European expert consensus on improving patient selection for the management of disabling spasticity with intrathecal baclofen and/or botulinum toxin type A.

OBJECTIVE: To develop an algorithm for the selection of adults with disabling spasticity for treatment with intrathecal baclofen (ITB) and/or botulinum toxin type A (BoNT A). METHODS: A European Advisory Board of 4 neurologists and 4 rehabilitation specialists performed a literature review on ITB and BoNT A treatment for disabling spasticity. An online survey was sent to 125 physicians and 13 non-physician spasticity experts. Information on their current clinical practice and level of agreement on proposed selection criteria was used to inform algorithm design. Consensus was considered reached when ≥75% of respondents agreed or were neutral. RESULTS: A total of 79 experts from 17 countries completed the on-line survey (57%). Agreement was reached that patients with multi-segmental or generalized disabling spasticity refractory to oral drugs are the best candidates for ITB (96.1% consensus), while those with focal/segmental disabling spasticity are ideal candidates for BoNT A (98.7% consensus). In addition the following are good candidates for ITB (% consensus): bilateral disabling spasticity affecting lower limbs only (97.4%), bilateral (100%) or unilateral (90.9%) disabling spasticity affecting lower limbs and trunk, and unilateral or bilateral disabling spasticity affecting upper and lower extremities (96.1%). CONCLUSION: This algorithm will support the management of adult patients with disabling spasticity by aiding patient selection for ITB and/or BoNT A treatments.

Botulinum Toxin Services for Neurorehabiliation: Recommendations for Challenges and Opportunities during the COVID-19 Pandemic.

The COVID-19 pandemic severely impacted the function of medical facilities and rehabilitation services worldwide, including toxin services delivering Botulinum toxin treatments for neuromuscular conditions such as spasticity, dystonia, and sialorrhea. The aim of this paper is to understand how toxin services have dealt with the situation and what strategies have been adopted to continue services. The recommendations are based on a virtual round table held with toxin services experts from different European countries who shared their experiences and discussed the best practices. The challenges for toxin services were reviewed based on the experts' experiences and on relevant literature from 2020 and 2021. A set of recommendations and best practices were compiled, focusing firstly on guidance for clinical practice, including assessing patients' health and risk status and the urgency of their treatment. Secondly, it was discussed how patients on botulinum toxin therapy can be cared for and supported during the pandemic, and how modern technology and tele-medicine platforms can be generally used to optimize effectiveness and safety of toxin treatments. The technological advances prompted by the COVID-19 crisis can result in better and more modern patient care in the future.

Spasticity treatment with onabotulinumtoxin A: data from a prospective German real-life patient registry.

This study aimed at providing real-life baseline, injection and outcome data for the treatment of various forms of spasticity with onabotulinumtoxin A in Germany. Prospective data were collected in an open multicenter patient registry from 2005 until 2010, encompassing the experience of ten specialized German centers in the treatment of spasticity using onabotulinumtoxin A in 508 patients with a total of 2005 treatment sessions. Disease entities comprised spasticity following stroke (both ischemic and hemorrhagic), traumatic brain injury, multiple sclerosis, cerebral palsy, and anoxia. Sustained improvement was observed in a variety of outcome parameters including goal attainment and motor performance scores for up to five repeated injection sessions. No significant differences between disease entities or between upper and lower limb treatment were observed with regard to efficacy and safety following onabotulinumtoxin A treatment. Minor to moderate side effects were reported in <1 % of the study population. We conclude that repetitive treatment of focal and multifocal spasticity with onabotulinumtoxin A provides a safe and efficacious therapeutic strategy for patients with different disease entities of the central nervous system.

Efficacy and safety of botulinum toxin type A (Dysport) for the treatment of post-stroke arm spasticity: results of the German-Austrian open-label post-marketing surveillance prospective study.

