Polyneuropathy. Kiril Kiprovski, M.D.

Transcription

1 Polyneuropathy Kiril Kiprovski, M.D.

2 Classification of Peripheral Nerve Diseases -Mononeuropathy -Plexopathy Brachial plexopathy Lumbar plexopathy Sacral plexopathy -Radiculopathy Cervical radiculopathy Thoracic radiculopathy Lumbosacral radiculopathy -Multiple mononeuropathy (mononeuritis multiplex) -Polyneuropathy Symmetrical -Polyradiculoneuropathy

3 Eight Patterns of Neuropathies 1. Symmetric proximal and distal weakness with sensory loss (GBS, CIDP) 2. Symmetric distal weakness with sensory loss (metabolic, drugs, toxins, amyloid, hereditary) 3. Asymmetric distal weakness with sensory loss (vasculitis, leprosy, Lyme sarcoid, HIV, compressive mononeuropathy) 4. Asymmetric distal weakness without sensory loss (ALS, MMN) 5. Asymmetric proximal and distal weakness with sensory loss (polyradiculopathy and plexopathy due to DM, meningeal carcinomatosis, idiopathic) 6. Symmetric sensory loss without weakness (cryptogenic sensory polyneuropathy, metabolic, drugs, toxins) 7. Asymmetric proprioceptive sensory loss without weakness (sensory neuronopathy - ganglionopathy) 8. Autonomic symptoms and signs

4 Etiology of Acquired Polyneuropathies Dysmetabolic Diabetes mellitus Renal disease, liver disease Vitamin deficiencies (B1, B2, B6, FA, B12) B6 toxicity Primary amyloidosis Immune-mediated GBS CIDP Vasculitis Connective tissue disease Monoclonal gammopathies, MGUS, MAG, GM1 Plexitis (brachial, lumbosacral) Infectious Herpes zoster Leprosy, Lyme, HIV, sarcoidosis Cancer related lymphoma, myeloma, carcinoma related, Drugs or toxins Unknown etiology cryptogenic sensory and sensorimotor

5 Neuropathies Traditional classification Sensory Neuronopathy (ganglionopathy) Target: sensory nerve cell bodies in the dorsal root and trigeminal ganglia Segmental demyelination (myelinopathy) Target: myelin sheaths or Schwann cells Remyelination causes onion bulb. Axonal degeneration (axonopathy) Target: distal axonal breakdown that progresses toward the nerve cell body, (dying-back or length-dependent polyneuropathy)

6 Axonal Advanced axonal Demyelinating Mononeuritis multiplex

7 Node of Ranvier-Focus of Nerve Injury Myelin Axon Paranode Node Paranode Juxtaparanode Internode The nodal axolemma and the paranode can be the focus of the nerve injury classified as nodo-paranodopathies.

8 Demyelinating Pathophysiology Segmental demyelination Conduction block Slowing of distal/f-wave latency & CV Abnormal temporal dispersion Franssen, Straver. MN (2013)

9 Nodo-paranodopathies (neuropathies associated with antibodies to gangliosides) Autoantibodies GM1 GD1a GT1a GQ1b GD1b AMAN IgG IgG AMSAN IgG IgG ASAN IgG PCB IgG FS IgG IgG MMN IgM AMAN, AMSAN, ASAN, PCB, FS, MMN, acute motor axonal neuropathy; acute motor-sensory axonal neuropathy; acute sensory ataxic neuropathy; pharyngeal-cervical-brachial weakness; Fisher syndrome; multifocal motor neuropathy.

10 EDX in polyneuropathy - Collective results of NCV and EMG define the polyneuropathy. -Requires -motor and sensory conduction studies -multiple nerves -upper and lower extremities bilaterally -needle EMG. - EDX to demonstrate the characteristic symmetry of abnormality.

11 Polyneuropathy EDX protocol NCV 1. Test most involved site when mild or moderate, least involved if severe. 2. Peroneal motor (EDB); If abnormal or no responses: Peroneal motor (TA). 3. Tibial motor (AH) 4. Ulnar motor. 5. Median motor. 6. F responses. 7. SNAP (sural, superficial peroneal, median, ulnar, radial nerve). 8. Evaluation of opposite extremity. 9. Evaluation of specific suspected abnormality. 10. If prominent cranial involvement: Facial CMAP, Blink reflex studies Needle EMG Examination TA, GA, EHL, FDI, paraspinal muscles. Intrinsic foot muscles can be considered. Abnormalities should be confirmed by examination of at least one contralateral muscle.

