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Increased plasma levels of thioredoxin in patients with coronary spastic angina.

To determine whether plasma levels of thioredoxin are associated with coronary spasm, we measured the plasma levels of thioredoxin in 170 patients who had <25% organic stenosis in coronary arteriography. According to the results of cardiac catheterization, we divided the patients into two groups: a coronary spastic angina group (n=84) and a chest pain syndrome group (n=86). The plasma levels of thioredoxin were significantly higher in the coronary spastic angina group than in the chest pain syndrome group (40.7 +/- 4.1 versus 18.2 +/- 1.1 ng/ml, p<0.0001). Furthermore, the increased plasma levels of thioredoxin were associated with high disease activity indicated by the frequency of angina attacks (p=0.0004). In multiple logistic regression analysis, the higher levels of thioredoxin [relative risk 14.8, 95% confidence interval (5.13-42.9), p<0.0001] and current smoking [relative risk 3.39, 95% confidence interval (1.31-8.75), p=0.012] were significant and independent variables associated with coronary spasm. We demonstrated that the plasma levels of thioredoxin were increased in the coronary spastic angina group, and increased levels of thioredoxin were associated with high disease activity. The plasma levels of thioredoxin and current smoking were risk factors for coronary spastic angina, and they were independent from other traditional risk factors.

Adult↗

Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm.

Coronary artery spasm is caused primarily by increased contractility of vascular smooth muscle. Excessive Ca2+ entry into vascular smooth muscle cells (VSMCs) may be one of the key mechanisms for the spasm, but no study has ever directly examined the possible alterations of Ca2+ channels in the spastic coronary artery. Here we show that L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery. In a porcine model of coronary spasm with balloon injury, both receptor-mediated stimulation of L-type Ca2+ channels by serotonin and direct stimulation of the channels by Bay K 8644 (a dihydropyridine Ca2+ channel agonist) repeatedly induced coronary spasm in vivo, which was abolished by pretreatment with nifedipine, a dihydropyridine Ca2+ channel antagonist. In a single VSMC freshly dispersed from coronary arteries in vitro, patch-clamp experiments showed that current density of L-type Ca2+ channel current was significantly increased in VSMCs from the spastic site compared with that from the control site even when the channels were maximally stimulated by Bay K 8644. There was no difference in the sensitivity of the channels to Bay K 8644. These results indicate that functionally available L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery in our porcine model, suggesting that increased expression of L-type Ca2+ channels and concomitant increase in Ca2+ entry into VSMCs through the channels may contribute, at least in part, to the pathogenesis of coronary artery spasm.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

A novel robot training system designed to supplement upper limb physiotherapy of patients with spastic hemiparesis.

Spasticity is velocity and acceleration dependent, and it is therefore important to execute physiotherapeutic exercises at a relatively low and constant velocity. This can be more accurately managed by a robot than by a person when such exercises are administered continuously for more than 15-20 min. The purpose of this project was to construct a robot-mediated system that could support upper limb physiotherapy of patients with spastic hemiparesis. The system, unlike any known robotic therapeutic system, uses unmodified industrial robots to carry out passive physiotherapy on the upper limb (including the movements of the shoulder and the elbow). An initial trial was executed in order to assess its safety and to gain experience of the robot-mediated therapy. Four healthy subjects and eight patients with spastic hemiparesis were included. Each subject received 30-min-long robotic physiotherapy sessions over 20 consecutive workdays. The 12 participants received, in total, 240 robot-mediated physiotherapeutic sessions. No dangerous situation or considerable technical problem occurred; the robots executed the therapy programme as intended. Investigation of the effectiveness of this kind of therapy was not an aim of this initial trial; however, the patients' clinical status was followed and some favourable changes were found regarding the spasticity of elbow flexors and shoulder abductors. According to the experiences of the first clinical investigation, the programming interface and the mechanical interface device between the patient and the robots had been improved. A controlled clinical study is under way to assess the effectiveness of the REHAROB movement therapy.

Adult↗

Comparison of the energy expenditure index and oxygen consumption index during self-paced walking in children with spastic diplegia cerebral palsy and children without physical disabilities.

The aim of this study was to assess whether the Energy Expenditure Index (EEI), based on heart rate (HR) adjusted for speed, was a clinical indicator of the Oxygen Consumption Index (OCI), oxygen consumption (VO(2)) adjusted for speed, during self-paced walking in children with spastic diplegia cerebral palsy (CP) and children without physical disabilities (ND). Ten children with spastic diplegia CP and 15 children who are ND participated. VO(2) and HR were measured at rest and during self-paced ambulation using an AeroSport KB1-C portable metabolic system, and the EEI and OCI were calculated. A fair to good correlation (r = 0.61) between EEI and OCI was found for children with spastic diplegia CP ambulating at self-paced speeds while only a moderate correlation (r = 0.40) was found for children who are ND. The results suggest that the EEI may be a useful clinical indicator of OCI at self-paced ambulation speeds in children with spastic diplegia CP and warrants further investigation.

