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Late flexion reflex in paraplegic patients. Evidence for a spinal stepping generator
Brain Reseurch Bulletin, Vol. 22, pp. 53-56. 0 Pergamon Press plc, 1989.Printed in the U.S.A.
0361.9230/89$3.00 + .OO
Late Flexion Reflex in Paraplegic Patients. Evidence for a Spinal Stepping Generator’ B. BUSSEL, A. ROBY-BRAMI,
A. YAKOVLEFF
AND N. BENNIS
INSERM U 215, Handicap Moteur Neurologique et croissance Hopital Raymond Poincark, 92380 Garches, France
BUSSEL, B., A. ROBY-BRAMI, A. YAKOVLEFF AND N. BENNIS. Lateflexion reflex in paraplegicpatients. Evidence for BRAIN RES BULL 22(l) 53-56, 1989. -We demonstrated previously that electrical stimulation of the Flexor Reflex Afferents (FRA) induces a late flexion reflex with a central conduction time longer than 100 msec. Its latency is prolonged by increasing the intensity or the duration of the stimulation. This late reflex is therefore similar to the late flexion reflex observed in acute spinal cat with DOPA. Some findings suggest that in man the late flexion reflex could be inhibited at a premotoneuronal level by contralateral FRA stimulation. In relation to the late flexion reflex, a late contralateral facilitation of soleus monosynaptic reflex (MSR) was observed. Rhythmical activity was observed in only one patient who had an exceptional form of spinal myoclonus. This myoclonus could be modulated by FRA stimulation. These facts show that the reflex organization in paraplegic patients is similar to the one described in acute spinal cat with DOPA and therefore suggest that a spinal stepping generator could exist in humans. a spinal stepping generator.
Man
Paraplegia
Late flexion reflex
Spinal stepping generator
FLEXION withdrawal reflexes are well known in patients with spinal lesions. They were recognized in patients with spinal cord section since the pioneer studies performed after the first world war. Flexor reflexes are usually the prominent characteristic of spinal automatic activity, and it is generally assumed that this is linked to the release of the flexion reflex pathways from supraspinal control. The electrophysiological study of the flexion reflexes in man began only in 1954 with Pedersen (17). The flexion reflex was elicited by electrical stimulation of a peripheral distal nerve and was recorded by Electromyography (EMG) in ipsilateral flexor muscles. In normal subjects, as well as in patients with lesions of the central nervous system, it was demonstrated (6, 10, 11, 17) that the minimum latency of the flexion reflex (100 msec or less), considering the length of the conduction pathway in man, was consistent with the classical description of flexion reflexes (14,20). These previous studies focused on the early response since in normal human or in patients who could voluntarily move their legs, the later responses could be due to a voluntary reaction independently from spinal reflexes. Recently, we systematically studied the flexor reflexes in a group of patients with a clinically complete spinal cord section (18). As described before (S), we observed that these reflexes could be separated into early and late EMG responses (Fig. 1). The early response did not differ from the flexion reflexes described in normal man (11,22) and was similar to the flexion reflex described in spinal animals. The late response was
characterized by its latency which could last longer than 130 msec, and vary with the intensity of the stimulation. Strangely, its latency was regularly longer when stronger stimulations were applied (Fig. 1). Its threshold was lower than the threshold of the early response. We investigated the nature of this late response. It obviously originated from spinal reflexes since the patients had a complete spinal cord section. However, it could be due to any other previous motor response: the movement activating afferents which could, in turn, act back at spinal level to elicit a later response. We demonstrated (18) that both the late response and its latency increase did not depend on any previous motor response (whatever it was, either a direct motor response or an early flexion reflex) and that they were directly related to the electrical stimulation. We estimated that its minimum central delay was of more than 100 msec. In addition we observed that the latency of the late reflex was increased if the duration of the electrical trains was increased (Fig. 2). Thus, the late response could be considered as a proper spinal reflex whose main property was that its latency could increase if the intensity of the stimulation was increased or if the duration of the train of electrical pulses was increased. These properties showed that the late reflex was similar to the late reflex described by Lundberg and co-workers in the acute spinal cat with DOPA [see review in (2,15)]: in the acute spinal cat, DOPA depresses the early flexion reflex and induces the appearance of a late flexion reflex, by releasing it from an
‘Service de reeducation neurologique du Professeur Held.
