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Introduction: Via mirror mechanism, motor training approaches based on the alternation of action observation and execution (i.e., Action Observation Training-AOT) promote the acquisition of motor abilities. Previous studies showed that both visual and auditory stimuli may elicit a common motor representation of music-related gestures; however, the potentialities of AOT for the acquisition of musical skills are still underexplored. Methods: Twenty-one music-naïve participants underwent two blocks of training: AOT and Key-light Observation Training (KOT). AOT consisted of the observation of a melodic sequence played on a keyboard with the right hand by an expert model, followed by participant's imitation. Observation and execution were repeated six consecutive times (T1-T6). KOT followed the same procedure, except for the visual content of the stimulus, depicting the sequential highlighting of the piano keys corresponding to the melody. The rate of correct notes (C), the trainee-model similarity of key-pressure strength (S), and the trainee-model consistency of note duration (R) were collected across T1-T6. Results: Both AOT and KOT improved musical performance. Noteworthy, AOT showed a higher learning magnitude relative to KOT in terms of C and S. Discussion: Action Observation Training promotes the acquisition of key elements of melodic sequences, encompassing not only the accurate sequencing of notes but also their expressive characteristics, such as key-pressure dynamics. The convergence of listening and observation of actions onto a shared motor representation not only explains several pedagogical approaches applied in all musical cultures worldwide, but also enhances the potential efficacy of current procedures for music training.
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Action Observation Training (AOT) promotes the acquisition of motor abilities. However, while the cortical modulations associated with the AOT efficacy are well known, few studies investigated the AOT peripheral neural correlates and whether their dynamics move towards the observed model during the training. We administered seventy-two participants (randomized into AOT and Control groups) with training for learning to grasp marbles with chopsticks. Execution practice was preceded by an observation session, in which AOT participants observed an expert performing the task, whereas controls observed landscape videos. Behavioral indices were measured, and three hand muscles' electromyographic (EMG) activity was recorded and compared with the expert. Behaviorally, both groups improved during the training, with AOT outperforming controls. The EMG trainee-model similarity also increased during the training, but only for the AOT group. When combining behavioral and EMG similarity findings, no global relationship emerged; however, behavioral improvements were "locally" predicted by the similarity gain in muscles and action phases more related to the specific motor act. These findings reveal that AOT plays a magnetic role in motor learning, attracting the trainee's motor pattern toward the observed model and paving the way for developing online monitoring tools and neurofeedback protocols.
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Mano , Aprendizaje , Humanos , Miembro Anterior , Mano/fisiología , Grabación de Cinta de VideoRESUMEN
In sports, understanding others' actions represents a fundamental skill that allows players to predict the outcome of teammates' and opponents' actions and counteract them properly. While it is well known that motor expertise sets better premises for predicting the result of an observed sports action, it remains untested whether this principle applies to a team where players cover different positions that imply different motor repertoires. To test this hypothesis, we selected rugby as a paradigmatic example in which only one or two players out of 22 train and perform placed kicks. We administered a placed kick outcome prediction task to three groups of participants, namely, rugby kickers, rugby non-kickers, and controls, thus spanning over different combinations of motor expertise and visual experience. Kickers outperformed both their non-kicking teammates and controls in overall prediction accuracy. We documented how the viewpoint of observation, the expertise of the observed kicker, and the position of the kick on the court influenced the prediction performance across the three groups. Finally, we revealed that within rugby players, the degree of motor expertise (but not the visual experience) causally affects accuracy, and such a result stands even after accounting for the level of visual experience. These findings extend the role of motor expertise in decoding and predicting others' behaviors to sports teammates, among which every member is equipped with a position-specific motor repertoire, advocating for new motor training procedures combining the gestures to-be-performed with those to-be-faced.
