Search Results (37)

Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research. Full article

Sensor technology plays a fundamental role in neuro-motor rehabilitation by enabling precise movement analysis and control. This study explores the integration of brain–machine interfaces (BMIs) and wearable sensors to enhance motor recovery in individuals with neuro-motor impairments. Specifically, different time-frequency transforms are evaluated to analyze the correlation between electroencephalographic (EEG) activity and ankle position, measured by using inertial measurement units (IMUs). A low-cost ankle exoskeleton was designed to conduct the experimental trials. Six subjects performed plantar and dorsal flexion movements while the EEG and IMU signals were recorded. The correlation between brain activity and foot kinematics was analyzed using the Short-Time Fourier Transform (STFT), Stockwell (ST), Hilbert–Huang (HHT), and Chirplet (CT) methods. The 8–20 Hz frequency band exhibited the highest correlation values. For motor imagery classification, the STFT achieved the highest accuracy (92.9%) using an EEGNet-based classifier and a state-machine approach. This study presents a dual approach: the analysis of EEG-movement correlation in different cognitive states, and the systematic comparison of four time-frequency transforms for both correlation and classification performance. The results support the potential of combining EEG and IMU data for BMI applications and highlight the importance of cognitive state in motion analysis for accessible neurorehabilitation technologies. Full article

Zinc contamination in aquatic environments has become a growing concern due to its potential to bioaccumulate and induce neurotoxic effects in aquatic organisms. As an essential trace element, zinc plays a crucial role in various physiological processes, but excessive exposure can disrupt the gut–brain axis, leading to cognitive and behavioral impairments. Recent studies have suggested that probiotics may offer protective effects against environmental neurotoxins by modulating the gut microbiota and associated neurological functions. The zebrafish (Danio rerio) has emerged as a valuable model organism for studying the biological mechanisms underlying neurotoxicity and potential therapeutic interventions. This study aimed to assess the effects of probiotics on cognitive impairments induced by zinc chloride (ZnCl₂) exposure in zebrafish. Specifically, zebrafish were exposed to ZnCl₂ at concentrations of 0.5 mg/L and 1.0 mg/L for 96 h, followed by a 7-day post-exposure period to probiotics (Bifidobacterium longum, Bifidobacterium animalis lactis, Lactobacillus rhamnosus). ZnCl₂ exposure at these concentrations is already known to induce behavioral and neuromotor deficits resembling Alzheimer’s disease-like symptoms in zebrafish models, making it a suitable model for evaluating the neuroprotective potential of probiotics. Behavioral assessments including sociability tests along with short- and long-term memory evaluations were conducted using EthoVision XT 16 software. Memory tests demonstrated that ZnCl₂ exposure impaired cognitive functions, while probiotic treatment did not significantly ameliorate these deficits. In the social behavior test, ZnCl₂ at 0.5 mg/L resulted in a marked decrease in sociability, whereas exposure to 1.0 mg/L did not induce significant changes. However, post-exposure probiotic administration following ZnCl₂ intoxication at 1.0 mg/L exhibited an anxiolytic effect on zebrafish. These findings suggest that probiotics may exhibit partial neurobehavioral benefits following zinc chloride-induced toxicity, particularly in mitigating anxiety-like behaviors rather than cognitive deficits. Further investigations are needed to elucidate the precise mechanisms by which probiotics interact with the gut–brain axis in the context of heavy metal neurotoxicity. Full article

Kinematics, kinetics and biomechanics of human gait are widely investigated fields of research. The biomechanics of locomotion have been described as characterizing muscle activations and synergistic control, i.e., spatial and temporal patterns of coordinated muscle groups and joints. Both kinematic synergies and muscle synergies have been extracted from locomotion data, showing that in healthy people four–five synergies underlie human locomotion; such synergies are, in general, robust across subjects and might be altered by pathological gait, depending on the severity of the impairment. In this work, for the first time, we apply the mixed matrix factorization algorithm to the locomotion data of 15 healthy participants to extract hybrid kinematic–muscle synergies and show that they allow us to directly link task space variables (i.e., kinematics) to the neural structure of muscle synergies. We show that kinematic–muscle synergies can describe the biomechanics of motion to a better extent than muscle synergies or kinematic synergies alone. Moreover, this study shows that at a functional level, modular control of the lower limb during locomotion is based on an increased number of functional synergies with respect to standard muscle synergies and accounts for different biomechanical roles that each synergy may have within the movement. Kinematic–muscular synergies may have impact in future work for a deeper understanding of modular control and neuro-motor recovery in the medical and rehabilitation fields, as they associate neural and task space variables in the same factorization. Applications include the evaluation of post-stroke, Parkinson’s disease and cerebral palsy patients, and for the design and development of robotic devices and exoskeletons during walking. Full article

