Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain.^[2][3] The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment.^[2] PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.^[2]

PSP affects about six people per 100,000.^[2] The first symptoms typically occur at 60–70 years of age. Males are slightly more likely to be affected than females.^[2] No association has been found between PSP and any particular race, location, or occupation.^[2]

Signs and symptoms

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.^{[4][citation needed]} Dementia symptoms are also initially seen in about one in five cases.^[5]

Other common early symptoms are changes in personality, general slowing of movement, and visual symptoms. The most common behavioural symptoms in patients with PSP include apathy, a lack of inhibition, anxiety, and a profound state of unease or dissatisfaction.^[5]

Later symptoms and signs can include, but do not necessarily include

A characteristic facial appearance known as procerus sign, with a wide-eye stare, furrowing of forehead with a frowning expression, and deepening of other facial creases, is also diagnostic of PSP.^[8]

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

Additionally, the H2 haplotype, combined with vascular dysfunction, seems to be a factor of vascular progressive supranuclear palsy.^[11]

Besides

The principal areas of the brain affected are the:^[citation needed]

• basal ganglia, particularly the subthalamic nucleus, substantia nigra, and globus pallidus
• tectum (the portion of the midbrain where "supranuclear" eye movement resides), as well as dopaminergic
  nuclei
• frontotemporal degeneration
  )
• dentate nucleus of the cerebellum
• spinal cord, particularly the area where some control of the bladder and bowel resides

Some consider PSP,

Magnetic resonance imaging (MRI) is often used to diagnose PSP. MRI may show atrophy in the midbrain with preservation of the pons giving a "hummingbird" sign.^[27]

Types

Based on the pathological findings in confirmed cases of PSP, it is divided into the following categories:

• classical Richardson syndrome (PSP-RS) ^{[citation needed]}
• PSP-parkinsonism (PSP-P) and PSP-pure akinesia with gait freezing (PSP-PAGF)^{[citation needed]}
• frontal PSP, PSP-corticobasal syndrome (PSP-CBS), PSP-behavioural variant of frontotemporal dementia (PSP-bvFTD) and PSP-progressive non-fluent aphasia (PSP-PNFA)^[28]
• PSP-C
• PSP induced by Annonaceae^[29]

Richardson syndrome is characterized by the typical features of PSP. In PSP-P features of Parkinson’s Disease overlap with the clinical presentation of PSP and follows a more benign course. In both PSP-P and PSP- PAGF distribution of abnormal tau is relatively restricted to the brain stem. Frontal PSP initially presents with behavioral and cognitive symptoms, with or without ophthalmoparesis and then evolve into typical PSP.^[8] The phenotypes of PSP-P and PSP-PAGF are sometimes referred as the "brain stem" variants of PSP, as opposed to the "cortical" variants which present with predominant cortical features, including PSP-CBS, PSP-bvFTD, and PSP-PNFA.^[30] Cerebellar ataxia as the predominant early presenting feature is increasingly recognized as a very rare subtype of PSP (PSP-C) which is associated with severe neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus.^[31]

Differential diagnosis

PSP is frequently misdiagnosed as

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.^[34] Early falls are also more common with PSP, especially with Richardson syndrome.^[35]

PSP can also be misdiagnosed as Alzheimer's disease because of the behavioral changes.^[36]

Chronic traumatic encephalopathy (CTE) shows many similarities with PSP, because both share the following attributes:^[37]

• Accumulations of
  hyperphosphorylated tau protein
  in neurons or glial cells
• Accumulation of tau-
  immunoreactive astrocytes
• Involve the superficial
  cortical layers

Two studies have suggested that rivastigmine may help with cognitive aspects, but the authors of both studies have suggested that larger studies are needed.^[47][48] There is some evidence from small-scale studies that the hypnotic zolpidem may improve motor function and eye movements.^[49][50]

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.^[51] There has been research in the use of robot-assisted gait training.^[52] 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.^[53]

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.^[51] 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 followed only one or two patients.^[51] 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.^{[citation needed]}

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

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.^[54] Severe dysphagia often follows, and at this point death is often a matter of months.^[38]

Prognosis

No effective treatment or cure has been found for PSP, although some of the

In 1877, Charcot described a 40-year-old woman who had rigid-akinetic parkinsonism, neck dystonia, dysarthria, and eye-movement problems. In 1951, Chavany and others reported the clinical and pathologic features of a 50-year-old man with a rigid and akinetic form of parkinsonism with postural instability, neck dystonia, dysarthria, and staring gaze. In 1974, the unique frontal lobe cognitive changes of progressive supranuclear palsy: apathy, loss of spontaneity, slowing of thought processes, and loss of executive functions, were first described by Albert and colleagues.^[58]

Between 1877 and 1963, 22 well-documented case reports of PSP, although not described as a distinct disorder, had been identified in the literature of neurology.^[59] Progressive supranuclear palsy was first described as a distinct disorder by neurologists John Steele, John Richardson, and Jerzy Olszewski in 1963.^{[2][60][61][62]} They recognized the same clinical syndrome in eight patients, and described the autopsy findings in six of them.^[60]

Society and culture

There are several organizations around the world that support PSP patients and the research into PSP and related diseases, such as corticobasal degeneration (CBD) and multiple system atrophy (MSA).

• Canada: PSP Society of Canada, a federally registered non-profit organization which serves patients and families dealing with PSP, CBD and MSA, set up in 2017 through the help of CurePSP in the USA^[63]
• France: Association PSP France, a nonprofit patient association set up in 1996 through the help of PSPA in the UK. It also gives support to French speaking patients in Quebec, Morocco, Algeria, Belgium and Lebanon^[64]
• UK: PSPA, a national charity for information, patient support and research of PSP and CBD, set up in 1995^[65]
• Ireland: PSPAI, an organization which aims to increase public awareness of PSP^[66]
• US: CurePSP, a nonprofit organization for promoting awareness, care and research of PSP, CBD, MSA "and other prime of life neurodegenerative diseases"^[67]

In popular culture

In the 2020 American

English actor, comedian, musician and composer Dudley Moore was diagnosed with PSP in 1999, and died of complications from the disease in 2002.

American singer Linda Ronstadt was diagnosed with PSP in 2019, following an initial diagnosis of Parkinson's disease in 2014.^[69]

US Representative Jennifer Wexton was diagnosed with PSP in 2023, after having been diagnosed incorrectly with Parkinson's disease earlier that year.^[70]

See also

• Lytico-bodig disease (Parkinsonism-Dementia Complex of Guam)
• Annonacin

References