Diagnosis

The diagnosis is clinical. The criteria for diagnosis are:^[3]

• 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 2 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.

Epidemiology

• The disease usually develops after the age of 50 years.
• The median interval between onset and diagnosis is 3 years, with a range of 6 months to 9 years.^[4]
• Most cases appear to be sporadic. Both environmental and genetic influences have been postulated.
• Point prevalence in the UK has been estimated at 3.1 per 100,000 (as reported by a collaborative network of doctors in the North of England).^[4] It may be as high as 6.5 per 100,000 if prevalence data in GP records are used.
• Slight male predominance in most studies.^[5]

Presentation

• 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. Also develop subtle personality changes, memory problems and pseudobulbar symptoms. The initial symptoms can often involve unexplained imbalance or falls.
• 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.
• In one study, the most common symptoms at disease onset were postural instability and falls, dysarthria, bradykinesia and visual disturbances such as diplopia, blurred vision, burning eyes, and light sensitivity. Cognitive dysfunction and personality change are common, with apathy, disinhibition, dysphoria and anxiety.^[6]
• Micturition disturbances, including urinary incontinence, are common in the later stages.^[7]

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.

Differential diagnosis

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

Investigations

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

• MRI.
• Functional neuro-imaging includes positron emission tomography and single-photon emission computed tomography.
• Sleep studies: sleep patterns are often abnormal.

Management

• No therapy is currently proven to be effective.
• 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.^[8]
• Electro-convulsive therapy may ameliorate motor symptoms in some patients, but significant adverse effects, eg confusion, limit its usefulness.

Complications

• 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.

Prognosis

• Although the clinical course is variable, the typical presentation is usually associated with mortality 5-9 years after the onset of symptoms.^[9]
• Main cause of death is infection.
• The interval from initial symptom occurrence to the need for a walking aid is 3.1 years, and the interval to being confined to a chair or bed is 8.2 years.^[4]