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geri:dementia:progressive-supranuclear-palsy-psp [on June 2, 2019]
geri:dementia:progressive-supranuclear-palsy-psp [on September 4, 2023] (current)
psychdb [Other Signs]
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 ====== Progressive Supranuclear Palsy (PSP) ====== ====== Progressive Supranuclear Palsy (PSP) ======
- 
 {{INLINETOC}} {{INLINETOC}}
 ===== Primer ===== ===== Primer =====
-**Progressive Supranuclear Palsy** (PSP) is a neurodegenerative disorder characterized by early postural instability,​ leading to falls, and a characteristic vertical supranuclear-gaze palsy on physical exam. It is classified as an atypical parkinsonian syndrome (or Parkinson'​s Plus).+**Progressive Supranuclear Palsy** (PSP) is a rare neurodegenerative disorder characterized by early postural instability,​ leading to falls, and a characteristic vertical supranuclear-gaze palsy on physical exam. It is classified as an atypical parkinsonian syndrome (or [[geri:​parkinsons|Parkinson'​s]] Plus)
 + 
 +== Epidemiology == 
 +  * The age-adjusted prevalence of progressive supranuclear palsy (PSP) is estimated to be about 3-6 cases per 100,000 population.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC8245849/​|Viscidi,​ E., Litvan, I., Dam, T., Juneja, M., Li, L., Krzywy, H., ... & Höglinger, G. U. (2021). Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database. Frontiers in neurology, 12.]])][([[https://​pubmed.ncbi.nlm.nih.gov/​11408338/​|Nath,​ U., Ben-Shlomo, Y., Thomson, R. G., Morris, H. R., Wood, N. W., Lees, A. J., & Burn, D. J. (2001). The prevalence of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome) in the UK. Brain, 124(7), 1438-1449.]])] 
 + 
 +== Prognosis == 
 +  * Individuals with PSP typically have a prognosis of living another 8 years of onset of first symptoms, but can live as long as 17 years.[([[https://​pubmed.ncbi.nlm.nih.gov/​20360166/​|Chiu,​ W. Z., Kaat, L. D., Seelaar, H., Rosso, S. M., Boon, A. J., Kamphorst, W., & van Swieten, J. C. (2010). Survival in progressive supranuclear palsy and frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry, 81(4), 441-445.]])] 
 + 
 +== Comorbidity == 
 +  * Individuals with PSP may often have gait abnormalities,​ muscle weakness, falls, speech difficulties,​ swallowing difficulties,​ dysphagia, and urinary tract infections. 
 +  * Hypertension is common in individuals with PSP (around 50%). 
 + 
 +== Risk Factors == 
 +  * Age is the only known risk factor for PSP.
  
-== Symptoms == 
-Pseudobulbar signs may be present, and retropulsion is often prominent. Cognitive testing will show psychomotor slowing, poor working memory, and executive dysfunction. 
 ===== Diagnostic Criteria ===== ===== Diagnostic Criteria =====
  
 ==== NINDS-SPSP Criteria ==== ==== NINDS-SPSP Criteria ====
-The National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria are the most widely used criteria for the diagnosis of PSP.[([[https://​www.ncbi.nlm.nih.gov/​pubmed/​8710059|Litvan,​ I., Agid, Y., Calne, D., Campbell, G., Dubois, B., Duvoisin, R. C., ... & Hallett, M. (1996). Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology, 47(1), 1-9.]])]+The "​classic"​ form of PSP is also called Richardson PSP phenotype (PSP-RS) (also known as Steele-Richardson-Olszewski syndrome). Patients report early difficulties with vertical gaze and pseudobulbar palsy, nuchal dystonia, and dementia. ​The National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria are the most widely used criteria for the diagnosis of PSP.[([[https://​www.ncbi.nlm.nih.gov/​pubmed/​8710059|Litvan,​ I., Agid, Y., Calne, D., Campbell, G., Dubois, B., Duvoisin, R. C., ... & Hallett, M. (1996). Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology, 47(1), 1-9.]])]