12 Demyelinating polyneuropathies A. Uniform demyelination B. Segmental demyelination

13 Acquired (segmental) vs Hereditary (uniform) 47 m/s 30 m/s 43 m/s 5 mv

14 Uniform demyelinating, mixed sensorimotor polyneuropathy CMT 1A CMT 1B DSD Metachromatic leukodystrophy Krabbe s globoid leukodystrophy Adrenomyeloneuropathy Congenital hypomyelinating neuropathy Tangier disease Cockayne s syndrome Cerebrotendinous xanthomatosis

15 Segmental demyelinating, motor > sensory polyneuropathy AIDP CIDP MMN POEMS MGUS NHPP CMTX1 Adrenomyeloneuropathy Refsum Diphtheria Acute arsenic polyneuropathy Pharmaceuticals Amiodarone Perhexiline High dose Ara-C Lymphoma Carcinoma Lyme disease Acromegaly Systemic lupus erythematosus Glue sniffing neuropathy Cryoglobulinemia

16 Axonal loss, motor > sensory polyneuropathy Porphyria Axonal Guillain- Barré syndrome CMT2 CMT4 (some) Lead neuropathy Dapsone neuropathy Vincristine neuropathy

17 Axonal loss sensory neuronopathy or neuropathy HSAN types I- V Friedreich's ataxia Spinocerebellar degeneration. Abetalipoproteinemia Primary biliary cirrhosis Acute sensory neuronopathy Cisplatinum toxicity Paraneoplastic sensory neuronopathy Chronic idiopathic ataxic neuropathy Sjogren's syndrome Fisher variant GBS Paraproteinemias Pyridoxine toxicity Idiopathic sensory neuronopathy Styrene-induced peripheral neuropathy Crohn's disease Thalidomide Nonsystemic vasculitic neuropathy Chronic gluten enteropathy Vitamin E deficiency.

18 Axon loss, mixed sensorimotor polyneuropathy Amyloidosis Chronic liver disease Nutritional diseases Vitamin B12 deficiency Folate deficiency Whipple s disease Post-gastrectomy syndrome Gastric restriction surgery for obesity Thiamine deficiency Alcoholism Sarcoidosis Connective tissue diseases Toxic neuropathy

19 Mixed axon loss and demyelinating sensorimotor polyneuropathy Diabetes mellitus Uremia

20 Classification of Diabetic Neuropathies Generalized Symmetrical Polyneuropathies Distal sensory or sensorimotor polyneuropathy Small-fiber neuropathy Autonomic neuropathy Large-fiber sensory neuropathy Focal and Asymmetrical Neuropathies Cranial neuropathy (single or multiple) Truncal neuropathy (thoracic radiculopathy) Limb mononeuropathy (single or multiple) Proximal motor neuropathy (radiculoplexopathy, amyotrophy) Combinations Polyradiculoneuropathy Diabetic neuropathic cachexia

21 Electrodiagnostic findings suggestive of demyelination 1. Conduction block 2. Conduction velocity slowing greater than can be explained by axonal loss A. Prolonged distal motor latencies B. Slow conduction velocity Motor conduction slowing <30 m/s arm 25 m/s in the leg C. Prolonged F-wave latency D. Prolonged H-reflex latency 3. Temporal dispersion 4. Prolongation of the duration of the distal CMAP

22 54 y man presented with: Several months history of insidious and progressive gait difficulty and clumsy hands Become bed ridden and incontinent one month prior to the referral Intermittent and migrating numbness in both legs PMH: DM-II, smoker, ETOH Mild neck flexor weakness 0/5 proximal and distal legs 4-/4- proximal arms 3/3 distal arms/ hands Reduced tone and atrophy of limb muscles B/L knee contractures (15 degree) Muscle stretch reflexes absent throughout

