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UMNSMuscle overactivity in the upper motor neuron syndrome Advisory Editors Alberto Esquenazi, MD
EtiologyThe upper motor neuron (UMN) syndrome is a collective term for motor behaviors that occur in patients who, for a variety of reasons, have sustained lesions to the descending corticospinal system (Mayer and Esquenazi, 2003). Lesions producing UMN dysfunction may occur in patients with cerebral palsy, in patients with neurodegenerative diseases such as multiple sclerosis, and in those who have experienced stroke, traumatic brain or spinal cord injury, or hypoxic encephalopathy at the level of the cortex, the internal capsule, the brain stem, or the spinal cord. Classic descriptions of the UMN syndrome have identified a number of positive and negative signs (Table 1, Figure 1)—combinations of which often impair performance of many of the motor skills required for normal mobility, activities of daily living, and independence, thereby adversely affecting a person’s quality of life. PhenomenologyTable 1. Positive and negative motor signs in the UMN syndrome.
Negative signs (“signs of absence”) are characterized by paresis, impaired voluntary control, and loss of dexterity, particularly finger dexterity (Mayer and Esquenazi, 2003; Carr and Shepherd, 1998). Negative signs of UMN result from deficient voluntary muscle activity and include muscle weakness, slow and effortful movement, loss of dexterity, impaired control and coordination of movement, and easy fatigability (Mayer and Esquenazi, 2003; Lance, 1980). Muscle weakness refers to difficulty generating and sustaining the necessary force for effective motor performance and can occur because of loss of motor unit activation, changes in the order of motor unit recruitment, and changes in motor unit firing rates (Mayer and Esquenazi, 2003; Rosenfalck and Andreassen, 1980). At the level of whole muscles, impairment in muscle force generation and the timing of that force relative to the task at hand may occur. Differential weakness also occurs within the same muscle group. Weakness is only a part of the story. The loss of selective control of voluntary movement probably accounts for more disability than frank weakness. Upper motoneuron paresis is unlike lower motoneuron weakness in which power loss impairs limb usage. In UMN, the loss of selective activation and control of limb segments, in part and as a whole, undermines voluntary goal-directed actions. Moreover, obligatory “synergies” (patterned movements of a relatively fixed nature) tend to impose features that flood the patient’s efforts to produce selective activation and control of action. Positive signs (“signs of presence”) are phenomena characterized by a variety of muscle overactivity types (Mayer and Esquenazi, 2003; Gracies, 2001; Mayer, 1997; Lance, 1980; Lance, 1984). For example, patients with hemiplegia commonly exhibit a flexed elbow attitude in the upper extremity along with equinus in the lower extremity. Phasic tendon jerk reflexes are typically increased, and tonic stretch reflexes generate a velocity-dependent resistance as the examiner passively stretches muscle groups crossing a joint at different rates of stretch. Figure 1. Pathophysiology of impairment.
Modified from Gracies JM. Pathophysiology of impairment in patients with spasticity and use of stretch as a treatment for spastic hypertonia. Phys Med Rehab Clin N Am. 2001;12:747-768 with permission. A number of different types of muscle overactivity are found in the UMN syndrome, including the following (Mayer, 1997; Gracies, 2001; Sheean, 2003):
Exaggerated tonic and phasic stretch reflexesSpasticitySpasticity is a term linked to the stretch reflex of skeletal muscle. It has a specific definition with respect to stretch reflexes, but it has often been used, confusingly, as a collective term for all positive signs, many of which are not based on stretch reflexes. Strictly speaking, the term “spasticity” refers to an increase in excitability of phasic and tonic muscle stretch reflexes that is present in most patients with an UMN lesion. Clinically, the defining characteristic of spasticity is excessive resistance of muscle to passive stretch. It is the nature of spastic resistance to increase as the examiner increases the velocity of stretch (Figure 2). Faster rates of stretch result in a sudden increase in resistance felt by the examiner after stretch has commenced. The clinical character of spastic stretch reflexes has been succinctly described by Peter Nathan: "Spasticity is a condition in which the stretch reflexes that are normally latent become obvious. The tendon reflexes have a lowered threshold to tap, the response of the tapped muscle is increased, and usually muscles besides the tapped one respond; tonic stretch reflexes are affected in the same way" (Nathan, 1973). The quick whack of a tendon tap results in a brief jerk response that is aptly classified as a phasic reflex because the output jerk response is phasic (transient). In contrast, longer duration passive stretch of a spastic muscle induces sustained tension for the duration of stretch and reflects underlying stretch reflex activity of the tonic type. Figure 2. Velocity sensitivity of spasticity.
As the rate of passive stretch increases, so does the resistance to stretch, as reflected by an increase in electromyographic activity of all muscles in the figure. Courtesy of Nathaniel Mayer. Physiologically, afferent information regarding stretch of the muscle and its muscle spindle is signaled to the central nervous system by group Ia and group II afferents. However, there has been no evidence to suggest that spindle afferent activity is increased in spastic patients (Burke, 1983). Rather, the central excitatory state of the cord appears to be high (Sheean, 2001). A number of theories of spasticity emphasize the concept of signal "mishandling" at the level of the spinal cord. For example, Delwaide points out that the normal mechanism of presynaptic inhibition in the spinal cord is altered for patients with hyperreflexia. Ia afferent activity from the muscle spindle is normally adjusted at a pre-motoneuronal level depending on supraspinal facilitatory influences and preceding Ia afferent discharges. In spasticity, according to Delwaide, the interneuron responsible for presynaptic inhibition becomes less active because of a reduction of supraspinal facilitatory influences. Accordingly, the stretch reflex of the patient with hyperreflexia is no longer subject to tonic inhibitory control by the mechanism of presynaptic inhibition (Delwaide, 1993). Instead, all proprioceptive afferent impulses are able to gain direct access to alpha motor neurons and hyperreflexia results. Other theories of signal "mishandling" at the level of the spinal cord include Veale, Mark, and Rees’ work on Renshaw system disinhibition and Jankowska’s work on abnormal handling of group II afferent activity from the muscle spindle by a specific interneuronal system in the spinal cord ( Veale et al, 1973; Jankowska et al, 1994). What is common to these theories is an enhanced central excitatory state that promotes exaggerated motor responses to ordinary cord inputs. Lance characterized spasticity as an increase in velocity-dependent tonic stretch reflexes along with exaggerated (phasic) tendon jerk responses ( Lance, 1980). The term “phasic” means time varying. “Tonic” has a time invariant quality, although time scales are always relative. The use of “phasic” and “tonic” in published literature can be confusing, however, because some authors describe the input stimulus as phasic or tonic whereas others describe the output response as phasic or tonic. Tonic stretch reflexes discussed by Lance refer to the output response of a muscle group that is being stretched at different rates of stretch. The output jerk response of a tendon tap is an example of a phasic stretch reflex. At the bedside, phasic stretch reflexes are tested by tendon taps whereas tonic stretch reflexes are tested by passively stretching a muscle group through the full (available) range of motion, repeating this maneuver a number of times to vary the velocity of stretch during repetition. When a patient is spastic, resistance to stretch experienced by the examiner will increase as the rate of stretch is increased. Physiologically, electromyographic (EMG) activity is generated by the stretched muscle, producing tension that opposes the stretching imposed by the examiner (Figure 3). Clinically, spasticity predisposes the patient to the development of disabling contractures (Mayer, 1997). Figure 3. Passive stretch of elbow flexors in a patient with an upper motoneuron syndrome produced stretch reflex electromyographic (EMG) activity in the brachioradialis muscle.
