Progression of Functional Gait in Hereditary Spastic Paraplegias

Cubillos-Arcila, Diana Maria; Machado, Gustavo Dariva; Sehnem, Lauren; Burguêz, Daniela; Zanardi, Ana Paula Janner; Martins, Valéria Feijó; Peyré‐Tartaruga, Leonardo Alexandre; Saute, Jonas Alex Morales

doi:10.1007/s12311-021-01302-2

Cited by 7 publications

(18 citation statements)

References 18 publications

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“…In a multicenter study on SPG5, the longitudinal evaluation of 21 patients over a mean of 31 months reported SPRS only, at a progression rate of 0.8 points per year 21 . In a Brazilian study of 17 HSP patients, gait analysis measures did not change after 18 months, but did show moderate correlations to SPRS changes, like our study 22 . An additional longitudinal study followed up a single HSP family and observed an improved gait performance over time 23 …”

Section: Discussionsupporting

confidence: 63%

“…21 In a Brazilian study of 17 HSP patients, gait analysis measures did not change after 18 months, but did show moderate correlations to SPRS changes, like our study. 22 An additional longitudinal study followed up a single HSP family and observed an improved gait performance over time. 23 Considering the slow progression in most HSP patients and the short-term variability of disease severity, we specifically analyzed the longest intervals available.…”

Section: Discussionmentioning

confidence: 99%

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Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Loris

Ollenschläger

Greinwalder

et al. 2023

Ann Clin Transl Neurol

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Progressive spasticity and gait impairment is the functional hallmark of hereditary spastic paraplegia (HSP), but due to inter‐individual variability, longitudinal studies on its progression are scarce. We investigated the progression of gait deficits via mobile digital measurements in conjunction with clinical and patient‐reported outcome parameters. Our cohort included adult HSP patients (n = 55) with up to 77 months of follow‐up. Gait speed showed a significant association with SPRS progression. Changes in stride time and gait variability correlated to fear of falling and quality of life, providing evidence that gait parameters are meaningful measures of HSP progression.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Loris

Ollenschläger

Greinwalder

et al. 2023

Ann Clin Transl Neurol

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“…This study is the long-term continuation of a prospective cohort ( Cubillos-Arcila et al, 2022 ), which was approved by the Ethics in Research Committee of HCPA (GPPG-HCPA-2017-0341), following the Declaration of Helsinki. Informed written consent was obtained from all subjects or their guardians.…”

Section: Methodsmentioning

confidence: 99%

“…The analysis exclusively involved adults, as supported by findings from the 1.5-year follow-up of the cohort. Unlike adults, children with HSP demonstrated PerFO improvements over time, possibly due to the biomechanical impacts of growth, including increased height and lower limb length ( Cubillos-Arcila et al, 2022 ). Moreover, validity studies of SPRS for this particular population had not been previously performed.…”

Section: Methodsmentioning

confidence: 99%

Long-term progression of clinician-reported and gait performance outcomes in hereditary spastic paraplegias

Cubillos Arcila,

Dariva Machado,

Martins

et al. 2023

Front. Neurosci.

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IntroductionHereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative diseases in which little is known about the most appropriate clinical outcome assessments (COAs) to capture disease progression. The objective of this study was to prospectively determine disease progression after 4.5 years of follow-up with different clinician-reported (ClinRO) and gait performance outcomes (PerFOs).MethodsTwenty-six HSP patients (15 SPG4, 5 SPG7, 4 SPG5, 2 SPG3A) participated in this single-center cohort study in which the ClinRO: Spastic Paraplegia Rating Scale; and the PerFOs: 10-meters walking test and timed-up and go (TUG), at self-selected and maximal walking speeds; Locomotor Rehabilitation Index; and 6-min walking test were performed at baseline and after 1.5 (18 patients) and 4.5 (13 patients) years.ResultsIn the 3-year interval between the second and third assessments, significant progressions were only found in PerFOs, while in the overall 4.5 years of follow-up, both PerFOs and ClinROs presented significant progressions. The progression slopes of COAs modeled according to the disease duration allowed the estimation of the annual progression of the outcomes and sample size estimations for future clinical trials of interventions with different effect sizes. TUG at maximal walking speed was the only COA capable of differentiating subjects with a worse compared to a stable/better impression of change and would require the smallest sample size if chosen as the primary endpoint of a clinical trial.DiscussionThese findings indicate that both performance and clinician-reported outcomes can capture long-term progression of HSPs, with some PerFOs presenting greater sensitivity to change. The presented data are paramount for planning future disease-modifying and symptomatic therapy trials for this currently untreatable group of diseases.

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“…Although the natural history of HSPs is largely unknown, the available studies point to a very slow progression [ 2 , 7 ] suggesting that clinical scales based on neurological examination might not present enough sensitivity to change for detecting disease progression, making the search for additional biomarkers a paramount task. Abnormalities in motor and somatosensory evoked potentials were previously described in HSPs, pointing neurophysiological measurements of the integrity of central motor and sensory pathways as candidate biomarkers of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Evoked potentials as biomarkers of hereditary spastic paraplegias: A case-control study

et al. 2021

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Introduction The Hereditary Spastic Paraplegias (HSP) are a group of genetic diseases that lead to slow deterioration of locomotion. Clinical scales seem to have low sensitivity in detecting disease progression, making the search for additional biomarkers a paramount task. This study aims to evaluate the role of evoked potentials (EPs) as disease biomarkers of HSPs. Methods A single center cross-sectional case-control study was performed, in which 18 individuals with genetic diagnosis of HSP and 21 healthy controls were evaluated. Motor evoked potentials (MEP) obtained with transcranial magnetic stimulation and somatosensory evoked potentials (SSEP) were performed in lower (LL) and upper limbs (UL). Results Central motor conduction time in lower limbs (CMCT-LL) was prolonged in HSP subjects, with marked reductions in MEP-LL amplitudes when compared to the control group (p<0.001 for both comparisons). CMCT-UL was 3.59ms (95% CI: 0.73 to 6.46; p = 0.015) prolonged and MEP-UL amplitudes were reduced (p = 0.008) in the HSP group. SSEP-LL latencies were prolonged in HSP subjects when compared to controls (p<0.001), with no statistically significant differences for upper limbs (p = 0.147). SSEP-UL and SSEP-LL latencies presented moderate to strong correlations with age at onset (Rho = 0.613, p = 0.012) and disease duration (Rho = 0.835, p<0.001), respectively. Similar results were obtained for the SPG4 subgroups of patients. Conclusion Motor and somatosensory evoked potentials can adequately differentiate HSP individuals from controls. MEP were severely affected in HSP subjects and SSEP-LL latencies were prolonged, with longer latencies being related to more severe disease. Future longitudinal studies should address if SSEP is a sensitive disease progression biomarker for HSP.

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Progression of Functional Gait in Hereditary Spastic Paraplegias

Cited by 7 publications

References 18 publications

Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Long-term progression of clinician-reported and gait performance outcomes in hereditary spastic paraplegias

Evoked potentials as biomarkers of hereditary spastic paraplegias: A case-control study

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