We fetch to your notice a new website where you can buy kamagra jelly australia at a low cost with fast delivery to Australia.

Intrathecal

HK J Paediatr (new series) 2000;5:125-131
Intrathecal Baclofen in Cerebral Palsied Children with Severe Spasticity: A Pilot Study and Review CH KO, PWT TSE, GMS WONG, JCZ LUI, M LEUNG, J MAN
Abstract
Continuous intrathecal baclofen infusion (CIBI) is an effective treatment in patients with severe spinalspasticity. Its use in spastic cerebral palsy (CP) is less well established. In the present study, we aim toevaluate the efficacy and safety of intrathecal baclofen in children with cerebral spasticity. Four non-ambulatory children with severe mental retardation were recruited, including two patients with spasticCP and two mixed spastic and dyskinetic CP. Bolus intrathecal baclofen was instillated via an indwellingcatheter in the lumbar subarachnoid space, starting at a dose of 25 µg and increased by 25 µg increments24 hours apart, with a maximum dose of 100 µg. The muscle tone of the upper and lower extremitieswere recorded by the Ashworth score at 2-hour, 4-hour and 6-hour post-injection. The average Ashworthscore of the lower extremities decreased from 2.1 to 1.5. The muscle tone started to decrease within twohours after injection, and remained low throughout the six hour observation period (p<0.05). Threechildren had their muscle tone reduced to nearly normal (Ashworth scores 1.0 to 1.3). The averagemuscle tone in the upper extremities was not significantly affected. Apart from mild drowsiness andskin infection, no severe adverse events were encountered. Our preliminary data suggests that intrathecalbaclofen is effective in reducing the lower extremity hypertonicity in spastic CP children. Patients withsevere spasticity refractory to conventional therapy may benefit from CIBI via subcutaneously placedprogrammable pumps.
Key words
Baclofen; Cerebral palsy; Intrathecal drug infusion; Spasticity Developmental Disabilities Unit, Department of Paediatrics,
Introduction
Caritas Medical Centre, 111 Wing Hong Street, Shamshuipo,
Hong Kong, China

Cerebral palsy (CP) is one of the major long-term CH KO ( 高震雄)
complications in premature and asphyxiated babies.
Despite of advances in neonatal care in the past two PWT TSE ( 謝韻婷)
decades, CP still affects 1.5 to 2.5 per 1000 live births in Department of Orthopaedics and Traumatology, Alice Ho
the United States.1 Two-third of the CP patients have Miu Ling Nethersole Hospital, Tai Po, Hong Kong, China
spasticity of variable severity, leading to significant GMS WONG ( 黃文遜) FRCS(Edin), M.Ch.Orth(Liverpool),
morbidity including gait disturbances, contractures, joint FHKCOS, FHKAM(Orth.), Chief of Service dislocations and decubitus ulcers. The care of spasticity Department of Anaesthesia, Caritas Medical Centre, Hong
poses major financial as well as psychosocial burden on Kong, China
the family. Traditionally, physiotherapy and splintage play JCZ LUI ( 雷操奭)
a major role to treat the hypertonicity and prevent (Anaesthesiology), Chief of Service contractures. In severe cases, soft tissue surgeries and Department of Physiotherapy, Alice Ho Miu Ling Nethersole
osteotomies are often required. It is not uncommon for Hospital, Tai Po, Hong Kong, China
children to undergo multiple operations to tackle the M LEUNG ( 梁素媚)
orthopaedic problems. The response to oral anti-spasticityagents such as diazepam, baclofen and dantrolene are often Department of Physiotherapy, Caritas Medical Centre, Hong
unsatisfactory. A high dose is often required to achieve Kong, China
tone reduction, which is accompanied by intolerable side J MAN ( 文偉麒)
effects on the central nervous system (CNS).
