WEBVTT 00:00.000 --> 00:30.000 position:50% align:top line:0% *This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.* 01:07.510 --> 01:10.340 Since their introduction into clinical medicine almost 01:10.340 --> 01:11.350 50 years ago. 01:11.890 --> 01:14.420 The techniques of Electro biography have added 01:14.420 --> 01:16.710 immeasurably to the recognition, 01:16.720 --> 01:19.680 understanding and direction of therapy of neuro muscular 01:19.680 --> 01:20.780 disease in man. 01:21.640 --> 01:24.420 What I shall attempt this afternoon is a 01:24.420 --> 01:27.380 definition of some of the techniques that are useful in 01:27.380 --> 01:27.890 vivo. 01:29.370 --> 01:32.350 I shall review their application limitations 01:32.350 --> 01:34.520 and value in disorders of the motor unit, 01:35.420 --> 01:38.340 and I shall attempt a prophecy of some of the innovative 01:38.340 --> 01:40.010 developments of recent years. 01:40.960 --> 01:43.880 Therefore this is by no means a compendium of a field that 01:43.880 --> 01:46.700 has already nurtured five International Congress is 01:46.960 --> 01:49.720 one in which several standard texts are extended. 01:51.100 --> 01:53.990 I shall try to give you some of the field for the 01:53.990 --> 01:55.730 fact that E. 01:55.730 --> 01:55.930 M. 01:55.930 --> 01:56.740 G. 01:56.750 --> 01:59.620 Must be clearly tailored to the clinical problem of the 01:59.620 --> 02:02.180 patient as a fishing expedition. 02:02.180 --> 02:04.820 It is rarely fruitful as an exercise in 02:04.820 --> 02:06.130 clinical physiology. 02:06.150 --> 02:09.060 It is often exciting if we can go to the 02:09.060 --> 02:09.840 first slide 02:11.840 --> 02:14.650 on this are depicted the various levels of the nervous 02:14.650 --> 02:17.490 system pathology at any 02:17.490 --> 02:20.240 level of which may lead to a complaint of 02:20.240 --> 02:20.870 weakness. 02:22.070 --> 02:25.030 The techniques of electro biography have their 02:25.040 --> 02:26.810 most application, 02:26.810 --> 02:29.540 their highest application in the motor 02:29.540 --> 02:30.150 unit, 02:30.160 --> 02:33.080 which is all you all of you recall, 02:33.090 --> 02:35.080 is the anterior horn cell. 02:35.080 --> 02:36.860 It's peripheral extension, 02:36.870 --> 02:38.690 the motor nerve fiber, 02:38.700 --> 02:41.680 the neuro muscular junction and all of 02:41.680 --> 02:44.410 the muscle fibers supplied by a given anterior horn 02:44.410 --> 02:44.840 cell. 02:45.740 --> 02:46.970 We go to the next slide, 02:49.290 --> 02:52.060 we can see that at the level of peripheral 02:52.060 --> 02:52.850 nerve. 02:52.860 --> 02:55.210 There are several techniques which are 02:55.210 --> 02:57.930 useful for studying the health of nerve. 02:58.760 --> 03:01.490 Basically these have to do with the 03:01.490 --> 03:04.450 measurement of conduction velocity of nerve in 03:04.450 --> 03:07.200 motor mixed and sensory nerve fibers and the 03:07.200 --> 03:09.100 excitability of peripheral nerve. 03:09.110 --> 03:09.790 The next slide, 03:09.790 --> 03:12.760 please this slide 03:12.760 --> 03:15.300 attempts a schematic representation 03:15.900 --> 03:18.830 of the techniques of nerve conduction velocity. 03:19.670 --> 03:21.660 Perhaps it is a bit simplistic, 03:21.670 --> 03:24.430 but I believe if one understands the simple 03:24.440 --> 03:27.020 factors behind the measurement of motor nerve conduction 03:27.020 --> 03:27.910 velocity, 03:27.930 --> 03:30.760 then some of the difficulties in the application of 03:30.760 --> 03:32.350 this technique become apparent. 03:33.390 --> 03:35.220 Under ordinary circumstances, 03:35.220 --> 03:37.630 a nerve is selected that may be stimulated 03:37.630 --> 03:40.510 distantly and proximately in 03:40.510 --> 03:42.730 order to give rise after a latent 03:42.730 --> 03:45.120 period to a muscle action potential. 03:46.770 --> 03:49.530 Now one would think that if velocity is distance per 03:49.530 --> 03:50.300 unit time, 03:50.300 --> 03:53.030 that all that needed to be done would be to measure the 03:53.030 --> 03:55.370 time from the stimulus to the response, 03:55.380 --> 03:57.810 divide that into the distance between 03:57.810 --> 04:00.500 stimulating point 04:00.500 --> 04:03.370 and recording point and come up with a 04:03.370 --> 04:04.080 velocity. 04:04.900 --> 04:05.990 However, 04:06.310 --> 04:08.780 the basic tenants of physiology 04:09.450 --> 04:12.360 have us to understand that nerve conduction 04:12.360 --> 04:13.420 velocity, 04:13.430 --> 04:16.010 in which we are interested is a 04:16.010 --> 04:18.420 phenomenon which in normal 04:18.430 --> 04:21.360 individuals occurs 04:21.360 --> 04:24.340 at a magnitude of 40 to 60 m per 04:24.340 --> 04:25.020 second, 04:25.030 --> 04:27.370 whereas muscle conduction velocity 04:27.380 --> 04:30.270 occurs in the range of 4 to 6 m 04:30.270 --> 04:31.280 per second. 04:31.290 --> 04:34.220 Thus one doesn't know where the nerve impulse leaves 04:34.220 --> 04:36.990 off and the muscle impulse starts. 04:37.640 --> 04:39.830 For this reason one must 04:39.830 --> 04:42.670 subtract the latency 04:42.680 --> 04:44.680 from a distal stimulus 04:45.570 --> 04:48.050 from the total latency from a proximal 04:48.050 --> 04:51.050 stimulus to come up with a latency difference 04:51.060 --> 04:54.020 that can be divided into the distance between 04:54.020 --> 04:56.890 stimulating electrodes and a 04:56.900 --> 04:59.220 velocity derived 05:00.560 --> 05:03.490 two other points should be evident from this slide 05:03.490 --> 05:05.980 that not only velocity can be calculated in this 05:05.980 --> 05:06.670 fashion, 05:06.680 --> 05:09.630 but also one can look at the 05:09.640 --> 05:12.500 distal latency itself, 05:12.520 --> 05:14.950 and one can as well look at the amplitude or 05:14.950 --> 05:17.080 size of the muscle action potential. 05:18.270 --> 05:20.830 Since velocity is distance per unit 05:20.830 --> 05:21.550 time, 05:21.560 --> 05:24.320 one would think that one could draw a 05:24.320 --> 05:27.000 plot between distal distance 05:27.010 --> 05:29.990 and distal latency And 05:29.990 --> 05:32.720 have a straight line relationship between the two. 05:33.470 --> 05:36.250 This is not true for distal distances 05:36.920 --> 05:39.080 rather over a wide range of 05:39.080 --> 05:40.040 distances. 05:40.810 --> 05:43.620 Distal latency occurs within a 05:43.620 --> 05:45.220 fairly narrow band. 05:45.350 --> 05:47.370 The absolute value of distal latency, 05:47.370 --> 05:49.440 therefore is quite important, 05:49.960 --> 05:52.910 irrespective of the distance over which the stimulus 05:52.910 --> 05:53.880 occurs. 05:53.890 --> 05:56.880 That absolute value may be the only 05:56.880 --> 05:59.530 indication of disease in nerves 05:59.540 --> 06:02.280 which is much more prominent distantly. 06:03.550 --> 06:04.200 Likewise, 06:04.200 --> 06:06.500 the amplitude of the muscle action potential 06:07.230 --> 06:09.980 itself may be a measure of the number of nerve 06:09.980 --> 06:11.780 fibers that are stimulus bill, 06:11.790 --> 06:14.740 or the number of muscle fibers which respond 06:14.740 --> 06:15.960 to that stimulus. 06:16.630 --> 06:18.090 In ordinary circumstances, 06:18.090 --> 06:21.040 that amplitude is expressed as a million volt 06:21.040 --> 06:24.000 phenomenon of the negative peak of 06:24.000 --> 06:26.920 the action potential on occasion as a peak to 06:26.920 --> 06:27.960 peak amplitude. 06:29.170 --> 06:29.680 Later, 06:29.680 --> 06:32.290 I think we shall see that with 06:32.300 --> 06:34.510 certain conditions of stimulation, 06:35.200 --> 06:37.820 the amplitude may appear to increase 06:37.820 --> 06:40.610 while the duration 06:40.620 --> 06:43.320 of the response decreases the 06:43.320 --> 06:44.070 total area, 06:44.070 --> 06:45.430 therefore not changing 06:47.330 --> 06:50.140 Edward Montgomery about two years ago introduced a 06:50.140 --> 06:52.510 technique for the automatic analysis 06:52.520 --> 06:55.320 of evoke muscle action potential 06:55.330 --> 06:57.960 area in the hopes that this would be a 06:57.960 --> 07:00.640 better measure of neuromuscular 07:00.640 --> 07:01.360 disease. 