WEBVTT 00:00.000 --> 00:00.666 [...] 00:00.666 --> 00:19.166 [The National Institute of Neurological and Communicative Disorders and Stroke] 00:19.166 --> 00:22.599 [Presents] 00:22.600 --> 00:39.833 [The Clinical Syndrome of A-L-S; Mayo Clinic, Rochester, Minnesota; Donald W. Mulder, M.D.] 00:39.833 --> 00:44.733 [...] 00:44.733 --> 00:45.799 [Color bars test pattern] 00:45.800 --> 00:46.666 [Audio technician says "sound"] 00:46.666 --> 00:49.832 [Donald W. Mulder, MD:] Thank you, Dr. Engel. 00:49.833 --> 00:51.599 Ladies and gentlemen. 00:51.600 --> 00:56.000 Dr. Engel has asked me to discuss with you this afternoon 00:56.000 --> 01:00.766 a clinical syndrome of amyotrophic lateral sclerosis. 01:00.766 --> 01:04.399 Perhaps in discussing this syndrome, I should rather discuss 01:04.400 --> 01:07.400 rather than knowledge by ignorance of the syndrome. 01:07.400 --> 01:11.266 Because, in truth, we know very little about this disease 01:11.266 --> 01:14.866 beside that which was described many year s ago. 01:14.866 --> 01:19.532 The first description that we know of was out of Aran. 01:19.533 --> 01:22.866 And there really is very little that we can add to that syndrome [F.A. Aran, 1850...projected slide] 01:22.866 --> 01:25.299 as he described it. 01:25.300 --> 01:27.533 If you read this initial description of his, 01:27.533 --> 01:33.266 you note that there is a certain gestalt one gets of hopelessness and despair. 01:33.266 --> 01:36.999 And this surely is the attitude of the patient and his relatives 01:37.000 --> 01:41.000 as they… as they confront this disorder. 01:41.000 --> 01:47.333 I'd like you to notice that he is talking about a syndrome which involves the skeletal muscle. 01:47.333 --> 01:51.866 It is a syndrome which begins usually asymmetrically and may involve 01:51.866 --> 01:56.832 any of the smo… skeletal musculature except for the eye muscles or the cardiac muscle. 01:56.833 --> 02:01.166 The syndrome is characterized by its relentless progression. 02:01.166 --> 02:05.266 If it begins about the throat, it’s called bulbar palsy. 02:05.266 --> 02:10.732 If it begins in one of the extremities, it’s called progressive muscular atrophy. 02:10.733 --> 02:14.999 Almost always associated with the disorder, there is hyperreflexia 02:15.000 --> 02:18.666 and other evidence of pyramidal tract signs. 02:18.666 --> 02:22.632 But as a disorder progresses, these signs disappear, 02:22.633 --> 02:27.533 and we have left only evidence of a flaccid paralysis. 02:27.533 --> 02:33.099 Perhaps this syndrome is most characterized by that which is ab… absent in this syndrome. 02:33.100 --> 02:36.800 For example, as I mentioned, the eye muscles are not involved. 02:36.800 --> 02:40.800 And the patient retains full motion of his… of his eyes. 02:40.800 --> 02:47.400 Except for that rare one or two percent of patients who do develop a conjid… a conjugate paralysis 02:47.400 --> 02:49.333 during their illness. 02:49.333 --> 02:53.599 Similarly, these patients maintain their mental faculties. 02:53.600 --> 03:00.200 Thus, they remain alert, intelligent, and are well aware what is happening to them 03:00.200 --> 03:03.033 well into the terminal course of their disease. 03:03.033 --> 03:10.599 In only about one percent of these patients is there evidence of a intellectual deterioration, 03:10.600 --> 03:14.700 which sometimes seems associated with motor systems disorder. 03:14.700 --> 03:20.433 Similarly, there is little if any sensory involvement unless one tests very carefully. 03:20.433 --> 03:24.833 And then one can usually find some minimal evidence of sensory loss 03:24.833 --> 03:27.999 even though this clinically is not evident. 