SPASTICITY, DECEREBRATE RIGIDITY AND THE CLASP-KNIFE PHENOMENON: AN EXPERIMENTAL STUDY IN THE CAT

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1 Brain (1972) 95, SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON: AN EXPERMENTAL STUDY N THE CAT BY DAVD BURKE, 1 LYNDSAY KNOWLES, 2 COLN ANDREWS 5 AND PETER ASHBY* (From the Division of Neurology, The Prince Henry Hospital and the School of Medicine, University of New South Wales, Australia) NTRODUCTON HUMAN spasticity has long been held by many authors to be analogous to decerebrate rigidity of the cat. One of the implications of this analogy is that the clasp-knife phenomenon is the equivalent of the lengthening reaction. Sherrington (1909) originally described phenomena which he termed "lengthening reactions" in both the spinal dog and the decerebrate cat, yet he recognized that these reactions differed in the two preparations, a fact overlooked by subsequent authors. The reaction described by Sherrington in the chronic spinal dog appears identical with the clasp-knife phenomenon encountered in human spasticity: if the examiner bends the knee "against the knee extensor's contraction he feels the opposition offered by the extensor give way almost abruptly at a certain pressure; the knee can then be flexed without opposition." The essential feature thus appears to be abolition of reflex resistance during the stretching movement. The lengthening reaction in the decerebrate cat was described as follows: "Starting with the knee in a posture of extension due to its extensor's rigidity, the observer forces it into flexion. On cessation of the flexion force the knee is found to remain approximately in the new posture." The essential feature of this reaction is that it occurs on cessation of the stretching movement and that, unlike that in the spinal dog, further flexion meets with further resistance. The clasp-knife phenomenon in the lower limbs of spastic man can be explained most satisfactorily by the autogenic inhibitory action of the secondary spindle ending and its afferent fibres on extensor motoneurons (Burke, Gillies and Lance, 1970, Commonwealth Postgraduate Scholar and Adolph Basser Research Fellow in Neurology. 2 National Health and Medical Research Council Research Assistant. "Edwin and Daisy Street Research Fellow in Neurology. Fellow of the Toronto Western Hospital, Toronto, Canada.

2 32 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY 1971; Burke, Andrews and Ashby, 1971). n the decerebrate cat Liddell and Sherrington (1924) were unable to demonstrate a similar length-dependent inhibitory response: "so long as the stretch increases the reflex continues to increase." Later authors have confirmed this by measuring the reflex response under static conditions (Granit, 1958) or dynamic conditions (Matthews, 1959). t is possible that the absence of a clasp-knife phenomenon in the stretch reflex of the decerebrate cat is due to tonic inhibitory control of the flexor reflex afferent ("FRA") pathways from the brainstem (Eccles and Lundberg, 1959). To test this hypothesis the stretch reflex of the decerebrate cat has been studied using techniques identical to those used in spastic man. By selective spinal cord and brain-stem lesions attempts have been made to reproduce the length-dependent responses which have been found to underlie the clasp-knife phenomenon of human spasticity. MATERALS AND METHODS Thirty cats, weighing 2-5 kg, were used in these experiments. n 18, spinal lesions were made one to four weeks before the definitive experiment. n the remaining 12, lesions were made during the course of the definitive experiment after the properties of the stretch reflex of the "intact" decerebrate cat had been documented. n addition incomplete chronic spinal lesions were often extended surgically during the definitive experiment. The chronic lesions were made under aseptic conditions after a lower thoracic laminectomy performed during intraperitoneal pentobarbitone sodium anaesthesia. The spinal lesion was made surgically in 11 cats after opening the dura transversely and infiltrating the dorsal columns with 1 per cent procaine. Despite this infiltration, touching the dorsal columns provoked excessive movements so that it was difficult to make a discrete lesion. n 7 cats diphtheria toxin was injected into the spinal cord to produce a more localized lesion, using a method similar to that described by McDonald and Sears (1970). Doses of 4-10 ixl of a solution containing a total of 0-6xl0~" to 18 X10"' Lf units of diphtheria toxin were injected rapidly through a shielded 26G needle into the spinal cord using a micrometer syringe mounted on a stereotactic micromanipulator. The dura was not opened for these lesions, and the post-operative course was less complicated than that of cats with surgical lesions. After an extensive cord lesion an indwelling urinary catheter was left in place. Penicillin and streptomycin were administered subcutaneously for five days post-operatively. For the definitive experiment, anaesthesia was induced with ethyl chloride, a tracheostomy was performed and the animal was maintained on an ether/oxygen mixture. A cannula was inserted into one carotid artery to monitor the blood pressure and the other was ligated. All animals were decerebrated in a Kopf stereotactic apparatus by mid-brain section, the ether then being discontinued. The level of decerebration was varied deliberately in different preparations, and in five cats the mid-brain was sectioned again at a lower level to study the effect of the level of section. Temperature was monitored by a rectal thermocouple and was maintained between 35 C and 38 C by an electric blanket. Blood pressure was monitored continuously and parenteral fluids administeied via the intracarotid cannula if necessary. Excessive laryngeal and bronchial secretions resulting from the administration of ether for decerebration were controlled by the prior administration of atropine 0-4 mg. intramuscularly. Acute spinal lesions were made surgically after a low thoracic laminectomy and incision of the dura. For these sections the cat was paralysed with gallamine triethiodide to prevent movements resulting from stimulation of the dorsal columns. The animals were artificially ventilated by a Palmer pump until recovery from the muscle relaxant, the stroke volume of the ventilator being adjusted for the weight of the animal. The wound was then closed to prevent cooling.