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24 Practical diagnostic criteria for CIDP 1. Progressive symmetrical weakness of arms and legs for at least 2 months 2. Sensory disturbances generally less prominent 3. Low or absent DTR 4. Sometimes cranial nerve palsies 5. CSF protein almost always elevated (albuminocytologic dissociation) 6. Delayed NCV in demyelinating range 7. Increased Distal latencies 8. Conduction block 9. Dispersion 10. Decreased excitability Other causes of chronic neuropathy must be ruled out

25 Motor NCV values needed to be considered demyelinating Motor NCV DL F If CMAP amp. is >80% <80% >80% <80% >80% <80% ULN >125% >150% ULN >120% >150% Median Ulnar Peroneal Tibial

26 Chronic Inflammatory Demyelinating Neuropathies: Clinical features Weakness and sensory loss CIDP Symmetric, distal and proximal (legs>arms) M>S Distal acquired demyelinating symmetric (MAG) Symmetric, mild distal (legs>arms) S>M Lewis Sumner syndrome Asymmetric, mostly distal, pain, Tinel s (arms>legs) MMN Pure motor, asymmetric, mostly distal (arms>legs) POEMS Symmetric, distal and proximal (legs>arms) Painful feet M>S CSF protein Elevated Elevated Elevated No Elevated M protein Uncommon IgM Uncommon Uncommon Lambda light chain Antineural Uncommon Anti MAG Uncommon Anti GM1 antibodies VEGF Systemic Uncommon (MGUS, MM, WM Connective tissue disease ) No No No Osteosclerotic myeloma Organomegaly Endocrinopathy Skin changes edema, ascites Motor NCV Demyelination Demyelination Demyelination Demyelination Demyelination, more uniform slowing, greater axonal loss in LE, higher terminal latency index Sensory NCV Abnormal Abnormal Abnormal Normal Abnormal Treatment Prednisone, IVIG, PLEX, immunosuppressants?rituxan?ivig IVIG Immunosuppressants Prednisone IVIG?cyclophosphamide Stem cell, dexamethasone Melphalan, Lenalidomide, Thalidomide, Bortezomib, anti-vegf antibody (bevacizumab)

27 World War 1: French Field Hospital

28 GBS - GBS is a rare but important disease that can lead to life threatening respiratory failure - Treatment consists of rapid administration of intravenous immunoglobulin or plasma exchange, which shortens the time to recovery - Around 10% of patients die from respiratory failure, pulmonary emboli, or infection - Around 20% of patients have residual disability, with weakness or persistent sensory disturbance - GBS should be considered in any patient developing rapidly progressive limb weakness - Absent reflexes are a red flag for GBS in patients with rapidly progressive weakness - Patients with suspected GBS should be referred to hospital as an emergency - A history of weakness preceded by respiratory or GI infection suggests GBS

29 Classification of Guillain-Barré syndrome and typical antiganglioside antibodies Clinical variants Antibodies - Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) Unknown - Acute motor and sensory axonal neuropathy (AMSAN) GM1, GM1b, GD1a - Acute motor axonal neuropathy (AMAN) GM1, GM1b, GD1a, GalNac-GD1a - Acute motor conduction block neuropathy (AMCBN) - Acute sensory neuronopathy GD1b - Acute pandysautonomia - Regional variants Fisher s syndrome Oropharyngeal cervical-brachial - Overlap Fisher s syndrome/ GBS overlap syndrome GQ1b, GT1a GT1a GQ1b, GM1, GM1b, GD1a,

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31 GBS and MFS (Miller Fisher Syndrome) GBS and MFS subtypes form a continuous spectrum GBS should always be considered if relatively symmetric limb or cranial nerve weakness and ataxia, follow antecedent upper respiratory infectious symptoms or diarrhoea. This is supported by the presence of distal paresthesias, CSF albuminocytological dissociation, abnormal nerve conduction studies, or anti-ganglioside antibodies. GBS is very likely in patients who develop acute flaccid paralysis with facial weakness. MFS and the pharyngeal-cervical-brachial variant of GBS are frequently mistaken for myasthenia gravis, botulism or brainstem stroke. 10% of patients with GBS have normal or exaggerated deep tendon reflexes.

