Stimulation of the subthalamic nucleus increases heart rate in patients with Parkinson disease.
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Aged↗
Biomedical subjects
J M Gracies
Publications and source records attributed to J M Gracies.
Neurophysiological modulation of the subthalamic nucleus by pallidal stimulation in Parkinson's disease.
OBJECTIVES: Current models of basal ganglia dysfunction in Parkinson's disease suggest a pivotal role of subthalamic nucleus (STN) hyperactivity. There is a direct excitatory output to the globus pallidus internus (GPi), which in turn hyperinhibits the motor thalamus and leads to a lack of cortical facilitation. The model, however, does not address the reciprocal influence of GPi on STN activity. METHODS: Measurement of immediate changes in STN single cell activity after GPi deep brain stimulation (DBS). RESULTS: An opposite effect of GPi DBS in the dorsal versus ventral STN was found. There was an almost exclusive reduction of firing rate in the dorsal region of the STN, whereas the cells in the ventral region exhibited facilitation similar to the recordings from the substantia nigra pars reticulata. CONCLUSION: Although these findings require confirmation, they suggest that the current theories of GPi DBS action, which do not include a GPi-STN modulation, are most likely incomplete.
Aged↗
Early morning off-medication dyskinesias, dystonia, and choreic subtypes.
BACKGROUND: Abnormal involuntary movements (dyskinesias) are common in patients with Parkinson disease (PD) as a consequence of the disease and dopaminergic replacement therapy. Early morning off-medication choreic dyskinesias have been recently reported after fetal dopaminergic cell transplantations in patients with advanced PD. OBJECTIVE: To determine the frequency and severity of the early morning off-medication dyskinesias in consecutive patients with advanced PD and an insufficient response to medical management before they undergo neurosurgery. METHODS: Consecutive patients with advanced idiopathic PD were examined and videotaped before undergoing neurosurgery that included pallidotomy, fetal transplantation, or deep brain stimulation. The examination took place in the morning in the practically defined off state, at least 12 hours after the last dose of dopaminergic drugs. Parkinson disease was characterized using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage. Dyskinesias were rated with the Abnormal Involuntary Movements Scale and the Rush Dyskinesia Rating Scale. Patients' characteristics and medications were compared using the Wilcoxon rank sum and the Fisher exact tests. RESULTS: Of 68 consecutive patients (44 [65%] men and 24 [35%] women), 11 (16%) had early morning off-medication dyskinesia, with a 95% upper confidence limit of 24%. Focal dystonia was the most common off-medication dyskinesia, and occurred in 10 patients (15%), with a 95% upper confidence limit of 22%; and off-choreic dyskinesia occurred in 1 patient (1.5%), with a 95% upper confidence limit of 4%. There was no difference in PD medications between the patients with and those without dyskinesias. CONCLUSIONS: The most common form of off-medication dyskinesia seen in patients with advanced PD is dystonia. Early morning off-medication choreic dyskinesias are rare but do occur in patients with advanced PD before surgical intervention. The presence and type of off-medication dyskinesias should be monitored in clinical and surgical studies in patients with PD as part of the safety and evaluation of clinical benefits.
Adult↗
Pathophysiology of impairment in patients with spasticity and use of stretch as a treatment of spastic hypertonia.
Paralysis, muscle shortening, and muscle overactivity are the three main disabling factors in patients with spasticity. Occurring after most central lesions, muscle overactivity and shortening are not equally spread throughout all muscles of the body. In an agonist-antagonist couple, there is invariably "greater" overactivity and shortening of one versus the other. This is the rationale for the use of targeted local treatments that train the weaker agonist and stretch and partially block the more overactive and shorter antagonist. Central paralysis, muscle shortening, and muscle overactivity are intertwined, and the three corresponding therapies, motor training, stretch, and local partial blocks, should be implemented in combination. This triple treatment is the main condition for any functional recovery. Muscle shortening occurs acutely after a central nervous system lesion; therefore its treatment should be implemented as rapidly as possible.