53
BUSSEL,
54
I
I
Id
I
lm I)
1
FIG. 1, Flexor responses obtained simultaneously in tibialis anterior (TA) and biceps femoris (BF) after sural nerve stimulation. Example of rectified EMG traces for different stimulation intensities (noted in the middle of the figure).
1mV I
8 : : : : 0200400600aoo FIG. 2. Responses obtained in posterior nerve stimulation. Each vidual rectified EMG recordings. mA (5 times the threshold for the cles). The stimulus artifact shows msec).
:
:
:
:
:
1
lOOOMl0 tibialis anterior (TA) after tibialis trace represents the average of 3 indiThe stimulation intensities were of 50 direct motor response of plantar musthe train duration (60, 160, 260, 360
inhibitory tonic control exerted by the early reflex pathways. In fact, their central conduction times are in the same range; both can be delayed by prolongation of the stimulation, the late reflex in human and the onset of the dorsal root potential associated with the late reflex in cat can be delayed by stronger
ROBY-BRAMI,
YAKOVLEFF
AND BENNIS
stimulations; the afferents responsible for the appearance and the delay of the late reflex are similar in man and in cat. The wiring connections proposed by Lundberg [see (15)] for the FRA (Flexor Reflex Afferent) pathways perfectly fit with our results in paraplegic man. An obvious difference between the reflexes observed in paraplegic patients and in the acute spinal cat injected with large doses of DOPA is that the late reflex was constantly obtained in man without any pharmacological activation. it must be pointed out that the late reflex was observed in the acute spinal cat before any injection as long as the early flexion reflex was mildly excitable. It is possible that in man, the oathwavs resnonsible for the earlv flexion reflex are less excitable (or iheir inhibitory influence-on the late reflex less important) than they usually are in the acute spinal cat. This may be due to some change linked to the chronicity of the lesion (such as denervation hypersensitivity or sprouting). Chronic spinal cats may also exhibit the late flexion reflex, but usually only if they are spinalized shortly after their birth (1,7). SIGNIFICANCE LATE
Ol-
I Ht
REFLEX
PRESbNC‘E IN
OF A
MAN
The resemblance between the late flexion reflexes observed in paraplegic man and in the acute spinal cat with DOPA has great consequences on practical and theoretical points of view. In fact, besides the ipsilateral flexion reflex, DOPA and other catecholaminergic drugs induce functional spinal reorganization. These changes, including the appearance of a presynaptic inhibition elicited by FRA on Ia terminals, converge on an “half center” organization (12,16) able to generate rhythmic motor activity. The presence of late reflexes in man led us to propose the hypothesis that the functional spinal reflex organization in paraplegic patients is related more closely to the “DOPA network” than to the usual reflex models, established mainly from the study of acute spinal animal preparations. According to this hypothesis, we systematically investigated the effects of FRA stimulation in paraplegic patients. Electrical stimulation of FRA usually induces only an ipsilateral late flexion reflex. As opposed to the acute spinal cat with DOPA, contralateral late extensor activity was seldom observed in man (3 among 16 patients) and was particularly labile. However, the excitability level of silent motoneurones may indirectly be studied by the means of monosynaptic reflex (MSR) studies (Fig. 3). It has been shown (4) that the FRA induce both early and late facilitation phases of the contralatera1 soleus MSR which probably reflects the subliminar contralateral extension reflexes. On the ipsilateral soleus, FRA induce two inhibitory phases, sometimes separated by facilitation, which delays correspond respectively to the latencies of the early and the late reflexes. Contralateral soleus MSR facilitation can be followed by later inhibition. It is possible that this late and prolonged (several seconds) inhibition observed on ipsilateral and sometimes contralateral soleus MSR is due to presynaptic inhibition on Ia terminals. However, until now, it has not been possible to test this hypothesis. As it has been shown by Jankowska et al. (12), the “half center organization relies on strong mutual inhibitory connections between the central pathways activated by ipsi- or contralateral FRA and connected respectively to flexors or to extensors.” This pattern cannot be studied in man since there was usually no late contralateral extensor activity in paraplegic patients. However, using bilateral stimulation of the FRA, we observed that the duration of the late flexion reflex was reduced if it was preceded (or followed) by contralateral FRA stimulation (Fig. 4). This fact cannot be due only to inhibition
FLEXION REFLEXES IN PARAPLEGIC
SOLEUS Ii REFLEX
PATIENTS
AFTER CONTROLATERAL FRA STIMJLATION
control
+ o FRA
-lO&, 0
4m 2m DaAY BETWEEN FRA AND
aw H REFLEX STIMULATIONS
aal
imo
(m.ec>
FIG. 3. Effect of sural nerve stimulation on the contralateral soleus H reflex. Each conditioned H reflex was compared to a control H reflex, adjusted at half its maximum size. The stimulation intensity was 50 mA. The delay between the sural nerve stimulation and the stimulation eliciting the H reflex is indicated in abscissa. The H reflex is expressed as a percentage of variation: (Conditioned - Control) x lOO/Control.