07:01.370 --> 07:02.970 Unfortunately, 07:02.980 --> 07:04.140 in normal subjects, 07:04.140 --> 07:07.010 the range of area is as great or greater 07:07.010 --> 07:09.110 than the range of amplitude itself. 07:10.130 --> 07:11.390 With that as a background. 07:11.390 --> 07:13.890 Let us go on to some of the applications of nerve 07:13.890 --> 07:16.270 conduction velocity in the next slide, 07:18.410 --> 07:21.260 which are a series of data obtained from a 07:21.260 --> 07:22.600 patient with the G. 07:22.600 --> 07:25.560 In barre syndrome of idiopathic pollen iritis. 07:25.570 --> 07:28.340 One can see that in the early 07:28.340 --> 07:30.950 stages of this illness on 07:30.950 --> 07:33.500 occasion with proximal stimulation, 07:33.510 --> 07:36.170 the response is often quite small and broken 07:36.170 --> 07:36.800 up, 07:36.810 --> 07:39.750 whereas with distal stimulation it is fairly 07:39.750 --> 07:40.420 large. 07:41.190 --> 07:43.700 This difference becomes apparent as the 07:43.700 --> 07:45.900 disease progresses but then is 07:45.900 --> 07:48.790 repaired so that in health 07:48.800 --> 07:51.660 at time d hear the response to a 07:51.760 --> 07:54.690 to a distal stimulus was about the same size 07:54.690 --> 07:56.970 and shape is that to a proximal stimulus. 07:56.980 --> 07:59.700 You will note that the latency 08:00.410 --> 08:03.220 two onset of distal stimulus at the 08:03.220 --> 08:05.800 height of the disease when the patient was first studied 08:05.810 --> 08:08.140 was quite prolonged compared to the 08:08.140 --> 08:10.250 latency in recovery. 08:11.400 --> 08:11.760 Thus, 08:11.760 --> 08:14.360 distal latency in this instance was an 08:14.360 --> 08:15.970 indication of neuropathy. 08:16.680 --> 08:18.870 These data are graphed out in the next slide 08:21.650 --> 08:23.000 with conduction velocity, 08:23.000 --> 08:25.540 showing at the top of the graph versus 08:25.540 --> 08:28.200 time distal 08:28.200 --> 08:30.780 latency in the middle graph and 08:30.790 --> 08:33.470 evoked muscle action potential amplitude. 08:33.480 --> 08:36.400 With distal stimulation shown with the 08:36.400 --> 08:39.210 crosses and proximal stimulation shown with 08:39.210 --> 08:42.010 the open circles In this 08:42.010 --> 08:44.900 particular patient changes in all three 08:44.900 --> 08:46.140 Parameters occurred. 08:46.810 --> 08:49.540 The initial study showed a very small action 08:49.540 --> 08:51.900 potential that improved as the patient 08:51.900 --> 08:54.850 improved with a prolonged distal latency that 08:54.850 --> 08:57.750 even got worse during the course of his illness, 08:57.760 --> 09:00.250 only to return to normal values and with the 09:00.250 --> 09:03.050 conduction velocity that at least for 09:03.060 --> 09:05.020 onset muscle uh 09:05.030 --> 09:07.890 latency differences was close to 09:07.890 --> 09:10.630 normal range but dipped down to clearly 09:10.630 --> 09:13.230 abnormal range is only to 09:13.230 --> 09:15.970 return as the patient's strength improved. 09:17.660 --> 09:20.420 This pattern of change in velocity, 09:20.480 --> 09:23.010 latency and amplitude in the next 09:23.010 --> 09:25.480 slide can 09:25.480 --> 09:28.150 be plotted against 09:28.160 --> 09:30.470 the months that it takes to recover 09:31.290 --> 09:33.330 and although the data are kind of scattered, 09:33.940 --> 09:35.970 a fairly straight line relationship 09:36.600 --> 09:39.270 With a correlation value that is not 09:39.280 --> 09:41.910 unrestricted ble can be seen from a 09:41.910 --> 09:44.520 series of 40 patients studied the 09:44.520 --> 09:47.420 University of Kentucky Medical Center over the past 09:47.420 --> 09:48.610 nine years. 09:48.620 --> 09:49.750 In this instance, 09:49.750 --> 09:52.600 it was of interest that the patients with the slowest velocities 09:52.610 --> 09:54.560 have the shortest kind of illness. 09:55.370 --> 09:58.140 The summary of this application of motor 09:58.140 --> 09:58.400 nerve, 09:58.400 --> 10:01.140 conduction velocity would be that it has 10:01.140 --> 10:02.110 great role, 10:02.120 --> 10:04.710 a great role to play in certain kinds of 10:04.710 --> 10:05.490 neuropathy. 10:05.600 --> 10:07.040 But in the next slide, 10:08.120 --> 10:11.050 The problems faced with this technique in other kinds 10:11.050 --> 10:13.430 of neuropathy should be evident. 10:13.830 --> 10:16.790 These data are taken from a paper by PK Thomas 10:16.790 --> 10:19.640 that appeared in the Lancet in 1959. 10:20.470 --> 10:23.420 At the top are shown data 10:23.430 --> 10:26.150 from patients in chronic renal 10:26.150 --> 10:27.960 failure and at the bottom. 10:27.970 --> 10:30.860 Normal controls on the left hand side and 10:30.860 --> 10:31.870 upper extremity nerve, 10:31.870 --> 10:34.640 the median nerve and on the right hand side, 10:34.650 --> 10:35.850 a lower extremity nerve. 10:35.850 --> 10:37.420 The lateral pop little nerve. 10:38.170 --> 10:40.820 Although the patients with chronic renal failure 10:40.830 --> 10:43.500 show a general skew of their velocities 10:43.500 --> 10:45.260 towards slower velocities. 10:45.270 --> 10:48.060 I think it is readily evident that many 10:48.060 --> 10:48.350 your E. 10:48.350 --> 10:51.290 Mc patients with obvious clinical neuropathy had 10:51.290 --> 10:53.350 velocities within normal range 10:54.210 --> 10:55.110 in the next slide, 10:56.420 --> 10:58.530 this problem of overlap cannot be 10:59.510 --> 11:02.250 gotten away from with 11:02.250 --> 11:05.210 serial measurements in this slide 11:05.220 --> 11:08.140 at the top are taken data from a paper that appeared in the 11:08.140 --> 11:10.850 new England Journal about five years ago. 11:11.470 --> 11:14.140 The patient whose data are reported here 11:14.150 --> 11:16.930 was quite seriously ill 11:16.940 --> 11:19.930 in renal failure with neuropathy at the time the 11:19.930 --> 11:22.540 initial media nerve conduction velocity was taken. 11:23.250 --> 11:25.980 Renal transplantation was performed then 11:25.990 --> 11:28.310 and over the next several months 11:28.320 --> 11:30.980 improvement occurred and improvement in his 11:30.980 --> 11:32.350 velocity occurred. 11:32.720 --> 11:35.540 The authors who published this data offered this as 11:35.550 --> 11:38.320 evidence for a technique to document 11:38.330 --> 11:41.310 changes in a condition known to 11:41.310 --> 11:43.400 be associated with neuropathy. 11:43.410 --> 11:46.290 The data at the bottom of the slide are taken 11:46.290 --> 11:49.030 from a paper that a medical student at the 11:49.030 --> 11:50.850 University of Kentucky published 11:51.200 --> 11:53.420 About seven years ago. 11:54.290 --> 11:57.260 These particular data are serial observations 11:57.270 --> 12:00.240 on a classmate of his who was no weaker at the 12:00.240 --> 12:03.140 beginning of the study than he was at the end of the study. 12:03.780 --> 12:06.320 The point of this slide is that even 12:06.320 --> 12:09.250 serial observations may show a random 12:09.250 --> 12:12.170 change that is as great as or 12:12.170 --> 12:14.670 perhaps even more than the 12:14.670 --> 12:17.070 observations from subjects with 12:17.070 --> 12:17.720 neuropathy. 12:18.450 --> 12:18.930 Therefore, 12:18.930 --> 12:21.800 there are limitations to the measurement of motor nerve conduction 12:21.800 --> 12:24.080 velocity in identifying 12:24.090 --> 12:26.290 patients with clear and unequivocal 12:26.290 --> 12:27.180 neuropathy, 12:27.190 --> 12:29.560 and how do we overcome these limitations? 12:29.570 --> 12:31.080 Let us look at the next slide. 12:33.990 --> 12:36.740 It has been suggested that one way to overcome the 12:36.740 --> 12:39.460 limitations is to look not only at the 12:39.460 --> 12:40.880 direct or M, 12:40.880 --> 12:43.780 or muscle response to nerve stimulation in this 12:43.780 --> 12:45.890 instance distantly and here 12:45.890 --> 12:46.950 approximately, 12:46.960 --> 12:49.340 but to look at a late wave as 12:49.340 --> 12:50.110 well, 12:50.120 --> 12:52.760 a wave which takes longer to occur the 12:52.760 --> 12:54.950 further away from the spinal cord one 12:54.950 --> 12:57.690 stimulates and a wave therefore which 12:57.690 --> 12:59.460 is reflex in character. 