The following is a transcript of the presentation video, edited for clarity. Click the PDF icon to download the presentation handout and references.
So I’m going to be reviewing the clinical syndromes of primary progressive aphasia. And that’s very important to think of them as clinical syndromes. They’re not diseases and I’m going to get back to that. That reflect the areas of brain that are most affected by pathology and grossly correspond to a particular pathology.
So this is the number one point I like to get across to patients when I diagnose them with primary progressive aphasia. I try to tell them it’s not a disease. No one dies of PPA. If they come to autopsy the pathologist never says this person had primary progressive aphasia and that was the cause of death. PPA is the clinical syndrome. It’s a collection of symptoms. And it reflects a neuordegenerative disease that causes that. And neuordegenerative diseases that cause primary progressive aphasia are pretty few. But they can affect different areas of the brain. And just like stoke that causes very different syndromes depending on where it is in the brain. These diseases cause very different syndromes depending on where they are– they first start in the brain. And it happens that these diseases have a predilection for certain parts of the brain. Some affect more frontal areas. Some reflect more parietal areas. One affects more inferior temporal and anterior temporal regions. And so the syndrome grossly corresponds to a particular pathology. But there’s no one to one correspondence.
But giving somebody a diagnosis of one particular variant of primary progressive aphasia can be helpful and I’ll try to show you that because it can kind of give them an idea of what problems might come next, what the course of their condition might be, what other problems they might develop, and so on. Now I’m going to be also describing some advances and diagnosis. I’m going to talk about some recently developed tests and imaging for identifying particular variants. There are three main variants of primary progressive aphasia and describe advances and prognosis, some imaging data that may help predict the rate of decline and describe advances and treatment, talk about some emerging investigational treatments for at least temporarily delaying or declining– delaying the decline or possibly then improving at least temporarily, language performance.
Before I go on, I want to disclose that I don’t have any financial relationship to disclose other than I get some financial support for some editorial activities. But mostly, I want to disclose that most of this work was done by my students and post-docs, and research assistants. And I just– I mentor them in this work. And all of this work was supported by NIH mostly NIDCD.
Primary Progressive Aphasia
Variants of PPA
Nonfluent/Agrammatic Variant PPA
So, nonfluent/agrammatic variant primary progressive aphasia is really characterize by effortful halting speech with inconsistent sound errors or apraxia of speech and or agrammatic language production, difficulty in producing complete grammatical sentences. Now, these two things do dissociate and Joe Duffy is going to be talking this afternoon about primary progressive apraxia of speech, when that’s the only problem, you can’t call them primary progressive aphasia because they don’t really have a language problem. They just have a motor speech problem. And so, it’s just the syndrome that he will be talking about. But if they also have aphasia, they have some spelling problems, they have naming problems and they have apraxia of speech, then it’s likely, it’s nonfluent/agrammatic variant primary progressive aphasia. Some supporting features are that they have impaired comprehension of syntactically complex sentences. Now those of you who work in stroke aphasia say, “Gosh, you know, some of these components sound a lot like Broca’s aphasia, effortful halting speech, agrammatic language production, impaired comprehension of syntactically complex sentences.” So, it’s not surprising that they also have spared word comprehension, spared object knowledge. And it’s not surprising that they sound a lot like patients with Broca’s aphasia. And they– I’ll show that area of brain is very similar.
Now, the pathology underlying this variant is usually tau pathology. Now, tau pathology is also seen in Alzheimer’s disease but this is a different isoform of tau. And the disease when they come to autopsy is almost always one of these three diseases; corticobasal degeneration, progressive supranuclear palsy or frontotemporal lobar degeneration caused by tau. Now, frontotemporal lobar degeneration can also be caused by TDP-43 which we’ll talk about can be caused by Pick’s disease or argyrophilic grain disease. Does everybody know what argyrophilic means? Argyrophilic is literally silver staining but philic means, “friends with”. So, argyrophilic is friends with Argye.
