High-Density Electromyography (HD-EMG) shows strong potential in research, but its translation into clinical rehabilitation remains limited. This pilot study explores the feasibility of integrating a portable HD-EMG system into a standardized rehabilitation test using the Lokomat, a robotic gait trainer widely employed in neurorehabilitation. By decomposing EMG signals and analyzing Motor Unit (MU) properties, this study aims to assess neuromuscular differences related to age and post-stroke conditions. Three groups (healthy young, healthy elderly, and chronic stroke survivors) performed isometric sub-maximal knee extensions at 30%, 50%, and 70% of their maximum force. EMG signals were recorded from the Vastus Lateralis muscle using a 64-channel electrode grid. Conventional EMG parameters (e.g., envelope and median frequency) failed to differentiate among groups. In contrast, MU-level analysis revealed fewer detected MUs and lower discharge rates in elderly participants, along with stroke-related alterations in MU recruitment and muscle relaxation. These findings demonstrate both the feasibility and added diagnostic value of HD-EMG in routine clinical robotic rehabilitation. HD-EMG offers objective, detailed insights into neuromuscular functions and could support the optimization of rehabilitation strategies. Further research is needed to validate its clinical applicability in larger populations and promote the adoption of HD-EMG as a standard diagnostic tool.

Motor activation in response to perception of action-related stimuli may depend on a resonance mechanism subserving action understanding. The extent to which this mechanism is innate or learned from sensorimotor experience is still unclear. Here, we recorded EEG while people with paraplegia or tetraplegia consequent to spinal cord injury (SCI) and healthy control participants were presented with action sounds produced by body parts (mouth, hands or feet) that were or were not affected by SCI. Non-action sounds were used as further control. We observed reduced brain activation in subjects affected by SCI at both pre- and post-stimulus latencies specifically for those actions whose effector was disconnected by the spinal lesion (i.e., hand sound for tetraplegia and leg sound for both paraplegia and tetraplegia). Correlation analyses showed that these modulations were functionally linked with the chronicity of the lesion, indicating that the longer the time the lesion- EEG data acquisition interval and/or the more the lesion occurred at a young age, the weaker was the cortical activity in response to these action sounds. Tellingly, source estimations confirmed that these modulations originated from a deficit in the motor resonance mechanism, by showing diminished activity in premotor (during prediction and perception) and near the primary motor (during perception) areas. Such dissociation along the cortical hierarchy is consistent with both previous reports in healthy subjects and with hierarchical predictive coding accounts. Overall, these data expand on the notion that sensorimotor experience maintains the cortical representations relevant to anticipate and perceive action-related stimuli.

Several technologies have been introduced into neurorehabilitation programs to enhance traditional treatment of individuals with Spinal Cord Injury (SCI). Their effectiveness has been widely investigated, but their adoption has not been properly quantified. The aim of this study is to assess the distribution of conventional (Treatment As Usual—TAU) and technology-aided (Treatment With Technologies—TWT) treatments conveniently grouped based on different therapeutic goals in a selected SCI unit. Data from 104 individuals collected in 29 months were collected in a custom database and categorized according to both the conventional American Impairment Scale classification and a newly developed Multifactor (MF) clustering approach that considers additional sources of information (the lesion level, the level of independence in the activities of daily living, and the hospitalization duration). Results indicated an average technology adoption of about 30%. Moreover, the MF clusters were less overlapped, and the differences in TWT adoption were more pronounced than in AIS-based clustering. MF clustering was capable of grouping individuals based both on neurological features and functional abilities. In particular, individuals with motor complete injuries were grouped together, whereas individuals with sensorimotor incomplete SCI were collected separately based on the lesion level. As regards TWT adoption, we found that in the case of motor complete SCI, TWT for muscle tone control and modulation was mainly selected (about 90% of TWT), while the other types of TWT were seldom adopted. Even for individuals with incomplete SCI, the most frequent rehabilitation goal was muscle tone modulation (about 75% of TWT), regardless of the AIS level, and technologies to improve walking ability (about 12% of TWT) and balance control (about 10% of TWT) were mainly used for individuals with thoracic or lumbar lesions. Analyzing TAU distribution, we found that the highest adoption of muscle tone modulation strategies was reported in the case of individuals with motor complete SCI (about 42% of TAU), that is, in cases when almost no gait training was pursued (about 1% of TAU). In the case of cervical motor incomplete SCI, compared to thoracic and lumbar incomplete SCI, there was a greater focus on muscle tone control and force recruitment in addition to walking training (38% and 14% of TAU, respectively) than on balance training. Overall, the MF clustering provided more insights than the traditional AIS-based classification, highlighting differences in TWT adoption. These findings suggest that a wider overview that considers both neurological and functional characteristics of individuals after SCI based on a multifactor analysis could enhance the personalization of neurorehabilitation strategies.