Tonic EMG activity, lasting for the duration of muscle stretch, is characteristic of spasticity. Reproduced from Mayer NH, Esquenazi A. Muscle overactivity and movement dysfunction in the upper motoneuron syndrome. Phys Med Rehabil Clin N Am. 2003;14:855-883 with permission. Dr. Mayer describes the pathophysiology of spasticity (Windows Media) Stretch reflex activity may also be triggered during voluntary movement when a shortening contraction produced by agonist muscles on one side of a joint is necessarily accompanied by lengthening (stretching) of antagonist muscles on the other side of the joint. Paretic patients often move slowly; therefore, low velocities of stretch during voluntary effort may not engage a spastic response from antagonist muscles. In addition to the tonic stretch reflex, hyperactivity of phasic stretch reflexes (exaggerated tendon jerks and clonus) is also considered spastic phenomena. Clonus is an exaggerated phasic stretch reflex characterized by repetitive, rhythmic contractions observed in one or more muscles of a single limb segment or even multiple limb segments. Clonus can be generated by rapid passive stretch of muscle groups, by cutaneous stimuli (eg, cold or noxious stimuli), or during muscle stretch produced in the course of a voluntary movement (Mayer and Herman, 2004). The frequency of clonus is approximately 6-8 Hz; that is, bursts of EMG at these frequencies can be seen in a stretched muscle; sometimes, clonic bursts of EMG alternate between agonists and antagonists (Figure 4). Figure 4. Clonus frequency.
Courtesy of Nathaniel Mayer. Co-contractionWhen an agonist muscle is involved in a voluntary effort, contraction of antagonist muscles may occur simultaneously, resulting in the phenomenon of co-contraction. Co-contraction of an antagonist muscle may act as a restraining force during movement (Figure 5). In this regard, co-contraction is a phenomenon that can be confused with spasticity. Co-contraction is characterized by simultaneous activation of agonist and antagonist muscles during voluntary movement. Spasticity depends on muscle stretch, and its onset occurs after movement has begun when some stretch-related displacement has already taken place. Simultaneous activation of agonists and antagonists is more easily observed on EMG records. Some authors believe that a lengthening co-contracting antagonist muscle can be aggravated by co-existing spasticity and, therefore, refer to the combination as spastic co-contraction (Gracies, 2005). Figure 5. Overactivity of antagonist muscles recorded during voluntary agonist effort.
Electromyographic activity reveals co-contraction in the biceps and brachioradialis (antagonist muscles) during the extension phase of voluntary alternating elbow movements; this co-contraction impairs extension generated by the medial triceps agonist muscle. Courtesy of Nathaniel Mayer. Associated reactionsAssociated reactions were first described by Walshe in 1923 as “released postural reactions deprived of voluntary control” ( Walshe, 1923). “Synkinesis” is a term used by Bourbonnais more recently ( Bourbonnais, 1995). An associated reaction refers to involuntary activity in one limb that is associated with a voluntary movement effort made by other limbs. Associated reactions may be due to disinhibited spread of voluntary motor activity into a limb affected by a UMN lesion. Figure 6a shows a patient with left hemiparesis due to a brain gunshot wound attempting to readjust his sitting position by pushing down on the wheelchair’s armrest with his right arm. The patient was unable to use the left upper extremity in this task because voluntary control was severely impaired. Dynamic EMG of elbow musculature during this activity revealed high EMG recruitment in flexor and extensor muscles about the elbow (Figure 6b). Despite elbow extensor activity, the photograph reveals flexed elbow posturing, indicating that a net balance of muscle forces about the elbow favored flexion. The intensity of an associated reaction may depend on how much voluntary effort is made. Dewald and Rymer thought that impaired descending supraspinal commands were involved in generating associated reactions ( Dewald and Rymer, 1993). They hypothesized that unaffected bulbospinalmotor pathways may have taken over the role of damaged UMN tracts during the transmission of descending voluntary commands. Figure 6a. Figure 6b.
A, a patient with left hemiparesis due to a brain gunshot wound attempting to readjust his sitting position by pushing down on the wheelchair’s armrest with his right arm. B, Dynamic EMG of elbow musculature during this activity revealed high EMG recruitment in flexor and extensor muscles about the elbow. Courtesy of Nathaniel Mayer. Flexor and extensor spasmsOther positive symptoms of UMN include flexor and extensor spasms. The flexor reflex, a polysynaptic reflex that results in flexor muscle contraction, is elicited by afferent stimuli collectively known as flexor reflex afferents (Whitlock, 1990). These afferents include exteroceptive cutaneous receptors responding to touch, temperature, and pressure, nociceptors responding to painful stimuli, secondary endings from muscle spindles (group II afferents) and free nerve endings scattered ubiquitously over muscles that generate slowly conducting afferent activity in group III and IV axons. The polysynaptic flexor reflex has a prolonged latency (more than twice that of a monosynaptic tendon jerk) due to slow afferent conduction to the cord and also to central delay. In the cord, flexor reflex afferent activity travels up and down to synapse in the internuncial pool, a system of spinal interneurons that is influenced by inputs coming from peripheral as well as central sources, including the brainstem. Compared with segmental stretch reflexes, the time course of polysynaptic flexor reflexes is slower, and, unlike segmental stretch reflexes, flexor reflexes represent coordinated activity of motoneuron pools spanning many segments, resulting in muscle contraction across several joints, sometimes bilaterally. By typically recruiting flexor muscles across several joints, the flexor reflex is an example of an interjoint reflex that has tissue protective value by enabling quick withdrawal from noxious stimuli. Extensor reflexes are also polysynaptic and interjoint in nature and may serve certain support functions. Flexor and extensor reflexes may be core substrate for more complex coordinated patterns such as locomotor stepping generators. According to Lance, a characteristic feature of UMN, both physiologic and clinical, is release of flexor reflex afferents (Lance, 1984). After UMN, particularly after spinal cord lesions, release of inhibitory descending influences makes reflexes such as the flexor reflex more pronounced. When complaints are traced to flexor and extensor spasms, it is likely that spasms represent disinhibited flexor and extensor reflexes. Overt stimuli can trigger flexor and extensor spasms, or they may be set off by covert stimuli such as a full bladder, a stool-distended bowel, a tight diaper, unseen skin ischemia from sitting or lying in one position too long, or other unobserved or masked sensory sources. Clinically, flexor reflexes can range from the familiar toe response of the Babinski sign to a mass flexor reflex characterized by intense, often painful interjoint flexion with spread to the abdominals. Patients may refer to these reflexes as “a muscle spasm,” but they mean whole limb involvement rather than focal spasm of a single muscle group. In UMN lesions, the elicitation threshold of the flexor reflex is reduced, the intensity of muscle contraction for the same stimulus input is increased, and interjoint components of the reflex are often expanded (ie, more muscles and more joints are recruited). Spastic dystoniaSpastic dystonia is a phenomenon that may contribute to limb deformities, muscle shortening, and disfigurement; it is characterized by tonic muscle contraction at rest, in the absence of passive stretch or voluntary effort (Gracies, 2001; Sheean, 2003; Mayer and Herman, 2004). Spastic dystonia is associated with tonic EMG activity associated with particular clinical postures (Figure 7a). Spastic dystonia is not the result of an aberrant spinal reflex, as shown experimentally by its continued presence after dorsal rhizotomy in the monkey (Denny-Brown, 1966), although it can be influenced by any stretch imposed on the affected muscle (Sheean, 2003). Denny-Brown produced spastic dystonia in monkeys by means of various ablative cortical and subcortical lesions (Denny-Brown, 1966). Electromyographic recordings revealed persistent muscle activity associated with specific postures. Transection of dorsal roots did not eliminate activity, suggesting to Denny-Brown that the persistent dystonic activity was of supraspinal, not segmental, origin. Some clinicians think that dystonic activity in patients with UMNS is stretch sensitive and hence use the term “spastic dystonia” (Figure 7b). Figure 7a. Spastic dystonia.
