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A method for estimating the refractory period of motor fibers in the human peripheral nerve
Journal of the Neurological Sciences, 1976, 28:485 490
485
~:) Elscvier Scientific Publishing Company, Amsterdam - Printed in The Netherhmds
A M E T H O D FOR E S T I M A T I N G THE R E F R A C T O R Y P E R I O D OF MOTOR FIBERS IN THE H U M A N P E R I P H E R A L NERVE
J U N K1MURA
Department of Nettrolo~'y and the Neurosensorj' Center, College of Medicine, University of Iowa, hm'a (Try, hm'a 52242 (U.S.A.)
(Received 25 November, 1975)
SUMMARY
A simple method has been devised to measure the refractory period of motor tibers in man. With paired shocks of just maximal intensity, the second response of the pair was first elicited at an interstimulus interval of 1.00 .- 0.20 msec (mean • SD in 24 ulnar nerves). With longer intervals there was progressive return of excitability until it recovered completely at 2.88 ]- 0.72 msec. When paired shocks of 50",i supramaximal intensity were used, return of the second response was faster, beginning at 0.77 :! 0.18 msec and achieving full recover}' at 2.03 0.57 msec. The impulse was conducted at a slower speed than normal, if transmitted at all, during the relative refractory period.
INI ROI)L;CTION The refractory period has long been studied in experimental animals (Bishop and Heinbecker 1930; Tasaki 1953), and, more recently, in the human peripheral nerve. To date, the sensory (Buchthal and Rosenfalck 1966: Tackmann and Lehmann 1974) and mixed fibers (Gilliatt and Willison 1963; Lowitzsch, Hopf and Schlegel 1973) have been tested in man by measuring the nerve action potentials elicited by pairs of stimuli. To test the motor tibers using the same principles, the muscle action potentials may be recorded after delivering paired stimuli to the nerve. However, the results are difficult to interpret because, with the short interstimulus interval required to study the refractory period, the muscle responses elicited by the first and The Neurosensory Center is supporled by Program Project Grant Number NS-03354 of the National Institute of Neurological Diseases and Stroke. This investigation was supported in part by a grant from the National Multiple Sclerosis Society.
486 s e c o n d stimuli o v e r l a p . T o m e a s u r e the s e c o n d r e s p o n s e , t h e r e f o r e , it is necessary to b l o c k the effect o f the first s t i m u l u s o f the p a i r w i t h o u t affecting t h a t o f the ~ccond. T h i s can be a c h i e v e d by c o l l i s i o n if a n o t h e r s t i m u l u s is d e l i v e r e d to the n e r v e tit ~ p o i n t distal to the p a i r e d stimuli ( K i m u r a 1974).
MEFHOF)S The ulnar nerve was stimulated percutaneously and the compound muscle
Col lision Technique Right Ulnar Nerve
Site of
Stimulation
J N Moy 20, 197,5
Wrist t
)~o~
@ s(w)
•
M(W)
Axillo S(A)
' a (A)
Collision Wrist and
Axilla
S(A)
S(W)
M(W)
Collision ,~l( Wrist and Paired Axilla
,~~
~'--
S(A=) S(A~/S(W)
~-("Y S(W)
S(A,)+S(A,)
u(w) M(A~)
~ 15mV Stimulation 5msec
Fig. 1. Compound muscle action potentials recorded by surface electrodes placed over the abductor digiti minimi after percutaneous stimulation of the ulnar nerve. The figures on the left are schematic diagrams showing orthodromic (solid arrows) and antidromic (dotted arrows) impulses. Axillary stimulation was given 5.0 msec after the wrist stimulus which triggered sweeps on the oscilloscope. With single stimulation at the wrist and the axilla (the third tracing from top), the orthodromic impulse from the axilla was extinguished by collision with the antidromic impulse from the wrist. When paired shocks were delivered at the axilla (bottom tracing), M(Ae) appeared because the first axillary stimulus cleared the path for the orthodromic impulse of the second stimulus. The size of M(A2) is proportional to the number of axons no longer refractory after the passage of a volley of the first axillary stimulus.
