Approach Considerations

Treatment of progressive supranuclear palsy (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 the disease; however, several medications, including dopamine agonists, tricyclic antidepressants, and methysergide, may provide modest symptomatic improvement with respect to some of the clinical features.

Electroconvulsive therapy (ECT) may ameliorate motor symptoms in some patients with PSP. However, long hospitalizations and significant adverse effects (eg, confusion) limit the usefulness of ECT.

Pharmacologic Therapy

The combination of carbidopa and levodopa generally produces no dramatic symptomatic improvement in patients with PSP, in sharp contrast with its effect in patients with idiopathic Parkinson disease. Accordingly, administration of carbidopa-levodopa 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, though 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.

OnabotulinumtoxinA has been found to be useful in the treatment of rigidity (nuchal rigidity in particular) and dystonia (eg, blepharospasm, bruxism, and focal limb dystonia).^[11]It may also be useful for sialorrhea.

A small phase II clinical trial using coenzyme Q10 in patients with PSP showed modest clinical improvement in the short term.^[48]

Chronic conjunctivitis is common in individuals with PSP because of the reduced blink rate in these patients. It can be treated with applications of methylcellulose or methyl alcohol drops in the eyes.

Consultations

Consultation with a neuro-ophthalmologist or an 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 in modifying the diet.

Diet and Activity

Patients should follow a well-balanced diet. When feeding becomes impossible because of dysphagia and the high risk of bronchoaspiration, patients should be encouraged to accept gastrostomy as a good option.

A double-blind, randomized, placebo-controlled, phase II trial found that supplemental coenzyme Q10, 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.^[48]

Gait disturbances and falls are 2 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.

Long-Term Monitoring

To help the patient and family adjust to the changing needs incurred by PSP, close follow-up care should be provided, with particular attention to potential adverse effects related to any medication trials. Often, family-directed education is the most valuable component of clinical visits. Patients and families often benefit from contact with a PSP support group (see Patient Education).

Physical therapy and rehabilitation medicine involvement may help maximize ambulation safety and facilitate instruction in the use of a walker, wheelchair, or other aids.

Preliminary evidence suggests that the combination of balance training complemented with eye movement and visual awareness exercises can be beneficial for enhancing suppression of fixation and gaze shift in patients with PSP.^[49]