13:00.000 --> 13:02.520 Richard Meier showed very nicely about 10 years 13:02.520 --> 13:05.060 ago that this waveform occurred in the upper 13:05.060 --> 13:07.860 extremities of patients whose dorsal nerve 13:07.860 --> 13:10.750 roots had been sectioned for the control of pain 13:10.750 --> 13:13.320 in carcinoma and therefore that this 13:13.320 --> 13:14.210 small muscle, 13:14.220 --> 13:16.780 small muscle or F wave was 13:16.790 --> 13:19.300 a axon axon reflex 13:19.310 --> 13:20.820 occurring with anti drama, 13:20.850 --> 13:23.840 traveling up the motor nerve through the motor nerve 13:23.840 --> 13:26.460 root and back out again Ortho dramatically 13:26.470 --> 13:28.530 from that initial stimulus. 13:29.170 --> 13:31.620 The latency over this much longer 13:31.620 --> 13:34.580 distance is a fairly regular phenomenon 13:35.530 --> 13:38.440 and disorders which selectively affect the nerve 13:38.440 --> 13:41.260 root may prolong that latency. 13:41.400 --> 13:44.290 And so just as distal latency may may may be a 13:44.290 --> 13:46.020 measure of distal neuropathy. 13:46.030 --> 13:46.490 So, 13:46.490 --> 13:48.440 to F wave latency, 13:48.450 --> 13:51.270 in the presence of normal velocities may 13:51.270 --> 13:53.990 give a clue to the presence of neuropathic 13:54.000 --> 13:54.670 weakness. 13:55.460 --> 13:57.850 If this sort of technique is normal, 13:57.850 --> 13:59.740 what else can be done in the next slide? 14:01.720 --> 14:04.710 A schematic representation of a nerve action 14:04.710 --> 14:05.550 potential, 14:05.560 --> 14:07.610 which is multiphasic. 14:07.620 --> 14:09.900 As one can see here with nerve 14:09.900 --> 14:11.920 stimulation can be seen 14:12.890 --> 14:14.020 look tall and Rosenfeld. 14:15.290 --> 14:18.030 Using averaging techniques with 14:18.040 --> 14:21.010 multiple sensory nerve stimuli 14:21.020 --> 14:23.950 have shown that one can in 14:23.950 --> 14:26.470 the intact human subject record a 14:26.470 --> 14:28.430 compound nerve action potential 14:28.440 --> 14:31.040 whose various 14:31.040 --> 14:33.700 components can be measured in terms of their 14:33.700 --> 14:36.680 velocity and in terms of the amplitude of 14:36.680 --> 14:39.120 the envelope conducting at that velocity. 14:39.690 --> 14:42.190 And they have shown very nicely in a paper reported in 14:42.190 --> 14:44.840 brain in 1972, 14:44.850 --> 14:47.720 a strong correlation between 14:47.730 --> 14:50.170 the changes either in 14:50.170 --> 14:52.550 velocity of one or another of these components 14:52.560 --> 14:55.450 or in the amplitude of the envelope and the 14:55.450 --> 14:58.020 histological appearance of that neuropathy. 14:58.630 --> 15:01.180 Since many Europa these are purely sensory. 15:01.190 --> 15:04.170 This technique of compound nerve action 15:04.170 --> 15:06.810 potential study is a very 15:06.810 --> 15:09.470 useful adjuvant to the analysis of 15:09.470 --> 15:10.960 peripheral nerve disease. 15:11.850 --> 15:14.340 Other techniques are shown in the ensuing slides. 15:14.350 --> 15:15.290 The next slide, 15:15.290 --> 15:18.090 please Here is graft 15:18.100 --> 15:20.920 the thesis behind the measurement 15:20.930 --> 15:22.570 of nerve excitability, 15:22.580 --> 15:25.220 which Wilson described in the journal of neurology 15:25.220 --> 15:27.870 neurosurgery and psychiatry more than 10 years 15:27.870 --> 15:28.480 ago. 15:29.150 --> 15:31.430 If one relates the intensity of a 15:31.430 --> 15:33.900 stimulus required 15:33.910 --> 15:36.410 to elicit a 15:36.410 --> 15:38.730 threshold nerve action potential, 15:39.890 --> 15:42.850 giving paired stimuli at 15:42.860 --> 15:45.760 various intervals and 15:45.770 --> 15:48.480 relating the intensity of the 15:48.480 --> 15:50.730 second or test stimulus. 15:50.740 --> 15:52.910 Following a super maximal 15:52.920 --> 15:55.190 conditioning first stimulus, 15:55.800 --> 15:58.500 one is able to define the absolute refractory 15:58.500 --> 16:01.270 period as the time during which a 16:01.270 --> 16:02.120 second stimulus, 16:02.120 --> 16:04.880 no matter how intense will not elicit a 16:04.880 --> 16:06.050 second response, 16:06.060 --> 16:08.930 the relative refractory period with the two 16:08.930 --> 16:11.530 stimuli or equal intensity and a 16:11.530 --> 16:14.230 following period called super normal 16:14.230 --> 16:16.620 period where the second 16:16.620 --> 16:19.550 stimulus needs to be even less than it 16:19.550 --> 16:21.600 is without the conditioning stimulus. 16:22.340 --> 16:25.300 I think you can tell or deduce from the description 16:25.300 --> 16:28.260 of this technique that it is a very meticulous one 16:28.270 --> 16:30.230 requiring a great deal of time. 16:30.850 --> 16:32.200 And so in the next slide 16:33.880 --> 16:34.800 James Heckman, 16:34.800 --> 16:37.540 then a medical student at the University of Kentucky 16:37.550 --> 16:40.440 decided to re approach the old 16:40.440 --> 16:43.240 concept of a strength duration curve. 16:44.160 --> 16:46.870 He noted that with the standard stimulator 16:46.880 --> 16:49.740 available for measuring strength duration curves 16:49.750 --> 16:52.410 uh in the normal 16:52.410 --> 16:55.250 fashion that any fizzy interest 16:55.260 --> 16:58.150 will use that stimulator while it could 16:58.150 --> 17:01.130 give a square wave that very brief stimulus 17:01.130 --> 17:04.120 durations had to have a superimposed 17:04.130 --> 17:04.390 R. 17:04.390 --> 17:04.560 F. 17:04.560 --> 17:07.490 Wave to give a pseudo square wave at 17:07.490 --> 17:08.750 longer durations. 17:10.220 --> 17:10.630 Thus, 17:10.630 --> 17:11.730 using this stimulator, 17:11.730 --> 17:14.500 one doesn't know really at what level the stimulus 17:14.510 --> 17:16.840 is at any moment during this long 17:16.840 --> 17:17.520 stimulus. 17:18.350 --> 17:21.090 Using a different light isolated stimulator. 17:21.170 --> 17:22.900 Even at the long intervals, 17:22.990 --> 17:25.950 a quite square wave was elicited and in 17:25.950 --> 17:26.770 the next slide, 17:28.130 --> 17:30.710 if one compared stimuli of 17:30.710 --> 17:33.650 varying strengths from this light 17:33.650 --> 17:36.640 isolated constant current stimulator over 17:36.640 --> 17:38.200 varying durations, 17:38.210 --> 17:41.130 one was able to depict a 17:41.130 --> 17:43.250 so called excitability curve. 17:44.110 --> 17:46.860 The response in the instance of the 17:46.860 --> 17:49.450 excitability curve was the nerve action 17:49.450 --> 17:52.180 potential elicited by per cutaneous 17:52.180 --> 17:55.000 nerve stimuli When Heckman 17:55.000 --> 17:57.860 compared these data In the same 17:57.860 --> 17:58.460 patients, 17:58.460 --> 18:01.260 or at least five out of the six of the same 18:01.260 --> 18:03.980 patients with a standard strength duration 18:03.980 --> 18:04.540 curve. 18:05.260 --> 18:07.980 He noted that this excitability curve 18:07.990 --> 18:10.000 was significantly more 18:10.000 --> 18:12.940 sensitive to this parameter of nerve 18:12.940 --> 18:15.880 function than the standard strength duration curve 18:16.600 --> 18:17.530 in the next slide. 18:18.590 --> 18:19.470 Elizabeth right, 18:19.470 --> 18:22.230 extending his technique even further has 18:22.230 --> 18:24.910 shown that there is a range of normal 18:24.910 --> 18:27.770 values depicted in the crosshatched area 18:27.770 --> 18:30.610 here against which can 18:30.610 --> 18:32.810 be compared a group of patients 18:32.820 --> 18:35.170 who have normal nerve conduction 18:35.170 --> 18:38.070 velocities but obvious clinical 18:38.070 --> 18:38.800 neuropathy, 18:40.070 --> 18:42.550 their conduction velocities did not pick out the 18:42.550 --> 18:43.450 neuropathy. 