Intrathecal baclofen in hereditary spastic paraparesis: benefits and limitations]

BACKGROUND: Chronic intrathecal delivery of baclofen has been introduced for treatment of severe spinal spasticity. Very little is known about this treatment in hereditary spastic paraparesis. Here we review the benefits and limitations of pump implantation for baclofen delivery in this population. METHODS: Consecutive patients presenting with hereditary spastic paraparesis were assessed for spasticity (Ashworth and Penn scores), muscular strength and walking (speed, comfort and perimeter length). The effect of intrathecal delivery of baclofen was judged after progressive bolus injections or chronic administration by electrical syringe. The pump implantation was proposed when spasticity scores decreased by 2 or more points, with muscular strength preserved and walking area increased. RESULTS: We investigated 6 patients (3 males; mean age 48 years) with hereditary spastic paraparesis. The mean follow-up was 19 years; for 4 patients who received pump implantation, the mean follow-up was 6.2 years. The mean baclofen daily dose was 75 mug. Satisfaction was high for patients who received implantation early instead of waiting for the natural course of the disease. DISCUSSION: Some patients with hereditary spastic paraparesis have good functional improvement with chronic intrathecal delivery of baclofen if walking is still possible. Despite the natural history of the disease, functional results are stable during the first 5 years of treatment. The data indicate a possible compromise between decreased spasticity and muscular strengthening with the treatment.     

Intrathecal baclofen for spasticity management in Rett syndrome

Intrathecal baclofen infusions have proven to be effective for management of spasticity during the last two decades. Efficacy of intrathecal baclofen for spasticity of spinal origin has been well established and has shown promise in treatment of spasticity that is not spinal in origin. Rett syndrome is a neurodevelopmental disorder primarily affecting girls and women. Manifested in the advanced stages of this syndrome is increased spasticity leading to functional decline. Presented is a case report of a 32-yr-old white woman with Rett syndrome, diagnosed before the age of 2 yr, and significant spasticity that was successfully managed with intrathecal baclofen. After placement of an intrathecal baclofen pump, the dose was increased slowly during 1 yr to 800 microg/day with good clinical response. There was observed a significant decrease in upper and lower limb Ashworth scores, from an average of 3-4 to 2-3, during this 1-yr period. The decrease in spasticity in this patient eventually led to improved range of motion, positioning, skin care, hygiene, and quality of life. Intrathecal baclofen is an effective option in managing severe spasticity from Rett syndrome.     

Intraspinal drug therapy

Intraspinal drug delivery provides agents directly to their site of action. These sites, receptors within the spinal cord, are bound to a greater degree when drugs are administered intraspinally. The purpose for drug therapy, the acute or chronic nature of delivery, and the drug administration system affect the choice of epidural versus intrathecal route of delivery. Pharmacologic properties, such as solubility, pH, and pKa, aid in dictating the drug chosen for administration. Intraspinal opiates and anesthetics have been used extensively since the 1970s in postoperative, postpartum, and cancer populations. Various delivery systems are in use, including external catheters and implanted ports and pumps. Nursing care includes titration of doses, prevention and management of side effects, and maintenance of delivery systems. Intrathecal baclofen is a new treatment for severe spasticity for patients with multiple sclerosis or spinal cord injury. Candidates include patients who experience persistent spasticity unrelieved by antispasmodics or who experience unacceptable side effects to those oral drugs. Nurses assess spasticity, titrate the intrathecal baclofen to obtain an acceptable degree of spasticity, and manage side effects associated with intrathecal baclofen. A long-term benefit of intraspinal drug delivery, potentially providing benefit to many patients, is the identification of experimental agents that do not cross the blood-brain barrier but prove effective when delivered intraspinally. Pharmacologists and others then might undertake the costly modifications necessary to improve the solubility of the drug. The analogue then might be given orally. "The feasibility of an operation is not an indication for its performance." These words, attributed to the late Lord Cohen, also apply to intraspinal drug delivery. As with any therapy, the simplest and least invasive course should be taken. If, for example, the patient experiences good relief without side effects when given oral opiates or baclofen, there is no good rationale for inserting an intraspinal catheter. The potential for increased morbidity and the escalated expense make this an illogical choice. There are, however, many patients who cannot tolerate oral opiates or baclofen but obtain significant benefit from intraspinal drug delivery. Those who benefit should not be denied this therapy. Much research is necessary as this modality develops. Nurses who comprehend the science of intraspinal drug delivery, as well as the art of patient management, can contribute to this advancing field.     