This patient with an upper motoneuron syndrome and left hemiparesis was asked to stand quietly “at rest.” The flexed posture of the elbow was persistent and the patient readily acknowledged that she was not making any voluntary effort to hold this position. Persistent elbow flexion was her chief complaint. An EMG record during “rest” revealed persistent activity in many muscles about the elbow and forearm. Courtesy of Nathaniel Mayer. Figure 7b. Passive stretch of the elbow flexors of the patient in Figure 7a revealed that her dystonic activity was stretch-sensitive.
According to Denny-Brown, the dystonic phenomenon (activity at rest) is of supraspinal origin and is mediated efferently, not afferently. However, the presence of stretch sensitivity suggests that some patients may also have a component of spasticity. Courtesy of Nathaniel Mayer. Rheologic abnormalitiesAlthough muscle overactivity is a dynamic force and key driver of deformity in the patient with the UMN syndrome, static forces generated by the stiffness or associated rheologic (resistive) properties of soft tissues also create or contribute to deformity in the UMN syndrome (Gracies, 2001; Sheean, 2003; Mayer, 1997). Joint immobilization caused by muscle weakness early after a UMN lesion along with overactivity brought on later decreases the compliance and elasticity of soft tissues. Such rheologic abnormalities further increase the resistance to passive stretch and reduce the range of motion around a joint. Although muscles on both sides of a joint may be overactive, a net balance of forces favoring one direction may result in permanent shortening of specific muscles, leading to permanent fixation at a shortened length (contracture). Contracture, a static phenomenon that has nothing to do with muscle contraction, requires a different treatment strategy from muscle overactivity. Altered balance of forces governing limb patternsMuscle strength is differentially affected by the UMN lesion, resulting in an imbalance of activity within muscle groups that leads to the clinical signs of the UMN syndrome. Positive signs (such as co-contraction and associated reactions) can contribute to an altered balance of muscle forces and soft tissue changes during limb posturing and movement and can further exacerbate the negative signs (ie, weakness and loss of dexterity of the syndrome) (Mayer and Esquenazi, 2003). Together, the positive and negative phenomena and the rheologic properties of muscle and tissues affected by the UMN syndrome produce unbalanced forces that ultimately affect patient functionality (Mayer, 1997). An understanding of the interplay of muscle forces contributing to deformity can help physicians comprehend the functional impact of the syndrome on patient activity and the potential roles for differing management strategies and therapeutic options. Pathophysiology Although much of the pathophysiology of the UMN syndrome is poorly understood, two models have been proposed to explain, in part, the unbalanced activity of muscle groups that occur in the UMN syndrome: the so-called “spinal” and “cerebral” models (Mayer, 1997). The key concepts behind these two models of muscle overactivity are summarized here. Box 1. The Spinal and Cerebral Models of Muscle Overactivity in the UMN Syndrome Spinal Model
Cerebral Model
Clinical presentationClinical patterns of UMN dysfunction such as a flexed elbow or an equinovarus foot develop as a result of muscle overactivity generated by the different types of positive phenomena described in previous sections. Commonly seen patterns of UMN dysfunctionThe symptoms of UMN often lead to the development of stereotypical patterns of deformity secondary to agonist muscle weakness, antagonist muscle spasticity, and changes in the rheologic (stiffness) properties of spastic muscles (Mayer et al, 1997). The patterns of UMN dysfunction are commonly associated with complaints of disfigurement and pain. Understanding the patterns of UMN dysfunction and identification of the contributing muscles can serve as a basis for several available treatment strategies including chemodenervation with botulinum neurotoxin (BoNT), neurolysis, and neuro-orthopedic surgery (Mayer and Esquenazi, 2003; Sheean 2003). Adducted/internally rotated shoulderMuscles that potentially contribute to the adducted/internally rotated shoulder pattern include the pectoralis major, teres major, latissimus dorsi, anterior deltoid, and subscapularis. The patient typically presents with the arm held tightly against the chest wall. The elbow is often flexed and, because of the internal rotation of the shoulder, the hand and forearm are draped on top of the chest anteriorly (Figure 8). Patients complain of shoulder stiffness and painful passive range of motion because the large adductor muscles of the shoulder can generate strong spastic tension when stretched. Severe adduction posturing and the resultant restricted and resisted motion hinder bathing, washing, deodorant application, and upper body dressing. Skin irritation, maceration, and malodor in the axilla may occur. Co-contraction of adductors and extensors may compromise voluntary abduction and limit voluntary forward reach, restricting a patient’s ability to reach targets in the environment and on the body or to apply directed upper extremity force (such as that required to stabilize or push an object). Figure 8. The adducted, internally rotated shoulder frequently has restricted shoulder flexion as well.
Pectoralis major, latissimus dorsi, teres major, and long head of triceps are often overactive. Courtesy of Nathaniel Mayer. Overactivity in muscles relevant to adducted/internally rotated shoulder can be treated with chemodenervation, neurolysis, and, when contracture is present, orthopedic interventions such as myotendinous lengthening. Phenol neurolysis and chemodenervation with BoNT can be used for large proximal muscles. Flexed elbowMuscles that potentially contribute to the flexed elbow deformity include the biceps, brachialis, and brachioradialis. Secondary contributory muscles might include the extensor carpi radialis and pronator teres. The patient typically presents with persistent elbow flexion during sitting (Figure 9), standing, and especially walking. Prolonged elbow flexion posturing is frequently associated with contracture. Stiffness is a frequently reported sensation. Patients complain that their elbow “rides up” (flexes markedly when they stand up and walk) and that their flexed elbow commonly hooks door frames, furniture, and even people. Shaking secondary to elbow clonus may also occur. Severe flexion posturing can lead to skin maceration, breakdown, and malodor in the antecubital fossa. Dressing can be difficult. Reaching for objects and bringing them to the body, closing a drawer or a door, and walking with a walker or crutch may be profoundly restricted. Figure 9. Flexed elbow.
The muscles contributing to flexed elbow are amenable to chemodenervation, neurolysis, and orthopedic lengthening. Courtesy of Nathaniel Mayer. Pronated forearmMuscles that potentially contribute to the pronated forearm include the pronator teres and the pronator quadratus. Both pronators can show varying degrees of volition, co-contraction, muscle overactivity, and spasticity. The patient typically presents with a forearm that is “pronated” fully, with pronation posturing more common than supination posturing (Figure 10). The pronated forearm is commonly associated with a flexed elbow. Passive stretching of stiff pronators is often uncomfortable or painful. Overactive pronator muscles inhibit supination; thus activities that depend on active pronation/supination movements, including many instrumental activities of daily living, become restricted. Persistent pronation makes it difficult for a person to reach underhand to a target; persistent supination impairs reaching for targets that require overhand reach. Activities such as turning the hand palm side up for fingernail trimming, using eating utensils, washing one’s face, reaching for a glass, and shaking hands become difficult. Figure 10. Pronated forearm.