03:28.000 --> 03:32.966 And finally, the patient's bladder and bowel function remains intact to the end. 03:32.966 --> 03:38.966 So that finally, we have this clinical picture described by Aran of a patient who lies in bed. 03:38.966 --> 03:41.966 Looking like a skeleton. 03:41.966 --> 03:44.999 Imprisoned in its own body. 03:45.000 --> 03:49.700 I first became involved and interested in this syndrome many years ago 03:49.700 --> 03:54.100 when I was assigned to… by the United States Navy to the island of Guam 03:54.100 --> 03:56.733 during the Korean conflict. 03:56.733 --> 04:02.099 It became apparent and had been known of course for many years that A-L-S 04:02.100 --> 04:04.400 was very common on the island. 04:04.400 --> 04:10.833 It was reported as early as the first medical officer assigned to the island in 1900. 04:10.833 --> 04:14.299 Subsequently, and particularly during World War Two, 04:14.300 --> 04:19.400 many medical officers noted the unusual frequency of the disorder on the island. 04:19.400 --> 04:24.500 And reported this to their… and reported this to the Surgeon General 04:24.500 --> 04:29.666 and also published reports about this unusual frequency. 04:29.666 --> 04:31.699 At the time I visited the island, 04:31.700 --> 04:33.500 this particular village. 04:33.500 --> 04:35.200 The village of Umatac, 04:35.200 --> 04:37.900 was one in which there were 200 adults. 04:37.900 --> 04:42.366 At that time, we found seven patients who had the disorder 04:42.366 --> 04:46.232 living among the… living in that village of 700 people. 04:46.233 --> 04:49.566 Thus the instance was almost 1000 times as high 04:49.566 --> 04:54.066 as elsewhere in the world in this particular village. 04:54.066 --> 04:57.799 If one looks at the patients who had the disorder, 04:57.800 --> 05:00.633 and this is one such patient who had the disorder in the island. 05:00.633 --> 05:03.333 You see that they fit Aran's description. 05:03.333 --> 05:06.933 The patient is alert, he’s following the camera with his eyes. 05:06.933 --> 05:09.733 He lies there like a skeleton. 05:09.733 --> 05:11.933 All of the skeletal muscles are involved, 05:11.933 --> 05:16.866 and the clinical syndrome looked for all the world as it did in the States. 05:16.866 --> 05:20.032 Similarly, when we looked at the laboratory tests. 05:20.033 --> 05:23.633 We found that those laboratory tests which were available to us. 05:23.633 --> 05:26.033 Including the neurophysiologic techniques. 05:26.033 --> 05:31.266 Seemed to demonstrate that the illness was similar to that seen in the United States. 05:31.266 --> 05:35.266 The cause of this disorder was of course of great concern to all who had seen 05:35.266 --> 05:37.066 this unusual instance. 05:37.066 --> 05:42.166 And many of us had the naive belief that anywhere where this disorder was so common, 05:42.166 --> 05:46.166 it should be relatively easy to find the etiology of the syndrome. 05:46.166 --> 05:49.932 Unfortunately, as you know, that has not proven to be so. 05:49.933 --> 05:52.833 We first thought that perhaps this disorder was hereditary, 05:52.833 --> 05:56.633 and the natives seemed to agree with this… us that this was possible. 05:56.633 --> 06:02.166 When we searched, we found that there were other neurologic diseases on the island. 06:02.166 --> 06:05.432 For example, there were a great many patients 06:05.433 --> 06:11.099 who had what we thought was a peculiar form of Parkinsonism associated with dementia. 06:11.100 --> 06:13.833 These patients look very similar to the patients 06:13.833 --> 06:19.533 who we had seen during and immediately after World War One. 06:19.533 --> 06:23.433 Those patients with a postencephalitic form of Parkinsonism. 06:23.433 --> 06:26.433 They were patients who had marked rigidity. 06:26.433 --> 06:28.533 Who had mental deterioration. 06:28.533 --> 06:31.833 And really had very little if any tremor. 