Intrathecal Baclofen Infusion: An Innovative Approach for Controlling Spinal Spasticity

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.     

Intrathecal baclofen overdose

Intrathecal baclofen administered by bolus or continuous infusion has been shown to be of benefit in the treatment of spinal spasticity. Reporting of complications has been limited, particularly in the emergency medicine literature. Reports have been primarily associated with clinical trials. We report a case of intrathecal baclofen overdose in a patient presenting to the emergency department with an altered level of consciousness and cardiorespiratory depression, who required mechanical ventilation, fluid resuscitation and intensive care admission. The literature is reviewed with respect to the action and effectiveness of intrathecal baclofen, use of the relevant implantable devices, suggested methods of management in overdose and the other reported complications from this treatment modality.     

Évaluation médico-économique du baclofène intrathécal chez les patients présentant une spasticité chronique sévère

A medicoeconomic evaluation of continuous intrathecal baclofen (Lioresal^®) infusion for symptomatic treatment of severe spinal spasticity was realised using a monocentric, comparative, retrospective approach where subjects were their own controls (n = 22). Study results confirm the efficacy of baclofen on symptoms, functional status of patients and on a non specific quality of life scale. Conversely, use of baclofen lead to a 67% increase of average annual costs of care for these patients and reaches around 173,500 French francs (~29,000 US$)/year. Such a cost seems to be acceptable with respect to clinical benefits. © 1998 Elsevier, Paris     

Death after acute withdrawal of intrathecal baclofen: case report and literature review

A 21-year-old man with C1 sensory-incomplete ventilator-dependent quadriplegia, treated with good results with an intrathecal baclofen pump for intractable spasticity since age 17, developed increasing spasticity and revers when his pump began to malfunction. He became unresponsive and developed hypotension, severe hyperthermia, and ventricular tachycardia that required chemical and electrical cardioversion. Although he was receiving oral baclofen when his pump failed, and he was given an intrathecal bolus of baclofen, he subsequently developed rhabdomyolysis, hepatic enzyme elevations, and a consumptive coagulopathy. Cerebral ischemia then occurred, causing brain death. The literature about intrathecal baclofen withdrawal is reviewed to illustrate that it can be a life-threatening event.     

Efficacy of intrathecal baclofen in the treatment of spasticity in stroke]

OBJECTIVE: To determine whether intrathecal administration of baclofen reduced spastic hypertonia in a hemiplegic patient after hemorrhagic stroke. METHODS: A trial of intrathecal administration of baclofen was carried out with bolus injections of 50 and 75 microg baclofen and clinical and functional evaluation (Aschworth, articular amplitude) before and after injection in a patient with hemorrhagic stroke. After these trials, the placement of a pump was proposed to the patient. RESULTS: Aschworth score improved from 4 to 3 on triceps, quadriceps and adductus, with functional improvement of gait quality and perimeter and position in the wheelchair. Cephalgia, present before the treatment, increased after the implantation of the pump. The patient had some ejaculation trouble with the treatment, as well as some neurological pains after the pump implantation but experienced no effect on upper limbs. DISCUSSION: The intrathecal administration of baclofen has been used in some studies of hemiplegic patients, with reduced spasticity and improved the kinematic parameters of gait. The intrathecal baclofen administration could complement other treatment to control spasticity after stroke. CONCLUSION: Intrathecal baclofen administration could be an interesting complementary therapeutic among patients with important spasticity not controlled by the usual treatments.     