32 Motor Nerve Conduction: Peroneal Nerve.R(EDB) absent Peroneal Nerve.R (TA) absent Tibial Nerve.R absent Ulnar Nerve.L absent Ulnar Nerve.R absent Median Nerve.R Latency-ms Amplitude -mv Conduction velocity m/s Wrist Elbow Wrist-Elbow 47 Axilla Elbow-Axilla 44 Median Nerve.L Wrist Elbow Wrist-Elbow 46 Axilla Elbow-Axilla 43 Sensory Nerve Conduction: Nerve and Site Latency -ms Amplitude -µv Conduction velocity m/s Sural Nerve.R Superficial Peroneal.R Radial Nerve.R Median Nerve.R Ulnar Nerve.R Radial Nerve.L Median Nerve.L Ulnar Nerve.L year-old man AMAN (acute motor axonal neuropathy) Needle EMG Examination: Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Increased None None Max. Peroneus longus.r Increased None None Max. Gastroc (Medial head).r Increased None None Max. Vastus medialis.r Increased None None Max. Rectus femoris.r Increased None Unstable Unstable Single unit Max. Deltoid.R Normal None Many Normal Normal Reduced Max. Triceps brachii.r Normal None Many Sl. Incr. Normal Single unit Max. Biceps brachii.r Normal None Few Normal Normal Single unit Max. Extensor dig communis.r Normal None Many Unstable Unstable Single unit Max. 1st dorsal interosseous.r Increased None None Max.

33 Motor Nerve Conduction: Peroneal Nerve.R(EDB) absent Peroneal Nerve.R (TA) absent Tibial Nerve.R absent Ulnar Nerve.L absent Ulnar Nerve.R absent Median Nerve.R Latency-ms Amplitude -mv Conduction velocity m/s Wrist Elbow Wrist-Elbow 47 Axilla Elbow-Axilla 44 Median Nerve.L Wrist Elbow Wrist-Elbow 46 Axilla Elbow-Axilla 43 Sensory Nerve Conduction: Nerve and Site Latency -ms Amplitude -µv Conduction velocity m/s Sural Nerve.R Superficial Peroneal.R Radial Nerve.R Median Nerve.R Ulnar Nerve.R Radial Nerve.L Median Nerve.L Ulnar Nerve.L year-old man AMAN (acute motor axonal neuropathy) Needle EMG Examination: Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Increased None None Max. Peroneus longus.r Increased None None Max. Gastroc (Medial head).r Increased None None Max. Vastus medialis.r Increased None None Max. Rectus femoris.r Increased None Unstable Unstable Single unit Max. Deltoid.R Normal None Many Normal Normal Reduced Max. Triceps brachii.r Normal None Many Sl. Incr. Normal Single unit Max. Biceps brachii.r Normal None Few Normal Normal Single unit Max. Extensor dig communis.r Normal None Many Unstable Unstable Single unit Max. 1st dorsal interosseous.r Increased None None Max.

34 Motor Nerve Conduction: Peroneal Nerve.R(EDB) absent Peroneal Nerve.R (TA) absent Tibial Nerve.R absent Ulnar Nerve.L absent Ulnar Nerve.R absent Median Nerve.R Latency-ms Amplitude -mv Conduction velocity m/s Wrist Elbow Wrist-Elbow 47 Axilla Elbow-Axilla 44 Median Nerve.L Wrist Elbow Wrist-Elbow 46 Axilla Elbow-Axilla 43 Sensory Nerve Conduction: Nerve and Site Latency -ms Amplitude -µv Conduction velocity m/s Sural Nerve.R Superficial Peroneal.R Radial Nerve.R Median Nerve.R Ulnar Nerve.R Radial Nerve.L Median Nerve.L Ulnar Nerve.L year-old man AMAN (acute motor axonal neuropathy) Needle EMG Examination: Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Increased None None Max. Peroneus longus.r Increased None None Max. Gastroc (Medial head).r Increased None None Max. Vastus medialis.r Increased None None Max. Rectus femoris.r Increased None Unstable Unstable Single unit Max. Deltoid.R Normal None Many Normal Normal Reduced Max. Triceps brachii.r Normal None Many Sl. Incr. Normal Single unit Max. Biceps brachii.r Normal None Few Normal Normal Single unit Max. Extensor dig communis.r Normal None Many Unstable Unstable Single unit Max. 1st dorsal interosseous.r Increased None None Max.

