Know what your EMG might miss!

 Speakers Tony Chiodo, MD Tony Chiodo, MD Timothy Dillingham, MD Timothy Dillingham, MD W. David Arnold, MD W. David Arnold, MD Shawn Jorgensen, MD Shawn Jorgensen, MD

 Blind spots

 “Electrodiagnostic impression: Normal study…”

 “Electrodiagnostic impression: No generalized peripheral neuropathy…”

 Patient #1 29 year old female with one week of numbness, prickly sensation and pain in the feet, progressing to the calves, later in the hands, lips, mouth. 29 year old female with one week of numbness, prickly sensation and pain in the feet, progressing to the calves, later in the hands, lips, mouth. Four days ago began having difficulty going up stairs, getting out of chairs, getting her legs in her pants, getting her arms overhead Four days ago began having difficulty going up stairs, getting out of chairs, getting her legs in her pants, getting her arms overhead Balancing is worsening Balancing is worsening No oculobulbar, bowel or bladder symptoms No oculobulbar, bowel or bladder symptoms 2 weeks prior saw PCP, diagnosed with a URI, given a tetanus and influenza vaccine 2 weeks prior saw PCP, diagnosed with a URI, given a tetanus and influenza vaccine

 Patient #1 Physical examination Physical examination  CN – normal  Motor  4/5 elbow extension, DIP flexion, ankle dorsiflexion, toe extension, 5-/5 hip flexion  Functionally could not get out of chair without using her arms  Sensory  Pinprick, vibration normal  Romberg positive  MSR  1+ brachioradialis, others areflexic

 Patient #1 Electrodiagnostics Electrodiagnostics  Motor – normal except  Left median to APB: decreased amplitude prox + distally  Right fibular: 25% amplitude loss proximal to distal, decreased CV  Left tibial: prolonged DML, decreased CV  Sensory – normal except  Right sural, bilateral medial dorsal cutaneous prolonged PL  Late responses  F-waves – decreased amplitude ulnar bilaterally, o/w normal  H-reflex – absent bilaterally  NEE  Left upper, lower, paraspinals normal

 Patient #1 “Electrodiagnostic Impression: “Electrodiagnostic Impression: Abnormal study. Mild generalized sensorimotor neuropathy.” Abnormal study. Mild generalized sensorimotor neuropathy.”

 Guillain-Barre Syndrome Acute, autoimmune neuropathy Acute, autoimmune neuropathy Clinically presents with acutely progressive sensory dysfunction and weakness, usually in an ascending pattern, progressing for less that four weeks Clinically presents with acutely progressive sensory dysfunction and weakness, usually in an ascending pattern, progressing for less that four weeks Exam should demonstrate sensory loss (particularly large fiber), weakness of both proximal and distal muscles, and hyporeflexia Exam should demonstrate sensory loss (particularly large fiber), weakness of both proximal and distal muscles, and hyporeflexia

 Guillain-Barre Syndrome EMG findings in GBS EMG findings in GBS  Sensorimotor  Non length-dependent  Acquired demyelination  Abnormal temporal dispersion  Conduction block

 Guillain-Barre Syndrome EMG findings in early GBS EMG findings in early GBS  Demyelination (Albers 1985)  Week % meet full demyelinating criteria  Week 5 – 87% meet criteria  Late Responses – week 1 (Gordon 2001)  97% abnormal H reflexes (88% day 4)  87% abnormal F waves

 Guillain-Barre Syndrome Non length-dependence Non length-dependence  Abnormal upper limb/normal lower limb  “Sural sparing”  50% of patients by week 1 (Gordon 2001)

 EMG BLIND SPOTS!! Guillain-Barre syndrome Guillain-Barre syndrome  Early normal/minimally abnormal EDX  Look for late responses  Normal sural  Look for abnormal upper limb

 Patient #1 – revised impression “Electrodiagnostic Impression: “Electrodiagnostic Impression: Abnormal study. Mild generalized peripheral neuropathy; cannot exclude early AIDP Abnormal study. Mild generalized peripheral neuropathy; cannot exclude early AIDP Clinical Impression: Clinical Impression: Monitor closely for worsening neurological symptoms and repeat NCS in one week if symptoms don’t improve or worsen. Consider consultation with a neuromuscular specialist.” Monitor closely for worsening neurological symptoms and repeat NCS in one week if symptoms don’t improve or worsen. Consider consultation with a neuromuscular specialist.”

