Movement Disorders 3 Flashcards
Progressive supranuclear palsy: epidemiology
PSP occurs more frequently in men.
The mean age of onset is 65 years.
Progressive supranuclear palsy: pathogenesis
Neuronal degeneration, neurofibrillary tangles and tau positive astrocytes in basal ganglia and brainstem structures.
Στους εναπομείναντες νευρώνες των περιοχών που υφίστανται εκφύλιση, ανευρίσκονται ενδοκυτταροπλασματικά έγκλειστα (νευροινιδιακά τολύπια)
Τα νευροινιδιακά τολύπια αποτελούνται από ανώμαλα φωσφορυλιωμένη πρωτείνη Tau η οποία χαρακτηρίζεται από την επικράτηση των ισομορφών Tau που περιέχουν 4 επαναλαμβανόμενες περιοχές.
Επιπλέον, έγκλειστα συσσωματωμάτων πρωτείνης tau βρίσκονται στα αστροκύτταρα (“φουντωτά αστροκύτταρα - tufted, που θεωρούνται τυπικά της νόσου) και στα ολιγοδενδροκύτταρα
The neurofibrillary tangles found in PSP, which contain the
microtubule-associated protein tau, differ from those seen in Alzheimer disease and other neurodegenerative disorders!
Why does PSP not usually respond to levodopa?
Because there is loss of striatal (basal ganglia) neurons and their postsynaptic dopamine receptors
Progressive supranuclear palsy: clinical findings
History notable for early onset of falls, freezing, and
parkinsonism.
Common examination findings early in the
course of disease include prominent axial rigidity, dystonic
retrocollis, and facial dystonia, giving patients an angry or
surprised look.
Typical eye findings include supranuclear ocular palsy, causing impairment of vertical gaze (more commonly downgaze), and ocular square-wave jerks (small horizontal saccades alternately to the left and right).
Patients may be unable to look downward voluntarily, yet reflex ocular movements remain normal.
Speech may be nasal, dysarthric, and slow; phonation is dystonic, giving a raspy growl.
Gait is wide-based, and postural reflexes are absent.
As the disease progresses, dysarthria, dysphagia, and cognitive impairment occur.
Cognitive impairment is notable for bradyphrenia, impaired verbal fluency, difficulty with sequential tasks, impulsivity, poor judgment, and unawareness of falling risk.
Emotional lability, with inappropriate weeping or laughing, may occur.
In some patients with facial dystonia, disabling blepharospasm may occur.
Rest tremor is distinctly uncommon, and there is no effective response to levodopa.
Progressive supranuclear palsy: imaging
Generalized brainstem atrophy, particularly involving the midbrain.
- “hummingbird sign” also called the “penguin silhouette”
- superior cerebellar peduncle atrophy is common in PSP and correlates with disease duration
- “morning glory” flower sign (concavity (κοίλανση) of the lateral margin of the midbrain tegmentum)
Aside from midbrain atrophy, degeneration of the pons, thalamus, and striatum, as well as atrophy of frontal, prefrontal, insular, premotor, and supplementary motor areas, has been demonstrated by voxel-based morphometry
Progressive supranuclear palsy: diagnostic criteria
Clinical Diagnosis of Progressive Supranuclear Palsy:
The Movement Disorder Society Criteria 2017
Basic features need to be present in a patient in order to be considered for the diagnosis of PSP of any phenotype and at any stage.
Mandatory inclusion criteria indicate the presence of a sporadic, adult-onset, gradually progressive neurodegenerative disease.
Mandatory exclusion criteria rule out PSP and need to be applied in any patient.
Context-dependent exclusion criteria also rule out PSP, but should be applied only in patients presenting with suggestive, unusual clinical features justifying further investigation.
Core features:
1) ocular motor dysfunction
2) postural instability
3) akinesia
4) cognitive dysfunction
Supportive Features are those having positive predictive values insufficient to qualify them as diagnostic features, but sufficient to provide helpful ancillary evidence to increase informal diagnostic confidence.
Progressive supranuclear palsy: core functional domains
1) ocular motor dysfunction
2) postural instability
3) akinesia
4) cognitive dysfunction
PSP mandatory inclusion and exclusion criteria
PSP context dependent exclusion criteria
PSP degrees of diagnostic certainty
PSP supportive features
Progressive supranuclear palsy: differential diagnosis
Progressive supranuclear palsy: management and prognosis
● Symptomatic pharmacotherapy –
Unlike in idiopathic Parkinson disease, levodopa and other dopaminergic therapies are not usually effective for motor parkinsonism in patients with PSP.
Nonetheless, a trial of levodopa is reasonable in patients with predominant parkinsonism, as some patients can derive benefit, particularly at first. Ineffective therapies should not be continued long-term.
● Nonpharmacologic interventions –
Multidisciplinary interventions for PSP include speech and language therapy for managing dysphagia and dysarthria and occupational and physical therapy for managing activities of daily living, postural instability, and falls. Advance care planning should be addressed early in the disease course.