The pronated forearm receives contributions from pronator teres and pronator quadratus . Courtesy of Nathaniel Mayer. Serial casting to diminish pronator contracture is difficult to implement, but both pronator muscles are amenable to chemodenervation, neurolysis, and orthopedic lengthening. Flexed wristMuscles that potentially contribute to the flexed wrist deformity include the flexor carpi radialis, flexor carpi ulnaris, palmaris longus, flexor digitorum sublimis, flexor digitorum profundus, and, in cases where there is ulnar deviation, the extensor carpi ulnaris. The patient typically presents with a wrist that is flexed, sometimes with radial deviation, sometimes with ulnar deviation (Figure 11). In many cases, a flexed wrist is associated with clenched fist deformity. The extrinsic finger flexors cross the wrist anterior to its axis of rotation and therefore act as accessory wrist flexors themselves. Passive stretching of stiff flexors can be uncomfortable or painful. Associated compression of the median nerve can produce carpal tunnel syndrome with hand pain. Severe flexion of the wrist hinders passive exercises, dressing, and washing. Wrist flexion posturing restricts hand placement during reaching, impairs positioning of objects held by the hand, and weakens grip strength. Figure 11. Flexed wrist.
The flexed wrist may receive contributions from the wrist flexors including palmaris longus, flexor carpi radialis, and ulnaris. The superficial and deep finger flexors may also contribute to wrist flexion, as they cross in front of the axis of rotation of the wrist. Courtesy of Nathaniel Mayer. Muscles contributing to flexed wrist are amenable to chemodenervation, neurolysis, and, in some cases, orthopedic myotendinous lengthening. Clenched fistMuscles that potentially contribute to the clenched fist pattern include the flexor digitorum sublimis and the flexor digitorum profundus. Both sets of extrinsic finger flexors can show varying degrees of volition, co-contraction, and spasticity. The patient typically presents with fingers flexed into the palm (Figure 12). Many patients have little or no active finger extension. The patient is unable to perform grasping an object or has limited hand opening during reach. In many cases, clenched fist is also associated with thumb-in-palm deformity. Fingernails tend to dig into the palmar skin causing pain. Access to the palm for washing and drying is difficult, and when access is chronically restricted skin maceration, breakdown, and malodor can develop. Putting on and wearing gloves and hand splints can be difficult. Grasp, manipulation, and release of objects from the hand is inhibited, thus restricting the accomplishment of activities of daily living. Chronically flexed fingers are likely to develop muscle, skin, and joint contractures. Figure 12a. Figure 12b.
Figure 12. Clenched fist associated with overactive flexor digitorum profundus. Clenched fist associated with overactive flexor digitorum profundus (a) is linked to flexion of the distal interphalangeal (DIP) joint. Clenched fist associated with overactive flexor digitorum superficialis is linked to proximal interphalangeal joint flexion and DIP extension (b). Courtesy of Nathaniel Mayer. The clenched fist deformity is amenable to treatment with chemodenervation and, in some cases, orthopedic lengthening. Chemodenervation with BoNT is especially useful because the affected small muscles of the hand are readily accessible for injection and only small doses of BoNT are required for efficacy. Thumb-in-palm deformityMuscles that potentially contribute to the thumb-in-palm deformity include flexor pollicis longus, flexor pollicis brevis, adductor pollicis, and first dorsal interosseous. The patient’s thumb is pulled into the palm and cannot extend during the reach phase of grasping an object (Figure 13). The thumb does not function well during handgrip and is limited in its capacity to serve as a post for the fingers. Putting on and wearing gloves or resting on hand splints can be difficult. Thumb extension and abduction that open up the palm before grasp are compromised, as is activation of common grasp patterns such as three-jaw chuck, lateral grasp, and tip pinch. Figure 13. Thumb-in-palm deformity.
Flexor pollicis longus, flexor pollicis brevis, adductor pollicis, and 1 st dorsal interosseous may contribute to closing off access to the webspace. Courtesy of Nathaniel Mayer. The muscles contributing to thumb-in-palm deformity are amenable to chemodenervation and, in selected cases, orthopedic lengthening. Chemodenervation with BoNT is especially useful because the affected small muscles of the hand are readily accessible for injection and only small doses of BoNT are required for efficacy. Excessive hip flexionMuscles that potentially contribute to an excessively flexed hip include the iliopsoas, the rectus femoris, and pectineus. The adductor longus and brevis may also contribute to hip flexion. The patient presents with sustained hip flexion that interferes with positioning in a chair or wheelchair, sexual activity, perineal care, and gait (Figure 14). Chronic flexion posturing leads to flexion contracture and may also contribute to knee flexion deformity. Patients complain of hip flexor spasms. Excessive hip flexion during the stance phase of gait interferes with limb advancement and results in a shortened contralateral step. Patients with bilateral muscle overactivity of the hip flexors may walk with a crouched gait pattern. The hips remain flexed throughout swing and stance. Crouched gait resulting from hip flexion can lead to compensatory knee flexion and continuous use of quadriceps, hip extensors, and calf muscles to maintain balance with increased effort and fatigue. Figure 14. Flexed hip.
Courtesy of Nathaniel Mayer. Chemodenervation of the iliacus and rectus femoris is feasible. Translumbar instillation of neurolytic agents to block a spastic psoas major muscle is also a useful technique. Muscles relevant to the flexed hip deformity are also amenable to orthopedic interventions. Adducted thighsMuscles that potentially contribute to adducted thigh include the adductor longus and brevis, adductor magnus, gracilis, iliopsoas, and pectineus. The patient presents with unilateral or bilateral scissoring thighs (Figure 15). Scissoring thighs interfere with perineal care, sexual intimacy, sitting, transfers, standing, and walking. Patients complain of stiffness. Severe hip adduction interferes with limb clearance and advancement during the swing phase of gait. The base of support is narrow during the stance phase with potential impairment in balance that usually requires an upper extremity assistive device. Figure 15. Adducted thighs.
Courtesy of Nathaniel Mayer. When many muscles are involved in producing adduction of the thigh, neurolysis of the obturator nerve might be more efficient than chemodenervation, which is restricted by dose limitations. Chemodenervation or neurolytic agents may help provide access to perineal care and other functions in addition to improvement in positioning and active gait function. Effective orthopedic interventions include transaction of the anterior branch of the obturator nerve (for dynamic deformity) and proximal release of the adductors (for static contracture). Stiff (extended) kneeMuscles that potentially contribute to stiff knee include rectus femoris, vastus intermedius, vastus medialis and lateralis, gluteus maximus, iliopsoas, and the hamstrings in their role as hip extensors. The stiff or extended knee typically presents as a gait deviation with the knee remaining extended through most of the gait cycle (Figure 16). A stiff knee is particularly problematic during the preswing, initial swing, and midswing subphases of the gait cycle. The limb becomes functionally longer because it remains extended throughout the swing phase. Toe drag in early swing can cause tripping and falling. To achieve limb clearance of the floor during swing phase, the patient attempts to compensate for a relative increase in limb length by ipsilateral circumduction or hiking of the pelvis or by contralateral vaulting, often at the expense of increased energy consumption. A stiff knee might fail to relax while the patient is seated and also requires elevated leg support. Standing and transfers are problematic. Figure 16. Stiff knee.
