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Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q.

OBJECTIVE: To describe clinical, electrophysiologic, neuroimaging, and muscle biopsy features in a hereditary spastic paraplegia (HSP) kindred linked to a new HSP locus on chromosome 8q. BACKGROUND: HSP is a genetically diverse group of disorders characterized by insidiously progressive spastic weakness in the legs. We recently analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage to a novel HSP locus on chromosome 8q23-24. METHODS: Clinical analysis, nerve conduction studies, electromyography, somatosensory evoked potentials, MRI of brain and spinal cord, and muscle biopsy for mitochondrial analysis were performed in members of the first HSP kindred linked to chromosome 8q. RESULTS: Fifteen individuals showed insidiously progressive spastic paraparesis beginning between ages 22 and 60 years (average, 37.2 years). Spinal cord MRI in 1 moderately affected subject showed significant atrophy of the thoracic spinal cord as determined by cross-sectional area measurements. Somatosensory evoked potential recording, electromyography, nerve conduction studies, and muscle biopsy, including histochemical and biochemical analysis of mitochondrial function, were normal. CONCLUSIONS: The phenotype in this family is that of typical, but severe, uncomplicated HSP. Other than apparently increased severity, there were no clinical features that distinguished this family from autosomal dominant HSP linked to loci on chromosomes 2p, 14q, and 15q. This clinical similarity between different genetic types of autosomal dominant HSP raises the possibility that genes responsible for these clinically indistinguishable disorders may participate in a common biochemical cascade. Normal results of muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked autosomal dominant HSP and may not be a common factor of HSP in general.

Adult↗

Variant Alzheimer's disease with spastic paraparesis: clinical characterization.

OBJECTIVE: To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype. BACKGROUND: The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores. PATIENTS AND METHODS: Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients. RESULT: The mean age at onset (+/-SD) was 50.9 +/- 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism. CONCLUSION: Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.

Age of Onset↗

X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation in the homeobox gene ARX.

OBJECTIVE: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. METHODS: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. RESULTS: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). CONCLUSIONS: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.

Adult↗

Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord.

Twelve female mongrel dogs were made paraplegic by midthoracic spinal cord transection. Beginning at 9 weeks posttransection, either glycine (50 mg/kg) or saline was injected intramuscularly each day and the signs of spinal spasticity were assessed clinically. After treating the dogs for 3 weeks, we removed the lumbar enlargement of each dog and microdissected it into gray and white areas which we assayed for glycine, glutamate, and aspartate content. Some of the clinical signs of spasticity improved in the animals injected with glycine compared to the saline-injected controls. The content of glycine was significantly elevated in the central gray matter and ventral medial white matter of the glycine-treated dogs. The levels of glutamate were also significantly elevated in the central, lateral ventral, and medial ventral gray matter and in the dorsal lateral and ventral medial white matter of the glycine-treated dogs. The possible role of these segmental putative neurotransmitters in spinal spasticity is discussed.

Animals↗

A prospective study of radiofrequency rhizotomy in the treatment of posttraumatic spasticity.

Posttraumatic spasticity severely impedes rehabilitation potential and nursing care. Treatment of severe spasticity has included medical therapy, spinal cord ablative procedures, anterior and posterior root lesions and peripheral denervations, and tendon releases. Open rhizotomy and percutaneous radiofrequency rhizotomy have achieved good results. We prospectively studied 25 patients with severe spasticity to assess the efficacy of percutaneous radiofrequency rhizotomy. All or most of the prospectively identified goals were accomplished in 24 of the 25 patients, with improvement persisting during an average follow-up period of 12 months. The improvement due to decreased tone was much greater than the improvement due to increased range of motion.

Adolescent↗

Control of intractable spasticity with intrathecal morphine sulfate.

