Spasticity management is pivotal for achieving functional recovery of stroke patients. The purpose of this study was to investigate the effects of a single trial of transcutaneous electrical nerve stimulation (TENS) on spasticity and balance in chronic stroke patients. Forty-two chronic stroke patients were randomly allocated into the TENS (n = 22) or the placebo-TENS (n = 20) group. TENS stimulation was applied to the gastrocnemius for 60 min at 100 Hz, 200 µs with 2 to 3 times the sensory threshold (the minimal threshold in detecting electrical stimulation for subjects) after received physical therapy for 30 min. In the placebo-TENS group, electrodes were placed but no electrical stimulation was administered. For measuring spasticity, the resistance encountered during passive muscle stretching of ankle joint was assessed using the Modified Ashworth Scale, and the Hand held dynamometer was used to assess the resistive force caused by spasticity. Balance ability was measured using a force platform that measures postural sway generated by postural imbalance. The TENS group showed a significantly greater reduction in spasticity of the gastrocnemius, compared to the placebo-TENS group (p < 0.05). TENS resulted in greater balance ability improvements, especially during the eyes closed condition (p < 0.05). However, these effects returned to baseline values within one day. This study shows that TENS provides an immediately effective means of reducing spasticity and of improving balance in chronic stroke patients. The present data may be useful to establish the standard parameters for TENS application in the clinical setting of stroke.

The development of catheter associated granulomatous masses in intrathecal morphine therapy is an uncommon, but potentially serious problem. While these systems have historically been used in patients with short life expectancies, more recently patients with pain from a benign source have benefited from this therapy, and new complications are being encountered secondary to the patients' longer life spans. Morphine is the most commonly used intrathecal opioid and evidence exists that the formation of granulomatous masses are related to the use of higher doses. When the patients' requirement of morphine increases significantly, the physician should be alert for signs of spinal cord compression, such as new neurological deficits, myelopathy, or radiculopathy. Patients that require these higher doses should be properly informed of the association with granulomas and their associated risks. Indolent infection may also be the etiology of granulomatous masses, and the presence of organisms, both aerobic and anaerobic, should be routinely investigated. Patients with catheter-associated granulomas appear to share several features. They exhibit the onset of symptoms several months following the initiation of intraspinal opioids and commonly present with an increase in pain that precedes signs and symptoms of neurological deterioration. While MRI might be the preferred method of detection of intrathecal granulomas, its cost and availability are prohibitive for routine screening. CT myelogram via pump side port injection of contrast can also be performed to detect catheter tip related granulomas/obstructions. Serial neurological examinations for new deficits may be performed and recorded during pump refill visits to recognize a granulomatous mass in its early stages. If an abnormality is identified, imaging studies are appropriate. Awareness of the condition and vigilance are the keys to successful management of this complication.

Case report.

To report a case and review the literature on development of scoliosis following intrathecally placed opioid pump for chronic low back pain.

Intrathecal opioid administration is a technique currently indicated for the management of chronic pain syndromes. Despite evidence of scoliosis occurring after baclofen pump insertion, there has been no evidence that development of scoliosis occurs following implantation of an intrathecally placed opioid pump for treatment of lower back pain (LBP).

A retrospective review of patients with adult onset scoliosis was performed at our institution. One patient was identified as showing significant scoliotic progression following implantation of an intrathecally placed opioid pump. Radiographs were analyzed to evaluate the magnitude and configuration of her kyphoscoliosis following pump insertion.

A 50-year-old woman with intractable LBP underwent placement of a spinal cord stimulator (SCS) followed shortly by removal of the SCS and placement of an intrathecal opioid pump. Five years later, she presented with severe kyphoscoliosis involving a left thoracolumbar curve of 84 degrees and sagittal balance of 158 mm. Because of intractable pain and progressive deformity, she underwent multilevel osteotomies, instrumented fusion, and replacement of her Dilaudid pump. Postoperative radiographs demonstrated a residual 23 degrees thoracolumbar curve with restoration of her sagittal alignment. No major morbidity/mortality occurred with treatment.

Although there may not be a direct correlation between implantation of an intrathecal opioid pump with subsequent development of adult onset scoliosis, deformity must be considered a potential sequela in patients treated with such neuromodulation.