Background: Over one billion people worldwide suffer from neurological conditions that cause mobility impairments, often persisting despite rehabilitation. Chronic neurological disease (CND) patients who lack access to continuous rehabilitation face gradual functional decline. The International Classification of Functioning, Disability, and Health (ICF) provides a comprehensive framework for assessing these patients. Objective: This study aims to evaluate the outcomes of a non-hospitalized neuromotor rehabilitation project for CND patients in Italy using the Barthel Index (BI) as the primary outcome measure. The rehabilitation was administered through an Individual Rehabilitation Plan (IRP), tailored by a multidisciplinary team and coordinated by a physiatrist. The IRP involved an initial comprehensive assessment, individualized therapy administered five days a week, and continuous adjustments based on patient progress. The secondary objectives include assessing mental status and sensory and communication functions, and identifying predictive factors for BI improvement using an artificial neural network (ANN). Methods: A retrospective observational study of 128 CND patients undergoing a rehabilitation program between 2018 and 2023 was conducted. Variables included demographic data, clinical assessments (BI, SPMSQ, and SVaMAsc), and ICF codes. Data were analyzed using descriptive statistics, linear regressions, and ANN to identify predictors of BI improvement. Results: Significant improvements in the mean BI score were observed from admission (40.28 ± 29.08) to discharge (42.53 ± 30.02, p < 0.001). Patients with severe mobility issues showed the most difficulty in transfers and walking, as indicated by the ICF E codes. Females, especially older women, experienced more cognitive decline, affecting rehabilitation outcomes. ANN achieved 86.4% accuracy in predicting BI improvement, with key factors including ICF mobility codes and the number of past rehabilitation projects. Conclusions: The ICF mobility codes are strong predictors of BI improvement in CND patients. More rehabilitation sessions and targeted support, especially for elderly women and patients with lower initial BI scores, can enhance outcomes and reduce complications. Continuous rehabilitation is essential for maintaining progress in CND patients. Full article

Lung injury caused by respiratory infection is a major cause of hospitalization and mortality and a leading origin of sepsis. Sepsis-associated encephalopathy and delirium are frequent complications in patients with severe lung injury, yet the pathogenetic mechanisms remain unclear. Here, 70 female C57BL/6 mice were subjected to a single full-body-exposure with nebulized lipopolysaccharide (LPS). Neuromotor impairment was assessed repeatedly and brain, blood, and lung samples were analyzed at survival points of 24 h, 48 h, 72 h, and 96 h after exposure. qRT-PCR revealed increased mRNA-expression of TNFα and IL-1β 24 h and 48 h after LPS-exposure in the lung, concomitantly with increased amounts of proteins in bronchoalveolar lavage and interstitial lung edema. In the cerebral cortex, at 72 h and/or 96 h after LPS exposure, the inflammation- and activity-associated markers TLR4, GFAP, Gadd45b, c-Fos, and Arc were increased. Therefore, single exposure to nebulized LPS not only triggers an early inflammatory reaction in the lung but also induces a delayed neuroinflammatory response. The identified mechanisms provide new insights into the pathogenesis of sepsis-associated encephalopathy and might serve as targets for future therapeutic approaches. Full article

Traumatic brain injury (TBI) and long bone fractures are a common injury pattern in polytrauma patients and modulate each other’s healing process. As only a limited number of studies have investigated both traumatic sites, we tested the hypothesis that brain–bone polytrauma mutually impacts neuro- and osteopathological outcomes. Adult female C57BL/6N mice were subjected to controlled cortical impact (CCI), and/or osteosynthetic stabilized femoral fracture (FF), or sham surgery. Neuromotor and behavioral impairments were assessed by neurological severity score, open field test, rotarod test, and elevated plus maze test. Brain and bone tissues were processed 42 days after trauma. CCI+FF polytrauma mice had increased bone formation as compared to FF mice and increased mRNA expression of bone sialoprotein (BSP). Bone fractures did not aggravate neuropathology or neuroinflammation assessed by cerebral lesion size, hippocampal integrity, astrocyte and microglia activation, and gene expression. Behavioral assessments demonstrated an overall impaired recovery of neuromotor function and persistent abnormalities in anxiety-related behavior in polytrauma mice. This study shows enhanced bone healing, impaired neuromotor recovery and anxiety-like behavior in a brain–bone polytrauma model. However, bone fractures did not aggravate TBI-evoked neuropathology, suggesting the existence of outcome-relevant mechanisms independent of the extent of brain structural damage and neuroinflammation. Full article

