FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL …€¦ · FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL NEUROLOGICAL PATHWAYS (MODULE ONE) Transcript – Basal Ganglia Presentation by Dr. Datis

MODULE ONE TRANSCRIPT –BASAL GANGLIA | COPyRIGhT © 2016 FUNCTIONAL NEUROLOGy SEMINARS LP | PAGE 1

FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL NEUROLOGICAL PATHWAYS (MODULE ONE)

Transcript – Basal Ganglia

Presentation by Dr. Datis Kharrazian

Okay, so let’s get into the basal ganglia. Now, you guys, the basal ganglia is one of those things that is what we call sub-cortical. So, it’s the area that’s underneath the cortex, it’s right around the thalamus. That’s the sub-cortical area. So we’ve covered the cortical areas. Dr. Brock has covered the vestibular cerebellar areas for you. We went over all the different regions of the cortex. Now we’re going a little bit midline and going into the cortex, or sub-cortical areas, and these conditions are really, really common. Basal ganglia, especially indirect pathway disorders with child developmental disorders, with anxiety disorders, cognitive disorders… they’re very common, and there’s lots of different mechanisms that cause them. So we’ll go over this in some detail.

Now, you have to realize that there’s two pathways to the basal ganglia: Direct pathway and indirect pathway. And we actually have an entire module organized for just the direct pathway, because we need that much time to cover it. We have an entire module just for the indirect pathway, because there’s a lot of depth, especially with applications to it. And what I want to cover just today as a neuroanatomical orientation to it is the general function of the basal ganglia, what are the presentations of the basal ganglia disorders, and what causes these basal ganglia disorders, or the mechanisms that cause them.

So, the key thing is, again, the focus of this module is: how do you identify symptoms just from their his-tory. But with basal ganglia you’re going to get a lot of it just from just looking at them, and their general movements altogether.

So, let’s do a learning exercise. So, I want you guys to think through this. So, if someone is performing finger-to-nose; so let’s say you put your finger out here, go ahead and just put your finger out, and then touch your nose. So, this action right here, pretty simple, pretty straightforward, right? So, in this type of action, what does the frontal cortex do? What does the cerebellum do? And what does the basal ganglia direct and indirect pathway do? Right? Fairly simple. So if you learn the concepts of it, then it’s not so much memorization.

So, if I were to try to touch my nose, and the only thing I were to engage is… if I were only to engage my frontal cortex, on the left side, I first have to plan the movement, right? And if I can’t plan the movement, and I can’t actually initiate it even though I don’t have any nerve pathology, muscle pathology, that’s dyspraxia. Like I’m trying to figure out how to do it but I just can’t do it. So injuries to the premotor cortex would do that. But if the motor strip fires, right, if the motor strip fires and I fire my frontal cortex without my basal ganglia, without my cerebellar involvement, if I was just trying to touch my nose with frontal cortex activity, this is what would happen. Ready? [puts arm over head] That’s it. I touch my nose, but all I have


is a frontal cortex. Ready? No basal ganglia, no cerebellum. You put some electrical shock, going to touch your nose, that’s it. What happens is, when you try to coordinate and have movement, these areas are all integrating together and they’re all having different roles that they play, right?

So, I’m going to simplify it, but it’s a good place to learn concepts. So, for the most part, try to think of the cerebellum as something that turns muscles on and off in sequence, or calibrates. So if I’m going to touch my nose, I have to have my motor system be able to decide how to… when do I turn off my triceps, when do I turn on my biceps, and how do I get supinators and pronators to turn on and off at a sequence for me to touch my nose? Does that make sense?

So, I’m trying to synchronize those things together. And if I have a cerebellar dysfunction, what’s going to happen is I won’t… as I get closer to fine-motor movement, if I can’t turn muscles on and off as well, I’ll start to get a little tremor. Does that make sense? That’s like what happens if the cerebellar’s dysfunctioning.

Now, the basal ganglia direct pathway is going to amplify or add movement to make it more efficient. If the basal ganglia direct pathway is not working, now as I attempt to do finger-to-nose, here’s what you would see [moves hand extremely slowly]. Almost there. So you need a basal ganglia direct pathway to get some amplitude through your thalamus to get some movement going. Make sense? Okay.

Now, if the indirect pathway was not working, I just… I’d have abnormal movement. I’m trying to touch my nose, I’m going to get ready, but I can’t… I have this movement happening. Okay? So that’s where these things play in. Just to give kind of give you some concepts, okay?

So one more time. Put your hand out, touch your nose, okay? If you just fire your cortical strip without anything, burst activity. Okay? If you can’t coordinate turning muscles on and off, and you’re trying to touch your nose, as you get closer to your target, you’ll start shaking a little. They call it termination tremor. If your basal ganglia direct pathway isn’t working, you’re going to be going really slow. So these… They call those hypokinetic movements. And if your basal ganglia indirect pathway’s not working, you’re just going to have hypokinetic movements before you even start. You guys understand?

So, here’s the simple thing when you look at basal ganglia. Your direct pathway adds amplitude to your motor pathway so you have somewhat fluidity and speed. Okay? Your corticospinal tract, your motor cortex, is going to have burst activity, and planned motor movements, but it needs the cerebellar basal ganglia to work together. Everybody okay with that? Okay.

So, that’s really the first initial concept that you understand, that these systems are working together. So if you see someone walking in with slowness, and they’re just walking slow and they’re moving slow and they’re doing things, which pathway is involved? Which pathway is compromised? Direct pathway. If someone has abnormal spontaneous movement of some kind, which pathway’s involved? Indirect, okay?

So that’s the very basic concept of this. So, I want to show you guys just some video clips of different types of basal ganglia, like disorders, just so you’re familiar with them. Take a look at this patient here. We have volume on these here, Ben?

So, this is the patients with Parkinsonism. You guys see the tremors on both sides? And the key feature with it is this pill-rolling type of tremor. You guys see that? Okay. And then with Parkinson’s tremors, when they put their hands out, the tremor stops and then it re-emerges. That’s a key feature of Parkinsonian tremor. And then he’s trying to go finger-to-nose, finger-to-thumb, but it’s very, very slow. That’s called bradykinesia. And then you guys see his feet is really moving slowly there? That’s hypokinetic, bradykinetic movement.


So what you guys will see with people that first start to have slowness, or Parkinsonian-type patterns, they’ll have slowness, and usually it starts on one side first, right? So easiest way to just to do… You know, you can have patients just rapidly move their fingers and thumbs as fast as they can, and if one side starts to slow down, if one side’s like this, one side’s slow like this, which basal ganglia pathway’s involved? The direct pathway. On which side? On the contralateral side. On the left. Okay?

This is good, this is slow. So basal ganglia direct pathway on the contralateral side. So you will see a lot of people that will start to have pathways involved with that, and you can check their feet by just having kind of… go ahead and try to tap the floor as fast as you can. Okay? And then try the other side, and see if they’re okay. Some of you might not be tapping the same, because you have dyspraxia, or other types of conditions, but it’s contralateral. So these movement mechanisms are contralateral. Okay?

Key thing with the Parkinsonian tremors is that they have pill-rolling tremor, but they put their hand out, the tremor stops, and then it re-emerges. Call that re-emergence tremor. Okay? Now, Parkinsonian patterns involve both the direct and indirect pathway, because they have over… they have hyperkinetic movement, which is what? The tremor. And that hypokinetic activity, which is their slowness. So it’s the Parkinsonianism, or Parkinsonian patterns, impact both direct and indirect. The tremor, the excessive movement, is involvement of the indirect pathway; the slowness is involvement of the direct pathway. You understand? I’ll show you guys these in a little more detail.