487 action polential was recorded by surface electrodes placed on the h y p o t h e n a r eminence. When paired shocks at the axilla were c o m b i n e d with a single shock at the ~rist, the orthodronfic impulse of the first of the paired axillary stimuli ,xas blocked by the a n t i d r o m i c impulse frorn the wrist (Fig. 1). Because the m o t o r axons were now cleared of antidrornic activity, the impulse of the second axillary stimulus was transmitted distally, but only if the axons were excitable after the passage of a wHley of
the first axillary stimulus. For stimulation, a Grass $8 stimulator with the output impedance of 250 ohnts was used coupled with a transformer. The stimulus was a slightly distorted sqt,are pulse of 0.05 msec duration. In preliminary experiments, the intensity of the second shock at the axiHa was systematically altered in an attempt to determine the voltage
Normal Control Time Interval (rnsec)
J.N. May :>0,1975
G.B.S. H.K. May 21, 1975
06 0.8 1.0 1.2 1.4 IB
1.8 2.0 2.2 2.4 2.6 2.8 3.0
M(W) Stimulation
M ( A 2)
LSm v 5 msec
t.ig. 2. Paired axillary shocks of just maximal intensity were combined with a single shock at the wrist (of. bottonl tracing in I-jg. IL Intersthllulus intervals between 2 axillary stimuli ranged from 0.6 to 3.0 reset. The shock intervals ~ere adjusted so that the second axillary shock always occurred 5.0 rnsec after the ;,, fist stimulus, which triggered s'~,eeps on the oscilloscope. In the normal subject, M(A2) firsl appeared (small arro,,v) at the interstimulus interval of 0.8 msec and recovered completely at 3.0 reset. In the patient with the Guillain BarrY.syndrome, M(A._,)first appeared at the time interval of 1.6 msec and did not recover completely 'it 3.0 reset.
488 change necessary to excite the lowest threshold fibers at different times after the lirsl shock of maximal intensity. At near threshold stimulus, however, the resulls obtained were very inconsistent not only among individuals but also from one trial to the next in the same subject. For this reason, we elected to use either just maximal or 50".. supramaximal intensity for paired stimuli at the axilla. The maximal ~tm~ulus a~ determined by delivering single shocks of increasing intensity and rect~rding the compound muscle action potential varied individually from 200 to 350 v. A single shock delivered at the wrist was always 50",i supramaximal to ensure a complete block of the first of the paired axillary stimuli. The interstimulus interval between the 2 axillary stimuli ranged from 0.5 to 5.0 reset. The muscle potential, M(A.,), elicited by the second axillary stimulu, must bc proportional to the number of axons no longer refractory when the second axillar.~ shock was applied. The muscle response, M(A). evoked by a single axillary shock alone represented the total number of axons available in the nerve. Hence. the amplitude ratio. M(Az).M(A). gave the excitability of the average motor axon to Ihe second stimulus, i.e. the degree of its rcctwery from the refractoriness induced b,, the voile3 of the tirst impulse. Since M(A,_,) fl~llowed a muscle potential. M(W). elicited by the wrist shock in each tracing (Fig. 2), change in neuromuscular excitabilily secondary to the volley of M(W) might have affected the size of M(Az). This effect, hc~wcver. could be made negligible if M(A,,) and M(W) were separated sufticiently b.~ deliverin~ the axillary shocks a few msec after the wrist ,;timulu.,,.
