in its usage using nonlatex gloves; pretreat area with 4% topical lidocaine for 60 min, confirm anesthesia, apply patch(es) to affected area (may cut to shape) for 60 min, wipe clean with provided soap | 4 patches per application | Avoid face or placing over broken skin | Localized skin irritation; no notable systemic toxicity | None | Postprocedural skin irritation common; prescription oral analgesics frequently required for 7-10 d after application; single application may provide pain relief for up to 3 mo |
Tier 2 | ||||||
Antidepressants | ||||||
Venlafaxine | 37.5 mg once (extended release) or twice (immediate release) daily; increase by 75 mg/d weekly to initial goal of 150 mg/d | 225 mg/d | Risk of serotonin syndrome; withdrawal syndrome with abrupt discontinuation; caution with cardiac disease or poorly controlled hypertension | Sedation, nausea, dizziness, headache, insomnia, nervousness, abnormal ejaculation, modest hypertension (dosage >150 mg/d) | Depression, anxiety, panic attacks, social phobia, hot flashes | Similar mechanism of action to duloxetine; consider trial if duloxetine not covered by insurance; higher dosages (150-225 mg/d) required for neuropathic pain; increasing blockage of norepinephrine reuptake at higher dosages causes increased risk of hypertension |
Analgesics | ||||||
Tramadol | 50 mg twice daily; increase every 4-7 d to maximum of 100 mg per dose 4 times per day | 400 mg/d | Caution if history of addiction, analgesic misuse or diversion, severe psychiatric comorbidities, seizure disorder, taking other serotonergic agents, hepatic or renal dysfunction | Nausea, constipation, sedation, dizziness, flushing, seizures (dosages >400 mg/d) | Is a nonspecific analgesic that will cover multiple pain types | Blocks reuptake of serotonin and norepinephrine (like antidepressants) in addition to being μ-opioid receptor agonist; risk of serotonin syndrome when used with other serotonergic agents |
Tier 3 | ||||||
Analgesics | ||||||
Tapentadol | 50 mg every 4-6 h prn; increase every 4-7 d to maximum of 100 mg every 4 h prn | 600 mg/d | Caution if history of addiction, analgesic misuse or diversion, severe psychiatric comorbidities, seizure disorder, taking other serotonergic agents, hepatic dysfunction | Nausea, sedation, constipation, dizziness, pruritus, headache, hypotension, respiratory depression, seizure | Is a nonspecific analgesic that will cover multiple pain types | FDA approved for painful diabetic peripheral neuropathy; blocks reuptake of serotonin and norepinephrine (like antidepressants) in addition to being μ-opioid receptor agonist; risk of serotonin syndrome when used with other serotonergic agents |
Opioids | 15 mg oral immediate release morphine (or another opioid of equianalgesic dose such as 10 mg oxycodone) 3-4 times per day, transition to long-acting agents if regular use of short-acting agents | No maximum dosage | Caution if history of addiction, analgesic misuse or diversion, severe psychiatric comorbidities | Nausea, sedation, constipation, dizziness, pruritus, headache, respiratory depression | Is a nonspecific analgesic that will cover multiple pain types | Neuropathic pain studies used long-acting agents that should not be used in opioid-naive patients; begin with short-acting agents |
Conclusion
Supplemental Online Material
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References
- Why patients visit their doctors: assessing the most prevalent conditions in a defined American population.Mayo Clin Proc. 2013; 88: 56-67
- National Ambulatory Medical Care Survey: 2007 summary.Natl Health Stat Report. 2010; 27: 1-32
Centers for Disease Control and Prevention. National Ambulatory Medical Care Survey factsheet: neurology. Centers for Disease Control and Prevention website. http://www.cdc.gov/nchs/data/ahcd/NAMCS_2010_factsheet_neurology.pdf. Accessed May 13, 2015.
