Movement dysfunction following central nervous system lesions: a problem of neurologic or muscular impairment?

Key Words: Hypertonicity, Movement, Muscle, Spasticity, Stiffness.

Hypertonia has been described as excessive resistance to passive movement of a limb, stemming from both reflex and nonreflex elements.[1] in patients with a central nervous system (CNS) lesion, hypertonia traditionally has been linked to velocity-dependent hyperactive stretch reflex activity. Researchers studying plantar-flexor,[2,3] quadriceps femoris,[4] and elbow flexor[5-8] muscles in patients with hypertonia primarily have explained the increased tension response to passive lengthening as a manifestation of abnormal stretch reflexes.

More important to functional activities, however, is the concern for impaired active movements. Pierrot-Deseilligny and Mazieres[9] contend that voluntary movement stretches antagonist muscles and that such elongation can trigger stretch reflexes that limit the extent and speed of the intended movement. Knutsson and Martensson[10] called this resistance to voluntary movement in patients with CNS lesions "antagonist restraint," as evidenced by inappropriate muscle activity recorded through the use of electromyography (EMG) of the antagonist muscles. These authors maintained that abnormal co-contraction creates an added load that the weakened agonist may not be able to overcome to produce the desired limb movement, which results in impairment of gait and other functions. They reported that the most likely cause of this problem was a facilitation of phasic stretch reflexes during the voluntary effort, but they also acknowledged misdirected descending motor command signals as another possible cause of the co-contraction.

Knutsson and Richards" differentiated three types of abnormal activation patterns of leg muscles in the gait of patients with hemiparesis: (1) premature muscle activation due to heightened stretch reflex responses in plantar-flexor muscles, (2) lack of muscle activation associated with paresis of two or more muscle groups, and (3) strong stereotyped coactivation of several or all leg muscles. Corcos et al[12] demonstrated in patients with CNS lesions that rapid active dorsiflexion movements were hindered or even reversed by hyperactive stretch reflex activity in the plantar-flexor muscles. McLellan,[13] however, showed in patients with CNS lesions that active cyclical flexion-extension tracking movements at the knee were impaired, not from abnormal stretch reflexes but from abnormal co-contraction of the quadriceps femoris and hamstring muscles. Similarly, McLellan et al[14] found in patients with CNS lesions that active flexion-extension tracking movements at the elbow were impaired by co-contraction of the flexor and extensor muscles.

Whether the movement is passive or active, clinical opinion frequently explains impaired movement in patients with a CNS lesion from a neurologic standpoint. Less emphasis has been given to nonreflexive, or mechanical, changes within muscles. The purpose of this article is to review the theory of abnormal crossbridge attachments as a possible mechanism of restrained movement in patients with CNS lesions.

Mechanical Hypertonia in Patients With Central Nervous System Lesions

Studies identified the conspicuous finding of increased stiffness, defined as the ratio of change in torque per change in joint angle, in the muscles of patients with CNS lesions with little or no EMG activity in the lengthened muscle. Dietz et al,[15] recorded the EMG activity of the dorsiflexor and plantar-flexor muscles in healthy subjects and patients with hyperreflexia while studying their ankle movement during gait. During the swing phase of gait, the patients with hyperreflexia were unable to move their foot through the dorsiflexion range of motion that was available to them, and EMG records showed that the plantar-flexor muscles were essentially inactive during the dorsiflexion effort. Moreover, the lack of dorsiflexion movement was not due to impaired function in the dorsiflexor muscles, because the EMG record for the tibialis anterior muscle showed considerable activity.

In the absence of antagonist EMG activity, Dietz et al[15] proposed that the observed limited dorsiflexion movement was due to plantar-flexor stiffness stemming from pathologic changes in the mechanical properties of the contractile element within these muscles. The authors, however, did not rule out that connective tissue within the plantar-flexor muscles as a possible cause of the restricted dorsiflexion movement. The same group[16] proposed the same hypothesis for the observed limited movement in a similar study of children with hypertonicity, but again the role of connective tissue stiffness was not ruled out.

