Progressive supranuclear palsy
|Progressive supranuclear palsy|
|Other names||Steele–Richardson–Olszewski syndrome|
|Symptoms||Impaired balance, slowed movements, difficulty moving eyes, dementia|
|Usual onset||60–70 years|
|Differential diagnosis||Parkinson's disease, Alzheimer's disease|
|Treatment||Medication, physical therapy|
|Frequency||6 per 100,000|
Progressive supranuclear palsy (PSP), also known as Steele–Richardson–Olszewski syndrome, is a degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and dementia. PSP may be mistaken for other neurodegenerative diseases such as Parkinson's and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.
PSP affects about six people per 100,000. The first symptoms typically occur in persons aged 60–70 years. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.
Symptoms and signs
The initial symptoms in two-thirds of cases are loss of balance, lunging forward when mobilizing, fast walking, bumping into objects or people, and falls.
Other common early symptoms are changes in personality, general slowing of movement, and visual symptoms.
Later symptoms and signs are dementia (typically including loss of inhibition and ability to organize information), slurring of speech, difficulty swallowing, and difficulty moving the eyes, particularly in the vertical direction. The latter accounts for some of the falls experienced by these patients, as they are unable to look up or down.
Some of the other signs are poor eyelid function, contracture of the facial muscles, a backward tilt of the head with stiffening of the neck muscles, sleep disruption, urinary incontinence, and constipation.
The visual symptoms are of particular importance in the diagnosis of this disorder. Patients typically complain of difficulty reading due to the inability to look down well. Notably, the ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement and the inability to make vertical saccades, which is often worse with downward saccades. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy. This vertical gaze paresis will correct when the examiner passively rolls the patient's head up and down as part of a test for the oculocephalic reflex. Involuntary eye movement, as elicited by Bell's phenomenon, for instance, may be closer to normal. On close inspection, eye movements called "square-wave jerks" may be visible when the patient fixes at distance. These are fine movements, that can be mistaken for nystagmus, except that they are saccadic in nature, with no smooth phase. Although healthy individuals also make square-wave jerk movements, PSP patients make slower square-wave jerk movements, with smaller vertical components. Assessment of these square-wave jerks and diminished vertical saccades is especially useful for diagnosing progressive supranuclear palsy, because these movements set PSP patients apart from other parkinsonian patients. Difficulties with convergence (convergence insufficiency), where the eyes come closer together while focusing on something near, like the pages of a book, is typical. Because the eyes have trouble coming together to focus at short distances, the patient may complain of diplopia (double vision) when reading.
- Supranuclear ophthalmoplegia
- Neck dystonia
- Pseudobulbar palsy
- Behavioral and cognitive impairment
- Imbalance and walking difficulty
- Frequent falls
The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17, has been linked to PSP. Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP. Especially, mitochondrial complex I inhibitors (such as acetogenins, quinolines, and rotenoids) are implicated in PSP-like brain injuries.
The affected brain cells are both neurons and glial cells. The neurons display neurofibrillary tangles (NFTs), which are clumps of tau protein, a normal part of a brain cell's internal structural skeleton. These tangles are often different from those seen in Alzheimer's disease, but may be structurally similar when they occur in the cerebral cortex. Their chemical composition is usually different, however, and is similar to that of tangles seen in corticobasal degeneration. Tufts of tau protein in astrocytes, or tufted astrocytes, are also considered diagnostic. Unlike globose NFTs, they may be more widespread in the cortex. Lewy bodies are seen in some cases, but whether this is a variant or an independent co-existing process is not clear, and in some cases, PSP can coexist with corticobasal degeneration, Parkinson's, and/or Alzheimer's disease, particularly with older patients.
The principal areas of the brain affected are the:
- basal ganglia, particularly the subthalamic nucleus, substantia nigra, and globus pallidus
- brainstem, particularly the portion of the midbrain where "supranuclear" eye movement resides
- cerebral cortex, particularly that of the frontal lobes
- dentate nucleus of the cerebellum
- spinal cord, particularly the area where some control of the bladder and bowel resides
Some consider PSP, corticobasal degeneration, and frontotemporal dementia to be variations of the same disease. Others consider them separate diseases. PSP has been shown occasionally to co-exist with Pick's disease.