18:43.460 --> 18:45.830 This excitability curve clearly did, 18:45.840 --> 18:48.490 especially at the long duration stimuli. 18:49.600 --> 18:52.200 This technique has been of a special use in the next 18:52.200 --> 18:55.180 slide in the analysis 18:55.220 --> 18:58.020 of peripheral nerve function in patients and 18:58.020 --> 18:59.230 chronic renal failure, 18:59.800 --> 19:02.780 where it can be seen That of a group of 19:02.780 --> 19:05.330 19 patients who had clinical neuropathy. 19:05.940 --> 19:08.480 Their upper extremity ulnar nerve conduction 19:08.480 --> 19:10.980 velocity was outside normal 19:10.980 --> 19:13.970 range only seven out of 19 times 19:14.640 --> 19:17.510 the perennial nerve conduction velocity was 19:17.510 --> 19:19.090 rather more sensitive. 19:19.100 --> 19:21.420 But ulnar nerve excitability 19:21.430 --> 19:23.820 identified every patient with neuropathy, 19:24.750 --> 19:25.780 there is a problem. 19:25.780 --> 19:27.990 Clearly in the excess 19:28.000 --> 19:30.390 sensitivity of both of these techniques. 19:30.400 --> 19:33.310 Since certain numbers of patients without clinical 19:33.310 --> 19:35.940 neuropathy in your E mia will have slow 19:35.940 --> 19:38.070 conduction velocities or decreased 19:38.070 --> 19:39.030 excitability. 19:39.720 --> 19:41.720 I think it should be recalled that nerve 19:41.720 --> 19:44.420 biopsy of all patients in your E. 19:44.420 --> 19:47.320 Mia in some studies will show clear 19:47.320 --> 19:48.910 cut changes. 19:48.910 --> 19:51.800 Histological E what Hickman's technique was 19:51.800 --> 19:54.600 after was a clinically useful way of 19:54.600 --> 19:57.290 approaching and identifying the patient who will 19:57.290 --> 20:00.150 have neuropathy or who may go on to develop it. 20:00.160 --> 20:01.280 And in the next slide, 20:01.280 --> 20:02.720 this question was looked at. 20:03.470 --> 20:05.830 Eight patients having serial studies 20:05.840 --> 20:08.740 showed a slow peroneal nerve conduction 20:08.740 --> 20:10.940 velocity before the onset of their 20:10.940 --> 20:13.760 neuropathy only in 25% or 20:13.760 --> 20:15.220 two out of eight of the times. 20:15.230 --> 20:17.750 Whereas six out of the eight patients had 20:17.750 --> 20:19.190 decreased excitability. 20:19.930 --> 20:22.680 This technique is in its infancy as a clinical 20:22.680 --> 20:23.400 tool, 20:23.410 --> 20:24.230 but may, 20:24.230 --> 20:26.980 together with the book tall way of looking at 20:26.980 --> 20:29.200 compound nerve action potential, 20:29.210 --> 20:32.050 be an extension of nerve function with electro maya 20:32.050 --> 20:33.190 graphic techniques. 20:33.890 --> 20:35.190 Let us go on to the next slide. 20:36.920 --> 20:39.570 Another extension has been developed 20:39.600 --> 20:42.480 by McComas and his colleagues 20:42.490 --> 20:44.460 initially in London and 20:44.460 --> 20:47.030 subsequently in Ontario. 20:47.950 --> 20:50.540 They have noted that if a peripheral nerve is 20:50.540 --> 20:53.220 stimulated and recording made from a 20:53.220 --> 20:55.160 muscle supplied from that nerve 20:56.110 --> 20:58.510 with a reference electrode in this instance, 20:58.520 --> 21:01.080 on the foot and a ground strap between the 21:01.080 --> 21:01.900 two. 21:01.910 --> 21:03.040 In the next slide 21:06.080 --> 21:09.080 that with increasing strength of 21:09.080 --> 21:10.130 stimuli, 21:10.140 --> 21:12.850 increasing size of surface 21:12.850 --> 21:15.340 recorded muscle action potentials can 21:15.340 --> 21:17.650 be had. 21:17.660 --> 21:20.610 If one looks at a reference electrode placed 21:20.610 --> 21:22.170 elsewhere on the foot. 21:22.180 --> 21:25.180 This particular extension digitally umbrellas muscle 21:26.290 --> 21:29.130 is the only muscle responding to perennial 21:29.140 --> 21:31.970 nerve stimulation and that perhaps is why 21:31.970 --> 21:34.850 they have chosen this preparation for most 21:34.860 --> 21:35.920 of their approach. 21:36.680 --> 21:38.580 Using threshold stimuli, 21:38.580 --> 21:40.530 one can define a 21:40.530 --> 21:42.700 minimal motor unit 21:42.700 --> 21:45.360 size and in McCormack's 21:45.380 --> 21:46.410 technique. 21:46.420 --> 21:49.060 this is referred to as the size of a 21:49.060 --> 21:50.320 single motor unit. 21:51.130 --> 21:53.920 One can therefore divide into the 21:53.930 --> 21:56.260 maximal response this single 21:56.260 --> 21:59.030 size to come up with a measure of the number of 21:59.030 --> 22:01.220 motor units in that particular 22:01.220 --> 22:03.670 patients extensive digital and bravest 22:03.670 --> 22:04.390 muscle. 22:04.400 --> 22:06.980 And what does this technique show us in the next 22:06.980 --> 22:07.530 slide? 22:09.310 --> 22:11.820 If one looks at control subjects, 22:12.590 --> 22:15.340 the amplitude of their motor unit, 22:15.350 --> 22:18.280 the size of the motor unit with the McComas 22:18.280 --> 22:21.230 technique is about the same as it is 22:21.230 --> 22:23.500 with limb girdle muscular dystrophy, 22:23.510 --> 22:24.370 and in fact, 22:24.370 --> 22:27.370 there may be some skew toward increasing 22:27.380 --> 22:30.110 amplitude of potentials 22:31.520 --> 22:33.370 in spinal muscular atrophy. 22:33.780 --> 22:36.680 There are many potentials which are of significantly 22:36.680 --> 22:37.960 larger amplitude, 22:38.660 --> 22:40.680 so that in McComas hands, 22:40.690 --> 22:43.370 the individual amplitude is 22:43.370 --> 22:45.710 perhaps of help in clearly 22:45.780 --> 22:47.260 neuropathic disorders, 22:47.270 --> 22:49.940 but not of much help in the limb girdle, 22:49.950 --> 22:51.600 muscular dystrophy, 22:51.610 --> 22:53.650 and other dis trophic disorders. 22:53.660 --> 22:56.260 But what is more amazing in the next slide, 22:57.540 --> 23:00.240 if one looks at the number of units 23:01.040 --> 23:03.890 from the extensive digital and bravest muscle in 23:03.890 --> 23:06.600 control subjects compared to a 23:06.600 --> 23:09.260 series of disorders which 23:09.270 --> 23:11.980 are at least traditionally held to be 23:11.990 --> 23:14.920 my opa thick one is struck that the McComas 23:14.920 --> 23:17.840 technique shows a drop out in the number 23:17.840 --> 23:18.840 of motor units. 23:18.850 --> 23:21.240 Now that's supposed to happen only with 23:21.240 --> 23:22.870 neuropathic disease. 23:22.880 --> 23:24.650 And so in the next slide, 23:25.430 --> 23:28.340 McComas has hypothesized that 23:28.340 --> 23:30.370 neuro muscular or motor unit 23:30.370 --> 23:33.220 disease may derive 23:33.230 --> 23:36.130 from a change in the motor unit, 23:36.140 --> 23:37.760 which ultimately 23:38.730 --> 23:41.340 occurs because the motor neuron itself 23:41.350 --> 23:42.250 becomes sick. 23:43.060 --> 23:45.150 And as that sickness progresses, 23:45.160 --> 23:47.590 single fibers drop out until 23:47.590 --> 23:50.480 generalized atrophy occurs and whole motor 23:50.480 --> 23:52.840 units are lost. 23:53.640 --> 23:56.430 It is this hypothesis which electrically 23:56.430 --> 23:59.120 gives support to the concept 23:59.130 --> 24:00.240 that much, 24:00.250 --> 24:01.090 if not all, 24:01.090 --> 24:03.870 of motor unit disease is ultimately 24:03.880 --> 24:05.370 neural in character. 24:07.140 --> 24:08.250 In the next slide, 24:08.880 --> 24:11.500 there are some who take issue with this 24:11.500 --> 24:14.420 particular way of looking at things and if 24:14.420 --> 24:17.350 they compare their control data in terms of 24:17.350 --> 24:20.150 motor unit potential amplitude with a 24:20.150 --> 24:22.230 variety of muscular dystrophy ease. 24:22.230 --> 24:24.980 And in this particular instance most of them were 24:24.980 --> 24:26.880 classic Duchenne dystrophy ease. 24:26.890 --> 24:29.880 I think it is fairly evident that the size 24:29.880 --> 24:32.210 the individual units with the McComas 24:32.210 --> 24:34.900 technique is here clearly shifted towards 24:34.900 --> 24:36.130 smaller units, 24:37.000 --> 24:38.890 looking at the total number of units, 24:38.890 --> 24:41.410 and I do not have a slide to show you from this 24:41.410 --> 24:44.030 author showed a a 24:44.030 --> 24:46.210 similar number of motor units. 