Weakness

1. EMG laboratory considerations – Demyelinating neuropathies Weakness Shawn Jorgensen Albany Medical Center AAPM&R Annual Assembly 2014

2. Financial disclosures • None

3. Possible neuropathy • When assessing whether someone presenting with weakness may have a neuropathic cause, main two questions are: • Is there any sensory deficit (by history, physical, and EDX)? • Time frame (acute/chronic)

4. Possible neuropathy • Sensory deficit • Is it real? • Is this likely to be related to the process, or an incidental, pre-existing process • Time frame • coincides with weakness • Degree of symptoms or findings • Major – more likely related

5. Possible neuropathy • Sensory involvement • Acute • AIDP • AMSAN • Chronic • CIDP

6. Possible neuropathy • No sensory involvement • Acute • AMAN • Chronic • MMN

7. Guillain-Barre Syndrome (GBS) • Acute, autoimmune, inflammatory neuropathy (polyradiculoneuropathy) • Most common cause of acute flaccid paralysis in the world (Ropper 1992) • Caused by molecular mimicry • 2/3 triggered by preceding infection or other process in the 6 weeks prior (Jacobs 1998)

8. Guillain-Barre Syndrome (GBS) • Collection of three different subtypes, all with essentially the same clinical presentation • AIDP – acute inflammatory demyelinating polyradiculoneuropathy • AMSAN – acute motor and sensory axonal neuropathy • AMAN – acute motor axonal neuropathy

9. Guillain-Barre Syndrome (GBS) • Typical presentation is acute ascending weakness and sensory complaints • Clinical criteria include • Weakness in proximal and distal muscles • Hyporeflexia • Progressing in less than 4 weeks

10. Guillain-Barre Syndrome (GBS) • Diagnosis • A combination of: • Clinical criteria above • EDX • CSF profile • Elevated protein, normal cell count (cytoalbuminic dissociation)

11. Guillain-Barre Syndrome (GBS) • Treatment • Intravenous immunoglobulin (IVIg) • Plasma exchange (PEX)/plasmapheresis • NOT steroids

12. AIDP • Demyelinating form of GBS • Sensory and motor • 90% of GBS in North America and Europe (Vucic 2009)

13. AIDP • Electrodiagnostics • Patchy, then diffuse, sensorimotor acquired demyelination • Sensorimotor • Demyelination • Acquired • Initially patchy, then diffuse • Predilection for nerve roots and distal motor terminals initially

14. AIDP • Electrodiagnostics • Demyelination • Inherited (uniform) • Prolonged motor, sensory, late response latencies • Decreased motor, sensory conduction velocities • Acquired (segmental) • Above, plus • Abnormal temporal dispersion • Conduction block

15. AIDP • Electrodiagnostics • Acquired demyelination • Abnormal temporal dispersion • Decreased amplitude • Increased duration • No change in area

16. AIDP • Electrodiagnostics • Acquired demyelination • Conduction block • Decreased amplitude • No change in duration • Drop in area

17. AIDP • Electrodiagnostics • Special considerations • “Sural sparing” • 2/3 will have a normal sural, abnormal upper limb sensory study (Gordon 2001)

18. AIDP • Electrodiagnostics • Special considerations • Early GBS • Only 50% meet demyelinating criteria in first week (Albers 1985) • May need to study many motor nerves, including proximal stimulation sites to find subtle areas of acquired demyelination • Late responses high yield • H-reflex abnormal in 97% in first week (Gordon 2001)

19. AIDP • Electrodiagnostics • Special considerations • Prognosis • CMAP amplitudes (Hadden 1998) • Inexcitable – poor prognosis at 2 weeks and beyond • Very low amplitude (<20% LLN) – poor prognosis at 2 weeks and beyond • Low amplitude (<80% LLN) – not a prognosticator in 2 weeks, poor prognosis at 6

20. AIDP • EDX assessment of possible AIDP • Technique • Include multiple motor studies, with multiple motor stimulation sites, loooking for evidence of acquired demyelination • Include late responses (especially H-reflex) • Interpretation • Don’t exclude AIDP if full criteria aren’t met • Don’t exclude AIDP if lower limb sensory studies are normal • Inexcitable CMAP and amplitude <20%LLN at 2 weeks indicates bad prognosis

21. AMSAN • Acute motor and sensory axonal neuropathy • One of the three subtypes of Guillain-Barre syndrome (GBS) • “Axonal GBS”

22. AMSAN • Electrodiagnostics • Sensorimotor axonopathy • Widespread and severe axonopathy, not necessarily length-dependent • NCS • Motor • Decreased amplitudes • Sensory • Decreased amplitudes • Needle EMG • Abnormal spontaneous activity

