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.* 00:02.010 --> 00:04.780 too many clinicians method pathology 00:04.790 --> 00:06.130 means the solution, 00:06.140 --> 00:08.400 the final answer to the problems in the 00:08.400 --> 00:10.690 diagnosis of neuromuscular diseases. 00:10.700 --> 00:13.630 Yet like all other methods 00:13.640 --> 00:14.720 of examination, 00:14.730 --> 00:17.600 his pathology of the muscle tissue has 00:17.600 --> 00:18.760 its restrictions. 00:18.770 --> 00:21.620 And it's just one of the many ways of reaching a 00:21.620 --> 00:22.620 diagnosis. 00:23.120 --> 00:26.020 Muscle tissue has only a limited range of 00:26.020 --> 00:28.680 histological changes in reaction to disease. 00:28.690 --> 00:30.220 But on the other hand, 00:30.260 --> 00:32.360 this number is so large that it is 00:32.370 --> 00:34.900 impossible to show you every way of 00:34.900 --> 00:35.470 reaction. 00:35.680 --> 00:36.510 Therefore, 00:36.520 --> 00:39.450 I have chosen a few pathological changes that 00:39.460 --> 00:42.340 illustrates very well the possibilities and 00:42.350 --> 00:44.920 the restrictions of muscle pathology. 00:44.950 --> 00:47.940 I shall demonstrate some special fibers like 00:47.950 --> 00:48.890 target fibers, 00:48.900 --> 00:51.720 rink fibers and ragged red fibers and 00:51.720 --> 00:54.410 some special morphological features like the 00:54.410 --> 00:56.620 formation of cuba integrates 00:56.630 --> 00:57.670 cars, 00:57.680 --> 01:00.200 roads and the focal loss of cross 01:00.200 --> 01:00.860 variation. 01:01.660 --> 01:02.720 On this slide. 01:02.730 --> 01:05.720 You see the five main methods 01:05.720 --> 01:07.940 of examination and neurovascular 01:07.940 --> 01:10.820 diseases and I want to 01:10.820 --> 01:13.350 put forward to you that the order 01:13.360 --> 01:15.460 is completely arbitrary 01:16.000 --> 01:18.760 and there is no one of 01:18.770 --> 01:21.510 these methods that is more important 01:21.520 --> 01:22.480 than the other. 01:23.040 --> 01:25.740 But I will talk about pathology 01:26.340 --> 01:27.880 and that will be history, 01:27.880 --> 01:28.680 pathology, 01:28.690 --> 01:29.220 enzyme, 01:29.220 --> 01:29.510 history, 01:29.520 --> 01:32.040 chemistry and when necessary. 01:32.050 --> 01:35.040 I'll show you some slides of the 01:35.040 --> 01:36.990 electron microscopic features. 01:38.140 --> 01:40.820 The first slide shows you a 01:40.820 --> 01:43.420 target fiber called by DR King Engel in 01:43.420 --> 01:46.370 1961 target fiber because it looks 01:46.370 --> 01:49.190 like a target and especially this guy. 01:49.190 --> 01:49.910 Graham ST, 01:49.910 --> 01:50.670 glamorous tye. 01:50.670 --> 01:53.280 Graham ST staying at the 01:53.290 --> 01:55.910 core of this target stains 01:55.920 --> 01:56.450 bread. 01:56.460 --> 01:57.160 Right? 01:59.420 --> 02:02.230 Then you see the target fiber with 02:02.240 --> 02:02.990 an enzyme, 02:02.990 --> 02:05.950 histone chemical reaction oxidative enzyme. 02:05.950 --> 02:08.720 And then you see that the center of the target 02:08.730 --> 02:10.550 is not stained at all. 02:10.560 --> 02:13.510 That is because there are no mitochondria in the 02:13.510 --> 02:15.300 center of these targets. 02:16.700 --> 02:19.380 Sometimes you will find many of these 02:19.380 --> 02:22.170 targets like here in the ordinary paraffin slides 02:22.170 --> 02:24.600 stained for or 02:24.600 --> 02:26.750 hear the cry state section. 02:26.760 --> 02:29.240 And then you see many of these targets. 02:29.250 --> 02:32.100 But in some cases you 02:32.100 --> 02:34.860 only find one or two of these targets. 02:34.870 --> 02:37.790 And in all cases you can say when you see targets 02:37.800 --> 02:39.570 that it is a 02:39.580 --> 02:42.130 involvement of the lower motor 02:42.130 --> 02:42.880 neuron. 02:43.210 --> 02:45.620 You cannot say that when there is an 02:45.620 --> 02:48.200 involvement of the lower motor your 02:48.210 --> 02:48.740 neuron, 02:48.750 --> 02:50.920 you always see targets. 02:50.930 --> 02:53.400 But when you see them then you 02:53.410 --> 02:56.400 are allowed to say that this must be a 02:56.400 --> 02:59.100 disease where the lower motor 02:59.100 --> 03:01.840 neuron is involved. 03:03.210 --> 03:05.510 Another special 03:05.510 --> 03:07.800 fiber is called the linked fiber. 03:07.800 --> 03:09.490 This is a fost relay staining. 03:09.500 --> 03:12.400 And then you see these rings and the cytoplasmic 03:12.400 --> 03:15.220 masters like here you see you're running ever and 03:15.220 --> 03:17.900 Maya Federal through the psych a pleasant. 03:18.620 --> 03:21.260 And when you look upon these 03:21.270 --> 03:24.270 fibers in longitudinal sections in 03:24.270 --> 03:27.010 the tristate stained sections. 03:27.010 --> 03:29.630 Then you see these psycho plastic masses and the rink 03:29.630 --> 03:31.850 fibers and here for instance is a high 03:31.850 --> 03:34.520 oxidative enzyme activity in 03:34.530 --> 03:36.590 this cycle plastic mass, 03:37.340 --> 03:39.920 rink fibers are called rink fibers 03:39.930 --> 03:42.550 because it looks if they have a ring 03:42.550 --> 03:43.370 around them. 03:43.380 --> 03:45.770 But actually this is not a ring with a 03:45.770 --> 03:48.510 spiral and there's an aberrant Maya Federal 03:48.520 --> 03:51.180 running like a spiral along the 03:51.180 --> 03:54.090 longitudinal axis of this fiber. 03:54.100 --> 03:57.020 And of course it's not often that you 03:57.370 --> 03:59.900 cut just in the plane of this 03:59.900 --> 04:00.630 spiral. 