Spasticity in children with cerebral palsy: a retrospective review of the effects of intrathecal baclofen

The administration of baclofen by intrathecal pump is a new technique used to reduce spasticity for individuals with upper motor neuron system injuries. Children with cerebral palsy often have difficulty in mobility because of this form of spasticity. The purpose of this study was to assess the functional outcomes of intrathecal baclofen pump therapy with spasticity in children with cerebral palsy. A retrospective review of medical records for pediatric cerebral palsy patients receiving intrathecal baclofen for intractable spasticity was performed. Of 23 sequential medical records meeting requirements for inclusion in the study, 17 subjects had sufficient recorded data to be included in the study. Data from the medical records included Ashworth scores, therapy complications, and changes in mobility and independence. Although no significant changes in the upper extremities with intrathecal baclofen occurred at one and three months, the trial bolus showed statistically significant changes in mean Ashworth scores. The pre- and posttrial bolus Ashworth scores for the lower extremities showed statistically significant decreases in the posttrial scores and at one and three months when compared with the pretrial scores (p < .001). Complications were resolved with conservative management without long-term sequelae. No infections, respiratory depressions, or deaths occurred as a result of intrathecal baclofen therapy in this study. Although intrathecal baclofen had a significant effect in reducing lower extremity spasticity in children with cerebral palsy, further prospective studies are needed to determine the effects of intrathecal baclofen on such indicators as activities of daily living.     

Motor function improvement following intrathecal baclofen pump placement in a patient with locked-in syndrome

We describe a patient with locked-in syndrome who had minimal volitional motor function and severe spasticity in all four extremities. The patient showed a significant improvement in volitional motor function following intrathecal baclofen pump therapy to control spasticity. This case study suggests that intrathecal baclofen pump therapy might improve motor function in select patients with locked-in syndrome.     

Intrathecal baclofen withdrawal mimicking sepsis

Baclofen (Lioresal™) is a drug of choice to treat spasticity and is increasingly being administered intrathecally via an implantable pump in cases refractory to oral therapy. Emergency physicians will likely treat patients with baclofen withdrawal or overdose as this treatment becomes more widespread. The syndrome of baclofen withdrawal presents with altered mental status, fever, tachycardia, hypertension or hypotension, seizures, and rebound spasticity, and may be fatal if not treated appropriately. Baclofen withdrawal may mimic other diseases including sepsis, meningitis, autonomic dysreflexia, malignant hyperthermia, or neuroleptic malignant syndrome. Treatment consists of supportive care, reinstitution of baclofen, benzodiazepines, and diagnosis and eventual repair of intrathecal pump and catheter malfunction.     

Long-term intrathecal (i.t.) infusion of bupivacaine relieved intractable pain and spasticity in a patient with multiple sclerosis

There is no reliable method to relieve both ‘refractory'; pain and spasticity in patients with multiple sclerosis (MS). This paper reports on the long-term use of continuous intrathecal bupivacaine infusion in such a patient. The patient under study was a 56-year-old woman affected for 18 years by MS, unsuccessfully treated with analgesics, baclofen, opioids, peripheral neurolysis (obturator nerves, lumbar plexus) and six intrathecal neurolyses of the L4-S3 nerve roots, each time with 1.5 ml of 50% phenol in glycerol. Intrathecal baclofen was not considered (MS with bulbar location and neurogenic pains). An intrathecal catheter was inserted via the L3-L4 interspace and its tip was placed at the height of the T12-L1 intervertebral disc. An intrathecal infusion of 0.5% bupivacaine at a rate of 3 ml (=15 mg)/day was started. The infusion rate was gradually increased from 20 mg on the first day to 95 mg/day after 68 days. The pain intensity decreased from a mean visual analogue score (VAS/_mean) of 7 before treatment to 1 (on a 0–10 scale) during the intrathecal treatment. The patient became free from pain and spasticity. No side-effects or complications were recorded. The treatment was given for 712 days, at which point the patient died (unrelated to the treatment). Intrathecal infusion of bupivacaine relieved ‘refractory'; spasticity and pain in a MS patient in whom administration of intrathecal baclofen was contraindicated and neurodestructive procedures had been inefficient.     

Intrathecal baclofen in hereditary spastic paraparesis.