3 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 33 Brain-stem lesions were made with a sharpened metal spatula. A posterior fossa craniotomy was performed and the dura overlying the cerebellum incised. The metal spatula was driven vertically through the cerebellum and brain-stem along stereotactic co-ordinates using a micromanipulator. A 2 mm wide spatula was used for unilateral lesions and a 4 mm wide spatula for bilateral lesions. A pool was fashioned out of skin flaps and the cerebellum immersed in warm paraffin. The temperature of the pool was monitored and maintained between 35 C and 38 C by radiant heat and immersed light bulbs. Stretch reflexes were not recorded until one and a half to two hours had elapsed after the cessation of ether anaesthesia. For testing, the cat lay in the prone position with its head held in the stereotactic frame and the hind-limbs fixed by steel pins driven through the lower end of the femur. f flexion of the knee resulted in excessive movement of the pelvis, clamps were placed on the iliac spines or greater trochanters. The limbs were not denervated routinely and the quadriceps and hamstrings muscles were stretched manually by passive movements of the knee-joint in order to reproduce a testing situation identical to that used in spastic man and comparable with that used by Sherrington (1909). The hind-limb and paw were strapped to the arm of a goniometer which measured knee-joint angle. The EMG of the quadriceps and hamstrings was recorded in most experiments by pairs of stainless steel needles or wire electrodes inserted transversely through the muscles. Extreme care had to be taken with the placement of these electrodes to ensure that the EMG traces were not contaminated by movement artefact. Despite continued attempts, EMG traces could not be obtained free of artefact in 9 cats, so an 80 cps low frequency filter was introduced into the recording system by passing the EMG potentials through Tektronix RM 122 low-level preamplifiers before displaying them on the paper recorders. The reflex component of the EMG tracing did not appear to be distorted by this filter. The responses to changes in muscle length were studied using linear movements divided into 3 sequential steps of equal amplitude, and sinusoidal movements of small amplitude in which the centre of oscillation was systematically varied. For these movements the goniometer output was differentiated (time constant 5 msec) to provide a voltage proportional to angular velocity, and the reflex EMG records were integrated (time constant 0-2 sec). The velocity of stretch, joint position, direct EMG and integrated EMG were recorded simultaneously on 2 four-channel paper recorders, one for the quadriceps and the other for the hamstrings. The experimental arrangement was otherwise as described by Burke, Gillies and Lance (1970,1971). The results obtained by these methods of stretching were confirmed by determining the relationship of the reflex response to the phase of a sinusoidal stretching movement. The raw EMG potentials were amplified and full-wave rectified, and the responses to a number of stretching cycles were averaged on afixed-programmeaveraging computer. The readout of the computer was displayed on an oscilloscope and photographed with a Polaroid oscilloscope camera. Details of the experimental arrangement and the interpretation of results were described by Burke, Andrews and Gillies (1971). Briefly, it is considered that if a reflex is length-dependent reflex EMG will become maximal in the second half of the stretching phase, close to the position of greatest stretch, but if it is velocity-dependent it will tend to reach a peak closer to the middle of the stretching phase where the velocity of stretch is maximal. Maximal EMG activity will therefore occur earlier in the cycle than the position of greatest stretch, the amount of this "phase lead" depending on the degree of velocity-dependence, but never exceeding 90 degrees in a sinusoidal cycle of 360 degrees. f the effect of muscle stretch is inhibitory then the reflex response should occur in the first half of the stretching phase, closer to the position of least stretch. The extent of brain-stem and spinal cord lesions was determined by serial frozen sections 65 ft thick. Sections were stained with Luxol fast blue and neutral red. The level of decerebration was checked at autopsy.