Medication

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. 1994 Nov. 44(11):2015-9. [QxMD MEDLINE Link].
Drayer BP, Olanow W, Burger P, et al. Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology. 1986 May. 159(2):493-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Stern MB, Braffman BH, Skolnick BE, et al. Magnetic resonance imaging in Parkinson''s disease and parkinsonian syndromes. Neurology. 1989 Nov. 39(11):1524-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Paviour DC, Price SL, Stevens JM, et al. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology. 2005 Feb 22. 64(4):675-9. [QxMD MEDLINE Link].
Aldrich MS, Foster NL, White RF, et al. Sleep abnormalities in progressive supranuclear palsy. Ann Neurol. 1989 Jun. 25(6):577-81. [QxMD MEDLINE Link].
Santamaria J, Iranzo A. Alteraciones del sueno en los trastornos del movimiento. Neurologia. 1997. 12 (Suppl 3):35-47.
Gross RA, Spehlmann R, Daniels JC. Sleep disturbances in progressive supranuclear palsy. Electroencephalogr Clin Neurophysiol. 1978 Jul. 45(1):16-25. [QxMD MEDLINE Link].
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). 1979 Feb. 135(2):127-41. [QxMD MEDLINE Link].
Polo KB, Jabbari B. Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Neurol. 1994 Feb. 35(2):237-9. [QxMD MEDLINE Link].
Golbe LI. Progressive Supranuclear Palsy. Curr Treat Options Neurol. 2001 Nov. 3(6):473-477. [QxMD MEDLINE Link].
Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012 Jan. 18 Suppl 1:S192-4. [QxMD MEDLINE Link].
Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009 Mar. 8(3):270-9. [QxMD MEDLINE Link].
Conrad C, Andreadis A, Trojanowski JQ, et al. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol. 1997 Feb. 41(2):277-81. [QxMD MEDLINE Link].
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. 2008 Mar 4. 70(10):802-9. [QxMD MEDLINE Link].
Golbe LI, Rubin RS, Cody RP, et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology. 1996 Jul. 47(1):148-54. [QxMD MEDLINE Link].
Tetrud JW, Golbe LI, Forno LS, Farmer PM. Autopsy-proven progressive supranuclear palsy in two siblings. Neurology. 1996 Apr. 46(4):931-4. [QxMD MEDLINE Link].
Kaat LD, Boon AJ, Azmani A, Kamphorst W, Breteler MM, Anar B, et al. Familial aggregation of parkinsonism in progressive supranuclear palsy. Neurology. 2009 Jul 14. 73(2):98-105. [QxMD MEDLINE Link].
de Yebenes JG, Sarasa JL, Daniel SE, Lees AJ. Familial progressive supranuclear palsy. Description of a pedigree and review of the literature. Brain. 1995 Oct. 118 ( Pt 5):1095-103. [QxMD MEDLINE Link].
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. 1964 Apr. 10:333-59. [QxMD MEDLINE Link].
Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology. 1988 Jul. 38(7):1031-4. [QxMD MEDLINE Link].
Jackson JA, Jankovic J, Ford J. Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol. 1983 Mar. 13(3):273-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson- Olszewski syndrome (progressive supranuclear palsy). Neurology. 1986 Jul. 36(7):1005-8. [QxMD MEDLINE Link].
Kristensen MO. Progressive supranuclear palsy--20 years later. Acta Neurol Scand. 1985 Mar. 71(3):177-89. [QxMD MEDLINE Link].
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. 1996 Jun. 60(6):615-20. [QxMD MEDLINE Link].
Barclay CL, Lang AE. Dystonia in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1997 Apr. 62(4):352-6. [QxMD MEDLINE Link].
Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain. 1989 Oct. 112 ( Pt 5):1171-92. [QxMD MEDLINE Link].
Sakakibara R, Hattori T, Tojo M, et al. Micturitional disturbance in progressive supranuclear palsy. J Auton Nerv Syst. 1993 Nov. 45(2):101-6. [QxMD MEDLINE Link].
Tolosa E, Espuna M, Valls J. Bladder dysfunction in PSP and other parkinsonian disorders. Mov Disord. 1997. 12:272.
Josephs KA, Duffy JR. Apraxia of speech and nonfluent aphasia: a new clinical marker for corticobasal degeneration and progressive supranuclear palsy. Curr Opin Neurol. 2008 Dec. 21(6):688-92. [QxMD MEDLINE Link].
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. 2009 Jan. 15(1):59-61. [QxMD MEDLINE Link].
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. 2007 Oct 31. 22(14):2123-6. [QxMD MEDLINE Link].
Litvan I, Mega MS, Cummings JL, Fairbanks L. Neuropsychiatric aspects of progressive supranuclear palsy. Neurology. 1996 Nov. 47(5):1184-9. [QxMD MEDLINE Link].
Litvan I, Agid Y, Jankovic J, et al. Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology. 1996 Apr. 46(4):922-30. [QxMD MEDLINE Link].
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. 1996 Jul. 47(1):1-9. [QxMD MEDLINE Link].
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. 2008 Nov 25. 71(22):1796-803. [QxMD MEDLINE Link].
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. 2004 Jun-Jul. 25(6):927-32. [QxMD MEDLINE Link].
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. 2012 Jan 30. [QxMD MEDLINE Link].
Foster NL, Gilman S, Berent S, et al. Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography. Ann Neurol. 1988 Sep. 24(3):399-406. [QxMD MEDLINE Link].
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. 1992 Aug. 55(8):707-13. [QxMD MEDLINE Link].
Blin J, Baron JC, Dubois B, et al. Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations. Arch Neurol. 1990 Jul. 47(7):747-52. [QxMD MEDLINE Link].
Mishina M, Ishii K, Mitani K, et al. Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy. Acta Neurol Scand. 2004 Aug. 110(2):128-35. [QxMD MEDLINE Link].
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. 1990 Oct. 28(4):547-55. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Sixel-Döring F, Schweitzer M, Mollenhauer B, Trenkwalder C. Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy. Sleep Med. 2009 Apr. 10(4):407-15. [QxMD MEDLINE Link].
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. 2008 May 15. 23(7):942-9. [QxMD MEDLINE Link].
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. 2009 Feb. 90(2):263-70. [QxMD MEDLINE Link].
23rd Meeting of the European Neurological Society (ENS). Abstract P729. Presented June 10, 2013.
Keller DM. Botulinum Toxin Benefits Many PSP Patients With Dystonia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/806471. Accessed: July 7, 2013.

Media Gallery

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.

of 2

Author

Eric R Eggenberger, DO, MS, FAAN Neurologist, Departments of Neurology and Ophthalmology, Mayo Clinic

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, North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Coauthor(s)

David Clark, DO Clinical Assistant Professor of Neurology, Western University of Health Sciences; Neuro-ophthalmologist, Oregon Neurology Associates

David Clark, DO is a member of the following medical societies: American Academy of Neurology, American Osteopathic Association, North American Neuro-Ophthalmology Society

Disclosure: Received honoraria from Teva for speaking and teaching; Received honoraria from Biogen Idec for speaking and teaching.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani 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, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Acknowledgements

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.