Plantarflexor central drive is a promising biomarker of neuromotor impairment; however, routine clinical assessment is hindered by the unavailability of force measurement systems with integrated neurostimulation capabilities. In this study, we evaluate the accuracy of a portable, neurostimulation-integrated, plantarflexor force measurement system we developed to facilitate the assessment of plantarflexor neuromotor function in clinical settings. Two experiments were conducted with the Central Drive System (CEDRS). To evaluate accuracy, experiment #1 included 16 neurotypical adults and used intra-class correlation (ICC_2,1) to test agreement of plantarflexor strength capacity measured with CEDRS versus a stationary dynamometer. To evaluate validity, experiment #2 added 26 individuals with post-stroke hemiparesis and used one-way ANOVAs to test for between-limb differences in CEDRS’ measurements of plantarflexor neuromotor function, comparing neurotypical, non-paretic, and paretic limb measurements. The association between paretic plantarflexor neuromotor function and walking function outcomes derived from the six-minute walk test (6MWT) were also evaluated. CEDRS’ measurements of plantarflexor neuromotor function showed high agreement with measurements made by the stationary dynamometer (ICC = 0.83, p < 0.001). CEDRS’ measurements also showed the expected between-limb differences (p’s < 0.001) in maximum voluntary strength (Neurotypical: 76.21 ± 13.84 ft-lbs., Non-paretic: 56.93 ± 17.75 ft-lbs., and Paretic: 31.51 ± 14.08 ft-lbs.), strength capacity (Neurotypical: 76.47 ± 13.59 ft-lbs., Non-paretic: 64.08 ± 14.50 ft-lbs., and Paretic: 44.55 ± 14.23 ft-lbs.), and central drive (Neurotypical: 88.73 ± 1.71%, Non-paretic: 73.66% ± 17.74%, and Paretic: 52.04% ± 20.22%). CEDRS-measured plantarflexor central drive was moderately correlated with 6MWT total distance (r = 0.69, p < 0.001) and distance-induced changes in speed (r = 0.61, p = 0.002). CEDRS is a clinician-operated, portable, neurostimulation-integrated force measurement platform that produces accurate measurements of plantarflexor neuromotor function that are associated with post-stroke walking ability. Full article

Background: The Tau58/2 and Tau58/4 mouse lines expressing 0N4R tau with a P301S mutation mimic aspects of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). In a side-by-side comparison, we report the age-dependent development of cognitive, motor, and behavioral deficits in comparison with the spatial-temporal evolution of cellular tau pathology in both models. Methods: We applied the SHIRPA primary screen and specific neuromotor, behavioral, and cognitive paradigms. The spatiotemporal development of tau pathology was investigated immunohistochemically. Levels of sarkosyl-insoluble paired helical filaments were determined via a MesoScale Discovery biomarker assay. Results: Neuromotor impairments developed from age 3 months in both models. On electron microscopy, spinal cord neurofibrillary pathology was visible in mice aged 3 months; however, AT8 immunoreactivity was not yet observed in Tau58/4 mice. Behavioral abnormalities and memory deficits occurred at a later stage (>9 months) when tau pathology was fully disseminated throughout the brain. Spatiotemporally, tau pathology spread from the spinal cord via the midbrain to the frontal cortex, while the hippocampus was relatively spared, thus explaining the late onset of cognitive deficits. Conclusions: Our findings indicate the face and construct validity of both Tau58 models, which may provide new, valuable insights into the pathologic effects of tau species in vivo and may consequently facilitate the development of new therapeutic targets to delay or halt neurodegenerative processes occurring in tauopathies. Full article

Thyroid hormone (TH) transporter MCT8 deficiency causes severe locomotor disabilities likely due to insufficient TH transport across brain barriers and, consequently, compromised neural TH action. As an established animal model for this disease, Mct8/Oatp1c1 double knockout (DKO) mice exhibit strong central TH deprivation, locomotor impairments and similar histo-morphological features as seen in MCT8 patients. The pathways that cause these neuro-motor symptoms are poorly understood. In this paper, we performed proteome analysis of brain sections comprising cortical and striatal areas of 21-day-old WT and DKO mice. We detected over 2900 proteins by liquid chromatography mass spectrometry, 67 of which were significantly different between the genotypes. The comparison of the proteomic and published RNA-sequencing data showed a significant overlap between alterations in both datasets. In line with previous observations, DKO animals exhibited decreased myelin-associated protein expression and altered protein levels of well-established neuronal TH-regulated targets. As one intriguing new candidate, we unraveled and confirmed the reduced protein and mRNA expression of Pde10a, a striatal enzyme critically involved in dopamine receptor signaling, in DKO mice. As altered PDE10A activities are linked to dystonia, reduced basal ganglia PDE10A expression may represent a key pathogenic pathway underlying human MCT8 deficiency. Full article