Three years ago we reported our preliminary results regarding treatment of intractable spasticity with use of intrathecal morphine. This paper is a follow-up report of 12 patients who underwent implantation of a pump or reservoir for delivery of intrathecal morphine sulfate for control of spasticity. Our primary concern initially was that patients would ultimately become drug tolerant and lose the beneficial effect of the morphine. Only one of these 12 patients has developed drug tolerance. The longest follow-up period has been 4.3 years, and this patient has maintained excellent control of his spasticity with a stable dose of 2 mg of morphine daily.

Drug Tolerance↗

Microsurgical DREZ-otomy for the treatment of spasticity and pain in the lower limbs.

The authors report on a series of 53 bedridden patients suffering from harmful spasticity in one (6) or both (47) lower limbs, who were treated with microsurgical DREZ-otomy. Surgery was performed to treat fixed abnormal postures in flexion in 49 patients and hyperextension in 3, and, additionally, to treat pain in 37 patients. Microsurgical DREZ-otomy was introduced in 1972, on the basis of anatomical studies of the human dorsal root entry zone (DREZ) showing a topographical segregation of the afferent fibers according to their size and functional destinations. It consists of a 2 mm deep microsurgical lesion directed at a 45 degrees angle in the posterolateral sulcus and penetrating the dorsal root entry zone in its ventrolateral aspect, at the level of all the rootlets considered involved in spasticity (and pain). It destroys mainly the lateral (nociceptive) and central (myotatic) afferent fibers as well as the facilitatory medial part of the Lissauer tract, while sparing most of the medial (lemniscal) fibers, the suppressor lateral part of the Lissauer tract, and more or less of the dorsal horn (DH). The postoperative results were evaluated after a mean follow-up period of 3 years and 4 months. Both spasticity and spasms were significantly decreased or suppressed in 75% and 88.2% of the patients, respectively. When present, pain was relieved without abolition of sensation in 91.6%. These benefits--combined with complementary orthopedic surgery in 23 patients--resulted in either disappearance or marked reduction of the abnormal postures in 85.3% of the patients and of articular limitations in 96.8%. Mild-to-severe complications occurred in 25 patients and precipitated or were responsible for death in 5. This is explained by the fact that the general and neurological conditions of most of the patients--especially those affected by multiple sclerosis--were precarious. MDT has, however, enabled a majority of these severely disabled patients to sit and lie comfortably, and has allowed them to reach a significantly improved quality of life.

Adolescent↗

Spastic equinus foot: multicenter study of the long-term results of tibial neurotomy.

OBJECTIVE: Tibial neurotomy is a surgical technique widely used for the treatment of spastic equinus foot, but it has rarely been evaluated. The primary objective of this prospective study was to provide an objective quantification of the long-term results of tibial neurotomy. METHODS: This multicenter prospective study was conducted from 1999 to 2003. Fifty-five patients with spastic equinus foot were treated in five neurosurgical centers. Preoperative and postoperative clinical evaluation comprised description of the foot deformity, study of stretch reflexes, evaluation of the repercussions of the deformity, and gait analysis. Selective neurotomy was performed in all patients. RESULTS: No postoperative complications were observed. The mean postoperative follow-up was 10 months. Tibial neurotomy improved the appearance of the foot (equinus and varus deformities, claw toes); the equinus score decreased from 1.54 to 0.273 after the operation. Stretch reflex scores were decreased significantly and for a long term after surgery; the mean triceps surae stretch reflex score decreased from 2.46 to 0.47. The angle of passive dorsiflexion of the ankle increased significantly (from -0.56 degrees to +6.85 degrees). Gait analysis demonstrated a statistically significant increase in the speed of the patient's gait after surgical treatment; the time taken by the patient to walk 10 m at a normal speed in shoes decreased from a mean of 55 seconds to 35.16 seconds. Postoperatively, 92.7% of preoperative objectives had been achieved. CONCLUSION: Tibial neurotomy ensures long-term functional improvement of patients with spastic equinus foot. It provides a lasting response for these patients compared with other, more transient treatments.

Adolescent↗

A review of intrathecal baclofen in the management of spasticity.