So, the cortico– this is important because these patients later in the disease, after a few years of having primary progressive aphasia, if they have corticobasal degeneration, they often develop symptoms as the disease spread of other symptoms of corticobasal degeneration which is often, in the case of nonfluent/ primary progressive aphasia where it starts on the left side of the brain, it’s right hemispastic, hemiplegia, a rigidity of the right– usually the right arm because that’s closest to the speech area. So, they have apraxia of speech and then, also apraxia– ideomotor apraxia. Then they develop rigidity of the right arm very often. They have some Parkinsonism. They may have tremor. They can develop gait difficulty particularly because of rigidity of the right leg.
Progressive supranuclear palsy is a very closely related tauopathy and in fact, it may very often has the same genetic mutation underlying these two diseases. So, you can have one person in a family with this genetic mutation who has corticobasal degeneration or corticobasal syndrome at least and another person who first presents with progressive supranuclear palsy syndrome and another person who first presents with a primary progressive aphasia. Just depending on exactly where the disease starts in the brain. So, lots of people think that corticobasal degeneration and PSP or progressive supranuclear palsy are really kind of the same underlying disease because they can be caused by the same underlying mutation. Now, progressive supranuclear palsy, many of you speech pathologists may see because of swallowing problems, when it presents with the PSP syndrome the main problems are swallowing problems, falls, and eye movement problems, particularly difficulty looking up. So, someone whose underlying disease is PSP may develop these problems later on after their apraxia of speech and speech– and language problems. They often develop eye movement problems, swallowing problems and falls. So, it’s important to look for these problems and be aware of them, especially the swallowing problems.
Frontotemporal lobar degeneration is also caused by tau. And it can cause changes in behavior and personality. So, if the disease is moving forward in the brain, particularly affecting orbitofrontal cortex, then they may develop more behavioral problems later on. Change in personality, comportment problems that we often see in behavioral variant frontotemporal dementia.
So, one of the problems you may see why this can be confusing to families is that, in neurodegenerative disease often the same word is used for both the pathology and the syndrome and that probably started with Alzheimer’s disease because Alzheimer’s disease is used for both a syndrome and a underlying pathology. So, it would be great if we got away from that and starting saying, “Alzheimer’s dementia” for the clinical syndrome of memory, primary memory problems and impairment, progressive impairment, in at least one other cognitive domain. And use Alzheimer’s disease for the proven pathology. The same thing with corticobasal degeneration, the syndrome of having rigidity on one side, Parkinsonism, apraxia is often or should probably best be labeled corticobasal syndrome. And corticobasal degeneration probably ought to be restricted to the pathological disease.
There’s no real PSP syndrome other than PSP. But it should probably be called exactly that, PSP syndrome. Again, Pick’s disease and argyrophilic grain disease are really just pathological diagnoses.
Less commonly, the nonfluent variant– nonfluent/agrammatic variant can be caused by TDP-43 or even Alzheimer’s disease pathology. Alzheimer’s disease can start anywhere in the brain. So, it can cause, as you may know, a primary visual problem. It can cause rare cases — this, any of the variants of primary progressive aphasia.
Semantic Variant PPA
So, a semantic variant primary progressive aphasia has two core features and both of these must be present, as supposed to the core features of nonfluent variant. And that is impaired naming of objects more than actions and impaired single word comprehension. So, they have to have impaired naming and difficulty with word comprehension but supporting the features are impaired object knowledge, particularly for low frequency or low familiarity items. The reading or writing is often impaired but they make regularization errors. So, what some people would call surface dyslexia, surface dysgraphia. So, they read the word yacht as yacht and so on. They read by phonics, spell by phonics. They have impaired reading and writing comprehension. Their repetition is generally spared and they have spared grammar and motor speech.
