Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome. Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity. Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6). Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection. Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.

Intrathecal Baclofen Therapy in Patients With Multiple Sclerosis: Improved Outcomes and Reduced Costs Through Identification of Catheter Malfunction.

INTRODUCTION: Two patients previously implanted with intrathecal Baclofen (ITB) pumps for management of intractable spasticity due to multiple sclerosis (MS) were referred to our center for ongoing management of their spasticity. Initial evaluation of these patients revealed high levels of spasticity in the presence of ITB doses 10 times the average daily dose of our other MS patients. CLINICAL FACTS: High doses of ITB required frequent clinical visits and result in high drug and procedure costs. Both patients' daily doses were greater than 1000 mcg/day resulting in clinical visits every 1-2 months with drug and procedure costs ranging from 16 to 23 thousand dollars annually based on Medicare national average pricing for physician's office. Of the 59 MS patients receiving ITB therapy at our institution, the mean, median, and mode daily doses for ITB are 184, 115, and 159 mcg/day, respectively. The high ITB doses in these patients and poor spasticity control raised suspicion for pump/catheter malfunction and prompted immediate troubleshooting. FINDINGS: One patient's catheter was found to be disconnected from the pump and the other's catheter tip was outside the intrathecal space. In both cases, the patients were not receiving the therapy. After pump/catheter replacement, both patients received excellent clinical benefits from ITB at significantly lower daily doses. This reduction in dose resulted in decreased frequency of medication refills (twice annually) which resulted in decreased cost of care (12-19 thousand dollars savings annually per patient). DISCUSSION: These cases illustrate the need for early ITB pump troubleshooting to identify catheter problems, improve efficacy, and avoid unnecessary healthcare costs.

OnabotulinumtoxinA for Lower Limb Spasticity: Guidance From a Delphi Panel Approach.

BACKGROUND: OnabotulinumtoxinA is approved for the treatment of upper and lower limb spasticity in adults. Guidance on common postures and onabotulinumtoxinA injection paradigms for upper limb spasticity has been developed via a Delphi Panel; however, similar guidance for lower limb spasticity has not been established. OBJECTIVE: To define a clinically recommended treatment paradigm for the use of onabotulinumtoxinA for each common posture among patients with poststroke lower limb spasticity (PSLLS) and to identify the most common PSLLS aggregate postures. DESIGN: Clinical experts provided insight regarding onabotulinumtoxinA treatment for PSLLS using an adaptation of the Delphi consensus process. SETTING: Delphi panel. PARTICIPANTS: Ten expert clinicians in neurology and physical medicine and rehabilitation who treat PSLLS. METHODS: A minimum of 2 rounds of anonymous voting occurred for each recommendation until consensus was reached (≥66% agreement). The first round was conducted via a survey; the second round was an in-person meeting. MAIN OUTCOME MEASUREMENTS: Reached consensus on muscle selection for injection, overall and per-muscle dose of onabotulinumtoxinA, number of injection sites/muscle, onabotulinumtoxinA dilution, and use of localization techniques. The most common PSLLS postures were reviewed. Recommendations were tailored toward injectors with less experience. RESULTS: Consensus was reached on targeted subsets of muscles for each posture. Doses ranged from 20 to 150 U for individual muscles and 50 to 300 U for limb postures. OnabotulinumtoxinA dilution 50 U/mL (2:1 ratio) was considered most appropriate but varied based on muscles selected (range, 2:1-4:1). Experts agreed that localization techniques for muscle identification during injection for all postures would be useful. For suboptimal response to injection, all panel members would increase the dose, and the majority (89%) would increase the number of treated muscles. The panel identified 3 common aggregating lower limb postures: (1) equinovarus foot and flexed toes; (2) extended knee and plantar flexed foot/ankle; and (3) plantar flexed foot/ankle and flexed toes. The recommended starting doses for each aggregate posture were 400 U, 400 U, and 300 U, respectively. CONCLUSION: The modified Delphi panel process provided consensus on common muscles and corresponding onabotulinumtoxinA treatment paradigms for postures associated with PSLLS that can be used for guidance in optimizing care delivery. LEVEL OF EVIDENCE: V.

OnabotulinumtoxinA Injection for Poststroke Upper-Limb Spasticity: Guidance for Early Injectors From a Delphi Panel Process.