So, this is a person who’s got what they call chorea, or this dance movement – in Latin, chorea means like a dance – and watch his face and lips, okay? You’ll see his face and lips are moving, but he’s not trying to move them. And then as he walks around you’ll see his limbs moving all over the place, and this is what… this is involvement of the basal ganglia indirect pathway. This is an autosomal dominant genetic disorder. You see him smacking his lips a little bit and moving there? That’s not intentional. That’s involuntary. Look at his face: You see his lips? Now he’s holding his hands up, and you’ll see that he can’t really keep his hands still. He’s trying to keep his hands still. He’s kind of dancing on his own. And as he walks, see how his arms are kind of moving on their own? And they kind of… like this? So that’s indirect pathway involvement. It’s bilateral, with these people that have bilateral involvement. They go… I’ll show you an image of that.

And this is another person that has dystonic posturing, and take a look here as he… Look at his head position. You see his muscle tone is stuck to the left. This is dystonic posturing. This is involving the indirect pathway. He can’t really move his head to the right. See the spasticity there? And then one of these things they do with some of these movement disorders is, they sometimes have sensory tricks. When he puts his hands on his chin, it changes the dystonia. And those eventually, over time, fade away. Because usually they’ll have some of those mechanisms that are involved. Okay?

So, here’s another person, and she’s got what are called myoclonic jerks and dystonia. See how she’s moving involuntarily like that, and she’s got those myoclonic burst activity, those jerks? So this is the basal ganglia indirect pathway.

So, for the most part, in your histories, if you hear “involuntary movements at rest,” you should be thinking basal ganglia indirect pathway. If you hear “slowness of movement,” you should be thinking something’s wrong with the basal ganglia indirect pathways. Just start with that. Slowness of movement: something’s going on with the basal ganglia direct pathway. Involuntary movement: something… Slowness of movement: something’s going on with the direct pathway. Involuntary movement: something’s happening with the indirect pathway. Right? Okay. Those are the key things.

Now, this is a person who has what I call vocal and motor ticks – Tourette’s type syndrome. [subject on video vocalizing] Wake up! Okay. Now, I was able to go to my daughter’s play. She’s ten years old. She’s in a Seussical play. And I can’t tell you how many basal ganglionic-type disorders I saw with people in her cast.


I’m not joking – I’m serious. She comes home one day and goes, “I really don’t really care for this person that I’m standing next to in my performance.” I’m like, “Well, you know, never mind.” And she goes, “Well, I’m getting hit.” I’m going, “Like on purpose?” She goes, “No, he’s just flinging all over the place.” And I’m like, “Well, you know, well, we’ll see.” So then I go to the first show, and he’s got motor ticks, and his arms are flailing all over the place, and I’m like, “Honey, that’s like… this… this… he has something going on with his brain, you know? Don’t be too hard on him. And then I showed her some of these movement disorders, and kind of explained, like, these videos of these types of things, and I go, “If you ever do drugs, this is what happens to your brain.” So just trying to get some of that influence in there.

But there is a little bit of truth to that. You can definitely fire basal ganglia with chemicals, and that’s definitely a well-known mechanism, right? So just so you guys know, there is a group of people in San Francisco a while ago that were – this is, like, maybe twenty years ago – they were trying to make crystal meth, and they made a chemical derivative instead, and all of a sudden, in the hospitals in San Francisco, all these people were coming in with Parkinsonian syndromes, but they were in their twenties. And they found out that they were all taking this chemical, and it was a toxin, and it impacted basal ganglia, and that started an explosion of research, because now they could induce Parkinson’s in animals with this chemical.

So, many of the drugs that people use that impact the dopamine pathways can cause some impacts on the basal ganglia. The basal ganglia is a very sensitive area. It’s sensitive because infections tend to end up there, hypoxia ends up there. It’s an area of the brain where there isn’t many antioxidants, so inflammation, free radicals cause injury to the basal ganglia. It has blood supply there that can easily be compromised with little microvascular strokes. So a lot of people… you may get… you can end up… all of a sudden you get a little stroke, and now you have one of these movement disorders. Okay? So it’s interesting.

Now, a lot of children will have basal ganglia disorders, because they can’t get… their frontal cortex isn’t developed, and the frontal cortex fires to these basal ganglia pathways and keeps it active. So you’ll see a lot of kids with developmental delays have tics, have akathisia, or they feel like they have to move all the time, they just can’t stand still. They’ll have all different types of these basal ganglia patterns. So this is an important area to look at.

Now, when you look at the basal ganglia, the key thing about this basal ganglia is that it surrounds the thalamus. So if you look these pictures here, this midline area here is the thalamus, and these areas around here in the beige are the basal ganglia and it surrounds it. And the basal ganglia direct pathway helps increase amplitude of movement and activity to the thalamus, and the indirect pathway gates it.

Now, here’s where we are. We covered yesterday all the cortical areas, right? Cortical areas are things on the outside. The basal ganglia’s now sub-cortical, sub-cortical areas. Right? So you guys know all the major lesions and seizure activities of the cortex, right? We went over them, you have notes, you have diagrams, you can review them. So now as we go into sub-cortical area, sub-cortical area we have this basal ganglia, and you know, the key mechanisms you want to make sure you can pick up on are direct and indirect pathway disorders.

The function of the basal ganglia, to make it very simple, is that it helps increase activity to the thalamus from the direct pathway, or decrease it from the indirect pathway. Or, in a sense, gate it. Now, the basal ganglia becomes narrower. A lot of people get confused because of all the names to these different struc-tures of it. I don’t want to play this naming game and confusion game with you, but at some point you’re just going to have to sit down and memorize them. And then you’re going to forget them, and then you’re going to have to memorize them. And then guess what? You’re going to forget them, and then you’re going to have to memorize them. Okay. Whether you forget the names or not, you know if you see slowness, you have involvement of the direct pathway; if you see hyperkinetic involuntary movements, you have something going on with the indirect pathway. Everybody okay with that?


Now, don’t confuse cerebellar essential tremor, tremor with movement, as a basal ganglionic disorder. So if the cerebellum isn’t calibrating muscles on and off, you’re going to see what they call an essential tremor. That’s with movement. Basal ganglia indirect disorders are happening at rest. They’re involuntary movements. Okay? That’s a key difference.

So, just to at least go over the anatomy really quickly: So, you have the striatum, what they call the corpus striatum, there’s a neostriatum, and then there’s the older paleo striatum. So the corpus striatum includes the entire basal ganglia and the neostriatum basically is the caudate and putamen, and the paleo striatum is this area in here called the globus pallidus. And then this area here, the putamen and the globus pallidus together is the lenticular nucleus, which is Latin for lens. It’s kind of like a lens shape, okay?

So, the basal ganglia seems really difficult to people, because they read all these names, they go, “Lennticular nucleus,” and they go, “Corpus pallidus excites or inhibits the projections here,” and they go, “Oh my God, it’s so complicated!” It’s not. Okay? Don’t let the names throw you off. I don’t want to spend a lot of time with names, but I just want you to be able to pick up on concepts, and what’s happening when people come in with chief complaints. Okay? At least you have them.

The key thing to really understand, though, is that this basal ganglia’s sub-cortical, and it basically surrounds the thalamus. Do you guys see this where my pointer is right here? That’s the thalamus. Basal ganglia surrounds it, because it’s going to excite it or inhibit it through the direct or indirect pathway, okay? Here’s another projection of it. Those are your internal capsule fibers, these are projections up and down to the cortex, and then you have the thalamus, and then you have the basal ganglia just wrapping itself, exciting or inhibiting it. Okay?

So think of the basal ganglia as something that is gating the thalamus, either making it fire more as needed, or suppressing it as needed, to have motor function and also cognitive function, and we’ll go through each one of those steps.

