Presentation on theme: "Peripheral Neuropathy and Neuropathic Pain Management"— Presentation transcript:
1 Peripheral Neuropathy and Neuropathic Pain Management Laurence J. Kinsella, M.D., F.A.A.N.
2 Outline: Case study Anatomy of the peripheral nerve Approach to NeuropathyOverview of nerve conduction studies and electromyographyLaboratory TestingTreatment
3 Case 1 75 year old man with numbness in the feet for 5 years. Numbness ascending up to knees for 3 yearsUnsteady walking, esp. at night.Has to lift the legs high over steps to prevent fallingNo back painCramping of small muscles of hands/feet
4 Why does he have to pick up his feet so high to clear steps? 50250Audience QuestionWhy does he have to pick up his feet so high to clear steps?Spastic weakness from spinal cord injuryBilateral foot drop from neuropathyOrthopedic ankle injuries
5 Case 1PMHx/SH - HTN; s/p CABG 1997; mild diabetes for 1 year, diet controlled; 2 oz scotch per night for 40 years, no tobacco.Plays tennis weekly, golf in the summer, fishes with grand kids - active lifestyle!
6 ExaminationMS/CN wnlMotor exam shows distal wasting of foot muscles with pes cavus, hammer toes. “Yea, I got my mother’s feet.”Toe flexion is weak, produces crampDistal sensory loss to foot filament, light touch, pinprick, vibration, position senseAnkle reflexes absentAbnormal tandem gait
8 Which tests are most likely to give a diagnosis? 48250Audience QuestionWhich tests are most likely to give a diagnosis?NCS/EMG, genetic testing for CMT1A, examination of family membersNCS/EMG, antibody testing for GM1, MAG, autoimmune disordersNCS/EMG, 2 hour glucose tolerance test, HbA1C
9 Evaluation B12, MMA, TSH - normal NCS - absent sural sensory slowed conduction velocities,peroneal and tibial motor nervesEMG - Distal muscle fibrillation and polyphasic motor units.Lumbar MRI - normal.Genetic Assay for Charcot Marie Tooth deletion abnormal.
10 DiagnosisHereditary distal symmetric demyelinating polyneuropathy (Charcot Marie Tooth)Treatment - Nortriptyline and genetic counseling
11 The sensorimotor Apparatus The 1a and 1b afferents carry sensory information from the tendon, synapse with the Renshaw interneuron, excite the alpha motor neuron causing contraction of the muscle.
13 Anatomy of the Peripheral Nerve The peripheral nerve is a bundle of myelinated and unmyelinated axons, akin to a telephone cord. The axon carries the signal, the myelin insulates and speeds conduction.
15 ExaminationSupine and standing BP and P - screen for autonomic neuropathyCranial nerves - rarely affectedMotor-distal greater than proximal weakness (contrast with myopathy)Sensory - test foot filament score, vibration, cold tuning forkDistal areflexiaFocal weakness, sensory loss in distribution of single nerve
16 Semmes - Weinstein Foot Filament 10 sites per foot tested10 gram filament for feet, 5 gram for handsScore each foot 0-10Record and follow sites with sensory lossCorrelates with loss of protective sensation
17 Approach to Neuropathy Is it focal (CTS), multifocal (vasculitis), or generalized (diabetes)?Is it acute (GBS, CTS) or chronic (diabetes)?What diseases does the patient have (EtOH, diabetes, thyroid, RA)?
19 MononeuropathyOnce a mononeuropathy is suspected (single limb paresthesias, weakness, pain) the NCS/EMG serves as an extension of the physical examIs the lesion a mononeuropathy, plexopathy, or radiculopathy?
20 This man demonstrates a focal neuropathy. What is the diagnosis? Audience Question50250This man demonstrates a focal neuropathy. What is the diagnosis?Diabetic thoracic radiculopathyVaricella zosterBlack widow spider biteThoracic T9 shingles with depigmentation
22 What is the most likely cause for this woman’s bilateral wrist drop? Audience Question53250What is the most likely cause for this woman’s bilateral wrist drop?Compressive neuropathyVasculitisLead toxicityOccurred after 4400 sit ups!
23 Distal Symmetric Polyneuropathy sensory symptoms of numbness, burning, tingling begin in toes, ascend to knees, then hands- “glove and stocking”“walking on bunched-up socks”distal leg weakness, areflexia at anklessensory loss leads to ulcers, Charcot joints
25 NCS/EMG2 part testNerve conduction of superficial nerves transcutaneouslysensory and motor nerves tested
26 Nerve conduction Studies Latency - time from the impulse to the response of the CMAPAmplitude - The height of the CMAP - indicates the number of functioning axonsConduction Velocity - the distance between two points along the nerve divided by the latency difference
27 Nerve Conduction Studies Prolonged latency and conduction velocity suggest pathology of the myelin sheath, which is most commonly affected in entrapment and demyelinating neuropathy.Reduced CMAP indicates a loss of axons, suggesting a more severe and longstanding compression or degeneration (axonal neuropathy).Answer to TQ#2
28 ElectromyographyA concentric needle is inserted into a variety of limb muscles, looking for evidence of denervation (fibrillations, fasciculations, positive waves, polyphasic MUPs with reduced recruitment).