Journal Article↗

Low-dose botulinum toxin with short-term electrical stimulation in poststroke spastic drop foot: a preliminary study.

OBJECTIVE: To compare low-dose botulinum toxin injections followed by short-term electrical stimulation with high-dose botulinum toxin for poststroke spastic drop foot. DESIGN: Twelve patients with spastic drop foot were randomly assigned to two treatment groups. The first group (n = 6) received low-dose (100 units) botulinum toxin injection to the posterior tibial muscle in combination with short-term electrical stimulation, and the second group (n = 6) received a total of 400 units of botulinum toxin injections in equal doses to the posterior tibial, soleus, medial, and lateral gastrocnemius muscles. The patients were evaluated before and 2, 4, 8, and 12 wks after the treatment by the following variables: resting position angle, active and passive ankle range of motion, Modified Ashworth Scale, time walking 10 m, clonus score, Brace Wear Scale, and Global Assessment of Spasticity Scale. RESULTS: Improvement was recorded in both groups for all variables except brace wear. No significant difference was found between the study groups after treatment. The effects lasted shorter in the first group, whereas more side effects were seen in the second group. CONCLUSIONS: Our preliminary single-blind study was unable to find a difference in terms of effectiveness between low-dose (100 units) botulinum toxin combined with short-term electrical stimulation and high-dose (400 units) application in spastic drop foot.

Anti-Dyskinesia Agents↗

Electrokinesiologic testing of walking in patients with spastic cerebral palsy.

Assessment of walking ability of patients with spastic cerebral palsy has long been a problem. In an attempt to obtain more precise and objective findings, we used the Polgon goniometry method. The study involved testing the gait of 36 spastic patients. We compared clinical findings and Polgon diagrams of healthy children and spastic patients pre- and postoperatively. The results were classified as very good to good, satisfactory, and poor. The advantages of Polgon are that it is painless, does not irritate the patient, and is a simple, objective method. Its disadvantages arise from a relatively large amount of artifacts and inadequacy when it is used on spastic patients.

Adolescent↗

Equilibrium reactions in the feet of children with spastic cerebral palsy and of normal children.

The foot-balancing reactions to posterior and lateral displacement of the body were compared in 20 normal children and 30 children with spastic cerebral palsy. The children were divided into five functional groups in order to describe the normal developmental sequence and to contrast the responses of the feet of the spastic children with those of normal children. Normal children who had been walking for more than six months (advanced walkers) showed adult-like reactions, including ankle and tow dorsiflexion, medial-arch reactions and stepping responses. Normal children who had been walking for less than six weeks (Beginning Walkers) showed less developed ankle and medial-arch reactions and exhibited clawing rather than toe dorsiflexion. Children with spastic cerebral palsy differed significantly from the normal Advanced Walkers in each of the reactions observed. When compared with the normal Beginning Walkers they demonstrated less ankle dorsiflexion and medial-arch reactions but appeared similar in other factors. Differences were noted between the three functional spastic groups.

Cerebral Palsy↗

Knee flexion deformity and patella alta in spastic cerebral palsy.

A study on spastic knee flexion deformity has revealed a recurrence rate of 32 per cent following attempted surgical correction on 170 knees (103 patients). This rate appeared to be unrelated to concomitant surgery for correction of hip and ankle deformity. An additional study demonstrated patella alta in 72 per cent of 100 spastic knees (50 patients) and only 2 per cent and 50 knees of a comparable group of 25 non-spastic patients. It is suggested that restoration of a normal patello-femoral relationship may reduce both the functional disability and recurrence rate of spastic knee flexion deformity when this disease is managed surgically.

Cerebral Palsy↗

A hypothesis for the aetiology of spastic cerebral palsy--the vanishing twin.

The aetiology of spastic cerebral palsy (CP), in the majority of cases, is not known but the general consensus is that cerebral impairment occurs prepartum. In monochorionic twin pregnancies, death of one twin late in gestation is recognised as being an important risk factor for the surviving cotwin to have CP. It has been suggested that a significant proportion of singletons with spastic CP may be the result of death of a cotwin in the second half of gestation. In this paper it is hypothesised that spastic CP of unknown aetiology is the result of the death of a monochorionic cotwin and that the death of the cotwin may impair the neurological development of the survivor throughout gestation. If so, vanishing-twin syndrome, which is now a recognised phenomenon revealed by ultrasound examination in early pregnancy, is important in the aetiology of spastic CP.

Adult↗

Voluntary and reflex control of the biceps brachii muscle in spastic-athetotic patients.

