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Chronic intrathecal baclofen administration for control of severe spasticity.

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.

Baclofen↗

Peripheral selective neurotomy of the brachial plexus collateral branches for treatment of the spastic shoulder: anatomical study and clinical results in five patients.

A new type of peripheral selective neurotomy involving the collateral branches of the brachial plexus has been perfected for treatment of the spastic shoulder. Anatomical study of six cadaveric shoulders led to the specification of a surgical approach to the pectoralis major and teres major nerves, which innervate the main muscles implicated in shoulder spasticity. Between August 1994 and September 1995, five patients (four men and one woman) underwent two to four associated neurotomies of the upper limb, which included neurotomies of the pectoralis major (all five patients) and the teres major (two patients). The average follow-up period was 11 months, during which there were no local or general complications. The spasticity of the treated muscles resolved in all five patients (Held score range 3-0). The neurotomies led to statistically significant average amplitude increases in shoulder mobility, especially in abduction (+30 degrees), antepulsion (+50 degrees), retropulsion (+20 degrees), and external rotation (+20 degrees). The functionally useful active amplitude scores increased from 2.66 to 5.16/6. This functional improvements mainly involved the standing position and walking stability, as well as improvement in the range of motion of the lower limb. These results encourage the increasing use of this new type of neurotomy in treatment of the spastic upper limb.

Adult↗

Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin.

Management of severe spasticity in children is often a difficult problem. Orally administered medications generally offer limited benefits. This study examines the value of intrathecally administered baclofen in the treatment of 19 children with severe spasticity of cerebral origin: eight of whom sustained brain injury associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy (spastic quadriplegia); and one child with Leigh's disease. At the time of entry into the study, patients ranged from 4 to 19 years of age, and all were completely dependent on caretakers for activities of daily living. Children who responded positively to a trial dose of intrathecal baclofen underwent insertion of a drug delivery system for continuous infusion. This was followed by a double-blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and yearly thereafter. Seven children did not undergo pump implantation because of excess sedation or poor response. The 12 remaining children have been followed for a period of 1 to 5 years. Favorable responses were present in all 12 children as determined by the Ashworth Scale, with the greatest benefit being reduction of lower limb tone. Except in the case of one child who had reduction in lower limb tone that resulted in difficulty with transfers, the caretakers all reported significant benefits from intrathecal baclofen, with improvement in muscle tone, behavior, sitting, and general ease of care being most commonly noted. Central side effects were seen in some children who received continuous intrathecal baclofen infusion and included hypotension (two patients), bradycardia (two), apnea or respiratory depression (two), and sedation (one). During a total of 568 months of pump operation there were 10 mechanical complications, including two related to pump or side port failure and eight related to catheter kinks, extrusions, or dislodgment. Pump pocket effusion occurred in five children and a cerebrospinal fluid fistula was seen in one child. Local infection occurred in three children and meningitis in two children. The results demonstrate the potential value of continuous intrathecal baclofen infusion for treatment of severe spasticity of cerebral origin. However, this treatment can result in significant complications and more experience is required before the long-term benefits can be determined.

Adolescent↗

Gait before and 10 years after rhizotomy in children with cerebral palsy spasticity.

OBJECT: Selective dorsal rhizotomy is a neurosurgical procedure performed for the relief of spasticity in children with cerebral palsy, but its long-term functional efficacy is still unknown. The authors sought to address this issue by means of an objective, prospective study in which quantitative gait analysis was used. METHODS: Eleven children with spastic diplegia (mean age at initial surgery 7.8 years) were evaluated preoperatively in 1985 and then at 1, 3, and at least 10 years after surgery. For comparison, 12 age-matched healthy individuals were also studied. Retroreflective targets were placed over the hip, knee, and ankle joints, and each individual's gait was videotaped. The video data were subsequently entered into a computer for extraction and analysis of the gait parameters. An analysis of variance yielded a significant time effect (p < 0.05), and post hoc comparisons revealed differences before and after surgery and with respect to the healthy volunteers. The knee and hip ranges of motion (59 degrees and 44 degrees, respectively, for healthy volunteers) were significantly restricted in children with spastic diplegia prior to surgery (41 degrees and 41 degrees, respectively), but were within normal limits after 10 years (52 degrees and 45 degrees, respectively). The knee and hip midrange values (31 degrees and 3 degrees, respectively, for healthy volunteers), indicative of posture, were significantly elevated preoperatively (42 degrees and 15 degrees) and increased sharply at 1 year (56 degrees and 18 degrees), but by 10 years they had decreased to within normal limits (36 degrees and 9 degrees). Step length and velocity improved postoperatively but were not within the normal range after 10 years. Ten years after surgery these patients not only had increased ranges of motion, but also used that movement at approximately a normal midrange point. CONCLUSIONS: Selective dorsal rhizotomy is an effective method for alleviating spasticity. Furthermore, the authors provide evidence to show that lasting functional benefits, as measured by improved gait, can also be obtained.

