Parkinson-Plus Syndromes: Progressive Supranuclear Palsy

00:01 Now let's talk about progressive supranuclear palsy.

00:05 PSP is a degenerative movement disorder that affects the brainstem, basal ganglia, diencephalon, and in some cases, the cortex causing gaze dysfunction, extrapyramidal symptoms and cognitive dysfunction.

00:19 And that's really important.

00:20 I want to highlight a few key features with PSP.

00:23 One is the diencephalon dysfunction.

00:26 And this contributes to early vertical gaze palsy, gaze dysfunction which is one of the things we look forward to differentiate PSP from other Parkinson's and Parkinsonian syndromes.

00:37 What brain areas are involved in PSP? Well, here we're thinking about the midbrain.

00:42 The brainstem can be involved but prominent diencephalon involvement, and upper midbrain involvement is a key feature of progressive supranuclear palsy.

00:54 Like other neurodegenerative conditions, it results from progressive deposition of an abnormal protein and PSP is a tauopathy.

01:04 So we can think of the other tauopathies and this acts similarly.

01:08 We define the tauopathies or we remember the tauopathies by that mnemonic APCP- Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration and what was previously called Pick's disease or frontotemporal dementia.

01:23 In this condition, we see hyper-phosphorylation of the tau protein leading to reduced affinity for the microtubules.

01:31 Hyper-phosphorylation of tau is resistant to proteolysis and forms neurofibrillary tangles aggregates of tau which leads to neuronal dysfunction.

01:42 What about the clinical manifestations in PSP? This is typically insidious in onset and relentlessly progressive like all of the Parkinson's-plus syndromes, it's a neurodegenerative syndrome.

01:53 Symptoms start and they progressed gradually and progressively and relentlessly over time.

01:59 Patients also present with a prominent akinetic-rigid form of parkinsonism.

02:05 So we can think about tremor-dominant parkinsonism where patients have prominent tremor or akinetic-rigid forms of parkinsonism where there's a reduction in movement and prominent axial rigidity.

02:17 And that axial rigidity over appendicular rigidity is a common feature of progressive supranuclear palsy.

02:24 Patients have frequent early falls, gait difficulty, they can have insomnia difficulty with maintaining sleep, personality changes.

02:32 Early Falls is a hallmark of PSP.

02:35 This is due to early downgaze palsy, upgaze palsy is not uncommon with aging.

02:40 We see many patients who are neurologically normal who have vertical upgaze palsy.

02:46 But a downgaze palsy is always abnormal and should prompt additional workup and PSP should be a consideration.

02:53 We also see cognitive dysfunction in this condition.

02:57 On physical exam, we're looking to evaluate for a Parkinsonism.

03:00 We're looking for bradykinesia, rigidity and postural instability, tremor is uncommon.

03:06 We may see other associated symptoms of diencephalon dysfunction, pseudobulbar palsy, spastic dysarthria, dysphagia.

03:16 Early dysarthria, dysphagia should prompt workup and consideration of PSP.

03:20 Focal dystonia is not uncommon.

03:23 Bradykinesia and micrographia can be seen.

03:27 On physical exam, we're also looking for supranuclear ophthalmoplegia.

03:31 And that's the hallmark of PSP.

03:32 That's a loss of supranuclear control of eye movements, a vertical downgaze palsy.

03:38 Blepharospasm, eyelid-opening apraxia and immobility of the eyes can be seen.

03:45 At the end of the disease patients may be completely ophthalmoplegic, unable to move their eyes.

03:52 Other findings that may be seen in PSP are the "drunken sailor" gait.

03:56 This is a stiff, broad-based gait with extended knees and trunk and it results from the axial rigidity that we see.

04:03 Patients turn by pivoting quickly on their toes rather than an "en bloc" turn that we may see with Parkinson's disease.

04:10 And occasionally, we can see pyramidal signs in PSP which would be very, very uncommon in idiopathic PD.

04:18 The diagnosis of PSP is made clinically.

04:20 We don't use imaging to establish this diagnosis.

04:23 But again, late in the disease, we can see findings on imaging that are supportive of this diagnosis.

04:30 Here we're looking at MRI images on the parasagittal plane On the right the normal image, we see a normally large pons and midbrain.

04:38 And on the left, we see an abnormality as a result of atrophy of that upper midbrain, slight reduction in the pons and that beaking of the anterior part of the midbrain owing to midbrain atrophy In terms of treatment, there is no definitive treatment, no disease modifying therapy.

04:59 Again with medical therapy, we think about an initial levadopa challenge.

05:03 Patients often have an incomplete or inconsistent or no levadopa response at all.

05:10 Botox can be used for focal dystonia.