06:31.833 --> 06:35.366 This too, was a disorder which went on to death. 06:35.366 --> 06:39.266 As we watched these patients over the next few years. 06:39.266 --> 06:44.599 We were impressed that they did not seem to be the same patients as those who had A-L-S, 06:44.600 --> 06:48.000 but rather that they seemed to be a separate group of patients 06:48.000 --> 06:53.333 within the Guamanian… within the Guamanian people, period. 06:53.333 --> 06:55.966 As we went further, 06:55.966 --> 07:02.366 we began investigating the possible, uh, hereditary aspects of this disorder. 07:02.366 --> 07:03.699 Can I have the next slide, please? 07:03.700 --> 07:06.333 We were impressed as the natives had told us 07:06.333 --> 07:09.299 that the disease had been present for many decades. 07:09.300 --> 07:13.333 For example, as you see on this sly… on this slide, 07:13.333 --> 07:20.299 which illustrates a page from the death records of the, uh, of the Navy records 07:20.300 --> 07:24.633 for the island of Guam. You can see two consecutive deaths. 07:24.633 --> 07:27.766 One… both of them from the village of Umatac. 07:27.766 --> 07:32.166 Both of them illustrating that the patients had died of paralysis, 07:32.166 --> 07:35.166 which is a Guamanian name for this disorder. 07:35.166 --> 07:39.399 So it was apparent that this disorder had been present on the island for decades, 07:39.400 --> 07:43.033 and it did seem to us that it ran in families. 07:43.033 --> 07:45.866 We had available the death records [of the] United States Navy. 07:45.866 --> 07:51.266 The birth, marriage, and death records of the Catholic Church back to 1830. 07:51.266 --> 07:58.566 And with these we were able to construct rather extensive family records on these patients. 07:58.566 --> 08:03.632 And we came up the records such as this. Which illustrate that in truth, 08:03.633 --> 08:08.566 there were within a single family group many individuals who had the disorder. 08:08.566 --> 08:10.766 These individuals marked here. 08:10.766 --> 08:13.466 But if you looked at this family pedigree carefully, 08:13.466 --> 08:18.399 you’d see that there is no evidence of any of the classic inheritance patterns. 08:18.400 --> 08:22.966 Rather, you see that there is sort of a random scatter. 08:22.966 --> 08:25.966 As if this might only be coincidental. 08:25.966 --> 08:29.332 That this very common disorder on the island of Guam 08:29.333 --> 08:34.933 occurred in this random fashion in a large family. 08:34.933 --> 08:38.733 In truth, we knew how the disorder was inherited in the United States 08:38.733 --> 08:40.333 and elsewhere in the world. 08:40.333 --> 08:44.899 And there the inheritance pattern is far different than what we would see here. 08:44.900 --> 08:48.633 This is the way it looks in the rest of the world. 08:48.633 --> 08:53.366 Where the inherited pattern is five to ten percent of all cases. 08:53.366 --> 08:54.966 As you can see here, 08:54.966 --> 08:59.932 the pattern is inherited as a dominant with really very good penetrance. 08:59.933 --> 09:06.899 This is a very famous family, the Weatherby family, who published their own records in 1870. 09:06.900 --> 09:11.866 So it did not seem that if A-L-S was inherited on the island of Guam 09:11.866 --> 09:18.732 that it was inherited in the pattern in which it was inherited elsewhere in the world. 09:18.733 --> 09:23.666 It is always seductive to speculate when you're in another culture 09:23.666 --> 09:27.099 and see people eating and living in a way that is foreign to you, 09:27.100 --> 09:31.433 to think that there may be some environmental factor which accounts for their illness. 09:31.433 --> 09:36.366 And it is true that on Guam there are things which are different than they are in the United States. 