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Objectives: To examine the prevalence, onset threshold, and response magnitude of stretch reflex response (SRR) in the knee extensors and flexors before and after an intrathecal baclofen (ITB) bolus injection in patients with moderate-to-severe hypertonia., Materials and Methods: SRRs were elicited by reciprocal passive knee extension/flexion movements at preset angular velocities of 5, 60, 120, 180, 240, and 300°/s using an isokinetic dynamometer and recorded with surface electromyographic (EMG) electrodes placed over the knee extensors and flexors in 53 neurologic patients before and at 2.5 and 5 hours after an ITB injection via lumbar puncture. Outcome measures included the number of patients with presence/absence of SRRs, the number of SRRs per session, SRR onset threshold angle and velocity, and response magnitudes (peak EMG and area under the EMG curve) for each muscle. Pre-post comparisons were completed using the Fisher's exact and Wilcoxon signed rank tests., Results: For both knee extensors and flexors, the proportion of patients with present SRRs (p < 0.0001) and the number of SRRs per session (p ≤ 0.027) decreased from pre- to post-ITB. The threshold velocity significantly increased post-injection in both muscles (p ≤ 0.001) without significant changes in the threshold angle. The response magnitudes significantly decreased in the knee extensors (p ≤ 0.016) but not the knee flexors after the injection., Conclusions: The prevalence and threshold velocity of SRR emerged as the most robust and practical parameters for assessing hyperreflexia during ITB bolus trial that can complement clinical assessment of muscle hypertonia., (© 2020 International Neuromodulation Society.)

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity., Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria., Results and Recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B)., (© 2016 American Academy of Neurology.)

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post-stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group-specific dose-response relationships. Our objective was to characterize dose-response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double-blind, placebo-controlled trials were pooled. Of 544 post-stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose-response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1-point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E(max)) model indicated a saturating dose-response relationship, with mean E(max) AshworthCBL values of -1.48, -1.48, -0.63, -0.77, and -0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1-point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post-stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population., (Copyright © 2010 Movement Disorder Society.)

Background: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared., Methods: This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE)., Results: BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (p<0.001 vs TZD; p<0.02 vs placebo) and 6 (p = 0.001 vs TZD; p = 0.08 vs placebo), and greater improvement in the cosmesis domain of the DAS at week 6 (p<0.01). TZD was not superior to placebo in tone reduction at either time point (p>or=0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001)., Conclusions: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.

Objective: The purpose of this study was to investigate the incidence of neutralizing antibody (NAb) formation in patients with poststroke spasticity treated with a specific formulation of botulinum toxin type A (BoNTA)., Methods: Data from 3 previous clinical trials of BoNTA in patients with upper and/or lower limb spasticity were pooled and evaluated. Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial of BoNTA in patients aged >/=21 years who had experienced a stroke >6 months before the initiation of the study. Study 2 was an open-label extension of study 1. Study 3 was a randomized, double-blind, multicenter trial of a specific BoNTA formulation in patients aged >/= 21 years who had experienced a stroke >/=6 weeks before study entry. Patients with a fixed contracture of the studied limb were excluded from participation in studies 1 and 2. Serum samples were obtained from each patient before each BoNTA treatment and at the end of each study. The mouse protection assay (MPA) was used for detection of NAbs to BoNTA in serum., Results: A total of 235 individual patients with post-stroke spasticity were enrolled in the 3 trials, including 126, 111 (all of whom participated in study 1), and 109 in studies 1, 2, and 3, respectively. Study 1 had an equal (50.0%) distribution of male and female patients (63/63). The distribution of male and female patients was 56 (50.5%) and 55 (49.5%), respectively, in study 2, and 55 (50.5%) and 54 (49.5), respectively, in study 3. The mean (SD) ages of patients in studies 1, 2, and 3 were 61.4 (13.8), 61.5 (14.1), and 58.5 (13.9) years, respectively. The MPA was used for detection of NAbs to BoNTA in the serum samples of 191 patients, including 64 from study 1, 111 from study 2 (55 of these patients were placebo recipients and 56 received their first BoNTA injection in study 1), and 72 (a sample was not obtained for 1 patient who had not received an injection) from study 3. The median number of BoNTA treatments received by these patients was 2 (range, 1-4 treatments) over a period lasting from 12 to 42 weeks. The mean dose of BoNTA was 241 U (range, 100-400 U), with a maximum dose of 960 U in any 1 patient. NAbs to BoNTA were detected in the serum sample of 1/191 (0.5%) patient who had participated in studies 1 and 2. Based on muscle-tone scores (3 and 4 for wrist and fingers, respectively) on a 5-point Ashworth Scale (0 = none to 4 = severe), the patient did not appear to exhibit a clinical response to BoNTA at any time during the studies., Conclusion: Formation of NAbs was rare (1/191) in this group of adults with poststroke spasticity from three 12- to 42-week clinical trials who received >/=1 treatment with a specific BoNTA formulation at doses ranging from 100 to 400 U.