With a special gauge fixed lateral to the Achilles tendon, Berger et al[17] evaluated the development of force in the Achilles tendons on both sides during gait in subjects with hemiparesis. During the stance phase, development of force in the unaffected leg was coupled to gastrocnemius muscle EMG activity. Force in the leg with spasticity, however, corresponded to muscle length and was not a reflection of gastrocnemius muscle EMG activity. From additional experiments involving gait perturbations, the authors reported that the hypertonia observed in their patients was not related to exaggerated reflexes. Instead, they again proposed that changes may occur in the mechanical properties of muscle fibers in individuals with impaired supraspinal input, resulting in abnormal resistance to muscle lengthening.

Dietz and Berger[18] described such stiffened behavior in muscles of patients with CNS lesions as a "pseudostretch reflex." They theorized that through unique muscular adaptations, such patients unconsciously shift from the normal neuronal control of muscle tension to a more mechanical control of tension. That is, instead of modifying muscle tension through active control of motor units, the mechanical properties of muscle itself change in patients with CNS lesions, and these lesions cause tension during muscle lengthening. As a result, these patients gain some postural stability of joints, but at the expense of rapid mobility.

In patients with hemiplegia, Hufschmidt and Mauritz[19] studied the resistance of the ankle to passive 20-degree dorsiflexion/plantar-flexion displacement cycles. Patients with hyperreflexia present for less than 1 year showed resistance to ankle dorsiflexion that was equivalent to normal values. In patients with hyperreflexia for more than 1 year, however, the resistance was increased significantly from normal, and it was not accounted for by plantar-flexor EMG activity. Furthermore, the authors observed a deformation of the length-tension curve when the interval between two successive stretch cycles exceeded 1 to 2 seconds. Under this circumstance, they noted a more rapid rise in resistance as the foot was dorsiflexed, even though the amplitude and velocity of stretch were the same as in previous cycles. As the dorsiflexion movement continued, the rapid rise in resistance was followed by a short leveling-off phase, called a "shoulder," which was followed by a slower rise in resistance.

The rapid rise in resistance was most pronounced in patients with hyperreflexia for more than 1 year. Hufschmidt and Mauritz[19] explained that the deformation in the length-tension curve following the short intervals of rest could not be due to stretching of shortened series elastic elements. Instead, the authors related the rapid rise in resistance to Hill's[20] theory of attached crossbridges, and they contended that their results support the idea that mechanical transformations, including abnormal crossbridge connections, occur in the muscles of patients with long-standing CNS lesions and contribute to hypertonia.

More recently, Dietz et al[21] found significantly higher torque: EMG ratios for the flexor and extensor muscles of the paretic side compared with the unaffected side during elbow flexion/extension displacements in patients with hemiparesis. The authors deduced that hypertonia is not always related to increased EMG activity, and they suggested that following a supraspinal lesion, mechanical muscle properties can change in these individuals so that their muscle develops more tension when it is stretched. Whereas earlier work by Dietz et al[15] on plantar-flexor muscles of patients with CNS lesions emphasized structural changes in the muscle fibers themselves, the more recent work of Dietz et al[21] demonstrates that a contribution of noncontractile elements of the muscle to the stiffness also is highly probable.

Tardieu et al[22] analyzed the relative contributions of passive and active components to the problem of toe walking in 13 children with cerebral palsy. They computed a ratio (R) of the passive moment of the plantar-flexor muscles to the total internal (active and passive) moment of these muscles. The passive moment was determined by an apparatus that applied dorsiflexion displacements with the subject positioned sidelying. There was an absence of any EMG activity in the plantar-flexor and dorsiflexor muscles, indicating resistance was passive. The total internal moment was determined through cinematic and force-plate measurements during gait. The results showed that five of the subjects had small R values, indicating excessive activity in the plantar-flexor muscles during gait, whereas six subjects showed high R values, indicating that structural change of the muscle or tendon was more responsible for the toe walking. The authors did not hypothesize whether such structural changes within the muscle were related to the contractile apparatus or to connective tissue. They concluded that although different children with cerebral palsy may exhibit similar toe-walking patterns, these patterns may be attributable to different mechanisms.

