An autopsy-confirmed case of progressive supranuclear palsy with predominant postural instability

Abstract

Postural instability and supranuclear gaze palsy represent the key symptoms of Richardson's syndrome, the most frequent clinical manifestation of progressive supranuclear palsy (PSP). However, a proportion of PSP patients never develops ocular motor symptoms, which prevents clinicians from establishing the diagnosis during lifetime according to current diagnostic criteria. We present one instructive autopsy-confirmed PSP case with prospective video-documented clinical course, showing striking temporal divergence of initially present postural instability and delayed development of ocular motor dysfunction. Brain imaging and autopsy findings were typical of PSP, but the temporal sequence of symptoms was unusual with isolated postural instability predominating the clinical course for many years and slowing of vertical saccades/supranuclear gaze palsy evolving not until the 9^th/11^th year after disease onset. Although other differential diagnoses were unlikely, this patient did not pass the threshold for possible or probable diagnosis of PSP according to current diagnostic criteria until very late in the disease course. This first well documented, autopsy confirmed case of PSP with predominant postural instability further expands the clinical spectrum of PSP and points out the need of new clinical diagnostic criteria with sufficient sensitivity and specificity for an early and reliable diagnosis.

Keywords: Atypical clinical phenotype; Magnetic resonance tomography; Neuropathology; Postural instability; Progressive supranuclear palsy.

Fig. 1

Case presentation. a Timeline of the evolution of clinical symptoms. b and c Demonstration of absent supranuclear gaze palsy (SNGP) despite clear postural instability (PI) in the 9^th year after symptom onset. d MRI showing predominant midbrain atrophy in the 13^th year after symptom onset. e Representative histopathological section (pallidum) showing the typical histopathological hallmarks of PSP), i.e. tufted astrocytes (TA), coiled bodies (CB), neurofibrillary tangles (NFT) and neuropil threads (NT) (Gallyas silver stain). f Histopathological section (globus pallidus) with loss of neurons, intracytoplasmic inclusions and gliosis (Hematoxilin-Eosin staining). g Tufted astrocytes in striatum (globus pallidus) as the neuropathological hallmark of PSP (Gallyas silver stain)