Progressive Supranuclear Palsy 

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

Background

Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, is a neurodegenerative disease that affects cognition, eye movements, and posture.[1, 2] PSP was first described as a clinicopathologic entity in 1964. Characteristics include supranuclear, initially vertical, gaze dysfunction accompanied by extrapyramidal symptoms and cognitive dysfunction. The disease usually develops after the sixth decade of life, and the diagnosis is purely clinical. Currently, no therapy is proven to be effective.

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Pathophysiology

Pathologically, PSP is defined by the accumulation of neurofibrillary tangles in the brain.[3] Different rates, localizations, and patterns of the accumulation of phosphorylated tau protein may account for the variation in clinical phenomena seen in patients with PSP.

The tau protein is important in maintaining neuronal morphology through microtubule binding. Abnormalities of this protein have been noted in several neurodegenerative diseases. Under abnormal circumstances, the normally soluble tau protein may collect in insoluble protease-resistant helical filaments. The exact triggers for the conversion from normal tau to the aggregate form are not completely understood.

This model shares some characteristics with prion disease (Creutzfeldt-Jakob disease), in which an abnormal insoluble prion protein isoform accumulates.

Work by Conrad et al demonstrated the overrepresentation of the homozygous tau A0 allele in patients with PSP compared to controls.[4] Accordingly, the tau A0 allele may be a genetic marker of increased susceptibility to the PSP pathophysiology. However, the tau A0 allele status is not required or sufficient to predict the occurrence of PSP.

Although the e4 allele of the apoprotein E gene (ApoE) is a significant risk factor for the development of Alzheimer disease and is overrepresented in individuals with Lewy body disease, it is not associated with PSP, Parkinson disease, or alcoholic dementia.

Liao et al found that during near viewing, the translational vestibulo-ocular reflex responses in patients with PSP were, on average, only 12% of those of control subjects, which suggested that abnormal otolith-mediated reflexes may be at least partly responsible for the frequent falls in patients with PSP.[5] The amplitude of vestibular-evoked myogenic potentials was also significantly lower in PSP patients than in normal control subjects.

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Etiology

The cause of PSP remains unknown. Most cases appear to be sporadic. Both environmental and genetic influences have been postulated. To date, there have been only a few epidemiologic studies investigating PSP associations.

In a questionnaire survey carried out on a cohort of 75 patients with PSP and matched controls, Golbe et al obtained information on exposures (eg, to hydrocarbons, pesticides and herbicides), urban versus rural living, occupation, trauma, education level, maternal age, and family history of neurologic diseases; patients with PSP were less likely than controls to have completed 12 years of education.[6] The authors speculate that education level may be a marker for more direct risk factors (eg, early life nutrition or occupational or residential exposure).

The role of heredity in the pathophysiology of PSP remains elusive. Although there are anecdotal reports in the literature that describe apparent familial PSP, several larger series have not noted this association. In one case-control questionnaire, a trend toward relatives with parkinsonism was reported.

Tetrud et al reported the occurrence of autopsy-proven PSP in a brother-sister pair.[7] Both developed parkinsonism in the eighth decade of life and subsequently exhibited typical features of PSP over the next 5 years. Their mother and possibly their maternal grandfather experienced a parkinsonian syndrome, and essential tremor was noted in their father and 2 of the brother’s 3 children. The probands exhibited typical pathologic features of PSP upon autopsy.

Although the current absence of a large kindred with PSP precludes molecular linkage studies, the authors suggest that pairs such as those in their report could be pooled for analysis[7] ; such occurrences are quite rare.

Kaat et al reported that of 57 (33%) of 172 patients with PSP had at least 1 first-degree relative who had dementia or parkinsonism, compared with 25% of control subjects.[8] More first-degree relatives with parkinsonism were observed in PSP patients than in controls.

Although most cases of PSP appear to be sporadic, rare genetically determined forms may exist. Garcia de Yebenes et al studied a 5-generation family in which PSP was transmitted as an autosomal dominant trait,[9] finding 2 instances of male-to-male transmission. The proband had the classic presentation of this disorder beginning with axial rigidity, slowness of movement, and gait difficulty. Over a period of 2 years, he progressed to complete vertical gaze palsy, axial dystonia, retrocollis, and generalized severe akinesia.

Postmortem examination demonstrated neurofibrillary tangles (NFTs) and gliosis without prominent senile plaques, the same pathology that was observed in the sporadic cases of PSP described by Steele et al.[10]

In addition, Garcia de Yebenes et al described 6 other families with multiple affected individuals. These included 2 in which a parent was affected, suggesting autosomal dominant inheritance, and 1 family in which parental consanguinity occurred, suggesting recessive inheritance.[9] In the cohort studied by Kaat et al, 12 of 172 patients with PSP (7%) fulfilled the criteria for an autosomal dominant mode of transmission.[8]

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Epidemiology

United States

A population-based study in New Jersey by Golbe et al revealed an overall prevalence of 1.39 cases per 100,000 population. The male prevalence was 1.53 in 100,000, whereas the female prevalence was 1.23 in 100,000; this finding was in accordance with a previously noted slight male preponderance. The adjusted prevalence ratio among patients older than 55 years was 7 in 100,000.[11] Prevalence data derived from tertiary centers suggest that PSP affects 4-6% of patients with parkinsonism.[12]

International

The incidence of PSP has been assessed in Perth, Australia; crude incidence rates are 3-4 per million cases per year, approximately 5% of the incidence of Parkinson disease.[13]

Age-, sex-, and race-related demographics

The mean age at onset is approximately 63 years (range, 44-75 years).[11, 14] The median interval between onset and diagnosis is 3 years (range, 0.5-9 years). PSP has a slight male predominance in most studies. According to Kristensen, the male-to-female ratio is 1.5:1.[15]

Most reported cases have been in whites. The affected cohort in Golbe’s study consisted entirely of white persons; however, the survey population included only 5.7% black individuals, thus preventing any meaningful analysis regarding race.[11]

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Prognosis

Studies of cohort patients dying under surveillance suggest that PSP is usually fatal within approximately 6 years of onset (range, 2-17 years); life table analysis among the entire cohort of Golbe et al revealed a median disease duration of 9.7 years.[11] Conflicting reports exist regarding the influence of age at diagnosis on survival; Golbe found a tendency for younger patients to survive longer, although this is not a uniform finding among other studies.[11, 14]

The primary causes of death in patients with PSP are infections and pulmonary complications (eg, pneumonia) that are frequently related to immobility. Often, the primary morbidity relates to imbalance leading to immobility, though dementia, visual symptoms, and dysphagia are major concerns. About 50% of patients require some aid to walk within 3 years of the initial onset of symptoms. The usual interval from initial symptom occurrence to the need for a cane or a walker is 3.1 years, and the interval to confinement to a chair or bed is 8.2 years.[11]

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Patient Education

The primary educational efforts related to PSP are focused on the patient and family and aimed at fostering an understanding of the disease, the patient’s prognosis, potential complications, and effective coping mechanisms. Many patients and families benefit from contact with and participation in a support group. Further information is available from CurePSP and The Parkinson’s Institute.

For patient education resources, see the Dementia Center, as well as Progressive Supranuclear 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)

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.

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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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