A practical guide to botulinum neurotoxin treatment of shoulder spasticity 2: Injection techniques, outcome measurement scales, and case studies.

Introduction: Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, the wrist, the hand, and/or the finger muscles but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. Methods: In part 2 of this two-part practical guide, we present an experts' consensus on the choice of outcome measurement scales and goal-setting recommendations for BoNT-A in the treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. Case studies are included as examples of approaches taken in the treatment of shoulder spasticity. Results: Although the velocity-dependent increase in muscle tone is often a focus of patient assessment, it is only one component of spasticity and should be assessed as part of a wider range of measurements. For outcome measurement following BoNT-A injection in shoulder muscles, shoulder-specific scales are recommended. Other scales to be considered include Pain Numerical Rating and/or global functioning, as well as the quality of life and global perception of benefit scores.Goal setting is an essential part of the multidisciplinary management process for spasticity; goals should be patient-centric, realistic, and achievable; functional-focused goal statements and a mixture of short- (3-6 month) and long-term (9-18 month) goals are recommended. These can be grouped into symptomatic, passive function, active function, involuntary movement, and global mobility.Clinical evaluation tools, goal setting, and outcome expectations for the multipattern treatment of shoulder spasticity with BoNT-A should be defined by the whole multidisciplinary team, ensuring patient and caregiver involvement. Discussion: These recommendations will be of benefit to clinicians who may not be experienced in evaluating and treating spastic shoulders.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 1: Anatomy, physiology, and goal setting.

Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, wrist, hand and/or finger muscles, but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. In part 1 of this two-part practical guide, we present an experts' consensus on the use of BoNT-A injections in the multi-pattern treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. A patient-centered approach was proposed by the expert consensus: to identify which activities are limited by the spastic shoulder and consider treating the muscles that are involved in hindering those activities. Two patterns of shoulder spasticity were identified: for Pattern A (adduction, elevation, flexion and internal rotation of the shoulder), the expert panel recommended injecting the pectoralis major, teres major and subscapularis muscles; in most cases injecting only the pectoralis major and the teres major is sufficient for the first injection cycle; for Pattern B (abduction or adduction, extension and internal rotation of the shoulder), the panel recommended injecting the posterior part of the deltoid, the teres major and the latissimus dorsi in most cases. It is important to consider the local guidelines and product labels, as well as discussions within the multidisciplinary, multiprofessional team when deciding to inject shoulder muscles with BoNT-A. The choice of shoulder muscles for BoNT-A injection can be based on spastic pattern, but ideally should also firstly consider the functional limitation and patient expectations in order to establish better patient-centered treatment goals. These recommendations will be of benefit for clinicians who may not be experienced in evaluating and treating spastic shoulders.

Exploratory Randomized Double-Blind Placebo-Controlled Trial of Botulinum Therapy on Grasp Release After Stroke (PrOMBiS).

Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = -0.44, 95% CI = -1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program.

The unsolved role of heightened connectivity from the unaffected hemisphere to paretic arm muscles in chronic stroke.

OBJECTIVE: Ipsilateral connectivity from the non-stroke hemisphere to paretic arm muscles appears to play little role in functional recovery, which instead depends on contralateral connectivity from the stroke hemisphere. Yet the incidence of ipsilateral projections in stroke survivors is often reported to be higher than normal. We tested this directly using a sensitive measure of connectivity to proximal arm muscles. METHOD: TMS of the stroke and non-stroke motor cortex evoked responses in pre-activated triceps and deltoid muscles of 17 stroke survivors attending reaching training. Connectivity was defined as a clear MEP or a short-latency silent period in ongoing EMG in ≥ 50% of stimulations. We measured reaching accuracy at baseline, improvement after training and upper limb Fugl-Meyer (F-M) score. RESULTS: Incidence of ipsilateral connections to triceps (47%) and deltoid (58%) was high, but unrelated to baseline reaching accuracy and F-M scores. Instead, these were related to contralateral connectivity from the stroke hemisphere. Absolute but not proportional improvement after training was greater in patients with ipsilateral responses. CONCLUSIONS: Despite enhanced ipsilateral connectivity, arm function and learning was related most strongly to contralateral pathway integrity from the stroke hemisphere. SIGNIFICANCE: Further work is needed to decipher the role of ipsilateral connections.