The study of visuomotor adaptation (VMA) capabilities has been encompassed in various experimental protocols aimed at investigating human motor control strategies and/or cognitive functions. VMA-oriented frameworks can have clinical applications, primarily in the investigation and assessment of neuromotor impairments caused by conditions such as Parkinson’s disease or post-stroke, which affect the lives of tens of thousands of people worldwide. Therefore, they can enhance the understanding of the specific mechanisms of such neuromotor disorders, thus being a potential biomarker for recovery, with the aim of being integrated with conventional rehabilitative programs. Virtual Reality (VR) can be entailed in a framework targeting VMA since it allows the development of visual perturbations in a more customizable and realistic way. Moreover, as has been demonstrated in previous works, a serious game (SG) can further increase engagement thanks to the use of full-body embodied avatars. Most studies implementing VMA frameworks have focused on upper limb tasks and have utilized a cursor as visual feedback for the user. Hence, there is a paucity in the literature about VMA-oriented frameworks targeting locomotion tasks. In this article, the authors present the design, development, and testing of an SG-based framework that addresses VMA in a locomotion activity by controlling a full-body moving avatar in a custom VR environment. This workflow includes a set of metrics to quantitatively assess the participants’ performance. Thirteen healthy children were recruited to evaluate the framework. Several quantitative comparisons and analyses were run to validate the different types of introduced visuomotor perturbations and to evaluate the ability of the proposed metrics to describe the difficulty caused by such perturbations. During the experimental sessions, it emerged that the system is safe, easy to use, and practical in a clinical setting. Despite the limited sample size, which represents the main limitation of the study and can be compensated for with future recruitment, the authors claim the potential of this framework as a useful instrument for quantitatively assessing either motor or cognitive impairments. The proposed feature-based approach gives several objective parameters as additional biomarkers that can integrate the conventional clinical scores. Future studies might investigate the relation between the proposed biomarkers and the clinical scores for specific disorders such as Parkinson’s disease and cerebral palsy. Full article

Epilepsy is characterized by a predisposition to generate recurrent and spontaneous seizures; it affects millions of people worldwide. Status epilepticus (SE) is a severe type of seizure. In this context, screening potential treatments is very important. In the present study, we evaluated the beneficial effects of rosmarinic acid (RA) in pilocarpine-induced in vitro and in vivo models of epileptiform activity. Using an in vitro model in combined entorhinal cortex–hippocampal from Wistar rats we evaluated the effects of RA (10 µg/mL) on the lactate release and a glucose fluorescent analogue, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NDBG), after incubation in high potassium aCSF supplemented or not with pilocarpine. In the in vivo model, SE was induced in male C57BL/6 mice by pilocarpine. At 1, 24, and 48 h after the end of SE mice were treated with RA (30 mg/kg/v.o.). We evaluated the neuromotor impairment by neuroscore tests and protein carbonyl levels in the cerebral cortex. In both in vitro models, RA was able to decrease the stimulated lactate release, while no effect on 2-NBDG uptake was found. RA has beneficial effects in models of epileptiform activity in vivo and in vitro. We found that RA treatment attenuated SE-induced neuromotor impairment at the 48 h timepoint. Moreover, post-SE treatment with RA decreased levels of protein carbonyls in the cerebral cortex of mice when compared to their vehicle-treated counterparts. Importantly, RA was effective in a model of SE which is relevant for the human condition. The present data add to the literature on the biological effects of RA, which could be a good candidate for add-on therapy in epilepsy. Full article