MATERIAI.S AND RESULI'S
Twenty-fl~ur ulnar nerves were studied in 12 healthy subjects, 5 males and 7 females with a mean age of 28 years. In each nerve tested, the recovery curves of motor fibers followed a predictable time course (Fig. 3). With axillary shocks of just maximal intensity, M(Ae) was tirst elicited at an interstimulus interval of t.00 0.20 msec (mean -- SD). With longer intervals, there was progressive increase in amplitudc of M(Az) until it recovered completely at 2.88 ! 0.72 msec. When the axi[lary shocks of 5 0 " supramaximal intensity were used, the return of M(Ae) was faster, beginning at 0.77 i 0.18 msec and achieving full recovery at 2.03 :! 0.57 reset. With still stronger stimulation, there was further reduction of the relative refractory period. Regardless of the shock intensity (up to 500 V, 0.05 msec duration), however, M(Ael was not recorded if the interstimulus interval was less than 0.5 reset. This lime interval must correspond closely if not exactly (Tasaki 1953) to the absolute refractory period of the motor fibers. With increasing interstimulus intervals of paired axillary shocks, the latency of M(A,~) progressively shortened indicating that the impulse, if transmitted at all, was conducted at a slower speed than normal during the relative refractory period. The time course of latency of M(Ae), however, was not determined in this experiment since change in amplitude was more easily detectable.
489 Ftetractory Period of Motor Fibers m the Ulnar Nerve
10o
.
xTTIii__-i
r
5
90
80
.% 6C SL 50
~" 4o %
k.
I ,
C
i
O2
i
,
i
04
06
08
10
•
|
12
InterstimutuS Interval
.
i
14
.
1
16
.
t
18
.
1
20
.
i
22
.
,
24
.
l
26
.
1
28
.
i
30
Between Paired Shocks (msec)
Fig. 3. The time course o f recovery of the moior fibers after the pa:~age of a preceding impulse in 12 health) subjects (24 responses considering right and left sides togctherL The response to the second shock of the pair. MfAe), was converted into a percentage of" the response to a single stimulus, M(A), at each interstmmlus interval of paired axilhiry stimuli. The return of M(A:J ,,,,as significantly faster with 50",; supramaxinml intensity than with just maxim:ll intensity. The gradual increase of M(Ae) indicates thai the absolute refractory periods of the different motor fibers vary considerabl}. full rcco,,cry being achieved when the lezlst c~:cilablc filx:rs arc no h mger refractory.
I)ISCI:SSI(J,N
The absolute refractory periods obtained in thi.,, study are in agreement with the previous results in experimental animals (Bishop and Hcinbecker 1930: Tasaki 1953) and in man (Buchthal arid Rosenfalck 1966: Gilliatt and Willison 1963; Lovdtzsch ct al. 1973: Tackmann and Lehmann 1974). Compared to the conventional method~, of recording nerve action potentials of the sensory or mixed fibers, the present technique allows, selective testing of the motor axons. Furtlaer. it is technically advantageous to measure large compound muscle action potentials rather than small nerve potentials, which m.ay be difficult to detect in some subjects. The decrease in amplitude of the compound muscle action potential could bc secondary to block of conduction or reduction of the nerve action potential of the individttal libers. Results ira animal experiments on single nerve fibers indicate that the anqHitude of the second potential of the pair recovers to a normal level as soon its it has traveled a few cm (Tasaki 19531. This in primarily because the slowing of the second impulse during the refractory period illlov..s an increasing inter,, al between the lirst and second impulses an they travel rut thor distally. In out" experiments, the second