They have paragrammatic speech like patients with Wernicke’s aphasia. But they’re not exactly like patients with Wernicke’s aphasia. Their language can sound very similar with extended English jargon. However, what’s different about them is they all eventually do have impaired object knowledge. So, with unlike a patient with Wernicke’s aphasia, who might speak in jargon but behave perfectly, normally, may be able to cook, may be able to mow his lawn, maybe– uses objects appropriately. This eventually affects both temporal cortices, left and right, and they have difficulty really understanding the meaning of an object. So, they put orange juice in the coffee maker. They– One of my patients boiled pizza for dinner. One patient spread peanut butter with a can opener. They use objects inappropriately because they don’t understand them. And one of the really key features of semantic variant, primary progressive aphasia is they’ll often say– repeat a word that you said and say, “I don’t know what that means.” So, they’ll say, “The glove, glove, I– that sounds familiar to me. I know I know one. I know I’ve had one. Yes, I think that’s one that I’ve done before. But the glove, glove, I don’t know what that is. I don’t know the glove.” And that they’ll say that very frequently in conversation.
So, this is a patient describing the cookie theft picture, or not. I’ve seen this so many times. I can tell you what she says. It’s very fluent speech. So, she’s a girl and he’s a girl and she’s– I know he’s the one that I did before. She was the one– she’s– I like that one. That’s the sort of thing they say. So, it’s mostly extended English jargon, lots of errors, like he’s a girl. And areas that are involved are mostly the anterior and inferior temporal cortex, more than a posterior temporal cortex that we see in stroke and it is bilateral but it’s more on the left than on the right.
The most common pathology is frontotemporal lobar degeneration caused by TDP-43. TDP-43 is tau DNA-binding protein, a 43 kilodaltons and it is less commonly caused by Alzheimer’s disease, dementia with Lewy bodies which you all may know Robin Williams just died of, he had at death and CJD, other mixed pathologies and so on. CJD is Creutzfeldt-Jakob disease. Usually, that’s a very rapid deterioration in cognition.
Logopenic Variant PPA
NACC FTLD Module
So, they’re– a group of us who study primary progressive aphasia we’re asked to get together, supported by NIH, to come up with a bunch of tests and also it’s supported by the FTD association– association for FTD, to come up with tests that would help identify some of these patients with primary progressive aphasia, as well as behavioral variant FTD and distinguish them from Alzheimer’s disease. And, particularly, to use these in the Alzheimer’s disease research centers. And so, we came up with a module of tests.
Now, these are just sort of ones that we– they had to be given really quickly and they had to be the ones that could be used very easily in a research center across the country and they aren’t perfect. And I’ll talk about some of the problems with them. But the idea of some of the language tests was specifically to try to distinguish between these variants. And so, this is a work in progress as I mentioned. Some of the things that were included were letter fluency and this is really used as an executive function test to evaluate for frontotemporal dementia, word and sentence reading, to look for that surface dyslexia. Semantic associates, and that’s just identifying which pairs of pictures are semantically associate– associated to identify patients with semantic variant primary progressive aphasia.
A sentence anagram test was used to evaluate sentence– a grammatical sentence production was the idea to try to identify those patients with agrammatic variant and I’ll talk about some problems with that. And the reason for using a sentence anagram test is, many of these people, as you heard, the first patient really couldn’t talk at all. So, how could you tell if she’s agrammatic? Now, she did write and she was agrammatic in writing. She had good single word writing. But if they can’t write, and sometimes they can’t, sometimes they can’t even use their dominant hand. We wanted something that could look at on a sentence, grammatical sentence production and we thought this would be a good idea. But it turns out it also requires semantics and executive function and is hard for all of the variants.
Sentence repetition, obviously, to identify the logopenic variant, noun and verb naming, some of the patients, as I mentioned, with nonfluent variant are only impaired in verb naming, and not in noun naming. Then there were something to– somethings just to make sure that they didn’t have a more global impairment. So, things like a Benson complex figure memory test. Then there are caregiver scales for observation of key behavioral variants to identify patients with behavioral variant FTD because remember, their problem is really a problem and deterioration in comportment and behavior. So, there are really good tests for that. It’s really observational scales that pick this up, and a neurologic evaluation and standardized diagnostic lists for symptoms.