4 34 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY RESULTS The Stretch Reflex of the Decerebrate Cat The stretch reflex of the quadriceps muscles of the decerebrate cat varied with the level of mid-brain section, the more caudal the lesion the more prominent the response to maintained stretch. n 6 cats with intercollicular decerebration (as used by Sherrington) the dynamic component of the stretch reflex was predominant, and on cessation of movement the EMG activity subsided to a lower level (fig. la). The force opposing knee flexion appeared greatest during the stretching movement. During maintained stretch the reflex EMG did not disappear entirely and further stretching again evoked a reflex response. Velocity Angle _) l_ A i r 0 2mV FG. 1. Stretch reflex of the decerebrate cat. Two types of decerebrate preparation are illustrated: the intercollicular decerebrate (a), and the precollicular decerebrate (b). n b, the stretch reflex consists of only a dynamic response to muscle stretch. n a, there is a prominent dynamic response, but this subsides to a plateau, static level on maintained stretch. n both preparations, the reflex response increases with increased muscle stretch. Time marker 1 second/division. Amplitude of stretch 100 degrees for both preparations. With precollicular lesions (6 cats) there was usually little or no static stretch reflex, the response to muscle stretch dying away once movement had ceased, although the dynamic component was prominent (fig. lb). n two of these preparations however a static stretch reflex of moderate degree was found, probably due to functional impairment of brain substance distal to the lesion. Low decerebration, through or below the inferior colliculi (5 cats), consistently caused a prominent static stretch reflex, except in preparations which had deteriorated, the dynamic response being more resistant to a fall in blood pressure. n some of these preparations, the static stretch reflex was so large that the dynamic response could not be distinguished. n all preparations the reflex response increased with increasing muscle stretch, becoming maximal when the quadriceps was fully stretched, shown by linear stretching in fig. 1 and by sinusoidal stretching in fig. 2. The length-dependent inhibition which underlies the clasp-knife phenomenon of spastic man could not be demonstrated.

5 SPASTCTY, DECEREBRATE RGroiTY AND THE CLASP-KNFE PHENOMENON 35 Velocity Angle r ntegrated EMC EMG FG. 2. The stretch reflex of the decerebrate cat. Small sinusoidal oscillations of the limb are made at different centres of oscillation. As the centre of oscillation moves to a more stretched position the reflex response increases. The effect of muscle stretch is facilitatory. Time marker 1 second/division; amplitude of stretch e 0 degrees, f 100 degrees; EMG calibration 0-5 mv; velocity calibration 300 degrees/i'ec. With sinusoidal stretching the peak of the reflex response of the quadriceps led the most stretched point of the cycle in all preparations, even those with such static bias that the dynamic response had been obscured during linear stretching movements. There was a response even with the slowest stretching movement and it was therefore not possible to define a threshold rate of stretching for the quadriceps stretch reflex. At 025 cps the peak EMG activity was advanced up to 45 degrees on the most stretched position, and at higher rates of stretching the lead increased towards 90 degrees (fig. 3). With rates of stretching up to 2 cps this phase lead did not exceed 90 degrees. No significant difference was found between the response of the more static or the more dynamic preparations at these rates of sinusoidal stretching. A phase lag of peak EMG behind the position of greatest stretch was not encountered. Occasionally a transient reflex response was obtained from the hamstrings using linear stretching movements but this occurred only at fast velocities of stretch at the most stretched position. With sinusoidal stretching a hamstrings reflex was obtained occasionally, but only at rates of stretching above 1 cps, the phase lead being approximately 90 degrees. Spinal Cord Lesions (a) Complete cord lesions. A stretch reflex could not be obtained from the quadriceps of animals with acute complete cord lesions. Of 6 cats with chronic complete cord lesions increased muscle tone was noted clinically in the quadriceps of 3 and this resistance was of clasp-knife variety. n 2 of

6 36 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY o-sacps FG. 3. Phase relationships of the quadriceps stretch reflex of the decerebrate cat. At 0-25 cps, the peak of the EMG activity occurs late in the stretching phase of the sinusoidal cycle, slightly in advance of position of greatest stretch. At 0-5 cps, this phase lead has increased to approximately 45 degrees. At 0-5 cps the gain of the amplifier was half that at 0-25 cps. Stretching is represented by an upward deflection of the angle record. Amplitude of stretch 100 degrees. these cats the lesion was surgical and in the third diphtheritic. n the remaining 3 cats the tone of the quadriceps was depressed clinically, and electromyographically there was no consistent response to muscle stretch. Occasional EMG potentials could be evoked, but these were sporadic and of low voltage. The posture of these 3 cats was that of "paraplegia-in-flexion," and each cat suffered from extensive sacral pressure sores and urinary infection. n the 3 cats with an exaggerated quadriceps stretch reflex and clasp-knife phenomenon, increasing muscle stretch resulted in suppression of the quadriceps stretch reflex. With sinusoidal stretching movements of small amplitude the reflex response was maximal when the limb was oscillating about the least stretched position of the quadriceps, but diminished and disappeared as the centre of oscillation was moved to a more stretched position (fig. 4a). f the stretching movement was divided into three steps the resultant EMG response was greatest during the first step, but was diminished or absent in subsequent steps of the movement (fig. 4b). A stretch reflex was prominent in the hamstrings of all 6 chronic spinal preparations. The reflex response of the hamstrings increased with increasing muscle stretch in much the same way as the quadriceps stretch reflex of the "intact" decerebrate cat. The phase relationships of the reflex responses to sinusoidal movements were studied in 3 preparations. n 2 of these tone in the quadriceps was increased and the peak of the reflex response occurred in the first hah 0 of the stretching cycle, close to