490 impulse follows the tirst for only a short distance b c l b r e the latter is extinguished b\ collision. The excitability change induced by the passage o f the a n t i d r o l n i c impulse frorn the wrist must be m i n i m a l by the timc thc sccond impulse reachc~, the distal nerve segment. The decrease in a m p l i t u d e o f the nerve potential o f the indviduat tibcrs still c a r r y i n g the second impulse, therefore, can be assumed negligible at the nerve terminal. Thus, the change in size o f the c o m p o u n d muscle action potential must be mainly ,,,econdary to a block o f c o n d u c t i o n r a t h e r than reduction of the second potential o f the individual tibers. Thc a b s o l u t e refractory period in thc pre~cnt study then c o r r e s p o n d s to that o f the most excitable fibers. The gradual increase i11 amplitude o f the second muscle response indicates that the absolute refractor_,, period o f different m o t o r fibers vary by a factor o f up to 2.9. This is consistent with tlw prcviou~, o b s e r v a t i o n in h u m a n sensory fibers in which the absolute refractory p e l l o d s also varicd by a factor o f 1.5 to 2.0 (Buchthal and Rosenfalck 1966). A b n o r m a l i t i e s o f the refractory period o f the sensory and mixed libers have been r e p o r t c d by others in diseases o f p e r i p h e r a l nerve (Lowitzsch el at. 1973: Tackm a n n and Lehrnann 1974). We havc found a p r o l o n g e d refractory period o l the n.1otor tibers (Fig. 2) in some cases o f the G u i l l a i n - B a r r 6 s y n d r o m e , but I1.1c u u m b e r o f patients tested to date is too ~mall to ju.,,tify any conclusion. F u r t h e r work is w a r r a n t e d to determine it" studies o f the refractory period arc o f value in diagnostic testing iu diseases o f the m o t o r tibers and in e v a l u a t i o n o f their p a t h o p h y s i o l o g y . A ( ' K N O W I . E D G E M t'~NTS
The a u t h o r wishes to t h a n k Dr. M a u r i c e W. Van Allen for reviewing the article, and Miss Sheila M e n n e n and Miss J o a n n e N a h n s e n for their technical assistance.
REFEREN('I-S Bishop. G. H. and P. Heint~ckcr (1930) Differentiation of axon types in ,,isceral nerxcs i~. means ,~1 the potential record, ,4mer. J. Ph.v.~hd., 94: 170-200. Buchthal, F. and A. Rosenfalck (1966) Evoked action potentials and conduction velocity in hurnan sensory nerves, Brain Res., 3 (I, Special Issue): 1 122. Gilliatt, R. W. and R. G. Willison (1963) The refractory and supernormal periods of human median nerve, J. Neurol. Neto'o.sttrlsy. Ps)'chiat., 26: 136-147. Kimura, J. (1974) F-wave velocity in the central segment of the median and ulnar ner,.c,, .... A stud~ in normal Subjects and in patients with Charcot-Marie-Tooth disease, Neurology (Minneap.). 24: 539.-546. Lowitzsch, K.. H. D. Hopf and H. J. Schlegel (1973) Conduction of two or more impulses in relation to the fibre spectrum in the mixed human peripheral nerve. In: J. E. Desmcdt (Ed.), New I)evelopntents in t-,h'ctromyography and Clinical Neurophy.siology, Vol. 2, Karger. Basel, pp. 272 -278. Tackmann, W. and H. J. Lehmarm (1974) Refractory period in human sensory nerve libres, t:'uro/,. Neurol., 12: 277- 292. Tasaki, I. (1953) Nervous Transmission, Thomas, Springtield, Ill.
485
~:) Elscvier Scientific Publishing Company, Amsterdam - Printed in The Netherhmds
A M E T H O D FOR E S T I M A T I N G THE R E F R A C T O R Y P E R I O D OF MOTOR FIBERS IN THE H U M A N P E R I P H E R A L NERVE
J U N K1MURA
Department of Nettrolo~'y and the Neurosensorj' Center, College of Medicine, University of Iowa, hm'a (Try, hm'a 52242 (U.S.A.)
(Received 25 November, 1975)
SUMMARY
A simple method has been devised to measure the refractory period of motor tibers in man. With paired shocks of just maximal intensity, the second response of the pair was first elicited at an interstimulus interval of 1.00 .- 0.20 msec (mean • SD in 24 ulnar nerves). With longer intervals there was progressive return of excitability until it recovered completely at 2.88 ]- 0.72 msec. When paired shocks of 50",i supramaximal intensity were used, return of the second response was faster, beginning at 0.77 :! 0.18 msec and achieving full recover}' at 2.03 0.57 msec. The impulse was conducted at a slower speed than normal, if transmitted at all, during the relative refractory period.
