Repetitive Nerve StimulationRepetitive Nerve Stimulation

Plan of the talkPlan of the talk

Physiology of Neuromuscular junctionPhysiology of Neuromuscular junction

Procedure, technical aspectsProcedure, technical aspects

InterpretationInterpretation

Application in various conditionsApplication in various conditions

definitionsdefinitions

Quantum. A quantum is the amount of Ach packaged in a single vesicle.

Each quantum (vesicle) 1 mV change of postsynaptic membrane potential.

Rest, MEPP The number of quanta released after a nerve

action potential depends on the number of quanta in the immediately available (primary) store and calcium stores

Normally 50-300(60) vesicles

definitionsdefinitions End plate potential -EPP is the potential

generated at the postsynaptic membrane following a nerve action potential and neuromuscular transmission.

60 mV change in the amplitude of the membrane potential.

Safety factor. The safety factor of neuromuscular transmission is simply defined as the difference between the EPP and the threshold potential for initiating an action potential.

MFAP CMAP

Calcium and quanta dynamicsCalcium and quanta dynamics calcium :diffuses slowly out of the

presynaptic terminal in 100–200 msec. Ach stores: immediately available

(primary) store and secondary (or mobilization) store

Inter stimulus interval rapid RNS (more than every 100 msec, or

stimulation rate >10 Hz), calcium influx is greatly enhanced and the probability of release of Ach quanta increases.

PotentiationPotentiation

voluntary activation or high frequency voluntary activation or high frequency stimulationstimulation

CMAP amp increasesCMAP amp increases

Facilitation-recruitmentFacilitation-recruitment Pseudo facilitation-synchronisation of Pseudo facilitation-synchronisation of

muscle activitymuscle activity

Relationship -EPP,AP,CMAPRelationship -EPP,AP,CMAP

NeuromuscularNeuromuscular junction disordersjunction disorders Post synapticPost synaptic Myasthenia gravisMyasthenia gravis Organophosphorus poisoningOrganophosphorus poisoning Curare induced paralysisCurare induced paralysis Congenital Myasthenic syndromesCongenital Myasthenic syndromes PresynapticPresynaptic BotulismBotulism LEMSLEMS Magnesium induced paralysisMagnesium induced paralysis Combined defectCombined defect Gallamine, amino glycoside antibiotics, Gallamine, amino glycoside antibiotics, quinine, suxamethonium.quinine, suxamethonium.

Repetitive nerve stimulationRepetitive nerve stimulation( RNS)( RNS)

Jolly in 1895 first described progressive Jolly in 1895 first described progressive reduction in visible muscle contraction in reduction in visible muscle contraction in MG (Myaesthenic reaction)MG (Myaesthenic reaction)

Harvey and Masland(1941) reported Harvey and Masland(1941) reported electrical decremental muscle response on electrical decremental muscle response on repetitive motor nerve stimulation. repetitive motor nerve stimulation.

Ekstedt in 1964 described SFEMGEkstedt in 1964 described SFEMG

RNS- techniqueRNS- technique

RNS is technically demanding procedure.RNS is technically demanding procedure.

Poor electrode placement, sub maximal Poor electrode placement, sub maximal stimulation, movement artifacts, causes stimulation, movement artifacts, causes false positive results false positive results

Minimise artifactsMinimise artifacts ImmobilisationImmobilisation

RNS-techniqueRNS-technique

RNS is performed on selected motor RNS is performed on selected motor nerves with recording by surface nerves with recording by surface electrodes.electrodes.

G1-motor point,G2-tendonG1-motor point,G2-tendon Supramaximal stimulusSupramaximal stimulus Initial sharp negative deflectionInitial sharp negative deflection

Muscle selectionMuscle selection

Clinically weak muscles should be selected.Clinically weak muscles should be selected. Usually facial and proximal limb muscles Usually facial and proximal limb muscles

shows greater abnormality than distal shows greater abnormality than distal muscles.muscles.

Nerves involved in other diseases should be Nerves involved in other diseases should be avoided.avoided.

Cholinesterase inhibitors should be stopped Cholinesterase inhibitors should be stopped 12-24 hrs before.12-24 hrs before.

Machine setup for RNSMachine setup for RNS

Sensitivity (mV/div)Sensitivity (mV/div) 2-52-5

Sweep time (ms/div)Sweep time (ms/div) 22

Low filter (Hz)Low filter (Hz) 2-52-5

High filter (KHz)High filter (KHz) 2-32-3

Stimulus duration (msec)Stimulus duration (msec) 0.10.1

Stimulus rate -lowStimulus rate -low <5<5

Stimulus rate -highStimulus rate -high 30-5030-50

temperaturetemperature

Cooling can cause false negative results.Cooling can cause false negative results.

Hand/foot muscles at 34c.Hand/foot muscles at 34c.