- Epidemiology of peripheral neuropathy.J Neurol Neurosurg Psychiatry. 1997; 62: 310-318
- Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions, I: Prevalence and general characteristics of the sample.Neurology. 1995; 45: 1832-1836
- Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus.N Engl J Med. 1995; 333: 89-94
- Management of diabetic peripheral neuropathy.Clin Diabetes. 2005; 23: 9-15
- The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study.Neurology. 1993; 43 ([published correction appears in Neurology. 1993;43(11):2345]): 817-824
- Prevalence of lower-extremity disease in the US adult population ≥40 years of age with and without diabetes: 1999-2000 National Health and Nutrition Examination Survey.Diabetes Care. 2004; 27: 1591-1597
- Standards of medical care in diabetes—2014.Diabetes Care. 2014; 37: S14-S80
- Comprehensive foot examination and risk assessment: a report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists.Diabetes Care. 2008; 31: 1679-1685
- Simple screening tests for peripheral neuropathy in the diabetes clinic.Diabetes Care. 2001; 24: 250-256
- Evaluation of three screening tests and a risk assessment model for diagnosing peripheral neuropathy in the diabetes clinic.Diabetes Res Clin Pract. 2001; 54: 115-128
- Effectiveness of Semmes-Weinstein monofilament examination for diabetic peripheral neuropathy screening.J Diabetes Complications. 2005; 19: 47-53
- Comparison of different screening tests for diagnosis of diabetic peripheral neuropathy in primary health care setting.Int J Health Sci (Qassim). 2012; 6: 127-134
- Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration.Arch Intern Med. 1998; 158: 289-292
- Diabetic neuropathies: a statement by the American Diabetes Association.Diabetes Care. 2005; 28: 956-962
- Comparison of neurologic changes in 'successfully aging' persons vs the total aging population.Arch Neurol. 1994; 51: 573-580
- Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review); report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation.Neurology. 2009; 72: 185-192
- Tests and expenditures in the initial evaluation of peripheral neuropathy.Arch Intern Med. 2012; 172: 127-132
- The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes.Diabetes Care. 2006; 29: 1518-1522
- Diabetic peripheral neuropathic pain: clinical and quality-of-life issues.Mayo Clin Proc. 2006; 81: S3-S11
- Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics.Diabetes Metab. 2009; 35: 206-213
- The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med. 1993; 329: 977-986
- Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus.Cochrane Database Syst Rev. 2014; 2: CD009122
- Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus.Cochrane Database Syst Rev. 2013; 11: CD008143
- Microvasculitis and ischemia in diabetic lumbosacral radiculoplexus neuropathy.Neurology. 1999; 53: 2113-2121
- Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy.Diabetes Care. 2001; 24: 1448-1453
- Painful sensory polyneuropathy associated with impaired glucose tolerance.Muscle Nerve. 2001; 24: 1225-1228
- The spectrum of neuropathy in diabetes and impaired glucose tolerance.Neurology. 2003; 60: 108-111
- Prevalence of complications among second-generation Japanese-American men with diabetes, impaired glucose tolerance, or normal glucose tolerance.Diabetes. 1987; 36: 730-739
- Impaired glycemia and diabetic polyneuropathy: the OC IG Survey.Diabetes Care. 2012; 35: 584-591
- Vitamin B12 deficiency.N Engl J Med. 2013; 368: 149-160
- Challenges in the identification of cobalamin-deficiency polyneuropathy.Arch Neurol. 2003; 60: 1296-1301
- The diagnostic yield of a standardized approach to idiopathic sensory-predominant neuropathy.Arch Intern Med. 2004; 164: 1021-1025
- Prevalence of monoclonal protein in peripheral neuropathy.Neurology. 1981; 31: 1480-1483
- Sensitivity of immunofixation electrophoresis for detecting IgM paraproteins in serum.Clin Chem. 1988; 34: 1633-1635
- Distal acquired demyelinating symmetric neuropathy.Neurology. 2000; 54: 615-620
- Clinical spectrum of chronic acquired demyelinating polyneuropathies.Muscle Nerve. 2001; 24: 311-324
- Chronic acquired demyelinating symmetric polyneuropathy classified by pattern of weakness.Arch Neurol. 2003; 60: 260-264
- Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP.J Neurol Neurosurg Psychiatry. 2012; 83: 480-486
- Celiac neuropathy.Neurology. 2003; 60: 1581-1585
- The neurologic significance of celiac disease biomarkers.Neurology. 2014; 83: 1789-1796
- Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration.Neurology. 2004; 63: 33-39
- A controlled study of peripheral neuropathy after bariatric surgery.Neurology. 2004; 63: 1462-1470
- Medication, toxic, and vitamin-related neuropathies.Continuum (Minneap Minn). 2012; 18: 139-160
- Chemotherapy-induced neuropathy.J Peripher Nerv Syst. 2008; 13: 27-46
- Peripheral neuropathy.Lancet. 2004; 363: 2151-2161
- Genetic epidemiology of Charcot-Marie-Tooth in the general population.Eur J Neurol. 2011; 18: 39-48
- Genetic and clinical aspects of Charcot-Marie-Tooth's disease.Clin Genet. 1974; 6: 98-118
- Genetic epidemiology of Charcot-Marie-Tooth disease.Acta Neurol Scand Suppl. 2012; : iv-22
- Charcot-Marie-Tooth disease and other inherited neuropathies.Continuum (Minneap Minn). 2014; 20: 1208-1225
- NeuPSIG guidelines on neuropathic pain assessment.Pain. 2011; 152: 14-27
- Clinical characteristics and economic costs of patients with painful neuropathic disorders.J Pain. 2004; 5: 143-149
- Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey.Diabetes Metab Syndr Obes. 2013; 6: 79-92
- Treatment of neuropathic pain: an overview of recent guidelines.Am J Med. 2009; 122: S22-S32
- Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.Mayo Clin Proc. 2010; 85: S3-S14
- EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.Eur J Neurol. 2010; 17 (1113-e88)
- The evidence for pharmacological treatment of neuropathic pain.Pain. 2010; 150: 573-581
- Pharmacologic management of neuropathic pain: evidence-based recommendations.Pain. 2007; 132: 237-251
- Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.Neurology. 2011; 76: 1758-1765
- Combination pharmacotherapy for the treatment of neuropathic pain in adults.Cochrane Database Syst Rev. 2012; 7: CD008943