Established post-traumatic spinal cord injuries can serve as an 'experimental model' in which trauma has partially separated the 'spinal neuronal pool' from supraspinal influence. Our findings show that: (1) when the muscle is deprived of upper motor neuron activity, fatigue resistance is diminished and external, electrically induced daily contractions will restore the level of fatigue resistance close to that of muscles in healthy, active subjects; (2) the spinal interneuron network, when completely deprived of brain influence, is a 'spinal reflex centre' with a relatively restricted and low excitability level; and (3) the 'discomplete spinal cord injury' model illustrates that spasticity is of supra-segmental origin and that there are two basic features of brain motor control of the spinal interneuron system: the command to restrict interneuronal pool activity and the command to activate the interneuronal network. Moreover, I have described the modifiability of fatigue resistance, locomotor patterns and different alternatives in the neurocontrol of motor activity, depending on the kind and degree of residual brain influence. Such significant modifiability can be thought of as plasticity of the neuromuscular system and impaired control of the nervous system.

Three patients with spinal cord injury (SCI) and 3 able-bodied (AB) patients were infused with naloxone during a study to examine their neuroendocrine function. An unanticipated side effect occurred during the naloxone infusion. All 3 patients with SCI, but none of the AB patients, experienced profoundly increased spasticity during the naloxone infusion. Our report describes this side effect, which has potential implications for the clinical treatment or scientific evaluation of individuals with SCI.

All patients were in good general health and medication free for 11 days or longer before the study. Each patient was placed on a 30-hour protocol to analyze pulsatile release of gonadotropins. Physiologic saline was intravenously infused on day 1 to serve as a control period for naloxone infusion on day 2.

AB patients experienced no muscle spasm activity or any other side effects at any time during the study. In contrast, all 3 patients with SCI experienced a profoundly increased frequency and duration of spasticity in muscles innervated by the nerve roots caudal to their level of injury. In all 3 patients with SCI, spasticity increased only during the period of naloxone infusion. Within 1 hour of stopping naloxone, spasticity returned to baseline levels.

Naloxone infusion produced a differential effect on the muscle activity of men with SCI compared to AB men with intact spinal circuits. Consistent with previous studies, the results of this study indicate a relationship between opioid neuromodulation and spasticity after SCI.

Case report.

To report treatment of spasticity in a spinal cord-injured person with intrathecal morphine after the person developed tolerance to intrathecal baclofen.

Spasticity in a 36-year-old man with T6 complete paraplegia was treated with increasing doses of intrathecal baclofen. When he developed tolerance to intrathecal baclofen, he was given continuous infusion of morphine intrathecally.

Regional Spinal Injuries Centre, UK.

Spasticity was adequately controlled by intrathecal morphine.

In spinal cord-injured patients with severe spasticity, who become tolerant to intrathecal baclofen, treatment with intrathecal morphine may be useful.

To present some recent developments and concepts emerging from both animal and human studies aimed at enhancing recovery of walking after spinal cord injury (SCI).

Researchers in the field of restoration of walking after SCI, as well as references extracted from searches in the Medline computerized database.

Studies that reported outcome measures of walking for spinal cord injured persons with an incomplete motor function loss or cats with either a complete or incomplete spinal section.

Data were extracted and validity was assessed by the authors.

This review shows that a multitude of interventions--mechanical, electrical, or pharmacologic--can increase the walking abilities of persons with SCI who have incomplete motor function loss.

A comprehensive evaluation of walking behavior requires tasks involving the different control variables. This comprehensive evaluation can be used to characterize the process of recovery of walking as well as the effectiveness of various treatments.

Moderate to severe pain is a common feature of central and peripheral demyelinating disorders. Pain in multiple sclerosis tends to occur when the disease is well-established and usually lingers infinitely. Pain in Guillain-Barré syndrome tends to be particularly severe at the time of initial presentation and usually resolves over 8 to 12 weeks. Pain in both conditions is generally caused by either the direct effects of nerve injury or the result of paralysis and prolonged immobilization. Pain syndromes are well-defined in each disorder based on the underlying pathophysiology. Treatment involves a variety of pharmacologic and nonpharmacologic approaches individualized for each specific pain syndrome.