Intrathecal baclofen has not been previously evaluated for the treatment of the disabling hypertonia associated with hereditary spastic paraparesis. Muscle tone and deep-tendon reflexes were evaluated in three patients with hereditary spastic paraparesis after a double-blind, cross-over bolus injection of intrathecal baclofen. Patients underwent placement of a subcutaneous pump for continuous infusion of intrathecal baclofen. Three months after implantation the muscle tone decreased 2.04 points (p less than .0001) and the reflex score decreased 2.25 points (p less than .001). Patients initially reported subjective weakness, but muscle testing revealed either an increase or no change in voluntary motor function. Baclofen doses of 60 to 264 micrograms per day were required for effective control of muscle tone and spasticity. Much of the disability in familial spastic paraparesis may be related to the loss of suprasegmental inhibition of spinal reflexes overwhelming the residual voluntary motor function.     

Continuous intrathecal baclofen in spinal cord spasticity. A prospective study.

Continuous intrathecal infusion of the well known antispastic medication baclofen was evaluated in ten consecutive patients. One year after pump implantation the average Ashworth scale for muscle tone decreased, compared with before treatment, 2.32 points (P < 0.0001), reflexes decreased 2.22 points (P < 0.0001) and the spasm score decreased 1.65 points (P < 0.0001). The average dose increased from 92.22 to 290.95 micrograms (P < 0.0001) between the 1st month of treatment and 1 yr of treatment. The dosage for all patients more than doubled (P < 0.0022) between 3 months and 1 yr postimplantation. There was no significant difference for muscle tone, reflexes or spasms at 3 months v 1 yr. Complications were not unusual and included temporary atelectasis, orthostatic hypotension with escalation of baclofen dose, loss of penile erections, postsurgical pseudo-meningoceles, catheter disruptions and exhausted pump reservoirs. One patient suffered a seizure apparently related to a rapid withdrawal from intrathecal baclofen as a result of catheter sequestration. All patients required a period of intensive inpatient rehabilitation to benefit functionally from the decreased motor tone and/or increased voluntary motor control. The procedure is expensive and close follow-up is necessary for assessing efficacy and refilling the pump. Intrathecal baclofen infusion by subcutaneous pump is useful in treating the effects of spinal spasticity resistant to oral medications. However, there appears to be accommodation to intrathecal baclofen necessitating escalating doses to maintain clinical effects.     

Intrathecal baclofen therapy: challenges in patients with multiple sclerosis.

Intrathecal baclofen (ITB) is a recognized therapy for severe spasticity of both spinal and cerebral origin, with documented positive clinical outcomes for many patients with multiple sclerosis (MS). This article reviews some specific considerations concerning the use of ITB in the MS population, based on the author's 10 years of clinical experience. The unpredictable and progressive nature of the disease affects the identification of appropriate goals, the patient's decision-making process, and the evaluation of the response to the treatment over time. Patients with MS may be more sensitive to intrathecal baclofen than patients with other diagnoses, and may need a lower dose for both the screening test and maintenance therapy. Subtle cognitive changes may affect the patient's ability to understand the education needed for successful management of ITB. Some practical strategies are offered for the nurse involved in the care of these patients in each stage of the therapy.     

New treatment for spasticity--intrathecal baclofen therapy

Since its introduction in the late 1980s, intrathecal baclofen(ITB) therapy has become the standard treatment for severe generalized spasticity of both spinal and cerebral origin. More than 50,000 pumps were implanted in the world. Long term efficacy of ITB therapy is excellent, although it is frequently associated with complications such as infections, catheter malfunctions, and cerebrospinal fluid leaks. There are some reports of death with withdrawal, overdose and infection. For a good results we need to discuss factors involved in selecting the appropriate treatment modalities for the individual. The treatment of these patients is optimized in the setting of a multidisciplinary team.     