Correspondence to: Dr CH KO
New treatment modalities, notably botulinum toxin and selective dorsal rhizotomy (SDR), have revolutionized the management of spasticity.2,3 SDR have been shown to and safety of bolus intrathecal baclofen in a group of reduce the lower limb spasticity and bring about long- cerebral palsied children with severe spasticity. Patients term functional improvement.4,5 Nonetheless, stringent were admitted for a screening trial to determine if single patient selection is required for an optimal outcome; intrathecal baclofen doses reduced their spasticity. The patients who utilize the spasticity to maintain upright effective dose to bring about tone reduction was postures against gravity are contraindicated to the determined for each child. Patients who responded to the trial dose might be suitable candidates for CIBI via In 1984, Penn and Kroin6 described the use of continuous intrathecal baclofen infusion (CIBI) to alleviatespasticity of spinal origin. Long-term studies revealed thatCIBI via an implanted pump was highly effective in reducing the rigidity and muscle spasms in patients withspinal cord injury and multiple sclerosis.7,8 Subsequent Patients
reports suggested that CIBI was also beneficial to Four children, aged five years eight months to 12 years supraspinal spasticity associated with cerebral palsy and six months, were recruited into the study. All of them were long-term residents in the Developmental Disabilities Unit Baclofen acts as a gamma-aminobutyric acid (GABA) of our hospital. All were severely mentally retarded, non- analogue. The active component of baclofen is β- ambulatory children with either spastic or mixed spastic (aminomethyl)-p-chlorohydrocinnamic acid. It binds to and dyskinetic CP of cerebral origin. They were barely GABA-B receptors within the brainstem, dorsal horn of able to attain sitting postures in CP chairs. There were the spinal cord, and other CNS sites, resulting in inhibition intermittent painful extensor spasms, and increasing of calcium reflux into presynaptic terminals and thus difficulty was encountered to manage their perineal suppressing the release of excitatory neurotransmitters.13 hygiene. The demographic data was shown in Table 2.
Orally administered baclofen has low lipid solublity and The initial evaluation included a thorough history and penetrates the blood-brain barrier poorly, leading to a low neurological examination. The previous medical treatment concentration of drug at the site of action even after large for spasticity was reviewed. The muscle tone in the upper doses.14 Lumber intrathecal administration of baclofen extremities (biceps and triceps) and lower extremities (hip results in a ten-fold increase in cerebral spinal fluid (CSF) adductors, quadriceps, hamstrings and gastrocnemius) was drug level with one percent equivalent of the oral dose.15 assessed by the 5-point Ashworth scale (Table 1)18 by two The lumber CSF level is four times of the level in the cisterna magna.16 In the CSF, baclofen has a half-life The inclusion criteria to the study included: (1) of about five hours and a duration of action of 10 to 12hours, with very little drug returning to the systemic Ashworth
Degree of muscle tone
The delivery system consists of a subcutaneously implanted pump with a reservoir. The pump is programmed to deliver various rates of the drug via a Slight increase in tone, giving a "catch" when catheter in the lumbar subarachnoid space. Direct delivery affected part is moved in flexion or extension of the drug to its site of action increases its effectiveness.
More marked increase in tone, but affected part It allows a reduction in dosage and minimizes the systemic side effects, such as drowsiness, confusion and lethargy.
Considerable increase in tone, passive movement By adjusting the infusion rate of the pump, the spasticity can be titrated to avoid excessive weakness.
Affected part rigid in flexion or extension In the present study, we aimed to evaluate the efficacy Average lower extremity Ashworth score at different doses of intrathecal baclofen Age (year)
Baseline
Side effects
CP: cerebral palsy; M: male; F: female; ND: not done Intrathecal Baclofen in Cerebral Palsied Children Moderate to severe spasticity of cerebral origin that Joint Hospital Management Committee of Caritas Medical interfered with postural control or function, or those who suffered from painful spasms; and (2) children who didnot respond to maximal dose of oral antispasticity agentssuch as diazepam or baclofen and/or those who experienced intolerable side effects from the medications.
The exclusion criteria included: (1) Known hypersensitivity Instead of presenting the Ashworth scores of individual to baclofen; (2) cardiovascular or pulmonary insufficiencies; muscle groups separately, we have calculated the mean (3) severely impaired liver or renal function; and (4) scores of the upper and lower extremities for each patient.
abnormal CSF flow such as hydrocephalus with shunt in- The average Ashworth scores for the upper and lower extremities after different doses of intrathecal baclofenwere listed in Tables 2 and 3. The average Ashworth scores Protocol
at different time intervals after injection were listed in Informed consent was obtained from the parents or guardians. Oral anti-spasticity agents were tailed off beforethe trial. Spinal needle was inserted by one of the Lower Extremities
investigators, a consultant anaesthetist, using aseptic The baseline average Ashworth scores in the lower technique at L3-L4 level. Intrathecal catheter was threaded extremities ranged from 2.0 to 2.4, with a mean of 2.1.
with catheter tip at around T12 level.