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The observation of other's actions represents an essential element for the acquisition of motor skills. While action observation is known to induce changes in the excitability of the motor cortices, whether such modulations may explain the amount of motor improvement driven by action observation training (AOT) remains to be addressed. Using transcranial magnetic stimulation (TMS), we first assessed in 41 volunteers the effect of action observation on corticospinal excitability, intracortical inhibition, and transcallosal inhibition. Subsequently, half of the participants (AOT-group) were asked to observe and then execute a right-hand dexterity task, while the controls had to observe a no-action video before practicing the same task. AOT participants showed greater performance improvement relative to controls. More importantly, the amount of improvement in the AOT group was predicted by the amplitude of corticospinal modulation during action observation and, even more, by the amount of intracortical inhibition induced by action observation. These relations were specific for the AOT group, while the same patterns were not found in controls. Taken together, our findings demonstrate that the efficacy of AOT in promoting motor learning is rooted in the capacity of action observation to modulate the trainee's motor system excitability, especially its intracortical inhibition. Our study not only enriches the picture of the neurophysiological effects induced by action observation onto the observer's motor excitability, but linking them to the efficacy of AOT, it also paves the way for the development of models predicting the outcome of training procedures based on the observation of other's actions.
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Corteza Motora , Destreza Motora , Humanos , Potenciales Evocados Motores/fisiología , Estimulación Magnética Transcraneal/métodos , Corteza Motora/fisiología , Mano/fisiología , Tractos Piramidales/fisiología , Músculo Esquelético/fisiologíaRESUMEN
Motor learning can be defined as a process that leads to relatively permanent changes in motor behavior through repeated interactions with the environment. Different strategies can be adopted to achieve motor learning: movements can be overtly practiced leading to an amelioration of motor performance; alternatively, covert strategies (e.g., action observation) can promote neuroplastic changes in the motor system even in the absence of real movement execution. However, whether a training regularly alternating action observation and execution (i.e., Action Observation Training, AOT) may surpass the pure motor practice (MP) and observational learning (OL) remains to be established. To address this issue, we enrolled 54 subjects requiring them to learn tying nautical knots via one out of three types of training (AOT, MP, OL) with the scope to investigate which element mostly contributes to motor learning. We evaluated the overall improvement of each group, along with the predictive role that neuropsychological indexes exert on each treatment outcome. The AOT group exhibited the highest performance improvement (42%), indicating that the regular alternation between observation and execution biases participants toward a better performance. The reiteration of this sequence provides an incremental, adjunct value that super-adds onto the efficacy of motor practice or observational learning in isolation (42% > 25% + 10%, i.e., OL + MP). These findings extend the use of the AOT from clinical and rehabilitative contexts to daily routines requiring the learning and perfectioning of new motor skills such as sports training, music, and occupational activities requiring fine motor control.
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Ensuring proper dosage of treatment and repetition over time is a major challenge in neurorehabilitation. However, a requirement of physical distancing to date compromises their achievement. While mostly associated to COVID-19, physical distancing is not only required in a pandemic scenario, but also advised for several clinical conditions (e.g. immunocompromised individuals) or forced for specific social contexts (e.g. people living in remote areas worldwide). All these contexts advocate for the implementation of alternative healthcare models. The objective of this perspective is to highlight the benefits of remote administration of rehabilitative treatment, namely telerehabilitation, in counteracting physical distancing barriers in neurorehabilitation. Sustaining boosters of treatment outcome, such as compliance, sustainability, as well as motivation, telerehabilitation may adapt to multiple neurological conditions, with the further advantage of a high potential for individualization to patient's or pathology's specificities. The effectiveness of telerehabilitation can be potentiated by several technologies available to date: virtual reality can recreate realistic environments in which patients may bodily operate, wearable sensors allow to quantitatively monitor the patient's performance, and signal processing may contribute to the prediction of long-term dynamics of patient recovery. Telerehabilitation might spark its advantages far beyond the mere limitation of physical distancing effects, mitigating criticalities of daily neurorehabilitative practice, and thus paving the way to the envision of mixed models of care, where hospital-based procedures are complementarily integrated with telerehabilitative ones.
