Progressive Supranuclear Palsy

HARVARD MEDICAL SCHOOLDEPARTMENT OF NEUROLOGY

MASSACHUSETTS GENERAL HOSPITAL

HARVARD MEDICAL SCHOOLDEPARTMENT OF NEUROLOGY

MASSACHUSETTS GENERAL HOSPITAL

HARVARD MEDICAL SCHOOLDEPARTMENT OF NEUROLOGY

MASSACHUSETTS GENERAL HOSPITAL

Shirley H. Wray, M.D., Ph.D.

Professor of Neurology, Harvard Medical School

Director, Unit for Neurovisual Disorders

Massachusetts General Hospital

Criteria for Dx PSP

Gradually progressive disorder

Onset at age 40 years old or later

Vertical supranuclear palsy

Slowing of vertical saccades

Postural instability with falls in the first year of disease onset

Supportive Criteria for Dx PSP

Symmetric akinesia or rigidityAbnormal neck posture, especially retrocollisPoor or absent response of parkinsonism to levodopa therapyEarly dysphagia and dysarthriaEarly onset of cognitive impairment, including at least 2 of these: apathy, decreased verbal fluency, impaired abstract reasoning, and utilization behavior

Clinical Features of PSP

Slow vertical saccades, especially down, with a preserved range of movement, may be the first sign of the disorder; later, loss of vertical saccades and quick phases

Horizontal saccades become slow and hypometric

Disruption of steady gaze by horizontal saccadic intrusions (square-wave jerks)

Impaired smooth pursuit, vertically (reduced range) and horizontally (with catch-up saccades)

Clinical Features of PSP

Smooth eye-head tracking may be relatively preserved, especially vertically

Preservation of vestibulo-ocular reflex

Horizontal disconjugacy suggesting INO

Loss of convergence

Ultimately, all eye movements may be lost, but vestibular movements are the last to go

Clinical Features of PSP

Eyelid disorders: delay in lid opening, lid lag, repetitive blinking in response to flashlight stimulus (failure to habituate), blepharospasm

Tonic head deviation opposite to direction of body rotation (vestibulocollic reflex)

Inability to clap just three times (applause sign)

Leigh RJ, Zee DS. Diagnosis of Central Disorders of Ocular Motility. Chpt 12: 598-718. The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY, 2006.

Neuroimaging

Figure 1: Sagittal T2-weighted MR in another patient with PSP shows the tectal plate is markedly thinned and atrophic. Courtesy Anne Osborn, MD.

Figure 2. Single photon emission tomography (PET) scan of a patient with PSP demonstrating frontal lobe hypoperfusion.

Figure 3. PET in a patient with PSP. Showing area of hypoperfusion (blue).

Pathology

Figure 4: PSP_pale locus ceruleus Figure 5: PSP_pale substantia nigra

Pathology

Figure 6: PSP-the-globose Tangle

Pathology

Figure 7: PSP-tau-globose-tangle Figure 8: PSP-tau-tufted

Tauopathies: Clinical Diseases

Alzheimer’s disease PSP

Dementia pugilistica MSA

Guam ALS/PD Corticobasogangli-

Pick disease onic degeneration

Argyrophilic grain FTDP-17

disease Postencephalatic PD

Nieman-Pick, type C Autosomal recess-

SSPE ive PD

References

Freidman DI, Jankovic, J, McCrary III JA. Neuro-ophthalmic findings in progressive supranuclear palsy. J Clin Neuro-ophthalmol. 1992 Jun; 12(2):104-109.

Growden JH, Rossor MN. The Dementias. Blue Books of Practical Neurology. Butterworth-Heinemann 1998; vol 19.

Richardson JC, Steele J, Oszewski J. Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. A clinical report on eight cases of heterogenous system degeneration. Trans Am Neurol Assoc. 1963; 88:25-29.

Stanford PM, Halliday GM, Brooks WS, Kwok JBJ, Storey CE, Creasey H, Morris JGL, Fulham MJ, Schofield PR. Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: explanation of the disease phenotype caused by tau gene mutations. Brain 2000; 123(Pt 5): 880-893.

http://www.library.med.utah.edu/NOVEL