And this is just really to show you, you don’t have to read any of these scores. Just to show you that it has been tested in a fair number of people so far with all of these variants and with FTD as well as normal controls, 160, this was actually a year ago and patients with behavioral variant FTD. And so, those tests are available if you’re associated with any Alzheimer’s disease research center, if you’re interested in giving them.
Refining the Battery
Development of a quick Test that Reliably Identifies svPPA Across Cultures
Short Form of Pyramids and Palm Trees Test Effectively Discriminates svPPA From Other Variants of PPA
So then some– Murray Grossman who is a collaborator at University of Pennsylvania and Chiadi Onyike who’s one of my collaborators in the psychiatry department and directs the behavioral variant frontotemporal dementia clinic at Hopkins and some other colleagues at University of Pennsylvania all got together, decided to see if this could really effectively discriminate sort of pathologically proven semantic variant primary progressive aphasia from other forms of primary progressive aphasia. And so we evaluated initially 50 primary progressive aphasia patients who either had pathologically confirmed diagnosis or pathology confirmed by proxy based on either genetic mutation or CSF correlates of pathology.
And they were fairly mild. This is their mini-mental status exam score which really didn’t vary significantly across the variants. And as you can see, this is really mild for a patient with aphasia. They tend– Patients with aphasia tend to do very poorly on the mini-mental. They had similar degrees of education and age. And what we found was there was a significant difference across groups on the 14-item Palm Trees and Pyramids. And even though they were very mildly impaired, semantic variant had significantly lower scores compared to logopenic variant and compared to the nonfluent/agrammatic variant. Logopenic variant did not differ from the nonfluent variant. So this just shows the performance on the 14-item Palm Trees and Pyramids in semantic variant versus nonfluent/agrammatic and logopenic variant.
So this 14-item test which is much faster to give seems to provide a rapid test of nonverbal semantics that can distinguish semantic variant from healthy controls and semantic variant from the other variants and correlates with anterior temporal and orbital frontal atrophy. And so may distinguish frontotemporal lobar degeneration pathology from other pathologies relatively early in the course.
Advances in Early Diagnosis of svPPA
Predicting the Course of Decline
Predicting Decline with Imaging
And then, I’m going to talk about some work now on imaging to help us with prognosis. And this work is really by my colleagues, Susumu Mori and Andreia Faria who are terrific collaborators in the radiology department. And we initially studied 16 patients with primary progressive aphasia using structural imaging resting state fMRI and DTI nine months apart and looked at their performance on naming test, the Boston naming test and Hopkins assessment of naming action to see if we could find any imaging predictor of– that could predict the decline in naming. And lots of people have shown that imaging– changes in imaging are associated with changes in performance over time, particularly decline in various things and I showed you that already. But that sort of the Holy Grail is that you want something that at time one can predict where they will be 9 months later or 12 months later. So we looked to a lot of things. We looked at volumes of gyri. We looked at various DTI measures of white matter tracks. We looked at correlations between homologous cortical regions on resting state fMRI. And the reason we looked at homologous correlations because these are the most stable over time that we lay you in the scanner and evaluate the correlation between both response in homologous regions between left and right and prefrontal cortex and superior temporal gyrus and any particular area on the left will be highly correlated with the right. And that’s really stable over time. And so we looked at those areas on– and that’s not as true with primary progressive aphasia in part because they have atrophy more on the left than on the right. So I’m not saying this as something, you know, deeply theoretically important, but it is a marker that might be able to tell us what’s happening in the brain.
So we found that baseline atrophy in any particular area really did not correlate with subsequent decline in naming. It did correlate with current decline and the change in atrophy in that– in specific areas as I showed you, did correlate with change in naming but at time one atrophy could not tell you what was going to happen nine months later. The initial structural MRI didn’t offer direct markers of subsequent decline in either the Boston naming or the HANA, using DTI measures also.
