Dysequilibrium and Cerebellar Diseases

00:01 In this lecture, we're going to talk about the approach to disequilibrium and the cerebellum.

00:07 When we're evaluating patients with dizziness, one of the first steps is to determine whether that dizziness is vertigo coming from the vestibular system, disequilibrium coming from the cerebellum, or syncope, presyncope coming from other causes.

00:22 And in this lecture, we'll focus on that second evaluation disequilibrium and the approach to the cerebellum.

00:31 As an overview, where are we headed with this lecture? When evaluating these patients, we start with the description.

00:37 And we want to understand whether the patient's talking about disequilibrium, vertigo, or syncope, presyncope.

00:44 Those descriptions that we look for from patients that hone us in on the cerebellum and disequilibrium, our sensations of drunkenness, a feeling of off balance or imbalance, or unsteadiness when patients are walking.

00:58 When we hear those descriptions, our approach to the patient is to look for cerebellar dysfunction.

01:04 And we do that on neurologic exam.

01:06 We're looking for dysmetria, with finger-to-nose finger testing, or heel-to-shin testing, or ataxia as the patient is sitting in an upright position, or walking in ambulatory.

01:18 And those physical exam findings either on the patient or in a clinical vignette point us into needing to evaluate the cerebellum further.

01:26 And typically, our diagnostic investigation will center around MRI of the brain.

01:31 We may do some other laboratory testing and perhaps some genetic testing.

01:35 But our first step is to typically image the cerebellum.

01:39 The history is told us that's where our concern is, the exam is pointed to that system as the problem, and our imaging is going to evaluate that.

01:47 So that's an overview of evaluating patients with cerebellar problems and cerebellar circuitry dysfunction.

01:52 Let's dive into the cerebellum and understand a little bit more about what's going on with these patients.

01:59 When we think about the cerebellum, most of us think about its importance in motor, movement, and coordination.

02:05 The cerebellum modulates motor movement and helps us to remain coordinated.

02:11 But it also does a number of other things.

02:13 It really coordinates everything that goes on in the brain.

02:16 It coordinates our attention, helps to coordinate and maintain coordination of language and language processing.

02:23 It's important in learning and memory, particularly motor memory, as well as even fear, and our pleasure responses.

02:30 So the cerebellum has been called the mini brain and helps to coordinate most of those brain functions.

02:38 When we think about the cerebellum, there are many problems that can develop.

02:41 Many diseases that affect the cerebellum.

02:44 And this table is an important table for organizing all of those conditions that we can see clinically.

02:50 When I think about cerebellar pathology diseases affecting the cerebellum, I categorize into those that occur sporadically.

02:59 They're acquired.

03:00 They develop over thecourse of lifetime, and those that are inherited.

03:04 The acquired sporadic conditions can be autoimmune things like multiple sclerosis, systemic lupus can affect the cerebellum.

03:12 A rare but important condition called Neuro-Behçet's and Sjogren's syndrome can all affect the cerebellum and cerebellar circuitry.

03:20 We also see infections that can affect the cerebellum.

03:22 Things like infectious cerebellitis or post-infectious cerebellitis, or even Creutzfeldt-Jakob Disease (CJD).

03:30 Neoplasms can affect the cerebellum, as well as paraneoplastic conditions.

03:35 And in terms of the paraneoplastic processes, we think about certain antibodies that have a predilection for cerebellar cells or fibers.

03:43 Anti-Yo, anti-re, and anti-hu are three paraneoplastic conditions that are, have a predilection for the cerebellum.

03:52 We also see congenital or abnormalities.

03:53 Those things in pediatrics or in kids that can affect the cerebellum.

03:57 Chiari malformations, which is distension of the cerebellar tonsils, Joubert disease, and Dandy-Walker syndrome.

04:05 Environmental toxins and ingestions can frequently affect the cerebellum.

04:09 The cerebellum is metabolically active, it's working all the time.

04:13 It's coordinating all those things and functions of the brain.

04:16 And so alcoholism is one of the most common causes of cerebellar dysfunction, as well as gluten enteropathy, it can affect cerebellar circuitry and cause ataxia, and dysmetria.

04:26 Many of our antiepileptic drugs and specifically Dilantin can cause long term cerebellar toxic toxicity.

04:34 Nitrous oxide, and various types of chemotherapy and cytarabine is the chemotherapy to think about that causes dysmetria and abnormalities with cerebellar function.

