progressive supranuclear palsy; Steele-Richardson-Olszewski syndrome (PSP)
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Introduction
Parkinsonism plus disturbances of ocular motility.
Epidemiology
- rare (4% of patients with parkinsonism)
- age of onset: after age 50, generally 60-70 years
Pathology
- aberration of tau protein
- abnormal staining in pretangles/neurofibrillary tangles
- tuft shaped astrocytes
- degenerative changes in:
- neuronal loss
- gliosis
- neurofibrillary tangles (different from Alzheimer's disease)
- 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
- supranuclear vertical ophthalmoplegia
- other oculomotor & eyelid disturbances
- wide-eyed
- square-wave jerks (fixation instability)
- intact Doll's eye movement
- gait ataxia, postural instability - early falls (often backward)
- parkinsonism
- axial rigidity > limb rigidity
- bradykinesia
- resting tremor (often not prominent)
- dysarthria, slurred speech
- dysphagia
- nuchal extension & rigidity (hyperextension of neck)
- facial dystonia:
- contracted facial muscles may give the appearance of sustained surprise[6]
- pyramidal tract signs
- cognitive or behavioral changes
- dementia
- slowed processing speed
- impaired executive function
- emotional lability
- apathy
- dementia
- hypertension may be present
- late stage: immobility
- 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
- magnetic resonance imaging & CT may be normal or may show frontal &/or midbrain atrophy
- PET scan is generally shows frontal hypometabolism (2-fluoro-2-deoxyglucose), but may be normal
Complications
- complications of immobility
Management
- poor response to Sinemet
- control of agitation, emotional lability
- local botulinum toxin A (Botox) may improve rigidity
- selective serotonin reuptake inhibitors (SSRI) may improve dysarthria & dysphagia[4]
- electroconvulsive therapy of limited benefit for improving bradykinesia, rigidity, gait instability
- avoid neuroleptics
- prognosis:
- marked incapacity in 3-5 years
- death < 10 years from complication of immobility
Clinical trials
- davunetide is not effective[9]
More general terms
References
- ↑ Lang AE & Lazano AM Parkinson's disease. First of two parts. NEJM 339(15):1044-53 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/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
- ↑ 4.0 4.1 Handforth CA, WLA VA Dept of Neurology {patient-related communication}
- ↑ Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004; 7th edition 2010
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/20813385
- ↑ 9.0 9.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24873720 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70088-2/fulltext
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/30882841 https://jamanetwork.com/journals/jamaneurology/fullarticle/2728174
- ↑ 11.0 11.1 11.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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
Patient information
progressive supranuclear palsy patient information