Spasticity is associated with damage to the corticospinal tract and is a common complication of neurological disease. Patients with spasticity complain of stiffness, involuntary spasm and pain. The majority of patients are managed conservatively with physiotherapy and/or oral medication. However, 25-35% of patients will develop unacceptable side-effects or fail to respond to oral doses of antispasmodics. Surgical procedures such as myelotomy, rhizotomy and neurotomy have not been universally successful. More recently, intrathecal baclofen has become established as an important adjunct in the management of spasticity. This article describes the mechanism of action of baclofen, the delivery systems available and the criteria for patient selection. The screening phase, surgical procedure and specific postoperative observations are also described.

Baclofen↗

[Effect of electroacupuncture combined with suspension exercise therapy on lower limb motor function in elderly patients with post-stroke spastic hemiplegia].

OBJECTIVE: To observe the efficacy of electroacupuncture (EA) combined with suspension exercise therapy in elderly patients with post-stroke spastic hemiplegia and its effect on lower limb motor function. METHODS: A total of 120 elderly patients with post-stroke spastic hemiplegia were enrolled. Using a 2&#xd7;2 factorial design, all the patients were assigned to a group A (conventional treatment), a group B (conventional treatment combined with suspension exercise therapy), a group C (conventional treatment combined with EA at Jiaji [EX-B2] and limb acupoints), and a group D(conventional treatment combined with suspension exercise therapy and EA at Jiaji [EX-B2] and limb acupoints), with 30 patients in each group. The main acupoints were bilateral Jiaji (EX-B2) points at the C2-C7, T2-T12, L1-L5, and S1 segments. The adjunct acupoints included Jianyu (LI15), Binao (LI14), Huantiao (GB30), Chengfu (BL36), etc. on the affected side.Continuous wave was applied at a frequency of 100 Hz with a current intensity of 1.5-3.0 mA, and needles were retained for 30 min, once daily for 4 weeks. Before treatment and after 2 and 4 weeks of treatment, the modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA), Berg balance scale (BBS), and Barthel index scores were evaluated in the four groups. Root mean square (RMS) values of surface electromyography (sEMG) of the erector spinae and rectus abdominis muscles on the affected side, as well as balance function indexes, including the mean pressure symmetry index (SI), contact area SI, ellipse area, and displacement distances of the center of pressure in the anteroposterior (AP) and mediolateral (ML) directions, were measured. Clinical efficacy was also compared among the four groups. RESULTS: After 2 and 4 weeks of treatment, MAS scores in all groups were lower than those before treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those before treatment (P<0.05). After 4 weeks of treatment, MAS scores were lower than those after 2 weeks of treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those after 2 weeks of treatment (P<0.05) in the four groups. At both 2 and 4 weeks after treatment, group D had lower MAS scores (P<0.05) and higher FMA,BBS, and Barthel index scores (P<0.05) than the other three groups. After 2 and 4 weeks of treatment, RMS values of sEMG of the erector spinae and rectus abdominis muscles on the affected side at all tested angles were higher than those before treatment in all groups (P<0.05), and the values after 4 weeks of treatment were higher than those after 2 weeks of treatment(P<0.05). At both 2 and 4 weeks after treatment, all these indexes in the group D were higher than those in the other three groups (P<0.05). After 2 and 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those before treatment (P<0.05). After 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those after 2 weeks of treatment (P<0.05). After 2 and 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those before treatment (P<0.05), and after 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those after 2 weeks of treatment (P<0.05);after 2 weeks of treatment, there was no statistically significant difference in AP displacement distance in the group B compared with before treatment (P>0.05), and after 4 weeks of treatment, the AP displacement distance of group B was lower than that before treatment (P<0.05). After 2 weeks of treatment, there was no statistically significant difference in ML displacement distance in group A compared with before treatment (P>0.05); after 4 weeks of treatment, the ML displacement distance of group A was lower than that before treatment (P<0.05). After 2 and 4 weeks of treatment, there was no statistically significant difference in ML displacement distance in the group B compared with that before treatment (P>0.05).After 2 and 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those before treatment(P<0.05), and after 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those after 2 weeks of treatment (P<0.05). At both 2 and 4 weeks after treatment, mean pressure SI, contact area SI, ellipse area, and AP and ML displacement distances in the group D were lower than those in the other three groups (P<0.05). Factorial analysis of variance showed that EA had the strongest main effect on FMA score (F=6.243, P<0.05), suspension exercise therapy had the strongest main effect on BBS score (F=6.292, P<0.05), and the interaction effect was most significant for MAS score (F=5.941, P<0.05), indicating that the combined therapy produced a greater synergistic effect on reducing muscle tone than on the other outcome measures. The total effective rate in the group D was 93.3% (28/30), which was higher than those in the group A (53.3% [16/30]), group B (56.7% [17/30]), and group C (66.7% [20/30], P<0.05). CONCLUSION: EA combined with suspension exercise therapy could effectively promote the recovery of lower limb function in elderly patients with post-stroke spastic hemiplegia, improve motor and balance functions, and enhance activities of daily living.

