Progressive supranuclear palsy

Progressive supranuclear palsy
Specialty	Neurology

Progressive supranuclear palsy (PSP; or the Steele-Richardson-Olszewski syndrome, after the doctors who described it in 1963) is a degenerative disease involving the gradual deterioration and death of specific volumes of the brain. Males and females are affected approximately equally and there is no racial, geographical or occupational predilection. Approximately 6 people per 100,000 population have PSP. It has been described as a tauopathy.

Symptoms and signs

This patient presented with progressive dementia, ataxia and incontinence. A clinical diagnosis of normal pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing abnormal nystagmus and eye movements were detected. A sagittal view of the CT/MRI scan shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "Hummingbird sign" or "Penguin sign". There is also atrophy of the tectum, particularly the superior colliculi. These findings suggest the diagnosis of progressive supranuclear palsy.

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. 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.

Cardinal manifestations:

• Supranuclear ophthalmoplegia
• Neck dystonia
• Parkinsonism
• Pseudobulbar palsy
• Behavioral and cognitive impairment
• Imbalance and walking difficulty
• Frequent falls

Cause

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.

Pathophysiology

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. 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 it is not clear whether this is a variant or an independent co-existing process, 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.

Diagnosis

MRI is often done to diagnose PSP. MRI may show atrophy in the midbrain with preservation of the pons giving a "hummingbird" sign apearance.

Differential diagnosis

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. Also, patients with the Richardson variant tend to have an upright or arched-back posture as opposed to the stooped-forward posture of other Parkinsonian disorders, although PSP-Parkinsonism (see below) may show the stooped posture. Early falls are characteristic, especially with Richardson-syndrome.

Treatment

There is no known cure for PSP 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 blephrospasm, 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.

Rehabilitation

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 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 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.

Prognosis

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. Pneumonia is a frequent cause of death.

Notable cases

• K. Lamar Alsop, concertmaster of the New York City Ballet Orchestra.
• John Attenborough, executive at Alfa Romeo and younger brother of Sir Richard Attenborough and Sir David Attenborough
• Teel Bivins (1947–2009), a former U.S. Ambassador to Sweden and a former member of the Texas State Senate. He was diagnosed in 2006 while in Stockholm.
• Teresa Brewer, American singer ("Music! Music! Music!") (1931-2007)
• Nigel Dempster, journalist, (1941-2007).
• Rae Ferren, American impressionist painter (1929-2016)
• Richard Frank, former leader of Population Services International and first husband of Jane Harman, died 20 April 2014, age 77
• Phyllis Frelich, actress (1944-2014)
• Bob Gibson (musician), influential American singer-songwriter of the 1950s and 1960s, died 28 September 1996, age 64.
• Jeff Golub, musician (1955-2015)
• Jon Hassler, author (1933-2008)
• Bob Hoskins, actor. He died on 29 April 2014 at age 71.
• Eric Jansson, chess master and musician.
• Shigeji Kaneko, Japanese featherweight boxer during the 1950s (1931-2016)
• Leonard Krieger (1918–1990), was an American historian of modern Europe. He taught at Columbia University and The University of Chicago until his death from PSP.
• Joshua Logan, film director and playwright (1908-1988)
• Abel John "Buddy" McNamara, member of the Louisiana House of Representatives and judge of the United States District Court for the Eastern District of Louisiana (1936-2014).
• Geoff Miller, co-founder, editor, and publisher of Los Angeles Magazine, husband of actress/author Kathryn Leigh Scott (1936-2011)
• Dudley Moore, actor/musician who increased public awareness of the disease. He died on 27 March 2002 at the age of 66 from its complications.
• Lee Philips, the 1950s actor-turned-director of such TV series as Peyton Place and The Ghost & Mrs Muir (1927-1999)
• Abe Pollin, D.C. sports mogul, longest tenured owner of an NBA franchise (since 1964) Washington Wizards, 85, died on 24 November 2009.
• Ira Progoff, American psychotherapist, developer of the Intensive Journal Method and founder of Dialogue House, died in January 1998.
• Richard Rainwater, investor (1944-2015)
• Abdus Salam (1926–1996), Nobel Laureate. To date is the 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.
• Peter Sarstedt (1941-2017), musician, initially diagnosed with dementia, was diagnosed with PSP in 2015
• Anne Turner, who was the basis of the BBC drama A Short Stay in Switzerland about assisted suicide.
• Teddy Wilburn, of country singers the Wilburn Brothers, was diagnosed with PSP in the late 1990s. He died of congestive heart failure, and PSP complications, on 24 November 2003.
• Dr. Mukund.K.Mehta, of Surat, India, died of PSP- Parkinsonism in the year of 2013 after suffering for 6 years from 2008-2013. He died of a number of injuries caused due to this disease on June 2, 2013.

Support groups

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 is based in the UK. The PSP-France association is based in Paris. With the help of the CurePSP Association based in the United States, in 2014/15 Canada will have its own CUREPSP organization.

External links

• 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?