Within 3-4 weeks after spinal transection, morphine-induced antinociception, assessed with the tail flick reflex in rats, is profoundly reduced. The cause of this decrement is unknown. The present studies were conducted to determine whether this phenomenon reflects a general loss in opiate activity or a selective decline in opiate antinociception. This was accomplished by assessing the effect of morphine on two different responses, the tail flick reflex and the hindlimb spasticity that develops in chronic spinal rats. Because excitatory amino acid antagonists are also antinociceptive in acute spinal rats, the effect of one such drug, dextrorphan, on these two behaviors was also evaluated in chronic spinal animals. The antinociceptive and antispastic effect of subcutaneous (6 mg/kg) and intrathecal (5 micrograms) morphine injections were assessed in intact and chronic (21-28 days) spinal rats, whereas the effect of subcutaneous (25 and 40 mg/kg) and intrathecal (350 micrograms) dextrorphan was assessed in acute (1 day) and chronic spinal rats. The antinociceptive effect of both drugs was significantly reduced in chronic spinal animals, relative to saline controls. However, each drug treatment produced a significant antispastic effect in the same animals, indicating a selective decline in opiate action. This outcome also suggests that excitatory amino acid antagonists may be useful as adjunct antispastic agents.

Severe spasticity unresponsive to oral drugs may respond satisfactorily to baclofen delivered intrathecally.

Intrathecal baclofen (IB) therapy delivered by means of implanted infusion pumps was used for nine patients with severe spasticity. Six patients had multiple sclerosis, two cervical spinal cord injury, and one head injury. All were non-ambulatory.

Patients showed improvement in many areas, including ability to transfer, seating, pain control, personal care, and liability to skin breakdown. Before IB therapy, only three of the nine patients were able to live at home in the community and six were institutionalized. At the end of our follow-up period, only one patient remained institutionalized, three lived in group homes and five lived at home in the community. In the year preceding pump implantation, the nine patients spent a total of 755 days in acute care hospitals. In the year following onset of IB therapy, they spent only 259 days in hospital.

IB therapy can improve patient quality of life and can be cost-effective in carefully selected patients with severe spasticity and disability. The drug delivery catheter is that part of the therapeutic system most vulnerable to failure. Because of the varied expertise required to manage these patients effectively, and the potential for a variety of complications, it is essential that an IB program is supported by a well-organized multi-disciplinary medical team.

We include in this article the results of a postal inquiry into chronic pain in SCI patients in Valencia (Spain), and our experience with their management. A mailed questionnaire including lesion and chronic pain data was sent to all of the 380 SCI patients who live in the region of Valencia. We received 202 answers, with 145 questionnaires being accurately answered and these were analysed for this study. The results show that chronic pain (that is, lasting more than 6 months) is very common (65.5%). The most frequent type was deafferentation pain (phantom pain), described as burning or a painful numbness. Since 1988 we have been treating a sample of 33 patients suffering from resistant pain according to the following therapies: 1 amitriptyline + clonazepam+NSAID (nonsteroidal antiinflammatory drugs); 2 amitriptyline + clonazepam + 5-OH-tryptophane + TENS (transcutaneous electrical nerve stimulation); 3 amitriptyline + clonazepam + SCS (spinal cord stimulation); 4 morphine, by continuous intrathecal infusion. After almost 4 years using these therapies we can affirm that the results regarding analgesia reached 80% in all cases, and that morphine used by intrathecal route is very safe and useful in selected patients.

Severe and disabling spasticity frequently occurs in people with multiple sclerosis and spinal cord injury. Approximately 30% of these people are treated with oral antispasmodic medications that do not provide adequate relief from spasticity (Hattab, 1980). Clinical trials with spinal stimulation and ablative neurosurgical procedures have not been as uniformly successful for controlling spasticity as has intrathecal baclofen injection (Kasdon, 1986). Delivered by an implantable programmable drug pump, intrathecal baclofen injection has proven to be successful in treating individuals with intractable spasticity. Significant reduction in muscle tone and frequency of spasms have contributed to improved function with activities of daily living, bladder management, overall comfort, and quality of sleep (Penn et al., 1989; Parke, Penn, Savoy, & Corcos, 1989). This article introduces an innovative therapy for controlling spasticity and discusses the nurse's role in patient selection and management.

A 36-year-old man with acquired immunodeficiency syndrome had incapacitating dysuria and vesical pain secondary to interstitial cystitis. When medical management and suprapubic urinary diversion failed to control the symptoms the patient was started on subarachnoid morphine sulfate. Bupivacaine was added 1 year later via an implanted Therex M-3000 implantable continuous infusion pump, which has continued successfully for more than 18 months. We believe that subarachnoid narcotics and other analgesic agents, such as clonidine, bupivacaine hydrochloride and baclofen, may prove equally valuable in the treatment of bladder spasm and pain. Furthermore, implanted intrathecal ports and pumps may have less associated risk of infection than the percutaneous vascular access catheters presently used for the continuous delivery of medications in immunosuppressed patients.