Adolescent↗

Brachial plexus dorsal rhizotomy in the treatment of upper-limb spasticity.

OBJECT: This study was conducted to evaluate the effects of dorsal rhizotomy on upper-limb spasticity, functional improvement, coordination, and hand sensibility. METHODS: Fifteen spastic upper limbs in 13 patients were selected and prospectively studied. Brachial plexus dorsal rhizotomy was performed in which two, three, or four dorsal roots were completely sectioned. Patients were followed up for at least 12 months after surgery; the mean follow-up period was 15.6 months and the maximum period was 30 months. A remarkable relief of spasticity was observed in all cases. Recurrence was observed in only one patient and was caused by insufficient dorsal root section. Functional improvement was observed in all cases, and functional improvement in the hand was found to be related to the presence of active finger extension in the preoperative period. Even when extended dorsal root section was performed, no hand anesthesia, either total or partial, was observed. No patient lost movement ability in the postoperative period, and no ataxic limbs were observed. CONCLUSIONS: Brachial plexus dorsal rhizotomy is very effective as a treatment for upper-limb spasticity and results in functional improvement without loss of sensation in the hand.

Adolescent↗

Functional benefits and cost/benefit analysis of continuous intrathecal baclofen infusion for the management of severe spasticity.

OBJECT: Intrathecally delivered baclofen has been used as a treatment for severe spasticity since 1984. Despite this, there are uncertainties surrounding the benefits of treatment and the costs involved. The authors assessed the evidence of benefits and identified costs and the cost/benefit ratio for continuous intrathecal baclofen infusion in the treatment of severe spasticity. METHODS: A systematic literature review was conducted to estimate the effect of continuous intrathecal baclofen infusion on function and quality-of-life (QOL) measures in patients with severe spasticity. Outcomes were related to standard QOL scores to estimate potential gains in quality-adjusted life years (QALYs). Information on the costs of continuous intrathecal baclofen infusion was obtained from hospitals in the United Kingdom. This information was combined to estimate the cost/benefit ratio for the use of continuous intrathecal baclofen infusion in patients with different levels of disability from severe spasticity. Studies indicate that bedbound patients are likely to improve their mobility and become able to sit out of bed. Patients with severe spasm-related pain are likely to have major improvement or complete resolution of this pain. Many other benefits are also reported. Such benefits are related to costs per QALY in the range of 6,900 pounds to 12,800 pounds ($10,550-$19,570 US). CONCLUSIONS: In carefully selected patients who have not responded to less invasive treatments, continuous intrathecal baclofen infusion is likely to lead to worthwhile functional benefits. Continuous intrathecal baclofen infusion has an acceptable cost/benefit ratio compared with other interventions that are funded by the health service.

Adolescent↗

Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin.