A cross-correlation technique of analysis was used to measure the transmission characteristics of tonic stretch reflex (TSR) pathways in spastic-athetoid subjects sustaining a voluntary contraction in the biceps brachii muscle. A comparison was made with the transmission characteristics of normal subjects measured by the same technique. It was found that gain and phase characteristics of spastic patients did not display the large resonant peaks present in normals. It is proposed that the resonant peaks in the TSR transmission of normal subjects were caused by long loop pathways. The absence of these peaks in the spastic patients supports the hypothesis that short-circuiting of long loop pathways by hyperactive spinal reflexes is part of the mechanism of spasticity.

Arm↗

The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries.

The effects of cyproheptadine, a serotonergic antagonist, were studied in seven patients with spastic paresis of spinal origin. Six patients were included in a double blind crossover trial (maximal dose 24 mg/day). The patients were evaluated on both their spasticity and locomotor function. Four of the patients also participated in an open trial in which cyproheptadine was administered for a minimum of six months at optimal dose. Patients walked on a treadmill at full weight bearing when possible, or with 40% of their body weight externally supported, as required, by an overhead harness system. Cyproheptadine considerably decreased the sustained ankle clonus and episodes of spontaneous spasms observed in all the patients who previously presented these manifestations of spasticity. Two patients who required body weight support (BWS) during locomotion could walk at full weight bearing during cyproheptadine therapy. A more normal timing of EMG patterns in these patients during cyproheptadine therapy was associated with temporal distance changes and marked improvement of joint angular displacement. In contrast, the other patients showed marginal changes in the EMG and the kinematic pattern but eventually managed to walk at a higher speed. These preliminary results suggest that cyproheptadine can reduce spasticity and enhance locomotor function in spinal cord injured patients.

Adult↗

Spasticity management: an overview.

Recent developments in therapeutic interventions for children with spasticity have complicated managerial decision making. A simplified paradigm for the pathophysiology of spasticity is presented, which emphasizes the ways in which treatment modalities disrupt hyperexcitable segmental spinal reflex arcs. Various techniques for the management of spasticity are reviewed, along with factors relevant to proper patient selection for therapeutic intervention. Potential goals for spasticity management are considered as are outcome measures for assessing the efficacy of these technologies.

Anti-Dyskinesia Agents↗

Relationship between serum lipoprotein(a) concentrations and coronary vasomotion in coronary spastic angina.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) concentrations are reported to impair endothelium-dependent vasodilatation of the epicardial coronary artery. However, the effects on vasomotor abnormalities in coronary spastic angina (CSA) have not been thoroughly investigated. METHODS AND RESULTS: In the present study 80 sites of spasm (spastic sites) without significant organic stenosis (% diameter stenosis <50%) were assessed in 80 patients with CSA diagnosed by intracoronary ergonovine (EM) test. Spastic sites were divided into 2 groups: Group 1 included 30 sites provoked by the full dose (=50 microg) of EM, and Group 2 included 50 sites provoked with less than 50 microg (34.7+/-8.2 microg). Control subjects (n=22) did not show coronary spasm with the EM test. Serum Lp(a) concentrations were measured in all patients. Group 2 had a significantly greater basal coronary artery tone in the spastic sites than Group 1 (p<0.001). Lp(a) level in Group 2 was significantly higher compared with both the control group and Group 1 (p<0.05 by analysis of variance). Multivariate analysis confirmed that only serum Lp(a) concentration was associated with low-dose EM spasm provocation. CONCLUSIONS: Serum Lp(a) concentration could be a marker for high disease activity in CSA.

Adult↗

Investigation of the most effective provocation test for patients with coronary spastic angina: usefulness of accelerated exercise following hyperventilation.

This study sought to compare the clinical usefulness of the hyperventilation plus cold stress test or the hyperventilation combined with accelerated exercise test with other single tests in patients with coronary spastic angina. The study examined 24 patients (23 men, mean age 66 years) with angiographically confirmed coronary spastic angina and less than 50% stenosis. Moreover, none had spontaneous ST segment elevation before the study. Under no medication for at least 24 h prior, 4 procedures were performed from 09.00 h to 11.00 h: (i) a hyperventilation test for 5 min (HV(5)); (ii) HV(5) combined with a cold stress test for the last 2 min (HV(5)+CS(2)); (iii) a treadmill exercise test based on Bruce's protocol (TM(3)); and (iv) a treadmill exercise test accelerated at 1 min intervals according to Bruce's protocol immediately after HV(5) (HV(5)+TM(1)). The rate of appearance of chest pain and ischemia-induced ECG changes due to HV(5)+TM(1) were significantly higher than the other 3 tests. HV(5)+CS(2) was not superior to HV(5) alone. The incidence of provoked ST segment elevation due to HV(5)+TM(1) was higher than with the other 3 procedures. Thus, in patients with coronary spastic angina, no spontaneous ST segment elevation and near normal coronary arteries, HV(5)+CS(2) was no more useful than HV(5) alone. It is recommended that the newly designed HV(5)+TM(1) combination test be used for documenting evidence of ischemia in patients with coronary spastic angina, low disease activity and near normal coronary arteries.