04:00.640 --> 04:03.470 And then you can actually see see the 04:03.480 --> 04:04.160 spiral. 04:04.170 --> 04:07.150 More often it happens that you cut through the 04:07.160 --> 04:09.540 spiral and then you only see 04:09.550 --> 04:11.740 part of these aberrant maya 04:11.740 --> 04:12.630 fables. 04:13.440 --> 04:15.720 When you cut a ring 04:15.720 --> 04:17.940 fiber transfer sections, 04:17.950 --> 04:20.920 then you of course don't see a close ring 04:20.930 --> 04:23.120 because it is not a ring but a 04:23.130 --> 04:23.970 spiral. 04:23.980 --> 04:26.270 And you always find somewhere 04:26.280 --> 04:29.200 a place where the spiral begins 04:29.200 --> 04:31.710 or ends like seen here in this 04:31.720 --> 04:34.670 transfer section of this particular muscle 04:34.670 --> 04:35.320 fiber. 04:35.330 --> 04:36.260 This is an E. 04:36.260 --> 04:36.690 M. 04:37.100 --> 04:38.740 Of a rink fiber. 04:38.740 --> 04:41.590 And you can see the event Maya fables running 04:41.600 --> 04:44.130 around this transfers 04:44.140 --> 04:46.850 section of the main fiber 04:46.860 --> 04:47.520 mass. 04:48.750 --> 04:51.420 And here is a 04:51.430 --> 04:54.180 example of linked fibers 04:54.190 --> 04:57.120 and our and cytoplasmic masses in 04:57.120 --> 04:58.380 10 autopsies. 04:58.390 --> 05:00.380 Then on elderly, 05:00.390 --> 05:02.800 normal people without any neuro muscular 05:02.800 --> 05:03.620 diseases. 05:04.000 --> 05:06.770 And you see here on the left side the blue 05:06.780 --> 05:09.550 missiles and here the other missiles. 05:09.560 --> 05:12.330 And these missiles have a lot of rink 05:12.330 --> 05:14.310 fibers and psycho plastic masses. 05:14.320 --> 05:17.040 And here on the left hand side there are 05:17.040 --> 05:19.670 only a few missiles containing one or 05:19.670 --> 05:22.160 several rink fibers. 05:22.170 --> 05:24.770 The difference between the left and the 05:24.770 --> 05:27.450 right group of missiles is 05:27.460 --> 05:30.440 that here all the missiles have a tenderness 05:30.450 --> 05:32.010 insurgent to bone. 05:32.020 --> 05:34.910 And these missiles do not have any 05:34.920 --> 05:37.110 tenderness insurgent to bone. 05:37.810 --> 05:40.520 When you take a missile of a guinea 05:40.520 --> 05:43.030 pig that normally does not 05:43.030 --> 05:45.770 contain any rink fibers and you 05:45.770 --> 05:48.740 make it a missile like in the normal human 05:48.750 --> 05:51.000 just by doing a sonata me. 05:51.010 --> 05:53.750 Then after half a year you will see these 05:53.760 --> 05:56.450 ringed fibers develop and then you just 05:56.450 --> 05:58.970 cut the missile fiber, 05:58.980 --> 06:01.340 the missile on a as a whole. 06:01.350 --> 06:03.150 Then again after half a year, 06:03.160 --> 06:05.760 you see these rink fibers and cytoplasmic 06:05.760 --> 06:07.180 masses appear. 06:08.130 --> 06:11.080 So if you see in 06:11.080 --> 06:11.860 a biopsy, 06:11.870 --> 06:13.040 ring fibers. 06:13.050 --> 06:15.380 And then I think pathology 06:15.390 --> 06:18.030 is very low in rank 06:18.040 --> 06:20.790 because actually ring fibers are 06:20.790 --> 06:23.490 not pathological in every case because 06:23.490 --> 06:25.390 normal people can have them. 06:25.620 --> 06:28.380 And furthermore you can say that rink 06:28.380 --> 06:31.190 fibers will develop in any 06:31.190 --> 06:33.880 case when the normal continuity of the 06:33.880 --> 06:36.840 missile fibers has been disrupted by 06:36.850 --> 06:38.690 pathological process. 06:38.690 --> 06:41.540 For instance replacement of the missile 06:41.550 --> 06:43.110 by fed tissue. 06:43.120 --> 06:46.040 Often people say that in 06:46.050 --> 06:48.980 my atomic dystrophy you see many 06:48.990 --> 06:51.470 ring fibers and that happens to be true. 06:51.480 --> 06:52.670 But on the other hand, 06:52.680 --> 06:55.450 my atomic dystrophy is one of the few neuro 06:55.450 --> 06:57.710 muscular diseases that you can easily 06:57.720 --> 07:00.630 recognize just by physical examination 07:00.640 --> 07:03.620 and so you don't need in this particular 07:03.620 --> 07:04.230 disease. 07:04.240 --> 07:06.880 A biopsy to confirm 07:06.890 --> 07:08.460 your diagnosis. 07:09.560 --> 07:11.780 Another kind of rings scene 07:12.500 --> 07:15.230 are these Granules around some of these 07:15.230 --> 07:16.420 muscle fibers, 07:16.430 --> 07:19.110 sip psychological collections 07:19.120 --> 07:21.600 of Granules and in longitudinal 07:21.600 --> 07:22.270 sections, 07:22.280 --> 07:24.710 you will see that again 07:24.720 --> 07:27.450 there are many of these Granules 07:27.460 --> 07:30.380 present in the cycle Emel region. 07:30.910 --> 07:33.570 Sometimes the whole of the 07:33.570 --> 07:36.070 fiber of part of the fiber is 07:36.070 --> 07:36.940 involved. 07:36.950 --> 07:39.460 And all these Granules happen to be a 07:39.460 --> 07:40.450 mitochondria. 07:41.710 --> 07:44.460 When you do a tri gram stain modified, 07:44.470 --> 07:47.120 try gram stain on christ eight 07:47.120 --> 07:47.840 sections. 07:47.850 --> 07:50.570 Then you see these collections of 07:50.580 --> 07:53.200 mitochondria are stained red and 07:53.200 --> 07:55.930 therefore they are called ragged red 07:55.940 --> 07:56.790 fibers. 07:58.300 --> 07:58.870 Right. 07:58.880 --> 08:01.740 Red fibers have a very 08:01.740 --> 08:04.720 high oxidative enzyme activity because 08:04.720 --> 08:07.170 they consist of a 08:07.180 --> 08:09.920 collection and increase of uh 08:09.930 --> 08:11.010 mitochondria. 