Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Loris, Evelyn; Ollenschläger, Malte; Greinwalder, Teresa; Eskofier, Bjoern M.; Winkler, Jürgen; Gaßner, Heiko; Regensburger, Martin

doi:10.1002/acn3.51725

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…In the largest study, measures of temporal stride variability such as Stride Time CV discriminated patients from controls and demonstrated cross-sectional correlation with SPRS (Regensburger et al, 2022). However, they did not show longitudinal progression on follow-up assessments (Loris et al, 2023). The cited studies were limited, however, by the inclusion of a genotypically mixed and thus phenotypically heterogeneous cohort of HSP patients.…”

Section: Discussionmentioning

confidence: 99%

“…Digital gait measures have demonstrated promising properties in hereditary ataxias, reliably discriminating between patients and controls, correlating cross-sectionally with clinical measures of disease severity and – in the few longitudinal studies conducted so far – also exhibiting sensitivity to capturing change (Ilg et al, 2020; Seemann et al, 2023; Shah et al, 2021; Thierfelder et al, 2022; Velazquez-Perez et al, 2021). In contrast, only few studies on sensor-based gait analysis have been conducted in hereditary spastic paraplegias (Loris et al, 2023; Regensburger et al, 2022), and no study has yet systematically employed body-worn sensors to examine gait in diseases like SPG7 or other spastic ataxias. Anticipated treatment trials in diseases like SPG7 will likely (i) focus on patients in early disease stages and (ii) involve multiple centers to reach sufficient power.…”

Section: Introductionmentioning

confidence: 99%

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Towards patient-relevant, trial-ready digital motor outcomes for SPG7: a cross-sectional prospective multi-center study (PROSPAX)

Beichert,

Seemann,

Kessler

et al. 2024

Preprint

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Background and Objectives: With targeted treatment trials on the horizon, identification of sensitive and valid outcome measures becomes a priority for the >100 spastic ataxias. Digital-motor measures, assessed by wearable sensors, are prime outcome candidates for SPG7 and other spastic ataxias. We here aimed to identify candidate digital-motor outcomes for SPG7 - as one of the most common spastic ataxias - that: (i) reflect patient-relevant health aspects, even in mild, trial-relevant disease stages; (ii) are suitable for a multi-center setting; and (iii) assess mobility also during uninstructed walking simulating real-life. Methods: Cross-sectional multi-center study (7 centers, 6 countries). Unaided walking was assessed in 65 patients with SPG7 and 50 unrelated healthy controls using 3 wearable sensors (Opal APDM). Digital gait measures were correlated to measures of disease severity (SARA, SPRS; including mobility-relevant subscores SPRSmobility, SARAPG) and activities of daily living (FARS-ADL). The task set included lab-based defined gait tasks, complemented by uninstructed 'supervised free walking'. Results: Among 30 hypothesis-based gait measures, 18 demonstrated at least moderate effect size (Cliff's δ>0.5) in discriminating SPG7 patients from controls, and 17 even in mild disease stages (SPRSmobility≤9). Spatiotemporal variability measures such as the spatial variability composite measure SPcmp (ρ=0.67, p=<0.0001), Stride Time CV (ρ=0.67, p=<0.0001) and Swing CV (ρ=0.64, p=<0.0001) showed the highest correlations with clinician-reported mobility scores (SPRSmobility), and overall disease severity (SPRS, SARA). Overall, top-ranked measures also correlated with patient-relevant functional deficits in everyday life activities (FARS-ADL). In mild disease stages (SPRSmobility≤9, n=41), Swing CV (ρ=0.53, p=<0.0001) and SPcmp (ρ=0.50, p=<0.0001) correlated with SPRSmobility. In the uninstructed 'supervised free walking' task, the correlations between spatiotemporal variability measures (Stride Time CV, Stride Length CV, Swing CV) and SPRSmobilitycould be confirmed; additionally, Gait Speed (ρ=-0.59, p=<0.0001) was highly correlated with SPRSmobility. Discussion: We here identified trial-ready digital-motor candidate outcomes for the spastic ataxia SPG7, all characterized by proven multi-center applicability, ability to discriminate patients from controls, and correlation with measures of disease severity - even in mild disease stages -, and patient-relevant everyday function. If validated longitudinally, these sensor outcomes might inform future natural history and treatment trials in SPG7 and other spastic ataxias.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Towards patient-relevant, trial-ready digital motor outcomes for SPG7: a cross-sectional prospective multi-center study (PROSPAX)

