Parkinson-Plus Syndromes: Multiple System Atrophy

00:01 All right, well let's talk about and learn a little bit more about the four common Parkinson's-plus syndromes, and we're going to review each of them.

00:09 First, let's start with multiple system atrophy.

00:12 MSA is an adult onset sporadic, rapidly progressive multisystem, neurodegenerative fatal disease that's characterized by Parkinsonian features, so bradykinesia, rigidity, postural instability.

00:25 And it can also include cerebellar dysfunction, autonomic dysfunction, or just primary Parkinsonian symptoms.

00:33 We often see urogenital dysfunction and prominent autonomic features, as well as in some cases, corticospinal disorders.

00:43 What's going on in MSA? Well, what we see here is spreading of aberrant alpha-synuclein.

00:50 MSA is an alpha-synuclein apathy like idiopathic parkinson's disease.

00:56 There spreading of alpha-synuclein deposits from neurons to glial cells.

01:00 This results in chronic alterations in glial cell function.

01:04 There's impairment of the trophic function between the oligodendrocytes and the axons, as well as secondary axonal damage and extensive demyelination that is occurring.

01:14 The glial and the myelin are both involved in multiple system atrophy and the pathology is spread throughout the brain.

01:23 There is an inflammatory cascade that is thought to be induced by this process, and then subsequently secondary neurodegeneration is thought to follow.

01:33 What are the clinical manifestations what a patients present with? Well, the history is important.

01:38 With MSA, we see early autonomic dysfunction.

01:41 Orthostasis, erectile dysfunction and incontinence.

01:44 We need to ask for those, we need to interrogate those.

01:47 They're not always apparent when evaluating a patient and their key features to cue in on in a test question or clinical exam.

01:57 On physical exam, we're looking for Parkinsonian symptoms as well as other associated symptoms.

02:02 And there are three types of the MSA.

02:04 MSA of the Parkinsonian type, MSA of the cerebellar type, and MSA that just involves early autonomic dysfunction.

02:12 In Parkinsonian predominant cases, we see akinesia or bradykinesia, prominent axial rigidity, postural instability.

02:20 We may or may not see tremor in the vast majority of these patients, we don't see tremor.

02:25 In contrast, a Parkinson's disease and cognitive function is typically preserved though we may see some subcortical dementia early in the disease.

02:34 In the cerebellar predominant cases, we see early ataxia.

02:38 We can see problems with equilibrium and gait problems in those patients.

02:43 Dysdiadochokinesis or difficulty with rapid alternating movements is present on exam and we really want to look for that when evaluating patients with a possible Parkinson's-plus syndrome.

02:55 And then dysarthria, as well as ocular abnormalities can be observed.

03:01 The diagnosis is made clinically we don't use imaging to diagnose multiple system atrophy.

03:07 But we can see imaging abnormalities and I'm demonstrating some of the more severe and significant in stage changes that we can see on the brain.

03:15 Here we're looking at MRI scans of the brain, the far left is a T2 and the others are sagittal T1 images.

03:22 All the way on the right is normal.

03:23 And we're looking at that midline, that parasagittal image, we see the brainstem, a nice healthy pons, midbrain on top of the pons, and a dominant corpus callosum with the cortex above it.

03:38 In moderate to severe cases of MSA, we can see atrophy of those subcortical brainstem and cerebellar circuits.

03:47 Here you can see on the axial section all the way to the left, atrophy of the middle cerebellar peduncles.

03:54 There's prominent basal cisterns, you see more spinal fluid in those basal cisterns than you would normally.

04:00 And this is indicative of atrophy.

04:02 We can't see a lesion.

04:03 We see what's leftover from neurodegeneration that's atrophy.

04:07 Similarly, on the 2 sagittal images in the middle, we see atrophy of the olive and the pons and the olivopontocerebellar circuits.

04:20 And you can see mild atrophy on the left image and then more severe atrophy on the right.

04:25 And all of this gives rise to Parkinsonian features and likely prominent cerebellar findings in these patients.

04:35 Now let's talk a little bit about some of the MSA variants.

04:38 There's an MSAP or a Parkinsonian type.

04:41 It was formerly called striatonigral degeneration, and this is MSA with prominent Parkinsonian features.

04:48 We may see tremor, we see the typical Parkinsonian signs, and early autonomic failure and that's really what differentiates this from PD.

04:57 In the cerebellar type, this was formerly called olivopontocerebellar atrophy.

05:02 And like the MRI scans we looked at in the last slide, we see prominent olive, pons and cerebellar atrophy.

05:09 Here, the patients present with prominent cerebellar dysfunction, gait ataxia, limb ataxia, ataxic, dysarthria, gaze-evoked nystagmus, axial rigidity problems and dysmetria.

05:22 In the MSA-A type, this was formerly known as shy drager disease.

05:27 This is MSA with prominent autonomic features and patients present with a predominance of orthostatic hypotension, as well as potentially incontinence and erectile dysfunction.

05:38 And this orthostatic hypotension is very, very difficult to control.

05:42 Patients stand up and become hypotensive and pass out.

05:45 And many of them develop supine hypertension.

05:48 So they lay down and they're hypertensive.

05:50 They stand up and they're hypotensive.

05:51 And it's very difficult to control their autonomic nervous system externally.

05:59 How about treatment? How do we treat MSA? Well, there's no definitive disease modifying therapy.

06:05 We do think about supportive care therapy.

06:08 Botox injections can be used for focal dystonia is that can develop.

06:12 Orthostatic hypotension is the most significant symptom we manage.

06:16 We think about using agents that will increase blood pressure.

06:19 Fludrocortisone is first line and midodrine is often second line and occasionally we'll need third or other fourth line agents.

06:26 And urogenital symptoms are not uncommon and we consider agents to treat a neurogenic bladder.