08:11.950 --> 08:14.900 And this is a higher magnification 08:14.910 --> 08:17.650 showing you the 08:17.660 --> 08:19.980 particular pattern that has gone. 08:19.990 --> 08:22.060 And all of the fibers 08:22.070 --> 08:24.750 are have a very high 08:24.760 --> 08:26.670 oxidative enzyme activity. 08:26.680 --> 08:29.410 Because most of the fibers a 08:29.420 --> 08:32.360 fiber has been replaced by 08:32.370 --> 08:33.610 mitochondria. 08:34.170 --> 08:37.040 This is an example of a paraffin slide. 08:37.050 --> 08:39.440 And here again you see this tri gram staining 08:39.440 --> 08:42.100 technique with this venue. 08:42.100 --> 08:44.990 Als And when you see a similar fiber like this 08:45.000 --> 08:47.970 in crime state section then of course all 08:47.970 --> 08:50.340 of the fiber has a very 08:50.350 --> 08:53.170 very high oxidative enzyme 08:53.180 --> 08:54.260 activity. 08:55.720 --> 08:58.190 Uh ultra structural. 08:58.400 --> 09:01.210 You see there is a collection of 09:01.850 --> 09:04.660 of mitochondria abnormal in 09:04.660 --> 09:07.160 shape and often the cursed 09:07.210 --> 09:09.380 are thickened. 09:09.390 --> 09:11.740 And here again you see the very 09:11.740 --> 09:14.520 bizarre formation and 09:14.520 --> 09:16.950 shape of this mitochondria. 09:17.560 --> 09:20.480 Most of the times in these particular 09:20.480 --> 09:23.080 collections the mitochondria are 09:23.090 --> 09:24.560 enlarged as well. 09:24.570 --> 09:27.440 And often you will find these 09:27.440 --> 09:30.400 particular uh so called para 09:30.400 --> 09:33.220 crystalline inclusions or parking lot 09:33.220 --> 09:33.990 inclusions. 09:34.000 --> 09:36.490 And these again are by no means 09:36.500 --> 09:39.390 very specific for this 09:39.400 --> 09:41.370 group of diseases. 09:42.810 --> 09:45.750 Uh sometimes these diseases 09:45.750 --> 09:48.610 or myopathy czar called mitochondrial myopathy. 09:48.620 --> 09:51.160 But the only thing they have in common is a 09:51.170 --> 09:53.670 increase of collections of 09:53.670 --> 09:56.300 mitochondria and you can have all 09:56.300 --> 09:58.380 kinds of muscular involvement, 09:58.390 --> 10:00.980 all kinds of other manage stations. 10:01.020 --> 10:03.450 And so when you see these 10:03.450 --> 10:04.350 mitochondria, 10:04.360 --> 10:06.820 you cannot say this is a mitochondrial disease. 10:06.830 --> 10:09.390 You only say that this is a 10:09.390 --> 10:12.030 myopathy with abnormal mitochondria. 10:12.040 --> 10:14.970 And then there are many possibilities left for a 10:14.980 --> 10:17.440 correct diagnosis in these cases. 10:20.380 --> 10:22.590 Another red 10:23.190 --> 10:25.880 collection in the diagram stain 10:26.440 --> 10:29.240 is the formation of so called tubular 10:29.240 --> 10:30.040 agra grades. 10:30.880 --> 10:33.630 And here you see this 10:33.640 --> 10:36.320 these two braga grades are only 10:36.320 --> 10:38.190 found in the dark fibers. 10:38.200 --> 10:39.930 Type two fibers. 10:39.930 --> 10:40.560 This is an A. 10:40.560 --> 10:40.710 T. 10:40.710 --> 10:40.920 P. 10:40.920 --> 10:41.090 S. 10:41.650 --> 10:41.930 A. 10:41.930 --> 10:42.090 T. 10:42.090 --> 10:42.290 P. 10:42.290 --> 10:43.040 A staining. 10:43.050 --> 10:45.820 And here again you 10:45.820 --> 10:48.820 see that in the light fibers there 10:48.820 --> 10:51.780 are there are collections 10:51.780 --> 10:54.040 of tubular Agra greats with a very high 10:54.040 --> 10:56.350 oxidative enzyme activity. 10:56.360 --> 10:58.390 That is to say when you use any D. 10:58.390 --> 10:58.740 H. 10:58.750 --> 11:00.470 Oxydol reductase 11:00.480 --> 11:03.220 methods on the other hand, 11:03.220 --> 11:05.470 the typical so called mitochondrial 11:05.470 --> 11:07.390 enzyme like 16 11:07.570 --> 11:10.020 hydrogen has no 11:10.030 --> 11:12.940 increase of his 11:12.950 --> 11:15.230 activity in this particular fibers. 11:15.240 --> 11:17.920 These are the type to fibers and here are the tubular 11:17.920 --> 11:20.910 aggregate but they have no increase 11:20.910 --> 11:23.130 of their this particular enzyme 11:23.130 --> 11:24.160 activity. 11:24.170 --> 11:26.690 And the same is true for this particular enzyme. 11:26.700 --> 11:29.690 Here are dark fibers are type two fibers and again 11:29.700 --> 11:32.250 no activity is seen in these 11:32.250 --> 11:32.900 regions. 11:32.910 --> 11:35.120 So apparently these are not 11:35.130 --> 11:36.060 mitochondria 11:37.330 --> 11:39.790 and there are two bills 11:39.800 --> 11:42.770 like seen here at the ultra structural level 11:42.780 --> 11:45.570 and therefore they are called tubular agra 11:45.570 --> 11:46.120 grids. 11:47.160 --> 11:49.920 Uh people still 11:49.920 --> 11:52.300 think that these are derived from 11:52.300 --> 11:53.240 mitochondria. 11:53.250 --> 11:56.100 but other people think that they 11:56.110 --> 11:58.990 consist of a market proliferation of 11:59.000 --> 12:01.110 the psycho plastic ridiculous. 12:02.000 --> 12:04.840 So when we see the features 12:04.850 --> 12:06.370 of these tubular aggregates, 12:06.380 --> 12:08.790 you can say that with the 12:08.790 --> 12:11.770 mitochondrial collections sub cycle 12:11.770 --> 12:14.360 um a collection of mitochondria they have in common 12:14.490 --> 12:17.490 that they stay in bright red with the modified tri 12:17.490 --> 12:18.170 gram stain. 12:18.180 --> 12:20.940 And both of them have no activity 12:20.950 --> 12:22.620 of minors in a TPS. 12:22.630 --> 12:25.510 But the big difference is the tuba aggregates 12:25.510 --> 12:28.320 are only situated in Type two fibers 12:28.330 --> 12:30.250 while the mitochondrial 12:30.260 --> 12:33.170 accumulations are often seen in 12:33.170 --> 12:34.270 Type one fibers. 