Progressive Supranuclear Palsy Workup

  • Author: Eric R Eggenberger, DO, MS, FAAN; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Apr 11, 2012
 

Laboratory Studies

Workup in the setting of suspected progressive supranuclear palsy (PSP) is directed principally at eliminating other diagnoses.

Borroni et al proposed evaluation of tau forms in cerebrospinal fluid (CSF) as a biomarker for PSP.[28] CSF contains both extended (55 kd) and truncated (33 kd) tau forms, and the truncated-to-extended ratio is significantly lower in PSP than in other neurodegenerative disorders. In this study, the ratio was 0.504 ± 0.284 in PSP patients, 0.899-1.215 in patients with other neurodegenerative conditions, and 0.989 ± 0.343 in controls. In addition, a decreased ratio was correlated with brainstem atrophy, as assessed by voxel-based morphometry. Further study of such biomarker candidates is required before these become incorporated into diagnostic algorithms or criteria.

Whipple polymerase chain reaction (PCR) may be helpful in eliminating the possibility of Whipple disease, a treatable infectious disorder.

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Magnetic Resonance Imaging

Although, magnetic resonance imaging (MRI) of the brain offers little help in the early stages of PSP, it may reveal the following abnormalities in some advanced cases[29, 30, 31, 32, 33] :

  • Atrophy of the midbrain (see the image below) with cisternal and ventricular dilatation
  • Thinning of the quadrigeminal plate
  • Dilation of the third ventricle
  • A nonspecific finding of increase in proton density images in the periaqueductal gray matter, compatible with gliotic changesSagittal T1-weighted image shows atrophy of midbraSagittal T1-weighted image shows atrophy of midbrain, preservation of pontine volume, and atrophy of the tectum, suggestive of progressive supranuclear palsy (Steele-Olszewski-Richardson disease).

Righini et al reported the usefulness of assessing the appearance of the superior profile of the midbrain on midsagittal T1-weighted MRI.[34] The appearance of a flat or concave profile (as opposed to the normal convex profile) was associated with a 68% sensitivity and an 89% specificity for the diagnosis of PSP as compared with the diagnosis of Parkinson disease.

It should be kept in mind that these imaging findings are not pathognomonic of PSP nor early findings; some of their components may be observed in several other diseases in the differential diagnosis.

A study from Hamburg, Germany, reported that an abnormal brain iron accumulation was a marker for ongoing neurodegeneration in both PSP and Parkinson disease, but the 2 conditions differed with respect to the anatomic distribution of this accumulation. The investigators found that regional decreases of T2' relaxation times in parts of the basal ganglia reflecting increased brain iron load were characteristic for progressive supranuclear palsy but not for Parkinson disease.[35]

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Other Neuroimaging

Neuroimaging is often performed to eliminate other entities in the differential diagnosis. The presence of significant abnormalities (eg, large vessel ischemic disease, hydrocephalus) casts doubt on the diagnosis of PSP. Functional neuroimaging includes positron emission tomography (PET) and single-photon emission computed tomography (SPECT).

PET may help reveal physiopathologic aspects of the disease. PET studies have documented a global cerebral hypometabolism with relative selectivity in the frontal cortex.[36, 37, 38] Regional cerebral blood flow and oxygen metabolism are decreased in the caudate and putamen and impaired in the thalamus and brainstem. PET studies have also documented significantly lowered glucose metabolism in the midbrain of PSP patients as compared with control subjects.[39]

Fluorodopa (F-dopa) PET has shown reduced F-dopa influx into the caudate and putamen. In idiopathic Parkinson disease, the caudate is affected less severely; therefore, this finding can help in differentiating the 2 conditions.[40] The costs of PET studies and their limited availability restrict this technique to experimental trials.

In some patients with PSP,123 I-iodobenzamide SPECT has demonstrated reduced striatal dopamine receptor binding.[41] This finding can be used to distinguish vascular white-matter lesions from PSP.