Casts, Surgical↗
Physical modalities other than stretch in spastic hypertonia.
This article reviews various physical modalities that have been used in spastic hypertonia, particularly superficial heat and cold, diathermies (ultrasound, microwave, and short-wave irradiation), electrical stimulation (transcutaneous electrical nerve stimulation), implanted spinal stimulation (rectal stimulation), and massage (deep friction, superficial contact). The duration of the effects of most physical therapies is relatively short (e.g., cooling, heating, and massage), which often may limit their application to immediate prestretch or pre-exercise periods. The potential capacity of ultrasound therapy to improve the efficacy of chronic stretch in lengthening muscle may be a promising option. The neurodestructive potential of high intensity microwave for the personnel involved and controlled evidence of its value is required before this modality can be recommended in spasticity. Overall, controlled, double-blind studies are mandated to evaluate the long-term impact of repeated use of these short-term modalities on function and recovery in patients with spasticity.
Animals↗
Short-term effects of dynamic lycra splints on upper limb in hemiplegic patients.
OBJECTIVE: To assess acceptability, effects on swelling, resting posture, spasticity, and active (AROM) and passive range of motion (PROM) of individually tailored upper limb Lycra garments, designed as dynamic splints to exert directional pull on certain limb segments, when worn for 3 hours by hemiplegic patients. DESIGN: Crossover trial. SETTING: Outpatient and inpatient rehabilitation center. PATIENTS: Convenience sample of 16 patients with hemiparesis and upper limb spasticity caused by a stroke more than 3 weeks before the study. INTERVENTIONS: Assessments performed at the start and end of a 3-hour period during a standard rehabilitation day when the patients were and were not wearing the garment. MAIN OUTCOME MEASURES: (1) Comfort assessed by questionnaire; (2) circumference of each limb segment; (3) resting posture at elbow and wrist; (4) spasticity at shoulder, elbow, and wrist using the Tardieu scale; and (5) AROM and PROM at shoulder, elbow, and wrist measured using a goniometer; (6) elbow proprioception using McCloskey's method; (7) visual neglect syndrome using the line bisection test. Differences between changes occurring with and without the garment were compared using Wilcoxon's signed rank test for ordinal variables (spasticity grading) and Student's t test for continuous variables (all other data). RESULTS: During 3 hours, garments worn on the arm by patients with hemiplegia (1) were comfortable, (2) improved wrist posture and reduced wrist and finger flexor spasticity, (3) reduced swelling in patients with swollen limbs (digit circumference decreased by 4%; p<.01), (4) improved PROM at shoulder (mean increase in range, 4.1 degrees +/- 13.0 degrees per shoulder movement; p<.01); and (5) impaired ability to flex fingers (range of voluntary flexion of digit III reduced from 107.3 degrees +/-79.6 degrees to 91.4 degrees +/-74.1 degrees; p<.05). CONCLUSION: Lycra garments, designed to produce continuous stretch of spastic muscles when worn for several hours each day, have rapid splinting and antispastic effects on wrist and fingers in patients with hemiplegia. These garments may help severely affected patients with major spasticity or painful swollen limbs.
Adult↗
Evidence for fusimotor drive in stroke patients based on muscle spindle thixotropy.
To study fusimotor function in stroke patients, we compared the amplitude of stretch reflexes elicited in flexor carpi radialis (FCR) after contraction of FCR with the wrist held flexed ('hold-short') or extended ('hold-long'). Seven subjects with impaired hand function and spasticity due to stroke, and seven healthy subjects were investigated. Surface electrodes recorded electromyographic activity of wrist flexors and extensors while subjects performed isometric wrist flexions with the wrist alternately in 15 degrees of flexion or extension. After contractions the wrist was moved passively to the mid-position, and stretch reflexes were elicited via controlled mechanical taps delivered over the FCR tendon. For both groups, the amplitude of the stretch reflex was greater after 'hold-short' than 'hold-long' contractions. This finding is consistent with the 'after-effects' of intrafusal fibre activation, and suggests that fusimotor neurones are activated during voluntary contractions of the paretic limb, just as in the limb of a healthy subject.