29 EMG - Normal Normal spontaneous activity - silent Normal Motor Unit -3 phasesNormal firing of multiple units, filling screen
30 EMG - Abnormal Fibrillations - single muscle fibers contract Polyphasic MUPs - reorganization of motor units due to axon loss and reinnervationRapid firing of single, polyphasic MUPs - indicates axon loss
32 57 year old auto dealer 2nd opinion for tarsal tunnel release 6 years of progressive numbness and burning feetBegan in toes, now up to anklesRecently moved into hands and arms
33 57 year old auto dealer PMHx - CAD, HTN, Chol, GERD Meds - nifedipine, Atenolol (Tenormin), Atorvastatin (Lipitor®), Gabapentin (Neurontin®), Loratadine (Claritin®), Omeprazole (Prilosec®), AspirinSeen by 15 physicians (3 neurologists)NCS/EMG x4 negative, except min. denervation of foot musclesRecommended tarsal tunnel release
34 Exam Normal strength, reflexes Pinprick < right ankle, left mid calfPS 50% normal responsesRydell-Seiffer tuning forkL toe - 1/8, R toe - 2/8 (nl > 4/8)Semmes-Weinstein filament score 7/10 (nl 10)Callus left solePhalen’s in both handsNeurology 2004;62:461.Answer to TQ#1
35 Lab evaluation TG 225 (< 150) BMP normal x Cr 1.5 Impaired fasting glucose 123 ( mg/dl)2 hour glucose tolerance test nl 105 (< 140 mg/dl)HbA1c (< 6.0)B12, methylmalonic acid, Immunofixation electrophoresis, liver function tests, HCV, anti gliadin antibody normal
36 Skin biopsy dermal plexus severe loss of small fibers Thigh fibers/mm (nl > 8)Calf fibers/mm (nl > 5)thighdermal plexuscalf
37 OutcomeSmall fiber neuropathy - idiopathic vs prediabetic vs. hypertriglycidemiaGabapentin (Neurontin®) 300 mg TID, Duloxetine (Cymbalta®) 20 mg q AMMarked improvement in painCounseled to lose 10% body weight, exercise
38 Small Fiber Neuropathy Affects A-delta (thinly myelinated), unmyelinated C fibersBurning, aching, lancinating pain in feetExam often normal, x pinprick, cold sensation.Vibration, position sense less commonUsually distal > proximalException - proximal > distal subtype, burning face and tongue, assoc dysautonomiaNCS are normal - test of largest fibers (1A)
39 Normal Epidermal Nerve Fiber Density (ENFD) Calf > 5 fibers/mm (≥ 5th percentile)Thigh > 8 fibers/mmUnmyelinated C fibersSubepidermal nerve plexus
40 Example of Normal ENF Density 41 M with paresthesias up to waist, dizzinessNormal Valsalva ratio, R-R interval by deep breathingNormal IENF density 7.07 (nl > 5.0/mm)Dermal plexusTerminal fibers
41 Nerve Fiber Density Consistent with Small Fiber Neuropathy 70 year old man with burning feet, normal NCS
42 Glucose Intolerance is an important cause of SFN Impaired glucose tolerance on 2 hour OGTT > 140 mg/dl or impaired fasting glucose ( )Found in 25-56% of patients with idiopathic neuropathy35-65% when the neuropathy is painfulHughes found less of an effect after controlling for age and sexFound differences in triglyceridesMost are overweight?metabolic syndromeNovella SP, Muscle Nerve 2001Singleton JR, Muscle Nerve 2001Sumner CJ, Neurology 2003Smith AG, Muscle Nerve 2004Hughes RA, Brain 2004
43 Skin Biopsy can document recovery of neuropathy 32 pts with prediabetic neuropathyLifestyle intervention-diet and exerciseBaseline and 1 yearskin biopsies of thigh and calfNCS, QST, QSART, OGTT, lipidsDiabetes Care Jun;29(6):
44 Distal IENFD improved 0.3 ± 1.1 fibers/mm, and the proximal IENFD improved 1.3 ± 2.2 fibers/mm (*P < 0.004).Improvement in proximal thigh IENFD was observed in 70% of subjects compared with 31% for the ankle.Diabetes Care Jun;29(6):
45 Treatment Diet and Exercise Control lipids AACE recommendation – metformin, othersNeuropathic pain managementDuloxetine 60 mg dailyPregabalinGabapentin, TCAsOpioids may be neededIVIG, Solu-Medrol experimentalAnswer to TQ#3