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COVID-19 , Telerrehabilitación , Realidad Virtual , Humanos , Distanciamiento Físico , SARS-CoV-2RESUMEN
There is rich clinical evidence that observing normally executed actions promotes the recovery of the corresponding action execution in patients with motor deficits. In this study, we assessed the ability of action observation to prevent the decay of healthy individuals' motor abilities following upper-limb immobilization. To this end, upper-limb kinematics was recorded in healthy participants while they performed three reach-to-grasp movements before immobilization and the same movements after 16 h of immobilization. The participants were subdivided into two groups; the experimental group observed, during the immobilization, the same reach-to-grasp movements they had performed before immobilization, whereas the control group observed natural scenarios. After bandage removal, motor impairment in performing reach-to-grasp movements was milder in the experimental group. These findings support the hypothesis that action observation, via the mirror mechanism, plays a protective role against the decline of motor performance induced by limb nonuse. From this perspective, action observation therapy is a promising tool for anticipating rehabilitation onset in clinical conditions involving limb nonuse, thus reducing the burden of further rehabilitation.
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Fuerza de la Mano/fisiología , Inmovilización/fisiología , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Observación , Rehabilitación , Extremidad Superior , Adulto JovenRESUMEN
While it is well documented that the motor system is more than a mere implementer of motor actions, the possible applications of its cognitive side are still under-exploited, often remaining as poorly organized evidence. Here, we will collect evidence showing the value of action observation treatment (AOT) in the recovery of impaired motor abilities for a vast number of clinical conditions, spanning from traumatological patients to brain injuries and neurodegenerative diseases. Alongside, we will discuss the use of AOT in the maintenance of appropriate motor behavior in subjects at risk for events with dramatic physical consequences, like fall prevention in elderly people or injury prevention in sports. Finally, we will report that AOT can help to tune existing motor competencies in fields requiring precise motor control. We will connect all these diverse dots into the neurophysiological scenario offered by decades of research on the human mirror mechanism, discussing the potentialities for individualization. Empowered by modern technologies, AOT can impact individuals' safety and quality of life across the whole lifespan.
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Calidad de Vida , Anciano , Humanos , Recuperación de la FunciónRESUMEN
OBJECTIVE: To explore neurophysiological features of musicogenic epilepsy (ME), discussing experimental findings in the framework of a systematic review on ME. METHODS: Two patients with ME underwent high-density-electroencephalography (hd-EEG) while listening to ictogenic songs. In one case, musicogenic seizures were elicited. Independent component analysis (ICA) was applied to hd-EEG, and components hosting interictal and ictal elements were identified and localized. Finally, the temporal dynamics of spike-density was studied relative to seizures. All findings were compared against the results of a systematic review on ME, collecting 131 cases. RESULTS: Interictal spikes appeared isolated in specific fronto-temporal independent components, whose cortical generators were located in the anterior temporal and inferior frontal lobe. In the patient undergoing seizure, ictal discharge relied in the same component, with the interictal spike-density decreasing before the seizure onset. CONCLUSION: Our study shows how ICA can isolate neurophysiological features of ictal and interictal discharges in ME, highlighting a fronto-temporal localization and a suppression of spike-density preceding the seizure onset. SIGNIFICANCE: While the localization of ME activity could indicate which aspect within the musical stimulus might trigger musicogenic seizures for each patient, the study of ME dynamics could contribute to the development of models for seizure-prediction and their validation.
