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Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and repetitive behavior. Postural and motor disturbances occur more often in ASD, in comparison to typically developing subjects, affecting the quality of life. Linear and non-linear indexes derived from the trajectory of the center of pressure (COP) while subjects stand on force platforms are commonly used to assess postural stability. The aim of the present feasibility study was to investigate whether combining linear and non-linear parameters of the COP during stance in subjects with ASD, could provide insight on specific features of motor dysfunction possibly linked to ASD cognition and clinical characteristics. Methods Twenty-two males, aged 10–15 years, including subjects with ASD and healthy controls (N = 11, respectively), were studied. They all had normal cognitive level and independent walking ability. A piezoelectric force platform was used to evaluate posture over three feet positions, with eyes open, closed and during visually-guided saccades. Linear (sway path, total area and root mean square) and non-linear parameters (fractal dimension and sample entropy) of the COP were measured to determine postural stability and the complexity and regularity of the COP signals. GLMM analyses were performed to assess COP parameter changes across experimental conditions and subject groups. Finally, Spearman correlations evaluated the significance of potential relationships between linear and non-linear measures as well as between non-linear parameters and clinical data in patients with ASD. Results Compared to controls, subjects with ASD showed reduced postural stability and complexity, with higher regularity of COP trajectories, particularly in the most unstable feet positions, during visually-guided saccades and in the medial-lateral direction. Spearman correlations indicated that, in the patients’ group, postural instability was associated with a decrease in the geometric complexity and an increase in the regularity of the COP trajectory. Moreover, the increase in regularity of the COP trajectory was associated to the severity of restricted and repetitive behavior. Conclusions The results of this study highlight the importance of combining linear and non-linear measures in evaluating postural control in patients with ASD, also with respect to the outcome of interventions on these patients targeting postural balance.

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.

Mucopolysaccharidosis III (Sanfilippo syndromes) types A–D are rare lysosomal storage disorders characterized by heparan sulfate accumulation and neurodegeneration. Patients with MPS III present with developmental stagnation and/or regression, sleep disturbance, and behavioral abnormalities usually in the first years of life. Epilepsy may occur in a proportion of patients during the disease course. However, the progression of epilepsy and EEG changes in MPS III have not been systematically investigated. We report electroclinical features in a cohort of patients with MPS III over a follow-up period ranging from 6.5 to 22 years. Participants include 15 patients (11 females; aged 7–31 years) with MPS III A (n = 7, 47%), MPS III B (n = 5, 34%), MPS III C (n = 2, 13%), and MPS III D (n = 1, 6%). At the time of this study, 8 out of 15 patients (53%) had epilepsy. Epilepsy occurred in patients with advanced disease even in the first decade of life (mean age at onset: 12.1 ± 6.7 years). However, seizure onset may also be associated with abrupt worsening of the neurobehavioral phenotype. The main epilepsy types observed were generalized (four out of eight, 50%), followed by focal (three out of eight, 37%) and combined (two out of eight, 25%) epilepsy and status epilepticus (one out of eight, 12.5%). Seizures were generally controlled by one antiepileptic drug (AED) and most patients (seven out of eight, 87%) were still on therapy after a median follow-up period of 5 years (range: 1–9 years). A total of 66 EEGs were analyzed with a median EEG follow-up duration of 7 years (range: 6 months−14 years). Slowing of the background activity occurred in 7 (46%) patients aged 4–19 years. Epileptiform EEG abnormalities were observed in 10 patients at a mean age of 9.6 ± 2.9 years. EEG epileptiform discharges were not unavoidably linked to epilepsy. Early recognition and careful monitoring of electroclinical features in MPS III is necessary for appropriate care and for the detection of disease progression.