  
 <panel type="​info"​ title="​ NINDS-SPSP PSP Criteria"​ subtitle="​Litvan,​ I., et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology 47.1 (1996): 1-9." no-body="​true">​ <panel type="​info"​ title="​ NINDS-SPSP PSP Criteria"​ subtitle="​Litvan,​ I., et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology 47.1 (1996): 1-9." no-body="​true">​
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 ^ Level 3              | **O3**: Frequent macro square wave jerks or\\ "​eyelid opening apraxia" ​ | **P3**: More than two steps backward on the pull-test within 3 years  | **A3**: [[geri:​parkinsons|Parkinsonism]],​ with tremor and/or asymmetric and/or levodopa responsive ​        | **C3**: [[geri:​dementia:​corticobasal-degeneration-cbd|Corticobasal syndrome]] ​                                                                                                          | ^ Level 3              | **O3**: Frequent macro square wave jerks or\\ "​eyelid opening apraxia" ​ | **P3**: More than two steps backward on the pull-test within 3 years  | **A3**: [[geri:​parkinsons|Parkinsonism]],​ with tremor and/or asymmetric and/or levodopa responsive ​        | **C3**: [[geri:​dementia:​corticobasal-degeneration-cbd|Corticobasal syndrome]] ​                                                                                                          |
 </​panel>​ </​panel>​
 +
 +==== Signs and Symptoms ====
 +<alert type="​info"​ icon="​fa fa-book fa-lg fa-fw">​
 +See also: **[[https://​pubmed.ncbi.nlm.nih.gov/​24992742/​|Yoshiike,​ T. et al. (2014). A clinical case of progressive supranuclear palsy with long-term frontal presentation preceding the onset of gaze palsy. Seishin shinkeigaku zasshi= Psychiatria et neurologia Japonica, 116(5), 359-369.]]**
 +</​alert>​
 +  * On [[:​cognitive-testing|cognitive testing]], letter fluency is worse than semantic fluency (versus in Alzheimer'​s,​ where semantic fluency is worse than letter fluency).[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3621037/​|Peterson,​ K. A., Patterson, K., & Rowe, J. B. (2021). Language impairment in progressive supranuclear palsy and corticobasal syndrome. Journal of neurology, 268(3), 796-809.]])]
 +  * Pseudobulbar signs may be present, and retropulsion is often prominent.
 +    * Patients typically have an early history of falls and difficulty with rising from chairs.
 +  * Spontaneous new episodes of anxiety or new psychiatric diagnoses in late life has been reported in cases of PSP.[([[https://​www.sciencedirect.com/​science/​article/​pii/​S2210833516300375|Chiu,​ Y. W., Lee, S. H., & Yeh, T. H. (2016). Diversified psychiatric presentation in a case of progressive supranuclear palsy. Journal of Clinical Gerontology and Geriatrics, 7(4), 164-167.]])]
 +    * Some individuals may have been treated as a primary psychiatric disorder (e.g. - late onset anxiety) for several years before being formally diagnosed with PSP, and may only come first in contact with psychiatric specialists.
 +  * Cognitive testing will show psychomotor slowing, poor working memory, and executive dysfunction.
 +    * Reduced cognitive processing speed is considered a hallmark of PSP.[([[https://​pubmed.ncbi.nlm.nih.gov/​3190499/​|Dubois,​ B., Pillon, B., Legault, F., Agid, Y., & Lhermitte, F. (1988). Slowing of cognitive processing in progressive supranuclear palsy: A comparison with Parkinson'​s disease. Archives of Neurology, 45(11), 1194-1199.]])]
 +  * Common psychiatric symptoms include apathy, depression, sleep disturbances,​ and disinhibition.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3840159/​|Gerstenecker,​ A., Duff, K., Mast, B., Litvan, I., & ENGENE-Psp Study Group. (2013). Behavioral abnormalities in progressive supranuclear palsy. Psychiatry research, 210(3), 1205-1210.]])]
 +  * Rarely, there can be hallucinations or delusions, but this may also be related to the use of dopaminergic agents in these individuals.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3840159/​|Gerstenecker,​ A., Duff, K., Mast, B., Litvan, I., & ENGENE-Psp Study Group. (2013). Behavioral abnormalities in progressive supranuclear palsy. Psychiatry research, 210(3), 1205-1210.]])]
 +  * Aphasia, including anomnia, and slowed speech can be a common feature of PSP, and as severe as the [[geri:​dementia:​primary-progressive-aphasia-ppa|primary progressive aphasias]].[([[https://​pubmed.ncbi.nlm.nih.gov/​29254097/​|Burrell,​ J. R., Ballard, K. J., Halliday, G. M., & Hodges, J. R. (2018). Aphasia in progressive supranuclear palsy: as severe as progressive non-fluent aphasia. Journal of Alzheimer'​s Disease, 61(2), 705-715.]])]