Acetylcholine↗

Adductor spastic dysphonia: three years after recurrent laryngeal nerve resection.

The voices of 33 patients, ages 44 to 79 years, were assessed after recurrent laryngeal nerve resection for adductor spastic dysphonia. Voice improvement was noted in all patients 24 hours after surgery: in 97% at 1 month, 97% at 6 months, 82% at 1 year, 70% at 1 1/2 years, 58% at 2 years, 52% at 2 1/2 years, and 36% at 3 years. Of the 64% with failed voices by 3 years, 48% were worse than before surgery. Of the 36% whose voices remained improved, 58% were worse than at any previous period and 42% were better. Failures among women (77%) were considerably higher than among men (36%). Except for one patient, none of the patients with improvement achieved a normal voice. Patients with improvement had varied types and degrees of dysphonia: breathiness, hoarseness, diplophonia, and falsetto pitch breaks. The voices of some patients approached normalcy. A high percent of patients had voice tremor and regular voice arrests on vowel prolongation, signaling that the spastic dysphonia may have been related to essential (voice) tremor and that the spastic dysphonia returned because of increased severity of the neurologic tremor. We conclude that recurrent laryngeal nerve surgery for adductor spastic dysphonia has long-term limitations and that the differential diagnosis between neurologic and psychogenic types is imperative prior to therapeutic decision making.

Adult↗

In vitro assay of contractile activities of spastic canine basilar artery and its surrounding blood clot.

A prolonged vasospasm was produced in the canine basilar artery by injection of fresh autogenous arterial blood into the chiasmatic cistern. Homogenates of lyophilized blood clot around the spastic artery, were made, and their contractile activities were studied in vitro. The homgenates of the lyophilized spastic arteries usually induced a dose dependent sustained contraction, whereas those of the lyophilized normal arteries often produced a dose-dependent transient contraction, and those of the lyophilized blood clot induced a dose-dependent transient or sustained contraction. The initial maximum contractions produced by the homogenates of the lyophilized normal and spastic arteries were significantly different in their values, suggesting the presence of a vasoactive agent in the spastic artery itself. Preliminary pharmacological analysis of the vasoactive agent was attempted using methysergide and phentolamine.

Animals↗

Efficacy of dorsal longitudinal myelotomy in treating spinal spasticity: a review of 20 cases.

The authors report their experience using dorsal longitudinal myelotomy in treating spasticity in 20 patients with complete spinal cord injuries. These patients suffered from severe painful flexor/extensor spasms that prevented them from wheelchair ambulation and/or their decubitus ulcers healing. All were receiving large doses of various oral drugs, including baclofen, which had failed to control their spasticity, and all underwent a modification of a posterior T-myelotomy as first described by Bischof. All 20 patients enjoyed immediate complete relief of their painful spasms, although two (10%) eventually experienced return of their spasms and are thus classified as long-term failures. Seventeen patients succeeded in markedly reducing, or being completely weaned from, their antispasmodic medications. In 11 of 14 patients, nonhealing decubitus ulcers subsequently healed with treatment. Bladder function was unchanged from the preoperative status in all patients. Chronic intrathecal baclofen infusion has recently been reported as an effective treatment of the spasticity of paraplegia. The results of this study, along with previous reports advocating dorsal longitudinal myelotomy, suggest that this approach is an efficacious alternative to chronic baclofen infusion in reducing spasticity for complete paraplegics. Considering the cost of the infusion pump, along with the fact that chronic intrathecal baclofen therapy necessitates long-term medical supervision, it appears that myelotomy is superior for this select group of patients who have no hope of regaining voluntary motor function.

Adult↗

Intrathecal baclofen for spasticity of spinal origin: seven years of experience.

A total of 66 consecutive patients with severe spasticity of spinal cord origin were screened with intrathecal baclofen, and all but two responded with a two-point decrease in their Ashworth spasticity scale and/or spasm scale score. Of these, 62 elected to receive chronic intrathecal baclofen administration by means of an implanted delivery system. These patients have been followed for an average of 30 months (the first three for 81 months). Intrathecal baclofen has been well tolerated and all serious side effects were transient and have been managed by dose adjustments. The pump presently available has worked safely; the only problem has been stalling in 7% of these devices. The catheter system has had to be repaired in just over one-half of the patients and is the main cause of interruption of drug delivery. Of the 62 patients implanted, 52 (84%) continue to be treated adequately for spasticity; there are three poor long-term responders, four deaths due to underlying disease, and three whose participation has been voluntarily withdrawn. It is suggested that long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients.

Adolescent↗