The average Ashworth score decreased from a baseline of The intrathecal baclofen used in the present study was 2.1 to 1.5 four hours after injection. Figure 1 shows the "Lioresal Intrathecal", which was supplied in single-use average lower extremity score from 2-hour to 6-hour post- ampules with a concentration of 500 µg/ml. The trial dose injection. The muscle tone was reduced within two hours was given in an open-label manner. Bolus injection of after the bolus injection of baclofen, and the effect persisted intrathecal baclofen , starting at a dose of 25 µg (given in throughout the 6-hour observation period (Friedman's test two ml saline slowly over at least one minute) and p<0.05). Figure 2 shows the average Ashworth score after increased by 25 µg increments at least 24 hours apart,until an optimum dose was reached for tone reduction.
The maximal bolus of baclofen was 100 µg, above which Average upper extremity Ashworth score at different there might be risk of respiratory complication. Children who did not respond adequately to 100 µg baclofen would Baseline
need very high daily dose for CIBI, which would be very Two designated physiotherapists assessed the children independently three times a day (at 2-hour, 4-hour and 6- hour after the bolus injection) during the study period.
Both were blinded to the dose of baclofen given. Muscletone of upper and lower extremities was measured byAshworth score. Reduction of one point or more was Average lower extremity Ashworth score at different time intervals after injection of baclofen All the children were transferred to a high dependency Baseline
area for close monitoring during the trial period. The potential side effects from the drug (e.g. hypertension, drowsiness, confusion) were monitored. The total duration of indwelling catheter would not exceed seven days to minimize the risk of infection. All intrathecal injectionswere given under aseptic conditions with bacterial filterin-situ.
Average upper extremity Ashworth score at different time intervals after injection of baclofen Statistical Analysis
Overall changes in the muscle tone over time within Baseline
the group were analyzed by Friedman's test, which is the non-parametric equivalent of a repeated measures analysis of variance (ANOVA) with a single group. The study protocol was approved by the Ethics Subcommittee of the Time after Baclofen injection
Average Ashworth score at different time intervals after baclofen injection Dosage of Baclofen administered
Average Ashworth score after different doses of baclofen injection different doses of baclofen. The average muscle tone was muscle tone of the upper extremities during the observation reduced after bolus injections of 75 µg and 100 µg of period (Figure 1). No definite reduction in the average baclofen. Three patients had their muscle tone reduced to Ashworth score was observed after different doses of nearly normal, with average Ashworth scores from 1.0 to Three children developed excessive drowsiness, two after 75 µg and one after 50 µg of baclofen injection. All Upper Extremities
of them recovered spontaneously without intervention.
The baseline average Ashworth scores in the upper One patient developed mild skin infection at the site of extremities ranged from 2.0 to 3.6, with a mean of 2.4 intrathecal catheterization, which resolved after catheter (Table 3). There was no significant change in the average Intrathecal Baclofen in Cerebral Palsied Children Discussion
Nonetheless, only one patient demonstrated a clinicallysignificant reduction in the tone (i.e. a reduction of one Spasticity is characterized by velocity-dependent point or more in the Ashworth score). The other two increase resistance to passive muscle movement. In CP patients were only mildly hypertonic with baseline scores associated spasticity, the imbalance between the of 1.6 and 2, so it was difficult to demonstrate a clinically descending inhibitory impulses and the afferent excitatory significant response. They appeared to be more hypertonic impulses from the extremities result in hypertonicity.9 on examinations prior to the study, yet it is not uncommon Baclofen is a GABA agonist which acts presynaptically for the tone in mixed spastic and dyskinetic children to at the spinal level to inhibit the release of excitatory vary from day to day. Concerning the patient who did not neurotransmitters. Baclofen is approximately 30% protein show a reduction in tone, she experienced excessive bound after oral administration. It has low lipid solubility drowsiness at 50 µg of baclofen, so we did not increase and penetrates the blood brain barrier poorly.14 The the dose further. It was not sure whether she might respond response to oral baclofen is highly variable; large doses may lead to lethargy, ataxia, confusion, decreased The tone in the upper extremities was not significantly concentration and respiratory depression. Whilst the CSF reduced in the present study. Similar observations have baclofen levels were less than 12 ng/ml after oral been made in previous studies.9,19 As the tone in the upper administration,15 patients who were receiving