Courtesy of Nathaniel Mayer. Lidocaine motor point blocks to identified muscles may reveal whether “weakening” strategies would be helpful in reducing stiff knee gait. Chemodenervation or neurolytic agents may then be used as a longer-term treatment option if indicated by the lidocaine blocks. Orthopedic intervention is also an option. The rectus femoris is a primary target for correcting stiff knee gait via transfer to the gracilis tendon on the posteromedial aspect of the knee. The extension force of the rectus femoris muscle across the knee is thus rerouted to serve as a corrective force acting to flex the knee. Flexed kneeMuscles that potentially contribute to flexed knee include the medial and lateral hamstrings. Weakness of the quadriceps or gastrocnemius exacerbates this condition. Hamstring contracture is likely after chronic muscle overactivity. The patient presents with a knee that remains flexed throughout the swing and stance phases of gait (Figure 17). A flexed knee during the stance phase requires compensatory ipsilateral hip flexion and might also induce contralateral hip and knee flexion (crouch gait pattern). Stretching of overactive hamstrings can be painful. Sitting and wheelchair positioning are hampered. During standing transfers body weight support is difficult because the body’s weight line causes the knees to flex even more, making the patient prone to collapse. A lack of full knee extension during terminal swing severely limits limb advancement, and short steps can result. The hamstring is a two-joint muscle. Overactive hamstrings can flex the knees or act posterior to the hip joints, causing the trunk to extend. As a result, seated patients with flexed knee tend to slide forward in their wheelchairs. Figure 17. Flexed knee.
Courtesy of Nathaniel Mayer. Targeted chemodenervation of hamstrings during the period of motor recovery may facilitate the use of other treatment modalities such as stretching and serial casting. Neurolysis is not usually considered, given the many motor branches of the hamstrings. Orthopedic lengthening is a viable treatment option for chronically flexed knee. Equinovarus footMuscles that can potentially contribute to equinovarus foot include tibialis anterior, tibialis posterior, the long toe flexors, medial and lateral gastrocnemius, soleus, extensor hallucis longus, and peroneus longus. Equinovarus foot, the most common pathologic posture seen in the lower extremity, presents as the foot and ankle turned down and in (Figure 18). Toe curling or toe clawing might co-exist. When lying down or sitting, the lateral border of equinovarus foot may be compressed against the mattress, bed rail, floor, or foot pedal of a wheelchair. Callus often develops. Skin breakdown over the fifth metatarsal head may develop. Severe deformity makes putting on and wearing shoes difficult or impossible. During the stance phase of gait, the patient’s initial contact with the ground occurs on the lateral border of the forefoot. The patient often complains of pain and instability on bearing weight in the region of the fifth metatarsal head. Dorsiflexion motion is limited during early and mid-stance and prevents forward progression of the tibia over the stationary foot, resulting in hyperextension thrust of the knee and dysrhythmic and restrained forward progression of body mass. Lift-off rather than push-off occurs in terminal stance and a short contralateral step results. Knee flexion during preswing is deviant and an early swing foot drag may occur. Figure 18. Equinovarus foot.
Courtesy of Nathaniel Mayer. Equinovarus with toe curling results in an inadequate base of support that leads to unstable gait. A goal of treatment is to stabilize the patient’s base of support. Given the many variations of muscular pathology that may contribute to equinovarus foot, treatment of the deformity should be specifically targeted. In general, equinovarus with toe curling is amenable to direct treatment with chemodenervation. Nerve blocks, chemodenervation, and serial casting are effective means of stretching a tight heel cord conservatively. Neurolysis is not recommended because of the risk of injury to multiple small sensory fibers in the area. Chemodenervation may also be used as adjunctive treatment to facilitate the use of other treatment modalities such as serial casting, manual stretching, and therapeutic exercise. Several orthopedic interventions have been used to stabilize the patient’s base of support, including Achilles tendon lengthening, split anterior tibialis tendon transfer, and lengthening of the tibialis posterior. Release of the toe flexors with transfer to the os calcis helps reinforce weak calf muscles in terminal stance. Striatal toe (hitchhiker’s great toe)An overactive extensor hallucis longus contributes to striatal toe. Persistent hyperextension is a common problem in UMN that can be seen in isolation or with some degree of equinovarus foot deformity (Figure 19). Patients complain of pain at the tip of the great toe and under the first metatarsal head during the stance phase of gait. Patients are often unable to wear shoes except by cutting out the toe box. Figure 19. Striatal toe (hitchhiker’s great toe).
Courtesy of Nathaniel Mayer. Chemodenervation of the extensor hallucis longus is effective. Orthopedic section of the extensor hallucis tendon is also effective. If co-contraction of the flexor hallucis longus is also present, section of both tendons or chemodenervation of both muscles will be required. Classification of clinical problems associated with the UMN syndromePatients with the UMN syndrome typically experience signs and symptoms—such as muscle spasms, clonus, pain, and postural disfigurement—that have a negative impact on functional ability and the normal execution of motor tasks requiring good mobility and dexterity; thus impaired quality of life and loss of independence are among the key issues facing patients with the UMN syndrome. The management plans and goals described in later sections aim to redress this imbalance and restore a degree of improved function and quality of life. Distribution of problems must be closely noted to allow for categorization of disabilities and impairments into the following broad groupings (Figure 20) (Brin et al, 1997):
Figure 20. Examples of focal (left), multifocal (center), and regional (right) muscle impairments seen in patients with the UMN syndrome.
Courtesy of Nathaniel Mayer. Initial assessment of the patient with the UMN syndrome requires an evaluation of symptoms, along with an assessment of how both active and passive patient functions are affected by the positive and negative signs of the syndrome (Box 2). Box 2. Classification of Clinical Problems in the UMN Syndrome SymptomaticPassive Function
Interference with transfersActive Function
When assessing active function, it is important to consider exactly how muscle overactivity impairs active movement and in particular to assess whether muscle performance can be improved if opposing abnormal muscle forces are reduced or removed. Similarly, when evaluating passive function, key consideration must be given to assessing which muscles are contributing to pathological postures and evaluating which muscles and soft tissue contracture impair movement. The treating physician must assess the level of assistance and performance time required for patients to attend to basic functions such as dressing, washing, toilet care, and feeding. Clinical descriptions coupled with photographs can be used to ascertain the status of skin and its integrity. For the clinical assessment of symptomatic problems, a variety of scales or assessment tools can be used (Table 2).
Although clinical description of the patient’s physical condition, dysfunction, and status remains the mainstay of patient assessment, the addition of diagnostic nerve or motor point blocks or dynamic electromyography (EMG) can be a valuable tool. Dynamic EMG can help to 1) identify target muscles for treatment, 2) evaluate muscle activity that could not otherwise be detected by clinical examination, and 3) assist in establishing whether resistance to passive stretch is attributable to muscle overactivity (spasticity) or to rheologic abnormalities (contractures). Integrated management of the UMN syndromeCare of the patient with the UMN syndrome typically requires a team approach and a management plan that integrates discussion and selection of goals with the patient and caregiver, along with physical and occupational therapies using surgical, pharmacological, and/or neuromusculoskeletal orthopedic approaches. Setting management goalsA primary management goal is to promote a greater degree of patient independence and mobility (Table 3). By allowing patients to adopt easier positions for the everyday tasks of eating, dressing, and attending to personal hygiene, marked improvements in well being and quality of life are possible. Improved posture and less restricted mobility assist with more comfortable sitting and sleeping positions. A more independent and functional patient is also one who requires less caregiver support. Table 3. Setting and coordinating patient and physician goals for the UMN syndrome management plan is a crucial first step in patient management.
