Parkinson-Plus Syndromes: Corticobasal (Ganglionic) Degeneration

00:01 Now let's talk about Corticobasal Degeneration or also called Corticobasal Ganglionic Degeneration.

00:08 Corticobasal degeneration is also a progressive, asymmetric, dementia-movement disorder with sporadic neurodegenerative 4-repeat tauopathy.

00:18 So it's a mouthful.

00:20 What it means is this is a tauopathy which makes it different in terms of what is depositing on the brain from Parkinson's disease and MSA.

00:28 It is asymmetric and that's a really important feature of CBD that we don't see with some of the other Parkinson's-plus syndromes.

00:35 But we do see with Idiopathic PD.

00:38 It is a movement dementia disorder.

00:40 It begins in the cortex, there's prominent parietal dysfunction as well as Parkinsonian features.

00:47 So let's talk about some of the brain areas that are involved and degenerate in corticobasal degeneration.

00:52 We see prominent parietal lobe atrophy, as well as involvement of the basal ganglia and to some degree, the brain stem.

01:02 What's going on in the brain? Well, this is a tauopathy.

01:05 So we see hyperphosphorylation of tau protein that leads to increase in microtubule formation and abnormalities.

01:14 Hyperphosphorylated tau protein resists proteolysis and forms aggregates and these aggregates come together in the neurons and have been termed neurofibrillary tangles which you can see in the schematic here.

01:28 As tau protein accumulates into these neurofibrillary tangles, this contributes to the degenerative pathology and abnormal neural function.

01:37 CBD is classified as a 4-repeat tauopathy which is a different interval of the number of taus compared to other tau-related syndromes.

01:48 Ballooned, achromatic, tau-positive neurons develop into astrocytic plaques, and other dystrophic glial tau findings are seen.

01:57 And this is similar to what's seen in other tauopathies such as PCP, Alzheimer's disease and Frontotemporal dementia or formerly Pick's disease.

02:08 And there is extensive neuronal loss in this condition, and that contributes to patient's symptoms.

02:16 What about the clinical manifestations? What do we hear from patients and what are we evaluating? Well, number one, we want to look for that asymmetric onset that's common in patients who have seen present with CBD.

02:28 Falls are not uncommon and behavioral changes consistent with a dementing illness are very common in this condition, and often are reported by caregivers, family members and loved ones of these patients.

02:40 On physical exam, we may see findings of asymmetric apraxia, bradykinesia, akinesia, rigidity and postural instability can be seen it as a Parkinsonism and we can see speech disturbances as well.

02:57 Some of the unique features of CBD include myoclonus or hyperreflexia in some rare cases.

03:05 Alien-limb phenomenon is a very unique phenomenon.

03:08 It's highly specific for CBD.

03:11 This is unintended motor actions such as grasping, groping, drifting or undoing of things that the patient is not aware of or in control of.

03:21 The arm literally does what it wants to do.

03:23 It buttons a shirt, it unbuttons a shirt, it moves something, it keeps something, it grabs a hold of things, and it's doing without the patient's willingness or volitional control.

03:34 Patients can also have slowed gait, Frank dementia, and slow saccadic movements or goal directed eye movements.

03:41 So this is really a multisystem disease with prominent parietal dysfunction.

03:48 Again, the diagnosis is made clinically.

03:50 We do not use imaging to diagnose this condition.

03:53 But late in the disease, we can see imaging findings that are indicative of a CBD diagnosis.

04:00 We're looking for atrophy, we don't see lesions on the brain.

04:03 Early brain imaging is important for excluding other causes.

04:06 And late in the condition, we see prominent atrophy.

04:10 We can see it throughout the entire brain, but we often see prominent atrophy in the parietal lobes.

04:15 And here on the axial T2 on the left, we're looking at diffuse atrophy with prominent atrophy in the parietal lobes.

04:22 That's evidence on the coronal, we're looking at a parietal section and you see deep sulci with a lot of CSF in those areas.

04:30 And then on the sagittal T1 here, we also see predominance of parietal lobe atrophy which is suggestive of a diagnosis of CBD in the appropriate clinical setting.

04:40 What about treatment? Well like all of the Parkinson-plus syndromes, we begin with a Levadopa trial.

04:47 And unfortunately, typically, this is met without much success.

04:51 Levadopa does not reduce symptoms in CBD unlike Parkinson's disease.

04:57 And that's really one of the important differentiators between idiopathic PD and all of the Parkinson's-plus syndromes.

05:05 There is no other disease modifying therapy, propranolol, and clonazepam can be used to treat tremors and myoclonus Cholinesterase inhibitors can help with cognitive dysfunction and we really focus on symptomatic management and supportive care.