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Encéfalo/fisiopatología , Epilepsia Refleja/fisiopatología , Música , Convulsiones/fisiopatología , Adulto , Electroencefalografía , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Here we describe a rare case of Capgras delusion - a misidentification syndrome characterized by the belief that a person has been replaced by an imposter - in a patient without evident neurological or psychiatric symptoms. Intriguingly, delusional belief was selective for both person and modality, as the patient believed that his son - not his daughter or other relatives - was substituted with an imposter only while being in presence of him and looking at his face, but not when merely listening to his voice. A neuroanatomical reconstruction obtained integrating morphological and functional patient's neuroimaging data highlighted two main peculiarities: a compression of the rostral portion of right temporal lobe due to a large arachnoid cyst, and a bilaterally reduced metabolism of frontal areas. Autonomic data obtained from thermal infra-red camera and skin conductance recordings showed that a higher sympathetic activation was evoked by the observation of daughter's face, relative to the observation of the son's face as well as of not-familiar faces; conversely, daughter and son voices elicited a similar sympathetic activation, higher relative to not-familiar voices, indicating a modality-dependent dissociation consistent with the delusional behavior. Our case supports the "two-hit hypothesis" about Capgras delusion etiopathogenesis: here, the first hit is represented by the right-temporal lesion impairing the association between familiar faces and emotional values, the second one is the frontal bilateral hypometabolism favoring delusional behavior. The selective occurrence of "imposter" delusion for a particular subject and for a specific perceptual modality suggests the involvement of modality-specific interactions in the retrieval of affective properties during familiar people recognition.
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Síndrome de Capgras , Deluciones , Encéfalo/diagnóstico por imagen , Humanos , Masculino , Reconocimiento en Psicología , Lóbulo TemporalRESUMEN
Slow gait speed has been shown to predict incident dementia and cognitive decline in older individuals. We aimed to summarize the evidence concerning the association of slow gait speed with cognitive decline and dementia, and discuss the possible shared pathways leading to cognitive and motor impairments, under the unifying hypothesis that body and mind are intimately connected. This is a scoping review supported by a systematic search of the literature, performed on PubMed and Web of Science. Longitudinal studies providing information on the role of gait speed in the prediction of cognitive decline and dementia in cognitively intact people and in those with initial cognitive impairment were eligible. Of 39 studies selected, including overall 57,456 participants, 33 reported a significant association between gait speed and cognitive outcomes, including dementia. Neurodegenerative pathology and cerebrovascular burden may damage cerebral areas involved in both cognitive functions and motor control. At the same time, systemic conditions, characterized by higher cardiorespiratory, and metabolic and inflammatory burden, can affect a number of organs and systems involved in motor functions, including the brain, having ultimately an impact on cognition. The interplay of body and mind seems relevant during the development of cognitive decline and dementia. The measurement of gait speed may improve the detection of prodromal dementia and cognitive impairment in individuals with and without initial cognitive deficits. The potential applicability of such a measure in both clinical and research settings points at the importance of expanding our knowledge about the common underlying mechanisms of cognitive and motor decline.
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Cognición , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Evaluación Geriátrica/métodos , Velocidad al Caminar , Anciano , HumanosRESUMEN
AIM: To evaluate the feasibility and effectiveness of an action observation treatment (AOT) home-based platform promoting child-to-child interaction to improve hand motor function in unilateral cerebral palsy (CP). METHOD: Twenty children (14 males, six females; mean age 6y 7mo, standard deviation 1y 7mo; range 5y 1mo-10y 6mo) with unilateral CP underwent 20 sessions where they had to observe and then imitate a wizard performing dexterity-demanding magic tricks; a child-to-child live video-session to practise the same exercise then took place. We assessed hand-motor skills with the Besta Scale, neurological motor impairment with Fugl-Meyer Assessment for upper extremity, as well as spasticity, muscle strength, visual analogue scale, and global impression of change 1-month before (T-1), at baseline (T0), and at the end of treatment (T1). RESULTS: We observed a T0 to T1 improvement in global hand-motor and bimanual skills, and a significant correlation between motor improvement and difference in hand motor skills relative to the peer (r=-0.519). INTERPRETATION: AOT associated with child-to-child interaction effectively improves hand motor function in unilateral CP. This improvement is linked to differences in hand motor ability among peers, suggesting that children should observe others with superior motor skills to their own. This study extends traditional AOT toward novel socially-enriched scenarios, where children might simultaneously be recipients and leaders within a motor learning process. WHAT THIS PAPER ADDS: Home-based action observation treatment (AOT) based on child-to-child interaction improves hand motor function in children with unilateral cerebral palsy. Interaction with a more capable peer increases the chances of positive outcome in child-to-child AOT.