24:46.220 --> 24:49.040 And so the McComas technique supported 24:49.040 --> 24:51.660 what standard electro media graphic techniques had 24:51.660 --> 24:53.080 suggested in the past. 24:53.660 --> 24:55.890 I would simply summarize my discussion of this 24:55.890 --> 24:58.750 technique by saying that there are many questions. 24:58.750 --> 25:01.670 It raises questions which are not yet answered. 25:02.450 --> 25:03.450 In the next slide, 25:04.840 --> 25:07.250 we go to the next level of the motor unit, 25:07.260 --> 25:09.810 the neuro muscular junction and at this 25:09.810 --> 25:12.630 level the response to repetitive nerve 25:12.630 --> 25:15.290 stimulation is the hallmark of a 25:15.290 --> 25:17.690 change of a sickness that may be 25:17.690 --> 25:19.540 productive of weakness. 25:19.550 --> 25:21.020 The next slide 25:22.250 --> 25:24.850 shows us the basic principle on which 25:24.860 --> 25:26.340 clinical E. 25:26.340 --> 25:26.540 M. 25:26.540 --> 25:26.800 G. 25:26.800 --> 25:29.190 Analysis of neuro muscular transmission is 25:29.190 --> 25:29.840 based. 25:30.760 --> 25:31.730 In this instance, 25:31.730 --> 25:34.590 a nerve stimulus is applied to the whole nerve 25:34.590 --> 25:37.310 supplying many motor units and a muscle 25:37.310 --> 25:40.160 action potential recorded with surface electrodes. 25:40.170 --> 25:43.020 In this instance it is of eight million volts 25:43.030 --> 25:45.690 theoretical amplitude as far as the 25:45.690 --> 25:48.520 negative wave is concerned if 25:48.520 --> 25:51.430 during the course of repetitive super maximal nerve 25:51.430 --> 25:52.500 stimulation, 25:52.530 --> 25:55.290 motor units drop out as indicated 25:55.290 --> 25:56.770 by the black marks. 25:56.770 --> 25:59.300 Here the evoked action 25:59.300 --> 26:02.250 potential amplitude will decrease and 26:02.250 --> 26:04.920 one can express The 26:04.930 --> 26:07.540 change during repetitive stimulation 26:07.550 --> 26:10.420 as a proportion in 26:10.420 --> 26:11.170 this instance, 26:11.170 --> 26:13.870 a 50% block in the next 26:13.870 --> 26:14.350 slide, 26:16.380 --> 26:18.860 this change is nowhere more clear 26:19.360 --> 26:20.310 than in the illness. 26:20.310 --> 26:21.570 Myasthenia gravis, 26:22.280 --> 26:25.100 in which paired stimuli At 26:25.110 --> 26:27.780 intervals less than 1/2. 26:28.490 --> 26:29.280 In this instance, 26:29.350 --> 26:32.220 100 and 60 milliseconds show a fall 26:32.220 --> 26:35.130 off in the amplitude of the second stimulus. 26:35.140 --> 26:37.690 In all instances the stimuli are super 26:37.690 --> 26:40.560 maximal for nerve you have 26:40.560 --> 26:43.480 heard earlier and I'm sure recall that 26:43.490 --> 26:45.830 the classic hallmark of Myasthenia 26:45.830 --> 26:48.830 gravis is a fall off during 26:48.830 --> 26:51.360 repetitive stimulation that repairs 26:51.360 --> 26:53.690 itself early on in the course of repetitive 26:53.690 --> 26:54.580 stimulation. 26:54.590 --> 26:55.750 In this instance, 26:55.760 --> 26:58.100 at 10 impulses per second. 26:58.110 --> 27:00.940 This so called early dip is seen 27:00.940 --> 27:03.940 classically in myasthenia gravis and only in 27:03.940 --> 27:06.350 one other setting in individuals 27:06.360 --> 27:09.160 who have been given a small amount of your 27:09.160 --> 27:11.940 r if the stimulation is continued for a 27:11.940 --> 27:12.990 long time, 27:13.000 --> 27:15.850 the fall off with a late exhaustion is 27:15.850 --> 27:18.580 observed and both of these phenomena can be 27:18.580 --> 27:21.560 ameliorated if colonist arrays inhibitors are 27:21.560 --> 27:23.820 given in the next slide, 27:24.980 --> 27:27.700 it is important to be certain that the response in 27:27.700 --> 27:30.600 muscle to nerve stimulation does not 27:30.600 --> 27:32.100 arrive at other levels. 27:32.110 --> 27:35.000 One way of looking at this is to apply a 27:35.000 --> 27:37.460 stimulus through a needle electrode in the 27:37.460 --> 27:40.410 distal portions of muscle away 27:40.410 --> 27:42.260 from the zone of innovation. 27:42.260 --> 27:44.940 The motor point and to record with needle 27:44.940 --> 27:47.700 recording electrodes at two points are one 27:47.700 --> 27:49.150 here and our two here. 27:49.740 --> 27:50.650 In this instance, 27:50.650 --> 27:53.420 the same repetitive stimulation was given 27:53.430 --> 27:54.530 and the response, 27:54.530 --> 27:57.020 aside from a little baseline artifact, 27:57.030 --> 27:59.750 was the same to the initial response as it was 27:59.750 --> 28:02.170 during the course of stimulation. 28:02.440 --> 28:05.010 There was a little change in conduction velocity during 28:05.010 --> 28:06.320 repetitive stimulation, 28:06.330 --> 28:07.620 but the amplitude, 28:07.620 --> 28:10.360 the size of the evoked response response 28:10.430 --> 28:13.110 in muscle to muscle stimulation stayed the 28:13.110 --> 28:14.850 same even though, 28:14.850 --> 28:16.610 as we saw in the former slide, 28:16.620 --> 28:18.840 it changed with nerve stimulation 28:19.890 --> 28:22.850 so much for the theory behind the analysis of 28:22.850 --> 28:24.000 neuro muscular disease. 28:24.000 --> 28:25.770 Let us go on into the next slide. 28:27.290 --> 28:29.590 This kind of technique can be 28:29.590 --> 28:32.410 applied to the study of Children 28:32.410 --> 28:34.890 born of my aesthetic mothers and I 28:34.890 --> 28:37.790 think in the case of the data on the 28:37.800 --> 28:39.050 right hand side, 28:39.060 --> 28:41.830 from a child who had transient neonatal 28:41.830 --> 28:42.970 myasthenia, 28:42.980 --> 28:45.870 one can see it fast rates of stimulation 28:45.880 --> 28:48.180 and its lower rates the early dip 28:48.180 --> 28:50.110 phenomenon once again, 28:50.120 --> 28:52.950 and in the case of a child born to 28:52.950 --> 28:55.020 a another mother with myasthenia, 28:55.030 --> 28:57.830 but a child not manifesting clinical weakness. 28:57.840 --> 29:00.000 No such early dip was observed. 29:00.710 --> 29:03.570 This is therefore a useful technique for 29:03.570 --> 29:05.860 the uncovering of myasthenia gravis. 29:06.410 --> 29:07.450 In the next slide 29:09.660 --> 29:11.650 There are a certain proportion of patients, 29:11.650 --> 29:12.050 however, 29:12.050 --> 29:14.900 who will not show any change 29:14.910 --> 29:16.820 with repetitive stimulation. 29:16.830 --> 29:17.430 Dr. 29:17.430 --> 29:20.420 Young and his associates have estimated that if one looks at a 29:20.420 --> 29:22.870 single nerve muscle 29:22.880 --> 29:25.470 junction preparation in Vivo, 29:25.480 --> 29:28.090 that the incidence of abnormalities even in the 29:28.090 --> 29:31.020 presence of defined Myasthenia is of the order of 29:31.020 --> 29:32.010 60%. 29:32.510 --> 29:35.310 If you look at two or three or more neuromuscular 29:35.310 --> 29:36.090 junctions, 29:36.100 --> 29:38.510 that incidents can be increased to 85, 29:38.510 --> 29:39.760 perhaps 90%. 29:39.770 --> 29:42.630 But the remaining portion of patients who have 29:42.630 --> 29:45.000 classic myasthenia in whom repetitive 29:45.000 --> 29:47.330 stimulation will give no abnormality 29:48.090 --> 29:51.000 for this reason Colin Brown reintroduced a 29:51.000 --> 29:53.320 technique of Regional Cure Ization, 29:53.900 --> 29:56.030 in which the same stimulus and recording 29:56.030 --> 29:58.710 parameters with an intervening 29:58.720 --> 30:01.560 uh ground 30:01.560 --> 30:04.440 strap are observed and under 30:04.440 --> 30:06.370 tourniquet conditions, 30:07.370 --> 30:10.280 an intravenous infusion of a small amount of 30:10.310 --> 30:13.030 Harare is given after a latent 30:13.040 --> 30:13.810 period. 30:13.820 --> 30:16.510 The tourniquet is released and after four 30:16.510 --> 30:19.390 minutes or so permitting restoration of 30:19.390 --> 30:20.490 normal function. 