Most patients become dependent for care within three or four years from presentation
The disorder culminates in death at a median of six to nine years after the diagnosis
Corticobasal degeneration: pathogenesis
Μακροσκοπικά: εστιακή ασύμμετρη ατροφία φλοιού στη μετωποβρεγματική περιοχή και στις ρολάνδειες περιοχές
Μικροσκοπικά: απώλεια νευρώνων και γλοίωση στον φλοιό, καθώς και σε άλλες περιοχές του εγκεφάλου (μέλαινα ουσία, υποθαλάμιο πυρήνα, κερκοφόρο και φακοειδή πυρήνα, θάλαμο και πυρήνες του στελέχους).
Το χαρακτηριστικό ιστολογικό εύρημα είναι η διόγκωση (balloon neurons) και αχρωμασία των νευρώνων στον φλοιό και σε άλλες περιοχές του εγκεφάλου.
Το κυτταρόπλασμα των διογκωμένων νευρώνων είναι γεμάτο από έγκλειστα που αποτελούνται από ανώμαλα φωσφορυλιωμένη πρωτείνη tau
4 repeat!!
Corticobasal degeneration: mean age at onset of symptoms
61 to 64 years
Corticobasal degeneration: clinical findings
The classic description of CBD is that of a progressive asymmetric movement disorder with symptoms initially affecting one limb, including various combinations of:
* akinesia and extreme rigidity
* dystonia
* focal myoclonus
* ideomotor apraxia
* alien limb phenomenon
Cortical sensory deficit
Cognitive impairment is also a common manifestation of CBD and may be a presenting feature.
Important cognitive features of CBD include executive dysfunction, aphasia, apraxia, behavioral change, and visuospatial dysfunction, with relatively preserved episodic memory
Corticobasal degeneration: imaging
In early stages of CBD, brain imaging with CT and MRI may be normal.
As the disease progresses, abnormalities in the form of asymmetric cortical atrophy are observed in up to half of patients.
Focal asymmetric atrophy predominantly involves the posterior frontal and parietal regions, along with dilatation of the lateral ventricles.
Atrophy of the corpus callosum is also detectable on imaging.
On T2-weighted images, there is signal hyperintensity of the atrophic cortex and underlying white matter and, in some cases, minor signal hypointensity of the putamina and pallida, while the signal in the rest of the basal ganglia remains normal.
Voxel-based morphometry using MRI has shown atrophy predominantly involving the frontal lobes, basal ganglia, and brainstem
Multiple system atrophy: management and prognosis
*Parkinsonism – Although a poor or unsustained response to levodopa therapy is generally observed in patients with MSA, some patients with clinically probable MSA do better with levodopa treatment than without it. The total daily dose of levodopa should be increased to 900 or 1000 mg daily before a trial of levodopa can be declared a failure.
*Dystonia – Focal dystonia may be alleviated by botulinum toxin injection.
*Orthostatic hypotension – Treatment of orthostatic hypotension includes nonpharmacologic and pharmacologic measures as well as avoidance of aggravating medications when possible.
*Laryngeal stridor – Patients with nocturnal stridor may benefit from nocturnal positive pressure ventilation; severe cases may necessitate tracheostomy.
*Sleep disturbances – REM sleep behavior disorder
Prognosis:
Disease progression in MSA is often faster than in idiopathic Parkinson disease, as illustrated by median times from MSA symptom onset to autonomic dysfunction (2.5 years), wheelchair confinement (3.5 to 5 years), and bedridden state (5 to 8 years). The median time from MSA onset to death is 6 to 10 years.
ET and PD differential diagnosis
In its classic form, tremor due to Parkinson disease is a rest tremor and at onset typically begins unilaterally, which distinguishes it from ET.
However, some overlap exists. Patients with PD can have a rapid postural or action tremor indistinguishable from ET.
In fact, it is not unusual for patients with PD to present with a postural tremor shortly before they display other signs of PD. The presence of subtle bradykinesia, rigidity, or micrographia in early cases of parkinsonian postural tremor supports the diagnosis of PD, although these signs may not appear until later.
In addition, a tremor of the same frequency and amplitude as the rest tremor may emerge after a latency during posture holding (the so-called re-emergent tremor). By contrast, ET is apparent immediately with a posture-holding maneuver.
Conversely, patients with severe ET may have a rest component to their tremor in the arms or hands. Older adult patients with ET may have subtle bradykinesia or limb cogwheel rigidity, which needs to be followed as it may signify the emergence of PD.
Involvement of certain body parts can also be helpful in distinguishing PD and ET. While a tremor of the head and neck is more likely to be a symptom of ET, tremor of the jaw or lips is more commonly due to PD. A rest tremor involving the foot or legs almost always suggests a parkinsonian tremor.
Evaluation for classic motor signs of PD (bradykinesia, rigidity, gait, and nonmotor features such as REM sleep behavior disorder and hyposmia) will further distinguish PD from ET.