23. AMSAN • EDX assessment of AMSAN • Technique • Utility of NEE before 21 days have elapsed due to distal axonopathy • Consider direct motor stimulation to distinguish motor axon loss and muscle denervation from conduction block at the distal motor terminal • Interpretation • Pay close attention to sensory studies to distinguish from AMAN / other pure motor phenomenon

24. AMAN • One of the three subtypes of Guillain-Barre syndrome (GBS) • Most common variety in China, other parts of the world • Pure motor, axonal variant

25. AMAN • Electrodiagnostics • Diffuse, widespread motor axonopathy with sensory sparing! • NCS • Motor • Decreased amplitudes • Sensory • Normal!! • Needle EMG • Abnormal spontaneous activity

26. AMSAN/AMAN • EDX assessment of AMSAN/AMAN • Technique • Utility of NEE before 21 days have elapsed due to distal axonopathy • Consider direct motor stimulation to distinguish motor axon loss and muscle denervation from conduction block at the distal motor terminal • Interpretation • Pay close attention to sensory studies to distinguish from AMAN / other pure motor phenomenon

27. CIDP • Chronic inflammatory demyelinatingpolyneuropathy

28. CIDP • Chronic inflammatory demyelinatingpolyneuropathy • “MS of the PNS” (Amato 2008) • Autoimmune • Demyelinating • Treatable • Can be relapsing / remitting

29. CIDP • Clinical features • Classic presentation • Progresses for >=8 weeks • Sensory dysfunction • Weakness – proximal and distal • Hyporeflexic • Unusual features • Asymmetrical • Distal weakness only

30. CIDP • Laboratory studies • CSF • Cytoalbuminic dissociation (high protein, normal cells) • EDX • Diffuse • Sensorimotor • Acquired demyelination • Non length-dependent • Secondary axon loss

31. CIDP • Diagnosis • Clinical and EDX criteria • Used for research studies • >= 17 different sets! • Miss treatable patients (low sensitivity) • include non-treatable patients (low specificity)

32. CIDP • Treatment • IVIg • PEX • Can use corticosteroids • Maintenance agents (methotrexate, azathioprine)

33. CIDP • Electrodiagnostic considerations • Acquired demyelination • Conduction slowing • Conduction velocity • <80%LLN (CMAP amplitude >80% LLN) • <70% LLN (CMAP amplitude <80% LLN) • CMAP, F-wave distal latency • >125% ULN (CMAP amplitude >80% LLN) • 120% for F-waves (Neuropathy association 2003) • >150% ULN (CMAP amplitude <80% LLN) • Sources: AAN 1991, Saperstein 2001, Neuropathy Association 2003

34. CIDP • Electrodiagnostic considerations • Acquired demyelination • Drop CMAP amplitude • >20% (AAN 1991) • >30% (Neuropathy association 2003) • >50% (Saperstein 2001, EFNS/PNS 2010, Koski 2009) • >30% probably, >50% definite (Van den bergh 2004) • Increase duration • >15% (AAN 1991, Neuropathy Association 2003) • >30% (Saperstein 2001, Van den bergh 2004, EFNS/PNS 2010)

35. CIDP • Electrodiagnostic considerations • Acquired demyelination • Distal CMAP duration (EFNS/PNS 2010) • Median >6.6ms • Ulnar >6.7ms • Fibular >7.6ms • Tibial >8.8ms

36. CIDP • EDX assessment of possible CIDP • Technique • Include multiple motor studies, with multiple motor stimulation sites, loooking for evidence of acquired demyelination • Include late responses (especially F-wave) • Interpretation • Don’t exclude CIDP if full criteria aren’t met • Don’t exclude CIDP if lower limb sensory studies are normal • Look for evidence of acquired demyelination, including increased duration of distal CMAP

37. Multifocal Motor Neuropathy (MMN) • Chronic demyelinating neuropathy • Involves primarily conduction block • ONLY MOTOR FIBERS!! • ?Variant of CIDP

38. Multifocal Motor Neuropathy (MMN) • Clinical features • Chronic, progressive weakness • Usually distal muscles of upper limbs initially • Fasciculations • Eventually atrophy • In discrete peripheral nerve distributions, non-entrapment sites • NO SENSORY SYMPTOMS!!