PSP is frequently misdiagnosed as Parkinson's disease because they both involve slowed movements and gait difficulty, with PSP being one of a collection of diseases referred to as Parkinson plus syndromes. Both Parkinson's and PSP have an onset in late middle age and involve slowing and rigidity of movement. However, several distinguishing features exist. Tremor is very common with Parkinson's, but rare with PSP. Speech and swallowing difficulties are more common and severe with PSP and the abnormal eye movements of PSP are essentially absent with PD. A poor response to levodopa along with symmetrical onset can also help differentiate PSP from PD. Patients with the Richardson variant of PSP tend to have an upright posture or arched back, as opposed to the stooped-forward posture of other Parkinsonian disorders, although PSP-Parkinsonism (see below) can demonstrate a stooped posture. Early falls are also more common with PSP, especially with Richardson syndrome.
PSP can also be misdiagnosed as Alzheimer's disease because of the behavioral changes.
Chronic traumatic encephalopathy shows many similarities with PSP.
No cure for PSP is known, and management is primarily supportive. PSP cases are often split into two subgroups, PSP-Richardson, the classic type, and PSP-Parkinsonism, where a short-term response to levodopa can be obtained. Dyskinesia is an occasional but rare complication of treatment. Amantadine is also sometimes helpful. After a few years the Parkinsonian variant tends to take on Richardson features. Other variants have been described. Botox can be used to treat neck dystonia and blepharospasm, but this can aggravate dysphagia.
Two studies have suggested that rivastigmine may help with cognitive aspects, but the authors of both studies have suggested a larger sampling be used. There is some evidence that the hypnotic zolpidem may improve motor function and eye movements, but only from small-scale studies.
Patients with PSP usually seek or are referred to occupational therapy, speech-language pathology for motor speech changes typically a spastic-ataxic dysarthria, and physical therapy for balance and gait problems with reports of frequent falls. Evidence-based approaches to rehabilitation in PSP are lacking, and currently, the majority of research on the subject consists of case reports involving only a small number of patients.
Case reports of rehabilitation programs for patients with PSP generally include limb-coordination activities, tilt-board balancing, gait training, strength training with progressive resistive exercises, and isokinetic exercises and stretching of the neck muscles. While some case reports suggest that physiotherapy can offer improvements in balance and gait of patients with PSP, the results cannot be generalized across all PSP patients, as each case report only followed one or two patients. The observations made from these case studies can be useful, however, in helping to guide future research concerning the effectiveness of balance and gait training programs in the management of PSP.
Individuals with PSP are often referred to occupational therapists to help manage their condition and to help enhance their independence. This may include being taught to use mobility aids. Due to their tendency to fall backwards, the use of a walker, particularly one that can be weighted in the front, is recommended over a cane. The use of an appropriate mobility aid helps to decrease the individual’s risk of falls and makes them safer to ambulate independently in the community. Due to their balance problems and irregular movements, individuals need to spend time learning how to safely transfer in their homes and in the community. This may include rising from and sitting in chairs safely.
Due to the progressive nature of this disease, all individuals eventually lose their ability to walk and will need to progress to using a wheelchair. Severe dysphagia often follows, and at this point death is often a matter of months.
Currently, no effective treatment or cure has been found for PSP, although some of the symptoms can respond to nonspecific measures. The average age at symptoms onset is 63 and survival from onset averages 7 years with a wide variance. Pneumonia is a frequent cause of death.
Internationally, several organizations serve the needs of patients with PSP and their families and support research.
- Canada: With the help of the CurePSP Association based in the United States, since 2014-2015, plans have been made for Canada to have its own CUREPSP organization, and in 2018, this reached fruition.
- France: PSP-France association, based in Paris
- UK: PSP Association
- US: The Foundation for PSP, CBD and Related Brain Diseases
- Golbe LI (April 2014). "Progressive supranuclear palsy". Seminars in Neurology. 34 (2): 151–9. doi:10.1055/s-0034-1381736. PMID 24963674.