 Patient #2 67 year old patient with slowly progressive ambulatory decline 67 year old patient with slowly progressive ambulatory decline Thinks it has been going on for 3 years Thinks it has been going on for 3 years Feels weakness is in his legs and has some in arms as well Feels weakness is in his legs and has some in arms as well When asked, notes numbness in feet and hands When asked, notes numbness in feet and hands No oculobulbar or sphincter complaints No oculobulbar or sphincter complaints PMH: DM2, mild CHF PMH: DM2, mild CHF

 Patient #2 Physical examination Physical examination  Cranial nerves - normal  Motor – normal excepts  3+/5 right, 4/5 left arm abduction  4/5 finger abduction  2/5 hip flexion  4/5 knee extension  4/5 right, 3-/5 left ankle dorsiflexion  MSR  Trace in uppers, 0 in lowers  Sensation  Absent vibration at ankles  Pinprick normal

 Patient #2 Electrodiagnostics Electrodiagnostics  Motor NCS  Diffusely diminished conduction velocities  Dramatic temporal dispersion across the forearm on right ulnar motor  Lower limb studies unobtainable  Sensory NCS  Lowers unobtainable  Ulnar sensory low amplitude  Needle EMG  Abnormal spontaneous activity, large amplitude MUAP in distal LE muscles

 Patient #2 “Electrodiagnostic Impression: “Electrodiagnostic Impression: Abnormal study. Generalized sensorimotor neuropathy with axonal and demyelinating features.” Abnormal study. Generalized sensorimotor neuropathy with axonal and demyelinating features.”

 CIDP Chronic inflammatory demyelinating polyradiculoneuropathy Chronic inflammatory demyelinating polyradiculoneuropathy MS of the PNS (Amato 2009) MS of the PNS (Amato 2009)  Autoimmune  demyelinating  often relapsing/remitting course, other progressive More common than you think! More common than you think!  Of those with cryptogenic neuropathy referred for intensive referral center investigation, about 1/5 have CIDP (and are treatable) (Dyck 1981)

 CIDP Clinical features Clinical features  Progresses for 8 weeks or more  Weakness classically proximal and distal, symmetrical  Hyporeflexia  Sensory complaints Lab features Lab features  EDX – diffuse sensorimotor acquired demyelination (similar to AIDP)  CSF – cytoalbuminic dissociation

 CIDP Atypical forms Atypical forms  Not all meet even basic clinical features  Asymmetrical or pure sensory in 50% cases (Breiner 2014)

 CIDP Criteria (AAN) Criteria (AAN)  Clinical  Motor and or sensory loss in >1 limb  Hyporeflexic  Over 2 months  Electrodiagnostic  3 out of 4  CB/TD in >=1 nerve  CV decreased in >=2 nerves  DL prolonged in >=2 nerves  FW prolonged in >=2 nerves

 CIDP Criteria Criteria  At least 15!  No consensus  Sensitivities range from 11-91% (Breiner 2014)  False negatives – treatable patients missed  Specificity range from % (Breiner 2014)  False positives – non-treatable patients exposed to unnecessary risks, MAJOR costs  Of those with treatable disease (by expert consensus), about 1/3 never met ANY criteria (Bromberg 1991)

 Patient #2 Diagnostics Diagnostics  CSF analysis  Protein 97, otherwise normal Treatment Treatment  Moderate improvement with IVIg  Strength improved to >=4/5 proximal muscles  Reflexes 2+ uppers, patella  Able to ambulate with walker and minimal assistance

 BLIND SPOTS!! CIDP CIDP  Not meeting criteria  Consider those with basic clinical features  Asymmetrical, no proximal and distal weakness  Consider asymmetrical, pure sensory forms

 Patient #2 – revised impression “Electrodiagnostic Impression: “Electrodiagnostic Impression: Abnormal study. Generalized peripheral neuropathy with features of acquired demyelination; suspicious for but not meeting research criteria for chronic inflammatory demyelinating polyneuropathy (CIDP)” Abnormal study. Generalized peripheral neuropathy with features of acquired demyelination; suspicious for but not meeting research criteria for chronic inflammatory demyelinating polyneuropathy (CIDP)” “Clinical Impression: “Clinical Impression: This patient may have a non-classic form of CIDP. Consultation with a neuromuscular specialist and lumbar puncture could be considered.” This patient may have a non-classic form of CIDP. Consultation with a neuromuscular specialist and lumbar puncture could be considered.”