Katz and Rymer[23] stated that earlier experimental findings suggesting mechanical changes in the contractile apparatus of patients with hypertonicity could be explained by degenerative or atrophic alterations in the muscle structure, such as muscle atrophy with collagenous and elastic tissue infiltration. They claimed that there is no evidence to support the idea of an anomalous change in the physiologic muscle response to stretch in patients with CNS lesions. They also argued that abnormal crossbridge connections could not easily account for many established findings such as enhanced phasic muscle stretch reflexes. Hagbarth et al,[24] however, proposed that crossbridge connections between the filaments of resting intrafusal muscle fibers can heighten a muscle's phasic stretch reflex activity.

Crossbridge Stiffness in Animals

Hill[20] studied the tension response in the isolated resting sartorius muscle of the frog (Rana temporaria) and the toad (Bufo bufo) as the muscle was lengthened systematically (Fig. 1). The characteristic response showed an initial rapid rise in tension, with a small change in length. As the muscle was lengthened further, the tension declined slightly from the peak but stayed at a high level until the lengthening ceased. Hill theorized that the initial stiffness was due to what he called the "short-range elastic component" of resting muscle. Such stiffness results from the "flexural rigidity" of a small proportion of myosin crossbridges that are connected to actin filaments, even while the muscle is at rest.

Hill[20] theorized that such crossbridge connections act as elastic springs that resist deformation during passive lengthening--but only up to a certain point, beyond which they slip. Such slipping accounts for the slight decline in tension from the initial peak during the length-tension experiments. Hill described the tension maintained during the continued lengthening as frictional resistance resulting from rapid reformation of crossbridge connections further along the actin filament. Hill explained that the observed tension within the muscle was not due to stretching of connective tissue. Otherwise, the tension would have continued to increase during the entire lengthening rather than stabilizing at a constant level.

Hill's explanation[20] of stiffness in resting muscle is contrary to that proposed by Ramsey and Street.[25] These researchers investigated the tension response to stretching in single frog (Rana pipiens) semitendinosus muscle fibers before and after a defect was created experimentally, causing the midportion of the fiber to be vacated of any contractile tissue but leaving the sarcolemma intact. The tension measurements of the fibers with disrupted contractile tissue were essentially the same as those of intact fibers. Ramsey and Street concluded that the resistance of resting muscle fibers to stretch is not due to muscle substance but rather to the connective tissue elements of the fiber.

The disparate findings of these two studies are difficult to explain, but they may be related to physiologic differences in the species of frogs or the specific muscles studied. The difference in findings could also be due to the solute concentrations of the external solutions that bathed the mounted muscle fibers in each study. Hill[20] emphasized that hypertonic solutions of nonionic solutes (sucrose) caused profound increases in the stiffness of the muscle. He theorized that with the resultant osmotic shrinkage of the muscle fiber, the associated decrease in transverse distance between filaments allowed for a magnified interaction of the crossbridges between the filaments. In addition, he theorized that the increased concentration of protein molecules in the sarcoplasmic fluid further potentiated the crosslinking process. Unfortunately, Ramsey and Street[25] did not report the osmotic strength of their solutions, nor did they study the effect of changing this variable.

More recently, investigators demonstrated that crossbridge stiffness depended on the recent history of movement in the muscle. Lakie and Robson[26] found that stiffness in frog (Rana temporatia) sartorius muscle was decreased greatly from baseline values by a series of small, passive oscillatory movements performed just prior to a second stiffness measurement. Furthermore, they found that the stiffness returned to near the baseline values when a third measurement was taken after the muscle had remained stationary for 1 minute.

Such labile stiffness behavior that depends on the past history of movement is termed "thixotropy." Although this term traditionally has been used for gels that become more fluid with movement and then gradually regain their gelatinous state with rest, the same term is appropriate for any system in which molecular bonds are disrupted by movement and are reformed when the movement forces cease.[24] According to this theory, prior movement decreases stiffness, whereas prior stillness increases stiffness. Lakie and Robson[27] also showed that tetanic electrical stimulation of frog (Rana temporaria) sartorius muscle applied under isometric conditions just prior to stiffness measurements produced a considerable decrease in stiffness from the prestimulation value. The authors postulated that both passive stretch and tetanic stimulation decrease resting muscle stiffness by temporarily disrupting the bonds between myosin and actin.

