John R. McGuire

Traditional pharmacological treatments for spasticity. Part II: General and regional treatments.

Systemic pharmacologic treatments may be indicated in conditions in which the distribution of muscle overactivity is diffuse. Antispastic drugs act in the CNS either by suppression of excitation (glutamate), enhancement of inhibition (GABA, glycine), or a combination of the two. Only four drugs are currently approved by the US FDA as antispactic agents: baclofen, diazepam, dantrolene soduim, and tizanidine. However, there are a number of other drugs available with proven antispastic action. This chapter reviews the pharmacology, physiology of action, dosage, and results from controlled clinical trails on side effects, efficacy, and indications for 21 drugs in several categories. Categories reviewed include agents acting through the GABAergic system (baclofen, benzodiazepines, piracetam, progabide); drugs affecting ion flux (dantrolene sodium, lamotrigine, riluzole); drugs acting on monoamines (tizanidine, clonidine, thymozamine, beta blockers, and cyproheptadine); drugs acting on excitatory amino acids (orphenadrine citrate); cannabinoids; inhibitory neuromediators; and other miscellaneous agents. The technique, advantages, and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitations appear throughout the controlled studies reviewed: the lock of quantitive and sensitive functional assessment and the lack of comparative trials between different agents. In the majority of trials in which meaningful functional assessment was included, the study drug failed to improve function, even though the antispastic action was significant. Placebo‐controled trails of virtually all major centrally acting antispastic agents have shown that sedation, reduction of global performance, and muscle weakness are frequent side effects. It appears preferable to use centrally acting drugs such as baclofen, tizanidine, and diazepam in spasticity of spinal origin (spinal cord injury and multiple sclerosis), whereas dantrolene sodium, due to its primary perpherial mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain in jury) where sensitivity to sedating effects is generally higher. Intrathecal adminstration of antispastic drugs has been used mainly in cases of muscle overactivity occurring primarily in the lower limbs in nonambulatory, severely disbled patients, but new indications may emerge in spasticity of cerebral orgin. Intrathecal therapy is an invasive procedure involving long‐term implantation of a foreign device, and the potential disadvantages must be weighted against the level of disability in each patient and the resistance to other forms of antispastic therapy.In all forms of treatment of muscle overactivity, one must distinguish disability in each patient and the resistance to other forms of antispastic therapy. In all forms of treatment of muscle overactivity, one must distinguish between two different goals of therapy: improvement of active function and improvement of hygiene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic drugs may be more acceptable when the primary goal of therapy is hygiene and comfort than when active function is a priority.

Traditional pharmacological treatments for spasticity part I: Local treatments

Spasticity is a velocity‐dependent increase in stretch reflex activity. It is one of the forms of muscle overactivity that may affect patients with damage to the central nervous system. Spasticity monitoring is relevant to function because the degree of spasticity may relect the intensity of other disabling types of muscle overactivity, such as unwanted antagonistic co‐contractions, permanent muscle activity in the absence of any stretch or volitional command (spastic dystonia), or inappropriate responses to cutaneous or vegetative inputs. In addition, spasticity, like other muscle overactivity, can cause muscle shortening, which is another significant source of disability. Finally, spasticity is the only form of muscle overactivity easily quantifiable at the bedside. Under the name pharmacological treatments of spasiticity, we understand the use of agents designed to reduce all types of muscle overactivity, by reducing excitability of motor pathways, at the level of the central nervous system, the neuromuscular junctions, or the muscle. Pharmacologic treatment should be an adjunct to muscle lengthening and training of antagonists. Localized muscle overactivity of specific muscle groups is often seen in a number of common pathologies, including stroke and traumatic brain injury. In these cases, we favor the use of local treatments in those muscles where overactivity is most disabling, by injection into muscle (neuromuscular block) or close to the nerve supplying the muscle (perineural block). Two types of local agents have been used in addition to the newly emerged botulinum toxin: local anesthetics (lidocaine and congeners), with a fully reversible action of short duration, and alcohols (ethanol and phenol), with a longer duration of action. Local anesthetics block both afferent and efferent messages. The onset of action is within minutes and duration of action varies between one and several hours according to the agent used. Their use requires resuscitation equipment available close by. When a long‐lasting blocking agent is being considered, we favor the use of transient blocks with local anesthetics for therapeutic tests or diagnostic procedures to answer the following questions: Can function be improved by the block? What are the roles played by overactivity and contracture in the impairment of function? Which muscle is contributing to pathologic posturing? What is the true level of performance of antagonistic muscles? A short‐acting anesthetic can also serve as preparation to casting or as an analgesic for intramuscular injections of other antispastic treatment. Alcohol and phenol provide long‐term chemical neurolysis through destruction of peripheral nerve. Experience with ethanol is more developed in children using intramuscular injection, while experience with phenol is greater in adults with perineural injection. In both cases, there are anecdotal reports of efficacy but studies have rarely been controlled. Side effects are numerous and include pain during injection, chronic dysesthesia and chronic pain, and episodes of local or regional vascular complications by vessel toxicity. In the absence of controlled studies, a theoretical comparison of neurolytic agents with botulinum toxin is proposed. Neurolytic agents may by preferred to botulinum toxin on a number of grounds, including earlier onset, potentially longer duration of effect, lower cost, and easier storage.

