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PubMed2006

Development of baclofen tolerance in a rat model of chronic spasticity and rigidity.

Systemic or spinal treatment with baclofen has been associated with the development of tolerance in patients with chronic spasticity. In the present study, we used a rat model of spinal ischemia-induced spasticity to characterize the development of baclofen tolerance after chronic intrathecal (i.t.) baclofen infusion. Following the induction of spinal ischemia and the development of behavioral spasticity, animals were implanted with i.t. catheters connected to osmotic pumps to continuously infuse baclofen (1.0 microg/0.5 microl/h). Hindleg peripheral muscle resistance (PMR) was measured periodically after initiation of chronic infusion and after bolus i.t. baclofen injection (1.0 microg). Peripheral muscle resistance was significantly decreased at the onset of baclofen infusion, however, after 5-7 days of infusion a progressive return of spasticity was noted, where baseline PMR values returned to preinfusion levels. At the same time, the efficacy of bolus i.t. baclofen treatment also decreased, where after 5 days of baclofen infusion 1.0 microg (i.t.) baclofen only reduced PMR by 10% (compared to 40-50% preinfusion). Baclofen efficacy progressively returned once continuous infusion was stopped. These data demonstrate that transient spinal ischemia leads to the development of spasticity which is sensitive to spinal baclofen. Chronic i.t. infusion leads to a progressive development of tolerance. This model offers potential to study tolerance mechanisms after spinal injury, and aid in drug discovery for use in baclofen-tolerant patients.

Animals↗
PubMed1995

Intrathecal baclofen for motor disorders.

To test the efficacy of intrathecal baclofen in various movement disorders, 18 patients with dystonia, head trauma, cerebral palsy, rigidity, or painful spasms underwent a trial of intrathecal baclofen. Ten went on to permanent implantation with an infusion pump to provide long-term treatment. Patients with a component of spasticity, painful spasms, or focal dystonias did best, and no response was seen in patients with rigidity due to anoxic encephalopathy. A videotape of responses is provided.

Adolescent↗
PubMed2006

A comparison of the effects of imposed extension and flexion movements on Parkinsonian rigidity.

OBJECTIVE: To test a hypothesis that Parkinsonian rigidity is more pronounced in imposed extension than flexion movement. METHODS: Twelve Parkinsonian subjects (both "Off" and "On" medication states) and seven control subjects participated in the protocol, in which a servomotor imposed wrist flexion and extension. Rigidity was quantitatively evaluated by the rectified torque integral with time, i.e., temporal score, and by the torque integral with joint angle, i.e., work score, for extension and flexion, respectively. RESULTS: In the "Off" state, the imposed extension induced a significantly higher resistance than did flexion. Dopaminergic medication significantly reduced the temporal score associated with imposed extension, and significantly decreased the work score of both movements. Compared with controls, the scores were higher for patients in the "On" state. CONCLUSIONS: Rigidity is more readily elicited in extension movement. The distinction is not evident in clinical practice, whereas it can be clearly revealed with the application of biomechanical analyses. SIGNIFICANCE: This distinction may prove to be a standard feature of rigidity. The procedures may be helpful in diagnosis and useful in evaluating new treatments and developing rehabilitation programs.

Aged↗
PubMed1987

Neurosurgical management of spasticity, rigidity, and tremor.

In this review, the authors present a critical overview of the historical development, indications, complications, operative techniques, and results of procedures for the alleviation of the major dyskinesias. Emphasis is placed upon recent refinement of technique, particularly stereotaxis, as well as neurophysiologic stimulation and recording, computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). Specific disorders that may be amenable to surgical therapy include spasticity secondary to spinal cord pathology, cerebral palsy, and multiple sclerosis; the tremor and rigidity of Parkinson's disease; essential tremor; dystonia; spasmodic torticollis; post-traumatic and postinfarction intention tremor; cerebral palsy with tremor; hemiballismus; myoclonus; and dyskinesias induced by L-DOPA.

Humans↗
PubMedDate not supplied

Haloperidol complications in burn patients.

Neuropsychiatric complications are commonly seen in major burn patients. Haloperidol is frequently used to treat severe psychopathic behavior. We have noted severe muscle rigidity-an extrapyramidal side effect of the agent-in a number of burn patients. Haloperidol causes a relative imbalance of dopaminergic and cholinergic neuronal activity in the basal ganglia with a relative increase in cholinergic activity being responsible for EPS. The burn patient may be more prone to extrapyramidal symptoms because of increased sensitivity of skeletal muscle neuromuscular junctions to acetylcholine after thermal injury.

Adolescent↗
PubMed1990

[Characteristics of the development of bilateral extrapyramidal symptomatology in patients with Parkinson disease].

The prevalence of extrapyramidal disorders was studied in 91 patients with bilateral parkinsonism. Formation of bilateral hyperkinesis or rigidity may take place according to the three variants: mirror, cross and mirror-cross. During the stage of the formed bilateral syndrome, the patients with rigid-trembling and trembling-rigid parkinsonism demonstrated predominant involvement into the pathological state of the upper limbs with a possible uniform of prevalent manifestation in them of extrapyramidal symptomatology.

Adult↗
PubMed2006

Bradykinesia in patients with essential tremor.

We compared the level of bradykinesia during rapid alternating movements (RAM) in patients with essential tremor (ET) with that of patients with Parkinson's disease (PD) having either the "tremor dominant" or "akinetic-rigid" form of PD, and 10 healthy controls. We found an increase of pronation-supination cycle duration in the PD and ET group, suggestive of bradykinesia. RAM range was, however, similar between groups. The akinetic-rigid group showed a distinct increase in RAM amplitude fluctuation, suggesting that rigidity modified the characteristics of the observed bradykinesia. In conclusion, slow movements should then be considered as part of the ET symptomatology.

