One decade ago, one decade ahead in progressive supranuclear palsy.

Fifty-five years have passed from the first description of PSP, but it is in the last decade that there has been a revolutionary change in understanding both clinical and pathophysiological aspects of this disease. Ten years ago, our knowledge about the clinical spectrum and pathophysiology of the disease was quite limited, and there was no credible clinical study on any drug treatment for this devastating disease. Today, we have discovered the wide clinical spectrum of PSP, and this led to the development of new diagnostic criteria in 2017, aiming to diagnose the disease earlier and include more phenotypes into clinical studies. Moreover, just over the past 10 years, numerous large, double-blind, clinical trials with disease-modifying agents have been conducted that provided important novel insights into disease biomarkers and progression. These studies were possible because of gained novel insights into pathophysiological processes of the disease and pave the way for the near future. In the next decade, we dare to predict the discovery of biomarkers for PSP, improvements in diagnosis using the new criteria in combination with these biomarkers, and ultimately the development of a neuroprotective therapy that could be applied to patients in a prodromal stage and spare them from this devastating disorder. © 2019 International Parkinson and Movement Disorder Society.

Historical perspectives and memories of progressive supranuclear palsy.

Parkinsonism recalls James Parkinson of London and his description of six patients with "paralysis agitans" in 1817, which neurologist Jean-Marie Charcot renamed Parkinson disease. Its variants, referred to as atypical parkinsonian disorders, are the subject of this issue of Seminars in Neurology through which we continue a journey toward understanding the pathogenesis of these diverse neurodegenerative diseases that are sometimes genetically determined, but are more often sporadic and without familial occurrence.

Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): a short historical review.

J. C. Richardson presented a clinical report of 8 cases of progressive supranuclear palsy (PSP, progressive supranuclear palsy) in June 1963. This paper briefly reviews the clinical, neuropathologic, and genetic features that subsequently have evolved, emphasizing the difficulties of differential diagnosis. Since PSP appears to be a heterogeneous syndrome, its precise nosology remains uncertain.

Progressive supranuclear palsy. Historical notes.

Progressive supranuclear palsy (PSP) is the name Dr. J. Clifford Richardson chose to designate an unusual clinical syndrome he first identified in the 1950s. Neurofibrillary degeneration is the hallmark of this fatal brain disease, and during our study of Richardson's patients, Professor Jerzy Olszewski and I also observed granulovacuolar degeneration, and widespread nerve cell loss and gliosis in subcortical and brain stem nuclei. The histopathological features bear a striking resemblance to those seen in postencephalitic parkinsonism after von Economo's epidemic encephalitis, and in the parkinsonism-dementia complex of Guam (PDC). During the past 30 years, neurologists confirm that progressive supranuclear palsy is a universal, sporadic and not uncommon neurodegeneration of middle and late life. Many fine studies, as reported here, have advanced our understanding of PSP but its cause, and thereby its cure, is still to be revealed. These historical notes tell of our observations from 1955 to 1975. We are pleased that colleagues remember these early descriptions and honor us by calling this disease, the Steele-Richardson-Olszewski (SRO) syndrome.

Differential diagnosis of PSP.

The clinical diagnosis of PSP depends primarily on the history and the physical findings. Clinicians should be alerted to the possibility of this condition in assessing patients presenting with atypical parkinsonism and other complex extrapyramidal syndromes in late middle age or later. The differential diagnosis includes MSA (both OPCA and SND), PD, CBD and cerebrovascular disease. PD is probably the most common erroneous diagnosis. Unfortunately, pathognomonic signs do not usually appear until several years, after symptom onset. No specific laboratory test is yet available. Neuroimaging studies show characteristic anatomic alterations only late in the course of the illness and must be correlated with the clinical findings.

J. Clifford Richardson and 50 years of progressive supranuclear palsy.

OBJECTIVE: To trace the historical events leading to Richardson's clinical description of progressive supranuclear palsy (PSP) in the context of subsequent observations of its clinical heterogeneity and pathologic overlap with other tauopathies. BACKGROUND: Fifty years ago, Canadian neurologist J. Clifford Richardson identified patients in Toronto with a syndrome of supranuclear vertical gaze palsy, pseudobulbar palsy, axial rigidity-in-extension, and cognitive impairment. In his seminal description, Richardson predicted that further clinicopathologic observations would broaden the clinical syndrome and that this was unlikely to be a disorder restricted to the Toronto region. METHODS: The recollections of two of Richardson's contemporaries and archival material from his time were used as primary materials. Publications that follow the evolution of his observations were examined. RESULTS: Recent factor analysis of pathologically verified PSP cases has confirmed the accuracy and uniformity of the original classic clinical description of PSP and vindicated Richardson's prediction of clinical variants. Most notably, a presentation with Parkinson syndrome and absent gaze palsy has been identified, with less severe PSP-tau pathology. CONCLUSIONS: In recognition of his seminal observations, we propose that the classic clinical presentation of PSP-tau pathology be renamed Richardson's disease, and that the commonest clinical variant be termed PSP-parkinsonism.

Cognitive and behavioral aspects of PSP since Steele, Richardson and Olszewski's description of PSP 40 years ago and Albert's delineation of the subcortical dementia 30 years ago.

Although researchers are now familiar with progressive supranuclear palsy (PSP) and its characteristic "subcortical" dementia, this was not the case prior to seminal descriptions by Steele, Richardson, Olszewski and Albert. In fact, the first three authors identified this disorder, and the last one introduced the classification of the dementias according to the anatomical involvement. This paper is in honor of their contributions, and will also outline the changes that have occurred since their seminal works.

Did Charles Dickens describe progressive supranuclear palsy in 1857?

A character from one of Charles Dickens's lesser known works is presented, whose attributes suggest a possible diagnosis of progressive supranuclear palsy.

Posey and Spiller and progressive supranuclear palsy: an incorrect attribution.

In 1904 and 1905, respectively, William Campbell Posey and William Spiller both described the case of a patient with progressive ophthalmoparesis and imbalance that has come to be regarded as the earliest report of progressive supranuclear palsy. No autopsy was thought to have been performed on this patient. In this report, we review the clinical history provided by Posey and Spiller. We also report on the subsequent autopsy of their patient, which was performed by Spiller in 1906. The chief finding was a tumor involving the right cerebral peduncle and periaqueductal area. The autopsy findings prove conclusively that the patient described by Spiller and Posey had a midbrain neoplasm and not progressive supranuclear palsy.

Progressive supranuclear palsy: new disease or variant of postencephalitic parkinsonism?

We review the etiological importance of the epidemic encephalitis for progressive supranuclear palsy (PSP) and addresses the question of whether the explosion of PSP literature in the mid-20th century reflects the appearance of a new disease. We examined 2,000 studies on Parkinson's disease from 1861 to 1963 and found PSP-like cases in the past, before the epidemic encephalitis era. It can be assumed that PSP is neither a new disease nor a variant of postencephalitic parkinsonism.