repetitive nerve stimulation

seminar on repetitive nerve stimulation physiology,application in various neuromuscular disorders

1. Repetitive Nerve StimulationRepetitive Nerve Stimulation

2. 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

5. 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

6. 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

7. 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.

8. 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

10. Relationship -EPP,AP,CMAPRelationship -EPP,AP,CMAP

11. 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.

12. 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

13. 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

14. 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

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

16. Machine setup for RNSMachine setup for RNS
30-50Stimulus rate -high
<5Stimulus rate -low
0.1Stimulus duration (msec)
2-3High filter (KHz)
2-5Low filter (Hz)
2Sweep time (ms/div)
2-5Sensitivity (mV/div)

17. 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

18. Effect of temperature on RNSEffect of temperature on RNS

19. 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

20. Effect of different stimulation ratesEffect of different stimulation rates

21. 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

24. 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

25. 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

26. Slow RNSSlow RNS

27. 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

28. Rapid RNSRapid RNS

29. Patterns of response to slow RNSPatterns of response to slow RNS

30. Activation cycle in MGActivation cycle in MG

31. 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

32. RNS in pre and post synaptic disordersRNS in pre and post synaptic disorders
Decrement or
normal
Increment High rate RNS
Decrement
Present
Present
Decrement
Present
Absent
Low rate RNS
 Resting
 Post exercise
facilitation
 Post exercise
exhaustion
Normal Small CMAP amplitude
Post-synaptic Pre-synaptic Parameter

33. 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 .

34. 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.

35. SFEMGSFEMG

36. Jitter and blockJitter and block

37. Myasthenia gravisMyasthenia gravis

38. 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

39. 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

41. Baseline and 10sec exerciseBaseline and 10sec exercise

42. 60sec exercise-exhaustion60sec exercise-exhaustion

43. 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.

44. Repetitive CMAPRepetitive CMAP

45. 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)

46. LEMS

47. 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.

48. 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).

49. Incremental response in LEMS

50. 50hz RNS-increments50hz RNS-increments

51. 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

52. 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

53. 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

57. Thank youThank you

58. 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 2
ndnd
ed ed
ShapiroShapiro
emedicine –web mdemedicine –web md

59. Thank you Thank you