Adult↗
Neuromuscular blockers.
The use of corrosive, injectable neuromuscular blockers has been a treatment option for many years; however, the more recent advent of botulinum toxin (BTX) treatment has revived interest in localized treatments. This article reviews the use of local anesthetics, alcohol, phenol, and BTX treatment for localized muscular overactivity syndromes.
Anesthetics, Local↗
Bilateral optic disk pallor after unilateral internal carotid artery occlusion.
Bilateral pallor of the optic disks was observed in a 52-year-old man after dissection of an internal carotid artery. Diffuse pallor of the ipsilateral optic disk reflected infarction of the ipsilateral optic nerve and "bow-tie" atrophy of the contralateral optic disk reflected infarction of the ipsilateral optic tract. The findings were due to an occlusion of the internal carotid artery proximal to the origin of the ophthalmic artery, resulting also in insufficiency in the area of supply of the anterior choroidal artery.
Aortic Dissection↗
Paraesthesiae induced by prolonged high frequency stimulation of human cutaneous afferents.
1. The present study has explored the behaviour of human cutaneous afferents following conduction of prolonged trains of impulses at 200 Hz for 10-20 min, correlating the resultant changes in excitability with the perception of paraesthesiae. 2. Tetanization for 10 min resulted in activity-dependent changes in axonal excitability, with an initial period of hyperexcitability, followed by a long-lasting subexcitability. All subjects experienced paraesthesiae soon after cessation of the tetanic train, and these subsided gradually over 16 min. 3. Longer tetanic trains of 20 min duration resulted in greater changes in axonal excitability, but with paraesthesiae of a similar time course. The post-tetanic increase in excitability was abolished when short tetanic trains were delivered > 30 min before long trains, but all subjects still experienced paraesthesiae. 4. Threshold distributions following tetanic stimulation for both 10 and 20 min established that all axons contributing to the sensory volley underwent a uniform pattern of post-tetanic threshold changes. There was no evidence of a bimodal distribution with some axons hyperpolarized and others depolarized, as occurs with motor axons. However, the excitability changes were graded, with axons of lowest threshold undergoing a proportionately greater increase in excitability than axons of higher threshold. 5. The post-tetanic excitability changes were greater at the site of stimulation than elsewhere along the peripheral nerve. However, DC polarizing currents applied at this site failed to alter the sensation of paraesthesiae in the post-tetanic period. Furthermore, local anaesthetic block of the peripheral nerve proximal to the stimulation site failed to suppress the paraesthesiae. 6. The uniform pattern of post-tetanic threshold changes for cutaneous afferents differs from the bimodal distribution seen with post-ischaemic and post-tetanic motor axons. This difference in behaviour may reflect greater inward rectification and greater expression of a non-inactivating threshold conductance in cutaneous afferents. It is suggested that the ectopic activity responsible for paraesthesiae in the post-tetanic period arises from a more central site than the peripheral nerve.
Action Potentials↗
Excitability changes in human cutaneous afferents induced by prolonged repetitive axonal activity.
1. The present study was undertaken to document the excitability changes produced by prolonged high-frequency trains of impulses in cutaneous afferents of six human subjects. 2. Trains of supramaximal stimuli at 200 Hz for 2 min or less produced a prolonged depression in excitability, consistent with activation of the electrogenic Na+-K+ pump. Trains of longer duration resulted in an initial period of hyperexcitability which, with 10 min trains, was associated with the sensation of paraesthesiae in all subjects. This transient hyperexcitability gradually gave way to a long-lasting period of hypoexcitability. 3. The excitability changes were reproducible, and were accompanied by corresponding changes in supernormality, refractoriness, strength-duration time constant and rheobase current, suggesting that the changes in axonal excitability reflected a change in membrane potential. 4. The transient increase in excitability that follows tetanic trains of 10 min had qualitatively similar effects on cutaneous axons as ischaemia or application of a depolarizing current. The post-tetanic changes in the supernormal period of sensory axons were those expected from the changes in excitability, without evidence of a gross distortion in its time course, as has been previously demonstrated in a hyperstimulated human motor axon. 5. It is concluded that the post-tetanic hyperexcitability of human sensory axons is probably driven by increased K+ accumulation in the restricted diffusion space under the myelin sheath, much as in motor axons, the differences in behaviour of sensory and motor axons being explicable by greater inward rectification in sensory axons.