Humans↗

Hereditary spastic paraplegia: clinical genomics and pharmacogenetic perspectives.

Hereditary spastic paraplegias (HSPs) are a group of single-gene disorders characterised by degeneration of the corticospinal tract axons, leading to bilateral, symmetrical, slowly-progressive spastic paraparesis, predominantly of the lower extremities. So far, ~ 30 different chromosomal HSP loci have been identified by genetic linkage analysis. Defects in intracellular trafficking and transport in myelination and abnormalities of mitochondrial proteins have been involved in HSP pathogenesis. At present, treatment of the HSPs is primarily directed symptomatically toward reducing muscle spasticity. Yet, recent progresses in the identification of HSP mutations are providing formidable tools to pharmacogenetic approaches of drug discovery, validation and prediction of individual response.

Baclofen↗

Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator.

Spastic (spa), spasmodic (spd), and oscillator (ot) mice have naturally occurring glycine receptor (GlyR) mutations, which manifest as motor deficits and an exaggerated "startle response." Using whole-cell recording in hypoglossal motoneurons, we compared the physiological mechanisms by which each mutation alters GlyR function. Mean glycinergic miniature IPSC (mIPSC) amplitude and frequency were dramatically reduced (>50%) compared with controls for each mutant. mIPSC decay times were unchanged in spa/spa (4.5 +/- 0.3 vs 4.7 +/- 0.2 ms), reduced in spd/spd (2.7 +/- 0.2 vs 4.7 +/- 0.2 ms), and increased in ot/ot (12.3 +/- 1.2 vs 4.8 +/- 0.2 ms). Thus, in spastic, GlyRs are functionally normal but reduced in number, whereas in spasmodic, GlyR kinetics is faster. The oscillator mutation results in complete absence of alpha1-containing GlyRs; however, some non-alpha1-containing GlyRs persist at synapses. Fluctuation analysis of membrane current, induced by glycine application to outside-out patches, showed that mean single-channel conductance was increased in spa/spa (64.2 +/- 4.9 vs 36.1 +/- 1.4 pS), but unchanged in spd/spd (32.4 +/- 2.1 vs 35.3 +/- 2.1 pS). GlyR-mediated whole-cell currents in spa/spa exhibited increased picrotoxin sensitivity (27 vs 71% block for 100 microM), indicating alpha1 homomeric GlyR expression. The picrotoxin sensitivity of evoked glycinergic IPSCs and conductance of synaptic GlyRs, as determined by nonstationary variance analysis, were identical for spa/spa and controls. Together, these findings show the three mutations disrupt GlyR-mediated inhibition via different physiological mechanisms, and the spastic mutation results in "compensatory" alpha1 homomeric GlyRs at extrasynaptic loci.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Use of intrathecal morphine infusion for spasticity.