OBJECT: The goal of this study was to ascertain the long-term effectiveness and safety of intrathecal baclofen (ITB) in the treatment of spasticity of cerebral origin in children and young adults. METHODS: A prospective, multicenter study was conducted in 68 patients who had been enrolled in the initial evaluation of ITB therapy and were willing to participate in long-term surveillance. Seventy-three percent of the patients were younger than 16 years of age at the time of study entry. The patients were examined at least every 3 months and were observed for an average of 70 months. At each follow-up visit, spasticity in the upper and lower extremities was evaluated by applying Ashworth scores. All adverse events and complications were recorded on standardized data forms. Spasticity in both upper and lower extremities decreased significantly (p < 0.005) and remained decreased up to 10 years. The dosage of ITB increased from a mean of 157 microg/day 3 months after pump insertion to 300 microg/day at 2 years postimplantation, and remained relatively stable thereafter. There were no significant differences in ITB dosage in children of different ages. Adverse events potentially related to ITB therapy occurred in 50% of patients within 2 months after pump insertion and in 50% of patients thereafter; hypotonia and lethargy were the two most common adverse events. The most common complications of surgery were catheter-related problems (31%), seromas (24%), and cerebrospinal fluid leaks (15%). CONCLUSIONS: Intrathecal baclofen provides effective long-term treatment of spasticity of cerebral origin and its effects do not appear to diminish with time. This therapy is frequently associated with adverse side effects that usually can be alleviated by adjustments in dosage.

Adolescent↗

Helping your patients with spasticity reach maximal function.

Familiarity with spasticity and its treatment options and a rational approach to care are necessary to achieve an optimal outcome in patients with this disorder. Not all spasticity needs to be treated. Functional problems experienced by the patient and feedback from caretakers should guide decisions of whether and how to treat. Primary care physicians may benefit from maintaining close working relationships with physical medicine and rehabilitation physicians (physiatrists), who are experienced in assessment of spasticity, especially in relation to function, and can help differentiate true spasticity from rigidity and contracture. After underlying exacerbating factors are ruled out, a treatment plan starting with conservative methods and advancing to more aggressive measures should be followed. Consultation with physiatrists may be useful in regard to antispasticity medications, nerve blocks, intrathecal pumps, and postrhizotomy care.

Botulinum Toxins, Type A↗

[Brain and spinal cord magnetic resonance imaging in spastic paraparesis associated to human T-lymphotropic virus].

BACKGROUND: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. AIM: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. MATERIAL AND METHODS: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). RESULTS: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87% of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80% of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. CONCLUSIONS: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis.

Adult↗

[Botulinum A in the treatment of equinus dynamic spasticity in children with cerebral palsy. Preliminary study].

PURPOSE OF THE STUDY: The purpose of this clinical prospective study is to better assess the efficacy of intramuscular injections of botulinum-A toxin in the treatment of spastic dynamic equinus deformities in children with cerebral palsy. MATERIAL: Ten walking children (14 feet) with cerebral palsy were treated with botulinum-A toxin (the American type, Botox) for spastic dynamic equinus, equinovalgus or equinovarus deformity of the foot. The mean age was 6 years (range 4 to 12 years of age). METHOD: Two units of botulinum-A toxin per kilogram were injected in each involved extremity: the lateral and medial gastrocnemius were injected in equinus or equinovalgus foot and one more injection was done in the tibialis posterior in equinovarus foot. A clinical assessment (based on opinion of caretakers, functional evaluation of gait, detailed orthopaedic clinical evaluation and video of the gait) and a gait analysis were performed prior to the first injections and then at 1, 3 and 6 months afterwards. RESULTS: All patients showed a clinical improvement. The functional possibilities increased in 6 out of the 10 children. Five children showed a better endurance in their walking capacities. The clinical orthopaedic exam showed improvement for 10 out of the 14 injected feet in passive dorsiflexion from 3 to 15 degrees at one month. Twelve feet improved their score on the Physician Rating Scale from 1 to 4 points. For gait analysis, 6 children (8 feet) had an improvement often minor of their curves in terms of improvement of the dorsal flexion of the ankle and the EMG of the gastrocnemius was improved in terms of decrease of spastic activity in 7 children (10 feet). The response to the injections was seen within 10 days (3 to 10 days) and lasted 3 to 6 months except in one child where it stopped already after 1 month. No side effect was noted. DISCUSSION: All ten patients of our study showed some type of improvement even if only minor or limited in time in some of them. These data corroborate previous studies performed by other authors. Since this study, the recommended dosage has greatly increased (from 2 U/kg up to 10 U/kg or even more). The most interesting new element is that we noted that it seems to increase the endurance of the patient regarding walking distance. CONCLUSION: The intramuscular injection of botulinum-A toxin in spastic dynamic equinus deformities in children with cerebral palsy is an useful treatment modality, but the indications have to be respected scrupulously. The subject needs more study with the higher dosage and clinical evaluation to confirm the possible increased endurance.