An overview of several perioperative complications and their management strategies is presented. Operative hypothermia, malignant hyperthermia, bronchospasm, and side effects of spinal opioid agents are discussed. Ramifications of these complications may extend well beyond the operative period and influence patient outcome. Therefore, it is necessary that the surgeon have a fundamental understanding of the pathophysiology and modalities of treatment in the context of anesthesia and surgery.

Recent data have shown that [125I]D-Ala2, MePhe4, Met(o)ol5-enkephalin (FK-33-824) is a highly selective and specific mu opioid receptor ligand [Moyse et al. (1986) Peptides 7, 351-355]. This probe was used here to investigate the detailed radioautographic distribution of mu sites at various levels of the spinal cord. [125I]FK-33-824 binding sites were localized by both tritium-sensitive film and liquid emulsion radioautography in the spinal cord of naive and deafferented rats. In naive animals, high densities of mu sites were apparent within laminae I-II at all levels of the dorsal horn, with higher levels of labelling seen in layer IIi as compared to IIo in the lumbar segment. Laminae III-IV contained about half the quantities of binding observed in superficial layers. Relatively high densities of sites were also seen over lamina VI in the upper cervical cord and throughout Clarke's column. Within the latter, [125I]FK-33-824 binding clearly spared the large perikarya of the spinocerebellar neurons. In the ventral horn, [125I]FK-33-824 binding was mainly concentrated in layer IX, at the level of cervical and lumbar enlargements. Labelled sites were confined to the neuropil, mostly sparing the soma of motoneurons. Significant decreases in [125I]FK-33-824 binding in laminae I-II (55%) and III-IV (28%) were detected four days following cervical (C3-C7) or lumbar (L1-L6) rhizotomies. These decrements were most evident at seven days post-lesion at C3-C7 levels (93 and 76% in laminae I-II and III-IV, respectively) and recovered slightly thereafter up to 28 days post-lesion. In contrast, dorsal rhizotomies did not influence mu labelling in either the ventral horn or Clarke's column. These results confirm the association of mu opioid binding sites with dorsal primary afferent fibres and demonstrate the presence of mu sites in Clarke's column and lamina IX of the ventral horn. These findings suggest that endogenous opioids in the spinal cord play a role in sensory motor integration as well as in the modulation of primary nociceptive inputs.

Sites of action of centrally active muscle relaxant drugs are not well defined. Clinical experience with such drugs suggests that the spinal cord may be one of the important regions from which pathologically increased muscle tone may be relieved. Supraspinal centers that may also be involved in the expression of muscle relaxant action have not yet been defined. We report here that microinjections of therapeutically relevant muscle relaxants into the midbrain tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra is the region from which midazolam, baclofen, and tizanidine (drugs used clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7-phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs active in animal models of spasticity), reduce muscle tone in genetically spastic rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs are topographically restricted to the substantia nigra pars reticulata and are receptor specific. These observations disclose a previously unknown function of the substantia nigra in mediating muscle relaxation.

This review presents the pharmacology of spinal opioid receptor systems which are primarily involved in pain processing. The major areas upon which we will focus are: the structure and cellular functioning of the opioid receptor systems; the physiologic effects induced by spinally administered opioids, particularly in pain modulation; and pharmacokinetic and dynamic considerations, with special attention to the problem of opioid tolerance development.

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.

Increasing knowledge of the neurochemical aspects of central nervous system function raises the possibility of treating Alzheimer's disease (AD) and other neurological diseases by the appropriate manipulation of neurotransmitters, neuromodulators, neurohormones or neurotrophic factors. Clinical application of this knowledge may, however, be inhibited by long standing problems with drug delivery to the central nervous system (CNS). Novel, CNS-directed, drug delivery systems might be used to overcome many of these problems. The problems encountered in drug delivery to the brain, present experience with the clinical use of some novel drug delivery systems and the advantages and disadvantages of these systems will be discussed.