So, here’s the key concept – and don’t get too fixated on the names for now – so, what you have here is… The first thing you want to understand is the cortex itself. The cortex, frontal cortex – okay? – fires to the striatum. You’re going to see a lot of kids that have lack of development in their frontal cortex. They can’t focus, they can’t concentrate, they may have their midline micturition centers involved, they have bedwet-ting, they walk around toe-walking – that’s what happens when you start to have lack of frontal cortex development – have a lot of basal ganglionic symptoms like tics or akathisia where they have to move, or various things, because they don’t have activation from their cortex to their basal ganglia.

So, the basal ganglia fires and keeps this thing going. Does that make sense? So a lot of these developmental delays in kids, with the basal ganglia, is because their frontal cortex is not really so developed. So if they do motor activity, do sports, become more active, can focus and concentrate, usually you see a lot of these basal ganglia patterns change. We’re going to go into clinical applications with these in different modules, alright? And some of the mechanisms, you can do a lot of things for a person; other mechanisms are very hard to do things, and they may need medications to get through the day, depending on what’s involved.

Now, let’s go through the direct pathway. So, here’s the key concept: Direct pathway increases excitation to thalamic input to the cortex. So it turns things up. So if it’s not working, everything’s what? Hypokinetic. Slow. Everything’s just moving slowly, okay? So the cortex fires to the striatum – it’s part of the basal ganglia – and excites it. And then you have excitation of an inhibition pathway, right? So if you excite inhibition, and then you excite inhibition of inhibition, that’s called disinhibition, which then excites.


Then you throw in the names, and you go, “Oh my God, I’ll never learn the basal ganglia! It’s so compli-cated!” It’s not, okay? Here’s the concept: Two negatives means excitation. If you inhibit inhibition, you get excitation. Just understand that. If you inhibit inhibition, right? you get excitation. They call it disinhibition.

So what you have is here. And this is really about if you excite inhibition to inhibition, you get disinhibition, or you get excitation. Okay, that’s it. I’m not going to go over it any more. I don’t want to confuse you. That’s it.

Direct pathway: excite. Okay?

Now, indirect pathway. You excite inhibition of inhibition, so you get disinhibition, which then excites excita-tion to an inhibitory pathway, and you get inhibition. It is what it is. So then you’re inhibiting the thalamus. So indirect pathway, you decrease excitatory thalamic input to the cortex. But if you don’t know functional neurology and someone is going, “You excite the pallidum to the striatum, and you excite and you inhibit to it,” and you go, “Oh my God, this is so hard.” It’s not hard. This is just where you memorize the names and you kind of go through this three times, and it’s pretty straightforward. Everybody okay with that? Okay.

Now, the key thing that you also want to understand… Everyone understands at this point: direct pathway and indirect pathway. Direct pathway excites input to the thalamus, indirect pathway gates, dampens it. Okay? If the direct pathway isn’t working, you get bradykinesia, slowness of movement. If the indirect pathway is not working, you can’t dampen the thalamus, so you get hyperkinetic movements, right? And the same thing happens with cognitive aspects too. The basal ganglia also impacts cognitive function. If the basal ganglia direct pathway’s not working, you have mental slowness. If the basal ganglia indirect pathway is not working, you can’t shut off your mind. Okay? So there… it’s not just motor, it’s also cognitive as well. Okay?

Now, here’s the key thing. Dopamine is produced through a part of the basal ganglia called the substantia nigra. Right? Everyone is familiar with that. Well, dopamine has impacts on the direct and indirect pathway by its receptors. So the direct pathway has what are called D1 receptors, and the indirect pathway has what are called D2 receptors. Okay? And you guys, you’ve got to realize, there’s D1, D2, D3 – there’s a lot of different receptors. But there’s not a D1 and D2 first. So when people have Parkinsonianism, or they have Parkinsonism where they have issues with producing dopamine, or the substantia nigra gets degenerative and they lose that production, there’s not enough dopamine to fire D1 receptors of D2 receptors to the striatum, so both pathways become impacted. Right?

So the only difference between these… They both use dopamine, but there’s a different effect on a D1 receptor than a D2 receptor. Dopamine activates the D1 direct pathway receptor, and dopamine activates the D2 receptor pathway… for the indirect pathway. So when people start to have low dopamine, that’s why in Parkinsonism, Parkinsonian patterns, you have tremor, which is hyperkinetic, and you have slowness, right? which is hypokinetic. Everybody okay? Okay. So this function here is at the striatum area. So lack of amount of dopamine impacts both pathways, so you lose direct and indirect type of functions altogether. Okay.

And then there’s pathways from acetylcholine, which activates these centers too – we’re just going to kind of skip through that for now.

Now, if you look at here, here’s another illustration of this. You have the striatum, which is, you know, the basal ganglia area. The substantia nigra comes in with dopamine. Here they’re illustrating D1 receptors, which impacts the direct pathway and D2 receptors which impact the indirect pathway. As you decrease dopamine, you have effects on both pathways. Okay?


So basically, you have three different types of basal ganglionic disorders. Pathways: direct pathway disor-ders, indirect pathway disorders, and those that impact both.

This is a paper that you have, and it goes into all these loops. I don’t want to go over it with you, but you have that pathway. It’s organize… we’re going to go do… excitation, inhibition, inhibition is going to make everyone, like, lose their mind. No point. Okay. But I do want to go over concepts with you. So lets go over these concepts here.

So what you’re seeing over here is this illustration of the sensory cortex and frontal and prefrontal cortex, and then you have descending pathways down the spinal cord to motor neurons to cause movement. That’s what you’re seeing here, okay? So you have frontal, prefrontal, somatosensory cortex in the brain, and you have the corticospinal tract that then fires to the spinal cord, to then cause movement, right? So corticospinal, just general gross movement.

You have another pathway down the back of the brain through the red nucleus called the rubrospinal tract that causes flexor tone, jaw clenching-type activity, like that, and then you have reticular pathways, reticulospinal pathways that cause you to have extensor type of functions, and then you have vestibular nuclei that fire into the intrinsic spinal muscles and keep your spine tone stable. Right? So they’re all working together. So you have corticospinal, rubrospinal, vestibulospinal, reticulospinal, all working together to make you have motor movement. Okay?

Now, what you see in this diagram is the basal ganglia, the cortex, the motor areas of the brain are firing to the basal ganglia, both direct and indirect pathways. That’s having inhibition excitation to the thalamus, ventrolateral nuclei of the thalamus, which then goes back to the cortex. So the basal ganglia is involved with gating and cleaning up movements, because if the basal ganglia didn’t clean up movements, then you just have burst explosive activities. You’ve got to excite-inhibit it so it fine-tunes it, so you can actually do things. You guys understand? Okay.

Now, if you add another layer to this, the cerebellum is constantly getting input from gravity, right? Muscle spindles and Golgi tendons are stretching these mechanoreceptors and joints feeding into the cerebellum; the vestibular system’s seeing your head position, firing into your cerebellum, and the cerebellum then fires to the ventrolateral nucleus, and the basal ganglia excites-inhibits it, and inputs from the basal ganglia modulation and cerebellum are then going back to the cortex. Okay?

Think of it this way. Another way. Let’s go down this way first. Let’s say you have motor cor… So, let’s say you plan movement. Plan to touch your nose. When your cortex gets input, it fires into the pontine nuclei. You guys ever seen the brainstem? The pons is where you have the belly? You have the belly there because those are pontine nuclei working on input from the motor cortex. So as your motor cortex plans what’s going on, it fires to those pontine nuclei at the belly, with all those nuclei that are there, and those pontine nuclei fire back to the cerebellum to let it know, “Hey, this is what we’re going to do.” The cerebellum then fires to the ventrolateral nucleus to try to coordinate muscles turning on and off, and the basal ganglia fine-tunes it, excites it or inhibits, takes off the edge, and then fires back to the cortex, and then you have smooth movement. Does that makes sense? This is kind of this loop that’s going on.