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Parálisis Cerebral/rehabilitación , Actividad Motora , Modalidades de Fisioterapia , Parálisis Cerebral/diagnóstico , Niño , Preescolar , Evaluación de la Discapacidad , Femenino , Mano , Humanos , Conducta Imitativa , Masculino , Destreza Motora , Resultado del Tratamiento , Grabación de Cinta de VideoRESUMEN
Drawings produced by children provide insights about their physical and psychological status. In children suffering from unilateral cerebral palsy (UCP), self-portraits constitute a unique opportunity to study whether and how their disease affects self-body representation. The aim of the present study is to evaluate self-body representation in UCP children, comparing it to the way they portray both healthy and hemiparetic peers. Ten UCP children were asked to perform 3 drawings: a self-portrait, a portrait of their best classmate, and finally a portrait of a hemiparetic peer who had joint them in a child-to-child rehabilitation protocol. As controls, 16 typically developing children were asked to perform a self-portrait, and their best-classmate portrait. The asymmetry index (AI), consisting of the difference between the upper limbs length expressed as percentage of their average, resulted greater in UCP than in controls' self-portrait. More interestingly, UCP children portrayed themselves more asymmetrically relative to their classmates and hemiparetic peers. No difference in terms of AI was found between self- vs. classmate-portrait in the control group. This study provides evidence that UCP affects body self-representation, but not body-representation in general. In fact, the asymmetry in upper limb representation observed in children with UCP does not constitute a mere picturing of the hemiparesis, but rather reflects the experienced status of functioning, that is valid only for one's own. The inclusion of portraits in pediatric neurorehabilitation programs might enable clinicians to collect additional evidence about the children self-perceived functioning, i.e., an information not easily obtainable in pediatric patients.
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OBJECTIVE: Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course. MATERIALS AND METHODS: This single-centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first-line disease-modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001-December 2005, and January 2006-September 2011. RESULTS: A total of 1068 relapsing-remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P < 0.0001), started more frequent treatment with high-dose interferon beta or glatiramer acetate (P < 0.0001), and had experienced a more frequent treatment escalation strategy (P = 0.004) than patients in other cohorts. The multivariate analysis adjusted for baseline characteristics showed that pwMS of the last cohort had a high probability of showing no evidence of disease activity (NEDA3) at 4 years (OR 3.22, 95% CIs 1.89-5.47; P < 0.0001). These results were confirmed in a propensity score analysis. CONCLUSIONS: Our study showed an improvement over the last 15 years in the treatment response; this observation can be associated to a paradigm shift in MS treatment strategies.
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Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Neurología/tendencias , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Acetato de Glatiramer/uso terapéutico , Humanos , Interferón beta-1a/uso terapéutico , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Péptidos/uso terapéuticoRESUMEN
Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.
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Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Desempeño Psicomotor , Adulto , Factores de Edad , Algoritmos , Análisis de Varianza , Mapeo Encefálico , Niño , Preescolar , Potenciales Evocados Motores , Femenino , Mano/fisiología , Humanos , Masculino , Modelos Teóricos , Movimiento , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
The neuronal mechanisms involved in brain plasticity after skilled motor learning are not completely understood. We aimed to study the short-term effects of keyboard training in music-naive subjects on the motor/premotor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS). Twelve subjects (experimental group) underwent, before and after a two week-piano training: (1) hand-motor function tests: Jamar, grip and nine-hole peg tests; (2) electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD) during keyboard performance; and (3) TMS, targeting bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), to obtain duration and area of ipsilateral silent period (ISP) during simultaneous tonic contraction of APB and ADM. Data were compared with 13 controls who underwent twice these measurements, in a two-week interval, without undergoing piano training. Every subject in the experimental group improved keyboard performance and left-hand nine-hole peg test scores. Pre-training, ISP durations were asymmetrical, left being longer than right. Post-training, right ISPAPB increased, leading to symmetrical ISPAPB. Mu TRD during motor performance became more focal and had a lesser amplitude than in pre-training, due to decreased activity over ventral premotor cortices. No such changes were evidenced in controls. We demonstrated that a 10-day piano-training was associated with balanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.