7 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 37 a b Velocity Angle JUT integrated EMG EMG l. f FG. 4. The quadriceps stretch reflex of the chronic spinaj cat. n a, the EMG activity becomes maximal when the limb is oscillating about its least stretched position. The effect of muscle stretch is inhibitory. n b, the stretching movement has been divided into three sequential steps performed at equal velocities. A significant reflex response occurs only during the first step. Calibrations velocity 300 degrees/sec; angle e 0 degrees; f 100 degrees; EMG 0-5 mv; time 10 seconds. the position of least stretch (fig. 5). n contrast, the reflex response of the hamstrings occurred late in the stretching cycle. (b) Partial cord lesions. Partial spinal cord lesions were made to define the smallest lesion necessary to reproduce the length-dependent inhibition of the quadriceps stretch reflex found in the chronic spinal cat. n two cats, chronic spinal hemisection produced such a response on the ipsilateral side and in one cat with chronic bilateral dorsal quadrant section length-dependent inhibition of both quadriceps stretch reflexes developed after the animal had been decerebrated. Diphtheritic toxin was injected into the spinal cord of 7 cats to produce more discrete lesions. The injection was made rapidly to try to minimize diffusion of the toxin, to produce necrosis rather than demyelination, and thus to ensure that conduction in fibres passing through the lesion would be maximally impaired. Disability was fully developed within thefirstforty-eight hours, and recovery occurred over the following three to four days. After a maximum of seven days the clinical condition remained stable. n one animal already mentioned a large dose of relatively concentrated toxin caused paraplegia and a histologically complete spinal cord lesion. n the other 6 preparations much smaller doses of toxin caused minimal clinical disability after one week. Diphtheritic lesions confined to the dorsal columns or central grey matter (fig. 6A) produced only mild ataxia, and had no effect on the stretch reflexes when the animals were later decerebrated. The quadriceps stretch reflex increased with increasing

8 38 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY Quadriceps v\ Hamstrings FG. 5. Phase relationships of the reflex responses of the chronic spinal cat at 0-75 cps that the quadriceps occurs early in the stretching phase, leading the position of greatest stretch by 130 degrees. The EMG of the hamstrings occurs late in the stretching phase, leading the position of greatest stretch by approximately 30 degrees. muscle stretch, as in the intact decerebrate cat (fig. 7a), and little EMG could be evoked from the hamstrings. From these experiments it seemed that the pathways controlling the response of the quadriceps to changes in muscle length traversed the dorsolateral funiculus. n 3 cats, small diphtheritic lesions were therefore made in different areas of the lateral column, predominantly the dorsal half. These lesions involved up to one-third of the dorsolateral funiculus but clinically the animals recovered completely, there being no apparent disability after six days. After decerebration length-dependent facilitation typical of the "intact" decerebrate cat was found. t was concluded that the pathway controlling the response to muscle length was not localized to any particular site within the dorsolateral funiculus but was dispersed throughout this area. n acute experiments with the animal paralysed by gallamine triethiodide, discrete lesions were made surgically in the ipsilateral dorsal quadrant of both "intact" decerebrate cats and those with incomplete diphtheritic lesions. A surgical lesion 1

9 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 39 Velocity Angle ^ j^-jawu Vj^jj* r i EMG FG. 7. Reflex response of the quadriceps after spinal lesions, a, After chronic diphtheritic lesion involving central grey matter and contralateral lateral column. The effect of muscle stretch is facilitatory, as in the intact decerebrate cat. A similar response was obtained on the contralateral side, b, After ipsilateral dorsal quadrant lesion in the same cat. The effect of muscle stretch is inhibitory, as in the chronic spinal cat. Only slight changes occurred in the reflex pattern of the contralateral quadriceps. Calibrations as in fig. 4. involving the entire ipsilateral dorsal quadrant (fig. 6B) reversed the effect of increasing muscle stretch from facilitation to inhibition (fig. 7b). Such lesions also released the hamstrings stretch reflex, and caused an increased reactivity to "noxious" stimuli, seen as EMG of hamstrings in response to cutaneous stimulation. As in chronic spinal preparations, the hamstrings stretch reflex increased with increasing muscle stretch. Sometimes the effect of muscle stretch on the quadriceps stretch reflex was only partially altered by a dorsal quadrant lesion, so that the EMG became maximal in the midposition. Some stretch was needed to produce a stretch reflex so that, in the first half of the range of stretch, the reflex increased as muscle length increased; later, as the quadriceps approached its full length, further stretching inhibited the reflex. The effects of unilateral dorsal quadrant section were predominately ipsilateral. Sometimes small but similar changes occurred in the stretch reflexes of the contralateral side, but histologically the contralateral lateral column was found to have been involved by the earlier diphtheritic lesion, if only to a minor extent, as in fig. 6A (Plate V). A lesion which reversed the effect of muscle stretch on the quadriceps stretch reflex also altered the phase relationships of the stretch reflex during sinusoidal stretching. The reflex response of the quadriceps occurred earlier in the stretching cycle at the same rate of stretching (fig. 8A).