So, one more time. You plan some kind of motor activity. You plan motor activity, that information has to communicate with the cerebellum basal ganglia. The motor cortex sends that input down to the pontine nuclei, the pontine nuclei fire into the cerebellum, the cerebellum’s turning, figuring out, “Well, how do I sequence and calibrate muscles turning on and off?” It also fires to the ventrolateral nucleus. The motor cortex is firing to the basal ganglia, trying to tell it what it’s going to do, it shaves off and adds to the smooth-ness of the movement, and if everything’s working great, you have smooth movement. Everybody okay?


If going down to the basal ganglia, the direct pathway’s not working, you get hypokinesia. If the indirect pathway isn’t dampening, you get hyperkinetic movement. If the cerebellum’s not calibrating, you get termination tremor. Everybody okay?

Let’s do it a different way. Even more, let’s add to this. I want to touch my nose. I have to plan touching my nose. If my premotor areas in my brain aren’t working, I can’t do it. I can’t figure out how to plan it. That’s called dyspraxia. I’m trying to figure out how to touch my nose, but I just can’t do it. I may try, I may attempt to do things, I just don’t know how to do it. That’s dyspraxia. It’s a premotor area. Can’t plan it. Okay? If my corticospinal tract is lesioned, I’m going to go into spasticity, and I’m going to try to touch my nose with spasticity. Okay? If my cerebellum is involved, I’m going to have hypotonia, and if I try to touch my nose, at the very end I’ll have a termination tremor. Okay? Direct pathway slowness, indirect pathway hyperkinesia. Does that make sense?

So you guys, just from finger-to-nose, you should go, “Is it in the premotor cortex causing dyspraxia? Is it corticospinal causing spasticity? Is it a direct pathway causing hypokinesia? Is it indirect pathway causing hyperkinetic movements? Or is it cerebellum causing, you know, termination type of tremors.” Right? So you… They’re easy. You can do simple tasks and then identify what areas are involved. Okay.

Now, there’s also another loop from the cerebellum to the red nucleus, which fires back to the inferior olivary complex and back. It’s just another mechanism to constantly recheck and check each other and communicate with each other so you have smooth, you know, accurate movement that’s happening. Right? So coordination is a really big deal. So just a simple task of having someone touch their nose can tell you a lot what’s going on with the person, right? So just by observing people as you get into the session next time, of just seeing how they reach out for things, and how they’re able to, like, walk around and move things, and hand you an office form, and you look at their handwriting, then you look at their speech, you could pretty much start to figure out where the involved region is before you even do your exam. Does that make sense? And we’re going to really go over that in great detail with everyone next time.

Now, the basal ganglia has different loops. It has a motor circuit, which is what we just discussed. It has a limbic circuit, which is all these things applied to emotions. Okay? So let me put it to you in a different way. Do you remember the limbic regions we talked about? The limbic regions where you have modulation of autonomics? Right? The midline prefrontal cortex. The midline prefrontal cortex fires into the sympathetic areas. Do you guys remember that? Familiar. Well, what gates that is the basal ganglia indirect pathway. Just like it gates abnormal motor movement, the basal ganglia gates limbic expressions and emotional discharge and things like that. So when people have lesions to their limbic loop of their basal ganglia, they’ll have autonomic dysfunctions, sympathetic dystonias, they can’t calm down their mind, they feel like they’re going crazy, they can’t shut things off. It becomes a problem. Okay?

And those are GABAergic pathways, and there’s also lots of mechanisms why those become dysfunctional. They can be dysfunctional because of autoimmunity. We just submitted a paper to a journal where we checked two hundred and twenty foods against cross-reactivity against GAD65, the enzyme that makes GABA, and GABA itself. We found thirty foods that people have antibodies to that cause molecular mimicry and cause progression of these disorders. Okay? So we know there’s foods that can do it, we know there’s antigens that can do it. There’s a whole list of things that can make this system dysfunction, okay? We’ll get into those more, but I just want you to understand that these pathways are very vulnerable for different things. Okay?

Now, here’s the thing. If the basal ganglia indirect pathway… So, here’s another… here’s a paper you guys have if you want to read more about this. We talked about the motor loop, and I’m talking about the anterior cingulate or the limbic loop. If this anterior cingulate limbic loop isn’t going, this is one of the mechanisms for OCD. Okay? They can’t stop being excessive about certain thoughts that they have. They


can’t shut it off. Not being able to shut it off… this basic ganglia indirect pathway. Okay? People that have problems there, they have to be distracted all the time. You want to torture them, you put them in a dark room with no noise, and just their mind. Leave them alone, and they’ll go crazy. They’ll start talking to themselves, they’ll start doing things, you know. So they’re always going to be doing multiple tasks, leaving the TV on when they try to sleep, do different types of things to keep that voice to not happen. With that suppressive type of thing.

Now, the oculomotor loop causes a whole list of things. Basal ganglionic disorders can cause all types of eye movement disorders. I’m not going to go… we’re not going to over all of them right now, but just as you know, you do have not only a general motor loop, you have an oculomotor loop which gives eye movement disorders, and you can find out a lot about the basic ganglia by identifying what type of abnormal eye movements people have, right? These are things we’ll cover, and the movement itself, by a neurology of eye movements. Okay.

So, this is another paper you guys can read, and it goes into how these limbic loops cause OCD. So just as the indirect pathway dampens hyperkinetic-type activity, overmovement, exaggerated movements, involuntary movements, it does the same thing through cognitive pathways. So we’ll have people that all of a sudden get a little stroke in their basal ganglia, and now they have OCD, or now they have restless leg and OCD, or now they have a tic disorder, and it is what it is. Okay.

Now, the other interesting thing to know about the basal ganglia is that it also has this somatotopic organization. So, you guys remember the parietal lobe has a somatotopic organization, right? The big lip and the feet and hands and so forth, and then your motor strip has one of those. Well, throughout the basal ganglia, that somatotopic patterns are there. So one of the theories why someone gets a cervical dystonia, or arm dystonia, or leg dystonia, is where the lesion hits on the somatotopic map. So if you have a lesion that’s impacting, let’s say, the feet, you may have something happening like restless leg, or foot dystonia. If it hits the areas in this region, you may have a cervical dystonia or some type of hypokinetic movement there, right? So these also… the basal ganglia also has a somatotopic map throughout it.

Now, this is another great paper that you have that goes into different concepts of the basal ganglia. So let’s just stop and review these seven concepts. This is a good review paper. The key fundamentals of the direct and indirect pathways. Okay?

So, dopamine has opposing physiological effects on the activity of striatal neurons, composing direct and indirect pathways, right? Because you have D1 receptors, which dopamine activates for direct pathway function, and D2 pathways for indirect function. Ablation, or inactivation of the indirect pathway neurons should lead to increased or excessive movement. Or, you guys, increased mind activity, cognitive activity. Ablation or inactivation of the direct pathway leads to decreased movement. Activation of the indirect pathway neurons should lead to decreased movement. Activation of direct pathway neurons should lead to increased or excessive movement. And decreases in basal ganglia output should correlate with increased movement, and increases in output should correlate with decreased movement.

There are some papers that just make everything easier to understand. This is one of them. And you get to have it. Read it. Okay? So come on. It summarizes all the key concepts. Okay?

Now, let’s talk about these indirect pathways. So, the indirect pathway – remember, it inhibits this whole thalamic projection of this loop, and one of the things that can happen is people can get hyperkinesia. This is an illustration of what they call hemiballistic movement, where the arm just flings all over the place. Usually happens after a stroke. And we have an illustration here: Huntington’s disease, which is another choreaform activity. And basically, at the end of the day, what you’ll see is these pathways going into the inhibition pathways become impaired.


Now, as far as hearing things from the history – and that’s the goal for this module, is try to teach you how to pick up on pathways involved with the history – here’s what we know. If someone tells you they have restless leg syndrome, you know something’s going on with the basal ganglia indirect pathway. Things like restless leg, things like tics, whether it’s a motor tic or a vocal tic, like Tourette’s – some people, Tourette’s is both vocal and motor together, right? Those types of components. Vocal and motor tics, those are the indirect pathway.

