Progressive Supranuclear Palsy

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Synonym: Steele-Richardson-Olszewski syndrome

Progressive supranuclear palsy is a neurodegenerative syndrome which was first described in 1964.[1] It affects cognition, eye movements and posture. Characteristics include supranuclear, primarily vertical, gaze dysfunction accompanied by extrapyramidal symptoms and cognitive dysfunction. The cause is unknown.

Progressive supranuclear palsy is the most common atypical Parkinsonian syndrome. There are two main clinical subtypes:[2][3] 

  • Richardson's syndrome: prominent postural instability, supranuclear vertical gaze palsy and frontal dysfunction.
  • PSP-Parkinsonism (PSP-P): asymmetrical onset, tremor and moderate initial therapeutic response to levodopa.

The diagnosis is clinical.[4] The criteria for diagnosis are:[5]

  • Criteria for possible progressive supranuclear palsy:
    • Gradually progressive disorder with onset when the individual is aged 40 years or older.
    • Either vertical gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset.
    • No evidence of other diseases that can explain the clinical features.
  • Criteria for probable progressive supranuclear palsy:
    • Vertical gaze palsy with prominent postural instability, falls in the first year of onset, and other features of possible progressive supranuclear palsy, as follows:
      • Symmetric proximal greater than distal akinesia or rigidity.
      • Abnormal neck posture.
      • Poor or absent response of Parkinsonism to levodopa therapy.
      • Early dysphagia and dysarthria.
      • Early cognitive impairment with at least two of the following: apathy, abstract thought impairment, decreased verbal fluency, imitation behaviour, or frontal release signs (re-emergence of certain primitive reflexes that are normally present in infants - eg, grasp and suck reflexes).
  • Criteria for definite progressive supranuclear palsy:
    • History of probable or possible progressive supranuclear palsy and histological evidence that is typical of the disease.

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  • The disease usually develops between the ages of 50 and 70 years.[6] 
  • The estimated annual incidence is 5.3 per 100,000 in Europe and the age-adjusted prevalence is approximately 6.4 per 100,000.[6] 
  • PSP is as common as motor neurone disease or multiple system atrophy but may be incorrectly diagnosed as Parkinson's disease, corticobasal degeneration or Alzheimer's disease.
  • Variable presentation.
  • The main clinical features are supranuclear ophthalmoplegia, pseudobulbar palsy, prominent neck dystonia, Parkinsonism, behavioural, cognitive and gait disturbances that cause imbalance and frequent falls.
  • Vertical gaze palsy is the most distinctive single clinical feature.

Symptoms

  • The onset is insidious and usually begins with a prolonged phase of vague fatigue, headaches, arthralgias, dizziness and depression. Patients also develop subtle personality changes, memory problems and pseudobulbar symptoms.
  • Common symptoms at disease onset include postural instability and falls, dysarthria, bradykinesia and visual disturbances such as diplopia, blurred vision, burning eyes, and light sensitivity.
  • Dysarthria, dysphagia and visual symptoms develop as the disease progresses.
  • Convergent eye movements are often impaired, and convergence insufficiency may produce episodic diplopia at near distances.
  • Cognitive dysfunction and personality change are common, with apathy, disinhibition, dysphoria and anxiety.
  • Micturition disturbances, including urinary incontinence, are common in the later stages.

Signs

  • The classic gaze palsy usually involves looking down before looking up. It affects horizontal, as well as vertical, eye movements. Complete ophthalmoparesis may develop late in the disease course.
  • Nearly continuous square wave eye jerks are common. They consist of small horizontal movements that take both eyes off target and then return the eyes to the target after a very brief pause.
  • Eyelid signs include lid retraction, blepharospasm and lid lag.
  • Bradykinesia with masked facies and a startled expression are frequent findings.
  • Increased rigidity that is not cogwheel in nature. Resting tremor is unusual.

Other causes of dementia, and other movement disorders - eg, Parkinson's disease.

Atypical Parkinsonian disorders include multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and dementia with Lewy bodies. Clinical differentiation between these can be difficult in the early stages of the disease.[7][8] 

There are no specific laboratory or imaging findings. Investigations are directed at eliminating other diagnoses.