a constant extremities was tested four hours after the bolus injection, intrathecal baclofen infusion of 400 µg/day had CSF levels there might not be enough time for the cephalic migration of 380 ng/ml. The concomitant serum level were less than of baclofen into the cervical spinal cord.9 Secondly, 5 ng/ml.16 The 4:1 ratio between lumbar and cervical dystonia contributed significantly to the upper extremity concentrations of baclofen also contribute to the relative hypertonicity in the two patients with mixed CP. The effect of bolus intrathecal baclofen is less predictable in Penn7 demonstrated that intrathecal baclofen effectively dystonia,10,20 and continuous infusion via an external reduced spasticity and spasms of spinal origin in 97% of micro-pump may occasionally be required to evaluate the patients. Coffey et al8 revealed that CIBI was effective for responsiveness to intrathecal baclofen.21 the long-term treatment of intractable spasticity in patients Three patients experienced excessive drowsiness during with spinal cord injury and multiple sclerosis. The use of the screening period. Two of them became drowsy at a intrathecal baclofen in spasticity of cerebral origin is less dose of 75 µg. The sedation effect was mild and transient well established. Albright et al9 demonstrated that bolus and did not preclude further increase in the dose. Both of intrathecal baclofen reduced the lower extremity muscle them recovered spontaneously four to six hours after the tone in 17 patients with congenital spastic CP. Tone in the injection. The third child developed drowsiness after upper extremities was not significantly affected. Meythaler 50 µg of baclofen. The dose was not increased further et al19 showed that bolus intrathecal baclofen significantly despite of inadequate clinical response. One patient reduced the Ashworth score, spasm score and reflex score developed fever and skin infection at the site of in the lower and upper extremities in 11 patients with catheterization. CSF culture was sterile and she recovered acquired brain injury. Long-term follow-up study in 37 after removal of the catheter and conservative treatment.
patients with cerebral spasticity treated by CIBI showed Bolus intrathecal baclofen might result in sedation, that muscle tone was significantly reduced in the upper bradycardia and hypotension.12 In addition to these side and lower extremities. Upper extremity function and effects, CIBI might also be complicated by respiratory activities of daily living were also significantly depression, apnea, blurred vision, slurred speech, improved.10 Becker et al11 reported 18 adult patients with confusion, dysmetria, seizures and meningitis. Most would supraspinal spasticity treated with CIBI for 13 to 54 resolve after dose reduction.7,12 Whilst respiratory months. Both the mean Ashworth score and the mean depression from overdose could be reversed by spasm frequency score were significantly reduced, with physostigmine,22 assisted ventilation might be required in improved pain control, nursing care and mobilization.
severe cases.23 No mortality related to CIBI have been Armstrong et al12 followed up 12 children with cerebral spasticity treated with CIBI for one to five years. All of There were some biases in this pilot study. The sample them showed reduction in Ashworth scores, while most size was small and the study was open-label. Nonetheless, caretakers reported improvement in muscle tone, the purpose of the screening trial was to ascertain the behaviour, sitting and general ease of care.
effective screening dose for tone reduction, which could In the present study, there was a reduction in the average be achieved by blinding the assessors to the dose of muscle tone of the lower extremities. Among the four baclofen given. The Ashworth score is a relatively patients with either spastic or mixed spastic and dyskinetic subjective scale for measuring spasticity, despite of the CP, the tone was reduced to nearly normal in three.
fact that it was widely used in previous studies.7-9 A more objective measurement of spasticity is required for future References
research. The presence of dystonic components in someof the subjects rendered it difficult to assess the baseline Paneth N, Kiely J. The frequency of cerebral palsy: a review tone and subsequent tone reduction. Nonetheless, both of population studies in industrialized nations since 1950. In:Stanley FJ, Alberman ED, editors. The Epidemiology of the patients with mixed CP were predominantly spastic.
Cerebral Palsies: Clinics in Developmental Medicine.
Moreover, as the response of dystonia to IT balcofen is Philadelphia: JB Lippincott, 1984:35-45.
less prominent and predictable as that in spasticity, the Carr LJ, Cosgrove AP, Gringras P, Neville BGR, on behalf of presence of dystonic components in the subjects would the UK Botulinum Toxin and Cerebral Palsy Working Party.
Position paper on the use of botulinum toxin in cerebral palsy.
be expected to result in bias towards no effect. Any tone reduction following the screening trial would thus Peacock WJ, Arens LJ, Berman B. Cerebral palsy spasticity.
