Goal-Setting in Multiple Sclerosis-Related Spasticity Treated with Botulinum Toxin: The GASEPTOX Study.

Spasticity is one of the most disabling symptoms in multiple sclerosis (MS). Botulinum toxin injection (BTI) is a first-line treatment for focal spasticity. There is a lack of evidence of a functional improvement following BTI in MS-related spasticity. To describe goal-setting for BTI in MS, and evaluate the degree of attainment, using goal attainment scaling (GAS) 4-to-6 weeks after injection session, a one-year multi-center retrospective observational study assessing goal-setting and achievement during BTI session in spastic patients with MS was set up. Following the GAS method, patients and their physicians set up to three goals and scored their achievement 4 to 6 weeks thereafter. Commonly used goals from three centers were combined into a standardized list and 125 single BTI sessions were analyzed. The most frequent goals regarded lower limb (LL) impairments (equinovarus foot, toe claw) or locomotion (stability, walking distance, clinging) and accounted for 89.1%, versus 10.9% for upper limb (UL), mostly for mild-to-moderate MS. Overall, goals were frequently achieved (85.77%) mainly when related to gait and mobility rather than hygiene and ease of care. This study gives an overview on the most frequent, relevant, and achievable goals to be set in real-life practice of BTI for spasticity management in MS.

Anodal tDCS of contralesional hemisphere modulates ipsilateral control of spinal motor networks targeting the paretic arm post-stroke.

OBJECTIVE: The role of ipsilateral motor cortex efferent pathways in the transmission of voluntary command to spinal motor nuclei remains controversial in humans. In healthy subjects, their implication in cortical control is hidden by predominant role of crossed corticospinal tract. However, evidence from electrophysiological and imaging studies suggest that ipsilateral tracts may contribute to functional recovery after unilateral brain damage. This randomized-sham control study aims to explore to what extent ipsilateral tracts from the undamaged hemisphere may strengthen corticospinal control onto spinal motor networks following stroke. METHODS: Anodal transcranial direct current stimulation (tDCS) was combined with monosynaptic H-reflex method to evaluate the variations of reciprocal inhibition (RI) in wrist flexors in 21 stroke participants. RESULTS: Anodal tDCS decreased RI in wrist flexors in stroke participants in both arms. tDCS unmasks an ipsilateral control from the undamaged hemisphere onto spinal motor networks controlling affected arm muscles in stroke participants. In the unaffected (contralateral) arm, effects in stroke participants were opposite to those induced in healthy subjects. CONCLUSIONS: Stimulation of the undamaged cortex in stroke participants induces modulation of ipsilateral motor networks controlling the hemiparetic side. SIGNIFICANCE: Rehabilitation could leverage stimulation of the undamaged hemisphere to enhance motor recovery post stroke.

Effects of a 6-month self-rehabilitation programme in addition to botulinum toxin injections and conventional physiotherapy on limitations of patients with spastic hemiparesis following stroke (ADJU-TOX): protocol study for a randomised controlled, investigator blinded study.

INTRODUCTION: Home-based self-rehabilitation programmes combined with botulinum toxin injections (BTIs) appear to be a relevant approach to increase the recommended intensive rehabilitation of patients with spasticity following a stroke. The literature highlights a lack of evidence of beneficial effects of this adjuvant therapy to reduce limitations of patients with stroke. The aim of this study is to assess the effects of a 6-month self-rehabilitation programme in adjunction to BTI, in comparison with BTI alone, to reduce limitations of patients with spasticity following a stroke. METHODS AND ANALYSIS: 220 chronic patients will participate to this multicentre, prospective, randomised, controlled, assessor blinded study. All patients will benefit from two successive BTI (3 months apart), and patients randomised in the self-rehabilitation group will perform in adjunction 6 months of self-rehabilitation at home. All patients continue their conventional physiotherapy. The main outcome is the primary treatment goal (PTG), which will be determined jointly by the patient and the medical doctor using Goal Attainment Scaling. Impairments and functions, quality of life, mood and fatigue will be assessed. Botulinum toxin will be injected into the relevant muscles according to the PTG. Patients in the self-rehab group will be taught the self-rehabilitation programme involving respectively 10 min of stretching, 10 min of strengthening and 10 min of task-oriented exercises, corresponding to their PTG. Compliance to the self-rehabilitation programme will be monitored. ETHICS AND DISSEMINATION: Patients will sign written informed consent. Ethical approval was obtained from ethics committee. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients. TRIAL REGISTRATION NUMBER: NCT02944929.