30:20.500 --> 30:22.680 Then studies of neuro muscular 30:22.680 --> 30:25.270 transmission are had in the next 30:25.270 --> 30:28.210 slide data from his paper in 30:28.220 --> 30:31.050 the Journal of neurology neurosurgery and 30:31.050 --> 30:34.010 psychiatry this year show what happens 30:34.010 --> 30:35.520 in three normal subjects. 30:36.420 --> 30:39.060 The response to repetitive stimulation before 30:40.130 --> 30:43.080 the administration of cure are at rates 30:43.080 --> 30:45.770 of two stimuli per second show no 30:45.770 --> 30:47.920 change afterwards. 30:47.930 --> 30:50.930 There is a minor fall off in 30:50.930 --> 30:53.140 the total amplitude of the response, 30:53.150 --> 30:55.820 but repetitive stimulation really doesn't do very 30:55.820 --> 30:56.380 much. 30:57.160 --> 30:59.970 But if we look at this in my aesthetic subjects in the 30:59.970 --> 31:02.490 next slide one can 31:02.490 --> 31:05.440 see that although ocular my aesthetics 31:05.440 --> 31:07.380 may not show very much change. 31:08.000 --> 31:10.180 Patients with generalized weakness, 31:10.190 --> 31:13.030 even though it may be mild without any 31:13.030 --> 31:15.940 evidence of change with repetitive stimulation to start 31:15.940 --> 31:18.760 with may show a complete and total block 31:18.770 --> 31:21.170 with very small doses of cure our 31:21.450 --> 31:24.160 regional cure Ization therefore 31:24.170 --> 31:27.120 may help to identify the 10 or 31:27.120 --> 31:30.110 15% of patients with 31:30.120 --> 31:32.860 classic myasthenia who do not show a 31:32.860 --> 31:35.120 defect on repetitive stimulation. 31:36.020 --> 31:36.840 The next slide 31:39.100 --> 31:41.790 not only is the detrimental response 31:41.800 --> 31:43.100 occasionally seen, 31:43.950 --> 31:46.420 But there are conditions in which very 31:46.430 --> 31:47.750 slow stimulation. 31:47.750 --> 31:48.760 In this instance, 31:48.770 --> 31:51.770 one per second will show a 31:51.770 --> 31:52.950 fall off, 31:52.960 --> 31:55.320 but very rapid stimulation. 31:55.320 --> 31:56.140 In this instance, 31:56.140 --> 31:58.740 20 per second will show a marked 31:58.750 --> 32:00.950 increase in the amplitude of the 32:00.950 --> 32:01.760 response. 32:02.720 --> 32:05.550 The next slide shows that this 32:05.550 --> 32:08.470 increase may in part be due to the 32:08.480 --> 32:11.170 narrowing of duration and increase in 32:11.170 --> 32:12.100 amplitude. 32:12.130 --> 32:14.440 The so called bunching phenomenon, 32:14.450 --> 32:17.340 but that if one looks at the response at the 32:17.340 --> 32:20.010 end of this stimulus train at 10 32:20.010 --> 32:22.990 cycles per second and compares it to 32:22.990 --> 32:23.980 the beginning. 32:23.990 --> 32:25.660 Not only is it shorter, 32:25.660 --> 32:28.110 but also it is significantly larger in 32:28.120 --> 32:29.060 area I. 32:29.060 --> 32:29.340 E. 32:29.340 --> 32:32.230 The increase in amplitude is even more than one 32:32.230 --> 32:34.210 would expect from the bunching phenomenon. 32:34.910 --> 32:37.370 That's important to realize because a certain amount of 32:37.370 --> 32:38.420 facilitation, 32:38.430 --> 32:41.380 perhaps up to as much as 20% can be 32:41.380 --> 32:44.120 seen in normal subjects because of bunching. 32:44.980 --> 32:47.800 This phenomenon of increase with fast repetitive 32:47.800 --> 32:50.150 stimulation is what one would expect 32:50.150 --> 32:52.760 theoretically with a defect in acetylcholine 32:52.760 --> 32:53.330 release. 32:53.800 --> 32:56.290 And these two slides have been taken from the classic 32:56.300 --> 32:58.870 defect in acetylcholine release 32:59.140 --> 33:01.930 that associated on occasion with a small cell 33:01.930 --> 33:03.220 carcinoma of the bronchus, 33:03.390 --> 33:05.460 the Eaton lambert syndrome. 33:06.290 --> 33:07.210 In the next slide, 33:08.440 --> 33:11.380 a similar defect can be seen particularly 33:11.380 --> 33:14.280 with fast repetitive stimulation and in this 33:14.280 --> 33:16.630 instance the 33:16.640 --> 33:19.640 enhanced potentially ation or facilitation and muscle 33:19.640 --> 33:22.310 action potential amplitude is expressed as a 33:22.310 --> 33:25.190 percentage of baseline stimulation during and 33:25.190 --> 33:27.680 after a train of repetitive stimuli. 33:27.690 --> 33:30.610 The marked increase to 2.5 33:30.610 --> 33:32.500 to 4 times the amplitude 33:33.210 --> 33:35.840 occurred in this young man seen in the next slide, 33:36.820 --> 33:37.250 who, 33:37.250 --> 33:39.600 when he was admitted to hospital, 33:39.610 --> 33:42.230 had a very blank face with immobile 33:42.230 --> 33:44.330 eyes and dilated, 33:44.330 --> 33:46.940 fixed pupils that would not respond to 33:46.940 --> 33:49.790 light seen in his hometown 33:49.800 --> 33:51.420 of Stinking Creek Kentucky. 33:52.600 --> 33:53.940 Two months after this, 33:53.950 --> 33:56.470 he was a tasseled haired little boy with 33:56.470 --> 33:58.820 quite evident open eyes, 33:58.830 --> 34:00.040 fully mobile, 34:00.050 --> 34:02.620 not only in his ocular and bulb our muscles, 34:02.630 --> 34:04.090 but also elsewhere. 34:04.750 --> 34:05.670 It is likely, 34:05.670 --> 34:08.520 although not proven beyond the shadow of a doubt that 34:08.520 --> 34:11.190 this child's pre synaptic defect in 34:11.190 --> 34:13.720 acetylcholine release was caused 34:13.720 --> 34:16.070 by the presence of botulinum 34:16.080 --> 34:18.820 toxin in some of the food found 34:18.820 --> 34:19.980 near of his home. 34:20.630 --> 34:21.650 In the next slide, 34:24.970 --> 34:26.730 a response halfway between 34:26.730 --> 34:28.960 myasthenia and 34:28.970 --> 34:31.880 the pre synaptic defects we've been 34:31.880 --> 34:34.220 considering can be seen on 34:34.220 --> 34:36.610 occasion in this 34:36.610 --> 34:39.410 instance an individual who became weak 34:39.410 --> 34:42.050 after the administration of a polyp 34:42.050 --> 34:44.960 peptide and an amino black aside antibiotic 34:44.970 --> 34:47.270 was studied not only was nerve 34:47.270 --> 34:50.080 stimulation given and muscle action potential 34:50.080 --> 34:50.850 recorded, 34:50.860 --> 34:53.820 but also the anti drama nerve action 34:53.820 --> 34:56.210 potential was recorded during repetitive 34:56.210 --> 34:57.380 stimulation. 34:57.390 --> 35:00.390 Thus in this instance the change which is 35:00.390 --> 35:03.370 occurring in muscle action potential was not seen in 35:03.370 --> 35:05.910 the nerve action potential and hence must 35:05.910 --> 35:08.550 be at the neuro muscular junction. 35:09.470 --> 35:11.800 This patient's response started off quite 35:11.800 --> 35:14.610 small and got seriously 35:14.610 --> 35:17.420 smaller with repetitive stimulation at 35:17.420 --> 35:19.950 slow rates with faster rates. 35:19.960 --> 35:22.400 The rate of decline was not so great. 35:23.410 --> 35:26.340 It wasn't a full potential ation But 35:26.340 --> 35:28.850 at least faster rates of stimulation 35:28.860 --> 35:31.850 overcame some of the block present in 35:31.850 --> 35:34.330 this instance when stimuli were given one every 10 35:34.330 --> 35:35.040 seconds. 35:35.610 --> 35:38.580 This defect has been shown with single 35:38.580 --> 35:39.330 fiber E. 35:39.330 --> 35:39.490 M. 35:39.490 --> 35:39.740 G. 35:39.740 --> 35:42.660 Studies in vitro to 35:42.660 --> 35:45.410 be associated with disordered pre synaptic 35:45.410 --> 35:47.160 acetylcholine metabolism. 35:48.100 --> 35:48.730 The next slide, 35:48.730 --> 35:49.190 please. 35:51.010 --> 35:53.590 I think it's important to call to mind 35:53.600 --> 35:56.330 the character of the defect once again 35:56.340 --> 35:59.250 with the early dip and late fall off during 35:59.250 --> 36:01.830 repetitive stimulation at varying frequencies. 36:01.840 --> 36:04.370 Because this hallmark of 36:04.370 --> 36:06.630 myasthenia gravis in the next slide 36:08.150 --> 36:11.070 Was what was clearly shown by Patrick and 36:11.070 --> 36:14.060 Lindstrom in their classic paper in science 36:14.060 --> 36:15.700 in 1973, 36:15.710 --> 36:18.390 in which they showed that Myasthenia gravis 36:18.400 --> 36:20.780 could be induced in laboratory 36:20.780 --> 36:23.160 animals by the administration of 36:23.160 --> 36:25.550 purified receptor protein. 