Activities of Daily Living↗

[Treatment of Spastic Gait Disorders Using an "Electro-Gait-Stimulator ("Schrittstimulator") (author's transl)].

A short historical outline of electric treatment of spasticity is given. A specially developed management with a "gait-stimulator" is described. Four muscles of each lower extremity being mainly engaged in walk were electrically stimulated in the physiological sequences according to the normal gait. The used electric impulses were of a duration of 0,25 msec and an intensity up to 700 V. Using such a "gain-stimulator" in spastic-paraparetic patients a reduced spasticity has been achieved. Positive effect of this treatment has been mostly pronounced, when the programming of impulses was adjusted to the end of the expected physiological contraction of the corresponding muscles. Physiological and pathological data of the "Silent period" is proposed to be mostly involved. The application of impulses in physiological sequences seems to reactivate normal reflex - mechanisms which are disturbed by supraspinal laesion. The results indicate that the electric impulses activates muscle-sensory - organs and that impulses on these organs produce a pace-making function on the spinal cord, which lessens spasticity.

Adult↗

[Increased activity of metalloproteinases and their inhibitors in cerebrospinal fluid of patients with tropical spastic paraparesis].

BACKGROUND: Proteolytic modifications of neuronal surfaces and the surrounding extracellular matrix are very important in neuronal development and regeneration. Increased activity of matrix metalloproteinases (MMPs) and their tissue inhibitors, due to secretion by macrophages and lymphocytes, occur in inflammatory processes that disrupt the blood brain barrier. However, neurons and microglia can also secrete these enzymes. AIM: To identify the type of MMP present in the cerebrospinal fluid (CSF) and changes in the expression of tissue inhibitors of metalloproteinases (TIMPs) in patients with HTLV-1 associated tropical spastic paraparesis. PATIENTS AND METHODS: CSF samples from 12 patients with HTLV-1 associated tropical spastic paraparesis and 12 healthy controls were obtained by an atraumatic lumbar puncture. The presence of MMPs was measured by zymography and the relative amounts of TIMPs were measured by immunowestern blot. RESULTS: In the CSF of both controls and patients, a similar gelatinolytic band corresponding to proMMP-2 (latent form) was observed. In 83.3% of patients with HTLV 1 associated tropical spastic paraparesis, the MMP-9 was also present. TIMP-1, TIMP-2 and TIMP-3 were elevated 2.24 +/- 0.72, 3.85 +/- 1.38 and 5.89 +/- 3.4 fold, respectively, in the CSF of patients as compared to controls. CONCLUSIONS: Patients with HTLV-1 associated tropical spastic paraparesis have elevated activity of MMP-9 and levels of TIMPs in the CSF, when compared to healthy controls.

Adult↗

Functional and clinical changes in upper limb spastic patients treated with botulinum toxin (BTX).

Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks. In order to study the usefulness of botulinum toxin type A (BTX) as a therapy for spasticity, we studied 15 patients affected by spasticity secondary to stroke. Tests included: clinical evaluation of tone (Ashworth scale); active angles of extension and flexion at elbow and wrist; Hmax/Mmax ratio from flexor carpi radialis (FCR); Hreflex presynaptic inhibition from FCR during vibration; Task score; and video recording. Patients were injected with BTX into one or more muscles with total doses not exceeding 200 International Units (IU). The tests were performed immediately prior to injection and repeated 2 weeks afterwards. Furthermore, in eight patients, testing was also performed one month after BTX injection. Between two weeks and one month after BTX there were no statistically significant differences. A statistically significant difference in the Task and Ashworth scores before and after treatment emerged (p < 0.0014), but only 6 patients showed a clear improvement in motor performance. Overall, we observed an improvement in the angle of active extension and flexion at the wrist and elbow. There were no significant changes in the Hmax/Mmax ratio and the Hreflex presynaptic inhibition during vibration. All the patients reported a subjective improvement. The results suggest that subjective benefits can be gained from the use of BTX in patients affected by spasticity, and that the degree of motor improvement seems to depend on the motor recovery obtained before treatment.