- Shukla R, Sinha M, Kumar R, Singh D (April 2009). "'Hummingbird' sign in progressive supranuclear palsy". Annals of Indian Academy of Neurology. 12 (2): 133. doi:10.4103/0972-2327.53087. PMC 2812742. PMID 20142864.
- Alexander RG, Macknik SL, Martinez-Conde S (2018). "Microsaccade Characteristics in Neurological and Ophthalmic Disease". Frontiers in Neurology. 9 (144): 144. doi:10.3389/fneur.2018.00144. PMC 5859063. PMID 29593642.
- Online Mendelian Inheritance in Man (OMIM) 601104
- Caparros-Lefebvre D, Sergeant N, Lees A, Camuzat A, Daniel S, Lannuzel A, Brice A, Tolosa E, Delacourte A, Duyckaerts C (April 2002). "Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy". Brain. 125 (Pt 4): 801–11. doi:10.1093/brain/awf086. PMID 11912113.
- Amano N, Iwabuchi K, Yokoi S, Yagishita S, Itoh Y, Saitoh A, Nagatomo H, Matsushita M (January 1989). "[The reappraisal study of the ultrastructure of Alzheimer's neurofibrillary tangles in three cases of progressive supranuclear palsy]". No to Shinkei = Brain and Nerve (in Japanese). 41 (1): 35–44. PMID 2655673.
- Buée L, Delacourte A (October 1999). "Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease". Brain Pathology. 9 (4): 681–93. doi:10.1111/j.1750-3639.1999.tb00550.x. PMID 10517507.
- Feany MB, Mattiace LA, Dickson DW (January 1996). "Neuropathologic overlap of progressive supranuclear palsy, Pick's disease and corticobasal degeneration". Journal of Neuropathology and Experimental Neurology. 55 (1): 53–67. doi:10.1097/00005072-199601000-00006. PMID 8558172.
- Uchikado H, DelleDonne A, Ahmed Z, Dickson DW (April 2006). "Lewy bodies in progressive supranuclear palsy represent an independent disease process". Journal of Neuropathology and Experimental Neurology. 65 (4): 387–95. doi:10.1097/01.jnen.0000218449.17073.43. PMID 16691119.
- Keith-Rokosh J, Ang LC (November 2008). "Progressive supranuclear palsy: a review of co-existing neurodegeneration". The Canadian Journal of Neurological Sciences. 35 (5): 602–8. doi:10.1017/S0317167100009392. PMID 19235444.
- Rigby HB, Dugger BN, Hentz JG, Adler CH, Beach TG, Shill HA, Driver-Dunckley E, Sabbagh MN, Sue LI, Caviness JN (March 2015). "Clinical Features of Patients with Concomitant Parkinson's Disease and Progressive Supranuclear Palsy Pathology". Movement Disorders Clinical Practice. 2 (1): 33–38. doi:10.1002/mdc3.12104. PMC 6183005. PMID 30363831.
- Gearing M, Olson DA, Watts RL, Mirra SS (June 1994). "Progressive supranuclear palsy: neuropathologic and clinical heterogeneity". Neurology. 44 (6): 1015–24. doi:10.1212/wnl.44.6.1015. PMID 8208392.
- Dugger BN, Adler CH, Shill HA, Caviness J, Jacobson S, Driver-Dunckley E, Beach TG, et al. (Arizona Parkinson's Disease Consortium) (May 2014). "Concomitant pathologies among a spectrum of parkinsonian disorders". Parkinsonism & Related Disorders. 20 (5): 525–9. doi:10.1016/j.parkreldis.2014.02.012. PMC 4028418. PMID 24637124.
- Kertesz A, Munoz D (2004). "Relationship between frontotemporal dementia and corticobasal degeneration/progressive supranuclear palsy". Dementia and Geriatric Cognitive Disorders. 17 (4): 282–6. doi:10.1159/000077155. PMID 15178937.