Lakie and Robson[28] considered the possibility that the mechanisms underlying thixotropic behavior observed in frog muscle could be situated in the connective tissue of the muscle rather than in the contractile tissue. They evaluated this concern in single iliofibularis muscle fibers of the frog (Rana temporaria) by chemically inducing rigor within the muscle. They theorized that if thixotropy is due to crossbridge behavior between actin and myosin, then permanent attachment of crossbridges, or rigor, should eliminate thixotropic behavior. The results showed that rigor did eliminate thixotropy, providing further support for the idea of crossbridge stiffness in relaxed muscle.

Certain animals are endowed with a unique type of muscle that is particularly resistant to stretch in the resting state. Such muscle, termed "catch muscle," is typically found in bivalve mollusks, such as oysters and scallops, and functions to hold the two halves of the shell firmly shut for prolonged periods with an economy of energy.[29]

Catch muscles are innervated by both cholinergic excitatory nerves and serotonergic relaxing nerves.[30] Stimulation by cholinergic nerves in the absence of serotonin leads to the catch state. While in this inactive state, the membrane potential is at resting level and the muscle exhibits stiffness that resembles rigor, even though adenosine triphosphate (ATP) concentrations do not decrease. Relaxation from the catch state is induced by release of serotonin. Catch muscle is characterized morphologically by extremely long, wide, and thick filaments composed of myosin surrounding a core of paramyosin.[30] The relationship of this structure to the catch, however, is unclear.[31] The mechanism of the extraordinary resistance of catch muscle to stretch is not known, but the consensus is that tension during catch is related to slowly cycling crossbridge attachments to actin.[30]

Although the catch state has primarily been studied in invertebrate smooth muscle, catch-like tension has been reported in invertebrate skeletal muscle,[32] vertebrate smooth muscle,[33] mammalian smooth muscle,[34] and frog tonus fibers.[35] Indeed, Twarog[36] argues that the ability of a muscle to resist stretch even after excitation ceases is probably a property of many muscles and it is a property that is extremely well developed in catch muscles.

Molecular Basis of Crossbridge Stiffness

Brenner[37] reviewed the conventional concept of the mechanical crossbridge cycle as a muscle goes from the relaxed state to a contracted state. in this scheme, depicted in Figure 2, the myosin crossbridge is detached from the actin filament in the relaxed state of the muscle. When ATP is hydrolyzed, however, an oarlike cycle of coordinated crossbridge movement begins. First, the crossbridge attaches to the actin filament. Next, the crossbridge undergoes structural change, imposing a strain on the elasticity of the crossbridge that results in force generation under isometric conditions or filament sliding under isotonic conditions. Finally, the crossbridge detaches and returns to the starting position. Although not depicted in Figure 2, [Ca.sup.2+] is the regulatory agent responsible for initiating the blocking and unblocking of the crossbridge attachment site in the first step of the cycle.

Contrary to this traditional view of the crossbridge cycle, Brenner[37] reviewed more recent evidence indicating that the myosin crossbridges with

actin may be classified as either strong binding or weak binding. Strong binding corresponds to muscle during contraction, whereas weak binding corresponds to relaxed muscle and involves a rapid oscillation between the actin-attached and actin-detached states, even in the absence of [Ca.sup.2+] of Ca

The kinetics of these protein-protein interactions have been studied on the organized contractile apparatus with rabbit skinned psoas muscle fiber preparations. In these preparations, the fiber membranes are removed chemically by dissolving them in a mild detergent.[41] Skinned fibers are permeable to water-soluble molecules such as [Ca.sup.2+], the nucleotide ATP, and spectroscopic probes[42] capable of specifically labeling the myosin crossbridge orientation. The contractile state and the corresponding stiffness of the skinned fibers can be studied by placing the fibers in different solutions: activating solution, consisting of [Ca.sup.2+] and ATP; relaxing solution, consisting of ATP without [Ca.sup.2+]; and rigor solution, containing neither ATP nor [Ca.sup.2+]

The measurement of the stiffness of muscle fibers in these situations serves an important role in the investigation of the molecular mechanism of muscle contraction, because fiber stiffness varies linearly with the number of crossbridges attached to actin. This relationship was established with tetanized intact frog fibers by Huxley and Simmons[43,44] and Ford et al.[45] They showed that stiffness of tetanized fibers was proportional to the amount of overlap between actin and myosin filaments. Furthermore, Brenner et al[46] showed that stiffness in rabbit skinned psoas muscle fiber preparations was proportional to the amount of overlap of the actin and myosin filaments.

