**1.1. Biomedical background**

Neuromuscular Rehabilitation is the science and practice of supporting the recovery of lost or impaired motor function, particularly due to damage of the Central Nervous System

(CNS). The established approach to treatment is physiotherapeutic, pharmacological and surgical, the choice of a specific line of action depending on the exact diagnosis, the general state of the patient, the severity of the damage, the time distance from the acute event, the evolution of sequelae, the presence of co-morbidities, etc.

In the general case, a patient undergoing neuromuscular rehabilitation was struck by a primary event (e.g. a stroke, a traumatic brain injury, an infection, hypoxia, a tumour,…) producing severe neuronal loss. According to the affected area of the CNS different scenarios may result, including a state of paresis (essentially, tetra- or hemi-plegia), and possibly other types of impairment, such as cognitive, sensory and so on. The recovery process from these initial insults often does not proceed independently of a series of interconnected secondary phenomena, which, if left uncontrolled, can undermine all hopes of an optimal final outcome. These phenomena include muscular contracture, spasticity, CNS remodelling and learned non-use.

With no ambition to be exhaustive, it can be pointed out here that the main mechanisms by which the human body, and in particular the neuromuscular system, react to the primary event are mediated by two functional disruptions of the physiological status, namely, *immobility* and *disuse*. Immobility is the absence of movement, especially of a limb or body joint; disuse is the lack of muscular activation and consequent mechanical loading of the skeleto-muscular structure. It is evident that both conditions are tightly connected to and often caused by the state of paresis. *Contracture* (shortening of the muscles) can occur due to prolonged (days or weeks) permanence of the body segment in a given position. This can be the case e.g. for a flexed elbow when patients sitting on wheelchairs keep their hands in their laps; or for an ankle joint that is maintained in an overly extended posture by gravity during continuous rest in bed. Muscular contracture produces, as a major consequence, a forceful and rigid ill-positioning of the adjacent joint, reduction of the available articular range of motion, and malformation. It can lead, in time, through reduced mobility, to structured calcifications of joints and retraction. Alongside contractures, the development of s*pasticity* is one of the most common and severe secondary events in the sub-acute phase of paresis. Spasticity is an abnormal and speed-dependent stiffening of the muscles due to hyperactive stretch reflex. This exaggerated response to muscle lengthening exacerbates the impossibility of movement and subjects the patient to discomfort and pain as soon as the limb is mobilised. In turn, contrasting immobility becomes an even harder challenge. The picture resulting from the instauration of contracture and spasticity is given the name of *spastic paresis*, which is a painful, disfiguring and severely disabling condition, and constitutes a serious obstacle to patients' recovery [1-2]. In fact, the increased rigidity of muscles and joints further hinders any voluntary or involuntary motion or use of the limb, thus creating a vicious circle towards greater disruption of neuromuscular functionality.

Besides producing peripheral modifications, the prolonged immobility and disuse of the limb appears to affect negatively the plastic reorganisation and remapping of brain structures, by which live neurons take over the role of lost ones. The manner of such remapping is bound to have a paramount influence on ultimate functional healing, and this is one more motivation for trying and avoiding those conditions in the first place. Their removal could shun the worsening of muscle stiffness and hypertone, while a sustained proprioceptive (sensorial) stimulation through movement may support appropriate cortical reorganisation. However, a complete picture of brain remodelling after a CNS insult and the effect of rehabilitation in modulating such a reorganisation is still not available. Studies of Neuroscience investigating in particular rehabilitation processes are certainly of great interest for physicians, neurologists, researchers and physiotherapists, as they can shed some light on those phenomena.

84 Smart Actuation and Sensing Systems – Recent Advances and Future Challenges

evolution of sequelae, the presence of co-morbidities, etc.

CNS remodelling and learned non-use.

(CNS). The established approach to treatment is physiotherapeutic, pharmacological and surgical, the choice of a specific line of action depending on the exact diagnosis, the general state of the patient, the severity of the damage, the time distance from the acute event, the

In the general case, a patient undergoing neuromuscular rehabilitation was struck by a primary event (e.g. a stroke, a traumatic brain injury, an infection, hypoxia, a tumour,…) producing severe neuronal loss. According to the affected area of the CNS different scenarios may result, including a state of paresis (essentially, tetra- or hemi-plegia), and possibly other types of impairment, such as cognitive, sensory and so on. The recovery process from these initial insults often does not proceed independently of a series of interconnected secondary phenomena, which, if left uncontrolled, can undermine all hopes of an optimal final outcome. These phenomena include muscular contracture, spasticity,