Athetosis, which is slow, rhythmic type of movement, or chorea, unpredictable dance-like movement that’s slow, those are basal ganglia indirect pathway. Ballistic movement, explosive movement that keeps hap-pening – we’ll show you some videos of that – basal ganglia indirect pathway. Dystonia, where someone’s stuck in a position and they’re contracting and moving like those video clips, those are basal ganglia indirect pathway. You can have muscles dance in the abdomen – they call it abdominal dyskinesia. Akathisia, a lot of kids have it with developmental delays. They can’t sit still. They always have to move. They’ve always got to touch something. They can’t stop. Those are basal ganglia indirect pathways. Stereotypy, where we have people that have to do ritualistic movements like clear their throats all the time, or just touch their shin, where you talk to someone and all they’re doing is just this the whole time, can’t stop it. Basal ganglia indirect pathway. Then there’s wing-beating tremors and dystonic tremors. Those are all types of basal ganglia indirect pathway.

So if someone comes into your office and says, you know, “All of a sudden, you know, my blood pressure’s elevated, I was stressed out, and I’ve had restless leg since that stressful event.” What do you think hap-pened? They probably had a little microvascular stroke, now injured the basal ganglia indirect pathway, now they have restless legs.

Someone else comes in and says, “Hey, my kid can’t focus. They’re… I think they’re diagnosed ADHD. They start to have, like, these types of tic movements all the time in their face, and they’re a toe walker.” What do you guys think? Probably the frontal cortex isn’t activating their basal ganglia, so they don’t have inactivity there, so now these hyperkinetic type of movements. Okay?

So, in your history, if you hear any of these types of clinical presentations, you should be just immediately thinking that the basal ganglia indirect pathway. Alright?

Now, let’s show some of these, how they look like. These are all indirect involvement. So this is a motor tic disorder. Take a look at his facial muscles.

This shows a young man with relatively minor motor tics involved in facial muscles. He exhibits and increase frequency of eye blinking…

See that blinking?

…now prolonged blepharospasm, and also exhibits frowning movements on his forehead and procerus muscles which are later in the video, increased while carrying out rapid movements.

You see this? Next time you go to a fourth-grade play, look for them.

The frowning movements need to be synchronous with his blinking movements.

They’re subtle, but that’s what they are. Okay.

This is choreaform activity. They call it dance-like movement. Look at the arms and legs. Which basal ganglia is involved? Left or right?


So this patient is sitting on a bed; exhibits fairly continuous…

Left. She’s all crossed.

…irregular choreaform movements of her extremities.

It’s not predictable it’s all over the place.

Right hand and right foot seem to be moving independent of…

This is happening involuntarily, on it’s own.

…the left hand and foot.

They can’t voluntarily stop this.

Here we see the repetitive but not entirely stereotyped jerking movements of her arm, hand, and fingers.

Okay? Just think indirect, indirect, indirect, indirect, get it in your head.

Okay. Here’s another case. This is hemiballistic activity after diabetic ketoacidosis.

“My sugar was way, way high, first in a long period of time.”

Is there anything happening by itself?

“Monday I just started gradually kind of losing control of the right side of my body. And Tuesday it was worse. On Tuesday, Wednesday, and today are all about the same.”

It’s all involuntary. Which basal ganglia? Left or right? Left. Okay?

So those are your indirect pathways. Does that make sense? Any involuntary movements, vocal tics, repetitive movements, inability to sit still, you’re thinking, “What’s going on with the basal ganglia indirect pathway?” Okay?

Now, we’ll go over mechanisms, con mechanisms in a little bit, that you’ll see, and then we’ll go into a great detail about what to do for them later on, but right now I just want you to pick those up.

So remember, the direct pathway is going activate the thalamus, to add amplitude to activity, movement, or cognition. And then they’re starting to see scans like you see this person here, you see this is a PET scan where we’re looking at dopamine tracers. You can actually see areas of the basal ganglia with less dopamine. This is a person who started to have right-sided Parkinsonian tremor.

Okay, now here’s the key clinical presentations of basal ganglia direct pathway involvement. Okay? Let’s go left to right slowly, so you guys are all familiar with it.

One of the key features of this is first, hypokinesia, slowness of movement. And the easiest way to check for this is just to have someone do, as fast as they can, rapid movement. Now if one side’s slow, then you’re thinking there could be some involvement of the contralateral direct pathway. It doesn’t mean they have Parkinson’s, but it is a common early feature of Parkinsonism patterns. Okay? Now, you could have what’s


called secondary Parkinsonism. You get head trauma, you injure your basal ganglia direct pathway, you have slowness too. So it’s not always a Parkinsonian disease. That’s neurodegenerative. Okay? We’ll go over the categories. But if the basal ganglia pathways that are direct get involved, you start with slowness of movement. Then it gets progressed into difficulty initiating movement, into eventually they have freezing. This is like end-stage Parkinson’s kind of disease. And that’s usually before they get freezing, they go on dopamine so they can move, and have some stiffness removed so they can, you know, function.

Now, another key feature of basal ganglia direct pathway is hypomimia, which is where they have hypotonic facial expression they call a “masked face.” So many people, when they have… when people start to develop this, people thing, “God, that person is so angry!” Because they don’t have any expressions, right? And they’re not trying to, they just don’t have any tone in their face. And then eventually it progresses into where they have reduced blinking, so they don’t blink as often, they don’t have any expression in their face, they give you that cold stare. That cold stare could just be loss of their motor activity in their facial muscles.

Now, another key feature with the direct pathway involved is people get muscle stiffness and rigidity. The corticospinal tract inhibits the anterior horn, they need that dopamine pathway to do it, and what you’ll see is first of all, when it starts to take place, is they have reduced arm swing and they eventually get into what’s called a writer’s cramp: when they start to write, they start cramping, because their muscles are stiff, and they end up with a cramp, and they eventually progress to shuffling gaits, frozen hips, and then they start to ambulate with rigidity. So, let’s say someone comes into your office, and they do this [walks stiffly]. You guys see that? And then they do this [moves right-hand fingers together slowly, then left-hand fingers together fast]. Where’s the area involved? Left basal ganglia, direct pathway. Okay.

Now, they eventually get dysarthria from lack of motor movement, and then they start to get constipation because the dopamine pathways, indirect pathway, also impact gut motility, and in Parkinsonianism, the protein aggregation, this protein buildup that we’ll talk about in a second here, starts in the gut first; they get constipation. So if a person comes in, they have frozen shoulder, constipation, they have slowness of movement, you should be thinking, What’s going on with their basal ganglia direct pathway?” Okay? What you see on the limb applies to the contralateral side.

So, here’s a case of a young-onset Parkinson’s, and take a look at this person’s gait, take a look at their facial tone, take a look at their arm swing, and just kind of see the features of it. And by the way, young-onset Parkinson’s is around age thirty. And it’s about thirty percent of cases. So we think that this condition happens in older people, in seniors, but it can happen in early onset with people in their thirties, okay?

Oops. Let’s see if I can get this to work. Whoops. Is it not working? Huh. Hm. Try something.

This patient with young-onset Parkinson’s disease exhibits relatively normal gait. There is reduced left-sided arm swing.

You guys see that? I’m going to have to put it in this view for a sec. You guys see the reduced arm swing?

There is apparent facial masking, and repetitive fine finger movements, and hand movements on the left are slow with some decay over time.

Yeah, the slowness on the left side? And then how slow it is on the other side? So. Again, slowing on that side.

Repetitive foot tapping movements are mildly slow and irregular on the left.


Which basal ganglia? Left or right? So you… This is important, because then you go, “Hey, how am I going to activate that basal ganglia? If I’m going to use cerebellar projections, I’m going to go from the left side.” Right? Or whatever it is. You think of your pathways you want to activate, and then you’ve got to know which side is involved.