On the basis of previous experimental and clinical studies patients with severe spasticity due to spinal cord damage from multiple sclerosis in 8 cases and postraumatic paraplegia in 6 and resistent to all conservative treatments were selected for a trial with morphine and baclofen administered intrathecally through a catheter placed in the spinal subarachnoid space rostral to the affected segments and attached to a subcutaneous reservoir. Whereas morphine single injection did not show any benefit, baclofen bolus injection 30 to 60 micrograms, revealed a marked decrease of spasticity and associated symptoms in 8 cases. After checking the clinical effect during 3 weeks and changes in electroneurophysiological studies and bladder manometry the catheter was attached to a subcutaneous programmable pump able to be refilled percutaneously and administered baclofen continuously or more often following a multistep complex programme in total doses of 90 to 150 micrograms per day. After a mean follow-up of 5 months all cases showed an absence of spasms and pain, a notable improvement for bettering of sphincter functions and a marked muscle relaxation that improves motor capacity, leading to increased ambulation or mobility. Neither complications nor side-effects were observed.

Spasms and spasticity constitute a significant problem in spinal cord injured individuals. Surgical intervention may be indicated when spasms and spasticity cannot be satisfactorily controlled by medications and physical therapy. Surgical procedures carried out on the nervous system include neurotomy, rhizotomy, myelotomy, cordectomy and spinal cord stimulation. The various procedures and their indications will be discussed.

In about one third of patients with violent spasticity due to spinal trauma, multiple sclerosis, and diffuse brain injury adequate control with oral antispastic medication cannot be achieved and successful rehabilitation is severely handicapped. In the past these patients were subjected to destructive chemical procedures or extensive surgery. The authors present the results of management of uncontrollable spasticity by means of continuous intrathecal administration of baclofen with a totally implantable gas driven pump system (Infusaid). 30 patients were treated between June 1985 and January. 1987. The main indication was incapacitating spasticity resistant to oral treatment with baclofen and caused by spinal cord injury or lesion (11 patients), multiple sclerosis (11 patients), infantile cerebral palsy (3 patients) and cerebral injury, hypoxia or ischaemia (5 patients). Clinical assessment included spasticity scores, integrated electromyography (Iemg) and motography. Effective control for spasticity with mean reduction of Iemg by 55%, decrease of Ashworth's score from 3 to 0 and improvement of life quality was obtained in all patients with daily dose of 10-800 micrograms of Baclofen. Voluntary resting motoricity was not impaired and there were no untoward central side effects. The excellent effect of intrathecal baclofen in comparison with oral therapy is explained by local, spinal GABAergic inhibitory action of the drug which is delivered directly into spinal subarachnoid space. Dose finding and dose adjustment is performed prior to pump implantation by intermittent injections into a subcutaneous port. The complications of the procedure were minor (catheter displacement, disconnection) and easily correctable.(ABSTRACT TRUNCATED AT 250 WORDS)

Several opiate receptor systems have been identified in the spinal cord. They produce a powerful analgesia when opioid agonists are administered intrathecally in the intact, unanesthetized animal. These effects appear mediated by an action on opioid receptors which are located presynaptically, in the terminals of primary afferents, and postsynaptically on certain dorsal horn neurons. Based on structure-activity relationships in different tests, quantitative studies of naloxone antagonism and selective cross tolerance, it appears that, in the spinal cord, there are three distinguishable populations of opioid receptors: mu, delta and kappa. Aside from the effects on nociception, these receptors are also associated with a variety of spinal mechanisms related to other aspects of sensory, autonomic and motor functions. Though in some cases these represent important side-effects (e.g. inhibition of the micturition reflex), in others, the subtle effects may have important therapeutic benefits (e.g. relieving spasticity in spinal injured patients).

Seven patients with spasticity of spinal cord origin have been maintained for up to 2 years with continuous spinal intrathecal infusion of baclofen. Prior to treatment, all of the patients had severe rigidity in their lower limbs and most had frequent and extensive spontaneous spasms, all of which greatly interfered with their activities of daily living. Oral antispasmodic medications were ineffective or caused central side effects. The patients underwent implantation of a programmable drug pump connected to a lumbar subarachnoid catheter. Within days of beginning continuous intrathecal baclofen infusion, the muscle tone was reduced to normal levels and spasms were eliminated. Over the ensuing months, muscle tone remained normal, but short-duration spasms could be induced by some activities. The greatest benefits to the patients were improvement in activities of daily living and better sleep due to reduced spasms. The baclofen doses were increased over the first few months but then were stabilized or only increased slightly, with the maximum dose being 650 micrograms/day. The most serious complications were two drug overdoses which took several days to clear up and were due to malfunctions of an earlier pump model. Baclofen clearance from the cerebrospinal fluid occurs with a half-life of 5 hours. The most serious concern in maintaining patients indefinitely on intrathecal baclofen is whether drug tolerance will eventually occur.