With no ambition to be exhaustive, it can be pointed out here that the main mechanisms by which the human body, and in particular the neuromuscular system, react to the primary event are mediated by two functional disruptions of the physiological status, namely, *immobility* and *disuse*. Immobility is the absence of movement, especially of a limb or body joint; disuse is the lack of muscular activation and consequent mechanical loading of the skeleto-muscular structure. It is evident that both conditions are tightly connected to and often caused by the state of paresis. *Contracture* (shortening of the muscles) can occur due to prolonged (days or weeks) permanence of the body segment in a given position. This can be the case e.g. for a flexed elbow when patients sitting on wheelchairs keep their hands in their laps; or for an ankle joint that is maintained in an overly extended posture by gravity during continuous rest in bed. Muscular contracture produces, as a major consequence, a forceful and rigid ill-positioning of the adjacent joint, reduction of the available articular range of motion, and malformation. It can lead, in time, through reduced mobility, to structured calcifications of joints and retraction. Alongside contractures, the development of s*pasticity* is one of the most common and severe secondary events in the sub-acute phase of paresis. Spasticity is an abnormal and speed-dependent stiffening of the muscles due to hyperactive stretch reflex. This exaggerated response to muscle lengthening exacerbates the impossibility of movement and subjects the patient to discomfort and pain as soon as the limb is mobilised. In turn, contrasting immobility becomes an even harder challenge. The picture resulting from the instauration of contracture and spasticity is given the name of *spastic paresis*, which is a painful, disfiguring and severely disabling condition, and constitutes a serious obstacle to patients' recovery [1-2]. In fact, the increased rigidity of muscles and joints further hinders any voluntary or involuntary motion or use of the limb, thus creating a vicious circle towards greater disruption of neuromuscular functionality.

Besides producing peripheral modifications, the prolonged immobility and disuse of the limb appears to affect negatively the plastic reorganisation and remapping of brain structures, by which live neurons take over the role of lost ones. The manner of such remapping is bound to have a paramount influence on ultimate functional healing, and this Recent trends in neuromuscular rehabilitation rely on pharmacological treatments against mild and severe spasticity, such as denervating neurotoxins (BOTOX) or myorelaxation agents (Baclofen) [3]; in most severe cases of contracture the approach can resort to surgical interventions such as tendon lengthening or transfer. The most widely used technique for all severities and types of spastic paresis is however physical therapy, which consists in static repositioning by means of splints and casting, controlled and gradual mobilisation of the limbs, muscular stretching and active exercising. It has been widely acknowledged that active work-out is a particularly important part of the rehabilitation program [4-5]. However, if autonomous control by the patient is absent or insufficient, passive mobilisation is utilised to try and maintain the viscoelastic properties of muscles and periarticular tissues. Furthermore, it is reasonable to think that minimising immobility and disuse, even by means of passive motion, can be advantageous for the prevention of the other adverse sequelae of CNS damage or to contrast their worsening.

Robotic tools are becoming very popular, as they make it possible to extend the duration of therapeutic sessions without the need for an individual involvement of human therapists, and reduce costs. In fact, though time-extensive physiotherapy is known to influence positively the rehabilitation outcome, organisational issues may limit the practical application of this principle, especially for passive mobilisation, in which case the physiotherapist has to move each affected joint one by one. In most situations, robotic tools provide repetitive and repeatable passive mobilisation of the whole limb [6], or joint by joint [7]. Moreover, several rehabilitation robots can assist active work-out, by completing patient's efforts to move [8] with the aim of improving muscle recruitment, by perturbing limb trajectories to enhance active control, or by contrasting movement [9] to strengthen muscles. Some drawbacks can be identified concerning the current use of robots in rehabilitation. First, as many of these machines are large, massive and costly, in a typical clinical environment the number of robots is limited and their use at home is ruled out. Second, most part of them require minimal skills by the patients, e.g. trunk control, equilibrium or cognitive abilities: that excludes very early or severe subjects, although they could benefit from extended sessions of passive mobilisation as well.

Robotic devices have been used for the mobilisation of body parts also in the field of Neuroscience [10-15]. Machines to manage the motion of the effectors (muscles) can in fact be used to support the measurement and visualisation of the interconnections between the activities of peripheral segments and the brain structures involved in their control. In this type of applications tight compatibility with Bioimaging and Biosignal technologies is mandatory [13].