Okay, here’s another case. Let’s look at this one. This is the key features of the re-emergent tremor.

…with tremor-dominant Parkinson’s disease, displays a very large amplitude resting tremor of her left upper extremity.

High amplitude [unintelligible]

Her arm’s elevated. After a period of several seconds she develops a re-emergent tremor of similar type in the left arm.

So usually with a lot of these tremors, once they lift their arm it stops for a second, and then…

The tremor does suppress during action, such as finger-nose-finger movements.

See how it slows down?

Once again, she displays very regular and rhythmic large-amplitude resting tremor of her left hand. It suppresses momentarily when she elevates her arms and then re-appears with similar amplitude to its appearance at rest. I’d say she clinically did not exhibit significant findings of bradykinesia or rigidity in left upper extremity. They were present but they were quite mild.

Now, one of the things that they do is, they measure these – let me see if I can get this – they measure these slowness with a scale: Unified Parkinson’s Disease Rating Scale. And then you can see the degree of slowness, or bradykinesia, with some of these video examples.

Here we see four patients with idiopathic Parkinson’s disease. They all showing rated scaling on the Unified Parkinson’s Disease Rating Scale, or the UPDRS. This first lady is normal on the right, 0. On the left hand she might have a score of 1, even a slight decrement in amplitude and speed of the motions. The second gentleman will probably score 2 as he has a few hesitations in his rapid repetitive movement, especially on the right upper extremity. This third person is a lady with much more significant bradykinesia. You can see she has frequent hesitations in performing these repetitive movements with very decreased amplitude and decreased speed. And this fourth gentleman is barely able to perform a task at all, so this would probably be graded a 4 on the UPDRS.

Okay. So the key thing with any of these… Most of these are degenerative diseases, idiopathic Parkinson’s pattern. The key thing with them is, you identify it early, and then you do all the different interventions. And you can identify it early by just having people rapidly move their arms. And don’t call it Parkinson’s, because you’re going to freak people out. If you’re not sure, don’t make the call. Just know that the direct pathway’s involved, and then consider those different types of possibilities. Okay?

So those are the rating scales involved.

Now, when you look at how this works, just so you understand the language, any type of slowness, brady-kinesia, stiffness, anything that involved a direct pathway, they just use the word Parkinsonism. Doesn’t have to be the neurodegenerative disease Parkinson’s. So any condition that causes movement abnormality similar to Parkinson’s disease, such as bradykinesia, muscle rigidity, is called Parkinsonism.


Then they have the idiopathic once, which is your classical Parkinson’s disease, right? A neurodegenerative disease, Parkinson’s. And then they have what are called atypical Parkinson’s disease, and the key feature between these two, commonly, is these ones are more aggressive. They cause more serious compromise of the brain over time, and they don’t respond to dopamine.

And these are a whole set of different disorders: Progressive supranuclear palsy, multiple systems atrophy, corticobasal basal degeneration, Lewy body dementia. Lewy body dementia is sometimes not… is pretty easy to diagnose, because as soon as they try dopamine with them, they get demented. Okay?

Now, they call people that have medications or strokes or head trauma impact the direct pathway secondary Parkinsonism. So the word Parkinsonism is now being used for any involvement of the direct pathway. So in your atypical Parkinsonism or secondary Parkinsonism, it’s not necessarily neurodegenerative Parkinson’s. Atypical actually is a neurodegenerative process, but it’s much more aggressive. Okay? So you could have a head trauma impact the direct pathway, and be considered having secondary Parkinsonism. But it’s not a neurodegenerative disease. Okay.

So let’s get into… then there’s the… let’s skip that one.

So the key thing now to discuss is, what are these mechanisms that actually cause the basal ganglia to fail? And let me put it to you this way: Your basal ganglia direct pathway disorders are usually neurodegenera-tive. Your basal ganglia hyperkinetic disorders are typically not degenerative. They’re usually genetic, or a stroke, or an infection. Something that injures the basal ganglia. Okay? So your hypokinetic ones are usually degenerative; your hyperkinetic ones are trauma, stroke, or genetic disorders. So we’ll go over some of these in detail.

So let’s talk about Parkinson’s itself. Degenerative pathways. So with Parkinson’s disease – I know we all think of it as a low dopamine or dopamine deficiency disorder, but it’s actually a protein aggregation disorder. This means proteins in the brain start to build up, and then immune cells wrap around them, and these are called Lewy bodies. So what happens is – and this is the key picture, these Lewy bodies; I’ll show you a better illustration – you normally have proteins that are involved with the structure of neurons. These alpha-synuclein start to build up, and the immune cells start to surround them, and this debris gets in the way of normal transmission, and eventually you start to have loss of pathways and degeneration, because neurons can’t excite each other.

This starts in Parkinson’s in the GI tract. The first initial symptom of neurodegenerative Parkinson’s is constipation. The second area that it hits is the olfactory bulb, and they lose smell. Someone who comes in to your office, chief complaint of constipation, and then they don’t smell well, and then you see hypokinetic movement and lack of arm swing, you’ve got to look at that constipation from a whole different perspective.

This alpha-synuclein buildup then eventually starts to infiltrate in, into the substantia nigra where they start to impact dopamine pathways and centers, and then they start to get both hypokinetic, hyperkinetic tremor and progression of the disease itself. Okay? So, what you want to really look for is, in the early stages you may have chief complaint only of constipation. If you have chronic constipation and nothing has every helped them, they’ve tried every supplement in the world, you should be looking for Parkinson’s pattern in your exam. Key things being hypokinetic issues.

Now, let’s say you have a patient that comes in and says, “Yeah I’ve had this constipation. I’ve tried all these different protocols. None of them really worked. I have to have coffee enemas regularly to have any kind of bowel movement. I have to take high doses of magnesium to function. And you know, these are things that I’ve been dealing with for a long time. It seems to be getting worse and worse over time.” And they also have a frozen shoulder no one can fix. Aghh!


You move their arm around, it’s stiff; you see them walk, they don’t have arm swing; and then you see bradykinesia. That’s not a chronic constipation, that is neurodegenerative changes in the early stage. Early Parkinson’s patterns. Does that make sense with everyone? Okay.

So eventually, as the alpha-synuclein builds up – and there’s some research showing that the alpha-synuclein actually starts in the gut and goes up the vagal motor complex into the brainstem and brain. It actually migrates from the gut all the way up. Really interesting stuff. And as it hits the substantia nigra – here’s the dopamine centers – there’s decreased dopamine. And what does dopamine do? Dopamine activates the D1, D2 receptors, and then you get clinical manifestations in the direct and indirect pathway. Progress. Okay?

Now, so that’s your… that’s one mechanism of basal… the most common mechanism of why you would see someone have basal ganglia direct pathway disorders, right? That whole hypokinetic type of thing.

Now, let’s talk about Huntington’s disease, which is a hyperkinetic disorder. It’s an autosomal dominant genetic disorder. They start to have loss of neurons and gliosis and its inflammatory response in the brain, and look what happens to the basal ganglia. Just degenerates away. It’s genetic. It’s not a… like these epigenetic things that are talked about. It’s an autosomal dominant disorder. Okay? It’s a very ugly disease. So you’ll actually see these with your basal ganglia indirect choreaform activity.

Now, a major cause of acute onset basal ganglia patterns are what are called lacunar or micro… small vessel disease strokes. And what this means is the small tiny little blood vessels get a little occlusion, and there’s pathways off the medial cerebral artery into the basal ganglia – they call these lenticulostriatal branches – and they’re a very common site for them to be occluded, and then they get basal ganglionic strokes.

