Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a 4 repeat tauopathy causing akinetic rigid parkinsonism with vertical gaze palsy.

• Prevalence about 5 to 7 per 100,000; onset after 60; median survival 6 to 8 years.

• Variants: Richardson syndrome (classic), PSP-parkinsonism (levodopa responsive initially), pure akinesia with gait freezing, corticobasal and speech language variants.

• Pathology: globose neurofibrillary tangles, tufted astrocytes in basal ganglia, brainstem.

• Early unprovoked falls (backward), postural instability within 1 year.

• Vertical supranuclear gaze palsy (downward first), square wave jerks, slow saccades, apraxia of eyelid opening, "surprised" stare.

• Axial rigidity, bradykinesia, dysarthria, dysphagia, frontal cognitive dysfunction, pseudobulbar affect, poor levodopa response, symmetric onset.

• Complications: aspiration pneumonia, injuries, immobility.

• Clinical (Movement Disorder Society criteria).

• MRI brain: midbrain atrophy ("hummingbird sign", reduced midbrain to pons ratio), "Mickey Mouse" sign, third ventricle dilatation.

• FDG PET: frontal and midbrain hypometabolism; DaTscan reduced (does not discriminate from Parkinson disease).

• Exclude Parkinson disease, multiple system atrophy, corticobasal degeneration, vascular parkinsonism, normal pressure hydrocephalus, Whipple disease, Niemann-Pick type C.

• Swallow assessment.

• No disease modifying therapy.

• Levodopa/carbidopa 100/25 mg three times daily up to 600 to 1000 mg levodopa trial (modest benefit in 30%); amantadine 100 mg twice daily.

• Dysphagia: speech therapy, thickened fluids, early gastrostomy discussion.

• Eye symptoms: lubricants, botulinum toxin for blepharospasm/apraxia; prism glasses.

• Falls: physiotherapy, weighted walkers, home adaptation, occupational therapy.

• Pseudobulbar affect: amitriptyline 10 to 50 mg, dextromethorphan/quinidine. Depression: SSRIs.

• Palliative care involvement and advance care planning.

• Clinical trials (tau directed therapies).