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Peripheral Neuropathy

Peripheral Neuropathy

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Peripheral Neuropathy

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  1. Peripheral Neuropathy Virginia Osteopathic Medical Association 2010 Spring CME Conference May 21, 2010 Andrew Galbreath, D.O. Sentara Neurology Specialists Virginia Beach, VA

  2. Opening Remarks

  3. Objectives To review and discuss… Basic epidemiology of peripheral neuropathy The diagnostic approach to progressive sensory and motor dysfunction in the ambulatory care setting Classification of nerve dysfunction Reasonable diagnostic work-up for idiopathic diffuse PN Updated treatment guidelines for neuropathic pain Prognosis of PN

  4. An estimated 20 million Americans suffer from PN¹ ~23.6 million people suffer from diabetes² 30% of PN is related to diabetes 30% of PN is idiopathic Annual cost to Medicare exceeds $3.5 billion Epidemiology ¹The Neuropathy Association ²American Diabetes Association

  5. Research has been underfunded • 2004 NIH funding: $35 million • 2005 NIH funding: $29 million • For other neurological disorders with similar scope (MS and epilepsy), funding is approximately 200 times that of PN Source: The Neuropathy Association

  6. Localization of “neuropathy” Mononeuropathy – one nerve Mononeuritis multiplex Radiculopathy – nerve root Plexopathy – brachial or lumbosacral plexus Cranial neuropathy – Bell’s Palsy, 3rd nerve palsy Distal symmetric peripheral neuropathy (DSPN) Small fiber versus large fiber Sensory only Motor only Sensorimotor

  7. “My feet feel like they’re too big for my shoes“ -Toes and feet are very sensitive to touch -He gets shooting pains into his feet and toes. -"dead" type of numbness (lack of sensation) on various spots of his feet and ankles. -has long standing xerostomia, but no xerophthalmia, orthostasis, or erectile dysfunction. 48 yr old man with no prior medical history…

  8. 85 yr old man… -No history of diabetes -Overall "heaviness" of legs and lost exercise tolerance over past 3-6 months -Used to be able to walk 3-4 miles without trouble. Now, can hardly walk 1/2 mile. -Has particular difficulty ascending stairs. -No back or limb pain, no cramping, bowel or bladder incontinence. -Denies symptoms or xerophthalmia, xerostomia, excessive constipation, urinary retention, and orthostasis.

  9. S: Numbness, or a feeling of walking on cotton wool or wearing a thick sock Pains that can be dull, constant and boring in type, or more spontaneous sharp, shooting, or stabbing in nature; a sensation as if walking on pebbles Tingling, pins and needles Hot or cold sensations (e.g., “burning feet”; “like walking on hot sand” Allodynia (pain caused by an otherwise non-painful stimulus, such as light touch or stroking); this can be very troublesome at night when the feet and legs rub against the bedclothes Cramps in the calves and foot muscles. Dyck, et. al. Peripheral Neuropathy, 4th Edition. 2005

  10. Sensory symptoms • Gains and/or Losses • Motor symptoms • Gains (cramps) and/or Losses (distal predominant) • Autonomic symptoms • Orthostasis • Impotence • Anhidrosis • Vascular instability in feet

  11. What other conditions must be considered? • Painful feet • Arthritis, including gout • Morton’s Neuroma • Tarsal tunnel syndrome • Arterial insufficiency • Tingling in the legs • Venous stasis/peripheral edema • Restless leg syndrome • idiopathic • Numbness/Weakness • Radiculopathy • CNS dysfunction (i.e. spinal cord pathology or stroke)

  12. O: General Exam: Ulcers? Trophic changes? Neurological Exam: Sensation in toes/feet 10-g Semmes-Weinstein monofilament vibration at great toes, 128 Hz tuning fork Muscle stretch reflexes (especially ankle jerks) Motor exam Bulk Tone Power

  13. Sensory Exam • 10-g Semmes-Weinstein monofilament • 3 applications at each site (one sham) • Insensate if fail at 1 or more sites Picture taken from American College of Physicians publication

  14. Sensory Exam • 128 Hz tuning fork • Lag time (normal less than 10 sec) • Start/stop

  15. Making an accurate diagnosis • History • Exam • EDX studies • Epidermal skin fiber density • Nerve biopsy Referral to Neurology

  16. Conditions Associated withPainful Peripheral Neuropathy • Diabetes and Pre-Diabetes • Alcohol neuropathy • Chemotherapy • Platinum-based • Paraproteinemia • Vasculitis and Connective Tissue Diseases • Heavy metals and other toxins • HIV • Amyloidosis • Porphyria

  17. The work-up

  18. Report of the Quality Standards Subcommittee of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation Practice Parameter: Evaluation of distal symmetric polyneuropathy: Role of laboratory, genetic, and autonomic testing; nerve biopsy; and skin biopsy (an evidence-based review) Neurology 2009;72:1–1 J.D. England, MD; G.S. Gronseth, MD, FAAN; G. Franklin, MD; G.T. Carter, MD; L.J. Kinsella, MD; J.A. Cohen, MD; A.K. Asbury, MD; K. Szigeti, MD, PhD; J.R. Lupski, MD, PhD; N. Latov, MD; R.A. Lewis, MD; P.A. Low, MD; M.A. Fisher, MD; D.N. Herrmann, MD; J.F. Howard Jr, MD; G. Lauria, MD; R.G. Miller, MD; M. Polydefkis, MD, MHS; and A.J. Sumner, MD Slide from presentation on