Spasticity and spastic dystonia: the two faces of velocity-dependent hypertonia.

BACKGROUND: Spasticity and spastic dystonia are two separate phenomena of the upper motor neuron syndrome. Spasticity is clinically defined by velocity-dependent hypertonia and tendon jerk hyperreflexia due to the hyper-excitability of the stretch reflex. Spastic dystonia is the inability to relax a muscle leading to a spontaneous tonic contraction. Both spasticity and spastic dystonia are present in patients who are at rest; however, only patients with spasticity are actually able to kept their muscles relaxed prior to muscle stretch. The idea that has inspired the present work is that also in patients with spastic dystonia the stretch reflex is likely to be hyper-excitable. Therefore, velocity-dependent hypertonia could be mediated not only by spasticity, but also by spastic dystonia. METHODS: Tonic stretch reflexes in the rectus femoris muscle were evoked in 30 patients with multiple sclerosis showing velocity-dependent hypertonia of leg extensors and the habituation of the reflex was studied. Moreover, the capability of relax the muscle prior to muscle stretch (spastic dystonia) was also investigated. RESULTS: A tonic stretch reflex was evoked in all the enrolled patients. 73% of the patients were able to relax their rectus femoris muscle prior to stretch (spasticity). In the overwhelming majority of these patients, the tonic stretch reflex decreased during repeated stretches. In the remaining 27% of the subjects, the muscle was tonically activated prior to muscle stretch (spastic dystonia). In the patients in whom spastic dystonia progressively increased over the subsequent stretches (50% of the subjects with spastic dystonia), the habituation of the reflex was replaced by a progressive reflex facilitation. DISCUSSION: This study shows for the first time that velocity-dependent hypertonia can be caused by two distinct phenomena: spasticity and spastic dystonia. The habituation of the tonic stretch reflex, which is a typical feature of spasticity, is replaced by a reflex facilitation in the half of the subject with spastic dystonia. These preliminary findings suggest that differentiating the two types of velocity-dependent muscle hypertonia (spasticity and spastic dystonia) could be clinically relevant.

Spinal plasticity in stroke patients after botulinum neurotoxin A injection in ankle plantar flexors.

The effect of botulinum neurotoxin A (BoNT-A) in stroke patients' upper limbs has been attributed to its peripheral action only. However, BoNT-A depressed recurrent inhibition of lumbar motoneurons, likely due to its retrograde transportation along motor axons affecting synapses to Renshaw cells. Because Renshaw cells control group Ia interneurons mediating reciprocal inhibition between antagonists, we tested whether this inhibition, particularly affected after stroke, could recover after BoNT-A. The effect of posterior tibial nerve (PTN) stimulation on tibialis anterior (TA) electromyogram (EMG) was investigated in 13 stroke patients during treadmill walking before and 1 month after BoNT-A injection in ankle plantar flexors. Before BoNT-A, PTN stimuli enhanced TA EMG all during the swing phase. After BoNT-A, the PTN-induced reciprocal facilitation in TA motoneurons was depressed at the beginning of swing and reversed into inhibition in midswing, but at the end of swing, the reciprocal facilitation was enhanced. This suggests that BoNT-A induced spinal plasticity leading to the recovery of reciprocal inhibition likely due to the withdrawal of inhibitory control from Renshaw cells directly blocked by the toxin. At the end of swing, the enhanced reciprocal facilitation might be due to BoNT-induced modification of peripheral afferent inputs. Therefore, both central and peripheral actions of BoNT-A can modify muscle synergies during walking: (1) limiting ankle muscle co-contraction in the transition phase from stance to swing, to assist dorsiflexion, and (2) favoring it from swing to stance, which blocks the ankle joint and thus assists the balance during the single support phase on the paretic limb.

Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A.

The natural target of the botulinum neurototoxin type A (BoNT-A) is the neuromuscular junction. When injected into a muscle, BoNT-A is internalized by motoneurone terminals where it functions as an endopeptidase, cleaving protein components of the synaptic machinery responsible for vesicle docking and exocytosis. As a result, BoNT-A induces a characteristic flaccid paralysis of the affected muscle. In animal models, BoNT-A applied in the periphery can also influence central activity via retrograde transport and transcytosis. An analogous direct central effect in humans is still debated. The present study was designed to address whether BoNT-A modifies the activity of the spinal recurrent inhibitory pathways, when injected at muscular level, in humans. To avoid methodological bias, the recurrent inhibition from an injected muscle (soleus) was investigated on an untreated muscle (quadriceps), and stimulation parameters (producing recurrent inhibition) were monitored on a third non-injected muscle but innervated by the same nerve as the soleus (flexor digitorum brevis). The experiments were performed on 14 post-stroke patients exhibiting spasticity in ankle plantarflexors, candidates for BoNT-A. One month after BoNT-A, the level of recurrent inhibition was depressed. It is suggested that the depression of recurrent inhibition was induced by BoNT-A, injected peripherally, through axonal transport and blockade of the cholinergic synapse between motoneurone recurrent collaterals and Renshaw cells.