Proximal/facial muscles need not be warmedProximal/facial muscles need not be warmed

Decrement is greater at 44c than at 22cDecrement is greater at 44c than at 22c

Effect of temperature on RNSEffect of temperature on RNS

Stimulus techniqueStimulus technique

Best at 3-5 hzBest at 3-5 hz

Decrement increases with stimulus rates Decrement increases with stimulus rates up to 10hz.up to 10hz.

Higher rates cause movement artifacts Higher rates cause movement artifacts and painfuland painful

Pseudo facilitationPseudo facilitation

Effect of different stimulation ratesEffect of different stimulation rates

ActivationActivation

Maximal voluntary contraction Maximal voluntary contraction

10 -30 sec for post exercise increment of 10 -30 sec for post exercise increment of baseline CMAPbaseline CMAP

60 seconds of exercise60 seconds of exercise High frequency stimulation 20-50hzHigh frequency stimulation 20-50hz Trains of low frequency stimulus at end of Trains of low frequency stimulus at end of

activation and one minute intervals for 5 minutesactivation and one minute intervals for 5 minutes Post activation exhaustionPost activation exhaustion

ll

Measurement techniqueMeasurement technique

Peak to peakPeak to peak Negative peak amplitudeNegative peak amplitude Display setting 50-100msec/screen can Display setting 50-100msec/screen can

detect technical problemsdetect technical problems Change in CMAP sizeChange in CMAP size

D4 =(V4 – V1)/V1 * 100D4 =(V4 – V1)/V1 * 100 Area vs amplitudeArea vs amplitude

Slow RNSSlow RNS supra maximal CMAP 3–5 stimuli to a mixed or motor nerve at a rate

of 2–3 Hz. slow enough to prevent calcium accumulation,

high enough to deplete the quanta maximal decrease in Ach release occur after the

first four stimuli reproducible decrement exercises for 10 seconds to demonstrate repair

of the decrement (‘‘post-exercise facilitation’’) No decrement-1 minute max voluntary exercise

–post exercise exhaustion

Slow RNSSlow RNS

Rapid RNSRapid RNS

optimal frequency is 20–50 Hz,for 2–10 seconds

brief (10-second) period of maximal voluntary isometric exercise has,the same effect as rapid RNS

Depletion of quanta vs calcium accumulation

Incremental response in LEMS

Rapid RNSRapid RNS

Patterns of response to slow RNSPatterns of response to slow RNS

Activation cycle in MGActivation cycle in MG

Criteria for abnormal decrementCriteria for abnormal decrement

Normal muscle -8% decrement at 3-5hzNormal muscle -8% decrement at 3-5hz

1.Reproducibility1.Reproducibility

2.Envelope shape2.Envelope shape

3.Activation cycle3.Activation cycle

4.Response to edrophonium4.Response to edrophonium

RNS in pre and post synaptic disordersRNS in pre and post synaptic disorders

ParameterParameter Pre-synapticPre-synaptic Post-synapticPost-synaptic

CMAP amplitudeCMAP amplitude Small Small Normal Normal

Low rate RNSLow rate RNS RestingResting Post exercise Post exercise facilitationfacilitation Post exercise Post exercise exhaustionexhaustion

Decrement Decrement

Present Present

AbsentAbsent

DecrementDecrement

PresentPresent

Present Present

High rate RNSHigh rate RNS Increment Increment Decrement or Decrement or normalnormal

Double step RNSDouble step RNS

Desmedt and Borenstein.Desmedt and Borenstein.

First step: 3-Hz supramaximal ulnar nerve First step: 3-Hz supramaximal ulnar nerve stimulation for 3 minutes with recording of electrical stimulation for 3 minutes with recording of electrical response of hand and forearm muscles.response of hand and forearm muscles.

Second step: procedure is repeated with circulation Second step: procedure is repeated with circulation arrested by inflated blood pressure cuff at 250 mm arrested by inflated blood pressure cuff at 250 mm Hg placed proximal to stimulation.Hg placed proximal to stimulation.

Rarely used .Rarely used .

Regional curare testRegional curare test

Small dose (0.2 mg) of D-tubocurarine is injected Small dose (0.2 mg) of D-tubocurarine is injected into arm rendered ischaemic by blood pressure into arm rendered ischaemic by blood pressure cuff around arm.cuff around arm.

RNS is done after several minutes of ischaemia.RNS is done after several minutes of ischaemia.

More sensitive.More sensitive.

Potentially dangerous.Potentially dangerous.

Rarely used.Rarely used.