35 NCS in GBS - The interpretation of NCS in GBS is not straightforward. - Conduction block is considered supportive of demyelination and AIDP - Short-lasting conduction block that resolves without temporal dispersion has also been observed in early stages of a GBS - Classification depends on the timing of NCS relative to disease onset. Serial NCS lead to reclassification in as many as 40% of patients (from AIDP to an axonal form)

36 Parallels and differences between GBS and CIDP Acute AIDP: no antibody AMAN: IgG anti-gm1 Fisher syndrome: IgG anti-gq1b Antecedent event in 70% Monophasic Steroids ineffective Both axonal and demyelinating forms Chronic CIDP: no antibody MMN: IgM anti-gm1 CANOMAD: IgM anti-gq1b and GT1A No antecedent event Requires continued Rx Steroids effective in CIDP Axonal forms not as well described CANOMAD: Chronic Ataxic Neuropathy Ophtalmoplegia IgM paraprotein Cold Agglutinins Disialosyl antibodies

37 57 y man presented with: Four months progressive proximal and distal symmetrical arm and leg weakness leading to wheelchair bound state No sensory symptoms Absent DTR in the legs, trace in the arms NCV-conduction block in motor fibers Normal SNAP IgM spike anti-gm1 = 1:58000 (repeated 1:100000) BM = low grade B-cell lymphoma (Waldenström's macroglobulinemia)

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39 Neuropathies associated with conduction block Inflammatory/immune-mediated Guillain Barre syndrome Acute motor axonal neuropathy (AMAN) Chronic inflammatory demyelinating polyneuropathy (CIDP) Lewis Sumner syndrome Multifocal motor neuropathy (MMN) Inherited Hereditary neuropathy with liability to pressure palsies (HNPP) Traumatic Acute compressive neuropathies Toxic Diphtheria, Buckthorn, Fish toxins, Tetrodotoxin, saxitoxin, ciguatera

40 Multifocal Motor Neuropathy-MMN Age of onset is generally between 20 and 75 Men are affected somewhat more commonly than women Weakness: Distal > Proximal Asymmetric Upper > Lower extremity Weakness in muscles with relatively normal bulk No upper motor neuron signs Sensory: Normal or minimal subjective symptoms Tendon reflexes: Preserved in proportion to strength Time course: Slowly progressive (years) High IgM vs GM1 ganglioside

41 Neurophysiology of conduction block Conduction block (CB) failure of a nerve impulse to propagate in a segment of an intact axon Temporal dispersion (TD) excessive desynchronization of the impulse (duration >15%) CB is suspected when proximal amplitude or area are smaller than distal No universally accepted criteria for CB parameters (amplitude difference 14-50%) CB and TD characteristic of acquired segmental demyelinating neuropathies CB and TD are absent in hereditary neuropathies

42 Normal CMAP mv Distal Proximal ms

43 Conduction block mv Distal Proximal ms

44 Temporal dispersion mv Distal Proximal ms

45 EDX Parameters: Conduction block Traditional Demyelination Nodal Na + channel Membrane depolarization Since not structural; reversible block Membrane hyperpolarization Uncini, Kuwabara. JNNP (2015)

46 AIDP Serial EDX Studies

47 Serial EDX Studies AMAN Reversible CB

48 Serial EDX Studies AMAN Axonal loss

49 Serial EDX Studies AMAN Reversible CB

50 Differential diagnosis MMN ALS CIDP Lewis Sumner Asymmetrical Distal > proximal /- ++ UL>LL +++ +/- - + Atrophy +/ Fasciculations Bulbar Diaphragm Sensory Cold worsening Reflexes Asymmetric reduced Brisk Symmetric reduced Reduced Course Slowly/ stepwise progressive/ Treatable Progressive/ invariably fatal Subacute progressive/ treatable Conduction block GM CSF protein IVIG response Steroids/PLEX Subacute/stepwise progressive/treatable

51 40 y man presented with: Progressive proximal and distal weakness (legs> arms) Distal dysesthesias and sensory loss Absent DTR Absent SNAP Slow NCV LP- albuminocytologic dissociation Monoclonal spike on IE