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.

Stroke Rehabilitation: Clinical Predictors of Resource Utilization

OBJECTIVE To identify predictors of rehabilitation hospital resource utilization for patients with stroke, using demographic, medical, and functional information available on admission. DESIGN Statistical analysis of data prospectively collected from stroke rehabilitation patients. SETTING Large, urban, academic freestanding rehabilitation facility. PARTICIPANTS A total of 945 stroke patients consecutively admitted for acute inpatient rehabilitation. MAIN OUTCOME MEASURES Resource utilization was measured by rehabilitation length of stay (LOS) and mean hospital charge per day (CPD). METHODS Independent variables were organized into categories derived from four consecutive phases of clinical assessment: (1) patient referral information, (2) acute hospital record review and patient history, (3) physical examination, and (4) functional assessment. Predictors for LOS and CPD were identified separately using four stepwise multiple linear regression analyses starting with variables from the first category and adding new category data for each subsequent analysis. RESULTS Severe neurologic impairment, as measured by Rasch-converted NIH stroke scale and lower Rasch-converted motor measure of the Functional Independence Measure (FIM) instrument predicted longer LOS (F2,824 = 231.9, p < .001). Lower Rasch-converted motor FIM instrument measure, tracheostomy, feeding tube, and a history of pneumonia, coronary artery disease, or renal failure predicted higher CPD (F6,820 = 90.2, p < .001). CONCLUSION Stroke rehabilitation LOS and CPD are predicted by different factors. Severe impairment and motor disability are the main predictors of longer LOS; motor disability and medical comorbidities predict higher CPD. These findings will help clinicians anticipate resource needs of stroke rehabilitation patients using medical history, physical examination, and functional assessment.

REORGANIZATION OF FLEXION REFLEXES IN THE UPPER EXTREMITY OF HEMIPARETIC SUBJECTS

We examined spatiotemporal abnormalities in the flexor reflex response in the impaired upper extremity of hemiparetic subjects. Electrical stimulation was used to elicit flexion reflexes in both upper extremities of 8 hemiparetic brain‐injured and 6 control subjects. Electromyograms (EMGs) were recorded from 12 arm muscles, and reflex forces and moments were recorded at the wrist with a load cell, and converted to shoulder and elbow torques. We found that the onset of reflex torque and EMG was delayed in the impaired arm and delays were greater at the shoulder than at the elbow. The normal reflex torque response consisted of elbow flexion, shoulder extension, and shoulder adduction. In contrast, in the impaired limb shoulder, flexion torque was observed in 7 subjects and shoulder abduction in 3. The delays in reflex onset and altered torque patterns in the impaired arm may be related to the abnormal movement synergies observed following stroke.

Poststroke Spasticity Management

Poststroke spasticity (PSS) is a common complication associated with other signs and symptoms of the upper motor neuron syndrome, including agonist/antagonist co-contraction, weakness, and lack of coordination. Together, they result in impairments and functional problems that can predispose to costly complications. The goal of PSS management should take into consideration not only reduction of muscle hypertonia but also the impact of PSS on function and well-being. Therapeutic interventions focus on peripheral and central strategies, such as physical techniques to increase muscle length through stretching and pharmacological modulation. Although there are few comparative studies on the superiority of one method over another, it appears that optimal management of PSS involves a combined and coordinated compendium of therapies that encompass cost-effective pharmacological and surgical interventions, along with rehabilitative efforts. Spasticity, commonly defined as “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome,”1 is a common complication of stroke. It contributes to the impairments and disabilities that negatively impact functional recovery. Consequently, PSS, along with weakness and lack of coordination, result in gait abnormalities and problems with arm use. In addition to functional limitations, spasticity, when inappropriately treated, may lead to reduced quality of life, increased pain, and joint contractures. Three community-based studies that followed-up stroke survivors for 3 to 12 months reported an incidence of PSS between 17% and 43%.2–4 Certain factors are recognized as predictors of PSS: stroke lesions in the brain stem; hemorrhagic stroke and younger age;5 and severe paresis and hemihypesthesia at stroke onset.3 To quantify the full impact of PSS, assessment should include a measure of passive stretch, volitional movement, and active/passive function.6,7 The benefit of …

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.

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. Muscle Nerve, 2007

Incidence and identification of intrathecal baclofen catheter malfunction.

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.

The Underutilization of Intrathecal Baclofen in Poststroke Spasticity

Abstract 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.