BACKGROUND: OnabotulinumtoxinA reduces muscle hypertonia associated with poststroke spasticity (PSS). PSS manifests as several common postures. OBJECTIVE: To define treatment paradigms for PSS upper-limb common postures. DESIGN: Modified Delphi method. SETTING: Expert panel. PARTICIPANTS: Ten injectors experienced in the treatment and clinical research of PSS (physiatrists and neurologists) were invited to participate in the Delphi panel. METHODS: The Delphi panel reviewed an electronic worksheet with PSS upper-limb postures to define onabotulinumtoxinA treatment paradigms (Round 1). During Round 2, panel members discussed in person Round 1 results and voted until consensus (≥66% agreement). Recommendations were geared toward those with new or early injection experience. MAIN OUTCOME MEASUREMENTS: Expert consensus on onabotulinumtoxinA treatment parameters for PSS including muscles to inject, dose per muscle and posture, and treatment adjustments for suboptimal response. RESULTS: For each posture, consensus was reached on targeted subsets of muscles. Doses ranged for individual muscles (10-100 U) and total doses per posture (50-200 U). An onabotulinumtoxinA dilution 50 U/mL (2:1 dilution ratio) was considered most appropriate; dilution ratios of 1:1 to 4:1 may be appropriate in some circumstances. The majority (89%) of panel members would increase the dose and/or the number of muscles treated for a suboptimal response to onabotulinumtoxinA. The panel identified 3 common aggregate upper-limb postures: (1) adducted shoulder + flexed elbow + pronated forearm + flexed wrist + clenched fist; (2) flexed elbow + pronated forearm + flexed wrist + clenched fist; and (3) flexed wrist + clenched fist. The recommended starting dose per aggregate was 300 U, 300 U, and 200 U, with a total maximum dose of 400 U, 400 U, and 300 U, respectively. Localization guidance techniques were considered essential for all postures. CONCLUSIONS: Consensus on common muscles and onabotulinumtoxinA treatment paradigms for postures associated with upper-limb PSS was achieved via a modified Delphi method. The purpose of this analysis is to educate early onabotulinumtoxinA injectors rather than provide an evidence-based review. LEVEL OF EVIDENCE: V.

Assessment of Kinematics and Electromyography Following Arthroscopic Single-Tendon Rotator Cuff Repair.

BACKGROUND: The increasing demand for rotator cuff (RC) repair patients to return to work as soon as they are physically able has led to exploration of when this is feasible. Current guidelines from our orthopedic surgery clinic recommend a return to work at 9 weeks postoperation. To more fully define capacity to return to work, the current study was conducted using a unique series of quantitative tools. To date, no study has combined 3-dimensional (3D) motion analysis with electromyography (EMG) assessment during activities of daily living (ADLs), including desk tasks, and commonly prescribed rehabilitation exercise. OBJECTIVE: To apply a quantitative, validated upper extremity model to assess the kinematics and muscle activity of the shoulder following repair of the supraspinatus RC tendon compared to that in healthy shoulders. DESIGN: A prospective, cross-sectional comparison study. SETTING: All participants were evaluated during a single session at the Medical College of Wisconsin Department of Orthopaedic Surgery's Motion Analysis Laboratory. PARTICIPANTS: Ten participants who were 9-12 weeks post-operative repair of a supraspinatus RC tendon tear and 10 participants with healthy shoulders (HS) were evaluated. METHODS: All participants were evaluated with 3D motion analysis using a validated upper extremity model and synchronized EMG. Data from the 2 groups were compared using multivariate Hotelling T2 tests with post hoc analyses based on Welch t-tests. MAIN OUTCOME MEASUREMENTS: Participants' thoracic and thoracohumeral joint kinematics, temporal-spatial parameters, and RC muscle activity were measured by applying a quantitative upper extremity model during 10 ADLs and 3 rehabilitation exercises. These included tasks of hair combing, drinking, writing, computer mouse use, typing, calling, reaching to back pocket, pushing a door open, pulling a door closed, external rotation, internal rotation, and rowing. RESULTS: There were significant differences of the thoracohumeral joint motion in only a few of the tested tasks: comb maximal flexion angle (P = .004), pull door internal/external rotation range of motion (P = .020), reach abduction/adduction range of motion (P = .001), reach flexion/extension range of motion (P = .001), reach extension minimal angle (P = .025), active external rotation maximal angle (P = .012), and active external rotation minimal angle (P = .004). The thorax showed significantly different kinematics of maximal flexion angle during the call (P = .011), mouse (P = .007), and drink tasks (P = .005) between the 2 groups. The EMG data analysis showed significantly increased subscapularis activity in the RC repair group during active external rotation. CONCLUSIONS: Although limited abduction was expected due to repair of the supraspinatus tendon, only a single ADL (reaching to back pocket) had a significantly reduced abduction range of motion. Thoracic motion was shown to be used as a compensatory strategy during seated ADLs. Less flexion of the thorax may create passive shoulder flexion at the thoracohumeral joint in efforts to avoid active flexion. The RC repair group participants were able to accomplish the ADLs within the same time frame and through thoracohumeral joint kinematics similar to those in the healthy shoulder group participants. In summary, this study presents a quantification of the effects of RC repair and rehabilitation on the ability to perform ADLs. It may also point to a need for increased rehabilitation focus on either regaining external rotation strength or range of motion following RC repair to enhance recovery and return to the workforce. LEVEL OF EVIDENCE: III.