04:45 And then lastly, we can see degenerative problems affecting the cerebellum.

04:49 And probably the one to remember the most is called multiple system atrophy of the cerebellar type.

04:54 This is atrophy of multiple areas of the brain, but there is a predilection of cerebellar atrophy.

05:00 And this was formerly called olivopontocerebellar atrophy, a degenerative condition.

05:06 So if those are the acquired conditions that affect the cerebellum, we can also think about inherited cerebellar diseases.

05:12 And we categorize those based on whether they're progressive or episodic.

05:16 The progressive conditions just get worse over time.

05:20 And the episodic conditions come and go.

05:23 Progressive conditions are typically inherited, and they can be inherited in an autosomal dominant fashion or autosomal recessive.

05:29 Most of the autosomal dominant progressive ataxia syndromes are the spinal cerebellar ataxias.

05:36 And we number them.

05:37 And you don't need to know all the individual details, but their spinal cerebellar ataxia 1 to 5, 7...

05:43 up to even over the 30s.

05:45 And each of those present often with progressive ataxia with an autosomal dominant inheritance.

05:51 As well as this rare condition, which is interesting dentatorubral-pallidoluysian atrophy, or it's just easier to say DRPLA.

06:00 The autosomal recessive cerebellar conditions are things like Friedreich's ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, and Wilson's disease.

06:11 And again, we can learn in another lecture about some of the details of each of these conditions.

06:16 But it's important to have an organizational structure for how to think of these.

06:20 And there are some other conditions that can cause progressive ataxia.

06:24 The paroxysmal, or episodic ataxias, we call them the episodic ataxias.

06:29 And there's a number of these based on the channel within the cerebellum, that is dysfunctional EA 1, 2, 3, and 4, and those present with episodes of ataxia, and in between the episodes, the patients are typically normal, or some varying degrees of abnormality interactively between those episodes.

06:48 So, if those are some of the conditions that affect the cerebellum, let's spend the rest of the talk talking about what is the cerebellum? How does it work? And what are some of the most common diseases that we should think about when there's a problem with the cerebellum or with disequilibrium? And I think an important tip for a place to start is the cerebellum has been called the mini brain, and it's organized a very similar to the brain.

07:09 And so we can use our understanding of how the brain is structured and organized to understand how the cerebellum is structured and organized? When we think about the brain, that the most outer area of the brain are the lobes, the cerebral lobes, the area of the cortex.

07:24 We think about the frontal lobe, parietal lobe, occipital lobe, and temporal lobes.

07:30 Beneath the lobes are the white matter, the subcortical white matter of the brain.

07:34 And we'll find that the cerebellum is organized similarly.

07:38 And then beneath the subcortical white matter, a deep further is the subcortical gray matter structures.

07:43 In the brain, that's the caudate-putamen, and globus pallidus as well as others accompanying structures.

07:48 And we'll see we have similar organization within the cerebellum.

07:53 So what does that look like in the cerebellum? Well, what are the lobes? The first is the vermis.

07:59 This is that midline lobe, in the center of the cerebellum that controls our trunk in coordination primarily of the trunk.

08:06 And that's the cerebellar vermis, one of the important lobes.

08:10 We also see the hemispheres. The cellar cerebellar hemispheres.

08:13 There's an anterior and a posterior, and a left and a right hemisphere.

08:18 And that controls the appendicular function and appendicular coordination, our arms and legs.

08:23 The last lobe of the cerebellum is the smallest but perhaps one of the more important and that's the flocculonodular lobe, the flocculus and the nodulus, which come together to control coordination of eye movements.

08:36 And these are the three lobes that are involved in cerebellar function.

08:40 Beneath the lobes we see the arbor vitae, that's the name for the subcortical white matter of the cerebellum.

08:46 And that's going to connect the cerebellum to all of the important structures to the brain and to various places within the spinal cord.

08:56 And then going deep further, just as in the cortex, we had deep subcortical gray matter in the cerebellum.

09:01 We also see, there is deep subcortical gray matter structures.

09:05 These are going to be the output relay for the cerebellum.

09:09 Information will come into the hemispheres in the vermis, and the flocculonodular lobe.

09:13 The cerebellum will work on that information to coordinate it and then send that to the deep subcortical gray matter structures to be sent back to the brain and back to the spinal cord, to coordinate our head, eye movement, and other functions.