The decline in volume of diverse brain regions correlated with the degree of decline on the Boston naming and the HANA and I’m going to show you those data. And that’s just consistent with things I’ve already shown you that progression of atrophy correlates with progression of functional deficits. The initial volume of the left inferior frontal gyrus and ventricles correlated with their further degree of atrophy and enlargement. So it could predict if you’re– the amount of atrophy you had in those areas could predict that those areas were going to show further atrophy. But that didn’t correlate with performance on naming. So that wasn’t as useful.
So this is just to show you the areas on– that were associated where change in atrophy or a change in the volume of these areas was all associated with change in the Boston naming test. So again, it’s not just the temporal– anterior temporal pulse but remember I said that all variants are impaired in naming and all of these areas were significantly associated. Atrophy over time was significantly associated with change in the Boston naming test over time in the left– sorry. This is actually the right obviously and this is the left. So, almost all of the temporal areas and the post– inferior parietal cortex as well as inferior frontal gyrus to lesser extent, just this pole area in the left. For the HANA the verb naming test, we see a lot more– the same regions in the temporal cortex and inferior parietal cortex on the left. But also a lot more in sort of Broca’s area here and that’s been shown in a number of studies of healthy controls. And in stroke patients, that inferior frontal gyrus seems to be strongly more associated with verb naming than with noun naming.
But that’s still not what we are most interested in. What we interested in is prediction of subsequent decline and the only baseline parameter that significantly correlated with the rate of subsequent decline in naming after correction from multiple comparisons was the resting state connectivity or functional correlation on resting state between homologous prefrontal cortices. And so we did this twice, the first time was even higher was the correlation of 0.80 and then the second time was 0.69. So these are two different populations of PPA patients. And so it seems to be really stable. And so the correlation– how– the bold activity at rest in the left versus right, how well they’re correlated could predict the rate of change in Boston naming test. And this just shows you, in 30 healthy controls, this shows you the– all of these 185 regions of interest that we look at. On the left, it shows you that 185 regions of interest on the right and the color depicts how well they’re correlated. The red is very strong correlations and blue is very strong negative correlations and brown or gray is weak correlations.
And so you can see homologous regions are strongly correlated in healthy controls. This is very stable over time. And this is what we find in PPA patients. This is a group average. And what we find is much less strongly– strong correlations between homologous regions. There are some areas that are highly correlated but others that aren’t. And we also find that sort of language cortex, the areas in green frontal– sorry– inferior frontal, Broca’s area, prefrontal cortex, all of the temporal cortex and inferior parietal cortex are strongly correlated with each other even at rest in healthy controls. Whereas in PPA patients, the frontal regions are not correlated with temporal regions. Temporal regions are not correlated with each other.
So this seems to be something promising. We’re going to continue to look at but it may tell you that, you know, give you an idea of how quickly the person is going to decline in naming. Now it may be that it just depicts. We don’t control for the degree of atrophy in the prefrontal cortex. So it may just reflect that there’s an imbalance in atrophy, that there’s more atrophy in the left is more neuronal dropout in the left compared to the right. So there’s less pole signal in the left compared to the right. But it sort of doesn’t matter what it reflects because this is just a very easy thing to measure. You stick someone in the scanner. They don’t have to do anything. They lie there for 10 minutes. If you can get a measure like this in 10 minutes, that can predict something later on, it’s really nice no matter, you know, why we get this.
Advances in Treatment: Augmenting Language Therapy with transcanial Direct Current Stimulation
Questions and Discussion
First of all, it’s about identifying these people with PPA in places where there is not as center or a lab dedicated to this. The first video you showed reminded me very much of a client who actually came to us with a vascular stroke but has declined so, so much, and so one part of my question is: Is that a common characteristic or a finding that you would see?