Adult↗
Lycra garments designed for patients with upper limb spasticity: mechanical effects in normal subjects.
OBJECTIVE: To assess the stretch of pronator muscles produced by a specifically designed upper-limb Lycra garment that could have a better acceptability than rigid splints in treating upper-limb spasticity. DESIGN: Double-blind comparison among three garments. They were designed to produce a supinating, a pronating, and no torsional force, and were individually manufactured and tested in 10 healthy volunteers. MAIN OUTCOME MEASURE: Angular position and passive rotational stiffness of the forearm were measured with and without each of the garments immediately after the garment was fitted and every hour for 6 hours. RESULTS: When put on by a trained person, the supinator garment supinated the forearm in all subjects (mean, 17 degrees; p < .01; range, 5 degrees to 44 degrees) while the pronator garment pronated the forearm in 8 of 10 subjects (mean, 5 degrees; p < .01). These effects gradually decayed over 6 hours, as garment position was not readjusted. Passive rotational stiffness of the forearm increased by about 30% with each type of garment. The garments designed to produce no torsional force exerted no intrinsic rotational effect. CONCLUSION: Individually made Lycra garments can produce continuous stretch of muscles for several hours and may be useful in the treatment of spasticity. The garments, however, must be put on by a trained person and their position adjusted when necessary.
Adult↗
Traditional pharmacological treatments for spasticity. Part I: Local treatments.
Spasticity is a velocity-dependent increase in stretch reflex activity. It is one of the forms of muscle overactivity that may affect patients with damage to the central nervous system. Spasticity monitoring is relevant to function because the degree of spasticity may reflect the intensity of other disabling types of muscle overactivity, such as unwanted antagonistic co-contractions, permanent muscle activity in the absence of any stretch or volitional command (spastic dystonia), or inappropriate responses to cutaneous or vegetative inputs. In addition, spasticity, like other muscle overactivity, can cause muscle shortening, which is another significant source of disability. Finally, spasticity is the only form of muscle overactivity easily quantifiable at the bedside. Under the name pharmacological treatments of spasticity, we understand the use of agents designed to reduce all types of muscle overactivity, by reducing excitability of motor pathways, at the level of the central nervous system, the neuromuscular junctions, or the muscle. Pharmacologic treatment should be an adjunct to muscle lengthening and training of antagonists. Localized muscle overactivity of specific muscle groups is often seen in a number of common pathologies, including stroke and traumatic brain injury. In these cases, we favor the use of local treatments in those muscles where overactivity is most disabling, by injection into muscle (neuromuscular block) or close to the nerve supplying the muscle (perineural block). Two types of local agents have been used in addition to the newly emerged botulinum toxin: local anesthetics (lidocaine and congeners), with a fully reversible action of short duration, and alcohols (ethanol and phenol), with a longer duration of action. Local anesthetics block both afferent and efferent messages. The onset of action is within minutes and duration of action varies between one and several hours according to the agent used. Their use requires resuscitation equipment available close by. When a long-lasting blocking agent is being considered, we favor the use of transient blocks with local anesthetics for therapeutic tests or diagnostic procedures to answer the following questions: Can function be improved by the block? What are the roles played by overactivity and contracture in the impairment of function? Which muscle is contributing to pathologic posturing? What is the true level of performance of antagonistic muscles? A short-acting anesthetic can also serve as preparation to casting or as an analgesic for intramuscular injections of other antispastic treatment. Alcohol and phenol provide long-term chemical neurolysis through destruction of peripheral nerve. Experience with ethanol is more developed in children using intramuscular injection, while experience with phenol is