12:34.280 --> 12:37.110 Although they can be found also 12:37.120 --> 12:38.420 in Type two fibers. 12:38.710 --> 12:41.480 And then of course mitochondrial 12:41.490 --> 12:44.030 AGRA grades have a high 12:44.030 --> 12:47.020 activity for these enzymes as 12:47.020 --> 12:47.530 well. 12:50.340 --> 12:53.100 Now I come to seven patients we saw 12:54.720 --> 12:55.760 recently, 12:56.760 --> 12:59.440 Men and women and you can see 12:59.440 --> 13:02.190 that this is a disease with a very 13:02.190 --> 13:04.660 long duration 25 years or 13:04.660 --> 13:05.980 13 years. 13:05.990 --> 13:08.670 And these people suffered from a 13:08.680 --> 13:11.270 very slowly progressive a 13:11.270 --> 13:13.830 proximal myopathy limb girdle type of 13:13.840 --> 13:16.730 myopathy without any special 13:16.730 --> 13:17.420 features. 13:17.960 --> 13:20.930 These little white stars means there is a 13:20.930 --> 13:23.650 slight elevation of the CPK level in the 13:23.650 --> 13:24.430 serum. 13:24.440 --> 13:26.160 But you see that this man, 13:26.160 --> 13:29.080 for instance has the disease for 25 years. 13:29.090 --> 13:32.030 And this man has also for 25 13:32.030 --> 13:34.810 years but his CPK is 13:34.810 --> 13:37.730 normal and this is just slightly elevated. 13:38.440 --> 13:40.970 So we had the hope that we could 13:40.970 --> 13:43.680 diagnose these cases by means of 13:43.690 --> 13:46.640 missile biopsy and I will now show you the 13:46.640 --> 13:49.260 missile biopsy of a few of these 13:49.260 --> 13:49.840 cases. 13:49.850 --> 13:52.820 And first of all you see here and transfer 13:52.820 --> 13:55.160 section of a perfect slide 13:55.160 --> 13:56.910 state stained with H. 13:56.910 --> 13:57.670 And E. 13:57.680 --> 14:00.550 And there's nothing much to 14:00.550 --> 14:01.380 see. 14:01.390 --> 14:04.150 There's a normal diameter of most of the 14:04.150 --> 14:04.930 fibers. 14:04.940 --> 14:07.200 There's no increase of fat tissue or 14:07.580 --> 14:09.500 increase of connective tissue. 14:09.500 --> 14:11.630 There are no cellular infiltrates. 14:11.640 --> 14:14.490 But yet you can see in this fiber 14:14.500 --> 14:17.430 very tiny little factual. 14:17.440 --> 14:20.200 And you see here in this fiber three 14:20.210 --> 14:21.710 factual as well. 14:22.510 --> 14:25.170 Another biopsy of another patient shows 14:25.170 --> 14:26.950 more of these vegetables. 14:26.970 --> 14:29.590 For instance here in many of the fibers 14:29.800 --> 14:31.270 are very large 14:31.850 --> 14:34.150 Victuals and some of the fibers. 14:35.230 --> 14:36.460 Another possibility. 14:36.460 --> 14:38.710 This is a crisis state section state with H. 14:38.710 --> 14:39.390 And T. 14:39.400 --> 14:42.230 Is that most of the fibers are normal and 14:42.230 --> 14:44.770 just one single fiber is involved. 14:44.780 --> 14:47.620 And then you see these very very many 14:47.630 --> 14:49.110 of these very tiny 14:49.120 --> 14:50.880 vegetables. 14:51.810 --> 14:54.640 Uh The solution is that 14:54.650 --> 14:56.940 when you see a child with the same 14:56.950 --> 14:59.540 uh kind of disease 14:59.550 --> 15:02.110 then it's called uh 15:02.460 --> 15:03.070 gino sis. 15:03.070 --> 15:04.530 This is pompous disease. 15:04.540 --> 15:07.460 And of course then there are no difficulties 15:07.470 --> 15:10.150 and recognizes in recognizing 15:10.160 --> 15:12.510 these particular cases. 15:12.520 --> 15:14.510 And when you do a P. 15:14.510 --> 15:14.640 A. 15:14.640 --> 15:14.840 S. 15:14.840 --> 15:17.220 Staining then of course you see the 15:17.230 --> 15:18.910 accumulation of P. 15:18.910 --> 15:19.000 A. 15:19.000 --> 15:19.240 S. 15:19.240 --> 15:21.000 Positive material. 15:21.550 --> 15:23.900 And all these patients 15:23.910 --> 15:26.380 showed seven patients were suffering 15:26.390 --> 15:28.810 from type two sm smell test 15:28.820 --> 15:30.020 deficiency. 15:30.030 --> 15:32.570 Type two uh 15:32.580 --> 15:34.130 glycogen storage disease. 15:34.140 --> 15:36.460 And in Children this is called pompous 15:36.460 --> 15:37.270 disease. 15:37.810 --> 15:40.780 You see that there are eight types 15:40.790 --> 15:42.900 and in many of these types. 15:42.910 --> 15:45.650 The missiles are involved as well. 15:45.660 --> 15:47.930 Andersons disease is very rare 15:47.940 --> 15:50.460 and forceful frank 15:50.460 --> 15:53.320 tokens deficiency also 15:53.330 --> 15:56.320 is very rare in the built patients. 15:58.390 --> 15:59.880 In most of these 15:59.890 --> 16:02.410 cases you can 16:02.420 --> 16:05.390 diagnose the enzyme deficiency 16:05.400 --> 16:07.740 by biochemical as say. 16:07.750 --> 16:09.100 And as a matter of fact, 16:09.110 --> 16:11.770 the seven patients I have shown the 16:11.780 --> 16:14.190 muscle tissue and leukocyte 16:14.200 --> 16:17.050 uh did not contain 16:17.060 --> 16:19.830 the asset melters 16:19.840 --> 16:21.160 enzyme. 16:23.940 --> 16:26.690 So in this particular group of 16:26.690 --> 16:27.300 diseases, 16:27.300 --> 16:30.240 glycogen storage diseases or glycogen Gnosis, 16:30.250 --> 16:32.980 biochemistry is the main thing 16:32.990 --> 16:34.910 for a correct diagnosis. 16:34.920 --> 16:37.510 Pathology may give you a 16:37.520 --> 16:40.500 clue when you see as is in 16:40.500 --> 16:42.640 the case in melted deficiency. 16:42.650 --> 16:45.150 When you see these Victuals. 16:45.160 --> 16:46.120 And by the way, 16:46.120 --> 16:48.910 these Victuals show a very high 16:48.920 --> 16:51.850 activity of a license thermal 16:51.860 --> 16:54.780 enzyme that is 16:54.790 --> 16:55.750 acid phosphate. 