OBJECTIVE: To study the efficacy of intrathecal morphine infusion to treat spasticity. SETTING: Functional Neurosurgery Division of University of São Paulo, Brazil. METHOD: Twelve patients with clinical refractory spasticity were studied. Two females and 10 males, with median age of 34.4 years (20 to 61 ys.). The initial Ashworth scale was 4.6. They were submitted to pump implantation for intrathecal morphine infusion. RESULTS: The final Ashworth scale was 2.2. The median dose concentration of Intrathecal morphine was 0.95 mg, with a mean frequency of 1.8 times a day. Four patients developed pruritus, two patients nausea, two patients urinary retention, however all improved after morphine concentration was decreased. One patient was submitted to pump review after extrusion catheter. CONCLUSIONS: Intrathecal morphine infusion is very helpful in patients with spasticity refractory to clinical treatment, and we observed only minor complications.

Adult↗

Common animal models for spasticity and pain.

Animal models of spasticity and pain have allowed for the elucidation of possible mechanisms and the evaluation of potential therapeutic interventions for these serious clinical problems. Each model mirrors the clinical appearance of many features of the syndrome, but few reproduce the myriad patient reports of either intensity or relevant contributing factors, especially in models of chronic neuropathic pain. Often these models have been used to predict the potency and efficacy of pharmacologic agents that work in human pain states. Pain models have relied on measurements of the shifts in behavioral hypersensitivity to tactile and thermal stimuli, tests that are not used quantitatively in human patients. Even with the multiple peripheral and central models of spasticity and pain used in animals, only a few actually test human conditions: namely, diabetic neuropathy, chemotherapy, and immunotherapy for tumors. However, all these models have allowed for the comparison of certain behavioral, cellular, biochemical, and molecular mechanisms with human patient populations. Here we review the few extant models of spasticity, nerve injury, and central injury models of pain, and describe their features and use.

Animals↗

Spasticity after stroke. Epidemiology and optimal treatment.

Spasticity following stroke reflects a spectrum of clinical problems including increased muscle tone, abnormal limb posture, excessive contraction of antagonist muscles and hyperactive cutaneous and tendon reflexes. The prevalence of stroke-related disability in stroke survivors is high, and spasticity may be a significant component of this. Management strategies include a multidisciplinary team approach utilising a variety of rehabilitation techniques. Although some interventions are well tolerated and fairly standardised, older adults may be particularly sensitive to drug treatment-related adverse effects. This article reviews some of the commonly employed interventions, such as oral medications, and some of the newer techniques, such as intrathecal baclofen infusion and botulinum toxin injections. The optimal management of spasticity following stroke in older adults requires careful goal setting and skilful combination of treatment modalities in order to produce the best outcome.

Cerebrovascular Disorders↗

Botulinum toxin A treatment of adult upper and lower limb spasticity.

This article discusses the treatment of spasticity with botulinum toxin A as a new approach in the neurological rehabilitation of patients after stroke. Clinical studies have been reviewed to provide information about target groups, technical aspects and the advantages and disadvantages of treating spasticity with botulinum toxin A. Open and controlled studies showed that the intramuscular injection of Dysport 500 to 1,500U or Botox 100 to 300U could reversibly relieve upper limb flexor and lower limb extensor spasticity. A reduced muscle tone, pain relief, better hand hygiene and improved walking function were the main benefits. Patients tolerated the treatment well. Activity or, if not possible, electrical stimulation of the injected muscles may enhance the effectiveness of the costly toxin. Serial casting is another option. With respect to the action of botulinum toxin A, it is suggested that the effect of the toxin could be mediated by paresis of both the extrafusal and intrafusal muscle fibres, thereby altering the afferent discharge in the muscle.

Adult↗

Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system.