39. Multifocal Motor Neuropathy (MMN) • Laboratory features • CSF • Normal • Anti GM-1 antibodies • High titers are specific, low non-specific (Kornberg 1994)

40. Multifocal Motor Neuropathy (MMN) • Treatment • IVIg • NOT PEX, corticostroids (can worsen)

41. Multifocal Motor Neuropathy (MMN) • Electrodiagnostic considerations • Conduction block (AANEM consensus criteria, Olney 2003) • Median, ulnar, fibular across fibular head • >50% amplitude, 40% area • Tibial, fibular across leg • >60% amplitude, 50% area • Can be other parameters of demyelination

42. Multifocal Motor Neuropathy (MMN) • Electrodiagnostic considerations • Test asymptomatic sites • May show abnormalities (Van Asseldonk 2003) • In areas of motor conduction block, test sensory study across same area

43. Multifocal Motor Neuropathy (MMN) • EDX assessment of possible MMN • Technique • Test asymptomatic sites • May show abnormalities (Van Asseldonk 2003) • In areas of motor conduction block, test sensory study across same area

44. Demyelinating neuropathies • Conclusions • In patients diffuse weakness and “real” sensory complaints, demyelinating neuropathies need to be considered • There are many subtleties in the EDX technique and interpretation of demyelinating neuropathies • Look for evidence of acquired demyelination • Use many motor studies • Use late responses • Do not dismiss cases that do not meet criteria

45. Thank you!!

46. References Dyck PJ, Thomas PK. Peripheral Neuropathy. Philadelphia, PA:Elsevier Saunders, 2005. Jacobs BC, Rothbarth PH, Van derMeche, et al. The spectrum of antecedent infections in Guillain-Barre syndrome. A case-control study. Neurology 1998;51:1110-1115. Vucic S, Kiernan MC, Cornblath DR. Guillain-Barre syndrome: an update. J ClinNeurosci 2009;16(6):733-741. Gordon PH, Wilbourne AJ. Early electrodiagnostic findings in Guillain-Barre syndrome. Arch Neurol 2001;58:913-917. Albers JW, Donofrio PD, McGonagle TK. Sequential electrodiganostic abnormalities in acute inflammatory demyelinatingpolyradiculoneuropathy. Muscle Nerve 1985;8:528-539. Hadden RD, Cornblath DR, Hughes RA, Zielasek J, Hartung HP, Toyka KV, Swan AV. Electrophysiological classification of Guillain-Barre syndrome: clinical associations and outcome. Plasma Exchange/SandoglobulinGuillain-Barre Syndrome Trial Group. Ann Neurol 1998;44:780-788. Cornblath DR, Asbury AK, Albers JW, et al. Research criteria for diagnosis of chronic inflammatory demyelinatingpolyneuropathy (CIDP). Neurology 1991;41:617-618. Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinatingpolyneuropathies. Muscle Nerve 2001:24:311-324. Berger AR, Bradley WG, Brannagan TH, Busis NA, Cros DP, Dalakas MC, Danon MJ, Donofrio P, Engel WK, England JD, Feldman EL, Freeman RL, Kinsella LJ, Lacomis D, Latov N, Menkes DL, Sander HW, Thomas FP, Triggs WJ, Windebank AJ. Wolfe GI; Neuropathy Association, Medical Advisory Committee. Guidelines for the diagnosis and treatment of chronic inflammatory demyelinatingpolyneuropathy. J Peripher Nerve Syst 2003;8:282-284.

47. References Koski CL, Baumgarten M, Magder LS, Barohn RJ, Goldetein J, Graves M, Gorson K, Hahn AF, Hughes RA, Katz J, Lewis RA, Parry GJ, van Doorn P, Cornblat DR. Derivation and validation of diagnostic criteria for chronic inflammatory demyelinatingpolyneuropathy. J NeurolSci 2009;277:1-8. Van den bergh PY, Pieret F. Electrodiagnostic criteria for acute and chronic inflammatory demyelinatingpolyradiculoneuropathy.. Muscle Nerve 2004;29:565-574. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinatingpolyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – First Revision. J PeripherNervSyst 2010;15:1-9. Kornberg AJ, Pestronk A. The clinical and diagnostic role of anti-GM1 antibody testing. Muscle Nerve 1994;17:100-104. Olney RK, Lewis RA, Putnam TD, Campelione JV Jr, American Association of Electrodiagnostic Medicine. Consensus criteria for the diagnosis of multifocal motor neuropathy. Muscle Nerve 2003:27:117-121. Van asseldonk JTH, Van den Berg LH, Van den Berg-Vos RM, Wieneke GH, Wokke JHJ, Franssen H. Demyelination and axon loss in multifocal motor neuropathy: distribution and relation to weakness. Brain 2003;126:186-198.