16:59.450 --> 17:02.230 Sometimes just the 17:02.230 --> 17:05.060 histone pathology may give you the 17:05.070 --> 17:06.630 correct diagnosis. 17:06.640 --> 17:07.710 For instance, 17:07.720 --> 17:10.600 as seen here in central 17:10.600 --> 17:11.570 core disease, 17:11.580 --> 17:14.440 the central cost and blue 17:14.450 --> 17:17.430 but it is very difficult to recognize them in an 17:17.430 --> 17:19.510 H and E stained section. 17:19.520 --> 17:22.320 And this is a long funeral section and again, 17:22.330 --> 17:25.070 you see easily these blue stained 17:25.080 --> 17:27.800 cause and it's very difficult to recognize them 17:27.810 --> 17:29.760 here in the H and E. 17:31.020 --> 17:33.600 This happened to be our first case of 17:33.610 --> 17:34.750 central core disease. 17:34.750 --> 17:37.340 And again you see the cars 17:37.350 --> 17:39.830 running along the longitudinal 17:40.340 --> 17:42.840 section of these particular 17:42.840 --> 17:45.680 fibers and all the cores are staying 17:45.680 --> 17:46.340 blue 17:48.730 --> 17:51.440 when you do cry state sections in these cases 17:51.450 --> 17:54.320 you see that the courts are found only in 17:54.320 --> 17:55.770 type one fibers. 17:55.780 --> 17:58.700 The light fibers here in the Maya february https 17:58.700 --> 18:01.290 staying are type one. 18:01.300 --> 18:03.770 And here the dark fibers are of type one. 18:03.780 --> 18:05.590 So you see many 18:05.880 --> 18:08.100 uh type one fibers 18:08.100 --> 18:10.590 containing these costs 18:10.630 --> 18:12.690 and this is another patient. 18:12.700 --> 18:15.320 And then you see that almost all type one 18:15.320 --> 18:17.850 fibers contain one or several 18:17.850 --> 18:20.780 cost and none of the type 18:20.790 --> 18:23.280 two fibers show any course at all. 18:25.030 --> 18:27.570 This is a higher magnification of a core 18:27.570 --> 18:30.500 region showing you that this region 18:30.500 --> 18:33.350 is devoid of any enzyme activity and that's 18:33.350 --> 18:35.680 because there are no mitochondria 18:35.690 --> 18:38.640 mitochondria in this particular area of 18:38.650 --> 18:39.690 the muscle fiber. 18:39.700 --> 18:42.280 And this is a transfer section showing 18:42.280 --> 18:45.250 again that the oxidative enzyme 18:45.250 --> 18:47.530 activity is present at the 18:47.540 --> 18:50.180 peripheral rim with this core 18:50.180 --> 18:53.130 region is almost devoid of enzyme 18:53.140 --> 18:53.980 activity. 18:56.660 --> 18:59.140 Another morphological feature 18:59.150 --> 19:01.700 readily seen is the 19:01.700 --> 19:03.990 formation of rods and this is a case of 19:03.990 --> 19:06.520 congenital name allene myopathy. 19:07.250 --> 19:10.010 And here is a transfer 19:10.010 --> 19:11.390 section of another case. 19:11.400 --> 19:14.300 And then it's very difficult to recognize the 19:14.300 --> 19:16.210 fiber not containing any roads. 19:16.210 --> 19:18.560 Most of the fibers contained rods 19:18.570 --> 19:21.090 and as you will see here, 19:21.100 --> 19:23.810 most of the roads have a sub 19:23.810 --> 19:25.470 cycle level position. 19:25.480 --> 19:28.260 But of course sometimes you see them in the 19:28.260 --> 19:30.510 middle of the fibers as well. 19:30.520 --> 19:33.000 And this is in direct microscopic 19:33.010 --> 19:35.790 picture showing you the sub cycle 19:35.970 --> 19:38.310 collections of these rods 19:39.200 --> 19:42.160 and the next one shows 19:42.160 --> 19:45.000 you that also in the interior 19:45.010 --> 19:47.520 of the fiber rods are 19:47.530 --> 19:48.390 present. 19:48.400 --> 19:49.660 And as you know, 19:49.670 --> 19:52.380 these rods derived from the C. 19:52.390 --> 19:54.430 Disk as seen here, 19:56.800 --> 19:59.260 another feature morphological feature of 19:59.270 --> 20:02.220 mammalian myopathy is a type 20:02.230 --> 20:05.120 one fiber predominance or as 20:05.120 --> 20:07.980 you can call it also type two fiber 20:07.990 --> 20:08.700 positive. 20:09.890 --> 20:11.980 And this is an 20:11.990 --> 20:14.540 example of a patient suffering from 20:14.540 --> 20:17.300 mammalian myopathy and it's obvious 20:17.310 --> 20:20.130 that this is an auto Zamel dominantly 20:20.140 --> 20:21.960 inherited disease. 20:23.190 --> 20:23.760 However, 20:23.760 --> 20:26.670 this is another case of typical mammalian 20:26.670 --> 20:29.590 myopathy and this 20:29.590 --> 20:32.340 patient has a healthy mother and 20:32.340 --> 20:33.770 unhealthy father. 20:36.330 --> 20:36.960 So 20:38.270 --> 20:41.050 uh you can say that is 20:41.050 --> 20:43.530 a AutoZone dominantly inherited 20:43.530 --> 20:46.130 disease called family myopathy. 20:46.140 --> 20:48.830 And maybe there is another disease 20:48.840 --> 20:51.740 that is a recessive inherited 20:51.750 --> 20:54.200 kind of Nummelin myopathy. 20:54.210 --> 20:56.390 So far there are seven 20:56.630 --> 20:58.590 publications of 20:58.600 --> 21:01.510 authors who have examined in cases 21:01.510 --> 21:02.930 of normally myopathy, 21:02.940 --> 21:05.200 the mother and the father as well. 21:05.210 --> 21:07.350 And then you see that in four of these 21:07.360 --> 21:10.220 cases the murder was suffering from muscular 21:10.220 --> 21:12.920 weakness and in two of these cases 21:12.930 --> 21:15.840 the mother was showing rods in her 21:15.840 --> 21:17.400 muscle biopsy as well. 21:17.410 --> 21:20.330 So apparently these are examples 21:20.340 --> 21:21.250 of autism, 21:21.250 --> 21:23.760 all dominantly inherited kind of 21:23.770 --> 21:26.300 type of Nummelin myopathy. 