OBJECTIVE: The purpose of our study was to analyse and evaluate the costs of continuous intrathecal baclofen administration as a modality in the treatment of severe spasticity in the Netherlands. DESIGN: A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary, randomised and placebo-controlled clinical trial. The study covered the period from December 1991 to September 1995. The data on medical consumption and costs were collected over a 3-year period from different sources: administrative databases of health insurance companies, hospital registries and a patient survey. These data were structured by means of a flowchart analysis of the medical decision-making by specialists and general practitioners (GPs). They included data on in- and outpatient care, home care and care in nursing homes. The cost analysis was conducted using data from 18 patients included in the trial and from 15 so-called 'match' patients. The latter group are patients with comparable diseases leading to spasticity and living in comparable circumstances. Next to absolute costs (direct and indirect) of care and treatment for the 2 groups of patients, cost differences between the 2 groups were considered (differential cost analysis). SETTING: Per patient cost data, collected prospectively for 2 years during the phase of clinical evaluation, and retrospectively 1 year before implantation. The data were collected on patients from in- and outpatient care, home care and care in nursing home settings. PATIENTS AND PARTICIPANTS: The trial patients (8 men) had a mean age of 46 years; 11 patients had multiple sclerosis and 7 patients had spinal cord injuries. The match patients (7 men) had a mean age of 48 years; 9 patients had multiple sclerosis and 6 patients had spinal cord injuries. INTERVENTIONS: Trial patients were treated with a subcutaneously implanted programmable continuous infusion pump (SynchroMed, Medtronic), filled with baclofen (a muscle relaxant) to treat patients with chronic disabling spasticity who did not respond to a maximum dose of oral baclofen, dantrolene and tizanidine. MAIN OUTCOME MEASURES AND RESULTS: An analysis of hospital stay between both groups showed a significant difference during the implantation year. The average number of hospital days per patient in the year in the treated group was 31.5 days and in the match group was 18.7 days. Significant cost differences between both groups in the year that started with pump implantation and the following year can be attributed mostly to the costs of implantation of the pump and related hospitalisation days. The total costs of patient selection, testing, implanting the pump and follow-up amounted to $US28,473 for the first year. Savings must be taken into consideration as well. The savings of direct costs were due to withdrawal of oral medication (estimated annual total of between $US1950 and $US2800 per patient). Indirect savings on employment and nursing home costs, amounted annually to $US1047 and $US5814, respectively. Scenarios make it possible to consider policy consequences. The case of 'extending' the indications for this treatment to a larger population has been calculated and visualised. CONCLUSIONS: The costs of the therapy (continuous intrathecal infusion of baclofen) can be attributed mostly to implantation of the pump and related hospitalisation days. Savings originated from withdrawal of oral medication, job preservation and avoidance or delay of admission to a nursing home.

Adult↗

Cost-effectiveness comparison of tizanidine and baclofen in the management of spasticity.

OBJECTIVE: Baclofen and tizanidine are both used for the treatment of muscle spasticity of spinal origin. Their effectiveness, cost and adverse-effect profiles differ. This paper sets out to estimate the cost effectiveness of each drug, and the impact of changing from baclofen to tizanidine. DESIGN: A simplified but realistic model of physician behaviour and patient response was developed as a decision tree and populated with data derived from the available published clinical comparative trials. We considered patients with spasticity caused by multiple sclerosis or spinal cord injury. The outcome measure used was 'cost per successfully treated day' (STD). Costs were estimated from the perspective of the UK National Health Service at 2000 values. RESULTS: Expected cost for a cohort of 100 patients over 1 year was estimated to be pound 181 545 with baclofen and pound 211 930 with tizanidine. The estimated number of STDs was 20,192 with tizanidine and 17,289 with baclofen. The overall cost effectiveness of managing spasticity using baclofen and tizanidine was very similar ( pound 10.50 and pound 10.49 per STD respectively). The incremental cost effectiveness (ICE) of using tinzanidine as an alternative to baclofen for first-line treatment was pound 10.47 per STD. Sensitivity analysis found the model to be robust to changes in key parameters CONCLUSION: Drug cost should not be a determining factor in making this treatment choice, as the cost effectiveness ratios are similar for both products.

Baclofen↗