Progressive Supranuclear Palsy

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Progressive Supranuclear Palsy
Shirley H. Wray, M.D., Ph.D. Professor of
Neurology, Harvard Medical School Director, Unit
for Neurovisual Disorders Massachusetts General
Hospital
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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

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Supportive Criteria for Dx PSP

• Symmetric akinesia or rigidity
• Abnormal neck posture, especially retrocollis
• Poor or absent response of parkinsonism to
  levodopa therapy
• Early dysphagia and dysarthria
• Early onset of cognitive impairment, including
  at least 2 of these apathy, decreased verbal
  fluency, impaired abstract reasoning, and
  utilization behavior

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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)

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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

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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.
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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.
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Figure 2. Single photon emission tomography (PET)
scan of a patient with PSP demonstrating frontal
lobe hypoperfusion.
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Figure 3. PET in a patient with PSP. Showing area
of hypoperfusion (blue).
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Pathology
Figure 4 PSP_pale locus ceruleus
Figure 5 PSP_pale substantia nigra
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Pathology
Figure 6 PSP-the-globose Tangle
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Pathology
Figure 7 PSP-tau-globose-tangle
Figure 8 PSP-tau-tufted
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Tauopathies Clinical Diseases

• Alzheimers 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

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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.

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• 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
  8825-29.
• 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.

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