Best Practices for Intrathecal Baclofen Therapy: Patient Selection.

INTRODUCTION: When spasticity interferes with comfort, function, activities of daily living, mobility, positioning, or caregiver assistance, patients should be considered for intrathecal baclofen (ITB) therapy. METHODS: An expert panel consulted on best practices. RESULTS: ITB can be considered for problematic spasticity involving muscles/muscle groups during all phases of diseases, including progressive neurologic diseases. ITB alone or with other treatments should not be exclusively reserved for individuals who have failed other approaches. ITB combined with rehabilitation can be effective in certain ambulatory patients. ITB is also highly effective in managing spasticity in children, who may suffer limb deformity, joint dislocation, and poor motor function from spasticity and muscle tightness on the growing musculoskeletal system. Spasticity management often allows individuals to achieve higher function. When cognition is impaired, ITB controls spasticity without the cognitive side effects of some oral medications. Goal setting addresses expectations and treatment in the framework of pathology, impairment, and disability. ITB is contraindicated in patients with hypersensitivity to baclofen, which is rare, or active infection. Some patients with an adverse reaction to oral baclofen may be mistakenly classified as having an allergic reaction and may benefit from ITB. Relative contraindications include unrealistic goals, unmanageable mental health issues, psychosocial factors affecting compliance, and financial burden. Vascular shunting for hydrocephalus is not a contraindication, but concurrent use may affect cerebrospinal fluid flow. Seizures or prior abdominal or pelvic surgery should be discussed before proceeding to an ITB screening test. CONCLUSIONS: ITB should be considered when spasticity interferes with comfort or function.

Unraveling the Role of Huntingtin in Breast Cancer Metastasis.

BACKGROUND: Huntingtin (HTT) is mutated in Huntington's disease but is ubiquitously expressed, and mutant HTT influences cancer progression. We investigated wild-type HTT function during breast cancer. METHODS: We analyzed HTT and ZO1 expression as well as the HTT phosphoserine 421-activated form (S421-P-HTT) in human breast cancer tissues by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. We performed in vitro migration and invasion assays as well as in vivo tail vein injections of the metastatic 4T1 cells in BALB/c mice (n = 11 per group). We analyzed tumor progression in knock-in mice with modified S421 crossed with the MMTV-PyVT mammary cancer model (at least n = 12 per group). Data were analyzed with unpaired t tests, analysis of variance, Pearson or Spearman correlation, and Mann Whitney or Kruskal-Wallis tests. All statistical tests were two-sided. RESULTS: Levels of HTT and of S421-P-HTT are abnormally low in poorly differentiated and metastatic human breast cancers. HTT expression is downregulated in invasive compared with in situ carcinoma (P < .001). In BALB/c mice, silencing of HTT promotes lung colonization by a metastatic mammary cancer cell line (P = .005) and S421-unphosphorylatable-HTT accelerates cancer progression. HTT interacts with ZO1 and regulates both its expression and its localization to tight junctions. In human breast tumors, the patterns of HTT and ZO1 expression are similar (Pearson correlation coefficient = 0.66, P < .001). CONCLUSIONS: HTT may inhibit breast tumor dissemination through maintenance of ZO1 at tight junctions. Downregulation of HTT transcript and protein levels is a prognostic factor for poor prognosis and metastasis development.

Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival.

BACKGROUND: A randomized phase II study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel. Final survival analyses and updated safety results are reported. PATIENTS AND METHODS: Three hundred two patients with no previous chemotherapy for MBC were randomized to receive nab-paclitaxel 300 mg/m(2) q3w, nab-paclitaxel 100 mg/m(2) or 150 mg/m(2) the first 3 of 4 weeks (qw 3/4), or docetaxel 100 mg/m(2) q3w. The trial was powered for analyses of antitumor activity and safety. RESULTS: Treatment with nab-paclitaxel 150 mg/m(2) qw 3/4 resulted in a median overall survival (OS) of 33.8 months compared with 22.2, 27.7, and 26.6 months for nab-paclitaxel 100 mg/m(2) qw 3/4, nab-paclitaxel 300 mg/m(2) q3w, and docetaxel, respectively (overall P = .047). Patients receiving 150 mg/m(2)nab-paclitaxel had prolonged median OS compared with those in the 100 mg/m(2)nab-paclitaxel arm (hazard ratio, 0.575; P = .008). A trend toward a longer OS was noted in the 150 mg/m(2)nab-paclitaxel arm versus docetaxel arm (hazard ratio, 0.688). Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms compared with docetaxel. CONCLUSIONS: Consistent with previously published efficacy results, these data suggest that 150 mg/m(2) qw 3/4 may represent the most clinically efficacious nab-paclitaxel dosing regimen for patients with no previous chemotherapy for MBC. A phase III trial confirming these results would be necessary and prudent before widespread adoption of the 150 mg/m(2) dose in clinical practice.

The underutilization of intrathecal baclofen in poststroke spasticity.

Stroke is one of the leading causes of adult disability in the United States, with a reported prevalence of 6.4 million people. Spasticity is one of the clinical features of the upper motor neuron syndrome seen after a stroke. The prevalence of spasticity after a stroke ranges from 17% to 42.6%, and an average of two-thirds of people with spasticity have upper and lower extremity involvement. Oral medications and botulinum neurotoxin injections are current treatments for problematic spasticity. However, these treatments are often limited by side effects or dose ceilings. Intrathecal baclofen (ITB) is a proven method for the management of disabling spasticity from multiple etiologies. Studies have demonstrated improved mobility, activities of daily living, and quality of life in spastic poststroke patients. Despite the benefits of ITB, fewer than 1% of stroke patients with severe disabling spasticity are being treated with ITB. This article will review the prevalence of severe poststroke spasticity and the rate of ITB use and will discuss reasons for its limited use in stroke survivors.

Incidence and identification of intrathecal baclofen catheter malfunction.

OBJECTIVE: A retrospective chart review was undertaken of cases of intrathecal baclofen (ITB) pump/catheter malfunction and the diagnostic tests performed to identify the problem. An internal review was performed to develop a diagnostic flow chart to have a systematic method for identifying ITB pump and catheter complications. DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. PARTICIPANTS: A total of 167 adult patients currently followed in outpatient clinic with intractable spasticity and ITB pump implanted between January 1994 and May 2009. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Catheter malfunction was identified either by anterior/posterior and lateral thoracic/lumbar radiographs, fluoroscopic guided side port access, contrast agent injection followed by CT (fluoro/CT) scan, or indium radionuclide studies. RESULTS: During the study period, 33 patients had 37 catheter revisions. Radiographs were obtained in all cases; fluoro/CT studies in 22, and indium studies in 6. Four cases had both fluoro/CT and indium studies. A total of 13 cases (35.1%) were diagnosed with radiographs; 9 cases (24.3%) were diagnosed by inability to withdraw cerebral spinal fluid from the side port; 13 cases (35.1%) were diagnosed with fluoro/CT studies; and 2 cases (5.4%) were diagnosed with indium studies. Fluoro/CT studies demonstrated subdural catheter location in 7 cases. A total of 2 of 4 cases with both fluoro/CT and indium studies had normal-appearing indium scans and an abnormal fluoro/CT study confirming subdural catheter placement. CONCLUSIONS: On the basis of an internal review of the diagnostic studies used to identify patients with suspected ITB pump/catheter malfunction, a troubleshooting flow chart was developed. Timely identification and correction of potential ITB complications could improve the clinical effectiveness of ITB and may reduce unnecessary health-care costs.