A muscle fiber in rigor has all of its myosin crossbridges bound to actin and has constant stiffness through a large range of length changes. Stiffness of fibers in rigor is essentially independent of the velocity of the length change of the fibers. In relaxed fiber states, however, in which the crossbridges are oscillating between attachment and detachment, fiber stiffness must be measured with length-change velocities that are much higher than the rate of crossbridge attachment. This high-velocity length change is necessary so that the biochemical/mechanical state of the crossbridges does not have time to alter during the length change. When this condition is satisfied, the stiffness measurement will correctly detect the number of actin-bound crossbridges.

When a slow stretch is applied to a relaxed muscle fiber, the apparent stiffness is zero. More rapid stretches indicate a nonzero apparent stiffness that is consistent with a crossbridge detachment rate of approximately [10.sup.4] per second.[37] The apparent stiffness is proportional to the amount of overlap between actin and myosin filaments, confirming that the stiffness is due to some crossbridges binding to actin, even in the relaxed state. Other techniques with rabbit psoas muscle, including x-ray diffraction[47,48] and optical spectroscopy,[49] indicate crossbridge orientation in relaxed muscle fibers is consistent with the notion that crossbridges are binding to actin in this relaxed condition. Experiments on muscle fibers in solutions of different ionic strength provide further evidence that the stiffness of relaxed fibers stems from interfilament connections. Charged particles, such as [Na.sup.+], [Cl.sup.-], and others, are small relative to the contractile proteins within the same solution. Still, these particles are attracted to the proteins, and if enough particles are present, they actually can block the attachment between myosin and actin. Thus, by varying the ionic strength of a solution, the degree of attachment between these proteins in the relaxed state can be regulated and the stiffness can be monitored accordingly.

The stiffness of relaxed fibers depends on ionic strength in a manner suggesting that the rate of detachment of crossbridges from actin increases with increasing ionic strength.[37] At present, the data from relaxed fibers at physiologic ionic strength are incomplete because of limitations in the speed of the length changes that can be achieved experimentally. Nonetheless, recent evidence strongly supports the idea that at physiologic ionic strengths, the myosin crossbridges are rapidly oscillating between attached and detached states.[37]

The implication of these findings for the molecular mechanism of muscle contraction is that the first step in the force-producing cycle is not binding to actin, as previously thought,50 but is an unidentified step subsequent to the myosin crossbridges binding to actin. This information suggests that crossbridges bind to actin in at least two different manners: (1) weakly and reversibly, such that binding actin does not cause the hydrolysis of ATP, and (2) strongly, when the crossbridge hydrolyzes ATP and produces force. Condition 1 presumably occurs in relaxed fibers in which strong binding is prevented by the [Ca.sup.2+] regulatory system.

Brenner[37] reported that this rapidly reversible attachment of myosin crossbridges to actin in relaxed fibers is a feature detectable in all species studied so far; only the magnitude of the binding strength and rate constants for attachment and detachment vary with the species and the ionic strength of the surrounding solution. Consequently, the question is not whether crossbridge binding between filaments exists, manifested as stiffness during muscle lengthening; rather, the question is the degree to which it exists. Muscles of patients with hypertonicity may represent an exaggerated case of such stiffness.

Crossbridge Stiffness in Humans

Lakie et al[51] studied the amplitude of passive wrist movements induced in healthy subjects by small sinusoidal torques applied with a motor. Perturbation of the system with large-amplitude movements just prior to the test torques caused a considerable decrease in wrist motion stiffness from baseline values. When the wrist was allowed to rest for 2 seconds or more without perturbations, the amplitude of movement during subsequent test torques returned to the baseline values. Electromyographic records showed no activity in the wrist muscles during the tests. The authors postulated that the formation of interfilament bonds in resting muscle may derive functional value by mechanically resisting small postural changes in the body without requiring constant activity of the nervous system. Lakie and Mutch[52] showed in patients with Parkinson's disease that large-amplitude finger movement immediately before tremor measurements unmasked a subtle finger tremor that previously was undetectable clinically. In other patients showing resting tremor, the prior movement provoked a larger-amplitude tremor.

