eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Progressive Supranuclear Palsy: Treatment & Medication

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
Coauthor(s): Zeba F Vanek, MD, MBBS, DCN, Associate Professor of Neurology, David Geffen School of Medicine at UCLA; Director, UCLA Spasticity Clinic
Contributor Information and Disclosures

Updated: Sep 4, 2009

Treatment

Medical Care

Treatment of PSP is challenging at best; only a few patients respond to dopaminergic or anticholinergic drugs, and responses often are short-lived and incomplete. No medication is effective in halting the progression of PSP. Several medications, including dopamine agonists, tricyclic antidepressants, and methysergide, may provide modest symptomatic improvement in some of the clinical features.

  • Levodopa and carbidopa (Sinemet) generally produce no dramatic difference in symptoms, sharply contrasting with their effect in idiopathic Parkinson disease. Accordingly, administration of Sinemet may serve as a diagnostic test to help eliminate the possibility of Parkinson disease.
  • Some clinicians think that bromocriptine may have somewhat greater effect in individuals with PSP, although the effect is modest and short-lived in most patients. Tricyclic antidepressants have also been used.
  • Other medications that have been tried with limited success include amantadine and trazodone.
  • Botulinum toxin A has been found to be useful in the treatment of rigidity, in particular nuchal rigidity, and dystonia, such as blepharospasm, bruxism, and focal limb dystonia.43 It may also be useful for sialorrhea.
  • Electroconvulsive therapy (ECT) may ameliorate motor symptoms in some patients with PSP. However, long hospitalizations and significant adverse effects such as confusion limit the usefulness.
  • Chronic conjunctivitis is common because of the reduced blink rate in individuals with PSP. This can be treated with applications of methylcellulose or methyl alcohol drops in the eyes.

Consultations

  • Consultation with a neuro-ophthalmologist or ophthalmologist may help define the cause and outline the treatment of symptoms such as episodic diplopia.
  • Consultation with a rehabilitation medicine specialist may assist in maximizing gait stability and safety.
  • When swallowing starts to become affected, consultation with a speech therapist may help with modifying the diet.

Diet

  • Recommend a good well-balanced diet. The authors encourage patients to accept gastrostomy as a good option when feeding becomes impossible because of dysphagia and the high risk of bronchoaspiration.
  • A double-blind, randomized, placebo-controlled, phase II trial found that supplemental coenzyme Q(10) (5 mg/kg/day) for 6 weeks produced favorable changes in cerebral energy metabolites and slight but significant improvement in some measures of motor and neuropsychological dysfunction.44

Activity

Gait disturbances and falls are two of the major causes of disability in individuals with PSP. Physiotherapy after gait analysis, occupational therapy to find the best solutions to improve mobility, safe exercise programs, and appropriate mobility aids may decrease falls and related morbidity.

Medication

No effective therapy for PSP is known. A trial of a dopamine agonist is often undertaken to help eliminate Parkinson disease in diagnostically confusing cases or to provide modest symptomatic improvement.

Antiparkinson/dopamine agonists

Dopamine agonists directly stimulate postsynaptic dopamine receptors to provide benefit against symptoms of Parkinson disease. In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes is currently unclear.


Levodopa and carbidopa (Sinemet)

Generally produce no dramatic difference in symptoms, sharply contrasting with effect in idiopathic Parkinson disease. Accordingly, may serve as a diagnostic test to help eliminate the possibility of Parkinson disease.
10/100, 25/100, 25/250 formulations (carbidopa/levodopa) are available

Adult

0.5-1 tab (10/100) PO tid initial, with increases prn and as tolerated

Pediatric

Not established

Numerous possible interactions include amantadine, anesthetics, antacids, anticonvulsants, benzodiazepines, other dopamine agonists, anticholinergics, or sympathomimetics

Documented hypersensitivity; acute angle-closure glaucoma; melanoma; MAOI use within 14 d; caution in psychosis, asthma, CAD, peptic ulcer disease, or impaired renal function

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are suggested during prolonged use; monitor patients with glaucoma for intraocular pressure changes; occasionally, a dark discoloration may involve saliva, sweat, or urine


Bromocriptine (Parlodel)

Semisynthetic ergot alkaloid derivative that is strong D2 receptor agonist and weak D1 receptor antagonist. FDA approved as adjunct to levodopa/carbidopa; less effective than other dopamine agonists. May relieve akinesia, rigidity, and tremor in PD. Mechanism of therapeutic effect involves direct stimulation of dopamine receptors in the corpus striatum.
Approximately 28% absorbed from GI tract and metabolized in liver. Elimination half-life is approximately 50 h, with 85% excreted in feces and 3-6% eliminated in urine. Initiate at low dosage and individualize. Increase daily dosage slowly until maximum therapeutic response achieved. If possible, maintain the dosage of levodopa during this introductory period. Assess dosage titrations q2wk to ensure that lowest dosage producing optimal therapeutic response is not exceeded. If adverse reactions mandate, reduce dose gradually in 2.5-mg increments.