 +
 ===== Pathophysiology ===== ===== Pathophysiology =====
-PSP is due to the intracerebral aggregation of the microtubule-associated protein tau (MAPT), predominantly ​involving ​isoforms ​with four microtubule-binding repeats (4R-tau), in neurofibrillary tanglesoligodendrocytic coils, and, specificallyastrocytic tufts. The definite ​diagnosis of PSP requires ​post-mortem neuropathological examination.+  * The major genetic risk factor for sporadic ​PSP is a common variant in the gene encoding ​microtubule-associated protein tau (MAPT) 
 +  * There is ontracerebral aggregation of MAPTwhich predominantly ​involves ​isoforms ​of the four microtubule-binding repeats (4Rtau 
 +  * The definite diagnosis of PSP requires a post-mortem neuropathological examination. 
 + 
 +===== Differential Diagnosis ===== 
 +The differential diagnosis for PSP is very broad and includes:​[([[https://​translationalneurodegeneration.biomedcentral.com/​articles/​10.1186/​s40035-019-0160-1|Phokaewvarangkul,​ O., & Bhidayasiri,​ R. (2019). How to spot ocular abnormalities in progressive supranuclear palsy? A practical review. Translational neurodegeneration8(1), 1-14.]])] 
 +<WRAP group> 
 +<WRAP half column>​ 
 +  * **Neurodegenerative** 
 +    * [[geri:​dementia:​lewy-body|Dementia with Lewy bodies (DLB)]] 
 +    * [[geri:​dementia:​corticobasal-degeneration-cbd|Corticobasal degeneration (CBD)]] 
 +      * Since PSP and [[geri:​dementia:​corticobasal-degeneration-cbd|corticobasal degeneration]] are both Four-repeat (4R) tauopathies,​ these two neurodegenerative disorders may be confused ​in the initial stages. 
 +    * [[geri:​dementia:​frontotemporal|Frontotemporal dementia (FTD)]] 
 +    * [[geri:​dementia:​alzheimers|Alzheimer’s disease (AD)]] 
 +  * **Heredodegenerative** 
 +    * Kufor Rakeb disease 
 +    * [[cl:​niemann-pick-type-c|Niemann-Pick diseasetype C]] 
 +    * Perry syndrome 
 +    * Mitochondrial disease (POLG) 
 +    * Dentatorubral pallidoluysian atrophy 
 +    * Gaucher disease 
 +    * [[cl:​huntingtons-disease|Huntington’s disease]] 
 +    * [[cl:​wilsons-disease|Wilson’s disease]] 
 +    * Neuroacanthocytosis 
 +</​WRAP>​ 
 +<WRAP half column>​ 
 +  * **Vascular** 
 +    * Vascular-Progressive supranuclear palsy (Vascular-PSP) 
 +    * Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) 
 +  * **Infectious** 
 +    * [[cl:​neurosyphilis|Neurosyphilis]] 
 +    * Whipple’s disease 
 +  * **[[geri:​dementia:​creutzfeldt-jakob-disease-cjd|Prion disease]]** 
 +  * **Immune-mediated** 
 +    * [[cl:​paraneoplastic-disorders|Paraneoplastic encephalitis]] (Anti-Ma1Anti-Ma2 antibodies) 
 +</​WRAP>​ 
 +</​WRAP>​ 
 + 
 + 
 +===== Physical Exam ===== 
 +==== Ocular Findings ​and Vertical Gaze Palsy ==== 
 +<alert type="​info"​ icon="​fa fa-book fa-lg fa-fw">​ 
 +See also: **[[https://​translationalneurodegeneration.biomedcentral.com/​articles/​10.1186/​s40035-019-0160-1|Phokaewvarangkul,​ O.& BhidayasiriR(2019). How to spot ocular abnormalities in progressive supranuclear palsy? A practical review. Translational neurodegeneration,​ 8(1), 1-14.]]** 
 +</​alert>​ 
 + 
 +<callout type="​info"​ title="​PSP with Vertical Gaze Palsy, Abnormal Optokinetic Nystagmus and Inability to Suppress Blinking to Light" icon="​fa fa-video-camera">​ 
 +[[https://​collections.lib.utah.edu/​ark:/​87278/​s6810bdv|PSP with Vertical Gaze Palsy, Abnormal Optokinetic Nystagmus and Inability to Suppress Blinking to Light]] 
 +</​callout>​ 
 + 
 +  * When examined with an [[https://​www.youtube.com/​watch?​v=Ul-tBMpiRrU|optokinetic flag]], there is slowing of vertical saccades (upwards and downwards) and also loss of the upward and downward fast phase. 