Treatments that ease the symptoms of stiffness, spasm, and pain and lessen disfigurement have the potential to change the outlook for patients with the UMN syndrome and contribute to prevention of future medical complications. Global managementAn important first step in patient care (Box 3) is to reduce or eliminate any noxious stimuli—for example, ingrown toenails—that could exacerbate muscle overactivity and spastic responses (Brin et al, 1997; Sheean, 2003). Box 3. Key Elements of Management of Muscle Overactivity.
All patients stand to benefit from exercise programs that may be administered at home or guided by a therapist. Such programs should emphasize stretching techniques, muscle strengthening, and motor training. Occupational therapy allows patients to deal with any handicaps and difficulties and complements the use of adaptive and orthotic devices designed to improve patient function. Management guidanceChoosing the most appropriate multimodal management program for a given patient requires consideration of the cause and nature of the UMN syndrome signs. Positive signs of the UMN syndrome are generally more amenable to pharmacologic management than negative signs. Treatment options will differ according to the problem distribution (Brin et al, 1997; Sheean, 2003). Focal and multifocal problems will benefit from “peripheral” treatment, while regional and generalized muscle overactivity may respond better to “central” therapies. The terms “peripheral” and “central” therapies are used to group treatments according to site of action and ability to target particular muscle groups (Table 4). Physical interventions such as serial casting and bracing, physiotherapy, and surgical interventions are also included within the category of “peripheral” treatment options. Table 4. Treatment options for management of muscle overactivity in the UMN syndrome.
CNS, central nervous system. The most effective treatment strategies usually involve a combination of procedures, interventions, and drug treatments tailored according to the needs of the individual patient. The Royal College of Physicians in the UK has produced management algorithms for adult spasticity to help guide and direct use of central and peripheral treatments (Figure 21). Figure 21. An algorithm for the management of the UMN syndrome.
Patients with severe rheologic changes (contracture) may benefit from orthopedic surgery, and those with evident muscle overactivity can achieve improved outcomes through use of therapies designed to target specific muscle groups contributing to dysfunction and deformity. The generally accepted view is that an integrated approach to patient management, rather than a sequential approach, allows for optimal improvements in patient function and well being. The following sections describe options for the pharmacological management of the UMN syndrome. Pharmacological management of the UMN syndromeTreatment options for managing muscle overactivity in the UMN syndrome can be broadly categorized as either systemic or peripheral. The peripheral agents used to provide more targeted treatment can be further subdivided into regionalized or localized therapies. Central treatment optionsSystemic agents exert diffuse effects on muscle tone, resulting in a generalized muscle relaxation effect that may be appropriate when an overall reduction in body tone is required to improve the patient’s condition (Goldstein, 2001). Through a variety of different mechanisms, systemic agents used in UMN syndrome management inhibit the actions of excitatory neurotransmitters or augment inhibitory neurotransmission in the central nervous system, thus inducing an overall reduction in motor tone (Table 5) (Gracies et al, 1997b; Nance and Young, 1999). Systemic therapies are often associated with generalized sedation, weakness, dizziness, and fatigue, which are attributable to the nonspecific mode of action of these agents on nervous function. Treatment with systemic agents is normally initiated as oral therapy, whereas intrathecal drug administration is considered only when oral regimens fail (Satkunam, 2003). Table 5. Oral and intrathecal drug treatments commonly used in the management of generalized muscle overactivity: a summary of the mode of action of drugs and their adverse effect profile.
CNS, central nervous system; GABA, gamma-aminobutyric acid. Adapted from Satkunam LE. Rehabilitation medicine: 3. Management of adult spasticity. CMAJ. 2003;169:1173-1179. Baclofen is one of the most widely used systemic treatments for generalized muscle overactivity and spasticity and may be given orally or administered by electronic intrathecal pump. Proper and careful candidate selection is the key to the successful use of baclofen, which can be associated with local complications (eg, injection- or pump-site infection), systemic problems (eg, drowsiness, respiratory depression), and troublesome withdrawal symptoms following treatment discontinuation (Satkunam, 2003; Gracies et al, 1997b). Oral agents may have significant adverse effects that can increase the risk of falls and fractures, particularly when used in elderly patients (Esquenazi, 2004). Peripheral treatment optionsOptions for more regionalized control of muscle overactivity in the UMN syndrome includetheuse oflocal anesthetic agents such as lidocaine, bupivacaine, and etidocaine, which afford short-duration nerve block. Distillation of local anesthetics into discrete neuronal segments can produce regionalized relief from muscle overactivity for 2 to 8 hours. This method also provides a valuable diagnostic tool to determine precisely which muscle groups and nerve pathways are affected by the UMN syndrome or to determine the presence of a soft tissue contracture (Gracies et al, 1997a; Catterall and Mackie, 1996; Esquenazi and Mayer, 2004). Short-acting local anesthetics are therefore often used as a means of “therapeutic testing” before selection of drug treatments that offer a more lasting chemodenervation of the motor pathways responsible for the pathophysiology of focal or multifocal muscle overactivity (Gracies et al, 1997a). Focal chemodenervationThe primary objective of chemodenervation is to restore a more appropriate balance between the agonist and antagonist forces governing muscle tone. Localized use of neurolytic agents such as phenol and alcohol can achieve muscle relaxation for an estimated 8 weeks to 36 months (Gracies et al, 1997a). Botulinum neurotoxin types A and B (BoNT-A, BoNT-B), which selectively block acetylcholine release from motor neurons, can produce chemodenervation effects lasting for 3 to 6 months (Brin, 1997; Brin et al, 1997; Bell and Williams, 2003; Brashear et al, 2002, Brashear et al, 2003; Gordon et al, 2002). Mechanism of action of neurolytic agentsPhenol (3%-5%) and alcohol (35%-60%) act on neuronal tissue to cause a nonspecific denaturation and disruption of normal tissue function (Gracies et al, 1997a). Phenol denatures protein and demyelinates axons when applied to specific nerves, thereby degenerating tissue and interrupting neuronal transmission. Although peripheral nerves will regenerate following a phenol or alcohol insult, rates of recovery can vary widely. Skill is required in using neurolytic agents. Scar tissue will develop at the injection site as a result of the injection and will eventually make reinjection more difficult. Phenol is more widely used than alcohol, and although the use of these drugs has declined since the introduction of BoNT, phenol continues to be employed in managing severe overactivity in large muscles such as the thigh. Despite a variable duration of action, the effects of phenol can be seen almost immediately after the injection, with reductions in overactivity and stretch reflex more evident than changes in muscle strength (Gracies et al, 1997a). The potential adverse effects associated with the use of phenol and alcohol include burning pain on injection, pain and dysesthesias lasting for several weeks after injection, and injection-site damage of a chronic nature that can preclude or complicate repeated treatments using these agents (Gracies et al, 1997a). Chemodenervation with BoNTBoNT is a preferred treatment for focal or multifocal muscle overactivity in the UMN syndrome. The bacterium Clostridium botulinum produces seven distinct serological forms of BoNT, labelled types A through G (A, B, C1, D, E, F, and G), all of which inhibit acetylcholine release (Brin, 1997). The neurotoxin is synthesized as a relatively inactive single-chain polypeptide with a molecular mass of approximately 150 kDa; its posttranslational activation occurs on proteolytic cleavage into the 100-kDa heavy and 50-kDa light chains, which remain linked by a disulfide bond. BoNT-A and BoNT-B are available for clinical use in the management of the UMN syndrome, although BoNT-A is the most widely studied and applied serotype for therapeutic purposes (Brin et al, 2002). BoNT-A is manufactured as BOTOX ® (Allergan, Inc., Irvine, CA) and as Dysport ® (Ipsen, Slough, UK). BoNT-A (BOTOX ®) is indicated in the