greater in adults with perineural injection. In both cases, there are anecdotal reports of efficacy but studies have rarely been controlled. Side effects are numerous and include pain during injection, chronic dysesthesia and chronic pain, and episodes of local or regional vascular complications by vessel toxicity. In the absence of controlled studies, a theoretical comparison of neurolytic agents with botulinum toxin is proposed. Neurolytic agents may be preferred to botulinum toxin on a number of grounds, including earlier onset, potentially longer duration of effect, lower cost, and easier storage. Conversely, pain during injection, tissue destruction with chronic sensory side effects, and lack of selectivity on motor function with neurolytic agents may favor the use of botulinum toxin. Neurolytic agents and botulinum toxin may be used in combination, the former for larger proximal muscles and the latter for selective injection into distal muscles. In the future, neurolytic agents may prove more appropriate in very severely affected patients for whom the purposes of the block are comfort and hygiene. (ABSTRACT TRUNCATED)
Adult↗
Traditional pharmacological treatments for spasticity. Part II: General and regional treatments.
Systemic pharmacologic treatments may be indicated in conditions in which the distribution of muscle overactivity is diffuse. Antispastic drugs act in the CNS either by suppression of excitation (glutamate) enhancement of inhibition (GABA, glycine), or a combination of the two. Only four drugs are currently approved by the US FDA as antispactic agents: baclofen, diazepam, dantrolene sodium, and tizanidine. However, there are a number of other drugs available with proven antispastic action. This chapter reviews the pharmacology, physiology of action, dosage, and results from controlled clinical trials on side effects, efficacy, and indications for 21 drugs in several categories. Categories reviewed include agents acting through the GABAergic system (baclofen, benzodiazepines, piracetam, progabide); drugs affecting ion flux (dantrolene sodium, lamotrigine, riluzole; drugs acting on monoamines (tizanidine, clonidine, thymoxamine, beta blockers, and cyproheptadine); drugs acting on excitatory amino acids (orphenadrine citrate); cannabinoids; inhibitory neuromediators; and other miscellaneous agents. The technique, advantages and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitations appear throughout the controlled studies reviewed: the lack of quantitative and sensitive functional assessment and the lack of comparative trials between different agents. In the majority of trials in which meaningful functional assessment was included, the study drug failed to improve function, even though the antispastic action was significant. Placebo-controlled trials of virtually all major centrally acting antispastic agents have shown that sedation, reduction of global performance, and muscle weakness are frequent side effects. It appears preferable to use centrally acting drugs such as baclofen, tizanidine, and diazepam in spasticity of spinal origin (spinal cord injury and multiple sclerosis), whereas dantrolene sodium, due to its primarily peripheral mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain injury) where sensitivity to sedating effects is generally higher. Intrathecal administration of antispastic drugs has been used mainly in cases of muscle overactivity occurring primarily in the lower limbs in nonambulatory, severely disabled patients but new indications may emerge in spasticity of cerebral origin. Intrathecal therapy is an invasive procedure involving long-term implantation of a foreign device, and the potential disadvantages must be weighed against the level of disability in each patient and the resistance to other forms of antispastic therapy. In all forms of treatment of muscle overactivity, one must distinguish between two different goals of therapy: improvement of active function and improvement of hygiene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic drugs may be more acceptable when the primary goal of therapy is hygiene and comfort than when active function is a priority.
Humans↗
The effect of stimulus duration on the latency of submaximal nerve volleys.
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Action Potentials↗
Non-monosynaptic transmission of the cortical command for voluntary movement in man.
