Progressive supranuclear palsy
|Progressive supranuclear palsy|
Main anatomical plans and axes applied to the sections of the brain.
|Classification and external resources|
|Patient UK||Progressive supranuclear palsy|
Progressive supranuclear palsy (PSP; or the Steele-Richardson-Olszewski syndrome, after the physicians who described it in 1963) is a degenerative disease involving the gradual deterioration and death of specific volumes of the brain.
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. Notably, the ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy. 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. 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 Difficulties walking
- Frequent falls
There is currently no effective treatment or cure 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.
PSP is frequently misdiagnosed as Parkinson's disease because of the slowed movements and gait difficulty, or as Alzheimer's disease because of the behavioral changes. It is one of a number of diseases collectively referred to as Parkinson plus syndromes. A poor response to levodopa along with symmetrical onset can help differentiate this disease from PD.
Genetics and causal factors
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.
The affected brain cells are both neurons and glial cells. The neurons display neurofibrillary tangles, 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. Lewy bodies are seen in some cases, but it is not clear whether this is a variant or an independent co-existing process.
The principal areas of the brain affected are:
- the basal ganglia, particularly the subthalamic nucleus, substantia nigra and globus pallidus;
- the brainstem, particularly the portion of the midbrain where "supranuclear" eye movement resides;
- the cerebral cortex, particularly that of the frontal lobes;
- the dentate nucleus of the cerebellum;
- and the 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.
Classification and treatment
|This section requires expansion. (November 2010)|
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 physiotherapy 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 patients with PSP 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 will help to decrease the individual’s risk of falls and make them safer to ambulate independently in the community. Due to their balance problems and irregular movements individuals will need to spend time learning how to safely transfer in their homes as well as in the community. This may include arising 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.
- Nobel Laureate Dr Abdus Salam (1926–1996), a world renowned scientist and first and only Muslim to win the Nobel Prize in Physics (1979) for his gauge unification of weak and electromagnetic interactions, which forms the basis of the Standard Model in particle physics.
- Teel Bivins (1947–2009), a former U.S. Ambassador to Sweden and a former member of the Texas State Senate from Amarillo, Texas, died at the age of sixty-one of progressive supranuclear palsy, first diagnosed in 2006, while he was in Stockholm, Sweden.
- Leonard Krieger (1918–1990), was an American historian of modern Europe, particularly known as an author on Germany. He was influential as an intellectual historian, and particularly for his discussion of historicism. Krieger taught at Columbia University and The University of Chicago until his death from PSP.
- Abel John "Buddy" McNamara, died December 2, 2014 at the age of 78 after a long battle with supranuclear palsy. From 1976 to 1980, he was a member of the Louisiana House of Representatives; from 1982 to 2001, he was a judge of the United States District Court for the Eastern District of Louisiana in his native New Orleans.
- Musician/actor Dudley Moore, who suffered from progressive supranuclear palsy, increased public awareness of this disease. He died on March 27, 2002 at the age of 66 from its complications.
- Country singer Teddy Wilburn, of The Wilburn Brothers, was diagnosed with PSP in the late 1990s. He died of congestive heart failure, and PSP complications, on November 24, 2003.
- Lee Philips, the 1950s actor-turned-director of such shows as Peyton Place and The Ghost & Mrs. Muir, also died after suffering from this disease.
- American singer Teresa Brewer ("Music! Music! Music!"), 76, died of this disease on October 17, 2007.
- Film director and playwright Joshua Logan
- Abe Pollin, D.C. sports mogul, longest tenured owner of an NBA franchise (since 1964) Washington Wizards, 85, died of this disease on November 24, 2009.
- Dr. Anne Turner, who was the basis of the BBC drama A Short Stay in Switzerland about assisted suicide.
- Jon Hassler, author
- Bob Gibson (musician), influential American singer-songwriter of the 1950s and 1960s, died September 28, 1996, age 64.
- Richard Rainwater, investor
- Geoff Miller, Co-founder, editor, and publisher of Los Angeles Magazine, 1936–2011
- K. Lamar Alsop, concertmaster of the New York City Ballet Orchestra.
- John Attenborough, executive at Alfa Romeo and younger brother of Sir David Attenborough
- Actor Phyllis Frelich, She died on April 10, 2014 at age 70.
- Musician Jeff Golub, died on January 1, 2015 at age 59.
