Conduction Studies Related to Peripheral Nerve Injury Classification

1/24/2018

CONDUCTION STUDIES RELATED TO PERIPHERAL NERVE INJURY CLASSIFICATION

ELECTRICAL STUDIES, in the ABSENCE of CLINICAL INFORMATION, ARE USELESS for the PURPOSE of MANAGEMENT and PROGNOSIS

J.A. Gehret, D.O., Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA

CONDUCTION STUDIES RELATED TO PERIPHERAL NERVE INJURY CLASSIFICATION

MYELINOPATHIES DYSMYELINATION (DEFINITION) DEMYELINATION = NEURAPRAXIA = CONDUCTION BLOCK

AXONOPATHIES AXONOTMESIS NEUROTMESIS

NORMAL CONDUCTION

G.J. Herbison, M.D. [email protected] IDEAL AXON TO MYELIN RATIO = 0.6 for MAXIMUM SPEED of CONDUCTION

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MYELINOPATHY EXAMPLES

NORMAL

DYSMYELINATION

DEMYELINATION G.J. Herbison, M.D. [email protected]

MYELINOPATHIES DISTAL INCOMPLETE NEURAPRAXIA DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY…. SLOW TEMPORAL DISPERSION…. DECREASED AMPLITUDE………………….. DECREASED

G.J. Herbison, M.D. IS the CONDITION of the MYELIN WORSENING or IMPROVING? [email protected] Do the CONDUCTION STUDIES POINT to SYMPTOMS at the TIME of the STUDY? WHY IS CONDUCTION VELOCITY SLOW?

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NERVE INJURY CLASSIFICATIONS ORIGINAL FOCUS: SITE of INJURY

CURRENT FOCUS on SCHWANN CELL & BASAL LAMINA SURVIVAL RELATED TO: DISTANCE BETWEEN INJURY & MUSCLE TIME RELATED DISTAL CHANGES

Seddon & Sunderland’s classification systems can be broadened to include the potential for an axonotmesis to evolve into an intraneural neurotmesis.

G.J. Herbison, M.D. Thomas Jefferson University

MYELINOPATHIES DYSMYELINATION: DISTAL FOCAL DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY… NORMAL TEMPORAL DISPERSION… NORMAL AMPLITUDE…………………. NORMAL

G.J. Herbison, M.D. IS the THIN MYELIN WORSENING or IMPROVING? Thomas Jefferson University [email protected]

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MYELINOPATHIES DYSMYELINATION: DISTAL FOCAL DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY… NORMAL

G.J. Herbison, M.D. Thomas Jefferson University [email protected]

MYELINOPATHIES DYSMYELINATION: DIFFUSE DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY… SLOW TEMPORAL DISPERSION… NORMAL AMPLITUDE…………………. NORMAL

G.J. Herbison, M.D. Thomas Jefferson University IS the CONDITION of the MYELIN WORSENING or IMPROVING? [email protected]

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MYELINOPATHIES DYSMYELINATION: MULTIFOCAL DISTAL DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY… NORMAL TEMPORAL DISPERSION… INCREASED AMPLITUDE…………………. DECREASED

IS the CONDITION of the MYELIN WORSENING or IMPROVING? G.J. Herbison, M.D. Do the CONDUCTION STUDIES POINT to SYMPTOMS at the TIME of the STUDY Thomas Jefferson University [email protected]

MYELINOPATHIES DYSMYELINATION: MULTIFOCAL DIFFUSE DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY… SLOW TEMPORAL DISPERSION… INCREASED (CMAP 1  and CAMP 2  > 30% of CMAP 1) AMPLITUDE…………………. DECREASED (CMAP 1  and CAMP 2  > 30% of CMAP 1)

IS the CONDITION of the MYELIN WORSENING or IMPROVING? G.J. Herbison, M.D. Do the CONDUCTION STUDIES POINT to SYMPTOMS at the TIME of the STUDY Thomas Jefferson University [email protected]

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MYELINOPATHIES PROXIMAL INCOMPLETE NEURAPRAXIA DISTAL LATENCY…………… NORMAL CONDUCTION VELOCITY…. NORMAL DISTAL to NEURAPRAXIA DECREASED PROXIMAL to NEURAPRAXIA TEMPORAL DISPERSION…. NORMAL DISTAL to NEURAPRAXIA DECREASED PROXIMAL to NEURAPRAXIA AMPLITUDE………………….. NORMAL DISTAL to NEURAPRAXIA DECREASED PROXIMAL to NEURAPRAXIA