United States for the treatment of glabellar lines, cervical dystonia, blepharospasm, hyperhidrosis, and strabismus. Dysport ®, which is currently unavailable in the United States, and Botox® are used in Europe and in some Asian and Latin American countries. Although BOTOX ® and Dysport ® are both BoNT-A preparations, these two treatments should not be considered interchangeable because of differences in their potency, efficacy, and formulation. The BoNT-B serotype, available as Myobloc ® (Neurobloc ® in Europe; Solstice Neurosciences, Malvern, PA) is indicated in the United States for treatment of cervical dystonia. It, too, has a unique formulation and potency with shorter effect and is not to be used interchangeably with other BoNT serotypes (Lang, 2003). BoNT in the treatment of muscle overactivityMechanism of actionThe clinical effectiveness of BoNT as a treatment for muscle overactivity in the UMN syndrome relates to its unique mode of action at the neuromuscular junction. When BoNT is injected into a target tissue the heavy chain of the neurotoxin binds to glycoprotein structures specifically found on cholinergic nerve terminals. Specificity for these docking glycoproteins explains, in part, BoNT’s high selectivity for cholinergic synapses. After internalization, the neurotoxin light chain selectively cleaves one of several proteins required for the formation of the SNARE* complex that mediates release of acetylcholine into the neuromuscular junction. The target proteins may vary among the BoNT serotypes: BoNT-A cleaves synaptosomal-associated proteins of 25 kDa (SNAP-25), and BoNT-B cleaves vesicle-associated membrane protein (VAMP), thereby preventing the docking of the acetylcholine vesicle on the inner surface of the cellular membrane and acetylcholine exocytosis (Figure 22). The resulting temporary inhibition of muscle contraction forms the basis of the therapeutic application of BoNT (Dolly, 2003). Without a functional and releasable store of acetylcholine, the motor neuron cannot affect sustained muscle contraction, resulting in a previously overactive muscle becoming relaxed and tension free. Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein binds avidly to preformed ternary complex, which, in turn, allows the association of NSF, hence the term SNAP receptors (SNAREs). The SNARE complex serves an essential role in exocytosis by bringing the vesicle membrane into close apposition to the plasma membrane. Dr. Dolly discusses the action of BoNT-A at the cellular level. (Windows Media ) Figure 22. Mechanism of action of BoNTs.
BoNT binds to the neuronal cell membrane at the nerve terminus and enters the neuron by endocytosis. The light chain of BoNT cleaves specific sites on the SNARE proteins, preventing complete assembly of the synaptic fusion complex and thereby blocking acetylcholine release. Serotypes B, D, F, and G cleave synaptobrevin; types A, C, and E cleave SNAP-25; and type C cleaves syntaxin. Without acetylcholine release, the muscle is unable to contract. Reproduced from Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon. Medical and public health management. JAMA. 2001;285:1059-1010 with permission. Although the inhibitory action of BoNT-A renders the motor neuron inactive, the effects are temporary and fully reversible; over time synaptic plasticity and remodeling return the affected neuron to normal functioning (Dolly, 2003). Importantly, dose adjustment and optimal injection technique can ensure a degree of precision over the management of muscle overactivity. Skilled targeted administration of an appropriate dose of BoNT-A allows some nerve terminals to remain unaffected, preserving some muscle strength and, at times, unmasking function. Clinical benefits of BoNT-A therapyThe highly selective mode of action of BoNT-A enables a precise and effective reduction in muscle overactivity. The onset of benefits (Box 4)—such as reduced muscle tone and improvements in mobility, limb positioning, and levels of patient activity—can be seen within a matter of 1 to 3 days after injection of BoNT-A and are usually maximal within 3 to 4 weeks and sustained for 3 to 6 months (Brin, 1997; Brin et al, 1997; Bell and Williams, 2003; Brashear et al, 2002, Brashear et al, 2004; Gordon et al, 2002). Box 4. Overview of the Clinical Benefits of BoNT-A Treatment of Overactive Muscle in the UMN Syndrome.
In comparison with phenol, BoNT-A offers titratable and adjustable control of muscle activity with a better side effect and tolerability profile (Table 6). Table 6. Clinical features of BoNT-A and phenol as treatments for focal and multifocal muscle overactivity in the UMN syndrome based on published data.
BoNT-A is a preferred treatment for focal and multifocal muscle overactivity in a variety of different patient groups with the UMN syndrome ( Sheean, 2003). BoNT-A’s emerging role as an adjunctive treatment is seen as an integral part of the management of regional or generalized muscle overactivity; use of BoNT-A–targeted injections can complement central therapies . Clinical evidence for use of BoNT-A in the UMN syndromeThe literature in support of BoNT therapy for muscle overactivity continues to expand. To date there are more clinical studies of BoNT-A than of BoNT-B in patients with the UMN syndrome (Pidcock, 2004; Brin et al, 2002). In a 12-week, multicenter, double-blind, placebo-controlled study, Brashear and colleagues (Brashear et al, 2002) evaluated the effects of BoNT-A (BOTOX®) in 126 patients with increased flexor tone in the wrist and fingers following a stroke. Patients were randomized to receive either placebo (n = 62) or BoNT-A (n = 64) at a dose of 200 to 240 units (U), given as 50 U per muscle in four wrist and finger muscles, with an optional 20 U per muscle in one or two thumb muscles. Six weeks after treatment, patient disability assessment scale scores were compared with those recorded at baseline in the domains of personal hygiene, dressing, pain, and limb positioning. From these domains, patients selected their principal therapeutic intervention targets at study outset. Comparisons were also made between BoNT-A and placebo with regard to change in the 5-point Ashworth scores for muscle tone of the wrist and finger flexors. Global assessment of the patients’ overall response to treatment was also performed. At all follow-up visits (ie, at weeks 1, 4, 6, 8, and 12), patients receiving BoNT-A had significantly greater improvements in flexor tone in the wrist and fingers compared with patients in the placebo group (P<.001). At weeks 4, 6, 8, and 12, patients treated with BoNT-A had significantly greater improvements in their principal therapeutic intervention targets versus placebo (P <.001, P<.001, P=.03, and P=.02, respectively). Compared with placebo, treatment with BoNT-A was also associated with a significantly greater increase in the proportion of patients reporting an improvement of at least one point in disability assessment scale scores (P<.001). At week 6, 62% of patients who were treated with BoNT-A had improved disability assessment scale scores for their principal therapeutic intervention targets compared with reported improvements in 27% of placebo-treated patients (P<.001). Th e overall safety profile of BoNT-A in this 12-week study was favorable, with no major adverse events associated with treatment. In an open-label, follow-up study of this same treatment cohort (Gordon et al, 2004), repeated administration of BoNT-A (BOTOX ®) in patients with poststroke spasticity was associated with sustained improvements in wrist, finger, and thumb flexor tone, as well as patient function—particularly as it relates to disability assessment scale scores for hygiene and limb position. In addition, repeated BoNT-A treatment continued to be well tolerated. Indeed, a recent systematic review and meta-analysis of the safety of therapeutic BoNT-A (BOTOX ®) attest to the sustained efficacy of this therapy and to its good safety profile (Naumann and Jankovic, 2004; Jankovic et al, 2004). Practical aspects of managing and treating the UMN syndrome with BoNTIdentification and selection of muscles for treatment with BoNT requires a close evaluation of the prevailing pattern and presentation of muscle overactivity on a case-by-case basis (Figure 23). BoNT-A has been widely used as a treatment for problematic muscle overactivity, allowing for some general guidance on which groups of muscles may benefit from treatment with BoNT-A injections. However, the nature and type of muscle overactivity seen in patients with the UMN syndrome vary from patient to patient and even within individual patients depending on the affected limb. Patients need to be made aware of the nature and onset of BoNT-A–induced changes and that the effects of medication may not become apparent until 5 to 7 days after injection. Figure 23. Common injection sites and potential target muscles in spasticity treatment. Shoulder Adductors
Adducted posturing interferes with washing, dressing, and other daily activities; patient is unable to reach forward or above the head.