SFEMGSFEMG

Jitter and blockJitter and block

Myasthenia gravisMyasthenia gravis

Electrophysiological investigationElectrophysiological investigation

Nerve conduction studies-usually Nerve conduction studies-usually normal (low CMAP in LEMS)normal (low CMAP in LEMS)

Concentric needle EMG-usually normalConcentric needle EMG-usually normal

Repetitive nerve stimulationRepetitive nerve stimulation

Single fiber EMGSingle fiber EMG

RNSRNS

Most commonly used test, easy.Most commonly used test, easy. RNS is relatively insensitive,10-50% in ocular RNS is relatively insensitive,10-50% in ocular

myastenia,75% in generalised MGmyastenia,75% in generalised MG RNS is relatively specific(90%)RNS is relatively specific(90%) SFEMG is Most sensitive.(90% in ocular,95% in SFEMG is Most sensitive.(90% in ocular,95% in

MG)MG) Normal baseline CMAPNormal baseline CMAP Greater than 10% decremental response at rest Greater than 10% decremental response at rest

and post exerciseand post exercise No role for high frequency stimulationNo role for high frequency stimulation

Baseline and 10sec exerciseBaseline and 10sec exercise

60sec exercise-exhaustion60sec exercise-exhaustion

Congenital Myasthenic SyndromesCongenital Myasthenic Syndromes

Newborns of non-Myasthenic mothers.Newborns of non-Myasthenic mothers. No Ach R antibodies.No Ach R antibodies. Respiratory distress, feeding difficulty, Ptosis are Respiratory distress, feeding difficulty, Ptosis are

common.common. Decremental response on 2 Hz RNS, abnormal Decremental response on 2 Hz RNS, abnormal

SF-EMG.SF-EMG. End plate acetyl cholinesterase deficiency and End plate acetyl cholinesterase deficiency and

slow channel syndrome , a repetitive CMAP is slow channel syndrome , a repetitive CMAP is elicited by a single supramaximal stimulus.elicited by a single supramaximal stimulus.

Repetitive CMAPRepetitive CMAP

Lambert Eaton Myasthenic Lambert Eaton Myasthenic Syndrome (LEMS )Syndrome (LEMS )

Weakness and fatigability of proximal Weakness and fatigability of proximal muscles.muscles.

Relative sparing of EOM, bulbar muscles.Relative sparing of EOM, bulbar muscles. HyporeflexiaHyporeflexia Dry mouthDry mouth Associated with SCC lungAssociated with SCC lung Antibodies against VGCC (voltage gated Antibodies against VGCC (voltage gated

calcium channel)calcium channel)

LEMS

LEMSLEMS Distal muscles RNS preferred Distal muscles RNS preferred 3 pattern recognized 3 pattern recognized Low normal CMAP amplitude, decremental Low normal CMAP amplitude, decremental

response at low rate RNS, normal at high rate.response at low rate RNS, normal at high rate. Low CMAP amplitude, decremental response at Low CMAP amplitude, decremental response at

low rate, and incremental response at high rate low rate, and incremental response at high rate RNS (>100%)—classical triadRNS (>100%)—classical triad..

Low CMAP amplitude, decremental low rate Low CMAP amplitude, decremental low rate RNS, initial decrement at high rate RNS. RNS, initial decrement at high rate RNS.

Incrementing response after brief exercise (10-15 sec) in LEMS. Increment is 10-fold, with CMAP of 3.2 mV.

CP CMAP amplitude is 0.35 mV (normal >1 mV).

Incremental response in LEMS

50hz RNS-increments50hz RNS-increments

BotulismBotulism

Defective release of Ach from nerve Defective release of Ach from nerve terminals.terminals.

It cleaves synaptic vesicle protein.It cleaves synaptic vesicle protein. Extra ocular and bulbar weakness Extra ocular and bulbar weakness limb limb

and respiratory weakness.and respiratory weakness. Blurred vision, dilated pupil, constipation, Blurred vision, dilated pupil, constipation,

urinary retention.urinary retention. Electro physiologically resemble LEMSElectro physiologically resemble LEMS

BotulismBotulism

Reduced CMAP in at least two musclesReduced CMAP in at least two muscles At least 20 percent CMAP amplitude At least 20 percent CMAP amplitude

facilitation on tetanic stimulationfacilitation on tetanic stimulation Persistance of facilitation atleast 2 minutes Persistance of facilitation atleast 2 minutes

after activationafter activation No postactivation exhaustionNo postactivation exhaustion

Miscellaneous conditionsMiscellaneous conditions

Amyotophic lateral sclerosisAmyotophic lateral sclerosis Oculopharyngeal dystrophyOculopharyngeal dystrophy Drugs(aminoglycosides,Anaesthetic,Beta Drugs(aminoglycosides,Anaesthetic,Beta

blockers)blockers) HypermagnesemiaHypermagnesemia OrganophosphateOrganophosphate Seasonal myaesthenic syndromesSeasonal myaesthenic syndromes

Thank youThank you

ReferencesReferences

American Association of electrodiagnostic American Association of electrodiagnostic medicine-Practice parameters on RNSmedicine-Practice parameters on RNS

Aminoff text book of electrophysiologyAminoff text book of electrophysiology Amato NMJ disordersAmato NMJ disorders Jun Kimura 2Jun Kimura 2ndnd ed ed ShapiroShapiro emedicine –web mdemedicine –web md

Thank you Thank you