IS the CONDITION of the MYELIN WORSENING or IMPROVING? Do the CONDUCTION STUDIES POINT to SYMPTOMS at the TIME of the STUDY? G.J. Herbison, M.D. WHY TEMPORAL DISPERSION DECREASED PROXIMAL to NEURAPRAXIA? Thomas Jefferson University

MYELINOPATHIES DISTAL INCOMPLETE NEURAPRAXIA DISTAL LATENCY…………… PROLONGED CONDUCTION VELOCITY…. SLOW TEMPORAL DISPERSION…. DECREASED AMPLITUDE………………….. DECREASED

IS the CONDITION of the MYELIN WORSENING or IMPROVING? G.J. Herbison, M.D. Do the CONDUCTION STUDIES POINT to SYMPTOMS at the TIME of the STUDY? Thomas Jefferson University WHY IS CONDUCTION VELOCITY SLOW? [email protected]

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MIXED MEDIAN MOTOR/SENSORY – WRIST TO ELBOW CONDUCTION

BAR RECORDING ELECTRODE RED REFERENCE PROXIMAL BLACK ACTIVE DISTAL GREEN: GROUND

HAND HELD STIMULATOR BLACK: CATHODE PROXIMAL RED: ANODE

G.J. Herbison, M.D., Thomas Jefferson University

AXONOPATHY: 1 MONTH POST INJURY of FASTEST 4 AXONS

DISTAL LATENCY…………..PROLONGED CONDUCTION VELOCITY…SLOW TEMPORAL DISPERSION…DECREASED AMPLITUDE………………….DECREASED

G.J. Herbison, M.D. Thomas Jefferson University, [email protected]

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CMAP DISTAL to INJURY NEURAPRAXIA AXONOPATHY DAY of/post INJURY 1 14 1 14

DISTAL LATENCY………….. N N N PROLONGED CONDUCTION VELOCITY… N N N SLOW TEMPORAL DISPERSION… N N N DECREASED AMPLITUDE…………………. N N N LOW

[email protected]

CMAP PROXIMAL to INJURY (STIM 3) NEURAPRAXIA AXONOPATHY DAY of INJURY 1 14 1 14 DISTAL LATENCY………….. N N N PROLONGED CONDUCTION VELOCITY… SLOW SLOW SLOW SLOW TEMPORAL DISPERSION…  AMPLITUDE…………………. 

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ALL CONDUCTION COMMENTS IDENTIFY FINDINGS DISTAL to INJURY SITE

DISTAL LATENCY…………..N CONDUCTION VELOCITY…N TEMPORAL DISPERSION…N AMPLITUDE………………….N

DISTAL LATENCY…………..PROLONGED CONDUCTION VELOCITY…SLOW TEMPORAL DISPERSION… AMPLITUDE………………….

DISTAL LATENCY………….. PROLONGED CONDUCTION VELOCITY…SLOW TEMPORAL DISPERSION… or N AMPLITUDE…………………. or N

G.J. Herbison, M.D., [email protected]

ALL CONDUCTION COMMENTS IDENTIFY FINDINGS DISTAL to INJURY SITE

DISTAL LATENCY…………..N CONDUCTION VELOCITY…N TEMPORAL DISPERSION…N AMPLITUDE………………….N

DISTAL LATENCY…………..PROLONGED CONDUCTION VELOCITY…SLOW TEMPORAL DISPERSION… AMPLITUDE………………….

DISTAL LATENCY………….. PROLONGED CONDUCTION VELOCITY…SLOW TEMPORAL DISPERSION… or N AMPLITUDE…………………. or N

G.J. Herbison, M.D. [email protected]

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PARTIAL PROXIMAL INJURY with: AXONOTMESIS  REINNERVATION of PROXIMAL MUSCLES AXONOTMESIS  DISTAL NEUROTMESIS

}CMAP: ABSENT STIMULATING at SITES 2 & 3

DISTAL LATENCY…………..Prolonged CONDUCTION VELOCITY…Slow TEMPORAL DISPERSION… AMPLITUDE………………….