09:36.366 --> 09:42.166 People eat different foods. They eat the cycad nut. They eat cassava. 09:42.166 --> 09:45.132 They chew betel, they drink tuba. 09:45.133 --> 09:48.033 They do many things which are different than what you and I do. 09:48.033 --> 09:52.966 And we all speculated that this might possibly be the etiology of the disorder. 09:52.966 --> 09:57.166 Some toxic factor within their environment which might account 09:57.166 --> 10:01.232 for this unique high instance of A-L-S. 10:01.233 --> 10:07.666 We fortunately had available to us a natural laboratory. In that, the Pacific Ocean 10:07.666 --> 10:11.032 in that area is scattered with thousands of these small islands 10:11.033 --> 10:14.833 on which people all live in a similar kind of way. 10:14.833 --> 10:17.699 They are different in one important respect, however, 10:17.700 --> 10:20.633 and that the Guamanian are a very… is a very distinct 10:20.633 --> 10:24.033 racial and cultural group from the remainder of the people 10:24.033 --> 10:26.633 in the islands scattered through the Pacific. 10:26.633 --> 10:30.266 But they do live in much the same fashion in the other islands, 10:30.266 --> 10:32.132 perhaps more primitively. 10:32.133 --> 10:38.133 And they surely use more of the unusual foods which may be toxic on the other islands. 10:38.133 --> 10:41.633 So we investigated very carefully some of these other islands. 10:41.633 --> 10:43.399 This is the island of Rota. 10:43.400 --> 10:45.300 We also examined many other islands. 10:45.300 --> 10:49.200 Examining the large numbers of patients with neurologic illness. 10:49.200 --> 10:54.933 Discussing with the priests and with the local magistrates on the islands. 10:54.933 --> 10:58.099 Sick people that they knew of, and to our amazement 10:58.100 --> 11:02.600 we found that there were no patients who had A- L-S in the other islands 11:02.600 --> 11:07.966 where they ate similar foods such as cycad and such as cassava. 11:07.966 --> 11:12.666 We did find, however, that wherever the Guamanian people themselves had moved, 11:12.666 --> 11:15.299 and they had moved to three other islands. 11:15.300 --> 11:18.333 The island of Saipan, Rota, and Tinian. 11:18.333 --> 11:24.266 That on these islands, there was an unusually high instance of A-L-S. 11:24.266 --> 11:27.699 So, at the conclusion of my military tour of duty, 11:27.700 --> 11:30.666 I was really quite stymied. 11:30.666 --> 11:34.366 We hadn't been able to demonstrate that the disorder was hereditary, 11:34.366 --> 11:36.399 nor had we been able to demonstrate 11:36.400 --> 11:40.700 that the disorder was secondary to some toxic factor 11:40.700 --> 11:43.266 which might be present on these islands. 11:43.266 --> 11:45.632 [...] 11:45.633 --> 11:47.933 We did, however, come to conclusion that 11:47.933 --> 11:51.466 one could at least classify the disorder in a reasonable way. 11:51.466 --> 11:55.099 One might classify it into the hereditary form 11:55.100 --> 11:57.500 as seen in the States and elsewhere in the world. 11:57.500 --> 12:02.000 And a disorder which was inherited as a dominant with good penetrance. 12:02.000 --> 12:06.566 One could certainly… should, we felt separate out the Guam form 12:06.566 --> 12:08.966 for which we do not as yet know the etiology. 12:08.966 --> 12:11.666 Then the classic or sporadic form, 12:11.666 --> 12:16.266 and then finally we had listed also those symptomatic forms 12:16.266 --> 12:18.566 of amyotrophic lateral sclerosis, 12:18.566 --> 12:22.399 for which we are able to demonstrate the etiology. 12:22.400 --> 12:24.500 [...] 12:24.500 --> 12:30.366 On my return to the States, obviously my interest in this disorder continued. 