10 40 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY A CONTROL B CONTROL A. ' SPNAL. LESON BRANSTEM LEBON FG. 8. Phase relationships of the quadriceps stretch reflex after surgical lesions, A, The effect of a dorsal quadrant lesion. n the control trace peak EMG activity occurs late in the stretching phase, leading the position of greatest stretch by almost 30 degrees. After the spinal lesion, at the same rate of stretching, the phase lead increases to 90 degrees. Same cat as in figs. 6 and 7. B, The effect of a brain-stem lesion. n the control trace the phase lead of EMG on length is approximately 45 degrees, but following the brain-stem lesion, the phase lead at the same rate of stretching exceeds 90 degrees. n each trace, stretching is represented by an upward deflection of the angle record, and the amplitude of stretch is 100 degrees. Brain-stem Lesions n 4 decerebrate cats transverse lesions were made in the caudal brain-stem to define the origin of the descending pathway controlling the responses of lower limb muscles to stretch. Angl* 1 FG. 10. The effect of a medial transverse lesion in the caudal pons on the reflex pattern of the quadriceps of the "intact" decerebrate cat. a, Control trace in the "intact" decerebrate cat. The effect of muscle stretch is facilitatory. b, After brain-stem lesion. The facilitatory effect of muscle stretch is abolished, and is replaced by a predominantly inhibitory response. Calibrations time maiker 1 sec/div; amplitude of stretch e 0 degrees, f 100 degrees; EMG 0-5 mv.

11 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 41 Medial transverse lesions immediately caudal to the facial colliculus, 7-10 mm posterior to the interaural line (fig. 9), reversed the effect of increasing muscle stretch on the quadriceps stretch reflex from facilitation to inhibition. This reversal was seen with small sinusoidal stretching movements (fig. 10) and with stepwise linear stretching movements (fig. 11). After the lesion continuous EMG activity was present in the quadriceps at rest at its position of least stretch, but this was inhibited by muscle stretch (fig. lib) and also by cutaneous stimulation (fig. lie). Angla ntegrated EMG EMC FG. 11. The effect of a medial transverse lesion in the caudal pons on the reflex pattern of the quadriceps of the "intact" decerebrate cat. a, Control trace in the "intact" decerebrate cat. The effect of muscle stretch is facilitatory. b, After brain-stem lesion. The effect of muscle stretch is inhibitory, c, Cutaneous stimulation. After the brain-stem lesion, there is continuous EMG activity in the quadriceps at rest in its least stretched position. This activity is inhibited by perineal stimulation, as indicated on the time marker, suggesting that flexor reflex afferents other than group have also been disinhibited by the lesion. Calibrations as for fig. 10. Lesions at this level had no effect on the hamstrings stretch reflex, so it was possible to release an extensor-inhibitory effect of the FRA without releasing a flexor stretch reflex. More caudal mid-line lesions in the upper medulla had no further effect on the quadriceps stretch reflex, but released both the reactivity of the hamstrings to cutaneous stimuli and the hamstrings stretch reflex, much as spinal lesions had done. With sinusoidal movements, the phase relationships of the quadriceps EMG were consistently altered by brain-stem lesions. The peak of the quadriceps EMG occurred earlier in the stretching cycle, leading the position of greatest stretch by more than 90 degrees (fig. 8B). Using a small spatula of 2 mm width, an attempt was made in 2 cats to determine whether the projections of these brain-stem centres were lateralized. A unilateral lesion which extended to within \-\ mm of the mid-line (fig. 9B) had little effect on the reflex pattern of the decerebrate cat. f the lesion extended over the mid-line (fig. 9c) bilateral release of the "extensor-inhibitory" effects resulted. Further extension of the lesion had only minimal effects. A wide brain-stem lesion extending laterally for 4-6 mm abolished decerebrate rigidity on the ipsilateral side presumably due to disturbance of the lateral vestibular nucleus and the vestibulospinal pathways.