r:::::::::1
the MSR in TA was not inhibited within the same delay) or to presynaptic inhibition from FRA to FRA (since the initial part of the late reflex was usually not depressed). These bilateral effects could be due to some inhibitory processes acting at internuncial level, this being consistent with the data obtained in spinal cat with DOPA. In paraplegic patients, we generally do not observe proper rhythmical activity. However, recently, we have had the opportunity to study a patient (5) with a clinically complete spinal cord section who exhibited rhythmical contractions in trunk and lower limb muscles. This is a rare symptom appearing after a spinal lesion, which is called “spinal myoclonus” in clinical neurology. The myoclonus consisted of rhythmical contractions, at approximately 0.5 Hz frequency, in some extensor muscles of the trunk and of both lower limbs. Several arguments show that the rhythm was unlikely due to a peripheral loop (such as one EMG discharge inducing reflexively another one) and so favour the hypothesis that this rhythmical EMG activity was due to an intrinsic spinal rhythmical activity. This myoclonus which appeared in phase in extensor muscles on both sides induced great functional disturbance and was clinically far from normal human locomotion. However three facts suggest that the spinal stepping generator could be involved. Firstly, it has been reported (13) that the spinal stepping generator, when activated, can induce other rhythmical activities such as rhythmical bilateral activity in extensor muscles. Secondly, its frequency was consistent with the one of human locomotion. Thirdly and mainly, this intrinsic spinal rhythm was greatly modulated by FRA stimulation. The rhythmic activity usually appeared after stimulation of the FRA, conversely FRA stimulation could interrupt rhythmical activity. When a flexion reflex was obtained, it appeared frequently as a rhythmic flexor activity intercalated between the extensor EMG bursts, thus constructing a true rhythmic flexor extensor activity. The rhythmic activity could be driven by iterative elecacting
directly
on the
motoneurones
(since
control
*
4
02a3400600800
+ c FRA 1ooome
FIG. 4. Effect of a contralateral FR.4 stimulation on the TA response. Each trace represents the average of 5 individual rectified EMG recordings obtained after an ipsilateral sural nerve stimulation (intensity 25 mA). For each figure, the upper trace (control) shows the effect of the ipsilateral stimulation alone and the lower trace (+ c FRA) the effect of the combined stimulations. The contralateral FRA stimulation is indicated by an arrow. Its intensity was 50 mA. It was delivered 200 msec before (A) or 200 msec after (B) the ipsilateral stimulation.
trical FRA stimulation (if the frequency of the stimulation was lower than the one of the spontaneous rhythm). Both the presence of the late reflex in paraplegic man and the observation of a proper spinal rhythm in one patient suggest that some elements of the spinal circuitry on which the generation of the stepping rhythm relies in lower vertebrates exist in adult man. The intimate constitution of the stepping generator and its relationship with the pathways of the late reflex are still controversial (9,16). Nevertheless in experiments obtained in acute spinal animals after DOPA (8, 12, 21) it was demonstrated that the presence of the late flexion reflex was linked to the occurrence of spinal locomotor activity, moreover both activities were also observed in mesencephalic cat after electrical stimulation of the mesencephalic locomotor region (19). Locomotor activity can be observed in spinal animals at a chronic stage, mainly in animals spinalized shortly after birth but also after a training period in animals spinalized at an adult stage (3). In such preparations the presence of the late reflex is not constant. Additional experiments in chronic animals are clearly necessary to precise the relationship between the pathways activated by the FRA and the spinal stepping generator and the influence of chronicity of the lesion on these phenomena. However, the results presented above converge on the hypothesis that the spinal stepping generator is present in the spinal cord of the adult man.
