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      Modulation of Locomotor Patterns and Spasticity with Clonidine in Spinal Cord Injured Patients

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          ABSTRACT:

          This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antogonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.

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          Different types of disturbed motor control in gait of hemiparetic patients.

          The pattern of muscle activation in walking was studied in a group of 26 hemiparetic patients. Electromyograms were taken with surface electrodes from 6 muscle groups of the paretic leg and analysed after rectification and time averaging. The sagittal rotations in hip, knee and ankle joint were determined with intermittent light photography. The muscle activation pattern of each patient was compared to that in healthy subjects as well as to the movements performed by the patient and to the normal movement pattern. The normal patterns of movement and muscle activation were assessed from compiled data from 10 healthy female volunteers and average values of angular displacements and amplitude of intergrated EMG were determined at each 5 per cent of the gait cycle. Change of muscle length was determined with a length recording transducer. Gait capacity varied highly in the group of patients studied and the movement pattern also varied markedly. Three types of abnormal muscle activation pattern were disclosed in the patients. In 9 patients, the calf muscles were prematurely activated in the stance phase, probably due to enhanced stretch reflexes (Type I). In another 9 patients, EMG activity was abolished or extremely low in 2 or more of the muscles examined (Type II). In 4 patients, there was a pathological coactivation of several or all of the muscles during part of the gait-cycle, thus disrupting the normal sequential shift of activity in antagonistic muscles (Type III). In the remaining 4 patients, the muscle activation pattern was more complex and no common pattern was discerned.
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            Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing.

            Spinopetal pathways may be activated by a variety of brainstem manipulations including microinjections of morphine which are known to modulate spinal nociceptive processing. Based on the ability of these manipulations to release spinal noradrenalin; the ability to reverse the antinociceptive effects by intrathecal adrenergic antagonists and the fact that intrathecal injections of noradrenalin mimic the antinociceptive effect, it appears that the descending modulation may be mediated by descending noradrenergic systems. Examination of the spinal receptor systems with intrathecally administered agents indicates that spinal alpha, but not beta adrenergic receptor agonists produce a powerful analgesia as measured on a variety of reflex and operant measures in mouse, rat, cat, primate and man. On the basis of agonist and antagonist structure-activity relationships it appears that a significant effect can be produced in the absence of any detectable effect on motor function by the occupation of spinal alpha 2 receptors. Distinguishable alpha 1 receptors also appear "analgetically-coupled," but their effects are uniformly contaminated by signs of cutaneous hyperreflexia at doses required to produce analgesia. The ordering of potency with which intrathecal adrenergic antagonists reverse the effects of intrathecal noradrenalin is indistinguishable from that of the reversal by these intrathecal agents of the antinociceptive effects evoked by brainstem morphine. This suggests that the population of spinal receptors acted upon by exogenously administered adrenergic agonists and endogenously released noradrenaline have indistinguishable characteristics.
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              The locomotion of the acute spinal cat injected with clonidine i.v.

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                Author and article information

                Journal
                applab
                Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
                Can. J. Neurol. Sci
                Cambridge University Press (CUP)
                0317-1671
                2057-0155
                August 1991
                September 18 2015
                August 1991
                : 18
                : 03
                : 321-332
                Article
                10.1017/S0317167100031887
                3f68977f-a933-43a0-b6fb-5be1d4a7761d
                © 1991
                History

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