PROXIMAL CMAP: ABSENT

DISTAL LATENCY…………..Prolonged CONDUCTION VELOCITY…Slow TEMPORAL DISPERSION… or N AMPLITUDE…………………. or N

COND VEL S3 to S2………..Slow TEMPORAL DISPERSION…N to  AMPLITUDE………………….N to 

DISTAL LATENCY…………..Prolonged CONDUCTION VELOCITY…Slow TEMPORAL DISPERSION… or N AMPLITUDE…………………. or N G.J. Herbison, M.D. [email protected]

DISTAL LATENCY…………..PROLONGED CONDUCTION VELOCITY…N MYELIN THINNING TEMPORAL DISPERSION…N AMPLITUDE………………….N

DISTAL LATENCY…………..PROLONGED CONDUCTION VELOCITY…SLOW MYELIN THINNING TEMPORAL DISPERSION… 2 AXONS BLOCKED AMPLITUDE………………….

DISTAL LATENCY…………. PROLONGED MORE MYELIN THINNING CONDUCTION VELOCITY…SLOW 2 AXONS AXONOMETSIS TEMPORAL DISPERSION…. AMPLITUDE…………………..

MORE MYELIN THINNING 2 AXONS PROGRESSED to INTRANEURAL NEUROTMESIS 1 AXON AXONOMESIS DISTAL LATENCY………….. PROLONGED CONDUCTION VELOCITY…SLOW DENERVATED MUSCLE TEMPORAL DISPERSION… or N FIBERS INNERVATED AMPLITUDE…………………. or N from SPROUTS from 35 m/s AXON

2 AXONS INTRANEURAL NEUROTMESIS 1 AXON REGENERATED AXONOMETSIS 2 AXONS: THIN MYELIN NORMALIZED DISTAL LATENCY………….. PROLONGED DENERVATED MUSCLE CONDUCTION VELOCITY…SLOW FIBERS INNERVATED TEMPORAL DISPERSION… or N from MORE MATURE SPROUTS of AMPLITUDE…………………. or N 35 m/s AXON [email protected]

10 1/24/2018

CONDUCTION STUDIES RELATED TO PERIPHERAL NERVE INJURY CLASSIFICATION

ELECTRICAL STUDIES, in the ABSENCE of CLINICAL INFORMATION, ARE USELESS for the PURPOSE of MANAGEMENT and PROGNOSIS

J.A. Gehret, D.O., Thomas Jefferson University, Philadelphia, PA, [email protected]

Bernstein JJ, Guth L. Nonselectivity in establiishment of neuromuscular connections folllowing nerve regeneration in the rat. Exp Neurol 1961; 4: 262-275

Brown MC. Ironton R. Sprouting and regression of neuromuscular synapses in partially denervated mamalian muscles. Journal of Physiology. 278:325-48, 1978

Buschbacher RM, Prahlow NH. Manual of Nerve Conduction. 2nd ed. Demos, New York 2006

Dumitru D, Amato AA, Zwarts M. Electrodiagnostic Medicine. 2nd ed. Henley & Belfus. Philadelphia 2001 a. A 0.6 axon to myelin ration optimizes the speed of conduction pg 18 1st edition of book 1994.

Court FA. Wrabetz L. Feltri ML. Basal lamina: Schwann cells wrap to the rhythm of space-time. Current Opinion in Neurobiology. 16(5):501-7, 2006 a. Schwann cells regulate the basal lamina and its receptors

Franssen H. Electrophysiology in demyelinating polyneuropathies. Expert Review of Neurotherapeutics. 8(3):417-31, 2008 a. “…demyelination of one internode may give rise to internode conduction slowing or conduction block” b. “… it was shown that a maximal amount of temporal dispersion could yield a CMAP amplitude reduction proximal/distal & a CMAP area reduction of up to 50%.