The current practice in Germany and Austria, and the safety and efficacy of botulinum toxin type A (BoNT-A; Dysport) in the treatment of patients with post-stroke arm spasticity (with no fixed upper-limb contractures), were assessed in this observational prospective non-interventional study. One treatment cycle was documented with assessments at baseline, approximately week 4 (optional), and approximately week 12. Pattern of spasticity, treatment goal, safety and efficacy were recorded. Overall response and goal achievement was rated on a 4-point scale ('no goal achievement', 'goal achievement', 'good goal achievement', 'best goal achievement'). In total, 409 patients were included and 99% assigned to one of five arm-spasticity patterns. Therapy goals included reduced muscle tone (92.6%), physiotherapy or occupational therapy support (63.8%), increased range of motion (61.8%), pain reduction (58.9%), facilitation of care or hygiene (55.7%), and functional improvement (17.0%). Goals were achieved in 84% of patients. The following factors had the most potential as predictors of treatment outcome: pre-treatment; time since onset of spasticity; pattern of arm spasticity. Mean Dysport dose was 728 U and an inverse dose-response relationship was observed. Treatment was well tolerated. 500-1000 U was a safe and effective treatment for post-stroke arm spasticity in this post-marketing evaluation.

Whole body vibration versus conventional physiotherapy to improve balance and gait in Parkinson's disease.

OBJECTIVE: To compare the effects of whole body vibration (WBV) and conventional physiotherapy (PT) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson's disease (PD). DESIGN: Randomized controlled rater-blinded trial comparing 2 active interventions, final follow-up assessment 4 weeks after termination of active intervention. SETTING: Specialized referral center, hospitalized care. PARTICIPANTS: Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication (N=27) were randomized (intent-to-treat population) to receive WBV (n=13) or conventional PT (controls, n=14). Twenty-one patients (per protocol population) completed follow-up (14 men, 7 women; mean age, 73.8 y; age range, 62-84 y; mean disease duration, 7.2 y; mean dopa-equivalent dose, 768 mg/d). INTERVENTION: Subjects were randomized to receive 30 sessions (two 15-min sessions a day, 5 days a week) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board. Twenty-one subjects (10 with WBV, 11 controls) were available for follow-up 4 weeks after treatment termination. MAIN OUTCOME MEASURES: The primary measure was Tinetti Balance Scale score. Secondary clinical ratings included stand-walk-sit test, walking velocity, Unified Parkinson's Disease Rating Scale (section III motor examination) score, performance in the pull test, and dynamic posturography. RESULTS: The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls. All secondary measures, except posturography, likewise improved at follow-up compared with baseline in both groups. Quantitative dynamic posturography only improved in patients with WBV (1937-1467 mm) whereas there was no significant change in controls (1832-2030 mm). CONCLUSIONS: Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program. There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training.

The effect of nabilone on neuropsychological functions related to driving ability: an extended case series.

The primary goal of this prospective extended case series was to obtain the first data about the potential influence of nabilone intake on driving ability related neuropsychological functions. Six patients were investigated within a placebo controlled, double-blind crossover study of this synthetic cannabinoid (2 mg/day) in patients with multiple sclerosis and spasticity associated pain. Five neuropsychological functions (reaction time, working memory, divided attention, psychomotor speed and mental flexibility) were assessed. No indication was found of a deterioration of any of the five investigated neuropsychological functions during the 4-week treatment period with nabilone.

Computerized tremor analysis of valproate-induced tremor: a comparative study of controlled-release versus conventional valproate.

PURPOSE: Valproate (VPA) induces postural tremor in 6-45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. METHODS: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n=10) or CR-VPA (n=8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of >or=8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. RESULTS: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. CONCLUSIONS: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak-trough variation with VPA than with CR-VPA.

Nociceptive EMG suppression in triceps brachii muscle in humans.

OBJECTIVE: Inhibitory spinal reflexes in human hand muscles mediated by cutaneous afferents (=cutaneous silent periods, CSPs) serve to protect the hand from injury. Proximal muscles are included in a complex protective pattern implementing both excitatory and inhibitory reflexes. METHODS: We investigated the functional organization of CSPs in the triceps brachii muscle (TB) - the prime elbow extensor - assessing different stimulus intensities and elbow positions. Thirteen healthy subjects underwent recurrent electrical index finger tip stimulation with different intensities while volitionally activating TB against resistance. The rectified and averaged electromyogram (EMG) was recorded from TB with surface electrodes while the elbow joint was held in full flexion, full extension, and at an angle of 90 degrees. RESULTS: Digit II stimulation resulted in distinct CSPs in TB. Increasing stimulus intensities caused a more profound EMG suppression. Different elbow positions had a significant influence on CSP onset and end latency, and duration. CONCLUSIONS: The present findings are consistent with a functional organization of protective reflexes in the proximal human upper limb across several metameric segments. Spinal inhibitory neurons serving to rapidly suppress basic muscle synergies may compete with neural circuitry involved in postural control.

Early consolidation in human primary motor cortex.

Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.