Beichert,

Seemann,

Kessler

et al. 2024

Preprint

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“…Correlation analyses were performed on individual changes between baseline and 1 month. Absolute differences were calculated for the clinical and patient‐reported measures and relative changes for gait parameters [23]. Spearman rank correlations ( ρ ) were calculated at α = 0.05.…”

Section: Methodsmentioning

confidence: 99%

Mobile digital gait analysis captures effects of botulinum toxin in hereditary spastic paraplegia

Ibrahim,

Ollenschläger,

Klebe

et al. 2024

Euro J of Neurology

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Background and purposeHereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has been approved for lower limb spasticity following stroke and cerebral palsy, but its effects in HSPs remain underexplored. We aimed to characterize the effects of botulinum toxin on clinical, gait, and patient‐reported outcomes in HSP patients and explore the potential of mobile digital gait analysis to monitor treatment effects and predict treatment response.MethodsWe conducted a prospective, observational, multicenter study involving ambulatory HSP patients treated with botulinum toxin tailored to individual goals. Comparing data at baseline, after 1 month, and after 3 months, treatment response was assessed using clinical parameters, goal attainment scaling, and mobile digital gait analysis. Machine learning algorithms were used for predicting individual goal attainment based on baseline parameters.ResultsA total of 56 patients were enrolled. Despite the heterogeneity of treatment goals and targeted muscles, botulinum toxin led to a significant improvement in specific clinical parameters and an improvement in specific gait characteristics, peaking at the 1‐month and declining by the 3‐month follow‐up. Significant correlations were identified between gait parameters and clinical scores. With a mean balanced accuracy of 66%, machine learning algorithms identified important denominators to predict treatment response.ConclusionsOur study provides evidence supporting the beneficial effects of botulinum toxin in HSP when applied according to individual treatment goals. The use of mobile digital gait analysis and machine learning represents a novel approach for monitoring treatment effects and predicting treatment response.

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“…Wearable IMU sensor technology has been identified as the most appropriate technology at this time to conduct such multicenter studies of digital gait and balance measures in ataxia [45], having shown to be able to sensitive and specific to simultaneously assess gait and balance [25,26]. Wearable IMU sensor technology has also demonstrated to be valid for the assessment of paraparetic gait [23,24] and was used for gait analysis in several studies [29,46]. Other technologies used for the assessment of gait analysis in HSP include infrared multicamera motion analysis system [22,47], pressure sensors [48], and 3D motion analysis [17,49].…”

Section: Digital Tools In Clinical Trials For Ataxia and Hspmentioning

confidence: 99%

The use of digital tools in rare neurological diseases towards a new care model: a narrative review

Torri,

Vadi,

Meli

et al. 2024

Neurol Sci

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Rare neurological diseases as a whole share peculiar features as motor and/or cognitive impairment, an elevated disability burden, a frequently chronic course and, in present times, scarcity of therapeutic options. The rarity of those conditions hampers both the identification of significant prognostic outcome measures, and the development of novel therapeutic approaches and clinical trials. Collection of objective clinical data through digital devices can support diagnosis, care, and therapeutic research. We provide an overview on recent developments in the field of digital tools applied to rare neurological diseases, both in the care setting and as providers of outcome measures in clinical trials in a representative subgroup of conditions, including ataxias, hereditary spastic paraplegias, motoneuron diseases and myopathies.

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Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Cited by 6 publications

References 23 publications

Towards patient-relevant, trial-ready digital motor outcomes for SPG7: a cross-sectional prospective multi-center study (PROSPAX)

Towards patient-relevant, trial-ready digital motor outcomes for SPG7: a cross-sectional prospective multi-center study (PROSPAX)

Mobile digital gait analysis captures effects of botulinum toxin in hereditary spastic paraplegia

The use of digital tools in rare neurological diseases towards a new care model: a narrative review

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