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progressive supranuclear palsy; Steele-Richardson-Olszewski syndrome (PSP)
Parkinsonism plus disturbances of ocular motility.
Epidemiology:
1) rare (4% of patients with parkinsonism)
2) age of onset: after age 50, generally 60-70 years
Pathology:
1) aberration of tau protein
- abnormal staining in pretangles/neurofibrillary tangles
- tuft shaped astrocytes
2) degenerative changes in:
- brainstem, midbrain (substantia nigra), cerebellum, nucleus basalis, cerebral cortex, diencephalon, basal ganglia (globus pallidus)
3) neuronal loss
4) gliosis
5) neurofibrillary tangles (different from Alzheimer's disease)
6) iron accumulation in brain
- astrocytes accumulate iron & iron deposition is found in regions with tau deposition [11]
- hemoglobin & neuroglobin are dysregulated in these same brain regions [11]
Genetics:
- associated with polymorphism (Arg-7) in saitohin gene
- subhaplotypes of MAPT associated with risk of PSP & severity of tau pathology [10]
Clinical manifestations:
1) supranuclear vertical ophthalmoplegia
a) inability to move the eyes vertically
b) not always 1st sign; generally present by year 4
c) downward gaze affected more than upward gaze
2) other oculomotor & eyelid disturbances
a) wide-eyed
b) square-wave jerks (fixation instability)
c) intact Doll's eye movement
3) gait ataxia, postural instability - early falls (often backward)
4) parkinsonism
a) axial rigidity > limb rigidity
b) bradykinesia
c) resting tremor (often not prominent)
5) dysarthria, slurred speech
6) dysphagia
7) nuchal extension & rigidity (hyperextension of neck)
8) facial dystonia:
- contracted facial muscles may give the appearance of sustained surprise [6]
9) pyramidal tract signs
10) cognitive or behavioral changes
a) dementia
- slowed processing speed
- impaired executive function
b) emotional lability
c) apathy
11) hypertension may be present
12) late stage: immobility
13) marked incapacity within 3-5 years
Laboratory:
- generally normal
- higher levels of neurofilament light chain in serum in multiple system atrophy or progressive supranuclear palsy than in Parkinson's disease & healthy controls
Radiology:
1) magnetic resonance imaging & CT may be normal or may show frontal &/or midbrain atrophy
2) PET scan is generally shows frontal hypometabolism (2-fluoro-2-deoxyglucose), but may be normal
Complications:
- complications of immobility
Management:
1) poor response to Sinemet
2) control of agitation, emotional lability
- selective serotonin reuptake inhibitor (SSRI)
3) local botulinum toxin A (Botox) may improve rigidity
4) selective serotonin reuptake inhibitors (SSRI) may improve dysarthria & dysphagia [4]
5) electroconvulsive therapy of limited benefit for improving bradykinesia, rigidity, gait instability
6) avoid neuroleptics
7) prognosis:
a) marked incapacity in 3-5 years
b) death < 10 years from complication of immobility
Clinical trials:
- davunetide is not effective [9]
Interactions
disease interactions
General
brainstem disease
neurodegenerative disease
parkinson plus syndrome
Properties
PATHOLOGY: neurofibrillary tangle
SITE: hippocampus
basal ganglia
brainstem
Database Correlations
OMIM correlations
References
- Lang AE & Lazano AM
Parkinson's disease. First of two parts.
NEJM 339(15):1044-53 1998
PMID: 9761807
- Bronstein J, In: Intensive Course in Geriatric Medicine &
Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- Miller B, UCSF Memory & Aging Center, 2001
- Handforth CA, WLA VA Dept of Neurology {patient-related
communication}
- Geriatrics Review Syllabus, American Geriatrics Society,
5th edition, 2002-2004; 7th edition 2010
- Medical Knowledge Self Assessment Program (MKSAP) 14, 16.
American College of Physicians, Philadelphia 2006, 2012
- Messina D, Cerasa A, Condino F et al
Patterns of brain atrophy in Parkinson's disease,
progressive supranuclear palsy and multiple system atrophy.
Parkinsonism Relat Disord. 2011 Mar;17(3):172-6
PMID: 21236720
- Wenning GK, Colosimo C.
Diagnostic criteria for multiple system atrophy and progressive
supranuclear palsy.
Rev Neurol (Paris). 2010 Oct;166(10):829-33
PMID: 20813385
- Boxer AL et al.
Davunetide in patients with progressive supranuclear palsy:
A randomised, double-blind, placebo-controlled phase 2/3 trial.
Lancet Neurol 2014 Jul; 13:676
PMID: 24873720
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70088-2/fulltext
- Heckman MG, Brennan RR, Labbe C et al
Association of MAPT Subhaplotypes With Risk of Progressive
Supranuclear Palsy and Severity of Tau Pathology.
JAMA Neurol. Published online March 18, 2019.
PMID: 30882841
https://jamanetwork.com/journals/jamaneurology/fullarticle/2728174
- Lee S et al.
Cell-specific dysregulation of iron and oxygen homeostasis as a novel
pathophysiology in PSP.
Ann Neurol 2022 Oct 30; [e-pub].
PMID: 36309960
https://onlinelibrary.wiley.com/doi/10.1002/ana.26540
- NINDS Progressive Supranuclear Palsy Information Page
https://www.ninds.nih.gov/Disorders/All-Disorders/Progressive-Supranuclear-Palsy-Information-Page