Using Downgaze Palsy Progression Rate to Model Survival in Progressive Supranuclear Palsy-Richardson Syndrome.

BACKGROUND: Rapid development of downgaze palsy, the most specific symptom of progressive supranuclear palsy (PSP), has been associated with shorter survival in small studies. OBJECTIVE: We hypothesized that the progression rate of downgaze palsy and other disease features could predict survival if assessed soon after the onset of downgaze palsy in a large data set. METHODS: We used a longitudinal database of 414 patients with probable PSP-Richardson syndrome from 1994 to 2020. The data set comprised demographics and, for each visit, 28 PSP Rating Scale (PSPRS) items and PSP stage scores. We calculated the rate of progression of each PSPRS item as its item score when the downgaze item first reached 1 or more (on a 0-4 scale) divided by disease duration at that point. Multivariate Cox regression was applied to identify variables independently associated with survival. We also explored the progression pattern of total PSPRS and downgaze palsy scores with disease course. RESULTS: Independently associated with shorter survival were older onset age and faster progression of downgaze palsy, dysphagia for liquids, difficulty in returning to seat, and PSP stage. Patients with survival duration within 1 year of the median survival (6.58 years) showed approximately linear progression of the PSPRS score and downgaze palsy score during years 2 through 6 of the disease course. CONCLUSIONS: Older onset age and faster progression of downgaze palsy and several axial features are associated with shorter survival. The disease typically progresses in approximately linear fashion during years 2 through 6. These results may aid study design and patient counseling. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Modified Progressive Supranuclear Palsy Rating Scale for Virtual Assessments.

BACKGROUND: The reliability of the Progressive Supranuclear Palsy Rating Scale (PSPRS) using teleneurology has not been assessed. OBJECTIVES: To test whether removing items inadequately assessed by video would impact measurement of PSP severity and progression. METHODS: We performed secondary analyses of two data sets: the phase 2/3 trial of Davunetide in PSP and a large single-center cohort. We examined two modifications of the PSPRS: (1) removing neck rigidity, limb rigidity, and postural stability (25 items; mPSPRS-25) and (2) also removing three ocular motor items and limb dystonia (21 items; mPSPRS-21). Proportional agreement relative to the possible total scores was measured using the intraclass correlation coefficient, compared to the original PSPRS baseline values and change over 6 and 12 months. We examined the ability of both scales to predict survival in the single-center cohort using proportional hazards models. RESULTS: The mPSPRS-25 showed excellent agreement (0.99; P < 0.001) with the original PSPRS at baseline, 0.98 (P < 0.001) agreement in measuring change over 6 months, and 0.98 (P < 0.001) over 12 months. The mPSPRS-21 showed agreement of 0.94 (P < 0.001) with the original PSPRS at baseline, 0.92 (P < 0.001) at 6 months, and 0.95 (P < 0.001) at 12 months. Baseline and 6-month change in both modified scales were highly predictive of survival in the single-center cohort. CONCLUSIONS: Modified versions of the PSPRS which can be administered remotely show excellent agreement with the original scale and predict survival in PSP. The mPSPRS-21 should facilitate clinical care and research in PSP via teleneurology. © 2022 International Parkinson and Movement Disorder Society.

Stride width and postural stability in frontal gait disorders and Parkinson's disease.

Older adults, as well as those with certain neurological disorders, may compensate for poor neural control of postural stability by widening their base of foot support while walking. However, the extent to which this wide-based gait improves postural stability or affects postural control strategies has not been explored. People with idiopathic Parkinson's disease (iPD, n = 72), frontal gait disorders (FGD, n = 16), and healthy older adults (n = 32) performed walking trials at their preferred speed over an 8-m-long, instrumented walkway. People with iPD were tested in their OFF medication state. Analyses of covariance were performed to determine the associations between stride width and measures of lateral stability control. People with FGD exhibited a wide-based gait compared to both healthy older adults and iPD. An increased stride width was associated with an increase in lateral margin of stability in FGD. Unlike healthy older adults or iPD, people with FGD did not externally rotate their feet (toe-out angle) or shift their center of pressure laterally to aid lateral dynamic stability during walking but slowed their gait instead to increase stability. By adopting a slow, wide-based gait, people with FGD take advantage of the passive, pendular mechanics of walking.

Balance and gait in progressive supranuclear palsy: a narrative review of objective metrics and exercise interventions.

Background: The use of objective gait and balance metrics is rapidly expanding for evaluation of atypical parkinsonism, and these measures add to clinical observations. Evidence for rehabilitation interventions to improve objective measures of balance and gait in atypical parkinsonism is needed. Aim: Our aim is to review, with a narrative approach, current evidence on objective metrics for gait and balance and exercise interventions in progressive supranuclear palsy (PSP). Methods: Literature searches were conducted in four computerized databases from the earliest record up to April 2023: PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. Data were extracted for study type (cross-sectional, longitudinal, and rehabilitation interventions), study design (e.g., experimental design and case series), sample characteristics, and gait and balance measurements. Results: Eighteen gait and balance (16 cross-sectional and 4 longitudinal) and 14 rehabilitation intervention studies were included. Cross-sectional studies showed that people with PSP have impairments in gait initiation and steady-state gait using wearable sensors, and in static and dynamic balance assessed by posturography when compared to Parkinson's disease (PD) and healthy controls. Two longitudinal studies observed that wearable sensors can serve as objective measures of PSP progression, using relevant variables of change in turn velocity, stride length variability, toe off angle, cadence, and cycle duration. Rehabilitation studies investigated the effect of different interventions (e.g., balance training, body-weight supported treadmill gait, sensorimotor training, and cerebellar transcranial magnetic stimulation) on gait, clinical balance, and static and dynamic balance assessed by posturography measurements. No rehabilitation study in PSP used wearable sensors to evaluate gait and balance impairments. Although clinical balance was assessed in 6 rehabilitation studies, 3 of these studies used a quasi-experimental design, 2 used a case series, only 1 study used an experimental design, and sample sizes were relatively small. Conclusion: Wearable sensors to quantify balance and gait impairments are emerging as a means of documenting progression of PSP. Robust evidence for improving balance and gait in PSP was not found for rehabilitation studies. Future powered, prospective and robust clinical trials are needed to investigate the effects of rehabilitation interventions on objective gait and balance outcomes in people with PSP.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Perspective: Balance Assessments in Progressive Supranuclear Palsy: Lessons Learned.

Many studies have examined aspects of balance in progressive supranuclear palsy (PSP), but guidance on the feasibility of standardized objective balance assessments and balance scales in PSP is lacking. Balance tests commonly used in Parkinson's disease often cannot be easily administered or translated to PSP. Here we briefly review methodology in prior studies of balance in PSP; then we focus on feasibility by presenting our experience with objective balance assessment in PSP-Richardson syndrome and PSP-parkinsonism during a crossover rTMS intervention trial. We highlight lessons learned, safety considerations, and future approaches for objective balance assessment in PSP.