12 42 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY DSCUSSON The classical features of the stretch reflex of the decerebrate cat demonstrated with linear stretching movements by Liddell and Sherrington (1924, 1925), Granit (1958) and Matthews (1959) and with sinusoidal stretching movements by Jansen and Rack (1966), have been confirmed in this electromyographic study. The stretch reflex was confined largely to extensor muscles, although at times an ill-sustained dynamic response was obtained from the hamstrings at high velocities of stretch. With linear stretching movements both dynamic and static components of the quadriceps stretch reflex could be distinguished, but the static component varied with the level of mid-brain section, being more prominent with more caudal lesions. With sinusoidal stretching EMG potentials occurred in advance of the position of greatest stretch, a criterion used by Jansen and Rack (1966) to indicate dynamic sensitivity. Such a phase lead was found in all decerebrate preparations, even those in which the dynamic component of the stretch reflex had been masked by a prominent static stretch reflex. The stretch reflex of the decerebrate cat increased as muscle stretch increased and a length-dependent inhibitory response such as is found in spastic man could not be demonstrated. By clinical and electromyographic criteria the reflex response of intercollicular decerebrate cats usually subsided when the stretching movement was stopped and the muscle held in the stretched position. With further stretching the resistance again built up, but again subsided on cessation of movement. t is possible that this dying away of the dynamic stretch reflex constitutes what has been called the "lengthening reaction." Thus in the intercollicular decerebrate cat the lengthening reaction may be due not to autogenic inhibition but merely to passive fall-off in reflex tension on cessation of movement. This conclusion is not really unexpected. The stretch receptors, the afferent fibres of which are known to be capable of producing autogenic inhibition of extensor reflexes, are the Golgi tendon organ and the secondary spindle ending, and indeed Granit (1964) has suggested that both receptors are responsible for the lengthening reaction. The Golgi tendon organ has been said to be insensitive to passive changes in muscle length (Houk and Henneman, 1967), but during a stretch reflex the stretched muscle is contracting so that passive stretch may result in a significant increase in tendon organ firing rate (Stuart, Mosher and Gerlach, 1971). However the reflex pathway from the Golgi tendon organ appears to be "switched off" in the decerebrate preparation (Eccles and Lundberg, 1959) so it is unlikely that an effective inhibitory action could result. Similar control of the group afferent pathway has been demonstrated (Eccles and Lundberg, 1959), so that it is also difficult to postulate a major inhibitory role for the secondary spindle ending in decerebrate rigidity. On the contrary, Matthews (1969) has suggested that in the decerebrate preparation activation of the secondary ending produces autogenic facilitation of extensor reflexes. n any event, the secondary spindle ending is unlikely to be of importance in the lengthening reaction of the intercollicular decerebrate cat. 1

13 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 43 Thus in the decerebrate preparation there appears to be no segmental reflex pathway capable of producing length-dependent autogenic inhibition of extensor reflexes. Moreover both this and earlier studies have failed to demonstrate such inhibition. The simplest and most satisfactory explanation, consistent with all the studies mentioned, is that the lengthening reaction of the decerebrate cat is due to the passive decline in reflex tension to a plateau "tonic" level on cessation of movement. This does not appear to be the case in the spinal preparation. The lengthening reaction described by Sherrington in the spinal dog appears analogous to the clasp-knife phenomenon of spastic man. Similarly in the chronic spinal cat, provided "paraplegia-in-flexion" does not supervene, extensor muscle tone may become exaggerated, with a clasp-knife phenomenon identical to that studied in spastic man by Burke, Gillies and Lance (1970, 1971) and Burke, Andrews and Gillies (1971). The pattern of extensor inhibition and flexor facilitation produced by muscle stretch is consistent with the reflex effects of the secondary spindle ending, and it is reasonable to presume that the absence of such reflex effects in the decerebrate cat PONS MEDULLA FRA ALPHA FG. 12. The dorsal reticulospinal system. The two components of this system are illustrated the pontine reticulospinal projections control the inhibitory actions of the FRA, and the medullary reticulospinal projections control the facilitatory actions of the FRA. The two components project bilaterally down the spinal cord, traversing the dorsolateral funiculus.

14 44 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY may be due to tonic inhibitory control of the group afferent pathway from the brain-stem. By selective spinal cord and brain-stem lesions it has been possible to delineate a pathway which in the decerebrate cat controls these presumed group reflex effects (fig. 12). This pathway appears to be functionally equivalent and anatomically identical to that described for the FRA by Holmqvist and Lundberg (1959, 1961) and Engberg, Lundberg and Ryall (1968a, b) using electrical stimulation of afferent fibres. The responsible pathway appears to be widely dispersed throughout the dorsolateral funiculus, and in this study the effects of this controlling pathway appeared to be predominantly unilateral. These results differ from those expected on the basis of the studies of Lundberg and colleagues only in the degree of lateralization, but on this point the results presented are in accordance with those of Liddell et al. (1932) who demonstrated release of flexion reflexes after purely unilateral cord lesions. The apparent discrepancy between this study and those of Lundberg and colleagues may well result from differences in technique. n the latter studies';, afferent fibres were activated electrically by single shock stimulation, while in the experiments reported here afferent fibres were activated more physiologically by muscle stretch. Holmqvist and Lundberg (1961) showed that the control of the FRA pathways arose from the ventromedial part of the reticular formation in the caudal brain-stem, and that medial transverse lesions in this area were capable of disinhibiting the reflex effects of the FRA. Analogous results have been obtained in this study: similar lesions have been found capable of reversing the effect of muscle stretch on the quadriceps stretch reflex from facilitation to inhibition. Low pontine lesions were found by Holmqvist and Lundberg (1961) to disinhibit only the inhibitory reflex effects from the FRA, while release of the facilitatory effects resulted only from more caudal lesions in the medulla. n equivalent experiments reported here, pontine lesions disinhibited the inhibitory effect of muscle stretch on the quadriceps stretch reflex but did not release a stretch reflex in the hamstrings or increase its reactivity to cutaneous stimulation. Medullary lesions released the hamstrings stretch reflex, in which the effect of muscle stretch was facilitatory, but had no further effect on the quadriceps stretch reflex. The centres responsible for the extensor inhibitory and flexor facilitatory reflex actions can thus be distinguished anatomically by the level of brain-stem lesion. These centres appear to arise from mid-line structures which project bilaterally down the spinal cord, traversing the dorsolateral funiculus. These reticulospinal pathways are not the only ones influencing transmission from the FRA. Stimulation of the pyramidal system increases the reflex effects of the FRA (Lundberg and Voorhoeve, 1962) probably by an action on the interneurons of these pathways (Lundberg, Norrsell and Voorhoeve, 1962). n spasticity a lesion of the pyramidal pathways would thus remove a supraspinal action facilitating transmission