52 POEMS Younger age, mostly man Osteosclerotic myeloma (3% of myeloma) Axial skeleton (spine, pelvis, ribs) Polyneuropathy (CIDP-like) Organomegaly (HSM) Endocrinopathy (gynecomastia, impotence, amenorrhea, DM, hypothyroidism) M-protein (lambda-chain) Skin changes (hyperpigmentation, hypertrichosis, thickening, hemangiomas) Pitting edema, ascites, pleural effusion, clubbing

53 50 y. patient Sensory Neuronopathy Motor Nerve Conduction: Nerve and Site Latency ms Amplitude mv CV m/s F-waves: Peroneal Nerve.R Ankle Fibular head ms Knee Peroneal Nerve (TA).R Fibular head Knee Tibial Nerve.R Ankle Pop. fossa ms Peroneal Nerve.L Ankle Fibular head ms Knee Peroneal Nerve (TA).L Fibular head Knee Tibial Nerve.L Ankle Pop. fossa ms Median Nerve.L Wrist Elbow ms Axilla Ulnar Nerve.L Wrist Below Elbow ms Above Elbow Axilla Median Nerve.R Wrist Elbow ms Ulnar Nerve.R Wrist Below Elbow ms Above Elbow Axilla Sensory Nerve Conduction: Sural Nerve.R Superficial Peroneal.R Sural Nerve.L Superficial Peroneal.L Radial Nerve.L Median Nerve.L Ulnar Nerve.L Median Nerve.R Ulnar Nerve.R Radial Nerve.R Absent Absent Absent Absent Absent Absent Absent Absent Absent Absent Needle EMG Examination: Spontaneous ActivityVolitional Activity Maximal Effort Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Normal None None None Few Normal Normal Full Max. Gastroc (Medial head).r Normal None None None Few Normal Normal Full Max. Extensor dig communis.r Normal None None None Few Normal Normal Full Max. 1st dorsal interosseous.r Normal None None None Few Normal Sl. Incr. Full Max. Extensor digitorum brevis.r Normal None None None Few Normal Normal Full Max.

54 50 y. patient Sensory Neuronopathy Motor Nerve Conduction: Nerve and Site Latency ms Amplitude mv CV m/s F-waves: Peroneal Nerve.R Ankle Fibular head ms Knee Peroneal Nerve (TA).R Fibular head Knee Tibial Nerve.R Ankle Pop. fossa ms Peroneal Nerve.L Ankle Fibular head ms Knee Peroneal Nerve (TA).L Fibular head Knee Tibial Nerve.L Ankle Pop. fossa ms Median Nerve.L Wrist Elbow ms Axilla Ulnar Nerve.L Wrist Below Elbow ms Above Elbow Axilla Median Nerve.R Wrist Elbow ms Ulnar Nerve.R Wrist Below Elbow ms Above Elbow Axilla Sensory Nerve Conduction: Sural Nerve.R Superficial Peroneal.R Sural Nerve.L Superficial Peroneal.L Radial Nerve.L Median Nerve.L Ulnar Nerve.L Median Nerve.R Ulnar Nerve.R Radial Nerve.R Absent Absent Absent Absent Absent Absent Absent Absent Absent Absent Needle EMG Examination: Spontaneous ActivityVolitional Activity Maximal Effort Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Normal None None None Few Normal Normal Full Max. Gastroc (Medial head).r Normal None None None Few Normal Normal Full Max. Extensor dig communis.r Normal None None None Few Normal Normal Full Max. 1st dorsal interosseous.r Normal None None None Few Normal Sl. Incr. Full Max. Extensor digitorum brevis.r Normal None None None Few Normal Normal Full Max.