BUSSEL, ROBY-BRAMI,
56
YAKOVLEFF
AND BENNIS
REFERENCES 1. Baker, L. L.; Chandler, S. H.; Goldberg, 1,. J. L-DOPA induced locomotor-like activity in ankle flexor and extensor nerves of chronic and acute spinal cats. Exp. Neurol. 86:515-526; 1984. 2. Baldissera, F.; Hultborn, H.; Illert, M. Integration in spinal neuronal systems. In: Brooks, V. B., ed. Handbook of physiology, the nervous system, motor control, sect. I, vol. II, part 1. Bethesda: American Physiological Society; 1981:509-595 (chapter 12). 3. Barbeau, H.; Rossignol, S. Recovery of locomotion after chronic spinalization in the adutt cat. Brain Res. 41284-95; 1987. 4. Bussel, B.; Roby-Brami, A. Effects of FRA in spinal man: late flexion reflex, crossed effects and modifications of the monosynaptic reflex arcs. Neurosci. Lett. [Suppl.] 26:S357; 1986. 5. Bussel, B.; Roby-Brami, A.; Azouvi, Ph.; Biraben, A.; Yakovleff, A.; Held, .I. P. Myocfonus in a patient with a spinal cord section. Possibfe involvement of the spinal stepping generator. Brain, in press; 1988. 6. Dimitrievic, M. R.; Nathan, P. F. Studies of spasticity in man. III. Analysis of reflex activity evoked by noxious cutaneous stimulation, Brain 91:349-368; 1968. 7. Grillner, S. Locomotion in the spinal cat. In: Stein, R. B.; Pearson, K. G.; Smith, R. S.; Redford, J. B., eds. Control of posture and locomotion. New York: PIenum Press; 1973:515-535. 8. Grillner, S. Locomotion in vertebrates: Central mechanisms and reflex interaction. Physiol. Rev. 55:247-304; 1975. 9. Grillner, S.; Wallen, P. Central pattern generators for locomotion with special reference to vertebrates. Annu. Rev. Neurosci. 8:233261; 1985. 10. Hagbarth, K. E. Spinal withdrawal reflexes in the human lower limbs. .I. Neural. Neurosurg. Psychiatry 23:222-227; 1960. 11. Hugon, M. Reflexes polysynaptiques et commandes volontaires. contribution a la connaissance de l’organisation nerveuse spinale de I’animal et de I’homme. These de sciences naturelles, Paris; 1967.
12. Jankowska, E.; Jukes, M. G. M.; Lund, S.; Lundberg, A. The effect of DOPA on the spinal cord, 6-Half center organization of interneurons transmitting effects from the flexor reflex afferents. Acta Physiol. Stand. 70:389-402; 1967. 13. Koehler, W. J.; Schomburg, E. D.; Steffens, H. Phasic modulation of trunk muscle efferents during fictive spinal locomotion in cats. J. Physiol. (Lond.) 353:187-197; 1984. 14. Lloyd, D. P. C. Functions organi~tion of the spinat cord. Physiol. Rev. 24:l; 1944. 15. Lundberg, A. Multisensory control of spinal reflex pathways. In: Granit, B.; Pompeiano, O., eds. Progress in brain research. vol. 50. Amsterdam: Elsevier; 1979:1l-28. 16. Lundberg, A. Half-centres revisited. In: Szentagothai, J.; Palkovits, M.; Hamori, J., eds. Regulatory functions of the CNS. Motion and organi~tion principles, advances in physiologic~ sciences. vol. 1. Budapest: Academiai Riado; f981:155-16’7. 17. Pedersen, E. Studies on the central pathway of the flexion reflex in man and animal. Acta Psychiatr. Neurol. Stand. [Suppl.] 88: 1-81; 1954. 18. Roby-Brami, A; Bussel, B. Long latency spinal reflex in man after flexor reflex afferent stimulation. Brain 110:707-725; 1987. 19. Shefchyk, S. J.; Jordan, L. M. Excitatory and inhibitory postsynaptic potentials in alpha motoneurons produced during fictive locomotion by stimulation of the mesencephaiic locomotor region. J. Neurophysiol. 53:1345-1355; 1985. 20. Sherrington, C. S. Flexion reflex of the limb, crossed extensionreflex, and reflex stepping and standing. J. Physiol. (Lond.) 40: 28-121; 1910. 21. Viala, D.; VaIin, A.; Buser, P. Relationship between the “late reflex discharge” and locomotor movements in acute spinal cats and rabbits treated with DOPA. Arch. Ital. Biol. 112:299-306; 1974. 22. Wilier, J. C. Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 3:69-80; 1977.