Objectives: The aim of this paper is to investigate the effects of dance therapy in children with neuromotor impairments (CNI), organizing the outcomes according to International Classification of Functioning Disability and Health (ICF) domains, and to investigate if there is adequate evidence of effectiveness to recommend dance as a therapy. Methods: Electronic searches were conducted in December 2021. We include studies assessing the effects of dance in CNI up to 18 years. Data extraction included studies’ populations, intervention features, and main outcomes. We classified outcomes according to the ICF framework. We used the Cochrane collaboration’s tool, modified by effective practice and organization of care (EPOC), to assess the methodological quality. The GRADE synthesized the body of evidence. Results: Twelve studies were included, with most of them addressing the body structure and function and activity components of ICF. Only three studies addressed components of participation, and four of personal factors. All these studies reported the positive effects of dance. Nevertheless, all of them presented high risk of bias. We found very low evidence level for improvement of body structure and function and activity components. Conclusion: Dance therapy presents low evidence level for improvements of body structure and function and activity in CNI. Further studies with low risk of bias and larger samples are needed. Full article

Parkinson’s disease is characterized by motor and cognitive deficits that usually have an impact on quality of life and independence. To reduce impairment, various rehabilitation programs have been proposed, but their effects on both cognitive and motor aspects have not been systematically investigated. Furthermore, most intervention is focused on lower limb treatment rather than upper limbs. In the present study, we investigated the effect of 3-week upper limb vibratory stimulation training on cognitive functioning in 20 individuals with Parkinson’s disease. We analyzed cognitive (Montreal Cognitive Assessment, Trial Making Test, Digit Symbol, Digit Span Forward and Backward and Alertness) and motor performance (Unified Parkinson’s Disease Rating Scale—part III; Disability of the Arm, Shoulder and Hand Questionnaire) before treatment, at the end of treatment and one month post treatment. After rehabilitation, a statistically significant improvement was observed in terms of global cognitive status, attention, global motor functioning and disability. The results suggest an impact of upper limb motor rehabilitation on cognition in Parkinson’s disease. Future studies on neuromotor interventions should investigate their effects on cognitive functioning to improve understanding of cognitive motor interaction in Parkinson’s disease. Full article

Background: Sex chromosome aneuploidies (SCAs) are a group of disorders characterised by an abnormal number of sex chromosomes. Collective prevalence rate of SCAs is estimated to be around 1 in 400–500 live births; sex chromosome trisomies (e.g., XXX, XXY, XYY) are most frequent, while tetra- and pentasomies (e.g., XXXX, XXXXX, XXXY, XXXXY) are rarer, and the most common is 48, XXYY syndrome. The presence of additional X and/or Y chromosomes is believed to cause neurodevelopmental differences, with increased risk for developmental delays, language-based learning disabilities, cognitive impairments, executive dysfunction, and behavioural and psychological disorders. Aim of the Study: Our review has the purpose of analysing the neurocognitive, linguistical and behavioural profile of patients affected by sex chromosomes supernumerary aneuploidies (tetrasomy and pentasomy) to better understand the specific areas of weakness, in order to provide specific rehabilitation therapy. Methods: The literature search was performed by two authors independently. We used MEDLINE, PubMed, and PsycINFO search engines to identify sources of interest, without year or language restrictions. At the end of an accurate selection, 16 articles fulfilled the inclusion and exclusion criteria. Results and Conclusions: International literature has described single aspects of the neuropsychological profile of 48, XXYY and 49, XXXXY patients. In 48, XXYY patients, various degrees of psychosocial/executive functioning issues have been reported and there is an increased frequency of behavioural problems in childhood. Developmental delay and behavioural problems are the most common presenting problems, even if anxiety, depression and oppositional defiant disorder are also reported. They also show generalized difficulties with socialization and communication. Cognitive abilities are lower in measures of verbal IQ than in measures of performance IQ. Visuospatial skills are a relative strength compared to verbal skills. In patients with 49, XXXXY, both intellectual and adaptive functioning skills fall into the disability range, with better non-verbal cognitive performance. Speech and language testing reveals more deficits in expressive language than receptive language and comprehension. Anxiety, thought problems, internalizing and externalizing problems, and deficits in social cognition and communication are reported. Behavioural symptoms lessen from school age to adolescence, with the exception of thought problems and anxiety. Individuals affected by sex chromosome aneuploidies show testosterone deficiency, microorchidism, lack of pubertal progression and infertility. Hormone replacement therapy (HRT) is usually recommended for these patients: different studies have found that testosterone-based HRT benefit a wide range of areas initiated in these disorders, affecting not only neuromotor, cognitive and behavioural profile but also structural anomalies of the brain (i.e., increase of volume of grey temporal lobe matter). In conclusion, further studies are needed to better understand the neuropsychological profile with a complete evaluation, including neurocognitive and psychosocial aspects and to establish the real impact of HRT on improving the cognitive and behavioural profile of these patients. Full article