Design and validation of low-cost assistive glove for hand assessment and therapy during activity of daily living-focused robotic stroke therapy.

Hand and arm impairment is common after stroke. Robotic stroke therapy will be more effective if hand and upper-arm training is integrated to help users practice reaching and grasping tasks. This article presents the design, development, and validation of a low-cost, functional electrical stimulation grasp-assistive glove for use with task-oriented robotic stroke therapy. Our glove measures grasp aperture while a user completes simple-to-complex real-life activities, and when combined with an integrated functional electrical stimulator, it assists in hand opening and closing. A key function is a new grasp-aperture prediction model, which uses the position of the end-effectors of two planar robots to define the distance between the thumb and index finger. We validated the accuracy and repeatability of the glove and its capability to assist in grasping. Results from five nondisabled subjects indicated that the glove is accurate and repeatable for both static hand-open and -closed tasks when compared with goniometric measures and for dynamic reach-to-grasp tasks when compared with motion analysis measures. Results from five subjects with stroke showed that with the glove, they could open their hands but without it could not. We present a glove that is a low-cost solution for in vivo grasp measurement and assistance.

Spastic hypertonia and movement disorders: pathophysiology, clinical presentation, and quantification.

A delayed consequence of a lesion affecting the upper motor neuron pathways is the appearance of some forms of motor overactivity, including spasticity. Many of these are caused by hyperexcitability of spinal reflexes, such as stretch reflexes (spasticity, tendon hyperreflexia) or flexor withdrawal reflexes (flexor spasms), and are elicited at rest by sensory stimulation. Spastic co-contraction is probably attributable to failure of reciprocal inhibition; it occurs only during active voluntary movement and constrains such movement. The basic underlying mechanism of these changes is not clear, although a change in the balance between the inhibitory and excitatory supraspinal upper motor neuron pathways toward net excitation most likely contributes. Increased intrinsic excitability of the alpha motor neurons is another possible factor. Spastic dystonia is most often seen as the presence of tonic muscle contraction in the absence of voluntary movement or spinal reflex activation, and the underlying mechanisms are obscure. Prolonged shortening of tissues, either because of weakness or muscle contraction, leads to stiffness of the soft tissues, which contributes to hypertonia and is thus self-perpetuating, and ultimately to contracture with fixed shortening. Some of these forms of motor overactivity produce involuntary movements (hyperkinetic), eg, flexor spasms, whereas others impair movement (hypokinetic), either voluntary movement, eg, spastic co-contraction, or passive movement, eg, spasticity. Quantification has mostly focused on hypertonia, that is, increased resistance at rest to passive movement. In the upper motor neuron syndrome, hypertonia could be caused by a combination of spasticity, spastic dystonia, and soft tissue stiffness (rheologic changes). Some measures, such as the Ashworth or Modified Ashworth Scales, quantify hypertonia but are very poor at distinguishing between spasticity and soft tissue stiffness. Another, the Tardieu Scale, is better at making this distinction, but quantification of the spasticity portion of hypertonia remains difficult, at least in a clinical setting.

Multijoint reflex responses to constant-velocity volitional movements of the stroke elbow.

Multijoint reflex coupling could impact the voluntary control of functional arm movements in people post stroke. The multijoint responses to active-assist, constant-velocity movements of the elbow joint were measured in 14 individuals post stroke and 9 neurologically intact controls. Resulting responses in the stroke group illustrated a change in the reflex coupling of the elbow and shoulder muscles compared with passive perturbations of the spastic elbow. Voluntary effort during constant-velocity elbow extension resulted in reflex shoulder abduction, differing from the reflex coupling observed between the elbow flexors and shoulder adductors observed during passive elbow extension. These results suggest that post stroke, voluntary drive alters reflex coupling of the elbow and shoulder. Flexion of the elbow during active-assist also resulted in reflex coupling. Shoulder abduction torque decreased with constant-velocity flexion of the elbow; however, no net adduction was observed at the end of the perturbation. Shoulder flexion/extension and internal/external rotation torque responses demonstrated similar modulations to imposed active-assist perturbations of the elbow in subjects post stroke. Responses were absent during passive perturbations of the control elbow; however, shoulder torque modulations were observed during constant-velocity, active-assist tasks. The active-assist response patterns in controls were similar to stroke subjects during the extension task but opposite during flexion of the elbow. This study provides evidence of a neural coupling between elbow and shoulder muscles and a modulation of this coupling during voluntary drive of the spastic arm.

Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin.

Mutant huntingtin accumulates in the neuronal nuclei and processes, which suggests that its subcellular localization is critical for the pathology of Huntington's disease (HD). However, the contribution of cytoplasmic mutant huntingtin and its aggregates in neuronal processes (neuropil aggregates) has not been rigorously explored. We generated an intracellular antibody (intrabody) whose binding to a unique epitope of human huntingtin is enhanced by polyglutamine expansion. This intrabody decreases the cytotoxicity of mutant huntingtin and its distribution in neuronal processes. When expressed in the striatum of HD mice via adenoviral infection, the intrabody reduces neuropil aggregate formation and ameliorates neurological symptoms. Interaction of the intrabody with mutant huntingtin increases the ubiquitination of cytoplasmic huntingtin and its degradation. These findings suggest that the intrabody reduces the specific neurotoxicity of cytoplasmic mutant huntingtin and its associated neurological symptoms by preventing the accumulation of mutant huntingtin in neuronal processes and promoting its clearance in the cytoplasm.

Multijoint reflexes of the stroke arm: neural coupling of the elbow and shoulder.

The reflex torque responses of the elbow and shoulder to constant velocity angular extensions of the full comfortable range of the spastic elbow were measured in 16 people with unilateral stroke and 6 neurologically intact controls in order to identify the interjoint reflex coupling that occurs after stroke. The resulting responses showed a substantial reflex torque at the elbow and shoulder in subjects with stroke, with 12 of the 16 subjects producing adduction of the shoulder in response to passive extension of the elbow. The presence of simultaneous shoulder flexion torque with elbow flexion torque and with an identical waveform indicated an active role of biarticular elbow/shoulder flexors, such as the biceps. As the biceps muscle produces a shoulder abduction moment, shoulder adduction produced during elbow extension was thought to be associated with neural rather than biomechanical coupling. These results suggest that spasticity in people with stroke is more complex than its traditional perception as a hyperexcitable stretch reflex, and includes potent heteronymous reflex pathways. The reflex coupling observed between the shoulder and elbow should be considered in the diagnosis and clinical management of spasticity. The potential impact of this reflex on the coordination of volitional arm movements will be examined in future studies.

Intrathecal baclofen management of poststroke spastic hypertonia: implications for function and quality of life.

OBJECTIVES: To evaluate the impact of intrathecal baclofen (ITB) on function and quality of life (QOL) and to obtain efficacy and safety data in poststroke spastic hypertonia. DESIGN: Prospective open-label multicenter trial with follow-up at 3 and 12 months. SETTING: Twenty-four stroke treatment centers in the United States. PARTICIPANTS: Ninety-four stroke participants (age range, 24-82 y) with spastic hypertonia. Seventy-four participants underwent ITB pump implantation. INTERVENTION: Participants were implanted with an ITB pump. MAIN OUTCOME MEASURES: FIM instrument and QOL (Sickness Impact Profile [SIP]) changes, spastic hypertonia (Ashworth Scale), and safety. RESULTS: FIM scores improved overall in repeated-measures analysis of variance (ANOVA) (P = .005) and by 3.00 +/- 7.69 (P = .001) at 3 months and by 2.86 +/- 10.13 (P = .017) at 12 months. Significant improvements in SIP scores were noted overall (repeated-measures ANOVA, P < .001) and at 3 (P = .003) and 12 months (P < .001). The combined average Ashworth Scale score of the upper and lower limbs decreased by 1.27 +/- 0.76 (P < .001) at 3 months and by 1.39 +/- 0.73 (P < .001) at 12 months from baseline, which was significant overall (repeated-measures ANOVA, P<.001). Strength in the unaffected side did not change overall (repeated-measures ANOVA, P = .321) or at either 3 (P = .553) or 12 months (P = .462). Minimal adverse events and device complications were reported. CONCLUSIONS: There was significant improvement in function, QOL, and spastic hypertonia at 3 and 12 months after implant, without adversely affecting muscle strength of the unaffected limbs. Data suggest that ITB therapy is a safe and efficacious treatment for spastic hypertonia resulting from stroke.