Movement Disorders. Treatment

There were two papers in 1992 in terms of broaching the issue of the differential diagnosis of parkinsonism. There are about 100 causes of parkinsonism, so I’m only asking for a 5th. So I ask them, “Can you name me 20 causes of parkinsonism?” and invariably there is a resident in that rotation – usually a very cocky resident – who says, “Sure, no problem. Thorazine, Haldol, blah, blah…” and he lists me some 20 neuroleptics. And I say, “No, that is not the idea.” But to broach this rather large differential diagnosis list that I’ll be spending more time talking about in the second lecture, I like these two studies by Hughes and the London Brain Group. So here’s the paradigm. They got 100 cases of pathologically confirmed Parkinson’s disease, by PATH. And they asked the musical question, “How often were these graybeard Brit neurologists right?” and you know as well as I do that in the UK it’s different. To be a senior attending neurologist, it’s different. No young codger like me could become an attending neurologist real quick. He’s got to wait until somebody dies. This is where they wear the long, flowing white coats, trains on the ground. Little men carrying them behind. All that kind of stuff. So these august British neurologists convinced in their diagnosis of Parkinson disease. How often, yea, how often were they right? And they were right 76% of the time. Well, you say that’s not bad. Ted Williams he batted 400 and we are still talking about him. This is good. Well, this is bad because one in four cases in those people admitted to research protocols, for example, don’t have it if you use that estimate. This is problematical, I think. So the question was, “What were the clues that they were wrong?” which is a very reasonable way to approach to those data. And some of those features that clued them to their wrongness included these atypical features: an extensor toe. Fair enough. I don’t expect to see an extensor toe in Parkinson’s disease, do I? I might expect to see a little bit of reflex asymmetry, more on the side involved initially. Asymmetric presentation, maybe a little bit of a reflex asymmetry. But no extensor toe. But I might see a striatal toe. Oh, no! I’m confused. But if you really see what you think is an extensor toe – not a striatal toe – then okay, that would put me in mind of something else like atherosclerotic parkinsonism. The story of an early dementia. No. I don’t hear the story of early dementia in Parkinson’s disease. I hear the story of an early asymmetrical tremor, I hear the story of an early asymmetrical clumsiness of the hand that the internist refers to me because, “I think this was a stroke”. Oh yeah, good. It could be something else. Early dementia is not characteristic of idiopathic Parkinson’s disease, nor is early dysautonomia, early orthostatic intolerance for example. No. These are features respectively of alzheimerian change or Shy-Drager or olivopontocerebellar atrophy or something else. The early falls issue, or supranuclear gaze palsy – and I’ll be talking much more about that a little bit later on – of course, progressive supranuclear palsy. Pretty straightforward, but they made these mistakes. So the typical features then, just by way of characterizing why they were right, is the story of asymmetrical onset, bradykinesia associated with resting tremor, a long clinical course, a robust and consistent response to levodopa. All these things sort of pointing you in the direction of idiopathic disease, including the development of levodopa-associated dyskinesia. I’ve always found it curious in my movement disorders practice that for all the levodopa I use for all kinds of indications – restless legs or levodopa-responsive dystonia, or all these other things – that I don’t see dyskinesia largely in that setting. I see it in idiopathic disease. So I think that in general that when you are talking about a case of parkinsonism, yeah they merit a trial of levodopa. What constitutes a reasonable trial? Well, you guys are clinicians as much as I. You tell me. I like to shoot for about 1 gram of levodopa, but that’s up to individual taste. A gram or gram and a half. Movement disorders

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