1. The possibility was investigated that, in man, some of the descending command for tonic voluntary wrist extension is transmitted to extensor motoneurones over a non-monosynaptic pathway. 2. Stimulation of the cutaneous superficial radial nerve at 3 times perceptual threshold depressed the electromyogram (EMG) of extensor carpi radialis (ECR) and the discharge of single ECR motor units, both with a mean central delay of 4.2 ms. Such stimuli depressed the response to transcranial magnetic stimulation of the motor cortex, but had little effect on the H reflex. 3. The possibility that the relative sparing of the H reflex was due to an alteration in transmission of the afferent volley for the H reflex was excluded. 4. The central latency of the cutaneous-induced depression of the discharge of single motor units in biceps brachii (C5-C6) was shorter by about 1 ms than that of the more caudal wrist and finger extensor motor units. This suggests that the locus for the cutaneous-induced effects was spinal but above the cervical enlargement. 5. The pattern of EMG depression (evoked by superficial radial but not palmar stimuli, in wrist extensors but not wrist flexors) is that previously described for the presumed propriospinal system of human subjects. 6. It is concluded that a significant component of the voluntary command for tonic wrist extension reaches the relevant motoneurone pool via a non-monosynaptic pathway. It is suggested that the interposed neurones could be C3-C4 propriospinal neurones.
Action Potentials↗
Evidence for corticospinal excitation of presumed propriospinal neurones in man.
1. The possibility that stimulation of the motor cortex facilitates transmission in the pathway mediating non-monosynaptic ('propriospinal') excitation from low-threshold afferents to upper limb motoneurones was investigated. 2. Convergence between peripheral afferent volleys (from the ulnar or musculo-cutaneous nerve) and corticospinal volleys (evoked by magnetic stimulation of the motor cortex) was investigated using the spatial facilitation technique. Thus the effects of these volleys on the flexor carpi radialis H reflex were compared when applied separately and together. When cortical stimulation was optimal for the muscle from which the conditioning volley originated the facilitation of the reflex on combined stimulation was significantly larger than the algebraic sum of the effects of separate stimuli. 3. The extra facilitation on combined stimulation had all the characteristics of 'propriospinal' excitation (low threshold, long central delay, brief duration and depression when the afferent input was increased), and it is suggested that this reflects corticospinal excitation of 'propriospinal' neurones. 4. When varying the time interval between cortical and test stimulations, it was shown that extra facilitation on combined stimulation began 1 ms later than the onset of the control reflex facilitation. Assuming that the latter onset reflects the arrival of the monosynaptic corticospinal volley at the motoneurone pool, this 1 ms delay suggests a disynaptic pathway for the cortical excitation of motoneurones through 'propriospinal' neurones. 5. As at the onset of voluntary movement, the pattern of the cortical excitation of 'propriospinal' neurones was quite specific: extra facilitation of the reflex on combined stimulation only occurred when the cortical volley was preferentially directed to motoneurones supplying the muscle from which the afferents used for the peripheral volley originated. 6. It is concluded that corticospinal axons activate human 'propriospinal' neurones and thereby produce disynaptic excitation of the motoneurone pool. Given temporal summation with the monosynaptic excitation, this 'propriospinally mediated' disynaptic excitation might make a significant contribution to the evoked EMG potential.
Adult↗
Evidence for further recruitment of group I fibres with high stimulus intensities when using surface electrodes in man.
Changes in the firing probability of voluntarily activated motor units in the human lower limb were recorded in response to stimuli applied to peripheral nerves of the lower limb using surface electrodes. In each instance the monosynaptic Ia excitation produced by heteronymous afferent volleys was studied. This peak of excitation was found to increase with the intensity of the stimulation up to 2.5-4 x the motor threshold (MT), i.e., 4-7 x the threshold of Ia afferents. It is concluded that, when using surface electrodes in human subjects, group Ia effects may not be maximal with stimulus intensities below 4 x MT, and the effects evoked by different afferent populations (e.g., Ia and II) cannot be clearly separated solely on the basis of the electrical excitability of these fibres.
Action Potentials↗