Adult↗

[Selective fasicular neurotomy for spastic equinovarus foot deformity in cerebral palsy children].

Spasticity is usually treated by rehabilitation, orthosis, chemical denervations, orthopaedic surgery and neurosurgery. Selective fascicular neurotomy is a neurosurgical procedure consisting in partial section of selected motor nerves innervating spastic muscles. Neurotomy is indicated in cases of localised disabling spasticity without musculotendinous shortening, resistant to chemical denervation and for which a motor nerve block with anaesthetic has given a good functional result. Neurotomy includes division of the afferent Ia and Ib fibers, unable to recover, leading to permanent disappearance of the spasticity. Neurotomy also includes section of the motor efferent fibers with transient paresis as a result. In adults, neurotomy provides functional improvement in 81 to 97% of cases. In case of posterior tibial neurotomy, improved walking stability and a decrease in foot equinus and knee recurvatum is observed. In children, the risk of deformity recurrence seems higher because of motor axonal reinnervation: indications must therefore be carefully considered and rehabilitation provided after surgery.

Afferent Pathways↗

[Possibilities of subjective and objective evaluation of spasticity].

In this paper the most commonly used methods of assessment patients with spasticity has been presented. "Measuring" of spasticity is necessary for evaluation of new methods of treatment. This could be made directly or indirectly--in that case the sequela of spasticity is measured. In this elaboration as well subjective as objective methods of examination in spasticity has been described. The tone intensity scales, spasm frequency scores, global scales of motor impairment, ADL scales, upper extremity dexterity and strength testing, examination techniques and maneuvers to differentiate rectus femoris from iliopsoas and gastrocnemius from soleus tightness, clinical gait scores, EMG and goniometric pendulum test has been mentioned.

Humans↗

Concept of spastic hypertonia.

This introductory article highlights the definition of spastic hypertonia, and briefly introduces the reader to the incidence and most frequent causes of spastic hypertonia. The article also discusses the functional losses caused by spastic hypertonia that will be reviewed more thoroughly in the following articles. Also discussed is the neural physiology and the locations of the structural lesions within the central nervous system that are involved in spastic hypertonia, with an emphasis on the different clinical presentations depending on the location of the lesion.

Humans↗

Anti-spasticity medications.

Spasticity is common in patients with a variety of central nervous system disorders. It can lead to significant disability or cause complications that may result in severe morbidity. In such patients, treatment of spasticity is warranted. Several oral and parenteral medications are available for use in the treatment of spasticity. This article reviews the pharmacological properties and therapeutic effectiveness of these medications to provide a practical objective guide for physicians who may be involved in the management of spasticity.

Baclofen↗

[Electrophysiological assessment of reflex pathways involved in spasticity].

Various spinal reflexes can be involved in spasticity. Monosynaptic Ia excitation of motoneurons is the most widely studied electrophysiological phenomenon and can be explored by recording the H-reflex, particularly in the soleus muscle. Using conditioning stimuli, the H-reflex technique can be used to study most of the many spinal mechanisms of motor control such as disynaptic, presynaptic, or reciprocal inhibition, post-activation synaptic depression, or facilitation by type I or II muscle afferents. The results obtained in spastic subjects show that the myotactic stretch reflex is exaggerated, but that all the other spinal reflexes are modified. The most recently reported results show an exaggeration of heteronymous facilitation in group II afferents could be one of the main mechanisms leading to spasticity. At the present time, results obtained for the various spinal pathways remain to be compared before concluding about the precise pathophysiology of spasticity, particularly concerning its origin in humans. Despite their complexity, electrophysiological reflex studies offer essential information to reach this goal.

Electrophysiology↗