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Sleep Studies

Sleep patterns are often abnormal in individuals with PSP. Polysomnography shows diminished total sleep time, increased awakenings, progressive loss of rapid-eye-movement (REM) sleep,[42, 43] and decreased REM–to–non-REM (NREM) quotient.[44, 45] REM sleep behavior disorder, consisting of motor activity associated with vivid dreams during REM sleep, also occurs in individuals with PSP.

These abnormalities are not specific for PSP. For example, Sixel-Döring et al found that although polysomnographically recorded sleep is more severely impaired in patients with PSP than in patients with Parkinson disease, Parkinson Disease Sleep Scale scores did not differ significantly between the 2 patient groups.[46]

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Histologic Findings

The histopathology of PSP involves diffuse brainstem disease. Neuronal loss, neurofibrillary tangles (NFTs), and gliosis affect the reticular formation and ocular motor nuclei. Early pathology is evident primarily in the midbrain; this may explain the early vertical eye movement characteristics. The pontine nucleus raphe interpositus and pedunculopontine and deep pontine nuclei are also affected.

The distribution and ultrastructure of NFTs in PSP are distinct from those of NFTs in Alzheimer disease. PSP is characterized by greater subcortical involvement, with single tubules 15-20 nm wide, whereas Alzheimer disease is characterized by cortically based paired helicoid filaments.

An examination of PSP cases revealed the uniform presence of tau-positive cortical lesions. These were found in highest concentration in the precentral and angular gyrus, primarily affecting the deep cortical layers, and involved both small and large neurons. Again, this pattern differs from the NFT pattern observed in Alzheimer disease. NFT concentration analysis appeared to implicate the pedunculopontine nucleus in lesion spread.

Although NFTs are the histologic hallmarks of PSP, neuropil threads have also been found extensively.

Besides the brainstem structures, the striatum, the medial pallidum, the subthalamic nucleus, and the substantia nigra are also affected.

There remain many unanswered questions about the pathologic features linking PSP, Alzheimer disease, idiopathic Parkinson disease, and, in particular, corticobasal degeneration. Further ultrastructural and genetic studies are needed to reveal the cause and the pathogenesis of the disease.

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Contributor Information and Disclosures
Author

Eric R Eggenberger, DO, MS, FAAN  Professor, Vice-Chairman, Department of Neurology and Ophthalmology, Colleges of Osteopathic Medicine and Human Medicine, Michigan State University; Director of Michigan State University Ocular Motility Laboratory; Director of National Multiple Sclerosis Society Clinic, Michigan State University

Eric R Eggenberger, DO, MS, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American Osteopathic Association, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Coauthor(s)

David Clark, DO  Chief Neurology Resident, Department of Neurology and Ophthalmology, Michigan State University College of Human Medicine

David Clark, DO is a member of the following medical societies: American Academy of Neurology and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Additional Contributors

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Zeba F Vanek, MD, MBBS, DCN Associate Professor of Neurology, David Geffen School of Medicine at UCLA; Director, UCLA Spasticity Clinic

Zeba F Vanek, MD, MBBS, DCN is a member of the following medical societies: Movement Disorders Society

Disclosure: Nothing to disclose.

References

  1. Golbe LI. Progressive Supranuclear Palsy. Curr Treat Options Neurol. Nov 2001;3(6):473-477. [Medline].

  2. Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. Jan 2012;18 Suppl 1:S192-4. [Medline].

  3. Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. Mar 2009;8(3):270-9. [Medline].

  4. Conrad C, Andreadis A, Trojanowski JQ, et al. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol. Feb 1997;41(2):277-81. [Medline].

  5. Liao K, Wagner J, Joshi A, Estrovich I, Walker MF, Strupp M, et al. Why do patients with PSP fall? Evidence for abnormal otolith responses. Neurology. Mar 4 2008;70(10):802-9. [Medline].