- Katsuse O, Iseki E, Arai T, Akiyama H, Togo T, Uchikado H, Kato M, de Silva R, Lees A, Kosaka K (September 2003). "4-repeat tauopathy sharing pathological and biochemical features of corticobasal degeneration and progressive supranuclear palsy". Acta Neuropathologica. 106 (3): 251–60. doi:10.1007/s00401-003-0728-8. PMID 12802605.
- Hattori M, Hashizume Y, Yoshida M, Iwasaki Y, Hishikawa N, Ueda R, Ojika K (August 2003). "Distribution of astrocytic plaques in the corticobasal degeneration brain and comparison with tuft-shaped astrocytes in the progressive supranuclear palsy brain". Acta Neuropathologica. 106 (2): 143–9. doi:10.1007/s00401-003-0711-4. PMID 12732936.
- Komori T, Arai N, Oda M, Nakayama H, Mori H, Yagishita S, Takahashi T, Amano N, Murayama S, Murakami S, Shibata N, Kobayashi M, Sasaki S, Iwata M (October 1998). "Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy". Acta Neuropathologica. 96 (4): 401–8. doi:10.1007/s004010050911. PMID 9797005.
- Zhu MW, Wang LN, Li XH, Gui QP (April 2004). "进行性核上性麻痹和皮质基底节变性的胶质细胞病变的观察" [Glial abnormalities in progressive supranuclear palsy and corticobasal degeneration]. Zhonghua Bing Li Xue Za Zhi = Chinese Journal of Pathology (in Chinese). 33 (2): 125–9. doi:10.3760/j.issn:0529-5807.2004.02.008. PMID 15132848.
- Wang LN, Zhu MW, Feng YQ, Wang JH (June 2006). "Pick's disease with Pick bodies combined with progressive supranuclear palsy without tuft-shaped astrocytes: a clinical, neuroradiologic and pathological study of an autopsied case". Neuropathology. 26 (3): 222–30. doi:10.1111/j.1440-1789.2006.00671.x. PMID 16771179.
- Sonthalia N, Ray S (September 2012). "The Hummingbird sign: a diagnostic clue for Steele-Richardson-Olszweski syndrome". BMJ Case Reports. 2012: bcr2012006263. doi:10.1136/bcr-2012-006263. PMC 4543120. PMID 22987902.
- "Progressive Supranuclear Palsy Fact Sheet | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. NIH. Retrieved 19 February 2019.
- Litvan I, Campbell G, Mangone CA, Verny M, McKee A, Chaudhuri KR, Jellinger K, Pearce RK, D'Olhaberriague L (January 1997). "Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study". Brain. 120 (Pt 1): 65–74. doi:10.1093/brain/120.1.65. PMID 9055798.
- Moore DP, Puri BK (2012-06-29). Textbook of Clinical Neuropsychiatry and Behavioral Neuroscience. pp. 400–401. ISBN 978-1-4441-6494-7.
- Williams DR, Watt HC, Lees AJ (April 2006). "Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study". Journal of Neurology, Neurosurgery, and Psychiatry. 77 (4): 468–73. doi:10.1136/jnnp.2005.074070. PMC 2077491. PMID 16543524.
- O'Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL, Revesz T, Lees AJ (May 2008). "Clinical outcomes of progressive supranuclear palsy and multiple system atrophy". Brain. 131 (Pt 5): 1362–72. doi:10.1093/brain/awn065. PMID 18385183.
- Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ (June 2005). "Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism". Brain. 128 (Pt 6): 1247–58. doi:10.1093/brain/awh488. PMID 15788542.
- Brooks DJ (March 2002). "Diagnosis and management of atypical parkinsonian syndromes". Journal of Neurology, Neurosurgery, and Psychiatry. 72 Suppl 1: I10–I16. doi:10.1136/jnnp.72.suppl_1.i10 (inactive 2019-05-25). PMC 1765580. PMID 11870198.
- "What is progressive supranuclear palsy?". Movementdisorders.org. Retrieved 2017-01-08.
- "Orphanet: Progressive supranuclear palsy". Orpha.net. Retrieved 2017-01-08.