12:30.366 --> 12:33.499 And we thought that perhaps by making a prospective study 12:33.500 --> 12:35.566 of a hundred consecutive patients, 12:35.566 --> 12:38.099 we might be able to turn up some leads 12:38.100 --> 12:41.766 as to what allowed certain individuals to develop disorder. 12:41.766 --> 12:46.599 What allowed them to become vulnerable to whatever the etiology was? 12:46.600 --> 12:50.600 We conducted extensive studies on these hundred consecutive patients. 12:50.600 --> 12:54.500 And the result of them really were all negative. 12:54.500 --> 12:58.900 As I followed these patients along, however, I found to my amazement 12:58.900 --> 13:04.133 that they did not seem to follow the characteristic pattern I had been led to believe was true. 13:04.133 --> 13:09.566 It is customarily said that patients with A-L-S die in two to three years. 13:09.566 --> 13:15.632 And yet as we followed our patients, we found… we found that approximately 20% of them 13:15.633 --> 13:17.933 were still living at five years. 13:17.933 --> 13:20.133 Ten percent of them were living at ten years. 13:20.133 --> 13:26.599 And some were still living for 20 or… for nineteen to 20 years. 13:26.600 --> 13:30.433 It became apparent to me that there must be something different 13:30.433 --> 13:32.099 about this group of patients. 13:32.100 --> 13:37.033 And we wondered whether or not we weren't overlooking some other etiology for A-L-S 13:37.033 --> 13:38.999 at this point in time. 13:39.000 --> 13:46.100 For this reason, we conducted rather extensive studies on varied forms of symptomatic A-L-S. 13:46.100 --> 13:49.000 In the hope that by doing so, we might find 13:49.000 --> 13:53.200 in what way these patients who lived for a long period were different. 13:53.200 --> 13:56.966 We actually were thinking or had thought that perhaps this… 13:56.966 --> 14:02.332 those patients with long duration had a different clinical disease. 14:02.333 --> 14:06.566 When one thinks about the syndromes which may imitate A-L-S, 14:06.566 --> 14:10.066 one finds they really are in two large groups. 14:10.066 --> 14:14.732 One of them are the group of patients which is… which is exemplified here. 14:14.733 --> 14:20.299 Those who have inflammatory changes in the spinal cord due to viruses, toxins, 14:20.300 --> 14:22.266 immune disease, 14:22.266 --> 14:24.366 a whole host of disorders. 14:24.366 --> 14:26.999 And hyperinsulinism is only one of them. 14:27.000 --> 14:31.733 Others, which are more common, include such syndromes as the Guillain-Barré syndrome. 14:31.733 --> 14:35.733 Certain toxins such as a [?] Tri-O-cresyl phosphate. 14:35.733 --> 14:38.233 There are many such disorders, 14:38.233 --> 14:40.999 and they can usually be readily differentiated. 14:41.000 --> 14:43.533 Hyperreninism, a very rare syndrome. 14:43.533 --> 14:46.133 But when hyperreninism does occur, 14:46.133 --> 14:49.266 approximately 20% of the patients who have it 14:49.266 --> 14:51.266 do develop a muscular atrophy, 14:51.266 --> 14:54.266 which resembles amyotrophic lateral sclerosis. 14:54.266 --> 14:58.666 The other important differential etiology is, 14:58.666 --> 15:00.199 as you all know, 15:00.200 --> 15:06.266 changes which cause compression of the spinal roots or the spinal cord itself. 15:06.266 --> 15:10.432 In the classic example of that of course are the hypertrophic changes 15:10.433 --> 15:12.199 in the cervical spine. 15:12.200 --> 15:16.466 Which are associated with compression of the motor roots 15:16.466 --> 15:20.099 There may be associated hypertrophic changes in the lumbar spine, 15:20.100 --> 15:22.233 causing changes in these roots. 15:22.233 --> 15:23.599 Surprisingly enough, 15:23.600 --> 15:26.733 this syndrome may present with a muscular atrophy 15:26.733 --> 15:29.366 with almost no sensory signs. 15:29.366 --> 15:32.232 A more exotic form of these same disorders 15:32.233 --> 15:36.633 is seen here on a patient who has a rheumatoid spondylitis. 