EFFECTIVENESS AND SAFETY OF CERVICAL CATHETER TIP PLACEMENT IN INTRATHECAL BACLOFEN TREATMENT OF SPASTICITY: A SYSTEMATIC REVIEW

ObjectiveTo evaluate the effectiveness and safety of intrathecal baclofen treatment of spasticity, administered via a cervical catheter tip.DesignA review of PubMed and the Cochrane Library up to September 2020. No restriction in study design. Two reviewers independently evaluated eligibility, extracted data and evaluated risk of bias. Studies were included in which patients were treated with intrathecal baclofen for spasticity, with the catheter tip at or above the first thoracic level, independent of diagnosis and age.ResultsThirteen studies were eligible, with a moderate to critical risk of bias. Improvement in spasticity was seen only in the upper extremity in 6% of subjects, only in the lower extremity in 2%, in both upper and lower extremities in 50% and without specification of location in 41%. Upper extremity function improved in 88% of cases. Neither drug-related (1%) nor technical (21%) complications occurred more often than in lower placement of the tip. Effects on respiratory function and sleep apnoea were not investigated.ConclusionCervically administered intrathecal baclofen seems to improve upper extremity spasticity and function, without causing more complications than thoracolumbar intrathecal baclofen. However, the mainly drug-related complications have not been thoroughly investigated and the available literature is of poor methodological quality. Further research is needed to confirm the efficacy and safety of this procedure.LAY ABSTRACTSpasticity is a common complication in central neurological disorders. It can lead to discomfort and functional limitations. To reduce spasticity, administration of baclofen via a catheter into the spinal canal has been used successfully for several years. However, this treatment often has limited effects on the upper limbs. The catheter tip is often situated in the thoracolumbar region. This review suggests that baclofen treatment via a cervically located catheter tip reduces spasticity of both arms and legs. Also, arm function improved in patients with a cervical catheter tip. Neither drug-related nor technical complications occurred more often than in lower placement of the cervical catheter tip. Few studies were found on this subject, and the available literature is of poor quality. Therefore, more research is needed to confirm the positive effect of this procedure on spasticity of the arms and to monitor for complications.Key words: intrathecal baclofen, tip placement, cervical, upper extremity, spasticity

Spasticity is a common complication after central nervous system injury with involvement of the upper motor neuron. The prevalence varies from 45% in stroke, 65% in spinal cord injury to 80% in multiple sclerosis (1–3).Spasticity is most commonly defined as “velocity-dependent increase in the tonic stretch reflex”, but has been redefined in 2005 by the European working group EUSPASM as “disordered sensori-motor control, resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles” (4, 5). Depending on the severity, spasticity can negatively influence voluntary movement and lead to discomfort and functional limitations (5, 6).In functionally limiting spasticity, non-invasive treatment options, such as elimination of spasm provoking stimuli and physical therapy, should be considered first. In case of insufficient effect, oral medication can be started for general spasticity, or botulinum toxin, phenol or surgery for focal spasticity (7). Baclofen is the most commonly used oral antispasmodic (8). It is a centrally-acting gamma aminobutyric acid (GABA)-B agonist that works as muscle relaxant by diminishing reflex transfer at the spinal cord level. As orally provided baclofen poorly crosses the blood–brain barrier, high doses may be needed to achieve a functional effect, which may induce side-effects, such as fatigue, respiratory depression and confusion. Baclofen can also be administered locally via an intrathecal catheter, resulting in fewer side-effects than systemic baclofen treatment (6). The lower occurrence of side-effects can be explained, on the one hand, by a lower required baclofen dose (as the blood–brain barrier no longer has to be crossed), resulting in fewer general side-effects, and, on the other hand, by a lower cerebral baclofen concentration, resulting in fewer central nervous side-effects.The effect of intrathecal baclofen (ITB) on spasticity of the lower extremity (LE) has been well described in numerous studies, whereas the effect on spasticity of the upper extremity (UE) is less certain (9, 10). This difference in effectiveness might be related to the position of the intrathecal catheter tip and the baclofen gradient in the cerebrospinal fluid. The catheter tip is often positioned at the thoracic or lumbosacral level, assuming that the cerebrospinal fluid flow distributes baclofen in the intrathecal space to the required site of action. However, 2 studies that have been conducted on ITB distribution in humans show a steep concentration gradient of baclofen (11, 12). Kroin et al. found a lumbar-to-cisternal decrease in concentration of approximately 75% (11), and Heetla et al. reported a decrease in concentration from T10 to 30% at 5 cm tip distance, 12% at 10 cm and 0.7% at cerebral level (12). This baclofen concentration gradient suggests that, for optimal treatment of UE spasticity, the catheter tip should be located at the high thoracic or cervical level.Balsara et al. and Albright et al. suggest that catheter tip position should be dependent on treatment goal: T10–12 for diplegia and C5–T2 for tetraplegia (8, 13). However, in clinical studies there is no consensus on the relationship between catheter tip position and the effect on spasticity (14, 15).The demand for adequate treatment of UE spasticity has increased, as there is a growing number of patients with cervical spinal cord injury (16–18). A cervically positioned catheter tip could ameliorate spasmolytic effects on the UE due to higher cervical concentration of baclofen. However, it might lead to an insufficient effect on LE spasticity. Cervical ITB could also influence respiratory function and sleep-related disorders, either positively or negatively (19–21). Furthermore, a high cervical concentration of baclofen could increase cerebral side-effects and thereby influence cognitive and emotional functions. In this systematic review, the effectiveness and safety of baclofen treatment via a cervical catheter tip is analysed.     