Implanted programmable pumps that infuse intrathecal baclofen (ITB) markedly enhance the ability of clinicians to manage severe spasticity in appropriately selected patients. Studies addressing the efficacy of this treatment modality have primarily used clinical outcome measures of impairment, particularly reduction in stiffness as measured by the Ashworth scale. Several recent studies, however, highlight comparalively higher sensitivity of neurophysiologic techniques, especially the H-reflex, as an objective index of spinal cord response to ITB administration. We review the conceptual, physiological, and methodological hases for use of the H-reflex as an adjunct to clinical evaluation among patients receiving ITB infusion, including published reports and selected case studies that address the potential advantages and limitations of such techniques when applied to dose titration and system "troubleshooting" scenarios, We also address the implications of such findings in the context of reported complications such as "tolerance" to ITB administration and catheter "microfracture". The accumulated knowledge suggests that H-reflex is a sensitive method for documenting altered spinal cord responsiveness in the presence of ITB delivery. We therefore recommend using H-reflex as an adjunct to clinical evaluation when judging the overall effectiveness of ITB administration.

Intrathecal baclofen (ITB) therapy has been increasingly employed for the management of poststroke spastic hypertonia, a complication that can lead to deformity, discomfort, and exacerbation of motor impairments. Because its use in stroke is not as established as other indications, ITB therapy has not been subjected to rigorous investigation. There is limited evidence to guide clinicians regarding application of this therapy in this patient population. This article aims to review the available scientific literature and the opinion of several experts on the topic. It will also describe the recommendations of these experts with regard to addressing common clinical situations that may influence treatment decisions in the stroke population.

Objective: To determine the relationship between the H-reflex (H/M ratio) and continuous intrathecal baclofen (CITB) dose after pump implantation for control of spastic hypertonia., Methods: Soleus H-reflexes were serially recorded in 34 subjects (19 men, mean age 32 years, mean follow-up 1.7 years) during simple continuous mode of CITB delivery. Different fitting methods were explored to determine which function best described changes in H/M ratio with increasing CITB dose. We then calculated effective CITB doses yielding H/M ratios equal to 75, 50, and 25% (ED75, ED50, ED25) of the baseline recorded before the implant in 22 subjects., Results: We found a significant dose-response relationship between the soleus H/M ratio and CITB dose. A two-decay exponential function was the best fit on each side for pooled data, but a general linear model when controlling for subject. The mean ED75, ED50, ED25 were 30, 70, and 110 mcg/day. Logistical regression predicted with high probability that the H/M ratio should be less than 30% at CITB doses above 150 mcg/day., Conclusions: H/M ratio is strongly dependent on CITB dose. It sharply decreases up to 150 mcg/day of CITB followed by a plateau., Significance: Establishing the relationship between the H/M ratio and CITB dose may be useful for dose titration and early identification of an ITB system malfunction.

Objectives: To compare clinical and neurophysiologic responses to intrathecal baclofen (ITB) bolus injection in subjects with spasticity after acquired brain injury., Design: Prospective case series., Setting: Tertiary care rehabilitation center., Participants: Thirty consecutive ITB pump candidates with dysfunctional spasticity caused by traumatic brain injury, hypoxic encephalopathy, or stroke., Intervention: A single 50-microg ITB bolus., Main Outcome Measures: Lower-extremity Ashworth Scale score at 2, 4, and 6 hours after ITB bolus; soleus Hoffmann reflex (H-reflex)/M-wave amplitude (H/M) ratio and abductor hallucis F-wave persistence and F/M ratio at 5 hours. Nonparametric repeated-measures analysis of variance and paired t test were used for statistical analyses., Results: The Ashworth score on the more involved side significantly decreased from 2.4+/-0.7 at baseline to 1.5+/-0.6 and 1.4+/-0.6 at 4- and 6-hour evaluations, respectively (P<.001). H/M ratio significantly decreased bilaterally (more involved side, 62%+/-28% to 14%+/-19%; less involved side, 59%+/-26% to 11%+/-20%; P<.001). F-wave persistence significantly decreased on the more involved side (86%+/-17% to 75%+/-13%, P<.05) with no change in F/M ratio. There was no significant correlation among these outcome measures before or after the ITB bolus injection., Conclusions: H/M ratio is more sensitive than the Ashworth score or F-wave persistence in detecting a physiologic response to ITB bolus. H-reflex is useful for verification of ITB bolus administration, as an adjunct to clinical evaluation, particularly among patients with moderate spasticity at rest or with small changes in Ashworth score. However, potential application of the marked sensitivity of the H-reflex to other clinically challenging situations, such as early detection of possible ITB system malfunction, awaits further investigation.