Fu SY. Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy. Journal of Neuroscience. 15(5 Pt 2):3876-85, 1995 a. …the principlal mecahanism for poor reinnervation after prolonged denervation is deterioration of the distal nerve rather than the inability of muscle to accept reinnervationion

Gordon T. Yang JF. Ayer K. Stein RB. Tyreman N. Recovert potential of muscle after partial denervation: a comparison between rats and humans. Brain Research Bulletin. 30(3-4):477-82, 1993. a. A single motor unit can enlarge five times its original size resulting in the ability to compensate up to 80% partial denervation in humans

Gordon T. Tyreman N. Raji MA. The basis for diminished functional recovery after delayed peripheral nerve repair. Journal of Neuroscience. 31(14):5325-34, 2011 a. Functional recuvery is limited primarily by the progressive fall in regenerative capacity of axotomized neurons and denervated Schwann cell. With time and distance

Guth L. Neuromuscular function afrer regeneration of interrupted nerve fibers into partially denervated muscle. Experimental Neurology. 6:129-41, 1962 a. Parent axons reinnervate denervated axons after sprouting form intact axons.

Hall SM. Regeneration in the peripheral nervous system. Neuropathology & Applied Neurobiology. 15(6):513-29, 1989 a. Few nerve injuries involve transection. Most involve soft tissue injury with sections of epineurium intact with long sections of intraneural neurotmesis

Hansen S. Ballantyne JP. A quantitative electrophysiological study of motor neuron disease. Journal of Neurology, Neurosurgery & Psychiatry. 41(9):773-83, 1978 a. “Reinnervation appears to cease when 5% or less of motor units remain viable”

Hoke A. Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans. Nat Clin Pract Neurol. 2006; 2: 448 – 554 a. Human nerves often have to grow long distances. And the distal portion loses its ability to support regeneration because of Schwann cell and basal lamina atrophy b. By 6 months of chronic denervation there is almost no regenerative support for axon growth.

Kimura J. Electrodiagnosis in Diseases of the Nerve and Muscle. 2nd ed. F. A. Davis Co. Philadelphia 1989 G.J. Herbison, M.D. Thomas Jefferson University Kimura J. Consequences of peripheral nerve demyelination: Basic and clinical aspects. Can J NeurolSci 1993; 20: 263–270 [email protected] a. Slowing of conduction by itself leads to little, if any clinical symptoms….”(pg 263) b Restoration of conduction follows remyelination unless another bout of demyelination takes place

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Kimura J. Facts, fallacies, and fancies of nerve conduction studies: twenty-first annual Edward H. Lambert Lecture. Muscle & Nerve. 20(7):777-87, 1997 a. Clinical and electrophysiologic findings together characterize conduction block (pg 785) b. Sensory conduction block is difficult because of phase cancellation (pg 785) 78

Kimura, J. Personal communication March 6, 2012. Slowing and temporal dispersion simply desynchronize the impulse. In case of motor fibers, as long as all the impulses arrive at the motor terminal, muscle strength remains normal. If you analyze a reaction time very precisely, you may find a little delay if the nerve is conducting very slowly but this difference is so small, it does not cause any detectable signs. The same probably hold with the sensory system. Here, each synaptic transmission on the way to the cortex actually tend to synchronize the impulse by summation so that temporal dispersion would become less as the signal reaches the cortex, again making no noticeable negative (or positive) signs.

Only detectable effect would probably related to the mono-synaptic stretch reflex, which become diminished or absent, once the afferent pulses become desynchronized (because it takes a very synchronized arrival of afferent impulse to reflexively activate motoneurones. Thus, you lose DTR early with a demyelinative neuropathy and late with axonal neuropathy. Slowing of impulse and temporal dispersion do alter the function of nervous system. But it usually falls short of causing any symptom or signs.

Ladak A. et al Side-to-side nerve grafts sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation. Neurosurgery 2011; 68:1654-1666

LaFontaine S, Rasminsky M, Saida T, Sumner AJ. Conduction block in rat myelinated fibers following acute exposure to anti-galactocerebroside serum. J Physiol 1982; 323: 287-306 a. demyelination across 2 adjacent internodes causes conduction block (pg305)

Luff AR. Hatcher DD. Torkko K. Enlarged motor units resulting from partial denervation of cat hindlimb muscles. Journal of Neurophysiology. 59(5):1377-94, 1988 a. After partial denervation most motor units increase in tension about 5 to 12 times normal although at times the for was 16 times normal

Lundborg, G. Nerve Injury and Repair. Churchill Livingstone. London 1988

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Zochodne DW. Reversing neuropathic deficits. J Peripher Nerv Syst. (Supplement 4-9) 2012; 17: 4 – 9. G.J. Herbison, M.D. Thomas Jefferson University [email protected]