Dataset Information

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

ABSTRACT:

Background

Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG. However, no specific gait assessment for PMM2-CDG is available. This study analyses gait-related parameters in PMM2-CDG patients using a standardized clinical assessment and instrumented gait analysis (IGA).

Results

Seven adult patients with a molecular diagnosis of PMM2-CDG were followed-up from February 2021 to December 2022 and compared to a group of healthy control (HC) subjects, matched for age and sex. Standardized assessment of disease severity including ataxia and peripheral neuropathy along with isometric muscle strength and echo-biometry measurements at lower limbs were performed. IGA spatiotemporal parameters were obtained by means of a wearable sensor in basal conditions. PMM2-CDG patients displayed lower gait speed, stride length, cadence and symmetry index, compared to HC. Significant correlations were found among the used clinical scales and between disease severity (NCRS) scores and the gait speed measured by IGA. Variable reduction of knee extension strength and a significant decrease of lower limb muscle thickness with conserved echo intensity were found in PMM2-CDG compared to HC.

Conclusions

The study elucidates different components of gait disturbance in PMM2-CDG patients and shows advantages of using wearable sensor-based IGA in this frame. IGA parameters may potentially serve as quantitative measures for follow-up or outcome quantification in PMM2-CDG.

SUBMITTER: Cirnigliaro L

PROVIDER: S-EPMC10837865 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

Cirnigliaro Lara L Pettinato Fabio F Valle Maria Stella MS Casabona Antonino A Fiumara Agata A Vecchio Michele M Amico Valerio V Rizzo Renata R Jaeken Jaak J Barone Rita R Cioni Matteo M

Orphanet journal of rare diseases 20240202 1

<h4>Background</h4>Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG. However, no specific gait assessment for PMM2-CDG is available. This study analyses gait-related parameters in PMM2-CDG patients usi ...[more]

PMID: 38308356

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Project description:BackgroundPhosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS results with the Nijmegen Pediatric CDG Rating Scale (NPCRS), neuroimaging, intelligence quotient (IQ) and molecular data.MethodsOur observational study included 13 PMM2-CDG patients and 21 control subjects. Ethical permissions and informed consents were obtained. Three independent child neurologists rated PMM2-CDG patients and control subjects using the ICARS. A single clinician administered the NPCRS. All patients underwent brain MRI, and the relative diameter of the midsagittal vermis was measured. Psychometric evaluations were available in six patients. The Mann-Whitney U test was used to compare ICARS between patients and controls. To evaluate inter-observer agreement in patients' ICARS ratings, intraclass correlation coefficients (ICC) were calculated. ICARS internal consistency was evaluated using Cronbach's alpha. Spearman's rank correlation coefficient test was used to correlate ICARS with NPCRS, midsagittal vermis relative diameter and IQ.ResultsICARS and ICARS subscores differed between patients and controls (p < 0.001). Interobserver agreement of ICARS was "almost perfect" (ICC = 0.99), with a "good" internal reliability (Cronbach's alpha = 0.72). ICARS was significantly correlated with the total NPCRS score (rs 0.90, p < 0.001). However, there was no agreement regarding categories of severity. Regarding neuroimaging, inverse correlations between ICARS and midsagittal vermis relative diameter (rs -0.85, p = 0.003) and IQ (rs -0.94, p = 0.005) were found. Patients bearing p.E93A, p.C241S or p.R162W mutations presented a milder phenotype.ConclusionsICARS is a reliable instrument for assessment of PMM2-CDG patients, without significant inter-rater variability. Despite our limited sample size, the results show a good correlation between functional cerebellar assessment, IQ and neuroimaging. For the first a correlation between ICARS, neuroimaging and IQ in PMM2-CDG patients has been demonstrated.

Project description:ImportanceRegaining the ability to walk safely is a high priority for adults with vestibular loss. Thus, practitioners need comprehensive knowledge of vestibulopathic gait to design, provide, and/or interpret outcomes of interventions. To date, few studies have characterized the effects of vestibular loss on gait.ObjectivesTo investigate the use of an instrumented 2-minute walk test in adults with vestibular loss, to further characterize vestibulopathic gait, and to assess whether those with chronic vestibular loss have enduring gait deficits.Design, setting, and participantsThis cross-sectional study, conducted between April 3, 2018, and June 27, 2019, recruited adults 20 to 79 years of age from an academic, tertiary, hospital-based, ambulatory care setting who were healthy or had confirmed unilateral or bilateral vestibular hypofunction. Of the 43 adults who were screened from convenience and referred samples, 2 declined, and 7 were excluded because of health conditions.ExposuresThe main exposure was the instrumented 2-minute walk test, which was conducted with participants using wearable inertial measurement units while they walked a 10-m path at their self-selected speed and turned 180° in their self-selected direction at either end.Main outcomes and measuresThe primary measures were spatiotemporal gait metrics (eg, stride length [SL] and peak whole-body turning velocity). Multivariate analysis of variance was used to assess between-group differences. Validity was assessed using the area under the curve from receiver operator characteristic analyses.ResultsData from 17 healthy adults (mean [SD] age, 39.27 [11.20] years; 13 [76%] female) and 13 adults with vestibular loss (mean [SD] age, 60.50 [10.81] years; 6 [46%] female) were analyzed. Very large between-group differences were found for SL (left) (estimated marginal mean [SE] for healthy vs vestibular groups, 1.47 [0.04] m vs 1.31 [0.04] m; Cohen d, 1.35; 95% CI, 0.18-2.52), SL (right) (estimated marginal mean [SE] for healthy vs vestibular groups, 1.46 [0.04] m vs 1.29 [0.04] m; Cohen d, 1.44; 95% CI, 0.25-2.62), and peak turn velocity (estimated marginal mean [SE] for healthy vs vestibular groups, 240.17 [12.78]°/s vs 189.74 [14.70]°/s; Cohen d, 1.23; 95% CI, 0.07-2.40). The area under the curve was 0.79 (95% CI, 0.62-0.95) for SL (left), 0.81 (95% CI, 0.64-0.97) for SL (right), and 0.86 (95% CI, 0.72-0.99) for peak turn velocity.Conclusions and relevanceIn this cross-sectional study, instrumented gait analysis had good discriminative validity and revealed persistent deficits in gait stability in those with chronic vestibular loss. The findings of this study suggest that these clinically and functionally meaningful deficits could be targets for vestibular rehabilitation.

Dataset Information

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

Background

Results

Conclusions

Publications

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

Similar Datasets

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