INI ROI)L;CTION The refractory period has long been studied in experimental animals (Bishop and Heinbecker 1930; Tasaki 1953), and, more recently, in the human peripheral nerve. To date, the sensory (Buchthal and Rosenfalck 1966: Tackmann and Lehmann 1974) and mixed fibers (Gilliatt and Willison 1963; Lowitzsch, Hopf and Schlegel 1973) have been tested in man by measuring the nerve action potentials elicited by pairs of stimuli. To test the motor tibers using the same principles, the muscle action potentials may be recorded after delivering paired stimuli to the nerve. However, the results are difficult to interpret because, with the short interstimulus interval required to study the refractory period, the muscle responses elicited by the first and The Neurosensory Center is supporled by Program Project Grant Number NS-03354 of the National Institute of Neurological Diseases and Stroke. This investigation was supported in part by a grant from the National Multiple Sclerosis Society.
486 s e c o n d stimuli o v e r l a p . T o m e a s u r e the s e c o n d r e s p o n s e , t h e r e f o r e , it is necessary to b l o c k the effect o f the first s t i m u l u s o f the p a i r w i t h o u t affecting t h a t o f the ~ccond. T h i s can be a c h i e v e d by c o l l i s i o n if a n o t h e r s t i m u l u s is d e l i v e r e d to the n e r v e tit ~ p o i n t distal to the p a i r e d stimuli ( K i m u r a 1974).
MEFHOF)S The ulnar nerve was stimulated percutaneously and the compound muscle
Col lision Technique Right Ulnar Nerve
Site of
Stimulation
J N Moy 20, 197,5
Wrist t
)~o~
@ s(w)
•
M(W)
Axillo S(A)
' a (A)
Collision Wrist and
Axilla
S(A)
S(W)
M(W)
Collision ,~l( Wrist and Paired Axilla
,~~
~'--
S(A=) S(A~/S(W)
~-("Y S(W)
S(A,)+S(A,)
u(w) M(A~)
~ 15mV Stimulation 5msec
Fig. 1. Compound muscle action potentials recorded by surface electrodes placed over the abductor digiti minimi after percutaneous stimulation of the ulnar nerve. The figures on the left are schematic diagrams showing orthodromic (solid arrows) and antidromic (dotted arrows) impulses. Axillary stimulation was given 5.0 msec after the wrist stimulus which triggered sweeps on the oscilloscope. With single stimulation at the wrist and the axilla (the third tracing from top), the orthodromic impulse from the axilla was extinguished by collision with the antidromic impulse from the wrist. When paired shocks were delivered at the axilla (bottom tracing), M(Ae) appeared because the first axillary stimulus cleared the path for the orthodromic impulse of the second stimulus. The size of M(A2) is proportional to the number of axons no longer refractory after the passage of a volley of the first axillary stimulus.
487 action polential was recorded by surface electrodes placed on the h y p o t h e n a r eminence. When paired shocks at the axilla were c o m b i n e d with a single shock at the ~rist, the orthodronfic impulse of the first of the paired axillary stimuli ,xas blocked by the a n t i d r o m i c impulse frorn the wrist (Fig. 1). Because the m o t o r axons were now cleared of antidrornic activity, the impulse of the second axillary stimulus was transmitted distally, but only if the axons were excitable after the passage of a wHley of
the first axillary stimulus. For stimulation, a Grass $8 stimulator with the output impedance of 250 ohnts was used coupled with a transformer. The stimulus was a slightly distorted sqt,are pulse of 0.05 msec duration. In preliminary experiments, the intensity of the second shock at the axiHa was systematically altered in an attempt to determine the voltage
Normal Control Time Interval (rnsec)
J.N. May :>0,1975
G.B.S. H.K. May 21, 1975
06 0.8 1.0 1.2 1.4 IB
1.8 2.0 2.2 2.4 2.6 2.8 3.0
M(W) Stimulation
M ( A 2)
LSm v 5 msec
t.ig. 2. Paired axillary shocks of just maximal intensity were combined with a single shock at the wrist (of. bottonl tracing in I-jg. IL Intersthllulus intervals between 2 axillary stimuli ranged from 0.6 to 3.0 reset. The shock intervals ~ere adjusted so that the second axillary shock always occurred 5.0 rnsec after the ;,, fist stimulus, which triggered s'~,eeps on the oscilloscope. In the normal subject, M(A2) firsl appeared (small arro,,v) at the interstimulus interval of 0.8 msec and recovered completely at 3.0 reset. In the patient with the Guillain BarrY.syndrome, M(A._,)first appeared at the time interval of 1.6 msec and did not recover completely 'it 3.0 reset.