36:26.480 --> 36:27.510 In the next slide, 36:28.590 --> 36:31.410 the MG defect in such an animal is seen 36:31.410 --> 36:33.670 much more clearly during 36:34.400 --> 36:36.410 and after repetitive stimulation, 36:36.410 --> 36:39.330 where an immediate post titanic facilitation sometimes 36:39.330 --> 36:42.150 occurs with a later post titanic fall 36:42.150 --> 36:42.730 off. 36:43.810 --> 36:46.640 This defect can be seen to be changed 36:46.650 --> 36:49.290 by the administration of a colonist arrays inhibitor 36:49.300 --> 36:50.320 in the rabbit. 36:51.560 --> 36:54.450 The point I'm trying to get across is that this 36:54.460 --> 36:54.650 E. 36:54.650 --> 36:54.810 M. 36:54.810 --> 36:57.630 G technique is the way in 36:57.630 --> 37:00.060 which we recognize and 37:00.060 --> 37:03.000 affirm that the animal model is truly 37:03.000 --> 37:05.280 an animal model of myasthenia gravis. 37:06.090 --> 37:07.020 In the next slide, 37:08.120 --> 37:10.600 the same defect was seen by Dr Druckman 37:11.610 --> 37:14.280 during immediately after and the post 37:14.280 --> 37:17.270 titanic exhaustion observed in 37:17.270 --> 37:19.650 a rat exposed to cobra venom 37:20.520 --> 37:23.510 in order that one could 37:23.510 --> 37:26.450 show that blocking of the N plate receptor 37:26.450 --> 37:29.280 protein could produce a neuro muscular 37:29.280 --> 37:30.030 disorder, 37:30.040 --> 37:32.920 a neuro muscular disorder recognized by 37:32.920 --> 37:35.710 the AMG hallmark of an early dip. 37:36.480 --> 37:39.380 And finally in the next slide Dr 37:39.380 --> 37:41.900 Jackman's delineation that such a 37:41.900 --> 37:44.760 defect occurs in mice who are 37:44.760 --> 37:47.230 given chronic administration of 37:47.230 --> 37:50.180 immunoglobulin from patients with myasthenia 37:50.190 --> 37:53.090 is one of the real breakthroughs and the 37:53.100 --> 37:55.480 understanding of myasthenia gravis, 37:55.490 --> 37:58.470 a breakthrough that supports the concept that 37:58.470 --> 38:01.410 it is a disorder associated with 38:01.420 --> 38:03.880 circulating antibodies to receptor 38:03.880 --> 38:04.520 protein. 38:04.830 --> 38:07.790 That this is clinically and electrically true 38:07.800 --> 38:10.370 is seen once again by the early dip 38:10.370 --> 38:11.040 phenomenon. 38:12.050 --> 38:14.070 So much for neuro muscular transmission. 38:14.070 --> 38:15.530 Let us move on to the next slide 38:17.840 --> 38:20.270 at the last level of the motor unit 38:21.020 --> 38:22.450 in muscle itself. 38:22.460 --> 38:25.300 Various needle electrode biographic techniques 38:25.310 --> 38:28.170 measuring conduction velocity and excitability 38:28.170 --> 38:30.570 of of muscle fibers directly as well 38:30.580 --> 38:32.850 are used to analyze 38:32.850 --> 38:33.660 disease. 38:33.670 --> 38:36.520 If we can see the theory behind these in the next 38:36.520 --> 38:37.070 slide. 38:38.960 --> 38:41.050 Under ordinary circumstances, 38:41.060 --> 38:44.040 two kinds of needles are used either a 38:44.040 --> 38:46.850 concentric needle or else 38:46.860 --> 38:49.760 a very fine multi electrode 38:50.850 --> 38:52.400 on occasion as well. 38:52.410 --> 38:55.260 Single mono polar electrodes are used 38:55.270 --> 38:57.950 and these techniques give different kinds of information. 38:57.950 --> 39:00.870 Let us explore that now in the next slide, 39:03.110 --> 39:04.450 schematically represented. 39:04.450 --> 39:07.240 Here is something that anyone who has ever listened to a radio 39:07.250 --> 39:10.230 realizes a multi electrode 39:10.230 --> 39:12.810 placed inside of a muscle In 39:12.810 --> 39:15.790 which only one motor unit in the center of the muscle 39:15.790 --> 39:18.410 at level two is being activated, 39:18.420 --> 39:21.400 will record a muscle action potential of a given 39:21.400 --> 39:24.230 amplitude and duration above and 39:24.230 --> 39:24.630 below. 39:24.630 --> 39:27.080 That active motor unit the same 39:27.080 --> 39:27.740 duration, 39:27.740 --> 39:29.010 the same frequency, 39:29.010 --> 39:30.580 the same tune if you were, 39:30.590 --> 39:33.340 is heard but at much lower amplitude. 39:33.350 --> 39:36.020 So that using concentric needles, 39:36.030 --> 39:38.480 the duration of the motor unit is the thing that 39:38.480 --> 39:41.080 counts book tall and his co 39:41.080 --> 39:43.970 workers have correlated motor unit duration 39:43.980 --> 39:46.830 with the size or the number of muscle 39:46.830 --> 39:49.560 fibers supplied by each anterior horn cell. 39:49.570 --> 39:52.110 And has shown that with very small motor units, 39:52.110 --> 39:54.360 such as occur in the extra ocular muscles, 39:54.370 --> 39:56.710 very brief motor units are 39:56.710 --> 39:59.560 recorded and with large ones and the large muscles of the 39:59.560 --> 40:00.170 thigh. 40:00.180 --> 40:02.000 Long motor units are recorded. 40:02.490 --> 40:05.270 He and his colleagues have established normal motor 40:05.270 --> 40:07.930 unit duration values for different 40:07.930 --> 40:10.720 subjects at different ages and in different muscles 40:10.730 --> 40:13.500 and has shown that if one can observe 40:13.510 --> 40:15.300 increased duration units, 40:15.360 --> 40:18.050 then one must postulate an increase in motor 40:18.050 --> 40:20.080 units size and again, 40:20.080 --> 40:22.980 that can only occur when there has been 40:22.980 --> 40:25.080 degeneration due to 40:25.090 --> 40:27.580 neuropathy with re innovation and 40:27.590 --> 40:30.030 increase in the size of the motor unit, 40:31.590 --> 40:34.300 decreased motor unit duration can be 40:34.300 --> 40:36.840 seen with decreased motor unit size 40:37.520 --> 40:40.180 and is often referred to as my opa thicken 40:40.180 --> 40:40.710 character. 40:41.480 --> 40:42.340 The next slide. 40:43.290 --> 40:46.170 Such brief motor units can be seen with 40:46.170 --> 40:49.150 weak effort when there is spotty drop out of 40:49.150 --> 40:50.240 muscle fibers, 40:51.060 --> 40:53.500 whereas with whole muscle fiber drop out 40:54.180 --> 40:55.630 and perhaps re innovation, 40:55.630 --> 40:57.160 the motor units are larger. 40:58.200 --> 41:00.770 There is some activity at rest in the next 41:00.770 --> 41:03.510 slide that has a 41:03.510 --> 41:06.230 particular and peculiar fashion. 41:06.230 --> 41:09.080 That sounds like a motorcycle revving up for those 41:09.080 --> 41:12.060 who remember the days of funds and 41:12.070 --> 41:14.800 his friends on Happy Days, 41:14.810 --> 41:17.660 the dive bomber of World 41:17.660 --> 41:18.570 War Two. 41:18.580 --> 41:21.550 A potential which increases in amplitude and 41:21.550 --> 41:23.870 frequency and later decreases in 41:23.870 --> 41:24.860 both. 41:24.870 --> 41:25.820 In this instance, 41:25.820 --> 41:28.820 the muscle was per cust with the needle in place 41:28.830 --> 41:31.380 and this phenomenon is the electrical 41:31.380 --> 41:33.600 concomitant of maya Tonia, 41:33.990 --> 41:36.350 a phenomenon missing from a normal muscle 41:37.510 --> 41:40.470 and a very clear and classic hallmark of the maya tonic 41:40.480 --> 41:42.690 disorders in the next slide, 41:43.440 --> 41:46.070 other sorts of abnormalities can be seen at 41:46.080 --> 41:46.900 rest. 41:46.910 --> 41:49.410 The slide was taken from dr lambert's 41:49.420 --> 41:51.700 article in the clinical 41:51.710 --> 41:54.600 examinations in neurology textbook from the Mayo 41:54.600 --> 41:55.360 clinic. 41:55.370 --> 41:57.960 Normally with insertion, 41:57.960 --> 42:00.650 a brief bursts of potentials occurs 42:00.660 --> 42:03.540 with no activity persisting at 42:03.550 --> 42:04.190 rest. 42:04.200 --> 42:06.920 If one gets right into the zone of 42:06.920 --> 42:07.870 innovation, 42:07.880 --> 42:10.170 miniature end plate potentials may be 42:10.170 --> 42:12.630 recorded with the Innovation. 