21:26.490 --> 21:27.860 But on the other hand, 21:27.870 --> 21:30.470 there are many patients with completely 21:30.470 --> 21:32.810 healthy fathers and mothers 21:32.820 --> 21:35.390 and non no 21:35.400 --> 21:37.620 roads in the biopsies 21:39.490 --> 21:40.300 dr arts. 21:40.300 --> 21:43.130 In our laboratory had the opportunity to examine 21:43.140 --> 21:45.910 six patients suffering from 21:46.080 --> 21:47.420 lean myopathy. 21:47.430 --> 21:50.080 And in all these patients the father and the murders 21:50.090 --> 21:53.040 were examined and then you see there's only one murder 21:53.050 --> 21:55.740 showing muscular weakness and in all the other 21:55.740 --> 21:58.470 cases no muscular weakness was was 21:58.480 --> 21:59.100 present. 21:59.110 --> 22:02.080 Yet in two parents, 22:02.090 --> 22:03.330 two pair of parents. 22:03.340 --> 22:05.260 There were rots in there 22:05.700 --> 22:08.510 In the biopsy and this was 22:08.510 --> 22:11.070 confirmed in three cases by electron 22:11.070 --> 22:11.990 microscopy. 22:14.540 --> 22:17.360 So coming back to that particular 22:17.360 --> 22:20.000 patient patient I showed you 22:20.010 --> 22:22.960 this patient is suffering from muscular weakness 22:23.560 --> 22:26.490 and he is showing rods in his biopsy. 22:27.550 --> 22:30.520 His pants are completely normal, 22:30.530 --> 22:33.500 but in the biopsy they 22:33.500 --> 22:35.640 also show rods. 22:35.650 --> 22:38.270 And that means that this is a auto so more 22:38.280 --> 22:40.660 recessive mode of transmission 22:42.210 --> 22:44.390 when you see rods in the missile biopsy. 22:44.400 --> 22:46.850 That by no means means that you 22:46.860 --> 22:49.220 have to do with a rod 22:49.230 --> 22:50.080 myopathy. 22:50.090 --> 22:52.650 Because ever since a 50 22:53.010 --> 22:55.740 in 1965 found rods 22:55.750 --> 22:58.540 so called secondary roads in central core 22:58.540 --> 22:59.000 disease. 22:59.010 --> 23:01.480 Almost every year year there has been 23:01.480 --> 23:04.070 somebody who found rods 23:04.080 --> 23:07.050 in all these kinds of different 23:07.060 --> 23:08.640 missile diseases. 23:10.690 --> 23:13.240 And this is an example of 23:13.320 --> 23:14.710 central Curtis's. 23:14.780 --> 23:17.220 This is the core showing 23:17.760 --> 23:20.540 like microscopically Rod's collection of 23:20.540 --> 23:22.990 sub cycle lemon rods and this is the E. 23:22.990 --> 23:23.420 M. 23:23.430 --> 23:25.010 Of the same patient. 23:27.320 --> 23:30.130 Another kind of morphological 23:30.140 --> 23:32.810 uh change in the 23:32.820 --> 23:35.820 missile fiber is the so called focal loss 23:35.830 --> 23:37.150 of cross stations. 23:37.160 --> 23:38.770 This is in trans first section. 23:38.780 --> 23:39.670 And first of all, 23:39.670 --> 23:42.560 you see the white variation of the 23:43.400 --> 23:45.260 diameter of the missile fibers. 23:45.260 --> 23:45.990 And moreover, 23:45.990 --> 23:48.670 you see the increase of internal nuclei 23:51.370 --> 23:53.980 trans in longitudinal sections 23:53.990 --> 23:55.020 stained with P. 23:55.020 --> 23:55.200 T. 23:55.200 --> 23:55.730 H. 23:55.740 --> 23:58.640 You will see that all of a sudden there is a loss 23:58.640 --> 24:01.630 of cross striations in these particular parts of the 24:01.630 --> 24:02.820 muscle fibers. 24:02.830 --> 24:03.950 And moreover, 24:03.950 --> 24:06.800 you will see see that in these particular 24:06.800 --> 24:09.560 regions there are many 24:09.570 --> 24:11.070 nuclei, 24:11.080 --> 24:13.140 this particular nuclear line. 24:13.150 --> 24:16.060 And again this is showing you a case 24:16.070 --> 24:18.270 of so called focal loss of cross 24:18.270 --> 24:19.160 creation. 24:19.170 --> 24:22.160 And here again you can see there 24:22.160 --> 24:24.560 are no cross striations in these particular 24:24.560 --> 24:25.240 areas. 24:25.250 --> 24:27.680 And again there is an increase of particular 24:27.680 --> 24:30.670 nuclei and you can see that the 24:30.680 --> 24:33.000 transition between normal and 24:33.010 --> 24:35.410 abnormal is very sharp. 24:35.950 --> 24:38.600 And here again is a chris state 24:38.600 --> 24:41.000 section stained for oxford enzyme 24:41.000 --> 24:41.890 activity. 24:41.900 --> 24:44.900 And in these zones where 24:44.900 --> 24:47.540 the loss of cross striations is 24:47.540 --> 24:48.170 present, 24:48.180 --> 24:49.680 there is no activity. 24:49.690 --> 24:51.470 And that is because there are no 24:51.480 --> 24:54.400 mitochondria as shown here in the 24:54.400 --> 24:54.560 E. 24:54.560 --> 24:54.750 M. 24:54.750 --> 24:55.470 Picture. 24:55.480 --> 24:58.300 This is the normal part of the missile showing 24:58.300 --> 25:01.230 many mitochondria and all of a sudden there's a 25:01.230 --> 25:04.120 very sharp transitional zone 25:04.120 --> 25:05.900 between normal and abnormal. 25:05.900 --> 25:08.680 This is the focal loss of cross creations 25:08.690 --> 25:11.660 zone and there is a streaming of the Z. 25:11.660 --> 25:14.660 Discs and there is no mitochondria. 25:16.440 --> 25:19.120 And again like in other types of 25:19.130 --> 25:21.500 so called congenital myopathy. 25:21.510 --> 25:24.290 You will see there is a type two 25:24.290 --> 25:27.230 positively or Type one predominance 25:29.410 --> 25:31.390 more often in these cases of 25:31.400 --> 25:34.070 uh focal loss of cross 25:34.070 --> 25:34.760 striations, 25:34.760 --> 25:37.680 there is not only a Type one predominance 25:37.690 --> 25:40.540 but the type one fibers are 25:40.550 --> 25:41.200 too small. 