The chapter traces the discovery of multiple sclerosis to Jean-Martin Charcot, who in 1868 linked plaques he found in patient autopsies to a specific cluster of symptoms, abnormal eye movements, intention tremors, and slurred speech, now known as Charcot's triad. For nearly a century MS remained a disease without a known mechanism, until an autoimmune hypothesis emerged after researchers found the immune system targeting specific myelin proteins. The arrival of MRI let doctors track white and gray matter changes in living patients, revealing a pattern of remission and relapse that suggested the brain has some capacity to repair myelin damage, but that this repair process weakens over time.
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The autoimmune hypothesis gained traction specifically because myelin basic protein and proteolipid protein were identified as major targets of immune attack.
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Charcot was also known for his work on hypnosis, using it in demonstrations on patients he diagnosed with hysteria.
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23:14correlation between those plaques when he did the autopsies of these patients and the patients conditions at the time. The patients conditions at the times were abnormal eye movements, intention tremors, slurred speech. This became known as shark cuts or sharos triad. And he recognized that these plaques in the white matter is probably what is causing these symptoms of early MS. This was the discovery of MS. >> We saw people having these conditions. We could see >> uh these physiological uh >> happenings. >> Yeah. when you then went and did an autopsy after the fact, there was something in the brain that looked different than everybody else.
23:55>> Yeah. There's a control and then there's >> So maybe they these things may be connected. >> Yeah. Yeah. And side note, um Charco was super into hypnosis. That's what he's most well known for. If you go back to that painting, >> this uh Yes. >> Uh yeah. Yeah. There he's he's showing a woman who's like in hysteria is what he called it. And then he hypnotized her and then all of these medical professionals are looking on like, "Oh my gosh, I can't believe you couldn't believe you've done this." >> Yeah. Yeah. Yeah. So, you know, you win some, you lose some, >> right? >> Um, so for for nearly a century though, this was in 1868. For nearly a century,
24:37MS was a disease without a mechanism. >> Yeah. Yeah. because we didn't actually know. Okay, so there's these plaques, but you know that's not good enough to really understand what is actually happening to create this. There was an autoimmune hypothesis that the immune system was attacking the myelin because maybe the immune system thought that it was some kind of foreign agent and that gained traction because there was a discovery that a lot of the proteins that are around in myelin are major targets for an immune attack. things like the myelin basic protein, the proteolipid protein and then also with the development of MRIs, we could literally track the the development of the white matter and the gray matter without actually, you
25:18know, doing an autopsy on a dead patient. Now there's a living patient. And now what we're seeing with MS is that it's kind of cycling. >> There's a remission and then and then and then things come back to normal. And then there's a remission and then there's things coming back to normal. What does that say? That says that there is a chance there is a mechanism inside the brain that is fixing this milein degradation. >> Right. >> Right. Right. >> But the fixing mechanism is deteriorating with time. >> The there's a there's an ongoing battle and the defense is uh losing the war of attrition. >> Exactly. Yeah. And so now that becomes
26:00kind of the focus. And with individuals suffering from multiple sclerosis, we we now have some kind of mechanism. It is the myelin sheath. And you can see now stains between normal control individual in A and um someone with MS in B. The stains are the myelin sheets. You can see in A there's so many around every single nerve fiber. There's a bunch of milein sheath. In B it's almost gone. >> Yeah. And the point here is now that it's gone, it means we lose that speed. We lose the other efficiencies that it provides, not just the physics perspective of what you get out of having that milein sheath be present. Yeah. >> Um and so now we're starting to >> we're starting to the detective work is
26:42>> progressing. >> We're starting to at least piece together what is going wrong. It's definitely the myelin. Yes. >> Okay. >> Right.
Evolutionary BiologyNeurobiologyPharmacologyRegenerative Medicine