The profile of patients and current practice of treatment of upper limb muscle spasticity with botulinum toxin type A: an international survey.

To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31 countries were studied. Most patients were over 40 years old and had a stroke. Improvement of active function was the most frequent treatment goal in the first 3 months after the onset of upper limb spasticity, but was less common than passive function in the chronic stage. Pain relief was a common goal in both the stages. As a rule, clinicians intended to assess the effectiveness of treatment with impairment level scales. Functional outcome measures seem to be rarely used in clinical practice. The use of these measures should be encouraged to assess whether the reduction in muscle tone translates into functional benefit to patients and their caregivers.

Effect of 1-methylcyclopropene on volatile emission and aroma in cv. Anna apples.

The rapidly ripening summer apple cultivar Anna was treated with 0.1 micro L(-1) and 1 microL L(-1) 1-methylcyclopropene (MCP) at harvest and kept at 20 degrees C, or stored for 5 weeks at 0 degrees C and then transferred to 20 degrees C. Total volatiles were not reduced by treatment with 0.1 microL L(-1) MCP, but were 70% lower in fruits treated with 1 microL L(-1) MCP than in untreated fruits. Ethylene production was 50% and 95% inhibited by 0.1 microL L(-1) and 1 microL L(-1) MCP, respectively. The volatiles produced by fruit at harvest were predominantly aldehydes and alcohols, with some acetate esters as well as 2-methyl butyl acetate and beta-damascenone. During ripening, the acetate and butyrate esters increased greatly and alcohols and aldehydes decreased. MCP-treated apples retained more alcohols, aldehydes, and beta-damascenone volatiles than did untreated apples. Sensory evaluation found that control and 0.1 microL L(-1) treated apples developed more fruity, ripe, and overall aromas, but the preference was for the 1 microL L(-1) treated apples with a less ripe aroma.

Effects of a lumbar support on spine posture and motion assessed by electrogoniometer and continuous recording.

OBJECTIVE: To determine whether belt wearing causes changes in lumbar posture and motion during standing and work-related activities. DESIGN: The lumbar spine sagittal kinematics of healthy subjects were assessed with an electrogoniometer during a dynamic test and continuous recording with and without a lumbar support. Correlation between data from electrogoniometer and X-ray was established in preliminary experiments. BACKGROUND: The effects of a lumbar support were previously investigated in few patients using radiological or invasive techniques under laboratory conditions, with special regard to the restriction of global motion in flexion and extension. Whether lumbar posture may also be involved during belt wearing remains unclear. There is also no evidence that these changes affecting lumbar motion and posture persist during prolonged activities. METHODS: The correlation between electrogoniometer and radiographic data was assessed in 12 subjects. Lumbar curve angles were evaluated in 15 healthy subjects, with and without one type of lumbar support, during standing in orthostatic, fully-flexed and fully-extended positions and during work-related activities with a portable computer. Lumbar motion parameters were flexion, extension and total range of motion. Lumbar posture parameters were lumbar curve angle in orthostatic position and mean lumbar curve angle during continuous recording. RESULTS: Electrogoniometric and radiographic data from lumbar curve angles and motion changes during flexion/extension of the spine were slightly different but reasonably well correlated (r = 0.58-0.77). The lumbar support decreased the mean total range of motion of the lumbar spine during a single flexion/extension movement by 17% and during continuous recording by 22%. The lumbar curve angle in the orthostatic position was reduced by 3 degrees and the mean lumbar curve (assessed by continuous recording) was reduced by 4 degrees (mean for 15 subjects). There were major individual changes in these two parameters and the reduction in lumbar curvature was correlated with the initial (r = 0.66-0.72). CONCLUSION: Electrogoniometer data on lumbar motion are reasonably well correlated with X-ray data. The comparative values registered during flexion/extension tests and continuous recording confirm that a support belt limits slightly global lumbar motion. As changes affecting postural parameters (orthostatic or mean values during continuous recording) depend on subject morphometry, individual parameters should be taken in account when evaluating and using a lumbar support.