Adult

1.25 mg (one half of a 2.5-mg tab) PO qd; increase by 1.25 mg/d per wk to 1.25 mg tid with meals; increase q2-4wk by 2.5 mg/d with meals; usual range 10-40 mg/d divided tid/qid; safety has not been demonstrated in dosages >100 mg/d

Pediatric

Not established

Ergot alkaloids increase toxicity; amitriptyline, butyrophenone, imipramine, methyldopa, phenothiazine, and reserpine may decrease effects

Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include nausea, hypotension, hallucinations, and somnolence; use cautiously in patients with renal or hepatic disease

Tricyclic antidepressants

A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission.


Amitriptyline (Elavil)

Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS.

Adult

Begin with low dose (eg, 10 mg PO qhs) with increases prn and as tolerated

Pediatric

Not established

Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Documented hypersensitivity; MAOI use within 14 d; acute MI recovery

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Both elevation and depression of blood sugar have been reported; patients with schizophrenia may develop increasing psychosis, while those with depression may shift to mania; write prescriptions for the smallest amount feasible

More on Progressive Supranuclear Palsy

Overview: Progressive Supranuclear Palsy
Differential Diagnoses & Workup: Progressive Supranuclear Palsy
Treatment & Medication: Progressive Supranuclear Palsy
Follow-up: Progressive Supranuclear Palsy
References
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References

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

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

  3. 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].

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

  5. 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].

  6. 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].

  7. 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].

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

  9. 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].

  10. 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].

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

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

  13. 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].

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

  15. 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].

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

  17. 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].

  18. 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].

  19. 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].

  20. 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].

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

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. 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].

  29. 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].

  30. 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].

  31. 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].

  32. 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].

  33. 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].

  34. 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].

  35. 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].

  36. 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].

  37. 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].

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

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

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

  41. Laffont F, Autret A, Minz M, 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].

  42. 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].

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

  44. Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM, et al. 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].

  45. 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].

  46. Albers DS, Augood SJ. New insights into progressive supranuclear palsy. Trends Neurosci. Jun 2001;24(6):347-53. [Medline].

  47. Hamilton SR. Neuro-ophthalmology of movement disorders. Curr Opin Ophthalmol. Dec 2000;11(6):403-7. [Medline].

  48. Jankovic J, Friedman DI, Pirozzolo FJ, McCrary JA. Progressive supranuclear palsy: motor, neurobehavioral, and neuro- ophthalmic findings. Adv Neurol. 1990;53:293-304. [Medline].

  49. Kuniyoshi S, Riley DE, Zee DS, et al. Distinguishing progressive supranuclear palsy from other forms of Parkinson''s disease: evaluation of new signs. Ann N Y Acad Sci. Apr 2002;956:484-6. [Medline].

  50. Laffont F, Autret A, Minz M, et al. [Polygraphic study of nocturnal sleep in three degenerative diseases: ALS, oligo-ponto-cerebellar atrophy, and progressive supranuclear palsy]. Waking Sleeping. Jan 1979;3(1):17-30. [Medline].

  51. Leigh JR, Zee DS. The neurology of eye movements. 3rd ed. New York, NY:. Oxford University Press;1999:521-525.

  52. Litvan I. Diagnosis and management of progressive supranuclear palsy. Semin Neurol. 2001;21(1):41-8. [Medline].

  53. Litvan I, Hauw JJ, Bartko JJ, et al. Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol. Jan 1996;55(1):97-105. [Medline].

  54. Mark MH. Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration. Neurol Clin. Aug 2001;19(3):607-27, vi. [Medline].

  55. Nath U, Ben-Shlomo Y, Thomson RG, et al. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain. Jul 2001;124(Pt 7):1438-49. [Medline].

  56. Osaki Y, Ben-Shlomo Y, Lees AJ, et al. Accuracy of clinical diagnosis of progressive supranuclear palsy. Mov Disord. Feb 2004;19(2):181-9. [Medline].

  57. Rafal RD, Friedman JH. Limb dystonia in progressive supranuclear palsy. Neurology. Sep 1987;37(9):1546-9. [Medline].

  58. Schrag A, Selai C, Davis J, et al. Health-related quality of life in patients with progressive supranuclear palsy. Mov Disord. Dec 2003;18(12):1464-9. [Medline].

  59. Tolosa E, Valldeoriola F. Progressive supranuclear palsy. In: Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders. 3rd ed. Baltimore, Md:. William & Wilkins;1998:221-243.

  60. Warmuth-Metz M, Naumann M, Csoti I, Solymosi L. Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol. Jul 2001;58(7):1076-9. [Medline].

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Further Reading

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Keywords

Steele-Richardson-Olszewski syndrome, PSP, parkinsonism, neurodegenerative disease, imbalance, immobility, dementia, visual symptoms, dysphagia, dysarthria, vertical gaze palsy

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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)

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.

Medical Editor

Joseph Quinn, MD, Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University
Joseph Quinn, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience, and Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
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: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
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: Nothing to disclose.

 
 
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