50 Years of Progressive Supranuclear Palsy Richardson’s Syndrome

Fifty years ago, Richardson, Steele and Olszewski presented at the American Neurological Association meeting the clinical and neuropathological features of eight patients, representing the first description of progressive supranuclear palsy (PSP). Their classical paper, remarkably accurate, insightful and complete, still forms the basis for recognizing this disease [1,2]. The post-mortem examination of their cases showed prominent nerve cell loss and gliosis in the pallidum, red nucleus and subthalamic nuclei, and in the reticular formation [2]. Similar changes were noted in substantia nigra, locus coeruleus, superior colliculi, vestibular and dentate nuclei. Neurofibrillary tangles and granuovacuolar changes were also noted with the same distribution. No cortical pathology was described in the original report. The biochemical underpinnings of PSP became clearer in 1986, when it was first reported that the filamentous aggregates found brain autopsies from patients with PSP shared antigenic determinants with microtubule-associated protein tau [3]. The advances in neurosciences of PSP during the last decades have led to the discovery that abnormal 4-repeat tau deposition in brainstem, basal ganglia and neocortical areas is the main event in the pathogenesis of the disorder. The most frequently reported symptoms at onset in the classic form of this disease are impaired balance, movement slowness, subtle personality changes (apathy, disinhibition), bulbar symptoms and impaired oculomotion [4]. In the early stage of the classic PSP phenotype, the motor symptoms already respond poorly to dopaminergic drugs [5]. In the more advanced stages, patients manifesting classic PSP generally have a motor disorder characterized by bilateral bradykinesia, axial rigidity, and imbalance with severe gait unsteadiness. The prominent axial rigidity influences the posture, which may be characteristically erect like the cases reported by Richardson and collaborators (who depicted it as 'nuchal dystonia'), or more closely resemble the stooped posture seen in Parkinson's disease (PD). Progressive imbalance leads to repeated and frequent falls (usually backward). Some patients may have postural tremor and less commonly tremor at rest resembling PD. Patients with PSP often develop dysphagia and a characteristic growling high-pitched severe dysarthria, with mixed spastic and parkinsonian features. The diagnostic feature that best distinguishes PSP is a vertical gaze limitation with preserved oculocephalic reflexes: however, vertical gaze problems may be absent in up to 50% of the cases, and are rarely the presenting symptom of PSP. Because upgaze limitations can be present also in healthy persons (owing to anatomical changes within the orbit during aging), downgaze limitations are a far more …