  19. Background • DSP is the most common type of neuropathy. • Prevalence is approximately 2,400 (2.4%) per 100,000 population but rises to approximately 8,000 (8%) per 100,000 in individuals older than 55 years. • Simple screening laboratory tests, along with medical history, neurological examination, and EDX studies, reveal the cause of DSP in 74 to 82% of patients with polyneuropathy. Slide from presentation on

  20. Gaps in Care • Since there are many etiologies of polyneuropathy, a logical clinical approach is needed for evaluation and management. • DSP diagnosis should be based on a combination of clinical symptoms, signs, and electrodiagnostic criteria. • Laboratory test results must be interpreted within the larger clinical context since the tests’ low specificity limits their etiologic yield. Slide from presentation on

  21. Clinical Questions 1. What is the yield of screening laboratory tests in the evaluation of DSP, and which tests should be performed? 2. How accurate is genetic testing for identifying patients with genetically determined neuropathies? 3. Which patients with polyneuropathy should be screened for hereditary neuropathies? Slide from presentation on

  22. Clinical Questions • What is the usefulness of clinical autonomic testing in the evaluation of polyneuropathy, and which tests have the highest sensitivity and specificity? • What is the usefulness of nerve biopsy in determining the etiology of distal symmetric polyneuropathy? • What is the usefulness and diagnostic accuracy of skin biopsy in the evaluation of polyneuropathy? Slide from presentation on

  23. Recommendations for lab testing: • Screening laboratory tests may be considered for all patients with DSP (Level C). • Tests with the highest yield of abnormality: 1. blood glucose (fasting) 2. serum B12 with metabolites (methylmalonic acid, homocysteine) 3. SPEP (Level C).

  24. Recommendations for lab testing: Other tests for prediabetes such as a GTT may be considered in patients with DSPN, especially if it is accompanied by pain (Level C). Clinical judgment correlated with the clinical picture will determine which additional laboratory investigations are necessary.

  25. Other laboratory studies • ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La, ANCA screen, cryoglobulins • Urine for heavy metals, porphyrins • IFE/urine IFE/ plasma light chain analysis

  26. Lab tests do not diagnose polyneuropathy • Yield of screening lab tests is variable

  27. PRACTICE PARAMETER: Evaluation of distal symmetric polyneuropathy: Role of autonomic testing, nerve biopsy, and skin biopsy (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;72:1–1

  28. Assessing Autonomic Nervous System • Cardiovagal • Heart rate variability • Adrenergic • Valsalva maneuver • Induces BP changes and monitors pulse reaction • Postganglionic sudomotor function • QSART

  29. 1000 ms Duration (ms) 1000 ms Duration (ms) 500 ms 500 ms R-R Cycles R-R Cycles Autonomic Testing: R-R’ interval analysis Normal Abnormal


  31. Skin biopsy “For symptomatic patients with suspected polyneuropathy, skin biopsy may be considered to diagnose the presence of a polyneuropathy, particularly SFSN.”

  32. DIAGNOSIS: • Lt Calf, Epidermal Nerve Fiber Density: • Skin with significantly reduced epidermal nerve fiber density, consistent with small fiber neuropathy • B. Lt Thigh, Epidermal Nerve Fiber Density: • Skin with normal epidermal nerve fiber density EPIDERMAL NERVE FIBER DENSITY TEST: Specimen Result Value ABNORMAL LOW NORMAL A. Lt Calf 1.95 < 5.4 5.4 - 5.7 B. Lt Thigh 13.29 < 6.8 6.8 - 8.0

  33. Genetic Testing

  34. www.

  35. What do they look like?

  36. Treatment of DSP • What is the target? • Pain? • Tingling? • Weakness? • FDA, non-FDA • Mainstream versus alternative • Oral, topical, devices, combination

  37. Options • First line? • Antidepressants • Anticonvulsants • Efficacy • Adverse effects/tolerability/cost • Second line? • Opioids • Pain clinic referral

  38. Antidepressants for neuropathic pain Cochrane Database of Systematic Reviews 2007. Issue 4. • 61 RCT • Results: • TCA are effective. • NNT 3.6 for at least moderate pain relief • DN: NNT = 1.3; PHN NNT 2.7 • Relatively safe (NNH 28) • Venlafexine • NNT 3.1 • NNH Venlafexine 16.2

  39. Tramadol for neuropathic painCochrane Database of Systematic Reviews 2006. Issue 3. • 7 trials analyzed • Results: • Tramadol is effective • NNT 3.8 for at least 50% pain relief • Insufficient data to compare with morphine

  40. EFNS guidelines on pharmacological treatment of neuropathic pain • In depth review of clinical trials looking at antidepressants and anticonvulsants in PPN, PHN • DPN and non-diabetic PPN appear to respond in similar fashion (except HIV neuropathy and chemotherapy neuropathy) Eur J Neurol 2006; 13: 1153-1169

  41. TCA - amitriptyline, desiprimine, nortriptyline • Amitriptyline first introduced 1961 • NNT PPN: 2.1 • Selective NE/Seratonin Reuptake Inhibitors • Venlafexine 150-225 mg/d: NNT 4.6 • Duloxetine 60-120 mg/d: NNT 5.2

  42. Antiepileptic drugs (AEDs) • Voltage gated calcium channel ligands • Gabapentin 1200-3600/d: NNT: 3.9 • Pregabalin 150-600mg/d also effective but data biased • Others • Carbamazepine (CBZ) – 2 older studies (1960s) – difficult to assess based on methods • Oxcarbazepine: unclear, one study NNT 5.9 • Lamotrigine: NNT 4.0 • Topiramate: negative results in 3 large trials

  43. Opioids • Oxycodone 37-60mg/d, NNT 2.6

  44. Anodyne

  45. Metanx

  46. Why is classification important? • Treatment • Further diagnostics • Prognosis – “Will this get any better?”