Progressive supranuclear palsy: progression and survival

Abstract

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by postural instability and falls, vertical supranuclear gaze palsy, parkinsonism with poor levodopa response, pseudobulbar palsy, and frontal release signs. The natural history of the disease has been previously described. However, the time frame of appearance of clinical milestones and how these symptoms may relate to survival in PSP are unknown. The primary objective was to determine the prevalence of symptoms at different stages of PSP and to estimate the time of appearance of clinical symptoms characteristic of the disease. Second, we determined the association between clinical symptoms and survival. We prospectively studied 35 PSP patients during assessments scheduled every 6 months for up to 2 years. We estimated symptoms prevalence and the association between symptoms and survival. The median age of onset was 65.9 years (IQR 60.6-70.0), and the median time from onset to first assessment was 3.0 years (IQR 2.4-3.9). The most commonly reported symptoms at baseline were: motor (100%) followed by cognitive/behavioral (89%), systemic and bulbar (80%), and sleep disturbances (60%). Slowness of movement, falls, neck stiffness and difficulty looking up/down had high prevalence from baseline, while balance and gait impairment were less common at baseline but increased in prevalence over time. The presence of sleep disturbances, and possibly hallucinations, was associated with increased death risk. Improved recognition of the clinical spectrum and milestones of PSP advances knowledge of the disease, helps earlier diagnosis, and allows prognostic predictions.

Midbrain/pons area ratio and clinical features predict the prognosis of Progressive Supranuclear Palsy

“…Few studies investigated the association between urinary incontinence and survival time, though it was one of the prevalent autonomic symptoms in PSP[5, 23,24]. In our study, we found the association between incontinence and survival and institutionalization in univariate model, but the association became negative in multivariate model.…”

“…Published studies found that the median survival time of patients with PSP-F was similar with PSP-RS and its cumulative mortality after 5 years was mildly higher than PSP-RS [25][26][27]. The dementia and frontal symptoms, the most common features in PSP-F, were also regarded associated with earlier death [4,23]. A recently published study found cognitive impairment in PSP, especially executive dysfunction, was associated with severity of PSP-related tau pathology in autopsy-confirmed PSP patients, which might explain the association with poorer prognosis [28].…”

An order in Lewy body disorders: Retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease

“…Hallucinations and a drift in psychiatric symptoms are usually regarded as diagnostic features of DLB . These are not frequent in clinically diagnosed PSP . Still, hallucinations have been noted in 6% of an autopsy‐verified series of PSP .…”

Mitochondrial Quality Control Proteases in Neuronal Welfare

“…For instance, metabolic enzyme aconitase plays an important role in mitochondrial physiology, and its attenuated activity is a contributing factor in progressive supranuclear palsy (PSP) (Park et al 2001) and influences the progression of Huntington's disease (HD) (Tabrizi et al 1999). PSP is characterized by progressive neurodegeneration resulting in postural instability and increased risk of falling, parkinsonism and pseudobulbar palsy (Arena et al 2016). The disease has late onset and commences with the symptoms of motor dysfunction (Boeve 2012).…”