25:41.200 --> 25:43.880 So there is a type one fiber hypertrophy 25:43.890 --> 25:46.880 according to Brooke and angle the 25:46.890 --> 25:49.750 normal diameter of this boy 25:49.760 --> 25:52.340 whose age is six years 25:52.350 --> 25:54.750 is 30 to 40 25:54.760 --> 25:55.590 microns. 25:55.600 --> 25:58.280 And you can see that his 25:58.280 --> 26:00.520 mean diameter is much 26:00.530 --> 26:01.310 smaller. 26:03.160 --> 26:05.400 So in focal loss of cross 26:05.400 --> 26:06.250 striations. 26:06.280 --> 26:07.630 Central core disease. 26:07.640 --> 26:09.220 Normally myopathy 26:09.820 --> 26:11.770 Pathology is # one. 26:12.310 --> 26:15.140 It's very important to know 26:16.160 --> 26:18.900 that when you see things 26:18.900 --> 26:21.660 like for instance a core 26:21.670 --> 26:22.540 or a rod, 26:22.550 --> 26:25.290 then you cannot diagnose this case 26:25.290 --> 26:26.950 without a muscle biopsy. 26:26.960 --> 26:28.340 On the other hand, 26:28.350 --> 26:31.050 I think it's you're not justified to 26:31.050 --> 26:33.100 say that a disease 26:33.110 --> 26:35.820 is rot myopathy 26:35.820 --> 26:38.440 because you see rods and I will give 26:38.440 --> 26:40.910 you an example of this 26:40.910 --> 26:43.190 particular difficulty we 26:43.190 --> 26:44.840 can encounter. 26:45.180 --> 26:48.150 This is a pedigree showing you a 26:48.150 --> 26:50.360 boy suffering from a congenital 26:50.370 --> 26:52.020 progressive myopathy. 26:53.450 --> 26:55.950 He has five completely 26:55.960 --> 26:58.810 normal healthy sisters and his 26:58.810 --> 27:01.580 mother and his father both are very, 27:01.590 --> 27:02.540 very healthy. 27:04.870 --> 27:07.520 Now I show you first of all the 27:07.530 --> 27:10.030 muscle tissue of this boy. 27:10.040 --> 27:12.910 And first of all you see that there is again 27:12.920 --> 27:14.940 a Type one predominance. 27:14.950 --> 27:17.880 All these type all these fibers are of 27:17.880 --> 27:18.600 type one. 27:20.690 --> 27:23.140 And then you see that he 27:23.150 --> 27:26.010 also has focal loss of cross 27:26.010 --> 27:28.990 striations here and there are no 27:29.000 --> 27:30.610 cross striations scene. 27:30.620 --> 27:31.810 And moreover, 27:31.820 --> 27:34.400 he has the typical collections of 27:34.500 --> 27:36.440 these particular nuclei. 27:37.940 --> 27:40.420 But in another part of his 27:40.430 --> 27:42.770 biopsy we found the 27:42.770 --> 27:45.740 collection of rods and this by the 27:45.740 --> 27:47.990 way was confirmed by electron 27:47.990 --> 27:48.880 microscopy. 27:50.920 --> 27:53.850 Then we did a biopsy in the deltoid 27:53.850 --> 27:56.660 missile of his completely normal father 27:56.660 --> 27:59.430 without any signs or symptoms of 27:59.440 --> 28:01.020 neuro muscular disease. 28:01.030 --> 28:03.210 And then you see this father 28:03.220 --> 28:06.220 also shows a predominance 28:06.230 --> 28:09.070 of Type one fibers or a positive of type 28:09.080 --> 28:09.780 two fibers. 28:09.790 --> 28:11.070 And moreover, 28:11.710 --> 28:12.680 These fibers, 28:13.170 --> 28:15.680 type two fibers angular dated and 28:15.680 --> 28:16.240 small. 28:18.020 --> 28:20.840 And this healthy man also 28:20.850 --> 28:23.350 showed collections of rods 28:23.360 --> 28:25.740 in the cryo states section stand 28:25.750 --> 28:28.400 for with a 28:28.410 --> 28:30.050 modified try growing state. 28:30.980 --> 28:33.790 Now I will show you The missile 28:33.790 --> 28:36.620 biopsy of the murder and she has a 28:36.620 --> 28:39.400 beautiful normal mosaic 28:39.410 --> 28:42.120 pattern of type one and type two 28:42.120 --> 28:42.920 fibers. 28:43.490 --> 28:45.760 But this lady again 28:45.770 --> 28:48.740 showed collections of roads 28:48.750 --> 28:51.480 and the modified tri 28:51.480 --> 28:52.520 gram stain. 28:53.130 --> 28:56.040 So when we look at the 28:56.040 --> 28:57.750 pathology in these cases, 28:57.760 --> 29:00.230 you can say that these 29:00.240 --> 29:02.720 people had rods 29:02.730 --> 29:05.640 and their son had rods and focal 29:05.640 --> 29:07.060 loss of cross striations. 29:09.140 --> 29:10.150 And you compare 29:11.420 --> 29:13.940 pathology with muscular 29:13.940 --> 29:14.520 weakness. 29:14.530 --> 29:16.900 Then you can say this 29:16.910 --> 29:19.420 apparently is an auto so more recessive 29:19.430 --> 29:20.180 disease. 29:20.190 --> 29:21.890 But that's all you can say. 29:22.420 --> 29:25.380 You are not allowed to say that this boy is suffering from 29:25.380 --> 29:28.130 Hamelin myopathy with some 29:28.140 --> 29:29.970 focal loss of crustaceans. 29:29.980 --> 29:32.970 And you are not allowed to say that he is suffering from 29:32.980 --> 29:35.450 focal loss of crustaceans with the formation of 29:35.450 --> 29:36.790 some rods. 29:36.800 --> 29:39.560 The name of this disease as yet 29:39.570 --> 29:40.970 is not known. 29:40.980 --> 29:43.650 And the same problem we had with the 29:43.660 --> 29:46.410 other family in which the 29:46.410 --> 29:48.500 disease apparently was autism, 29:48.500 --> 29:51.220 A dominantly dominant inherited. 29:51.500 --> 29:53.360 And here you see the grand matter, 29:54.090 --> 29:56.700 Her son and a little girl 8 29:56.710 --> 29:57.260 7. 29:57.270 --> 29:58.270 When we saw her, 29:58.620 --> 30:01.210 I first will show you a few slides 30:01.470 --> 30:02.880 of the grand murder. 30:04.290 --> 30:06.920 And here again you see the 30:06.920 --> 30:09.810 cycle sub cycle Imo collections of 30:09.810 --> 30:10.310 roads. 30:10.320 --> 30:13.240 Beautiful roads are seen here and there is an 30:13.240 --> 30:15.050 increase of vesicular nuclei. 