 +    * These are commonly early signs in PSP, and often precedes the development of the onset of full on downgaze or vertical palsy.[([[https://​collections.lib.utah.edu/​ark:/​87278/​s6810bdv|PSP with Vertical Gaze Palsy, Abnormal Optokinetic Nystagmus and Inability to Suppress Blinking to Light]])] 
 +  * Patients with PSP also tend to to have difficulty suppressing blinks when a bright light is shone into the eyes, this is a frontal release sign similar to the [[neurology:​neuro-exam:​home|glabellar reflex]], which can be present in Parkinson'​s disease. 
 + 
 +==== Motor ==== 
 + 
 +  * As per the diagnostic criteria, patients typically have more axial rigidity 
 + 
 +==== Other Signs ==== 
 +  * The "​Applause sign" may help discriminate PSP from [[geri:​dementia:​frontotemporal|]] and [[geri:​parkinsons|]]. To elicit the sign, patients are asked to clap ''​3''​ times. If they clap more than 3 times, it is a positive sign.[([[https://​pubmed.ncbi.nlm.nih.gov/​15985587/​|Dubois,​ B., Slachevsky, A., Pillon, B., Beato, R., Villalponda,​ J. M., & Litvan, I. (2005). “Applause sign” helps to discriminate PSP from FTD and PD. Neurology, 64(12), 2132-2133.]])] 
 +  * There may also be a so-called "​dirty-tie sign," because individuals cannot see that they are dropping food when they eat.  
 +  * However, more recent studies have suggested that the applause sign should be interpreted as a merely a sign of frontal lobe dysfunction,​ and that it can be found in FTD and AD.[([[https://​pubmed.ncbi.nlm.nih.gov/​21245475/​|Luzzi,​ S., Fabi, K., Pesallaccia,​ M., Silvestrini,​ M., & Provinciali,​ L. (2011). Applause sign: is it really specific for Parkinsonian disorders? Evidence from cortical dementias. Journal of Neurology, Neurosurgery & Psychiatry, 82(8), 830-833.]])] 
 + 
 +===== Neuroimaging ===== 
 +==== MRI ==== 
 +<alert type="​info"​ icon="​fa fa-book fa-lg fa-fw">​ 
 +See also: **[[https://​pubmed.ncbi.nlm.nih.gov/​15985570/​|Oba,​ H. et al. (2005). New and reliable MRI diagnosis ​for progressive supranuclear palsy. Neurology, 64(12), 2050-2055.]]** 
 +</​alert>​ 
 + 
 +<WRAP group> 
 +<WRAP half column>​ 
 +Differentiation ​of PSP from Parkinson'​s disease (PD) and Multiple System Atrophy (MSA) can be difficult, particularly in the early stages of the disease. The hummingbird sign (also known as the penguin sign) refers to the appearance of the midbrain in patients with progressive supranuclear palsy (PSP).[([[https://​pubmed.ncbi.nlm.nih.gov/​12736089/​|Kato,​ N., Arai, K., & Hattori, T. (2003). Study of the rostral midbrain atrophy in progressive supranuclear palsy. Journal of the neurological sciences, 210(1-2), 57-60.]])][([[https://​pubmed.ncbi.nlm.nih.gov/​15985570/​|Oba,​ H., Yagishita, A., Terada, H., Barkovich, A. J., Kutomi, K., Yamauchi, T., ... & Sonoo, M. (2005). New and reliable MRI diagnosis for progressive supranuclear palsy. Neurology, 64(12), 2050-2055.]])][([[https://​pubmed.ncbi.nlm.nih.gov/​19398699/​|Graber,​ J. J., & Staudinger, R. (2009). Teaching NeuroImages:​“Penguin” or “hummingbird” sign and midbrain atrophy in progressive supranuclear palsy. Neurology, 72(17), e81-e81.]])][([[https://​pubmed.ncbi.nlm.nih.gov/​29643007/​|Mueller,​ C., Hussl, A., Krismer, F., Heim, B., Mahlknecht, P., Nocker, M., ... & Wenning, G. K. (2018). The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism. Parkinsonism & Related Disorders, 54, 90-94.]])] 
 +</​WRAP>​ 
 +<WRAP half column>​ 
 +<​imgcaption image1|Hummingbird Sign: note the atrophy of the midbrain above the white marker>​{{ :​geri:​dementia:​hummingbird_sign.jpg?​nolink&​300 |}} 
 +</​imgcaption></​WRAP>​ 
 +</​WRAP>​ 
 + 
 +===== Treatment ===== 
 +  * If there are features of parkinsonism,​ some patients may benefit from [[meds:​dopamine-agonists:​carbidopa-levodopa|levodopa]] trial.