Progressive Supranuclear Palsy

Epidemiology

Prevalence: 1 / 20000

Age of onset: 50s – 60s

Risk factor: only ‘hard’ one is age

Pathogenesis

PSP is an idiopathic neurodegenerative disorder. It is characterised by intracellular aggregates of phosphorylated 4-repeat tau protein in neurons and glia. Tau aggregates are thought to impair axonal transport, mitochondrial function, and synaptic function. These events lead to death of neurons, astrocytes, and oligodendrocytes in the basal ganglia, midbrain, cortex, and brainstem.

Presentation

The classic presentation is with a constellation of progressive symptoms and signs:

  • Gaze palsies: initially supranuclear, i.e. above the level of the cranial nerve nuclei therefore causing a loss of voluntary gaze with preservation of the vestibulo-ocular reflex
  • Gait instability and falls: often fall backward due to hyperextended posture
  • Parkinsonism: rigidity is mainly axial
  • Startled facial appearance: ‘startled’ look due to facial dystonia
  • Cognitive dysfunction: mainly frontal lobe features, i.e. apraxia, dysexecution, disinhibition
  • Bulbar weakness: dysphagia, dysphonia, dysarthria

In addition to these features people with PSP can develop pyramidal weakness, cerebellar ataxia, and urinary incontinence.

PSP is sometimes categorised based on the predominant symptoms and signs in the history. The most classic form, described above, is called Richardson Syndrome. Other forms include PSP-P (parkinsonism-predominant), PSP-OM (oculomotor dysfunction-predominant), and PSP-PI (postural instability-predominant). These subtypes can be helpful to predict the course of the disease.

Investigation

Diagnosis of PSP is clinical based on a typical age, lack of evidence of another degenerative disorder, and a typical constellation of findings. Blood tests and structural imaging with MRI may be useful to exclude differential diagnoses.

The most common differential diagnoses to consider in someone presenting with parkinsonian features (i.e. bradykinesia, rigity, +/- tremor) are:

  • Degenerative
    • Idiopathic Parkinson’s Disease
    • Multiple System Atrophy
    • Corticobasal Degeneration
  • Vascular: multi-infarct Parkinsonism
  • Drug-induced parkinsonism

Features which help to distinguish PSP from idiopathic PD, the most likely differential diagnosis in most cases, are as follows:

PSP Idiopathic PD
Posture Extended Flexed
Symmetry Symmetric Asymmetric
Falls Early Late
Oculomotor abnormalites Prominent Absent
Tremor Mild Prominent
Rigidity Axial Limb
Autonomic dysfunction Mild Moderate
Cognition Apraxia

Dysexecution

Hallucinations

Dementia

Response to L-Dopa Poor Excellent

 

MRI shows midbrain atrophy  – the Hummingbird and ‘Mickey Mouse’ signs – but these are neither sensitive nor specific.

Definitive diagnosis is at post-mortem.

Management

There is no effective disease-modifying therapy.

Supportive management includes:

  • Levodopa-carbidopa: may be of symptomatic benefit in people with predominant parkinsonian symptoms
  • Non-pharmacologic:
    • Speech and language therapy
    • Occupational therapy
    • Dietician: many people require parenteral feeding in late-stage disease

Prognosis

Progression is inevitable. Median time to death is 6 – 9 years.