42:12.630 --> 42:15.110 There are lots of 42:15.120 --> 42:18.070 different six simple waves and occasionally 42:18.070 --> 42:20.340 positive sharp waves as well. 42:20.350 --> 42:23.090 The Maya tonic phenomenon we've commented on, 42:23.100 --> 42:26.080 and a bizarre high frequency discharge can be 42:26.080 --> 42:28.930 seen in a variety of non specified 42:28.930 --> 42:30.500 neuro muscular disorders. 42:30.510 --> 42:33.360 In the next slide I will review for 42:33.360 --> 42:36.010 you motor units, 42:36.020 --> 42:36.600 which, 42:36.610 --> 42:38.380 if each box here represents, 42:38.380 --> 42:40.960 10 milliseconds are seen to be quite 42:40.960 --> 42:43.890 brief and therefore deriving from 42:43.890 --> 42:46.790 motor units whose size 42:46.790 --> 42:49.190 whose number of muscle fibers is reduced 42:49.800 --> 42:52.570 in the next slide at rest from the 42:52.570 --> 42:55.240 same muscle from which the prior slide was recorded 42:55.250 --> 42:57.880 are seeing positive sharp waves and 42:57.880 --> 42:59.510 fibrillation potentials. 42:59.520 --> 43:01.880 The hallmarks largely of D 43:01.880 --> 43:02.600 innovation. 43:03.670 --> 43:06.620 Thus it can be seen that brief motor units 43:06.640 --> 43:08.740 can arise when leaves, 43:08.740 --> 43:11.560 drop off a sick rooted tree 43:12.080 --> 43:15.070 and are not necessarily myopathy 43:15.530 --> 43:16.090 in a path, 43:16.090 --> 43:17.080 a demonic sense. 43:17.720 --> 43:18.930 With that. 43:18.940 --> 43:20.120 As a background, 43:20.120 --> 43:22.550 one can simply relate motor unit, 43:22.550 --> 43:25.460 size two must to motor 43:25.460 --> 43:28.390 unit uh duration and 43:28.400 --> 43:31.120 derive some physiologic thoughts about the 43:31.120 --> 43:33.850 character of the problem facing you. 43:34.500 --> 43:35.390 In the next slide 43:37.360 --> 43:38.110 is depicted. 43:38.120 --> 43:39.820 Another way of looking at E. 43:39.820 --> 43:40.010 M. 43:40.010 --> 43:40.400 G. 43:41.420 --> 43:42.750 With increasing effort, 43:43.530 --> 43:46.090 increased numbers of motor units are recruited 43:46.370 --> 43:49.150 such that at maximal effort and interference pattern is 43:49.150 --> 43:49.950 observed. 43:50.520 --> 43:53.470 If there has been a neuropathy with drop out 43:53.470 --> 43:54.440 of motor units, 43:54.480 --> 43:57.150 the recruitment must perforce be 43:57.150 --> 43:59.810 less such that at maximal effort. 44:00.450 --> 44:02.500 Single motor units are observed 44:03.340 --> 44:04.190 with a myopathy. 44:04.190 --> 44:05.090 On the other hand, 44:05.520 --> 44:08.140 since each motor unit is reduced in size, 44:08.840 --> 44:11.410 increased numbers must be recorded per unit 44:11.410 --> 44:13.070 effort and a more dense, 44:13.070 --> 44:15.950 lower amplitude interference pattern and maximal 44:15.950 --> 44:16.880 effort is seen. 44:17.490 --> 44:20.200 There have been a variety of electronic 44:20.210 --> 44:23.160 averaging techniques that have been used 44:23.170 --> 44:25.960 to define the differences between these 44:25.970 --> 44:28.680 kinds of activity and between various 44:28.680 --> 44:30.470 points on this curve. 44:30.480 --> 44:33.010 Suffice it to say that when one 44:33.010 --> 44:35.940 compares these techniques to the analysis 44:35.940 --> 44:37.320 of motor unit duration, 44:37.850 --> 44:40.770 the motor unit duration techniques show a much 44:40.770 --> 44:43.260 higher correlation with the ultimate clinical 44:43.260 --> 44:44.630 diagnosis of the patient. 44:45.290 --> 44:46.160 In the next slide, 44:48.130 --> 44:51.050 different kinds of activity with 44:51.060 --> 44:53.250 maximal effort are observed, 44:53.260 --> 44:55.860 I believe these were shown schematically in the last 44:55.860 --> 44:56.500 slide. 44:56.510 --> 44:57.820 In the next slide, 44:59.410 --> 45:02.370 one must recall when doing AMG studies 45:02.550 --> 45:05.020 something which King angle showed us quite 45:05.030 --> 45:07.570 elegantly several years ago that 45:07.580 --> 45:10.190 inflammatory change in muscle may 45:10.190 --> 45:12.770 occur as it did in this guinea pig muscle 45:12.780 --> 45:15.630 within days after Needling the 45:15.630 --> 45:17.770 muscle for electro maya graphic study. 45:18.420 --> 45:20.700 And so the studies of E. 45:20.700 --> 45:20.880 M. 45:20.880 --> 45:21.170 G. 45:21.170 --> 45:23.720 Must be done in conjunction with 45:23.720 --> 45:26.510 examination of the whole patient and biopsy 45:26.510 --> 45:29.240 must not be taken from an area previously 45:29.240 --> 45:31.270 needled the next slide 45:33.720 --> 45:36.560 because of the limitations of standard needle E. 45:36.560 --> 45:36.720 M. 45:36.720 --> 45:36.950 G. 45:36.950 --> 45:37.680 Techniques, 45:38.440 --> 45:41.080 Stalberg and his associates over the past 45:41.090 --> 45:43.770 10 and now almost 13 years have 45:43.770 --> 45:46.630 introduced a new way of looking at the motor unit. 45:47.480 --> 45:49.930 That new way involves very small multi 45:49.930 --> 45:52.340 electrodes and the 45:52.350 --> 45:55.340 recording is made from 45:55.350 --> 45:57.900 one or another point on the multi 45:57.900 --> 46:00.390 electrode in response to voluntary 46:00.390 --> 46:03.020 stimulation or in this instance, 46:03.030 --> 46:05.750 repetitive threshold nerve stimulation. 46:06.360 --> 46:09.200 In normal subjects 12 46:09.200 --> 46:12.000 and often three fibers from 46:12.010 --> 46:14.840 that region can be recorded. 46:14.850 --> 46:17.290 And if the response to subsequent 46:17.290 --> 46:19.430 stimuli is measured, 46:19.990 --> 46:22.580 Each of these responses bear the 46:22.580 --> 46:25.580 same time relationship to each other within 46:25.580 --> 46:28.090 less than 40 milliseconds. 46:29.370 --> 46:31.590 If we compare this in the next slide, 46:31.590 --> 46:32.520 however, 46:32.530 --> 46:35.090 to similar observations made in 46:35.090 --> 46:37.140 patients with myasthenia gravis, 46:38.090 --> 46:40.720 two things are observed in the first 46:40.720 --> 46:41.520 instance, 46:41.530 --> 46:42.580 the 2nd, 46:42.590 --> 46:45.130 3rd and 4th units drop 46:45.130 --> 46:48.020 out with repetitive stimulation 46:48.030 --> 46:50.960 and in the second instance the timing of the second 46:50.960 --> 46:52.870 one gets much later. 46:52.880 --> 46:55.580 A so called jitter response 46:55.590 --> 46:58.420 and increased duration between 46:58.430 --> 47:01.170 the 1st and 2nd 47:01.170 --> 47:03.110 responses is observed. 47:03.120 --> 47:05.980 This jitter phenomenon is the 47:05.980 --> 47:08.430 hallmark of disordered neuro muscular 47:08.430 --> 47:09.470 transmission. 47:09.480 --> 47:12.460 It is seen preeminently with Stalberg 47:12.460 --> 47:15.240 single fiber AMG technique in the illness 47:15.240 --> 47:16.540 Myasthenia gravis, 47:16.590 --> 47:19.500 but obviously and logically can be seen in 47:19.500 --> 47:22.220 any other disorder of peripheral nerve 47:22.230 --> 47:24.670 or muscle in which delay in 47:24.670 --> 47:27.490 conduction in nerve fibers or at the 47:27.490 --> 47:30.180 neuro muscular junction or muscle fibers themselves can 47:30.180 --> 47:30.710 occur? 47:31.250 --> 47:32.850 I believe that's all the slides. 47:33.020 --> 47:36.010 Is there any way we can have the slides off at this 47:36.010 --> 47:38.530 stage of the game and simply summarize 47:39.840 --> 47:42.550 by saying that we have attempted to review the 47:42.550 --> 47:45.220 theoretical basis behind the 47:45.220 --> 47:47.980 various standard clinically MG techniques, 47:48.000 --> 47:50.940 we have indicated some of their limitations 47:51.120 --> 47:53.940 and their application in diseases at various levels of the 47:53.940 --> 47:54.630 motor unit, 47:55.230 --> 47:56.100 and indicated, 47:56.110 --> 47:58.420 I hope that if these techniques are 47:58.420 --> 48:01.410 applied with reference to the patient's clinical 48:01.410 --> 48:02.350 problem, 48:02.360 --> 48:05.350 the experience will be an enjoyable one for 48:05.350 --> 48:05.610 you, 48:05.610 --> 48:06.810 as well as for the patient. 48:06.820 --> 48:07.550 Thank you.