0361.9230/89$3.00 + .OO
Late Flexion Reflex in Paraplegic Patients. Evidence for a Spinal Stepping Generator’ B. BUSSEL, A. ROBY-BRAMI,
A. YAKOVLEFF
AND N. BENNIS
INSERM U 215, Handicap Moteur Neurologique et croissance Hopital Raymond Poincark, 92380 Garches, France
BUSSEL, B., A. ROBY-BRAMI, A. YAKOVLEFF AND N. BENNIS. Lateflexion reflex in paraplegicpatients. Evidence for BRAIN RES BULL 22(l) 53-56, 1989. -We demonstrated previously that electrical stimulation of the Flexor Reflex Afferents (FRA) induces a late flexion reflex with a central conduction time longer than 100 msec. Its latency is prolonged by increasing the intensity or the duration of the stimulation. This late reflex is therefore similar to the late flexion reflex observed in acute spinal cat with DOPA. Some findings suggest that in man the late flexion reflex could be inhibited at a premotoneuronal level by contralateral FRA stimulation. In relation to the late flexion reflex, a late contralateral facilitation of soleus monosynaptic reflex (MSR) was observed. Rhythmical activity was observed in only one patient who had an exceptional form of spinal myoclonus. This myoclonus could be modulated by FRA stimulation. These facts show that the reflex organization in paraplegic patients is similar to the one described in acute spinal cat with DOPA and therefore suggest that a spinal stepping generator could exist in humans. a spinal stepping generator.
Man
Paraplegia
Late flexion reflex
Spinal stepping generator
FLEXION withdrawal reflexes are well known in patients with spinal lesions. They were recognized in patients with spinal cord section since the pioneer studies performed after the first world war. Flexor reflexes are usually the prominent characteristic of spinal automatic activity, and it is generally assumed that this is linked to the release of the flexion reflex pathways from supraspinal control. The electrophysiological study of the flexion reflexes in man began only in 1954 with Pedersen (17). The flexion reflex was elicited by electrical stimulation of a peripheral distal nerve and was recorded by Electromyography (EMG) in ipsilateral flexor muscles. In normal subjects, as well as in patients with lesions of the central nervous system, it was demonstrated (6, 10, 11, 17) that the minimum latency of the flexion reflex (100 msec or less), considering the length of the conduction pathway in man, was consistent with the classical description of flexion reflexes (14,20). These previous studies focused on the early response since in normal human or in patients who could voluntarily move their legs, the later responses could be due to a voluntary reaction independently from spinal reflexes. Recently, we systematically studied the flexor reflexes in a group of patients with a clinically complete spinal cord section (18). As described before (S), we observed that these reflexes could be separated into early and late EMG responses (Fig. 1). The early response did not differ from the flexion reflexes described in normal man (11,22) and was similar to the flexion reflex described in spinal animals. The late response was
characterized by its latency which could last longer than 130 msec, and vary with the intensity of the stimulation. Strangely, its latency was regularly longer when stronger stimulations were applied (Fig. 1). Its threshold was lower than the threshold of the early response. We investigated the nature of this late response. It obviously originated from spinal reflexes since the patients had a complete spinal cord section. However, it could be due to any other previous motor response: the movement activating afferents which could, in turn, act back at spinal level to elicit a later response. We demonstrated (18) that both the late response and its latency increase did not depend on any previous motor response (whatever it was, either a direct motor response or an early flexion reflex) and that they were directly related to the electrical stimulation. We estimated that its minimum central delay was of more than 100 msec. In addition we observed that the latency of the late reflex was increased if the duration of the electrical trains was increased (Fig. 2). Thus, the late response could be considered as a proper spinal reflex whose main property was that its latency could increase if the intensity of the stimulation was increased or if the duration of the train of electrical pulses was increased. These properties showed that the late reflex was similar to the late reflex described by Lundberg and co-workers in the acute spinal cat with DOPA [see review in (2,15)]: in the acute spinal cat, DOPA depresses the early flexion reflex and induces the appearance of a late flexion reflex, by releasing it from an
‘Service de reeducation neurologique du Professeur Held.