Multimodal physiological monitoring and related estimation of the PsychoPhysiological (PP) state play an essential role in investigating the physical and cognitive workload of people executing a motor task. The aim of this work was to develop a data-driven Fuzzy Logic method to estimate four PP indicators, i.e. Energy Expenditure, Fatigue, Attention, and Stress, and test it in a study including ten healthy participants walking while assisted by a lower limb treadmill-based exoskeleton. PP indicators were compared with participants’ self-reported evaluation of the human-robot interaction experience following the administration of a dedicated questionnaire. Results from a correlation analysis demonstrated that the output of the Fuzzy Logic method was consistent with the participants’ subjective assessment.

To exploit the benefits of treadmill-based exoskeletons, it is crucial to assess possible deviations from natural walking depending on assistive parameters. This study evaluated the biomechanics of exoskeleton-assisted treadmill walking by comparing it with free gait. Five healthy participants walked freely on a treadmill and with the assistance of the Lokomat gait trainer, while changing Body Weight Support (BWS), Gait Speed (GS), and Guidance Force (GF). Results showed that the hip and knee joint kinematics depended on BWS and GS, while changes due to GF were limited. Moreover, joint kinematics and the activity of related muscles were altered with respect to free gait, for any combination of robot parameters in the case of the ankle, and especially for low GS and with BWS in the case of hip and knee. Overall, walking with the Lokomat can mostly resemble free gait at high speed and without BWS.

Most neurological pathologies that afflict humans are associated with the abnormal accumulation and aggregation of specific proteins into the cytoplasm and with mitochondrial dysfunction. Neuronal health is sustained by the fine regulation of protein synthesis and organelle biogenesis and their degradation to ensure efficient turnover. Autophagy is a powerful process for removing such proteins and for maintaining mitochondrial homeostasis. Thus, the autophagic activation may play important roles in neuronal cell survival and neuronal function under both physiological and pathological conditions. It is well accepted that the loss of basal autophagy or imbalance of autophagic flux leads to neuronal death. Autophagosomes accumulate abnormally in affected neurons of several neurodegenerative diseases such as AD, HD, PD, as well as brain and spinal cord trauma. Thus, knowledge of crosstalk between autophagy impairment and pathophysiological mechanisms is a prerequisite for successful therapeutic interventions in neurological disorders. This chapter summarizes the most up-to-date studies of whether autophagy perturbations affect neuronal function contributing to neurodegeneration in chronic and acute brain pathologies.

Background Electroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study. Methods The Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered. Discussion The Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data. Trial registration ClinicalTrials.gov NCT04353297 . Registered on April 15, 2020.

Introduction Dementia occurring in young people may be difficult to recognize. We compared the time to diagnosis between young- (YOD, age < 65) and late-onset dementia (LOD). Methods Time between the onset of symptoms and the diagnosis was measured in YOD and LOD patients consecutively seen in a cognitive neurology clinic. Multivariable regression analyses were performed to identify determinants of time to diagnosis. Results Mean time to diagnosis in 95 YOD patients was 11.2 months longer than in 73 LOD patients ( p = 0.022). The delay was driven by a longer time taken by YOD patients to be seen in the specialist centre, which in turn was related to the presence of language disturbances and coexisting depression. Discussion Young people take longer than elderly people to receive a dementia diagnosis because they take longer to be referred to dementia specialist centres. More awareness on YOD is needed in primary care and the public.