This is a great paper for you guys to read. It goes into these lacunar infarcts and small vessel disease. The most common location of these lacunar infarcts are the putamen and the pallidum, followed by the pons, thalamus, and caudate. So, the key feature of these is acute onset. Acute onset restless leg. Acute onset OCD. Acute onset tics. You should be considering a lacunar stroke; like these little small vessel strokes. Like, here’s one. It’s not a major artery, so they don’t have a spastic posture and they can’t walk and talk; they just have boom! one area of their little brain, and the area of the region of the brain involved that gets injured, basal ganglia is a common site for it. Key thing, that it’s acute onset. All of a sudden. Okay?

Stress activates these, and anything that causes hypertensive responses tends to promote these. So it’s not uncommon to see. Here’s another one. You can see a little lacuna small vessel stroke right there.

In that paper you can see, here’s the major artery, and then these small branches, they get a little atheroma blocks it, and it starts to cause tissue death on the opposite side. Different illustrations of how these work.

Here you go, basilar artery, get a little branch off it, boom, you get an occlusion, you get a little lacune lesion. So, basal ganglia’s very, very vulnerable for those. And people that have hypertension, they’re at high risk. Guys: hypertension is real. Hypertension cause… leads to stroke. It’s not the whole cholesterol model controversy. If you have hypertension, you have high risk for stroke. It’s fact. So if you see hypertensive people, you have to consider… and you see history of hypertension, all of a sudden indirect pathway or direct pathway involvement, that’s a cue, you’re thinking that they had a lacunar stroke. Okay?

Now, there’s also mechanisms that injure the basal ganglia. This is a study that was published in Lancet, and they were looking at all the different mechanisms that can cause this disease or dysfunction in the basal ganglia pathways. Parkinson’s was the most common thing, but look at over here: carbon monoxide poisoning was one, brain tumor not as frequent. And then this was another paper where they looked at all these different causes, the things that can impact the basal ganglia, and you see again: carbon monoxide poisoning; you see chemical poisoning, toluene, ethanol, thallium. Chemicals tend to be very destructive


to the basal ganglia. So people that get toxicity, get exposure, can have degeneration of their basal ganglia. People that work around industrial chemicals have a problem.

Now, you see manganese up here? It’s not the mineral manganese. It’s magnesium oxide, what hey use for metals in industrial work. I mean, I’ve had this… this one time, this person had early Parkinson’s syndrome, went to see the neurologist, and go, “Oh, what are you taking? You taking supplements? What are you taking?” Well, one of the ingredients was manganese. He goes, “Oh, you can’t be on manganese.” Do not confuse manganese the mineral with manganese oxide, the industrial compound. Okay?

So, we know that those things are there. Celiac disease has also been shown to be a problem with basal ganglia disorders. But also look at this: ovarian and lung tumors can lead into basal ganglionic disease as well. So, these are called paraneoplastic movement disorders. So when you actually have a tumor that develops in your body, whether it’s in the lungs or breasts or tissue, your immune system starts to make antibodies against those tumor cells. Okay? Well, those antibodies can have molecular mimicry, or amino acid sequences, close to cerebellum tissue. So when you end up with, let’s say, an ovarian tumor or a lung tumor, and you begin to make antibodies against those, those antibodies have the ability to bind to cerebellar… basal ganglia-like target sites, and then cause immune destruction against those tissues. So if you see new onset basal ganglia symptoms, there’s a possibility that it could be paraneoplastic. Okay? So be aware of that.

This is an image, T2-weighted MRI scan of a person with carbon monoxide poisoning. A really good friend of mine had carbon monoxide poisoning. And when I heard about it, I’m going, “Man, I hope his brain’s intact, because he’s got a really good brain.” He was okay though. As far as we know. So far. We’ll see in a few years, but for now we’re all good.

So you can see these lesions throughout the brain. The basal ganglia is very vulnerable to hypoxia, to chemicals, to free radicals. It can be impacted very quickly with them.

This is a case that was put up of a pesticide-induced destruction of the basal ganglia. Let’s take a look at that.

This individual developed…

Volume please?

…fairly acute Parkinsonism by ingestion of a large quantity of pesticides of uncertain type. There’s marked facial masking with reduced facial expression, increased blink frequency…

Look at his hand. You see the hand on the left side?

…there’s a dystonic posture in his left upper extremity…

See all that blinking?

…as well as some dystonia in the right hand. With his arms extended, the dystonic posture’s evident in both hands, but asymmetric; more severe on the left side.

See the slowness?

His rapid open-close hand movements are slow and very limited in excursion on the left, whereas they’re not as involved on the right side. Rotational movements of the right wrist are mildly impaired and he’s not


able to carry these out on the left. He’s able to get up from the chair with his arms crossed, and gait is burst. Right-arm swing is possibly mildly reduced, and close to normal while there is no arm swing on the left.

See the arms?

Dystonic upper extremity.

So listen: If you see someone come in, you see their facial tone drop like this, you see lack of arm swing, you see slowness, which pathway? Basal ganglia direct pathway. Okay? And there’s definitely involvement more on the right. It’s probably bilateral, but greater involvement on one side, okay?

Now, there’s a lot of chemicals that have been shown to cause Parkinsonism. And yes, they’re not just all mercury. Please don’t be that person. Please don’t be the person that every neurological disease in the world is mercury and you have to chelate everyone. Don’t be that person. Okay? Because you can actually harm a lot of people with chelation. You can really promote neurodegenerative disease with chelation. If they’ve lost their blood-brain barrier and you chelate them, you can absolutely make them worse. There are now multiple publications that show that DMPS, DMSA, EDTA actually push metals into brain. You have a compromised blood-brain barrier, you add a chelate agent on top of it, that person will get worse. It’s not a detox reaction; you’ve induced greater degenerative changes with those types of treatments, right? And you guys, a lot of these chemicals that can cause Parkinsonisms and stuff, you can’t… it doesn’t even bind to a chelator. It’s not a heavy metal. It’s an industrial compound, you know? It’s not the same thing. So you’re not going to chelate out pesticides. Those are phase one, phase two metabolic pathways that need to be addressed.

Now, in 2014 we published a paper in Journal of Applied Toxicology. We took four hundred people, we checked them against chemicals bound to albumen, and what we found was, about twelve percent, twelve to eighteen percent of the population had chemicals that are known to cause Parkinsonism. Okay? And we checked isocyanates and formaldehydes and benzenes and different compounds, and we found them in more… over ten percent of the population. These were chemicals bound to human tissue, they become new antigens. We have now gone through and are doing correlation studies, with if they cause neurological disease, and guess what? They do.

We found very, very… the first paper we just submitted, we found compounds like plastics are highly cor-relative with myelin autoimmunity. So chemicals are really this kind of underlying thing, but we’re going to talk about the difference between heavy metal toxicity, chelation, acute stages versus loss of chemical tolerance, versus immune reactivity to chemicals. These are all different factors. You’ve got to be very, very careful how you look at… what you do with chelation and looking at chemicals altogether. PCBs, pesticides, are a common trigger for basal ganglionic disorders. There is a panel you guys can order. Genova has one, where they can look at pesticide levels and see what the total load of a person is. These aren’t bad things to consider running, just to see what levels are. Cyrex has another test where they look at chemicals bound to proteins. So sometimes when you see degenerative changes, it’s not a bad idea to look at these different types of profiles. Okay?

You guys, these profiles, where you look at pesticides and chemicals and PCBs, and panels like this with immune reactivity to chemicals, is much better than – let’s just say – total mercury post-challenge, because these are very high levels acute triggering events. Okay?

Now there’s a paper I have put for you guys in your notes, and it goes… it’s a paper I published: “Toxicant Loss of Immune Tolerance, Neurologic Disease, and Nutritional Strategies.” I don’t want to go into all the details, but you have a summary paper of the research of what nutritional strategies can be used with toxic


insult to neurodegenerative diseases. So those are things we always consider when we see some conditions that may be involved.