- "What's New in Progressive Supranuclear Palsy?" (PDF). Acnr.org. Retrieved 2017-01-08.
- "Progressive Supranuclear Palsy – NORD (National Organization for Rare Disorders)". Rarediseases.org. Retrieved 2017-01-08.
- Williams DR, Lees AJ (March 2009). "Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges". The Lancet. Neurology. 8 (3): 270–9. doi:10.1016/S1474-4422(09)70042-0. PMID 19233037.
- Barsottini OG, Felício AC, Aquino CC, Pedroso JL (December 2010). "Progressive supranuclear palsy: new concepts". Arquivos de Neuro-Psiquiatria. 68 (6): 938–46. doi:10.1590/s0004-282x2010000600020. PMID 21243256.
- Nijboer H, Dautzenberg PL (2009). "Progressieve Supranucleaire Verlamming. Interventie middels acetylcholineesteraseremmer?". Tijdschrift voor Gerontologie en Geriatrie. 40 (3): 133–137. doi:10.1007/BF03079574.
- Liepelt I, Gaenslen A, Godau J, Di Santo A, Schweitzer KJ, Gasser T, Berg D (January 2010). "Rivastigmine for the treatment of dementia in patients with progressive supranuclear palsy: Clinical observations as a basis for power calculations and safety analysis". Alzheimer's & Dementia. 6 (1): 70–4. doi:10.1016/j.jalz.2009.04.1231. PMID 20129321.
- Abe K (January 2008). "Zolpidem therapy for movement disorders". Recent Patents on CNS Drug Discovery. 3 (1): 55–60. doi:10.2174/157488908783421519. PMID 18221242.
- Barsottini OG, Felício AC, Aquino CC, Pedroso JL (December 2010). "Progressive supranuclear palsy: new concepts". Arquivos de Neuro-Psiquiatria. 68 (6): 938–46. doi:10.1590/S0004-282X2010000600020. PMID 21243256.
- Zampieri C, Di Fabio RP (June 2006). "Progressive supranuclear palsy: disease profile and rehabilitation strategies". Physical Therapy. 86 (6): 870–80. PMID 16737412.
- van Balken I, Litvan I (May 2006). "Current and future treatments in progressive supranuclear palsy". Current Treatment Options in Neurology. 8 (3): 211–23. doi:10.1007/s11940-006-0012-z. PMID 16569380.
- Golbe LI (November 2001). "Progressive Supranuclear Palsy". Current Treatment Options in Neurology. 3 (6): 473–477. doi:10.1007/s11940-001-0010-0. PMID 11581524.
- Tomita S, Oeda T, Umemura A, Kohsaka M, Park K, Yamamoto K, Sugiyama H, Mori C, Inoue K, Fujimura H, Sawada H (August 13, 2015). "Impact of Aspiration Pneumonia on the Clinical Course of Progressive Supranuclear Palsy: A Retrospective Cohort Study". PLOS ONE. 10 (8): e0135823. Bibcode:2015PLoSO..1035823T. doi:10.1371/journal.pone.0135823. PMC 4536232. PMID 26270456.
- Richardson JC, Steele J, Olszewski J (1963). "Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. a clinical report on eight cases of "heterogenous system degeneration"". Transactions of the American Neurological Association. 88: 25–9. PMID 14272249.
- Steele JC, Richardson JC, Olszewski J (April 1964). "Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, Basal Ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia". Archives of Neurology. 10 (4): 333–59. doi:10.1001/archneur.1964.00460160003001. PMID 14107684.
- The New Home For Progressive Supranuclear Palsy Information in Canada at pspsocietycanada.ca, accessed 4 November 2018
- About Us pspsocietycanada.ca, accessed 4 November 2018
- Accueil (Welcome) pspfrance.org, accessed 4 November 2018
- ...PSPA is a registered charity in England and Wales and in Scotland... pspassociation.org.uk, accessed 4 November 2018
- CurePSP, Unlocking the Secrets of Brain Disease psp.org, accessed 4 November 2018