488 change necessary to excite the lowest threshold fibers at different times after the lirsl shock of maximal intensity. At near threshold stimulus, however, the resulls obtained were very inconsistent not only among individuals but also from one trial to the next in the same subject. For this reason, we elected to use either just maximal or 50".. supramaximal intensity for paired stimuli at the axilla. The maximal ~tm~ulus a~ determined by delivering single shocks of increasing intensity and rect~rding the compound muscle action potential varied individually from 200 to 350 v. A single shock delivered at the wrist was always 50",i supramaximal to ensure a complete block of the first of the paired axillary stimuli. The interstimulus interval between the 2 axillary stimuli ranged from 0.5 to 5.0 reset. The muscle potential, M(A.,), elicited by the second axillary stimulu, must bc proportional to the number of axons no longer refractory when the second axillar.~ shock was applied. The muscle response, M(A). evoked by a single axillary shock alone represented the total number of axons available in the nerve. Hence. the amplitude ratio. M(Az).M(A). gave the excitability of the average motor axon to Ihe second stimulus, i.e. the degree of its rcctwery from the refractoriness induced b,, the voile3 of the tirst impulse. Since M(A,_,) fl~llowed a muscle potential. M(W). elicited by the wrist shock in each tracing (Fig. 2), change in neuromuscular excitabilily secondary to the volley of M(W) might have affected the size of M(Az). This effect, hc~wcver. could be made negligible if M(A,,) and M(W) were separated sufticiently b.~ deliverin~ the axillary shocks a few msec after the wrist ,;timulu.,,.
MATERIAI.S AND RESULI'S
Twenty-fl~ur ulnar nerves were studied in 12 healthy subjects, 5 males and 7 females with a mean age of 28 years. In each nerve tested, the recovery curves of motor fibers followed a predictable time course (Fig. 3). With axillary shocks of just maximal intensity, M(Ae) was tirst elicited at an interstimulus interval of t.00 0.20 msec (mean -- SD). With longer intervals, there was progressive increase in amplitudc of M(Az) until it recovered completely at 2.88 ! 0.72 msec. When the axi[lary shocks of 5 0 " supramaximal intensity were used, the return of M(Ae) was faster, beginning at 0.77 i 0.18 msec and achieving full recovery at 2.03 :! 0.57 reset. With still stronger stimulation, there was further reduction of the relative refractory period. Regardless of the shock intensity (up to 500 V, 0.05 msec duration), however, M(Ael was not recorded if the interstimulus interval was less than 0.5 reset. This lime interval must correspond closely if not exactly (Tasaki 1953) to the absolute refractory period of the motor fibers. With increasing interstimulus intervals of paired axillary shocks, the latency of M(A,~) progressively shortened indicating that the impulse, if transmitted at all, was conducted at a slower speed than normal during the relative refractory period. The time course of latency of M(Ae), however, was not determined in this experiment since change in amplitude was more easily detectable.
489 Ftetractory Period of Motor Fibers m the Ulnar Nerve
10o
.
xTTIii__-i
r
5
90
80
.% 6C SL 50
~" 4o %
k.
I ,
C
i
O2
i
,
i
04
06
08
10
•
|
12
InterstimutuS Interval
.
i
14
.
1
16
.
t
18
.
1
20
.
i
22
.
,
24
.
l
26
.