Sure. I would say about half of my patients come to me with previous diagnosis at least somewhere with a diagnosis of stroke. But what tells you it’s not stroke is their MRI and the fact that they’re getting worse. Now, I did present some data that some patients get worse after stroke. But usually, they don’t decline to the degree that these patients decline. And it’s usually not really in the deficits caused by the stroke. It’s not specifically language. If stroke patients decline, it’s sort of more generally in the cognition. It’s not specifically in their aphasia. So if you see really worsening of aphasia, it’s usually primary progressive aphasia but look at their– somebody needs to look at their MRI. Often, they’re read as normal.
So neuroradiologists, and I love neuroradiologists, I couldn’t deal without them, but they’re very reluctant to read focal atrophy. And the reason is there’s a huge amount of variation in what’s normal. And so they won’t– they’re great at telling you what a lesion is. They’re much better that I am at saying, you know, this is a stroke or this is a tumor or what kind of tumor it is or they’re terrible at telling you where that is in the brain. So sometimes, they will say it’s on the parietal lobe and it’s really in the temporal lobe or, you know, it’s– so don’t just read the report if you want to know where something is. But they don’t read focal atrophy. So they’ll usually say it’s normal if it’s PPA. But if it’s a stroke, they’ll say it’s a stroke though. And occasionally they will– if it’s late PPA, they will misread it as a late– as chronic stroke. Because if there’s just encephalomalacia in a focal area, it looks kind of– it could be a stroke particularly if it, you know, if it’s in Broca’s area, there’s just kind of missing tissue in Broca’s area which there is in some of these nonfluent patients. They might read it as stroke but then if they get another scan, a CT or MRI and it’s bigger, it’s less– a whole lot less likely to be a stroke. So– Or if you see a lot gliosis around it and it’s not in vascular territory, it’s not a stroke. So, vascular lesions or vascular territories.
Thank you. The second part of my question is: I was encouraged that language therapy at least at some level seems to be helpful in slowing progression. And I work in a college based clinic and that seems like a good place for some of these people to come if we can find them and get them there. I’m wondering if you have any suggestions about how to do that, how to outreach, who to outreach to if we’re in an area without a known center that’s working with these patients?
I just want to say, in follow up to that, I was at poster that I did yesterday and this man came up and said, “I’m really no one” and I was, well of course you’re someone. But what he was the husband of someone with PPAOS. And he said just what you just said now is, there’s no place for them to go to be with people that understand them and can help them and he’s linked in to some good places where they are but you’d spoke directly to that. So, I think that really does seem like a very good direction. So thank you for that very much.
I’m Fatima from Ohio University. My first question is regarding the core features or the associated features for the different types of PPA, do you have any specific reading or writing features that can be related to the different types of PPA?
So the question was, are there specific reading or writing features related to each of these variants? I actually published a paper on this a long time ago and, well, I don’t know, couple– several years ago on the spelling types associated with different primary progressive aphasias. There’s not a one to one correlation. The most strong association is that, the semantic variants have this sort of surface dyslexia and surface dysgraphia and that patient with nonfluent variant have agrammatic writing very often. They often have more trouble with verbs than nouns as I mentioned. But they can have a variety of types of spelling problems and reading problems. Sometimes we see and I– you know, maybe Joe can say more to this but I’ve seen a couple of cases of deep dyslexia in patients with nonfluent variant which is sort of surprising. You think, well, they don’t have semantic deficits but they’re– the variant of a deep dyslexia where they say a semantic paraphasia. Like, they’ll look at the word fox and say, woof or, you know, might distort it more than that but say, woof. Or if you ask them to spell fox they’ll write, woof. But then they’ll say, “Yeah, not that.” They know it’s not quite right but it’s similar. So, they’re kind of aware of it and if you give them a picture of fox and woof and say point a fox, they’ll get it right. So, they know the difference but they do have these semantic problems and sometimes. They actually read and write. There have been several cases where they– their reading comprehension is better than their auditory comprehension. So, it’s fairly late in that course. So, Audry Holland actually published a paper ages ago on this where a patient with Pick’s disease had– could write but couldn’t speak and could understand written language more than he could understand spoken language. And I’ve seen a few other cases like this but they often do actually make semantic errors in auditory comprehension and auditory– and if you give him an auditory word they might even write a semantic paraphasia. But if you give it to them in writing, they understand it much better. So, they have some really interesting disassociation. There’s not single– there’s not a single pattern in the nonfluent variant and logopenic variant, I think.