  6. Golbe LI, Rubin RS, Cody RP, et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology. Jul 1996;47(1):148-54. [Medline].

  7. Tetrud JW, Golbe LI, Forno LS, Farmer PM. Autopsy-proven progressive supranuclear palsy in two siblings. Neurology. Apr 1996;46(4):931-4. [Medline].

  8. Kaat LD, Boon AJ, Azmani A, Kamphorst W, Breteler MM, Anar B, et al. Familial aggregation of parkinsonism in progressive supranuclear palsy. Neurology. Jul 14 2009;73(2):98-105. [Medline].

  9. de Yebenes JG, Sarasa JL, Daniel SE, Lees AJ. Familial progressive supranuclear palsy. Description of a pedigree and review of the literature. Brain. Oct 1995;118 ( Pt 5):1095-103. [Medline].

  10. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy. A heterogenous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol. Apr 1964;10:333-59. [Medline].

  11. Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology. Jul 1988;38(7):1031-4. [Medline].

  12. Jackson JA, Jankovic J, Ford J. Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol. Mar 1983;13(3):273-8. [Medline].

  13. Mastaglia FL, Grainger K, Kee F, et al. Progressive supranuclear palsy (the Steele-Richardson-Olszewski syndrome) clinical and electrophysiological observations in eleven cases. Proc Aust Assoc Neurol. 1973;10(0):35-44. [Medline].

  14. Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson- Olszewski syndrome (progressive supranuclear palsy). Neurology. Jul 1986;36(7):1005-8. [Medline].

  15. Kristensen MO. Progressive supranuclear palsy--20 years later. Acta Neurol Scand. Mar 1985;71(3):177-89. [Medline].

  16. Litvan I, Mangone CA, McKee A, et al. Natural history of progressive supranuclear palsy (Steele-Richardson- Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry. Jun 1996;60(6):615-20. [Medline].

  17. Barclay CL, Lang AE. Dystonia in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. Apr 1997;62(4):352-6. [Medline].

  18. Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain. Oct 1989;112 ( Pt 5):1171-92. [Medline].

  19. Sakakibara R, Hattori T, Tojo M, et al. Micturitional disturbance in progressive supranuclear palsy. J Auton Nerv Syst. Nov 1993;45(2):101-6. [Medline].

  20. Tolosa E, Espuna M, Valls J. Bladder dysfunction in PSP and other parkinsonian disorders. Mov Disord. 1997;12:272.

  21. Josephs KA, Duffy JR. Apraxia of speech and nonfluent aphasia: a new clinical marker for corticobasal degeneration and progressive supranuclear palsy. Curr Opin Neurol. Dec 2008;21(6):688-92. [Medline].

  22. Cooper AD, Josephs KA. Photophobia, visual hallucinations, and REM sleep behavior disorder in progressive supranuclear palsy and corticobasal degeneration: a prospective study. Parkinsonism Relat Disord. Jan 2009;15(1):59-61. [Medline].

  23. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C. Pupil diameter in darkness differentiates progressive supranuclear palsy (PSP) from other extrapyramidal syndromes. Mov Disord. Oct 31 2007;22(14):2123-6. [Medline].

  24. Litvan I, Mega MS, Cummings JL, Fairbanks L. Neuropsychiatric aspects of progressive supranuclear palsy. Neurology. Nov 1996;47(5):1184-9. [Medline].

  25. Litvan I, Agid Y, Jankovic J, et al. Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology. Apr 1996;46(4):922-30. [Medline].

  26. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. Jul 1996;47(1):1-9. [Medline].

  27. Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, et al. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology. Nov 1994;44(11):2015-9. [Medline].

  28. Borroni B, Malinverno M, Gardoni F, Alberici A, Parnetti L, Premi E, et al. Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology. Nov 25 2008;71(22):1796-803. [Medline].

  29. Drayer BP, Olanow W, Burger P, et al. Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology. May 1986;159(2):493-8. [Medline].