46 Therapies for Regeneration? Diet and Exercise for Prediabetic SFNAlpha Lipoic Acid 600mg daily shows moderate benefit for neuropathic pain (NNT 2.7)Topiramate up to 400 mg daily - modest response - 30% less pain for 50% of patients (NNT 7.4)Nerve regeneration documented in small series using skin bxTang J, et al Alpha lipoic acid may improve symptomatic diabetic polyneuropathy. Neurologist. 2007;13(3):Raskin P, et al. Topiramate vs placebo in painful diabetic neuropathy:analgesic and metabolic effects. Neurology. 2004;63(5):865-73Vinik A, Neurodiab 2005
48 Topical analgesics High potency Capsaicin 0.25% in Lidocaine cream Capsaicin or 0.075% QID x 1 month trialLidoderm Patch q 12 hrs5% Ketoprofen CreamDoxepin 5% (Zonalon® cream) x 1-2 weeksKetamine ( mg/gm) creamMagnetic InsolesDworkin, Arch Neurol 2003;60:Lynch M, et al. Topical Amitriptyline and Ketamine inNeuropathic Pain Syndromes: An Open-Label Study. The Journal of Pain, Volume 6, Issue 10, Pages
49 Number Needed to Treat (NNT) to give 50% improvement Tricyclic Antidepressants 2.6carbamazepine 2.6tramadolgabapentincapsaicinSSRImexiletineSindrup SH, Jensen TS. Neurology 2000
50 Duloxetine (Cymbalta®) 60 or 120 mg./ dayFirst FDA indication for DPNPlacebo 30% pain reduction, drug 50%Side effects - nausea, somnolence, dizziness, dry mouthPain Jul;116:109-18
51 Pregabalin (Lyrica®) Binds Ca Channels, reduces NT release FDA indication for diabetic neuropathic pain, Post herpetic neuralgia50 100 mg TIDFew drug interactionsSE - dizziness, somnolence, ataxiaGajraj. Pregabalin: Its Pharmacology and Use in Pain Management Anesth. Analg. 2007;105:
52 Gabapentin (Neurontin®) Off-label indication for neuropathic painRange from mg TIDBegin with 300 mg qHS and rapidly titrate over several weeks TID to 50% pain reduction or side effect or 3600 mg daily.Side Effects - sleepiness, ataxiaVery well-tolerated drugGeneric price reductionVinik et al. Use of Antiepileptic Drugs in the Treatment ofChronic Painful Diabetic NeuropathyJ. Clin. Endocrinol. Metab. 2005;90:
53 Nortryptiline (Pamelor®) Pt instructed to increase med until 50% pain reduction or side effectSE - dry mouth, blurred vision, lightheadedness, palpitations, urinary hesitancy, worsening glaucoma, insomniaAge > 70, History of Coronary Artery Disease - use cautionFewer anticholinergic side effects than amitriptylineLess sedatingBegin with 10 mg q HS x 1 week, then increase by 10 q week to max of mgSindrup SH, Jensen TS. Pharmacologic treatment of pain in polyneuropathy. Neurology 2000;55:
54 What can the patient do?No more than 4 drinks /week (may worsen neuropathy)exerciseavoid smokinggood dietvitamins/supplements?wash feet dailyThorlo sockssoft shoesorthotics/ shoe insertsmagnetic insolescut toenails straight across
55 Symptomatic Treatment of Painful Neuropathies Treatment recommendationsIt is essential to start a given medication at a low dose, and gradually titrate to efficacySet expectations - 50% improvementIf a patient experiences partial pain relief with 1 drug as monotherapy, a combination of 2 or more drugs with complementary mechanisms can often yield better results in terms of efficacyIn general, when a patient remains pain-free for 3 months on a current treatment regimen, consider a slow taperThese recommendations apply despite agent used treating neuropathic pain.
57 ReferencesGoldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain Jul;116:Management of chronic pain syndromes: issues and interventions. Pain Med Jul-Aug;6 Suppl 1:S1-S20;Dworkin RH, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:Lynch M, et al. Topical Amitriptyline and Ketamine in Neuropathic Pain Syndromes: An Open-Label Study. J Pain 2005; 6:Gajraj. Pregabalin: Its Pharmacology and Use in Pain Management Anesth. Analg. 2007;105:Sindrup SH, Jensen TS. Pharmacologic treatment of pain in polyneuropathy. Neurology 2000;55:Barohn RJ. Approach to peripheral neuropathy and neuronopathy. Semin Neurol 1998;18:7-18.