Well, in that case, how significant is it for the clinicians to really identify the variants in order to plan for therapy?
I think it’s less important for you to identify. It’s just this– I would say the same as for vascular aphasia syndromes. It’s less important to identify the variant or the classification than to identify the problems that the patient is having. That’s really the important thing is to characterize the best you can of what problems the patient’s having. If they have apraxia of speech, they have apraxia of speech and you should treat that. If they have agrammatic speech production, you should treat that. If it doesn’t quite fit because they also have word comprehension problems, treat the word comprehension problems and the agrammatic speech production. You don’t care that they don’t fit into– into a category very nicely. These are not perfect. Like I said, they are sort of clinical syndromes and not everybody is going to fit. Half of our patients– it’s just like the Boston diagnostic aphasia examination, half patients are not classifiable and half the patients or at least a quarter of the patients are not classifiable using these categories I just described.
Lastly, it’s just my curiosity, with the TDCS, how feasible it is to be used in clinical setting?
So, it probably shouldn’t be used in a clinical setting just yet. We need more data. We need more evidence that it’s useful, particularly, in this condition but it is not difficult to use. So, I think if we get enough data, there’s a lot of evidence that it works, that it’s more useful than language therapy alone, then it should be use in a clinical setting and if it proves to be, it’s very easy and very inexpensive.
My name is Jordan Green. I’m from MGH Institute of Health Professions. And maybe I miss this but for the TDCS, was that anodal? And if so, what’s was the rationale for using that over cathodal?
My question is, if the TDCS studies used any social validity measures to measure the life parts patient functions of people that the primary progressive aphasia. And if yes, what were the assessment measures that you used?
I’m Isabel Hubbard from the University of California, San Francisco and University of Texas at Austin. I’ve been thinking a lot about TDCS and its effect on disease process and primary progressive aphasia. And I was wondering if you could tell me a little bit more about what you think the simulation is doing to the tissue that is unaffected but as you point out time and time again, beautifully in stroke, aphasia that unaffected tissue, is it necessarily health tissue and if may be vulnerable to disease. So, do you have a theory for how the simulation maybe positively or negatively impacts its vulnerability especially in your language network?
Well, so there are– you’re right. There are neurons that drop out but there are also neurons that are alive. You know, these people are producing speech and language. So the network is there and then we have done fMRI, test related fMRI studies. I mean it’s a great question but they’re– we’ve done some test related fMRI studies and they do show, you know, a network associated with language production. So there’s still a language network in there. So those neurons are working together to produce language. So we think if you stimulate, as I mentioned, stimulation is very broadly localized. So we think if you do the task at the same time and you do TDCS. The TDCS is going to change the membrane excitability over that network wherever it is. It’s finding those healthy neurons that still exists in our– then are doing language when they can do it. So I think that that what’s its doing, is that they’re making those neurons that are still there and still healthy and still able to produce a direct response more able– more likely to fire the next time they get the stimulus. So that’s what’s LTP is. It’s– you just, you know, makes it more likely to fire with the same stimulus the next time.
Isabel Hubbard :
Thanks. And where was your cathodal placement?
So, we do one– so, what, Kyrana Tsapkini who’s my colleague that’s actually carrying this out. She does IFG and then the control is actually on the jaw. And she’s worked with Miriam Begsun [unsure] who’s localized this now to show that that actually does show most active change or just the most activity in kind of Broca’s area.