 Patient #3 47 year old with 2 months of cramping, numbness and tingling on the anterolateral ankle and dorsal foot 47 year old with 2 months of cramping, numbness and tingling on the anterolateral ankle and dorsal foot Has had numbness in the right hand for years Has had numbness in the right hand for years Balance is fine Balance is fine No orthostatic hypotension, constipation, nausea No orthostatic hypotension, constipation, nausea Strength is normal Strength is normal Blurry vision, otherwise no oculobulbar complaints or trouble controlling her bowel or bladder Blurry vision, otherwise no oculobulbar complaints or trouble controlling her bowel or bladder

 Patient #3 Physical examination Physical examination  Cranial nerves – normal  Motor exam – normal  Sensory exam  Decreased pinprick sensation in the distal foot, otherwise normal  Normal vibration, light touch, temperature sensation  Reflexes - normal  Coordination - normal

 Patient #3 Electrodiagnostics Electrodiagnostics  CMAP – normal median, ulnar, fibular  SNAP – normal sural, medial dorsal cutaneous, median, ulnar, radial  NEE – normal UE/LE

 Pictures of EDX

 Patient #3 “Electrodiagnostic impression: “Electrodiagnostic impression: Normal study. No generalized peripheral neuropathy or lumbosacral radiculopathy.” Normal study. No generalized peripheral neuropathy or lumbosacral radiculopathy.”

 Subtle neuropathies EDX techniques to increase sensitivity EDX techniques to increase sensitivity  Medial plantar  Mild diabetics – 50% with prolonged sural latency, 70% prolonged/absent medial plantar (Reeves 1984)

 Small fiber neuropathy Sensory fibers for pain, temperature, autonomic fibers Sensory fibers for pain, temperature, autonomic fibers Clinical presentation with pain, burning Clinical presentation with pain, burning Usually no numbness, tingling, weakness Usually no numbness, tingling, weakness Physical examination Physical examination  Loss of pinprick and temperature sensation with normal light touch, proprioception and vibration  Normal strength  Normal MSR

 Small fiber neuropathy Studies Studies  Electrodiagnostics – normal!!!  Skin biopsy  Measurement of intraepidermal nerve fiber density  Decreased in 77% of patients at the distal calf with clinical suspicion of small fiber neuropathy (Holland 1998)  Autonomic testing  Different tests, yields

 EMG BLIND SPOTS!! Subtle neuropathies Subtle neuropathies  Consider tests with increased sensitivity (medial plantar) Small fiber neuropathy Small fiber neuropathy  Remember standard EDX only tests large fibers

 Patient #3 – revised impression “Electrodiagnostic Impression: “Electrodiagnostic Impression: Normal study. No generalized peripheral neuropathy affecting large fibers. Normal study. No generalized peripheral neuropathy affecting large fibers. Clinical Impression: Clinical Impression: A neuropathy primarily affecting small fibers cannot be excluded with standard electrodiagnostic studies. Specialized testing (skin biopsy, autonomic testing) could be considered to further assess this possibility.” A neuropathy primarily affecting small fibers cannot be excluded with standard electrodiagnostic studies. Specialized testing (skin biopsy, autonomic testing) could be considered to further assess this possibility.”

 EMG BLIND SPOTS!! – summary GBS GBS  Be aware of low yield in early testing – use H-reflex  Be aware of non length-dependent findings (sural sparing) CIDP CIDP  Be aware of low sensitivity of research criteria  Be aware of relatively high frequency of atypical presentations Possible subtle neuropathies Possible subtle neuropathies  Consider testing with increased sensitivity (i.e. medial plantar)  Remember small fiber neuropathies have negative EDX!

Thank you!!

 Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barre syndrome. Ann Neurol 1990;27(suppl):S21-S24.  Albers JW, Donofrio PD, McGonagle TK. Sequential electrodiagnostic abnormalities in acute inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 1985;8:  Gordon PH, Wilbourne AJ. Early electrodiagnostic findings in Guillain-Barre syndrome. Arch Neurol 2001;58:  Amato AA, Russell JA. Neuromuscular disorders. New York: McGraw Hill Medical;  Dyck PJ, Oviatt KF, Lambert EH. Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol 1981; 10:  AAN – change to EFNS  Breiner A, Brannigan TH. Comparison of sensitivity and specificity among 15 criteria for chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2014;50:  Bromberg M. Comparison of electrodiagnostic criteria for primary demyelination in chronic polyneuropathy. Muscle Nerve 1991;14:  Reeves ML, Seigler DE, Ayyar DR, et al. Medial plantar sensory response. Sensitive indicator of peripheral nerve dysfunction in patients with diabetes mellitus. Am J Med 1984;76(5):  Holland NR, Crawford TO, Hauer P, Cornblath DR, Griffin JW, McArthur JC. Small-fiber sensory neuropathies: clinical course and neuropathyology of idiopathic causes. Ann Neurol 1988;55(1):47-59.