15 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 45 from the FRA. Since the reflex effects of the secondary ending are readily demonstrable in spastic subjects in the form of the clasp-knife phenomenon, the removal of the pyramidal influence on FRA transmission must be compensated by lesions in pathways inhibiting FRA transmission. n spinal spasticity the causative lesion probably interrupts the dorsal reticulospinal system. The release of the group afferent pathway to the motoneuron would result in the extensor inhibitory action seen clinically as the clasp-knife phenomenon. The release of other FRA pathways would increase the tendency to flexor spasms. Complete disinhibition resulting from bilateral cord lesions or complete transverse cord section would greatly bias the spinal reflex pattern in favour of flexor muscles. n the neglected patient the constant stimulation of cutaneous and bladder afferents would cause inhibition of extensor motoneurons and facilitation of flexor motoneurons so that the posture adopted would be that of "paraplegia-inflexion." n spasticity due to brain-stem lesions the dorsal reticulospinal system would be interrupted near its source of origin. With a bilateral pontine lesion release of only the inhibitory reflex effects of the FRA would produce the clasp-knife phenomenon, but due to the absence of the facilitatory effects on flexor muscles, it would be expected that flexor spasms would be rare in comparison with the spinal patient. Following bilateral medullary lesions, should the patient survive, release of the facilitatory effects of the FRA would tend to allow flexor spasms as in the spinal patient. A unilateral brain-stem or spinal lesion would partially disinhibit these pathways but the effects would not be as profound due to the persistence of control from the intact contralateral side. n spasticity due to cortical or internal capsular lesions, the precise role of the dorsal reticulospinal system is not clear. The extensor-inhibitory actions of the FRA may be seen in the form of the clasp-knife phenomenon but whether this arises from a low degree of activity in the dorsal reticulospinal system or from a lesion in corticoreticular pathways controlling the dorsal reticulospinal system, is at this stage conjectural. t may be concluded that the activity of the dorsal reticulospinal system plays a major role in determining the clinical manifestations of spasticity and in differentiating the spastic and decerebrate states. The absence of a clasp-knife phenomenon in the stretch reflex of the decerebrate cat may be attributed to a high degree of activity in this system, while in spasticity the presence of a clasp-knife phenomenon suggests either a lesion of, or a low degree of activity in, the dorsal reticulospinal system. SUMMARY The stretch reflexes of the decerebrate cat have been analysed using electromyographic methods. Dynamic and static components of the stretch reflex were identified, and both were found to increase with increasing muscle stretch. t was

16 46 DAViD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY therefore suggested that the "lengthening reaction" of the intercollicular decerebrate cat is not an autogenic inhibitory phenomenon, but is due to passive decline in reflex resistance on cessation of movement. n the chronic spinal cat, increasing muscle stretch inhibited the stretch reflex of extensor muscles, thus producing a clasp-knife phenomenon. On the other hand, muscle stretch facilitated the stretch reflex of flexor muscles. This pattern is consistent with the activation of secondary spindle endings whose group afferent pathways have been disinhibited by spinal transection. The pathway responsible for the control of such group reflex effects in the decerebrate preparation was investigated by acute and chronic spinal lesions and by acute brain-stem lesions. The pathway thus delineated arose from the brain-stem reticular formation and projected bilaterally down the spinal cord traversing the dorsolateral funiculus. t appeared identical to the "dorsal reticulospinal system" described by Lundberg and colleagues as responsible for the decerebrate control of the flexor reflex afferents. The role of this dorsal reticulospinal system in spasticity is discussed. ACKNOWLEDGMENTS The authors thank Professor James W. Lance for his advice and constructive criticisms throughout this study. Dr. David Gillies helped in some of the earlier experiments and Dr. Ross Mellick with the preparation of diphtheritic lesions. Mr. Ken Norcross and Mr. Neville Skuse gave technical help. llustrations were photographed by the Department of Medical llustration, University of New South Wales. These investigations were supported by grants from the National Health and Medical Research Council of Australia, the Adolph Basser Trust, Mr. and Mrs. Edwin Street and the University of Toronto, Canada. REFERENCES BURKE, D., ANDREWS, C, and ASHBY, P. (1971) Autogenic effects of static muscle stretch in spastic man. Arch. Neurol., 25, ,, and GLLES, J. D. (1971) The reflex response to sinusoidal stretching in spastic man Brain, 94, , GLLES, J. D., and LANCE, J. W. (1970) The quadriceps stretch reflex in human spasticity. J. Neurol. Neurosurg. Psychiat., 33, ,, (1971) Hamstrings stretch reflex in human spasticity. /. Neurol. Neurosurg. Psychiat., 34, ECCLES, R. M., and LUNDBERG, A. (1959) Supraspinal control of interneurones mediating spinal reflexes. /. Physiol., Lond., 147, ENGBERG,., LUNDBERG, A., and RYALL, R. W. (1968a) Reticulospinal inhibition of transmission in reflex pathways. /. Physiol., Lond., 194, ,, (19686) Reticulospinal inhibition of interneurones. /. Physiol., Lond., 194,