  30. Schonfeld SM, Golbe LI, Sage JI, et al. Computed tomographic findings in progressive supranuclear palsy: correlation with clinical grade. Mov Disord. 1987;2(4):263-78. [Medline].

  31. Stern MB, Braffman BH, Skolnick BE, et al. Magnetic resonance imaging in Parkinson's disease and parkinsonian syndromes. Neurology. Nov 1989;39(11):1524-6. [Medline].

  32. Savoiardo M, Girotti F, Strada L, Ciceri E. Magnetic resonance imaging in progressive supranuclear palsy and other parkinsonian disorders. J Neural Transm Suppl. 1994;42:93-110. [Medline].

  33. Paviour DC, Price SL, Stevens JM, et al. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology. Feb 22 2005;64(4):675-9. [Medline].

  34. Righini A, Antonini A, De Notaris R, et al. MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol. Jun-Jul 2004;25(6):927-32. [Medline].

  35. Boelmans K, Holst B, Hackius M, Finsterbusch J, Gerloff C, Fiehler J, et al. Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy. Mov Disord. Jan 30 2012;[Medline].

  36. Foster NL, Gilman S, Berent S, et al. Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography. Ann Neurol. Sep 1988;24(3):399-406. [Medline].

  37. Foster NL, Gilman S, Berent S, et al. Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities. J Neurol Neurosurg Psychiatry. Aug 1992;55(8):707-13. [Medline].

  38. Blin J, Baron JC, Dubois B, et al. Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations. Arch Neurol. Jul 1990;47(7):747-52. [Medline].

  39. Mishina M, Ishii K, Mitani K, et al. Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy. Acta Neurol Scand. Aug 2004;110(2):128-35. [Medline].

  40. Brooks DJ, Ibanez V, Sawle GV, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol. Oct 1990;28(4):547-55. [Medline].

  41. Arnold G, Tatsch K, Oertel WH, et al. Clinical progressive supranuclear palsy: differential diagnosis by IBZM- SPECT and MRI. J Neural Transm Suppl. 1994;42:111-8. [Medline].

  42. Aldrich MS, Foster NL, White RF, et al. Sleep abnormalities in progressive supranuclear palsy. Ann Neurol. Jun 1989;25(6):577-81. [Medline].

  43. Santamaria J, Iranzo A. Alteraciones del sueno en los trastornos del movimiento. Neurologia. 1997;12 (Suppl 3):35-47.

  44. Gross RA, Spehlmann R, Daniels JC. Sleep disturbances in progressive supranuclear palsy. Electroencephalogr Clin Neurophysiol. Jul 1978;45(1):16-25. [Medline].

  45. Laffont F, Autret A, Minz M, Beillevaire T, Gilbert A, Cathala HP, et al. [Polygraphic sleep recordings in 9 cases of Steele-Richardson's disease (author's transl)]. Rev Neurol (Paris). Feb 1979;135(2):127-41. [Medline].

  46. Sixel-Döring F, Schweitzer M, Mollenhauer B, Trenkwalder C. Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy. Sleep Med. Apr 2009;10(4):407-15. [Medline].

  47. Polo KB, Jabbari B. Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Neurol. Feb 1994;35(2):237-9. [Medline].

  48. Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov Disord. May 15 2008;23(7):942-9. [Medline].

  49. Zampieri C, Di Fabio RP. Improvement of gaze control after balance and eye movement training in patients with progressive supranuclear palsy: a quasi-randomized controlled trial. Arch Phys Med Rehabil. Feb 2009;90(2):263-70. [Medline].

 
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Sagittal T1-weighted image shows atrophy of midbrain, preservation of pontine volume, and atrophy of the tectum, suggestive of progressive supranuclear palsy (Steele-Olszewski-Richardson disease).
Characteristic facial appearance of patient with progressive supranuclear palsy.
 
 
 
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