15:36.633 --> 15:42.833 This syndrome in this particular patient presented as a… as a muscular atrophy 15:42.833 --> 15:45.033 and might have been confused with A-L-S. 15:45.033 --> 15:47.599 But the cause of the motor atrophy 15:47.600 --> 15:51.900 was this hemorrhagic granulomatous pachymeningitis. 15:51.900 --> 15:55.933 A similar pachymeningitis, such as that can occur with [?], 15:55.933 --> 15:58.033 or more commonly now, 15:58.033 --> 16:01.333 with with men… with meningeal carcinomatosis. 16:01.333 --> 16:07.633 May also present as a muscular atrophy which could be confused with A-L-S. 16:07.633 --> 16:10.933 It became apparent, however, as we studied these patients 16:10.933 --> 16:15.099 that this did not explain those patients with A-L-S 16:15.100 --> 16:18.000 who lived for a long period of time. 16:18.000 --> 16:22.033 These were the differential diagnosis it is true of A-L-S, 16:22.033 --> 16:25.133 but they were not the same as those patients 16:25.133 --> 16:29.866 whose course persisted for so long a period of time. 16:29.866 --> 16:34.932 In 1968, I had the opportunity of returning to the island of Guam. 16:34.933 --> 16:39.899 While there, I again saw a number of patients with A-L-S, 16:39.900 --> 16:41.400 and to my surprise, 16:41.400 --> 16:46.466 three of the 52 I had originally seen in ’53 were still living. 16:46.466 --> 16:48.799 One of them is this very nice man who, 16:48.800 --> 16:52.666 as you can see again, fits Aran's description. 16:52.666 --> 16:54.932 He's lying there, still in bed. 16:54.933 --> 16:58.633 He's like a cadaver with his muscular atrophy. 16:58.633 --> 17:03.233 His eyes however, are focused on us, and he's alert and intelligent 17:03.233 --> 17:07.966 and remembered me after having… not having seen me for all those years. 17:07.966 --> 17:13.632 Further, the clinical syndrome, in his instance, 17:13.633 --> 17:19.699 had begun with bulbar pal… palsy, and he himself died the following year, 17:19.700 --> 17:20.666 and that autopsy 17:20.666 --> 17:28.299 seemed to be clearly that of a classic A-L-S as seen on Guam. 17:28.300 --> 17:32.633 Thus, it became apparent that A-L-S also could live… 17:32.633 --> 17:35.499 could last for a much longer period of time on Guam, 17:35.500 --> 17:38.800 then we had ordinarily expected. And more recently, 17:38.800 --> 17:42.800 Reed, and his colleagues have published the duration of life 17:42.800 --> 17:45.133 in their patients from the island of Guam. 17:45.133 --> 17:47.633 And I think it's rather interesting to see 17:47.633 --> 17:50.933 that this duration of life is almost identical 17:50.933 --> 17:54.333 with that seen in our patients in States. 17:54.333 --> 17:58.833 You can see that approximately at about 20% of them 17:58.833 --> 18:01.033 live for at least five years or more. 18:01.033 --> 18:04.966 Ten percent lived for ten years or more, and some of his patients 18:04.966 --> 18:11.499 didn't die until… until they had had the illness for 20 years. 18:11.500 --> 18:16.666 Thus it becomes apparent, I believe, that there are patients with A-L-S 18:16.666 --> 18:21.532 in whom the clinical spectrum must be widened, and there must be a difference 18:21.533 --> 18:25.566 in the vulnerability of the patient who have their disorder. 18:25.566 --> 18:27.699 This concept, I believe, 18:27.700 --> 18:30.900 becomes of particular importance in two ways. 18:30.900 --> 18:34.966 First of all, perhaps, in what we tell patients. 18:34.966 --> 18:40.899 Perhaps secondarily in that it gives us some hope that if the disease is so variable 18:40.900 --> 18:43.566 that if we can understand why these variations occur, 18:43.566 --> 18:49.699 we may be able to understand and begin to get a clue as to how to treat these disorders. 