Abstract Study design Case report. Objectives To report a clinical case of spinal cord infarction due to cocaine use. Setting Spinal Center, IRCCS Fondazione S. Lucia, Rome (Italy). Case presentation Two days after recreational use of cocaine, a 27-year-old Caucasic man was admitted to the emergency department for acute cervical pain, weakness in all four limbs, and urinary retention. A cervical spinal magnetic resonance imaging scan, performed after 2 days, showed a “pencil-like” lesion extending from C4 to T1 metamer, compatible with acute ischemia in the anterior spinal artery territory. Other causes of vascular disorders, as well as inflammatory and infectious disorders were ruled out. At admission in our department, the patient had an incomplete tetraplegia at level C6, an indwelling catheter, and was unable to stand and walk. After 3 months of rehabilitation, he had an AIS score D tetraplegia at level C7, was able to stand and walk using parallel bars, and indwelling catheter was replaced by intermittent catheterization. Discussion and conclusions The etiology of medullary infarction may remain unexplained in nearly 30–40% of cases. Even if rare, cocaine-induced ischemic myelopathy should be considered and ruled out in the differential diagnosis of any acute nontraumatic myelopathy, especially in young patients.

We have recently provided evidence that cerebellar damage affects the spatiotemporal but not the spatial organization of the muscle patterns, suggesting that the cerebellum plays a key role in shaping their spatiotemporal organization. Here we show that the reconstruction of muscle patterns using spatiotemporal muscle synergies from healthy subjects unveils specific features in the muscle patterns of individuals with cerebellar ataxia. These results suggest a prediction power of time-varying muscle synergies that may provide novel markers of disease state after cerebellar damage. Understanding the changes in the modular organization of the motor system after neurological lesions is highly relevant for upper limb rehabilitation. Identification of an “abnormal” EMG feature in cerebellar disorders may have important clinical applications, because it may lead to the development of novel objective and quantitative indicators of motor impairment directly related to the specific pathophysiology.

Background: Crutches are the most common walking aids prescribed to improve mobility in subjects with central nervous system (CNS) lesions. To increase adherence to the appropriate level of crutch usage, providing load-related auditory feedback (aFB) may be a useful approach. We sensorized forearm crutches and developed a custom software to provide aFB information to both user and physical therapist (PhT). Aim: Evaluate aFB effects on load control during gait by a self-controlled case series trial. Methods: A single experimental session was conducted enrolling 12 CNS lesioned participants. Load on crutch was recorded during 10 Meter Walk Test performed with and without aFB. In both cases, crutch load data, and gait speed were recorded. Usability and satisfaction questionnaires were administered to participants and PhTs involved. Results: Reliable data were obtained from eight participants. Results showed that compared to the no FB condition, aFB yielded a significant reduction in the mean load on the crutches during gait ( p = 0.001). The FB did not influence gait speed or fatigue ( p > 0.05). The experience questionnaire data indicated a positive experience regarding the use of aFB from both participants' and PhTs' perspectives. Conclusion: aFB significantly improves compliance with crutch use and does not affect gait speed or fatigue by improving the load placed on crutches. The FB is perceived by users as helpful, safe, and easy to learn, and does not interfere with attention or concentration while walking. Furthermore, the PhTs consider the system to be useful, easy to learn and reliable.

Scientific literature provides weak attempts in analyzing user experience during the use of rehabilitation and assistive wearable robotic devices. The objective of this study is to develop and preliminary test a new questionnaire evaluating the subjective perspective of people using lower limb exoskeletons. A literature search was conducted to investigate acceptance and usability/quality models, theories and questionnaires with the aim of extracting relevant factors to be considered. A four-factor questionnaire was developed and its feasibility was tested on four participants with central nervous system lesions walking with overground and treadmill-based exoskeletons in rehabilitation scenarios.

