EDX · EP 10 · ELECTRODIAGNOSTICS
Before You Listen
Set the stage
- Prerequisites: basic nerve conduction study (NCS) interpretation; the meaning of the compound muscle action potential (CMAP) and the sensory nerve action potential (SNAP); how a needle electromyography (EMG) examination is performed; the difference between fibrillation potentials, positive sharp waves, and motor unit action potentials (MUAPs); familiarity with F-waves and the H-reflex as late responses; the basic anatomy of a peripheral nerve including the axon, the myelin sheath, and the node of Ranvier.
- Runtime: 1 hour 8 minutes 30 seconds.
- Topic in one line: the Seven Key Questions framework, the axonal vs demyelinating distinction, the uniform vs non-uniform split separating hereditary from acquired disease, GBS and its three subtypes (AIDP, AMAN, AMSAN), CIDP, CMT and HNPP, MMN vs ALS, diabetic neuropathy, CIP vs CIM, and the medication and paraproteinemic neuropathies.
Vignette. A 34-year-old previously healthy man presents to the emergency department with five days of progressive ascending weakness that began with tingling in his toes and now involves both legs and his hands. He cannot climb stairs and has fallen twice today. He had a self-limited diarrheal illness three weeks ago. On exam he has symmetric lower extremity weakness 3/5, mildly reduced grip, areflexia at the patellae and Achilles, and no sensory level. Cerebrospinal fluid (CSF) shows protein 92 mg/dL with 3 cells/microL. Forced vital capacity (FVC) is 2.0 L (declining). NCS at day 6 show normal sural SNAP amplitudes bilaterally with reduced median SNAPs, mildly slowed motor conduction velocities, and absent F-waves in the tibial and median nerves.
Which subtype of GBS does this picture suggest, what is the named EDX pattern that points specifically to this subtype, what is the most important EDX prognostic feature you should look for on the CMAPs, what infectious trigger is most likely, and what is the correct treatment (and equally important, what treatment is NOT effective)?
(Answer at the end of this chapter)
Section 1: The Seven Key Questions and the Axonal-Demyelinating Split
Bottom line: every polyneuropathy study answers seven questions in order: is it a polyneuropathy, axonal or demyelinating, which fiber types, what distribution, what time course, how severe, and is there a superimposed focal lesion. The axonal vs demyelinating split is the single most consequential branch point because it bifurcates the differential into two largely non-overlapping lists.
The Seven Key Questions framework is the scaffold every EDX study should answer. Question one asks whether a polyneuropathy is even present. The diagnosis requires abnormalities in multiple nerves following a symmetric, length-dependent gradient: at least two nerves in one limb, ideally confirmed in additional limbs. The American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) recommends a minimum study battery of up to 4 motor and 4 sensory NCS distributed as 2M+2S in one leg, 1M+1S in the contralateral leg, and 1M+1S in one arm, with H-reflexes and F-waves from 2 nerves added for diagnostic value. The sural SNAP is the most commonly tested sensory nerve and is typically the earliest abnormality in length-dependent polyneuropathies because the sural is among the longest sensory nerves studied.
Question two (axonal or demyelinating) drives every subsequent step. In axonal polyneuropathy the primary process is loss of axons via Wallerian-type degeneration in a length-dependent pattern. Surviving axons retain their myelin sheaths and conduct normally, so amplitude falls but velocity is preserved. Conduction velocity remains above 75% of the lower limit of normal (LLN) unless axonal loss is severe; distal latencies remain within 130% of the upper limit of normal (ULN). There is no conduction block and no temporal dispersion. F-wave latencies are normal or mildly prolonged. Needle EMG shows fibrillation potentials (active denervation) plus large-amplitude, long-duration MUAPs (chronic reinnervation). Mnemonic: amplitude down, velocity preserved.
In demyelinating polyneuropathy the primary process is loss of myelin while the underlying axon is initially spared. Demyelination disrupts saltatory conduction at the node of Ranvier. Hallmark findings include conduction velocity slowed below 75% LLN, distal motor latency prolonged beyond 130% ULN, F-wave latency above 130% ULN or absent, conduction block with greater than 20% amplitude drop between proximal and distal stimulation (some criteria use greater than 50% for definite block), and temporal dispersion with greater than 15% increase in CMAP duration between proximal and distal stimulation. SNAP amplitudes may be preserved early because axons remain intact, then reduce as secondary axonal loss develops.
Questions three through seven sharpen the diagnosis. Question three asks which fiber types are involved: pure sensory, pure motor, mixed sensorimotor, or small-fiber (which produces normal standard NCS because conventional studies assess only large myelinated fibers). Question four asks distribution: length-dependent stocking-glove for metabolic and toxic causes; non-length-dependent multifocal for inflammatory, vasculitic, or infiltrative disease; proximal-distal polyradiculoneuropathy for GBS and CIDP. Question five asks time course: acute (days to 4 weeks; GBS), subacute (4-8 weeks; toxic, nutritional), chronic (months to years; metabolic, hereditary, CIDP), or relapsing-remitting (CIDP, porphyria). Question six grades severity by SNAP and CMAP amplitudes and EMG denervation. Question seven asks for a superimposed focal neuropathy: diabetic patients have a two-to-three-fold increased risk of carpal tunnel syndrome, ulnar neuropathy at the elbow, and fibular neuropathy at the fibular head.
High Yield — Seven Questions and axonal-vs-demyelinating
- Seven Key Questions in order: presence, axonal vs demyelinating, fiber type, distribution, time course, severity, superimposed focal lesion.
- AANEM minimum = up to 4 motor + 4 sensory NCS (2M+2S leg 1; 1M+1S leg 2; 1M+1S arm) plus H-reflexes/F-waves from 2 nerves.
- Axonal: reduced SNAP/CMAP amplitudes; CV >75% LLN; distal latency <130% ULN; no conduction block, no temporal dispersion; F-waves normal or mildly prolonged; fibrillations + chronic neurogenic MUPs on EMG.
- Demyelinating: CV <75% LLN; distal latency >130% ULN; F-wave >130% ULN or absent; conduction block (>20% amplitude drop); temporal dispersion (>15% duration increase); SNAPs preserved early, reduced later.
- Mnemonic: axonal = amplitude down, velocity preserved; demyelinating = velocity slow, with block and dispersion.
- Sural SNAP = the most commonly tested sensory nerve and the earliest abnormality in length-dependent neuropathy.
- DANG THERAPIST mnemonic for axonal polyneuropathy: Diabetes, Alcohol, Nutritional, GBS axonal, Toxins, Hereditary, Endocrine, Renal, Amyloid, Paraproteinemic, Infectious, Systemic, Treatment-related.
The axons that do survive this toxic or metabolic insult are structurally completely normal. Their myelin sheaths are perfectly intact. So while there are fewer fibers carrying the signal, the fibers that remain carry that signal at a completely normal lightning-fast speed. That gives us our absolute hallmark finding for axonal polyneuropathy: reduced amplitudes with preserved conduction velocity.
— EDX-10 podcast, ~11:14