I run a nonprofit organization for people of aphasia. And our goal is participation. So we actually have run primary progressive aphasia groups. We used to put the people with PPA into the regular aphasia groups, and that didn’t work. We had to separate that group out, and then we have to further separate it now to a lower level group and a higher group because people that are more recently diagnosed are freaked-out by people that had started to have some behavioral components. So that’s one issue.
The second issue is that [the patient has] usually seen another neurologist who has either not known what it was or said. Yeah, you have PPA and I’ll see you in six months or a year, and doesn’t make any other referrals. Or we have issues — we don’t do individual therapy at the nonprofit, so, I refer out for speech therapy — and the speech therapists are very concerned about the insurance okaying therapy because it says “progressive” and they need a quicker battery than, you know, some of the testing that you had suggested. But could you identify maybe some of the tests that they really should kind of rise to the top — and then, how to reassure them that this therapy is doing some good and especially in collaboration with a nonprofit like us.
This is wonderful. My name is Becky Khayum and I collaborate with Northwestern and I see most of Dr. Mesulam’s patients. And to answer the last question, I bill Medicare all the time. So this is what I’ve found to be helpful. It really depends if you’re a speech language pathologist if you’re going to be doing for diagnostic purpose or if you’re really going to be doing this for treatment. And if you’re on a team helping to diagnose someone for PPA, obviously then you’ll be doing a lot of standardized tests. But I think most of the speech therapists in the clinics, they’ve already gotten the diagnosis. So what I find is most helpful is more of a life participation, person centered approach. So I will really focus the evaluation on just talking with the person and their spouse and finding out, you know, what their frustrations are. And I completely agree that subtyping and focusing the treatment strategies on the subtyping. To me, I don’t do that either. I look at the clinical profile and what their strengths and weaknesses are but even more importantly what’s frustrating to them.
How you get reimbursement for that is all in how you write the goals. So Medicare is very, very concerned about functional goals and meaningful goals. They’re focusing more on person or the patient rated outcomes. And so if you were focusing all of your goals on their frustrations and what they want to work on and then you make them measurable and you make them attainable. So even if they need a moderate level of queuing to use a communication book, that’s OK. That’s increasing communication. In that way, we can document that and show Medicare that absolutely we can very much show a level, you know, on functional progress. A lot of standardized tests would not reflect that progress. So what I’ll do is throw in a couple of subtest at the end of my evaluation, just what Medicare is auditing. They will see the subtest on there but, well, how I’m proving medical necessity as to my functional goals and outcomes.
Thank you so much and I was curious to hear, is the language study that you’re starting with Georgetown is it opening soon or is it already in rolling right now?
We’ve actually been going on for five years. It’s really to improve or maintain naming. So it’s with all variants. And it’s using a lot of repartition and copying and so on. So it is– we will be submitting competing renewal but it is currently and its fifth– or it’s about to be in its fifth year.
So thank you very much for your comments. And Medicare, I’m sure you all know this. But Medicare did make a decision a couple of years ago that you don’t really have to show progress or improvement in people with neurodegenerative disease. That it is OK to show the people with neurodegenerative disease are just maintaining improvement. As long as your goals reflect that and you show that they are maintaining improvement despite the fact that they have neurodegenerative disease which would otherwise deteriorate then they supposedly will continue pay. It’s not an excuse to say that they’re not improving if they have a neurodegenerative disease. So I really appreciated your comments.
And the other thing about the variants, I think there is usefulness of the variants but they are more for research and for helping us identify more as– perhaps as a neurologist. But you all also– for projecting what other problems they might develop. So, you know, if they have nonfluent variant they might develop problems with– And you can look for this too– for problems with swallowing problems or problems with using their right hand. You know, it kind of predicts the next things that might come up because of the underlying disease. They have semantic variant you might look for behavioral problems. It might not surprise you that they have poor insight and comportment problems that might interfere with their ability to carry out your goals for interacting in society. They become disinhibited and that kind of thing. So, it can help you adjust your goals if you know what to expect.