55 50 y. patient Sensory Neuronopathy Motor Nerve Conduction: Nerve and Site Latency ms Amplitude mv CV m/s F-waves: Peroneal Nerve.R Ankle Fibular head ms Knee Peroneal Nerve (TA).R Fibular head Knee Tibial Nerve.R Ankle Pop. fossa ms Peroneal Nerve.L Ankle Fibular head ms Knee Peroneal Nerve (TA).L Fibular head Knee Tibial Nerve.L Ankle Pop. fossa ms Median Nerve.L Wrist Elbow ms Axilla Ulnar Nerve.L Wrist Below Elbow ms Above Elbow Axilla Median Nerve.R Wrist Elbow ms Ulnar Nerve.R Wrist Below Elbow ms Above Elbow Axilla Sensory Nerve Conduction: Sural Nerve.R Superficial Peroneal.R Sural Nerve.L Superficial Peroneal.L Radial Nerve.L Median Nerve.L Ulnar Nerve.L Median Nerve.R Ulnar Nerve.R Radial Nerve.R Absent Absent Absent Absent Absent Absent Absent Absent Absent Absent Needle EMG Examination: Spontaneous ActivityVolitional Activity Maximal Effort Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort Tibialis anterior.r Normal None None None Few Normal Normal Full Max. Gastroc (Medial head).r Normal None None None Few Normal Normal Full Max. Extensor dig communis.r Normal None None None Few Normal Normal Full Max. 1st dorsal interosseous.r Normal None None None Few Normal Sl. Incr. Full Max. Extensor digitorum brevis.r Normal None None None Few Normal Normal Full Max.

56 Sensory neuronopathy vs length dependent sensory neuropathy Sensory neuronopathy (non- length dependent) Symmetric or asymmetric Proximal and distal, UE, LE, truncal nerves Profound proprioceptive loss (all modalities) No motor weakness Generalized areflexia Absent SNAP LE and UE Motor NCV normal High signal posterior columns Present DRG - positive pathology Sensory predominant polyneuropathy (length dependent) Symmetric Distal sensory nerves, feet usually Rare to no proprioceptive loss In severe cases distal motor deficit Distal areflexia (ankle jerks) SNAP abnormal LE Distal decreased amplitude CMAP High signal posterior columns - Absent DRG - normal

57 Causes of sensory neuronopathy Cancer (paraneoplastic) Sjögren syndrome and other inflammatory dss. Idiopathic sensory Cisplatinum, Paclitaxel Vitamin B6 toxicity HIV-related sensory

58 Cryptogenic sensory polyneuropathy Decreased sensation, paresthesias, dysesthesias, allodynia and pain in length dependent fashion At least 3 months duration and no symptoms of weakness Symptoms of gait unsteadiness and autonomic dysfunction are allowable Sensory signs in symmetrical fashion ( vibration, proprioception, light touch, pain, temperature ± reflexes (AJ) Minimal weakness of the toes allowable ± EMG/NCV changes (axonal) ± QST abnormalities ± Skin biopsy ± QSART ± Autonomic testing Stable course, no functional disability

59 Painful Polyneuropathies Cryptogenic Paraproteinemic In malignancies Diabetes mellitus Vasculitis GBS Amyloidosis Toxic (arsenic, thallium) HIV-related Fabry s disease

60 Useful Blood Studies CBC, CMP, U/A, ESR, A1C, TFT? Immunofixation, Quant. Ig B12, B6, B1, Folate, MMA, homocysteine Anti-MAG, GM1, GD1B, GQ1B VDRL, RF, ANA, ANCA, Lyme, HIV SS-A, SS-B, ANNA-1 Heavy metal screen (urine, blood) Hepatitis screen, cryoglobulins

61 Investigations EMG/NCV large fibers S Q proprioception, pain, temperature QSART postganglionic sudomotor Autonomic reflex testing (DB, Valsalva, Tilt) Cardiovagal, cardiovascular adrenergic Sympathetic skin response Thermoregulatory sweat test - TST Skin or salivary gland biopsy, abdominal fat aspiration Skeletal survey, LP Imaging (chest, abdomen, pelvis)

62 Nerve Biopsy is useful in: Vasculitis Sarcoidosis Amyloidosis Leprosy Tumor infiltration CIDP?

63 PN with autonomic involvement Diabetes mellitus Amyloidosis GBS Vincristine Porphyria HIV-related PAF

64 A partial list of clinical characteristics and treatments for six common forms of systemic vasculitis affecting small and/or medium-sized vessels of nerve Characteristic Wegener Granulomatosis Churg-Strauss syndrome Polyarteritis nodosa Microscopic polyangiitis Rheumatoid vasculitis Mixed Cryoglobulinemia Peripheral nerve disease Vessel size involved 40% 50% 65% 80% 35% 75% 60% 70% small to medium vessels (eg, capillaries, venules, arterioles, arteries) small to medium vessels medium to small arteries (not arterioles, capillaries or venules) small vessels (eg, capillaries, arterioles, venules) 50% (of cases of rheumatoid vasculitis -- a secondary vasculitis that occurs in 5% - 15% of cases of RA Medium to small arteries (histologically indistinguishable from polyarteritis nodosa) 20% - 90% Small (eg, capillaries, arterioles, venules)