Studies evaluating stiffness in the index finger of healthy subjects also provide evidence for thixotropy in muscles. Lakie and Robson[53] studied stiffness in the index finger at specified times during a rest period after vigorous active or passive movement of the finger. They reported that as the finger remained inactive, the muscles showed increasing levels of stiffness that progressed for 30 minutes before leveling off. They attributed this behavior to reformation of crossbridge connections within resting muscle.

Hagbarth et al[24] reported changes in stiffness in the finger flexor muscles in healthy subjects in response to contractions and length changes of the same muscles. They evaluated the muscle stiffness by monitoring the speed and amplitude of finger movements at the metacarpophalangeal (MP) joint induced by repetitive extension torque pulses of constant strength applied to the fingers by a torque motor. Stiffness in the finger flexor muscles was decreased by a single, large passive extension movement and was increased by a single, large flexion movement (Fig. 3A). With a series of reciprocal extension and flexion movements as a conditioning maneuver, the authors showed that subsequent stiffness changes in the finger flexor muscles depended on whether the last finger movement of the series was one of extension or flexion. Movements ending in extension just prior to testing decreased stiffness, whereas movements ending in flexion increased stiffness (Fig. 3B). Isometric voluntary contractions of the finger flexor muscles decreased finger flexor stiffness (Fig. 3C), but resisted (Fig. 3D) and unresisted shortening contractions of the same muscles increased stiffness. The authors explained the observed stiffness changes in response to the various conditioning maneuvers in terms of thixotropic interfilament bonds in muscle.

Hagbarth et al[24] theorized that large-amplitude finger extension movements disrupt many of the preexisting bonds, thereby loosening the flexor muscles during subsequent extension movements. Conversely, large-amplitude flexion movements and flexor muscle shortening contractions promote the formation of new bonds in the shortened position of the flexor muscles, resulting in an aftereffect of increased flexor stiffness. The authors postulated that the loosening effect of isometric contractions was due to the disruption of preexisting crossbridges by actively sliding filaments. Finally, and in agreement with Lakie and Robson,[53] they also reported that during the rest period that followed each loosening maneuver, a progressive stiffening effect was observed. They related this effect to the reformation of bonds that were previously broken by the loosening maneuver.

Carey[54] evaluated control of active movement of the index finger in 16 subjects with hemiparesis and reported impaired movement that may correlate with crossbridge stiffness. With an electrogoniometer attached to the index finger, subjects attempted to track a sine-wave target on a computer screen with careful extension and flexion movements of the MP joint of the index finger. The accuracy of the tracking responses in these subjects was below normal, and the responses, in general, showed an impaired ability to reach the extension peaks of the target track, even though they were well within each subject's active range of motion. Although most of the subjects showed considerable EMG activity in the extrinsic finger flexor muscles concomitant with the extension effort and the EMG activity (normalized to maximum) of these muscles was greater than normal, three subjects showed impaired finger extension movement with little or no evidence of antagonistic co-contraction (Fig. 4). Furthermore, a conspicuous finding seen in most of the tracking records was the impaired finger extension movement that followed the first flexion movement.

These findings are consistent with the crossbridge stiffness described by Hagbarth et al.[24] In Figure 4, the resting stiffness of the flexor muscles may be surmountable by the extensor muscles when the finger starts in the midposition and, accordingly, the first extension movement is successful. The system appears perturbed during the substantial flexion movement that follows, however, because the next extension effort falls far short of the target. The third and fourth extension efforts fall equally short, despite a growing extensor EMG record and a nearly silent flexor EMG record.

These findings, in combination with previous discussions of possible structural changes in muscles of patients with CNS lesions,[15,19] invite further exploration of the concept of exaggerated crossbridge stiffness. A particular concern is whether such stiffness may be triggered by a prior shortening contraction of these muscles. Perhaps after myosin crossbridges engage with actin during an active contraction, they fail to disengage readily or reengage spontaneously, but with a much lower detachment rate. Consequently, an added frictional resistance[20] in the flexor muscles may prevail, which weakened extensor muscles may not be able to overcome fully.

A functional situation that may correlate with this explanation of impaired finger extension movement after a recent flexion effort is the handshake of some patients following a stroke. A common finding among these individuals is that a forceful squeeze by the patient on someone's hand is followed by an impaired ability to release the grip. Similarly, gripping a glass of water may be quite simple for these individuals, but frustration follows when the subject cannot let go in a timely fashion. Abnormal descending motor commands[13] and reciprocal innervation problems[55] also could account for these functional difficulties following a CNS lesion.