Now, infections love the basal ganglia. So many infections tend to destroy the basal ganglia. This is a care of an HIV-induced destruction of basal ganglia. And go ahead and watch.

This woman with HIV Parkinsonism displays generalized bradykinesia, very prominent facial masking, and a fixed stare.

See how slow she’s moving?

She’s able to protrude her tongue, but it’s side-to-side, horizontal tongue movements, so it’s slow. Again, the finger-tapping movements are markedly slow with area[? 1.11.57] reduced amplitude of movement.

Okay. Look at it. You guys, it’s good to see the slowness, see the masked face, see the lack of arm swing. So you start to connect with what those patterns are.

Now, that was HIV-induced infection. One of the most common ones is streptococcus. PANDAS. PANDAS is real. PANDAS is very common. The rates of PANDAS exceed the rates of autism. So what happens is, these kids get infection. The most common one is streptococcus, and PANDAS stands for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus. Okay? But what happens is, they get a streptococcus infection, and here’s the key thing: Their blood-brain barrier’s breached. The antibodies they make against streptococcus have immune cross-reactivity with the cerebellum. So what that means is this: Antibodies attach to an amino acid sequence. So the amino acid sequencing against strep has a sequence change where the amino acid sequence of the basal ganglia is almost identical. So when people have an infection with strep, and antibodies get produced, it not only attaches to the strep antigen, but also attaches to the basal ganglia. If the basal ganglia is vulnerable because the blood-brain barrier’s breached, then those strep antibodies attach to the basal ganglia and then T-cells and immune cells go in and start to destroy and eat up the basal ganglia. That’s PANDAS. Now they’re finding other infections do it. And this is a – you know – not uncommon. You see it all the time.

So this is a child who is… that’s suffered through this whole PANDAS response.

You see the vocal motor tics. PANDAS is scary stuff.

So, some of these kids, when they get this immune response against their basal ganglia, they do terrible things. Some of them will be in a car and just jump out of the car. Some of them have severe psychiatric reac-tions. The basal ganglia is very, very vulnerable for certain infections because of antibody cross-reactivity. Okay?

Now, at this point, like, you guys, when these things happen, they need to have their brain rehabbed. They have to go through it, and have the blood-brain barrier heal, and go through all the different strategies. We will talk about that when we get into the basal ganglia for the treatment modules.

So, here’s the illustration of this whole PANDAS effect. They get a streptococcus infection, there’s molecular mimicry that binds to different areas of target sites in the basal ganglia, and then they have an immune response against it. Okay? So, infections can destroy the basal ganglia.

Iron accumulation. Some people have had very high iron levels, hemochromatosis. They can have the basal ganglia destroyed. This is an example.


This individual with neurodegeneration with brain iron accumulation displays while sitting a fairly gen-eralized dystonia, predominantly affecting the trunk and cervical region. While walking, he displays slow involuntary movements involving his left upper extremity with flexion at the elbow and adduction at the shoulder. Gait is characterized by short stride lengths and shuffling, and the associated left upper extremity movements.

Okay. Then you can see iron accumulation MRIs. And this is one of the reasons you want to look at iron. I cant tell you how many times we just run routine lab work and we see people that have hemochromatosis, iron overload disorders. Again, once blood-brain barriers get breached, and you get accumulation in the brain, goodbye basal ganglia. Okay?

Now, why does he have a cervical dystonia? Because the areas in the homuncular map that were hit in the basal ganglia had… were cervical in region. Does that make sense? Could have been an arm region, or certain areas. So… and these things can be subtle. This seems to be extreme, like these cases, but they do occur.

So, the basal ganglia is a vulnerable tissue. It’s vulnerable to oxidative stress, free radicals, iron accumula-tion, manganese accumulation, and antibodies, streptococcus. Here’s… copper toxicity causes very unique impact to the basal ganglia. Copper toxicity tends to cause what they call this wing-beating tremor. Let’s see if I can play it here.

This patient with Wilson’s disease displays a very characteristic wing-beating tremor of both upper extremities.

And you can see there’s a region that copper responses take place in. Wilson’s disease is a genetic copper metabolism disorder, and it can infiltrate into the basal ganglia.

The basal ganglia’s also very prone to autoimmunity. This is…

This patient with anti-NMDA receptor encephalitis is seen in an intensive care unit setting. She displays a repetitive, somewhat complex involuntary movement with rhythmic facial and chewing movements…

Direct or indirect pathway? Indirect. Hyperkinetic. They’re all going to be different. They’re not going to all be the same.

…as well as continuous stereotypic jerking movements of her extremities.

Alright. So, they’re not fun to look at, but they are what they are. Now, what you’re probably going to see in a common practice environment are kids that have tics, vocal tics, motor tics. You’re going to definitely see some types of dystonias, tightness. They’re not uncommon. You see those all the time. You see restless leg all the time. You see OCD all the time in – you know – in general practice.

And the thing is, there’s been injury to the basal ganglia. So there’s been injury to it? What do you do next? Just think about it. If somebody had an injury to the basal ganglia, what does the health care model have to offer for them? Like, “That’s it! Too bad for you! Maybe you’ll recover, maybe you won’t.” This is where functional neurology shines, because you can go in there and try to activate regions, try to get connectivity, try to get plasticity, see what mechanisms are going on. You want to look at underlying mechanisms that are taking place. Does that make sense? I don’t know how to say this, but this kind of treatment, this kind of model, is really what they need, what can potentially make a big difference for them. Okay?

So, you know, look at those, look at these things as situations where it’s not totally hopeless. You can do a lot of things for them.


There’s a paper that I also put in your notes for you, that I published, that’s on nutritional and dietary considerations for the basal ganglia. There was a period of time where we had some really crazy talk, where people were saying you can’t give antioxidants to basal ganglia. All the research shows, one of the things you do to protect the basal ganglia is, you load up on antioxidants. So it’s one of the tissues that is very vulnerable to oxidative stress. There’s a summary paper I put in for you that goes through all the major research that you can use to protect the basal ganglia.

Now, whatever the mechanism of injury was, it’s still a good consideration to consider some of these antioxidants that you can use for them. And you know, you can look at the papers yourself to get a general idea of what they are.

Okay. So, let’s go over the key concepts, make sure you guys understand them.

Now, in your notes, in your module on the basal ganglia, I wrote a… we put together a key concept paper that summarizes all the things we just went over. Okay? So again, I would encourage you guys to read those key concept papers in the next couple of weeks, really ingrain it into the time we spent this weekend.

So, what are the general functions of the basal ganglia? So, the basal ganglia has a direct pathway; has an indirect pathway. There’s a hyper-direct pathway that… we’ll talk about that later. The direct pathway and an indirect pathway. The direct pathway helps activate the thalamus; the indirect pathway gates it and dampens it. You have to have a balance between both types of areas for movement that’s proper, and cognitive types of responses in the brain, okay?

The minute you guys see lack of arm swing, slowness, constipation, muscle stiffness, frozen shoulder, you should be thinking what? Which pathway? Potentially basal ganglia direct pathway, contralateral to the involved side. If you see restless leg, OCD, Tourette’s, motor tics, vocal tics, you should be thinking basal ganglia indirect pathway. Okay?

So, those are the first key things that you want to take away. Once you see those disorders, here’s the basic concept. If someone has direct pathway involvement, and they have hypokinesia or bradykinesia, slowness, stiffness, movements, the most common cause for those is what? Degenerative. Those are usually Parkinsonian. People that have indirect pathways are not typically neurodegenerative. Something usually injures the basal ganglia. They get an infection. They get iron accumulation. They get cross-reactivity. They get a stroke, right? So they tend to be more acute onset versus progressive over time, okay?

So those are the key things that you really want to understand from these basal ganglionic types of presentations and concepts.

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FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL …€¦ · FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL NEUROLOGICAL PATHWAYS (MODULE ONE) Transcript – Basal Ganglia Presentation by Dr. Datis