  • MRI, positron emission tomography (PET) and single-photon emission computed tomography (SPECT).[9] 
  • Sleep studies: sleep patterns are often abnormal.
  • No therapy is currently proven to be effective.[6] 
  • Only a few patients respond to dopaminergic or anticholinergic drugs, and responses often are short-lived and incomplete. No medication is effective in halting the progression of the disease.
  • Chronic conjunctivitis is common because of the reduced blink rate and often requires treatment.
  • Several medications, including dopamine agonists, tricyclic antidepressants, and methysergide, may provide modest symptomatic improvement in some of the clinical features.
  • Levodopa generally produces no dramatic difference in symptoms.
  • Bromocriptine may have a better effect, but this is modest and short-lived in most patients.
  • Botulinum toxin A may be useful in the treatment of rigidity, in particular nuchal rigidity, and dystonia, such as blepharospasm and focal limb dystonia. It may also be useful for sialorrhoea.
  • Electroconvulsive therapy may ameliorate motor symptoms in some patients, but significant adverse effects (eg, confusion) limit its usefulness.

Davunetide is a neuroprotective peptide which has preclinical evidence for neuroprotective, neurotrophic and cognitive protective properties. Potential clinical uses of davunetide include neurodegenerative disorders such as Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia. Data from clinical trials of davunetide have shown evidence that davunetide is generally safe and well tolerated, and has shown some signs of clinical efficacy.[10] 

  • Complications are mainly due to impaired balance, reduced cognition and immobility late in the disease process.
  • Complications related to falls may cause significant injuries.
  • Immobility in late disease leads to an increased risk of infection, especially pneumonia, urinary tract infection and skin infection.
  • Although the clinical course is variable, the typical presentation is usually associated with mortality 5-9 years after the onset of symptoms.[11]
  • The main cause of death is infection.
  • The loss of independent gait and the inability to stand unassisted occurs less than three years after disease onset.[6] 

Further reading & references

  1. Williams DR, Lees AJ; Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009 Mar;8(3):270-9.
  2. Boeve BF; Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S192-4. doi: 10.1016/S1353-8020(11)70060-8.
  3. Liscic RM, Srulijes K, Groger A, et al; Differentiation of progressive supranuclear palsy: clinical, imaging and laboratory tools. Acta Neurol Scand. 2013 May;127(5):362-70. doi: 10.1111/ane.12067. Epub 2013 Feb 13.
  4. Williams DR, de Silva R, Paviour DC, et al; Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism. Brain. 2005 Jun;128(Pt 6):1247-58. Epub 2005 Mar 23.
  5. Litvan I, Agid Y, Calne D, et al; Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9.
  6. Gold M, Lorenzl S, Stewart AJ, et al; Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy. Neuropsychiatr Dis Treat. 2012;8:85-93. doi: 10.2147/NDT.S12518. Epub 2012 Feb 9.
  7. Wenning GK, Colosimo C; Diagnostic criteria for multiple system atrophy and progressive supranuclear palsy. Rev Neurol (Paris). 2010 Oct;166(10):829-33. doi: 10.1016/j.neurol.2010.07.004. Epub 2010 Sep 1.
  8. Kurata T, Kametaka S, Ohta Y, et al; PSP as distinguished from CBD, MSA-P and PD by clinical and imaging differences at an early stage. Intern Med. 2011;50(22):2775-81. Epub 2011 Nov 15.
  9. Mascalchi M, Vella A, Ceravolo R; Movement disorders: role of imaging in diagnosis. J Magn Reson Imaging. 2012 Feb;35(2):239-56. doi: 10.1002/jmri.22825.
  10. Morimoto BH, Fox AW, Stewart AJ, et al; Davunetide: a review of safety and efficacy data with a focus on neurodegenerative diseases. Expert Rev Clin Pharmacol. 2013 Sep;6(5):483-502. doi: 10.1586/17512433.2013.827403. Epub 2013 Aug 24.
  11. Houghton DJ, Litvan I; Unraveling progressive supranuclear palsy: from the bedside back to the bench. Parkinsonism Relat Disord. 2007;13 Suppl 3:S341-6.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Colin Tidy
Current Version:
Peer Reviewer:
Dr Adrian Bonsall
Last Checked:
13/01/2014
Document ID:
2668 (v23)
© EMIS