1
28
.
i
30
Between Paired Shocks (msec)
Fig. 3. The time course o f recovery of the moior fibers after the pa:~age of a preceding impulse in 12 health) subjects (24 responses considering right and left sides togctherL The response to the second shock of the pair. MfAe), was converted into a percentage of" the response to a single stimulus, M(A), at each interstmmlus interval of paired axilhiry stimuli. The return of M(A:J ,,,,as significantly faster with 50",; supramaxinml intensity than with just maxim:ll intensity. The gradual increase of M(Ae) indicates thai the absolute refractory periods of the different motor fibers vary considerabl}. full rcco,,cry being achieved when the lezlst c~:cilablc filx:rs arc no h mger refractory.
I)ISCI:SSI(J,N
The absolute refractory periods obtained in thi.,, study are in agreement with the previous results in experimental animals (Bishop and Hcinbecker 1930: Tasaki 1953) and in man (Buchthal arid Rosenfalck 1966: Gilliatt and Willison 1963; Lovdtzsch ct al. 1973: Tackmann and Lehmann 1974). Compared to the conventional method~, of recording nerve action potentials of the sensory or mixed fibers, the present technique allows, selective testing of the motor axons. Furtlaer. it is technically advantageous to measure large compound muscle action potentials rather than small nerve potentials, which m.ay be difficult to detect in some subjects. The decrease in amplitude of the compound muscle action potential could bc secondary to block of conduction or reduction of the nerve action potential of the individttal libers. Results ira animal experiments on single nerve fibers indicate that the anqHitude of the second potential of the pair recovers to a normal level as soon its it has traveled a few cm (Tasaki 19531. This in primarily because the slowing of the second impulse during the refractory period illlov..s an increasing inter,, al between the lirst and second impulses an they travel rut thor distally. In out" experiments, the second
490 impulse follows the tirst for only a short distance b c l b r e the latter is extinguished b\ collision. The excitability change induced by the passage o f the a n t i d r o l n i c impulse frorn the wrist must be m i n i m a l by the timc thc sccond impulse reachc~, the distal nerve segment. The decrease in a m p l i t u d e o f the nerve potential o f the indviduat tibcrs still c a r r y i n g the second impulse, therefore, can be assumed negligible at the nerve terminal. Thus, the change in size o f the c o m p o u n d muscle action potential must be mainly ,,,econdary to a block o f c o n d u c t i o n r a t h e r than reduction of the second potential o f the individual tibers. Thc a b s o l u t e refractory period in thc pre~cnt study then c o r r e s p o n d s to that o f the most excitable fibers. The gradual increase i11 amplitude o f the second muscle response indicates that the absolute refractor_,, period o f different m o t o r fibers vary by a factor o f up to 2.9. This is consistent with tlw prcviou~, o b s e r v a t i o n in h u m a n sensory fibers in which the absolute refractory p e l l o d s also varicd by a factor o f 1.5 to 2.0 (Buchthal and Rosenfalck 1966). A b n o r m a l i t i e s o f the refractory period o f the sensory and mixed libers have been r e p o r t c d by others in diseases o f p e r i p h e r a l nerve (Lowitzsch el at. 1973: Tackm a n n and Lehrnann 1974). We havc found a p r o l o n g e d refractory period o l the n.1otor tibers (Fig. 2) in some cases o f the G u i l l a i n - B a r r 6 s y n d r o m e , but I1.1c u u m b e r o f patients tested to date is too ~mall to ju.,,tify any conclusion. F u r t h e r work is w a r r a n t e d to determine it" studies o f the refractory period arc o f value in diagnostic testing iu diseases o f the m o t o r tibers and in e v a l u a t i o n o f their p a t h o p h y s i o l o g y . A ( ' K N O W I . E D G E M t'~NTS
The a u t h o r wishes to t h a n k Dr. M a u r i c e W. Van Allen for reviewing the article, and Miss Sheila M e n n e n and Miss J o a n n e N a h n s e n for their technical assistance.
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