18:49.700 --> 18:56.533 And finally, of course, it becomes of particular importance in attempting to interpret therapy. 18:56.533 --> 19:01.899 Therapy in these disorders is really non-existent, 19:01.900 --> 19:07.766 except for the ameliorate of techniques that you and I carry out as good physicians. 19:07.766 --> 19:12.599 There are always, however, cures reported, and they just keep on going. 19:12.600 --> 19:16.833 And there at the present time as always are four or five cures which are being touted. 19:16.833 --> 19:21.799 I have come to the belief that these cures have occurred and are reported by 19:21.800 --> 19:25.766 reputable physicians because they're not aware of this clinical characteristic 19:25.766 --> 19:32.499 of the disorder that approximately ten percent of the patients live for these long periods of time. 19:32.500 --> 19:36.600 This is a group of seventeen patients who I treated many years ago 19:36.600 --> 19:40.200 with whole hog raw gastric mucosa. 19:40.200 --> 19:44.400 I'm not sure that I could get that by any kind of a committee at the present time, 19:44.400 --> 19:46.600 but at least this is what we did. 19:46.600 --> 19:49.700 And you can see the clinical course of those patients 19:49.700 --> 19:55.700 was almost identical to what has occurred in the hundred patients who I described to you. 19:55.700 --> 19:59.666 Obviously, if you obtain these patients late in their course, 19:59.666 --> 20:03.499 say that you only get patients after they've had the illness for three years. 20:03.500 --> 20:07.066 Then you, of course, will get more of these with a long clinic course. 20:07.066 --> 20:09.999 And I have seen a number of these patients, as many of you have, 20:10.000 --> 20:15.500 I'm sure, who have gone from one center to another. Having been in this clinical… 20:15.500 --> 20:22.066 clinical course and who have been reported as cures with a variety of treatments. 20:22.066 --> 20:28.899 Obviously, you and I know this isn't the only reason that therapy is reported as helpful. 20:28.900 --> 20:33.266 The other reason is exemplified on this statement by a patient, 20:33.266 --> 20:39.666 the great need of the patient and the physician to have therapy, to be helpful. 20:39.666 --> 20:44.999 And this, of course, enters into all of our… into all of the treatment 20:45.000 --> 20:49.600 that we give and is one of the reasons that there are so many therapies, 20:49.600 --> 20:54.666 even for such a hopeless disease as A-L-S. 20:54.666 --> 20:56.766 Perhaps then we might add: 20:56.766 --> 21:00.666 is A-L-S really as hopeless as we've always believed? 21:00.666 --> 21:06.232 It is almost unorthodox to talk about patients who may have gotten better. 21:06.233 --> 21:09.633 I think all of us have a tendency to discard from 21:09.633 --> 21:13.366 our consciousness patients who have shown improvement. 21:13.366 --> 21:17.432 We intend not to include them in our classifications 21:17.433 --> 21:19.233 or in our reported cases. 21:19.233 --> 21:21.833 And yet I know that many neurologists 21:21.833 --> 21:26.066 who have seen a great number of patients have seen such individuals. 21:26.066 --> 21:27.632 This is one such patient. 21:27.633 --> 21:30.499 I show him to you only to illustrate 21:30.500 --> 21:34.066 that there are many things we don't really understand about this disorder, 21:34.066 --> 21:38.266 yet, here is a physician who is in the neural sciences 21:38.266 --> 21:40.032 who believed he had A-L-S. 21:40.033 --> 21:41.433 He had progressive muscular atrophy 21:41.433 --> 21:45.266 involving both an upper and lower extremity with hyperreflexia. 21:45.266 --> 21:48.066 He was seen by a neurologist and had an EMG, 21:48.066 --> 21:50.366 and the tests were confirmatory. 