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Potenciales Evocados Motores/fisiología , Lateralidad Funcional/fisiología , Corteza Motora/fisiología , Música , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Adulto , Estimulación Eléctrica , Electroencefalografía , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Corteza Motora/anatomía & histología , Red Nerviosa/anatomía & histología , Inhibición Neural/fisiología , Estimulación Magnética TranscranealRESUMEN
Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows-23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.
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Cannabidiol/efectos adversos , Cannabidiol/uso terapéutico , Dronabinol/efectos adversos , Dronabinol/uso terapéutico , Esclerosis Múltiple/complicaciones , Espasticidad Muscular/tratamiento farmacológico , Adulto , Estudios de Cohortes , Combinación de Medicamentos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Espasticidad Muscular/etiología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Despite the proven efficacy of Sativex(®) (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects. The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS. This was a randomized, double-blind, placebo-controlled, crossover study. Consecutive subjects with progressive MS and lower limb spasticity referred to our center were randomized to 4 weeks' treatment (including 2 weeks' titration) with Sativex or placebo, with crossover after a 2-week washout. Clinical and neurophysiological measures (H/M ratio and cortical excitability) of spasticity were assessed. The H/M ratio was the primary outcome, with sample size calculation of 40 patients. Of 44 recruited patients, 34 were analyzed due to 6 drop-outs and 4 exclusions, which lowered the power of the study to show differences between treatments. Neurophysiological measures did not differ significantly according to treatment and did not correlate significantly with clinical response. Response on the modified Ashworth scale (at least 20 % improvement) was significantly more frequent after Sativex than placebo (50 vs 23.5 %; p = 0.041; McNemar). Side effects did not differ significantly according to treatment. Our findings confirm the clinical benefit of Sativex on MS spasticity. The lack of corresponding changes in corticospinal excitability and on the monosynaptic component, of the stretch reflex, although in a limited sample size, points to the involvement of other spinal and supraspinal mechanisms in the physiopathology of spasticity in progressive MS.
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Corteza Cerebral/efectos de los fármacos , Potenciales Evocados Motores/efectos de los fármacos , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Extractos Vegetales/farmacología , Adulto , Cannabidiol , Estudios Cruzados , Método Doble Ciego , Dronabinol , Combinación de Medicamentos , Estimulación Eléctrica , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/complicaciones , Espasticidad Muscular/etiología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Índice de Severidad de la Enfermedad , Estimulación Magnética TranscranealAsunto(s)
Adenosina Trifosfatasas/genética , Distrofia Muscular Facioescapulohumeral/complicaciones , Distrofia Muscular Facioescapulohumeral/genética , Proteínas Nucleares/genética , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/genética , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Proteínas de Microfilamentos , Persona de Mediana Edad , Linaje , Fenotipo , Proteínas de Unión al ARN , Espastina , Adulto JovenRESUMEN
OBJECTIVES: To assess the efficacy of high-frequency (20 Hz) brain stimulation on lower limb motor function in subjects with chronic (> 6 mo) subcortical stroke. DESIGN: Double-blind, placebo-controlled crossover study. SETTING: University hospital. PARTICIPANTS: Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. INTERVENTIONS: Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. MAIN OUTCOME MEASURES: Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. RESULTS: Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. CONCLUSIONS: These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.