65 Pitfalls in EDX in polyneuropathy I The primary sources are errors of omission, ie, drawing conclusions based upon a limited data. Overemphasizing the value of conduction velocity. This measure is sensitive to demyelination but may remain normal in the setting of axon degeneration. Distal latencies are markedly prolonged only in demyelination, moderately prolonged in association with entrapment, and only mildly prolonged in axonal degeneration. Failure to exclude from interpretation focal slowing of conduction velocity due to specific entrapment mononeuropathies before concluding that a generalized process of reduced conduction exists. Markedly reduced motor evoked amplitudes (CMAP) with normal sensory responses (SNAP) are unusual in polyneuropathy; further investigation usually demonstrates a polyradiculopathy, motor neuron disease, or defective neuromuscular transmission (LEMS) Sensitivity of conduction velocity, distal latency, and amplitude are temperature dependent

66 Pitfalls in EDX in polyneuropathy I The primary sources are errors of omission, ie, drawing conclusions based upon a limited database. Overemphasizing the value of conduction velocity. This measure is sensitive to demyelination but may remain normal in the setting of axon degeneration. Distal latencies, another barometer of conduction rate, are markedly prolonged only in demyelination, moderately prolonged in association with entrapment, and only mildly prolonged in axonal degeneration. Failure to exclude from interpretation focal slowing of conduction velocity due to specific entrapment mononeuropathies before concluding that a generalized process of reduced conduction exists. Markedly reduced motor evoked amplitudes (CMAP) with normal sensory responses (SNAP) are unusual in polyneuropathy; further investigation usually demonstrates a polyradiculopathy, motor neuron disease, or defective neuromuscular transmission (LEMS) Sensitivity of conduction velocity, distal latency, and amplitude are temperature dependent

67 Pitfalls in EDX in polyneuropathy II Difficulties in obtaining supramaximal stimulation proximally (Erb s point, tibial nerve in the posterior knee, radial nerve in the axilla). The longer the nerve segment the greater the area/ amplitude reduction required for CB. Excessive stimulation distally - Particularly an issue with median nerve stimulation at the wrist. Excessive stimulation can recruit ulnar innervated motor units. For all cases of median CB in the forearm, one needs to stimulate the ulnar nerve at the wrist and record over the thenar eminence. If a CMAP is obtained, median nerve stimulation at the wrist needs to be done with gradual increments to make sure that ulnar stimulation does not occur. Martin Gruber anastomosis Ulnar CMAP on proximal stimulation can appear reduced if there is median-ulnar anastomosis. In all cases of suspected ulnar CB in the forearm, one needs to stimulate the median nerve at elbow recording at Abductor Digiti Minimi to check. Partial conduction block cannot be reliably recognized in the context of severe axon loss. Amplitude below 20% of the lower limit of normal at the most distal stimulation site is sufficiently small to preclude the confident recognition of partial conduction block.

68 Pitfalls in EDX in polyneuropathy II Difficulties in obtaining supramaximal stimulation proximally (Erb s point, tibial nerve in the posterior knee, radial nerve in the axilla). The longer the nerve segment the greater the area/ amplitude reduction required for CB. Excessive stimulation distally - Particularly an issue with median nerve stimulation at the wrist. Excessive stimulation can recruit ulnar innervated motor units. For all cases of median CB in the forearm, one needs to stimulate the ulnar nerve at the wrist and record over the thenar eminence. If a CMAP is obtained, median nerve stimulation at the wrist needs to be done with gradual increments to make sure that ulnar stimulation does not occur. Martin Gruber anastomosis Ulnar CMAP on proximal stimulation can appear reduced if there is median-ulnar anastomosis. In all cases of suspected ulnar CB in the forearm, one needs to stimulate the median nerve at elbow recording at Abductor Digiti Minimi to check. Partial conduction block cannot be reliably recognized in the context of severe axon loss. Amplitude below 20% of the lower limit of normal at the most distal stimulation site is sufficiently small to preclude the confident recognition of partial conduction block.