Several international organizations serve the needs of patients with PSP and their families and support research. The Foundation for PSP, CBD and Related Brain Diseases is based in the US and the PSP Association (PSP-Europe Association) is based in the UK. The PSP-France association is based in Paris. With the help of the PSP Association based in the United States, in 2014/15 Canada will have its own CUREPSP organization.
- Richardson JC, Steele J, Olszewski J (1963). "Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. A clinical report on eight cases of 'heterogeneous 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 brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia". Archives of Neurology 10: 333–59. doi:10.1001/archneur.1964.00460160003001. PMID 14107684.
- Rizzo G, Martinelli P, Manners D et al. (October 2008). "Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease". Brain 131 (Pt 10): 2690–700. doi:10.1093/brain/awn195. PMID 18819991.
- Litvan I, Campbell G, Mangone CA, Verny M, McKee A, Chaudhuri KR, Jellinger K, Pearce RK, D'Olhaberriague L. (Jan 1997). "Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study". Brain. 120 (1): 65–74. doi:10.1093/brain/120.1.65. PMID 9055798.
- Online 'Mendelian Inheritance in Man' (OMIM) 601104
- Amano N, Iwabuchi K, Yokoi S (January 1989). "[The reappraisal study of the ultrastructure of Alzheimer's neurofibrillary tangles in three cases of progressive supranuclear palsy]". Nō to Shinkei (in Japanese) 41 (1): 35–44. PMID 2655673.
- Luc Buée; André Delacourte (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.
- 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. PMID 19235444.
- 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; Andrew Lees et al. (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 (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; 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. et al. (Oct 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.
- Wang, LN; Zhu, MW; Feng, YQ; Wang, JH (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 : official journal of the Japanese Society of Neuropathology 26 (3): 222–30. doi:10.1111/j.1440-1789.2006.00671.x. PMID 16771179.
- Williams, DR; De Silva, R; Paviour, DC; Pittman, A; Watt, HC; Kilford, L; Holton, JL; Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ.; Lees, AJ (Jun 2005). "Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism". Brain 128 (6): 1247–58. doi:10.1093/brain/awh488. PMID 15788542.
- Nijboer H, Dautzenberg PL. (Jun 2009). "[Progressive supranucleair palsy: acetylcholineeserase-inhibitor a possible therapy?]". Tijdschr Gerontol Geriatr. 40 (3): 133–7. PMID 19731749.
- Liepelt I, Gaenslen A, Godau J, Di Santo A, Schweitzer KJ, Gasser T, Berg D. (Jan 2010). "Rivastigmine for the treatment of dementia in patients with progressive supranuclear palsy: Clinical observations as a basis for power calculations and safety analysis". Alzheimers Dement. 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, Cris; Di Fabio, Richard (June 2006). "Progressive Supranuclear Palsy: Disease Profile and Rehabilitation Strategies". Physical Therapy 86 (6): 870–80. PMID 16737412.
- van Balken, Irene; Litvan, Irene (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, Lawrence (November 2001). "Progressive Supranuclear Palsy". Current Treatment Options in Neurology 3 (6): 473–477. doi:10.1007/s11940-001-0010-0. PMID 11581524.
- "Teel Bivins Services Held Today in Amarillo, October 29, 2009". Texas Insider. Retrieved October 30, 2009.
- "Retired U.S. District Court Judge A.J. "Buddy" McNamara, 78, died Tuesday". New Orleans Times-Picayune. Retrieved December 3, 2014.
- "Dr Anne Turner". Dignity in Dying. Retrieved 2009-01-25.
- Elkind, Peter; Sellers, Patricia; Burke, Doris (November 21, 2011). "The Fight of Richard Rainwater's Life". Fortune 164 (8): 126–140.
- "K. Lamar Alsop, Violinist in a Musical Family, Dies at 85". Retrieved 2014-02-09.
- "John Attenborough, youngest brother of David and Richard Attenborough (obituary)". Daily Echo (Bournmouth). 31 December 2012. Retrieved 8 December 2013.
- The Foundation for PSP | CBD and Related Brain Diseases ("CurePSP")
- The PSP Association (UK)
- psp at NINDS
- Medical Notes at BBC
- Houston PSP Review at Baylor College
- 02040 at CHORUS
- synd/3806 at Who Named It?