联合用药治疗脊髓损伤中重度痉挛的临床观察

目的观察联合应用巴氯芬、替扎尼定和乙哌立松治疗脊髓损伤中重度痉挛患者的临床效果。方法住院脊髓损伤中重度痉挛患者18 例,采用2 种或3 种药物联合应用,所有患者连续服药2 个月,并随访4 个月以上。采用改良Ashworth 评分进行评定,同时观察痉挛缓解持续时间及血压、血尿常规和肝肾功能。结果重度痉挛患者16 例中,3 例改良Ashworth 评分降低3 级,12 例降低2 级,1 例降低1 级,伴神经痛明显减轻;2 例中度痉挛患者均降低1 级,伴神经痛明显减轻。服药后肝肾功能未见异常,出现轻度嗜睡2 例。结论联合用药对脊髓损伤中重度痉挛患者的解痉效果明显,副作用小。     

Dysesthesia perceived as painful spasticity: A report of 3 cases

Lesions of the central nervous system often involve the pyramidal tracts and the sensory pathways to produce spasticity, paresthesias, and dysesthesia. Three patients with intractable spasticity were treated with intrathecal baclofen. Two had an implanted Medtronic SynchroMed pump for long-term delivery of the muscle relaxant. The third patient had undergone a screening trial in which the baclofen was delivered into the intrathecal space through a lumbar catheter. All had excellent relief of spasms on clinical examination, but they reported painful spasms particularly at night. Two of the patients were successfully treated for dysesthesia.     

Symptoms of recurrent intrathecal baclofen withdrawal resulting from drug delivery failure: a case report.

A 24-yr-old, completely (T8) paraplegic male patient presenting with severe spasticity had a drug administration device implanted in April 1991 for continuous intrathecal administration of baclofen. After a period of remarkable improvement in both the spasticity level and his quality of life, the patient experienced several short-lasting episodes of increased spasticity, with severe spasms. Among the possible causes of these deleterious episodes were microcrystalluria, obstipation, a decubitus ulcer, a foreign body in the buttocks, drug tolerance to baclofen, electromagnetic interference, and erroneous filling and programing of the pump. The catheter was the most common source of intrathecal baclofen withdrawal symptoms and had to be changed four times in 5 yr. Intrathecal baclofen administered through an implantable drug administration device is a highly effective but complex and expensive procedure that requires careful patient selection and close monitoring by highly qualified and well-trained health professional. Withdrawal symptoms may be related to noncompliance on the part of the patient, erroneous filling or programing of the pump, depletion of the battery, random component failure, concomitant illness, drug tolerance, or advancement of the disease itself. When failure of the device is suspected, substitution with oral baclofen is recommended until a full work-up is performed to determine the defect.