53
BUSSEL,
54
I
I
Id
I
lm I)
1
FIG. 1, Flexor responses obtained simultaneously in tibialis anterior (TA) and biceps femoris (BF) after sural nerve stimulation. Example of rectified EMG traces for different stimulation intensities (noted in the middle of the figure).
1mV I
8 : : : : 0200400600aoo FIG. 2. Responses obtained in posterior nerve stimulation. Each vidual rectified EMG recordings. mA (5 times the threshold for the cles). The stimulus artifact shows msec).
:
:
:
:
:
1
lOOOMl0 tibialis anterior (TA) after tibialis trace represents the average of 3 indiThe stimulation intensities were of 50 direct motor response of plantar musthe train duration (60, 160, 260, 360
inhibitory tonic control exerted by the early reflex pathways. In fact, their central conduction times are in the same range; both can be delayed by prolongation of the stimulation, the late reflex in human and the onset of the dorsal root potential associated with the late reflex in cat can be delayed by stronger
ROBY-BRAMI,
YAKOVLEFF
AND BENNIS
stimulations; the afferents responsible for the appearance and the delay of the late reflex are similar in man and in cat. The wiring connections proposed by Lundberg [see (15)] for the FRA (Flexor Reflex Afferent) pathways perfectly fit with our results in paraplegic man. An obvious difference between the reflexes observed in paraplegic patients and in the acute spinal cat injected with large doses of DOPA is that the late reflex was constantly obtained in man without any pharmacological activation. it must be pointed out that the late reflex was observed in the acute spinal cat before any injection as long as the early flexion reflex was mildly excitable. It is possible that in man, the oathwavs resnonsible for the earlv flexion reflex are less excitable (or iheir inhibitory influence-on the late reflex less important) than they usually are in the acute spinal cat. This may be due to some change linked to the chronicity of the lesion (such as denervation hypersensitivity or sprouting). Chronic spinal cats may also exhibit the late flexion reflex, but usually only if they are spinalized shortly after their birth (1,7). SIGNIFICANCE LATE
Ol-
I Ht
REFLEX
PRESbNC‘E IN
OF A
MAN
The resemblance between the late flexion reflexes observed in paraplegic man and in the acute spinal cat with DOPA has great consequences on practical and theoretical points of view. In fact, besides the ipsilateral flexion reflex, DOPA and other catecholaminergic drugs induce functional spinal reorganization. These changes, including the appearance of a presynaptic inhibition elicited by FRA on Ia terminals, converge on an “half center” organization (12,16) able to generate rhythmic motor activity. The presence of late reflexes in man led us to propose the hypothesis that the functional spinal reflex organization in paraplegic patients is related more closely to the “DOPA network” than to the usual reflex models, established mainly from the study of acute spinal animal preparations. According to this hypothesis, we systematically investigated the effects of FRA stimulation in paraplegic patients. Electrical stimulation of FRA usually induces only an ipsilateral late flexion reflex. As opposed to the acute spinal cat with DOPA, contralateral late extensor activity was seldom observed in man (3 among 16 patients) and was particularly labile. However, the excitability level of silent motoneurones may indirectly be studied by the means of monosynaptic reflex (MSR) studies (Fig. 3). It has been shown (4) that the FRA induce both early and late facilitation phases of the contralatera1 soleus MSR which probably reflects the subliminar contralateral extension reflexes. On the ipsilateral soleus, FRA induce two inhibitory phases, sometimes separated by facilitation, which delays correspond respectively to the latencies of the early and the late reflexes. Contralateral soleus MSR facilitation can be followed by later inhibition. It is possible that this late and prolonged (several seconds) inhibition observed on ipsilateral and sometimes contralateral soleus MSR is due to presynaptic inhibition on Ia terminals. However, until now, it has not been possible to test this hypothesis. As it has been shown by Jankowska et al. (12), the “half center organization relies on strong mutual inhibitory connections between the central pathways activated by ipsi- or contralateral FRA and connected respectively to flexors or to extensors.” This pattern cannot be studied in man since there was usually no late contralateral extensor activity in paraplegic patients. However, using bilateral stimulation of the FRA, we observed that the duration of the late flexion reflex was reduced if it was preceded (or followed) by contralateral FRA stimulation (Fig. 4). This fact cannot be due only to inhibition
FLEXION REFLEXES IN PARAPLEGIC
SOLEUS Ii REFLEX
PATIENTS
AFTER CONTROLATERAL FRA STIMJLATION
control
+ o FRA
-lO&, 0
4m 2m DaAY BETWEEN FRA AND
aw H REFLEX STIMULATIONS
aal
imo
(m.ec>
FIG. 3. Effect of sural nerve stimulation on the contralateral soleus H reflex. Each conditioned H reflex was compared to a control H reflex, adjusted at half its maximum size. The stimulation intensity was 50 mA. The delay between the sural nerve stimulation and the stimulation eliciting the H reflex is indicated in abscissa. The H reflex is expressed as a percentage of variation: (Conditioned - Control) x lOO/Control.