Chronic Stroke Survivors Improve Reaching Accuracy by Reducing Movement Variability at the Trained Movement Speed.

BACKGROUND: Recovery from stroke is often said to have "plateaued" after 6 to 12 months. Yet training can still improve performance even in the chronic phase. Here we investigate the biomechanics of accuracy improvements during a reaching task and test whether they are affected by the speed at which movements are practiced. METHOD: We trained 36 chronic stroke survivors (57.5 years, SD ± 11.5; 10 females) over 4 consecutive days to improve endpoint accuracy in an arm-reaching task (420 repetitions/day). Half of the group trained using fast movements and the other half slow movements. The trunk was constrained allowing only shoulder and elbow movement for task performance. RESULTS: Before training, movements were variable, tended to undershoot the target, and terminated in contralateral workspace (flexion bias). Both groups improved movement accuracy by reducing trial-to-trial variability; however, change in endpoint bias (systematic error) was not significant. Improvements were greatest at the trained movement speed and generalized to other speeds in the fast training group. Small but significant improvements were observed in clinical measures in the fast training group. CONCLUSIONS: The reduction in trial-to-trial variability without an alteration to endpoint bias suggests that improvements are achieved by better control over motor commands within the existing repertoire. Thus, 4 days' training allows stroke survivors to improve movements that they can already make. Whether new movement patterns can be acquired in the chronic phase will need to be tested in longer term studies. We recommend that training needs to be performed at slow and fast movement speeds to enhance generalization.

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study.

BACKGROUND: Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities. METHODS: We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used. RESULTS: One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls. CONCLUSIONS: We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.

Anaesthesia changes perceived finger width but not finger length.

The brain needs information about the size of the body to control our interactions with the environment. No receptor signals this information directly; the brain must determine body size from multiple sensory inputs and then store this information. This process is poorly understood, but somatosensory information is thought to play a role. In particular, anaesthetising a body part has been reported to make it feel bigger. Here, we report the first study to measure whether changes in body size following anaesthesia are uniform across dimensions (e.g. width and length). We blocked the digital nerves of ten human subjects with a clinical dose of local anaesthetic (1 % lignocaine) and again in separate sessions with a weaker dose (0.25 % lignocaine) and a saline control. Subjects reported the perceived size of their index finger by selecting templates from a set that varied in size and aspect ratio. We also measured changes in sensory signals that might contribute to the anaesthetic-induced changes using quantitative sensory testing. Subjects perceived their finger to be up to 32 % wider during anaesthesia when compared to during a saline control condition. However, changes in perceived length of the finger were much smaller (<5 %). Previous studies have shown a change in perceived body size with anaesthesia, but have assumed that the aspect ratio is preserved. Our data show that this is not the case. We suggest that nonuniform changes in perceived body size might be due to the brain increasing the body's perimeter to protect it from further injury.

An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition.

Theta burst stimulation in the rehabilitation of the upper limb: a semirandomized, placebo-controlled trial in chronic stroke patients.

BACKGROUND: Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke. However, its clinical value, including anticipated size and duration of the treatment effects, remains largely unknown. OBJECTIVE: The authors designed a small semi-randomized clinical trial to explore whether long-lasting clinically important gains can be achieved by adding theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), to a rehabilitation program for the hand. METHODS: A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers; each active group was compared with a group receiving sham TBS. TBS was followed by physical therapy for 10 working days. Patients and therapists were blinded to the type of TBS. Primary outcome measures (9-hole Peg Test [9HPT], Jebsen Taylor Test [JTT], and grip and pinch-grip dynamometry) were assessed 4, 30, and 90 days post treatment. The clinically important difference was defined as 10% of the maximum score. RESULTS: There were no differences between the active treatment and sham groups in any of the outcome measures. All patients achieved small sustainable improvements--9HPT, 5% of maximum (confidence interval [CI] = 3%-7%); JTT, 5.7% (CI = 3%-8%); and grip strength, 6% (CI = 2%-10%)--all below the defined clinically important level. CONCLUSIONS: Cortical stimulation did not augment the gains from a late rehabilitation program. The effect size anticipated by the authors was overestimated. These results can improve the design of future work on therapeutic uses of TMS.