Clinical studies described emotional and social behaviour alterations in patients with cerebellar diseases, proposing a role of specific cerebello-cerebral circuits in social cognition. However, for a long time these difficulties were underestimated, and no studies have addressed the correlation between social cognition deficits and topography of the cerebellar damage. The present study aims to investigate the social cognition impairment and the neuroanatomical alterations in patients with spinocerebellar ataxia type 2 (SCA2) and to analyze their relationship. To this purpose a social cognition battery composed by three tests, and a MRI protocol were administered to 13 SCA2 patients and 26 healthy subjects. The pattern of gray matter (GM) atrophy was analyzed by voxel-based morphometry, and the GM volumes of each altered area were correlated with the behavioral scores to investigate anatomo-functional relationships. In addition, we investigated the relationship between social deficits and damage to the cerebellar peduncles using DTI diffusivity indices. Our patients showed impairment of the immediate perceptual component of the mental state recognition (i.e., to recognize feelings and thoughts from the eyes expression), and difficulties in anger attribution, and in the understanding of false or mistaken beliefs. They showed a pattern of GM reduction in cerebellar regions, including lobules IX and VIIIb and Crus II, all of which are involved in specific components of the mentalizing process. Interestingly, the behavioral performance, in which SCA2 patients showed impairments compared to controls, correlated with the degree of cerebellar GM reduction and with the presence of microstructural abnormalities in the cerebellar peduncles. The present study provides the first characterization of the social cognition deficits in a homogenous cohort SCA2 patients and demonstrates that alterations in specific cerebellar regions should represent the neurobiological underpinning of their social behavior difficulties. Our results offer a new point of view in considering these aspects in the clinical practice.

Abstract Background Spasticity and neuropathic pain are common in patients after spinal cord injury and negatively affect patients’ quality of life. Gabapentin and baclofen are frequently used to treat these conditions. We present a flumazenil-reversed gabapentin-induced coma case, which, to our knowledge, is the second one described in scientific literature. Case presentation A 70-year-old Caucasian man was admitted to our neurorehabilitation ward following a fall with cervical trauma that resulted in immediate tetraplegia. During his stay, he suffered from lower limb pain, both neuropathic and due to severe spasticity. Gradual baclofen and gabapentin administration was prescribed, with reduction in both pain and spasticity. One morning, the patient was found unresponsive, with a Glasgow Coma Score of 3. Head computerized tomography, electrocardiogram, electroencephalogram, vital signs, blood tests, breathing, and blood oxygenation were normal. Renal and liver failure were ruled out. Intravenous 0.25 mg of flumazenil (Anexate) was administered, resulting in complete neurocognitive recovery with a Glasgow Coma Score of 15. Discussion and conclusions This case report highlights the importance of the individual response to certain pharmacological agents and suggests that further studies need to be conducted both on flumazenil and gabapentin pharmacodynamics to better understand their molecular–receptor activity, and on possible multiple flumazenil mechanisms of action, beyond its classical strict benzodiazepine antagonist action.

Insanity defense is sometimes invoked in criminal cases, and its demonstration is usually based on a multifactorial contribution of behavioural, clinical, and neurological elements. Neuroradiological evidence of structural alterations in cerebral areas that involve decision-making and moral reasoning is often accepted as a useful tool in these evaluations. On the other hand, the genetic predisposition to anti-social behavior is still controversial. In this paper, we describe two cases of violent crimes committed by young carriers of genetic variants associated with personality disorder; both the defendants claimed to be insane at the time of the crime. We discuss these cases and review the scientific literature regarding the relationship between legal incapacity/predisposition to criminal behavior and genetic mutations. In conclusion, despite some genetic variants being able to influence several cognitive processes (like moral judgement and impulse control), there is currently no evidence that carriers of these mutations are, per se, incapable of intentionally committing crimes.

In this paper, we present the design, control, and preliminary evaluation of the Symbitron exoskeleton, a lower limb modular exoskeleton developed for people with a spinal cord injury. The mechanical and electrical configuration and the controller can be personalized to accommodate differences in impairments among individuals with spinal cord injuries (SCI). In hardware, this personalization is accomplished by a modular approach that allows the reconfiguration of a lower-limb exoskeleton with ultimately eight powered series actuated (SEA) joints and high fidelity torque control. For SCI individuals with an incomplete lesion and sufficient hip control, we applied a trajectory-free neuromuscular control (NMC) strategy and used the exoskeleton in the ankle-knee configuration. For complete SCI individuals, we used a combination of a NMC and an impedance based trajectory tracking strategy with the exoskeleton in the ankle-knee-hip configuration. Results of a preliminary evaluation of the developed hardware and software showed that SCI individuals with an incomplete lesion could naturally vary their walking speed and step length and walked faster compared to walking without the device. SCI individuals with a complete lesion, who could not walk without support, were able to walk with the device and with the support of crutches that included a push-button for step initiation Our results demonstrate that an exoskeleton with modular hardware and control allows SCI individuals with limited or no lower limb function to receive tailored support and regain mobility.