Objective: To evaluate changes in temporospatial gait parameters after intrathecal baclofen (ITB) bolus administration in patients with spasticity resulting from acquired brain injury by using computerized gait analysis., Design: Case series; before-after intervention. Walking performance and spasticity in lower-extremity muscles were assessed before and at 2, 4, and 6 hours after ITB bolus injection., Setting: Tertiary care free-standing rehabilitation hospital., Participants: Consecutive sample of 28 adults with acquired brain injury due to stroke, trauma, or anoxia., Intervention: A 50-microg ITB bolus injection (2 subjects received 75 microg and 100 microg, respectively)., Main Outcome Measures: Ashworth Scale scores, self-selected gait velocity, stride length, cadence, step length symmetry, step width, and percentage of single support on the more involved side., Results: Ashworth score decreased from 2.0+/-0.5 at baseline to 1.3+/-0.3 at peak response ( P <.001), whereas gait velocity increased from 41+/-26 to 47+/-31 cm/s ( P <.001). Significant improvements also occurred in stride length ( P <.05) and step width ( P <.001). Gait velocity was the most sensitive temporospatial outcome measure for differentiating functional response to ITB bolus injection. Sixteen patients increased velocity by an average of 12 cm/s, representing a mean gain of 33% over their baseline walking speed, while 5 decreased (mean loss, -6 cm/s [52% of baseline]) and 7 were unchanged. There was a significant correlation between baseline velocity and peak change in velocity after ITB bolus ( r =.39, P <.05). Baseline Ashworth score correlated inversely with velocity, stride length, cadence, and percentage single support (r range, -.46 to -.57). No significant correlations were found between change in Ashworth score and change in any temporospatial outcome measure., Conclusions: ITB bolus injection consistently reduces spasticity in ambulatory patients with acquired brain injury but may result in a range of changes in walking performance that can be reliably detected using computerized motion analysis. Velocity appears to be the most sensitive parameter with which to classify individual patient response. The relation between baseline gait velocity and peak change in velocity after bolus administration may have application in predicting the outcome of screening trials for pump implantation; it warrants further investigation.

A number of techniques attempt to objectively quantify various clinical characteristics associated with spastic hypertonia and related motor disorders. These range in cost, complexity, physiologic basis of measured response, and invasiveness. With a greater range of treatment options for spasticity and an increase in the number of centers participating in studies of interventions for spasticity, published reports reflect increasing use of objective quantification techniques. We review studies that highlight the potential utility of neurophysiologic techniques, including the H-reflex, F-wave, and flexion withdrawal reflex, in the objective evaluation of response to intrathecal baclofen administration. The accumulated knowledge suggests that neurophysiologic evaluation is useful for assessing spinal cord responsiveness, and we recommend it as an adjunct to clinical evaluation when judging the overall effectiveness of intrathecal baclofen administration.

There is a range of interventions available in the management of spastic hypertonia among patients with central nervous system injury. Many of these treatment options can be used concurrently with great effectiveness. Although manifestations of spastic hypertonia vary from patient to patient, they usually are not limited to one site. Nevertheless, problematic spastic muscle overactivity may be localized to one or more specific extremities, and these may be referred to as examples of focal dysfunctional spasticity. Botulinum neurotoxin (BTX) intramuscular chemodenervation procedures are an important therapeutic technique in focal spasticity management. Magnitude and duration of response varies with successful selection and localization of targeted muscles, spasticity severity, BTX dosage, and chosen functional goals. In focal dysfunctional spasticity and related motor disorders, BTX injections have demonstrated efficacy and safety when performed by clinicians familiar with the agent, regional anatomy, the specific condition, and patient being treated.

Spasticity from an upper motor neuron syndrome may cause a variety of symptoms that interfere with function. Decisions regarding spasticity treatment are influenced by the chronicity, severity, and distribution of the spasticity; the locus of injury; the presence and severity of co-morbidities; the availability of support; and the goals of treatment. Not all spasticity can or even should be treated; tone reduction is indicated only if spasticity interferes with some level of function, positioning, care, or comfort. Treatment goals should be well outlined before treatment begins. Botulinum toxin may be used to treat focal spasticity as part of an overall treatment plan.

We studied the effect of botulinum toxin A (BTXA) among patients with traumatic brain injury (TBI) and severe spasticity unresponsive to conservative management. Twenty-one consecutive adult patients with severe spasticity involving the wrist and finger flexor musculature were treated with BTXA injection (20 to 40 units per muscle) under EMG guidance. After injection, patients received passive range of motion (ROM) exercise, with modalities and casting as clinically indicated. Outcome measures, including wrist ROM and the modified Ashworth Scale (MAS), were assessed 2 to 4 weeks after injection. Among the respective acute and chronic groups, mean ROM improved 42.9 (p = 0.001) and 36.2 degrees (p < 0.001). Mean MAS rating improved 1.5 (p = 0.01) and 1.47 (p = 0.002) points. There were no significant adverse effects. BTXA, in conjunction with conventional modalities, significantly improves spasticity and ROM in the distal upper extremity musculature of patients with TBI.

Clonidine, a centrally acting alpha 2 receptor adrenergic agonist, has been successfully used as adjunctive therapy in patients with spinal cord injury with problematic spasticity not adequately controlled by recognized spasmolytic agents. A transdermal system providing approximately constant and continuous systemic delivery of clonidine has been recently introduced to enhance patient compliance. However, experience with transdermal clonidine in the management of spasticity is limited. Three cases are presented of patients with spasticity as the result of cervical spinal cord injury, inadequately managed by oral baclofen, in whom transdermal clonidine was administered. Significant improvement in spastic hypertonia was observed in all three cases. Transdermally delivered clonidine was well tolerated, with reported side effects limited to dryness of the mouth.