17 SPASTCTY, DECEREBRATE RGDTY AND THE CLASP-KNFE PHENOMENON 47 GRANT, R. (1958) Neuromuscular interaction in postural tone of the cat's isometric soleus muscle. /. Physiol., Lond., 143, (1964) The gamma (y) loop in the mediation of muscle tone. Clin. Pharmac. Ther., 5, HOLMQVST, B., and LUNDBERG, A. (1959) On the organization of the supraspinal inhibitory control of interneurones of various spinal reflex arcs. Archs ital. Biol., 97, , (1961) Differential supraspinal control of synaptic actions evoked by volleys in the flexion reflex afferents in alpha motoneurones. Actaphysiol. scand., 54, Suppl HOUR, J., and HENNEMAN, E. (1967) Responses of Golgi tendon organs to active contractions of the soleus muscle of the cat. /. Neurophysiol, 30, JANSEN, J. K. S., and RACK, P. M. H. (1966) The reflex response to sinusoidal stretching of soleus in the decerebrate cat. /. Physiol., Lond., 183, LDDELL, E. G. T., MATTHES, K., OLDBERG, E., and RUCH, T. C. (1932) Reflex release offlexormuscles by spinal section. Brain, 55, , and SHERRNGTON, C. S. (1924) Reflexes in response to stretch (myotatic reflexes). Proc. R. Soc. B, 96, , (1925) Further observations on myotatic reflexes. Proc. R. Soc. B., 97, LUNDBERG, A., NORRSELL, U., and VOORHOEVE, P. (1962) Pyramidal effects on lumbo-sacral interneurones activated by somatic afferents. Acta physiol. scand., 56, , and VOORHOEVE, P. (1962) Effects from the pyramidal tract on spinal reflex arcs. Acta physiol. scand., 56, MCDONALD, W.., and SEARS, T. A. (1970) Focal experimental demyelination in the central nervous system. Brain, 93, MATTHEWS, P. B. C. (1959) The dependence of tension upon extension in the stretch reflex of the soleus muscle of the decerebrate cat. /. Physiol., Lond., 147, (1969) Evidence that the secondary as well as the primary endings of the muscle spindles may be responsible for the tonic stretch reflex of the decerebrate cat. /. Physiol., Lond., 204, SHERRNGTON, C. S. (1909) On plastic tonus and proprioceptive reflexes. Q.~ Jl exp. Physiol, 2, STUART, D. G., MOSHER, C. G., and GERLACH, R. L. (1971) Properties and central connections of Golgi tendon organs with special reference to locomotion. n: "Symposium on Muscle and the Muscle Spindle." Edited by B. Banker, R. J. Pryzbylsky, J. Van der Meulen and M. Victor, Excerpta Medica, Amsterdam.

18 48 DAVD BURKE, LYNDSAY KNOWLES, COLN ANDREWS AND PETER ASHBY LEGENDS FOR PLATES PLATE V FG. 6. Extent of spinal lesions, A, Diphtheritic lesion (chronic spinal lesion). Reflexes tested on the right side of the preparation (fig. 7a). B, Acute spinal lesion (surgical) made during the definitive experiment in the same cat, altering the reflex pattern as shown in fig. 7b. PLATE V FG. 9. Brain-stem lesions, A, Longitudinal section showing 3 parallel lesions traversing the brain-stem. The most rostral lesion, involving predominately the ipsilateral side, altered the quadriceps stretch reflex as in figs. 10 and 11, but did not release a reflex response in the hamstrings. The middle lesion extended further over the mid-line to involve the contralateral side, but did not further alter the reflex pattern. The caudal lesion in the upper medulla released a hamstrings stretch reflex, B and c, A 2 mm. wide mid-line lesion (c) was sufficient to produce the effects seen in figs. 11 and 12, but a more lateral lesion (B) had no effect on the reflex pattern. (Received 6 July 1971)

19 PLATE V Fio. 6. To illustrate article by David Burke, Lyndsay Knowles, Colin Andrews and Peter Ashby.

20 PLATE Vf FG. 9A. FG. 9B. FG. 9C. To illustrate article by David Burke, Lyndsay Knowles, Colin Andrews and Peter Ashby.