30:15.060 --> 30:17.810 And another picture of her 30:17.820 --> 30:20.710 biopsy shows again the sub cycle M. 30:20.710 --> 30:20.800 O. 30:20.800 --> 30:22.910 Collections of these rods 30:22.920 --> 30:24.120 everywhere. 30:24.130 --> 30:26.570 And I must say that seven years 30:26.570 --> 30:29.450 ago I diagnosed this case as a 30:29.460 --> 30:31.880 case of normal in myopathy. 30:33.020 --> 30:35.460 Now I will show you a picture 30:35.880 --> 30:37.850 of a vessel biopsy of her sin, 30:38.420 --> 30:40.660 the father of this little girl. 30:40.670 --> 30:42.990 And then you see that this 30:43.000 --> 30:45.610 man shows focal 30:45.610 --> 30:47.580 loss of cross striations. 30:47.590 --> 30:50.340 Typical picture of focal loss of cross striations. 30:51.230 --> 30:53.820 And here is in a state section 30:53.820 --> 30:56.820 showing you the loss of enzyme 30:56.830 --> 30:59.790 activity in these regions because I know 30:59.800 --> 31:02.490 mitochondria and this 31:02.490 --> 31:05.400 is again a very sharp 31:05.410 --> 31:07.600 demarcation between normal and 31:07.610 --> 31:08.590 abnormal. 31:08.600 --> 31:09.640 But moreover, 31:09.640 --> 31:12.440 you see a collection of rods here 31:12.450 --> 31:15.180 and a collection of rods there and this again 31:15.190 --> 31:17.690 was confirmed by 31:17.690 --> 31:20.630 electron microscopic investigations. 31:22.490 --> 31:25.390 And now I'll show you the biopsy of 31:25.400 --> 31:28.140 this seven years old girl. 31:28.150 --> 31:30.240 And she again 31:30.250 --> 31:33.250 showed a typical picture morphological 31:33.250 --> 31:35.830 picture of focal loss of cross station. 31:37.100 --> 31:39.040 Here is a beautiful 31:39.050 --> 31:40.130 zone. 31:40.140 --> 31:42.350 All the cross stations are 31:42.350 --> 31:43.150 lost. 31:43.160 --> 31:45.430 And here is the 31:45.430 --> 31:48.130 collection of physical er 31:48.130 --> 31:48.820 nuclei. 31:48.830 --> 31:50.600 And again this 31:50.610 --> 31:53.150 lady showed 31:54.130 --> 31:56.670 a collection of rods seen at the ultra 31:56.670 --> 31:57.590 structure level. 31:58.350 --> 32:00.440 So when we compare 32:01.720 --> 32:04.220 pathology with clinical 32:04.220 --> 32:04.750 features, 32:04.750 --> 32:07.390 then you see that the grandmother 32:07.400 --> 32:09.820 had normally myopathy 32:09.830 --> 32:12.350 because he had so many name a leans. 32:12.360 --> 32:15.220 But after re examination of 32:15.230 --> 32:17.850 her biopsy I found two fibers, 32:17.850 --> 32:20.480 just two fibers showing focal loss of cross 32:20.480 --> 32:21.160 station. 32:21.700 --> 32:23.800 And this man showed both of them. 32:23.810 --> 32:26.160 And this little girl showed 32:26.170 --> 32:29.050 mainly focal loss of crustaceans with a 32:29.050 --> 32:31.710 few uh rods 32:31.720 --> 32:33.990 seen at the ultra structure level. 32:34.740 --> 32:37.350 And when we compare these two 32:37.360 --> 32:39.910 muscular weakness and the pathology again, 32:39.920 --> 32:42.770 the only thing you can say is that there is 32:42.770 --> 32:45.160 a lot a zonal dominantly 32:45.170 --> 32:47.030 inherited myopathy. 32:47.550 --> 32:50.220 And you cannot say that 32:50.230 --> 32:53.060 this girl is suffering from mammalian myopathy 32:53.070 --> 32:55.620 with rods with 32:55.630 --> 32:58.500 uh focal loss of crustacean or her 32:58.500 --> 33:01.350 grandmother from focal loss of crustaceans with 33:01.350 --> 33:01.820 rods. 33:01.830 --> 33:04.200 Of course all these people are suffering 33:04.210 --> 33:06.320 from the same disease. 33:06.330 --> 33:08.840 And this last picture gives you 33:08.850 --> 33:10.560 a symbolic 33:11.160 --> 33:13.850 impression of what I like to say. 33:13.950 --> 33:16.320 This is a painting 33:16.920 --> 33:19.370 of the well known dutch artist Asher 33:19.380 --> 33:22.350 for this reason for this occasion stained with 33:22.360 --> 33:25.160 a and then you 33:25.160 --> 33:27.690 see that there are people who have 33:27.690 --> 33:30.450 caused in their biopsy 33:31.120 --> 33:34.020 and there are people who have focal loss and there are 33:34.020 --> 33:36.820 people with formation of roads. 33:36.830 --> 33:39.400 But in some biopsies you can 33:39.400 --> 33:42.100 find cause and roads or you can 33:42.100 --> 33:44.340 find focal loss and roads. 33:44.350 --> 33:46.140 And so far, 33:46.150 --> 33:49.070 I've never came across a biopsy in 33:49.070 --> 33:52.050 which you see cause and focal loss together. 33:52.940 --> 33:55.590 So I hope that I have given 33:55.590 --> 33:58.290 you at least an impression of some of the 33:58.290 --> 34:00.490 pathological reactions of muscle 34:00.490 --> 34:01.470 tissue. 34:01.480 --> 34:04.120 In conclusion we can say that muscle 34:04.120 --> 34:06.270 pathology can be the answer too many 34:06.270 --> 34:09.220 questions and in some cases may even be 34:09.220 --> 34:10.490 the very last answer. 34:11.150 --> 34:14.100 MR pathology often shows a lot of 34:14.100 --> 34:16.940 non specific reactions and in these 34:16.940 --> 34:19.250 cases gives no answer at all. 34:19.420 --> 34:21.790 Mr pathology may be dangerous 34:21.800 --> 34:24.390 because it can tempt people to name a 34:24.390 --> 34:27.040 disease after only one pathological 34:27.040 --> 34:29.590 feature seen under the microscope. 34:29.710 --> 34:30.340 Both all, 34:30.350 --> 34:31.310 however, 34:31.320 --> 34:34.050 we must be aware that MR pathology is 34:34.050 --> 34:37.040 just one of the many ways that can lead to 34:37.040 --> 34:38.440 a correct diagnosis. 34:38.450 --> 34:39.260 Thank you.