21:50.366 --> 21:53.099 He also had a spinal fluid and a myelogram. 21:53.100 --> 21:55.533 He was sent to us at the Mayo Clinic, 21:55.533 --> 21:59.499 and Dr. Frank Howard and Dr. Clark Millikan saw him 21:59.500 --> 22:01.266 and agreed with the diagnosis 22:01.266 --> 22:06.366 but felt that they should wait at least six months before coming to a final decision. 22:06.366 --> 22:10.966 When the patient returned, to their surprise, he was much improved, 22:10.966 --> 22:13.999 and the electomyogram was A-L-So improved. 22:14.000 --> 22:16.566 This patient has continued to show improvement, 22:16.566 --> 22:19.266 and at least for the last ten years 22:19.266 --> 22:22.066 has been able to engage full time in his practice 22:22.066 --> 22:24.066 and on careful examination, 22:24.066 --> 22:28.166 we are unable to find any evidence of neurologic disorder. 22:28.166 --> 22:30.899 I'm not sure whether this means that we ought to include 22:30.900 --> 22:34.900 in the spectrum of A-L-S even patients who show improvement. 22:34.900 --> 22:36.666 I think only time will tell 22:36.666 --> 22:40.399 as we try to find the etiology of this disorder. 22:40.400 --> 22:43.433 What do we know about the etiology? Really very little. 22:43.433 --> 22:46.766 All of our leads have tom… come to nothing. 22:46.766 --> 22:48.532 One of the most recent leads 22:48.533 --> 22:52.099 was a suggestion that this disorder occurred in individuals 22:52.100 --> 22:56.433 who had a particular kind of psychologic bent. 22:56.433 --> 23:00.166 A particular kind of psychologic problem, 23:00.166 --> 23:03.266 and that this in some way accounted for their disorder. 23:03.266 --> 23:06.199 This was based on the M-M-P-I studies 23:06.200 --> 23:08.600 and other psychologic studies on ten cases. 23:08.600 --> 23:12.166 When we tried to reproduce this work, using 50 patients 23:12.166 --> 23:15.266 and comparing it with our control series. 23:15.266 --> 23:18.366 We’d found that our psychologic studies were normal 23:18.366 --> 23:23.066 and that, as you can see. The M-M-P-I in the males were almost identical, 23:23.066 --> 23:28.199 and the M-M-P-Is in the female were identical. 23:28.200 --> 23:30.600 Thus it would seem that at least in our patients, 23:30.600 --> 23:36.800 there were no psychologic traits which characterized the patients with A-L-S. 23:36.800 --> 23:39.800 Most of us, I think at this point in time, or many of us, 23:39.800 --> 23:43.233 have the belief and it's really only a… a hunch 23:43.233 --> 23:47.099 that this disorder must be due… may well be due to 23:47.100 --> 23:51.800 a slow virus which attacks certain vulnerable people. 23:51.800 --> 23:56.333 Perhaps made vulnerable through some hereditary factor. 23:56.333 --> 23:59.566 Having told you about… of my ignorance about this disorder. 23:59.566 --> 24:03.499 And having shown you the limits of at least part of that ignorance. 24:03.500 --> 24:07.633 I can only plead with you that at the present time, 24:07.633 --> 24:12.199 what we need are people who can devise the proper question. 24:12.200 --> 24:15.300 Because if we can put the proper question, 24:15.300 --> 24:18.833 perhaps we can obtain the answer to this disorder. 24:18.833 --> 24:23.599 Perhaps we will be able to find a treatment for these truly pathetic patients. 24:23.600 --> 24:24.566 Thank you. 24:24.566 --> 24:33.032 [The National Institute of Neurological and Communicative Disorders and Stroke] 24:33.033 --> 24:39.299 [The Clinical Syndrome of A-L-S; Mayo Clinic, Rochester, Minnesota; Donald W. Mulder, M.D.] 24:39.300 --> 24:42.666 [This presentation sponsored by] 24:42.666 --> 24:47.666 [The National Institutes of Health, Public Health Service] 24:47.666 --> 24:52.432 [Department of Health Education and Welfare] 24:52.433 --> 24:54.299 [...]