Adult↗
PubMed1985

Continuous intrathecal baclofen for severe spasticity.

Baclofen is the most effective drug for the treatment of rigidity and spasms caused by damage to the spinal cord, but frequently, relatively little relief is afforded and dose is limited by central side-effects. To improve the efficiency of drug delivery 6 patients received implantable programmable pumps with a catheter going into the lumbar subarachnoid space. Baclofen, at doses of 12 micrograms to 400 micrograms per day, was given for up to 7 months. With intraspinal treatment there was an immediate reduction of muscle tone to normal levels, and spontaneous spasms were eliminated. Patients experienced less discomfort, and daily activities were more easily accomplished.

Adult↗
PubMed2002

Transmission of group II heteronymous pathways is enhanced in rigid lower limb of de novo patients with Parkinson's disease.

A potent heteronymous excitation of quadriceps motoneurones via common peroneal group II afferents has recently been demonstrated in normal subjects. The aim of this study was to investigate whether this group II excitation contributes to rigidity in Parkinson's disease. The early and late facilitations of the quadriceps H reflex elicited by a conditioning volley to the common peroneal nerve (CPN) at twice motor threshold, attributed to non-monosynaptic group I and group II excitations, respectively, were investigated. The comparison was drawn between results obtained in 20 "de novo" patients with Parkinson's disease (hemiparkinsonian, 17; bilateral, three) and 20 age-matched normal subjects. There was no statistically significant effect of "group" (patients/controls), "duration", "global severity" [Unified Parkinson's Disease Rating Scale (UPDRS)] or "side" (unilaterally versus bilaterally affected) factors on either group I or group II facilitations. To further the analysis, the factors of status (affected or non-affected limb), akinesia (lower limb akinesia score) and rigidity (lower limb rigidity score) were entered in a general linear model to explain the variations of the quadriceps H reflex facilitation. Rigidity was the only factor useful in predicting the value of the group II facilitation of the quadriceps H reflex (P < 0.007). Group I and group II facilitation was then compared between the rigid, non-rigid and control lower limbs [multivariate analysis of variance (MANOVA)]. Results are represented as mean +/- SEM (standard error of the mean). Group II facilitation was enhanced in the rigid lower limb of unilaterally affected patients (153.2 +/- 7% of control H reflex) compared with non-rigid lower limbs (124 +/- 4% of control H reflex; P < 0.007) or control lower limbs (126.1 +/- 4.1%; P < 0.01). There was no difference between the non-rigid lower limbs of the unilaterally affected patients and the control lower limbs, but a difference was observed between the rigid lower limbs of unilaterally less affected and bilaterally more affected patients (153.2 +/- 7% and 123.8 +/- 7.5% of control H reflex, respectively; P < 0.04). These results suggest a facilitation of the transmission in the interneuronal pathway activated by group II afferents in rigid lower limb of de novo hemiparkinsonian patients, probably resulting from a change in their descending monoaminergic inhibitory control.

Adult↗
PubMed1988

The association of gegenhalten in the upper limbs with dyspraxia.

Ten patients with gegenhalten of the upper limb of mixed aetiology were studied, in nine of whom an association with dyspraxia was found. In four of the patients, the rigidity became more pronounced after the instruction to relax, and only one patient showed improvement after this instruction. In these patients, the resistance to movement, evident as gegenhalten, may be a direct consequence of the dyspraxia.

Aged↗
PubMed2005

Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter.

In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion resistance meter which permits a semi-automated, computer-controlled measurement of peripheral muscle resistance (PMR) in the lower extremities during a forced flexion of the ankle in the awake rat. Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After ischemia the presence of spasticity component was determined by the presence of an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive or proprioceptive afferent activation and by velocity-dependent increase in muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of morphine. Animals with defined ischemic spasticity or morphine-induced rigidity were then placed into a plastic restrainer and a hind paw attached by a tape to a metal plate driven by a computer-controlled stepping motor equipped with a resistance transducer. The resistance of the ankle to rotation was measured under several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50 degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4 sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone treatment. In animals with ischemic paraplegia an increased EMG response after peripheral nociceptive or proprioceptive activation was measured. In control animals average muscle resistance was 78 mN and was significantly increased in animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a significant increase in measured muscle resistance was seen after increased velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of pretreatment values. Systemic treatment with morphine induced muscle rigidity and corresponding increase in muscle resistance. Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotation and was reversed by naloxone. These data show that by using this system it is possible to objectively measure the degree of peripheral muscle resistance. The use of this system may represent a simple and effective experimental tool in screening new pharmacological compounds and/or surgical manipulations targeted to modulate spasticity and/or rigidity after a variety of neurological disorders such as spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or Parkinson's disease.

Anesthetics, Inhalation↗
PubMed2000

Decrease in presynaptic inhibition on heteronymous monosynaptic Ia terminals in patients with Parkinson's disease.

PURPOSE: Heteronymous Ia facilitation from the quadriceps to the soleus was studied to clarify central motor control through presynaptic inhibition (PSI) on Ia terminals of spinal motoneurons in Parkinson's disease. METHODS: 17 patients with Parkinson's disease and 36 control subjects participated in the study. Because the early part of facilitation reflects the degree of PSI, the extent of facilitation was quantified as the slope, within 0.8 msec of onset. RESULTS: Heteronymous Ia facilitation in the patients was greater than in the age-matched control participants. PSI was negatively correlated with the walking speed of the patients. In the patients examined twice, lessening of bradykinesia was correlated to a decrease in PSI but not lessening of rigidity. CONCLUSION: These findings indicate that the degree of PSI is decreased and disturbance of the central control of PSI may relate to gait disturbance in Parkinson's disease.

Adult↗