To consider only understandable reflex- and neural control-based mechanisms, however, may be simplistic. Even if EMG activity were present in the flexor muscles to a mild or moderate degree during the time when the patient desired to open the hand, the mere presence of antagonistic EMG activity does not mean it is the sole or primary cause of the functional problem. Crossbridge stiffness could be present but masked by stretch reflexes or co-contractions, in combination with an uncertain understanding of the response of the contractile apparatus to CNS lesions.

The connective tissue of joint capsules, ligaments, and muscle also may contribute to impaired movement in persons with CNS lesions. These tissues, however, become more compliant with repetitive movement rather than becoming stiffer.[56] The behavior of these tissues, therefore, cannot account for the impaired finger extension movements seen in the tracking response described. Nonetheless, information on tracking responses remains inconclusive because other factors, including abnormal motor programming or perceptual difficulties, also could account for impaired extension effort.

Discussion

Alexander and Johnson[57] evaluated the slow length changes of the frog sartorius muscle during loading and unloading cycles in which brief intermittent muscle contractions were evoked by electrical stimulation. They found that the contractions significantly decreased the elongation of the resting muscle. They postulated that the stiffened response was due to a resetting of the crosslinkages between myosin and actin, which stabilize the resting muscle at a set length until sufficient external force is applied to disconnect them.

To the contrary, Lakie and Robson[27] found that, in frog (Rana temporaria) muscle, prior tetanic electrical stimulation under isometric conditions produced a decrease in the muscle's stiffness. The observed response, however, occurred only in summer frogs, and a stiffening effect was observed in winter frogs. They state that these differences may be due to seasonal changes in the proportion of tonic fibers. Perhaps the detachment rate between crossbridges and actin in the weak-binding state of muscle is a mutable characteristic, dependent on the demands placed on the muscle. Muscles in patients with long-standing CNS lesions may experience a severe slowing of this detachment rate, producing abnormal stiffness. This could be an adaptation for the loss of cerebral control of tension. The idea that such stiffness may result from myosin crossbridges that fail to disengage rapidly from actin after a contraction is consistent with the finding of prolonged twitch contraction times in muscles of patients with spasticity.[58,59]

Without more direct evidence for crossbridge stiffness in persons with CNS lesions and without a clear physiologic mechanism, treatment based on this mechanism is premature. Hagbarth et al[24] speculated, however, that brief vibration of the bellies or tendons of healthy muscle, which did not induce a tonic vibration reflex, caused a decrease in stiffness. As a test maneuver, perhaps such mechanical agitation applied to muscles of patients with hypertonia after a contraction could dislodge the purported crossbridge connections between filaments and produce a similar beneficial effect unrelated to neurophysiologic mechanisms.

In vivo testing for conclusive evidence of crossbridge stiffness in patients with CNS lesions is currently impossible. The following approach, however, would add valuable information to this topic. The resistance to passive movement of a limb segment would be measured with the muscles crossing the joint temporarily paralyzed by proximal nerve blocks. Stiffness measurement in this state would exclude any contribution from active or reflex excitation of the pertinent muscles, but it would not distinguish between the contributions from connective tissue and crossbridge attachments. Low stiffness measurements in this state would not necessarily rule out crossbridge stiffness, because its occurrence may depend heavily on the recent history of a shortening muscle contraction.[24]

With the nerves still blocked, a shortening contraction would be evoked by stimulating the appropriate nerve distal to the nerve block, followed by another stiffness measurement immediately after cessation of the contraction. Any increased stiffness from the previous measurement noted in this circumstance would probably be due to abnormal crossbridge attachments, because adaptive shortening of connective tissue could not occur in such a short time frame.

Conclusion

Evidence suggests that crossbridge stiffness exists in isolated animal preparations and in in vivo studies on healthy humans. Direct evidence of exaggerated crossbridge stiffness in muscles of patients with CNS lesions does not exist. Such stiffness, however, may be an important unrecognized contributor to the impaired movement of such patients. Scientific and clinical attention must expand beyond the reflex and neural control components of CNS lesions to address possible mechanical factors as well.

References

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