Elbow Flexors
Flexion of the elbow prevents extension of the arm for dressing, reaching, and washing, and limits activities of daily living; patient may also have limited ability to operate an electric wheelchair.
Wrist Flexors
Flexion of the wrist interferes with dressing and washing and limits the manipulation of objects; patient may also experience pain and signs and symptoms of carpal tunnel syndrome due to compression of the median nerves.
Finger Flexors
Overactive finger flexors can result in clenched fist posturing, which prevents the grasping of objects and limits activities of daily living; patient may often experience pain from fingernails digging into the palm, and placing hand splints may also be difficult in such patients.
Hip Flexors
Flexion of the hip interferes with gait and sexual intimacy, as well as with passive posturing such as seating and sleeping; patient may frequently report hip flexor spasms that can spread to the knee.
Hip Adductors
Adducted posturing of the hip results in scissoring thighs that interfere with washing, urination, sexual activity, and gait; passive postures such as standing or sitting can be difficult, and patients may often complain of leg stiffness.
Ankle Plantarflexors and Invertors
Potential target muscles from Sheean G. Botulinum toxin treatment of adult spasticity. Expert Rev Neurother. 2003;3:773-785. Identifying and selecting overactive muscles for treatment with BoNTDynamic EMG recording can provide valuable insights into which muscles and muscle groups exhibit overactivity. As described previously, EMG can be performed in patients during passive and voluntary muscle stretching to locate the main source of overactivity. The traces shown in Figure 24 demonstrate how EMG recording can be used to guide the clinician towards affected muscle groups (in this case the biceps and brachioradialis were overactive) and to assess the impact of treatment on muscle activity. Figure 24. Muscle activity before and after use of BoNT-A in a patient with overactivity in the elbow. Treatment was injected into the biceps and the brachioradialis, as these were identified as the primary areas of muscle overactivity by EMG. Note the reduction in muscle activity after therapeutic use of BoNT-A and improvements in elbow displacement.
Courtesy of Nathaniel Mayer. The differentiating powers of poly-EMG recording are clearly illustrated in the case shown in Figure 25. With different muscle groups in each leg showing different degrees of overactivity, treatment options would differ for each limb. In this patient, treatment of the right limb would require BoNT-A injections of the tibialis posterior, whereas injection of the tibialis anterior would be a more appropriate treatment for the left limb. Figure 25. A patient with traumatic brain injury and severe equinovarus of ankles and feet. Poly EMG recording showed that despite a similar clinical presentation of spasticity and deformities in both limbs there were differences in the distribution of muscle overactivity between the right and left limbs in response to ankle passive stretch. Courtesy of Nathaniel Mayer. Injection techniquesElectrical stimulation and EMG recording or devices that emit auditory signals are also useful for localizing the muscle and guiding needle positioning at the time of BoNT injection. Dosing by muscle sizeWhen establishing the optimal dose of BoNT for the treatment of muscle overactivity, it is advisable to use as small a dose as possible to achieve the desired treatment outcome, whether the outcome involves a reduction in muscle tone or an improvement in range of motion, active function, or hygiene (Francisco, 2004). Other factors that require consideration include the severity of muscle overactivity, the number of muscles involved, the degree of contracture, age and body mass, prior response to treatment, and other concurrent therapies. Clinicians familiar with BoNT therapy may prefer to modify previous treatment styles and techniques based on their personal experience and patient outcomes; others may choose to consult consensus treatment guidelines (Gormley et al, 1997). When all factors related to both patient and clinician are considered, BoNT therapy can be tailored to best treat the individual needs of the patient (Jankovic et al, 2004). Safety profileBoNT is well tolerated with few reports of serious adverse events. The excellent safety profile of BoNT-A was recently highlighted in a large-scale, systematic review and meta-analysis of safety data from a wide variety of clinical studies involving this neurotoxin (Naumann and Jankovic, 2004). A pooled analysis of data from 9 double-blind and placebo-controlled studies involving patients with limb spasticity following stroke has also been recently reported (Turkel et al, 2004). Local adverse events result from excessive action of BoNT-A in the target muscle or adjacent muscles (Klein, 2004). Systemic adverse events are the result of effects of the toxin in distant muscles or organs and may include dry mouth, double vision, diminished bowel and bladder control, generalized weakness, dysphagia, and dysarthria (Borodic et al, 1990). Adverse effects—including flu-like syndrome, fatigue, minor local skin reactions, and pain at the site of injection—are largely related to the mechanism of action or injection technique and can usually be tolerated or managed with dose reductions (Goldstein, 2001). Development of antibody-mediated resistance to BoNT-A is characterized by lack of muscle relaxation and/or atrophy after the injection and is estimated to occur in 3% to 10% of cases (Brin, 1997). Using the minimum dose necessary to produce a clinically significant effect and employing less frequent treatments may reduce the likelihood of antibody development. Moreover, the newer formulation of BoNT-A (BOTOX®), which has a reduced protein load, may further reduce the risks for antibody-mediated resistance. Jankovic and colleagues recently reported on the results of a study in which none of the 119 patients evaluated had developed antibodies in response to the new formulation of BoNT-A (BOTOX®) (Jankovic et al, 2003). BoNT-A and physical therapyStrengthening of the opposing muscles, coupled with aggressive stretching of the injected muscles and functional retraining with the aid of a therapist, is of great importance in ensuring that patients derive the most benefit from BoNT-A treatment for muscle overactivity. Splinting and bracing to maintain the limb in the adequate position can also help improve treatment outcomes. SummaryComplex interactions among the positive and negative signs, as well as rheologic changes in affected muscles and other soft tissues, result in functional impairments and limb deformities associated with the UMN syndrome. In its various forms, the positive signs of UMN syndrome reflect muscle overactivity, which is an important factor when considering treatment strategies. With the goal of promoting a greater degree of patient comfort, independence, and mobility, management strategies should aim to incorporate a multimodal approach while optimizing the use of pharmacological agents based on the distribution and pattern of muscle overactivity. Centrally acting agents exert diffuse effects on muscle excitability but are frequently associated with undesirable adverse effects such as generalized sedation, dizziness, and fatigue. Peripheral agents may be more suitable for regional or focal control of muscle overactivity and include the use of local anesthetics, focal chemodenervation with BoNT, and focal neurolysis with phenol. BoNT is a preferred treatment for focal or multifocal muscle overactivity associated with the UMN syndrome. A growing body of evidence supports the use of BoNT-A as a valuable treatment in the care and management of patients with the UMN syndrome. Clinical studies have shown that selective use of this treatment can help patients achieve predetermined treatment goals. ReferencesArnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon. Medical and public health management. JAMA. 2001;285:1059-1010. Bell KR, Williams F. Use of botulinum toxin type A and type B for spasticity in upper and lower limbs. Phys Med Rehabil Clin N Am. 2003;14:821-835. Borodic GE, Joseph M, Fay L, Cozzolino D, Ferrante RJ. 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