r:::::::::1
the MSR in TA was not inhibited within the same delay) or to presynaptic inhibition from FRA to FRA (since the initial part of the late reflex was usually not depressed). These bilateral effects could be due to some inhibitory processes acting at internuncial level, this being consistent with the data obtained in spinal cat with DOPA. In paraplegic patients, we generally do not observe proper rhythmical activity. However, recently, we have had the opportunity to study a patient (5) with a clinically complete spinal cord section who exhibited rhythmical contractions in trunk and lower limb muscles. This is a rare symptom appearing after a spinal lesion, which is called “spinal myoclonus” in clinical neurology. The myoclonus consisted of rhythmical contractions, at approximately 0.5 Hz frequency, in some extensor muscles of the trunk and of both lower limbs. Several arguments show that the rhythm was unlikely due to a peripheral loop (such as one EMG discharge inducing reflexively another one) and so favour the hypothesis that this rhythmical EMG activity was due to an intrinsic spinal rhythmical activity. This myoclonus which appeared in phase in extensor muscles on both sides induced great functional disturbance and was clinically far from normal human locomotion. However three facts suggest that the spinal stepping generator could be involved. Firstly, it has been reported (13) that the spinal stepping generator, when activated, can induce other rhythmical activities such as rhythmical bilateral activity in extensor muscles. Secondly, its frequency was consistent with the one of human locomotion. Thirdly and mainly, this intrinsic spinal rhythm was greatly modulated by FRA stimulation. The rhythmic activity usually appeared after stimulation of the FRA, conversely FRA stimulation could interrupt rhythmical activity. When a flexion reflex was obtained, it appeared frequently as a rhythmic flexor activity intercalated between the extensor EMG bursts, thus constructing a true rhythmic flexor extensor activity. The rhythmic activity could be driven by iterative elecacting
directly
on the
motoneurones
(since
control
*
4
02a3400600800
+ c FRA 1ooome
FIG. 4. Effect of a contralateral FR.4 stimulation on the TA response. Each trace represents the average of 5 individual rectified EMG recordings obtained after an ipsilateral sural nerve stimulation (intensity 25 mA). For each figure, the upper trace (control) shows the effect of the ipsilateral stimulation alone and the lower trace (+ c FRA) the effect of the combined stimulations. The contralateral FRA stimulation is indicated by an arrow. Its intensity was 50 mA. It was delivered 200 msec before (A) or 200 msec after (B) the ipsilateral stimulation.
trical FRA stimulation (if the frequency of the stimulation was lower than the one of the spontaneous rhythm). Both the presence of the late reflex in paraplegic man and the observation of a proper spinal rhythm in one patient suggest that some elements of the spinal circuitry on which the generation of the stepping rhythm relies in lower vertebrates exist in adult man. The intimate constitution of the stepping generator and its relationship with the pathways of the late reflex are still controversial (9,16). Nevertheless in experiments obtained in acute spinal animals after DOPA (8, 12, 21) it was demonstrated that the presence of the late flexion reflex was linked to the occurrence of spinal locomotor activity, moreover both activities were also observed in mesencephalic cat after electrical stimulation of the mesencephalic locomotor region (19). Locomotor activity can be observed in spinal animals at a chronic stage, mainly in animals spinalized shortly after birth but also after a training period in animals spinalized at an adult stage (3). In such preparations the presence of the late reflex is not constant. Additional experiments in chronic animals are clearly necessary to precise the relationship between the pathways activated by the FRA and the spinal stepping generator and the influence of chronicity of the lesion on these phenomena. However, the results presented above converge on the hypothesis that the spinal stepping generator is present in the spinal cord of the adult man.
BUSSEL, ROBY-BRAMI,
56
YAKOVLEFF
AND BENNIS
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