Selective posterior rhizotomy. Pediatr Neurosci 1987;13: Over the past decade, CIBI has proven to be an effective Peacock WJ, Staudt LA. Functional outcomes following treatment for severe spasticity of spinal and supraspinal selective posterior rhizotomy in children with cerebral palsy.
origins. It helps to alleviate hypertonicity and painful spasms. Nursing care and mobilization became Vaughan CL, Berman B, Peacock WJ. Cerebral palsy and much easier, with improvement in activities of daily rhizotomy. A 3-year follow-up evaluation with gait analysis. J living.7,8,10-12,24 CIBI resulted in a decrease in the average Penn RD, Kroin JS. Intrathecal baclofen alleviates spinal cord length of subsequent hospitalizations.25 Gerszten et al.26 spasticity [letter]. Lancet 1984;1:1078.
reported that among 28 patients who were planned to Penn RD. Intrathecal baclofen for spasticity of spinal origin: undergo orthopaedic operations at the time of pump seven years of experience. J Neurosurg 1992;77:236-40.
placement, 18 patients eventually did not require surgery Coffey RJ, Cahill D, Steers W, et al. Intrathecal baclofen forintractable spasticity of spinal origin: results of a long-term for their lower extremity spasticity. Becker et al27 found multicenter study. J Neurosurg 1993;78:226-32.
that CIBI also helped to alleviate autonomic dysfunctions Albright AL, Cervi A, Singletary J. Intrathecal baclofen for such as hypertension, tachycardia, hyperhidrosis, spasticity in cerebral palsy. JAMA 1991;265:1418-22.
hypersalivation and bronchial hypersecretion associated 10. Albright AL, Barron WB, Fasick MP, Polinko P, Janosky J.
Continuous intrathecal baclofen infusion for spasticity of with supraspinal spasticity. The functional intelligibility cerebral origin. JAMA 1993;270:2475-7.
of speech might also be improved.28 Recently, Middel et 11. Becker R, Alberti O, Bauer BL. Continuous intrathecal baclofen al.29 reported an one year follow-up study on 22 patients, infusion in severe spasticity after traumatic or hypoxic brain showing that CIBI resulted in improved self-reported 12. Armstrong RW, Steinbok P, Cochrane DD, Kube SD, Fife SE, Farrell K. Intrathecally administered baclofen for treatment CIBI is an expensive form of therapy. A programmable of children with spasticity of cerebral origin. J Neurosurg 1997; implantable pump device (Medtronic) costs about HK $60,000. The estimated cost of drug is about HK$1200 13. Z i e g l g a n s b e r g e r W, H o w e J R , S u t o r B . T h e neuropharmacology of baclofen. In: Muller H, Zieski J, Penn to $1800 per month, based on a daily dose of 200 µg to RD, editors. Local-Spinal Therapy of Spasticity. New York: 300 µg (10 µg vial of intrathecal baclofen costs about HK$2000). This is compared to a monthly cost of HK$100 14. Albright AL. Baclofen in the treatment of cerebral palsy. J to $200 for oral baclofen. However, it is not uncommon for children with severe spasticity to receive two to three 15. Muller H, Zierski J, Dralle D, et al. Pharmacokinetics of intrathecal baclofen. In: Muller H, Zieski J, Penn RD, editors.
anti-spasticity agents. Nance et al30 reported the Local-Spinal Therapy of Spasticity. New York: Springer- hospitalization costs related to spasticity for six patients amount to Canadian$306 in two years. As a result of 16. Kroin JS, Ali A, York M, Penn RD. The distribution of decrease in hospitalization after pump implantation, there medication along the spinal canal after chronic intrathecaladministration. Neurosurgery 1993;33:226-30.
was a net saving of about Canadian$153 in the following 17. Penn RD, Kroin JS. Long-term intrathecal baclofen infusion two years. The costs on nursing care and physiotherapy for treatment of spasticity. J Neurosurg 1987;66:181-5.
should also be taken into account for an accurate cost- 18. Asworth B. Preliminary trial of carisoprodal in multiple sclerosis. Practitioner 1964;192:540-2.
19. Meythaler JM, DeVivo MJ, Hadley M. Prospective study on In conclusion, our preliminary data suggests that the use of bolus intrathecal baclofen for spastic hypertonia intrathecal baclofen is effective in lowering the lower due to acquired brain injury. Arch Phys Med Rehabil 1996; extremity muscle tone in children with spastic CP. Children with severe spasticity who do not respond to conventional 20. Ford B, Greene P, Louis ED, et al. Use of intrathecal baclofen in the treatment of patients with dystonia. Arch Neurol 1996; therapy should be recruited for a screening trial. Those who respond to bolus intrathecal baclofen may benefit 21. Albright AL, Barry MJ, Fasick P, Barron W, Shultz B.
from CIBI via programmable infusion pumps.
Continuous intrathecal baclofen infusion for symptomatic Intrathecal Baclofen in Cerebral Palsied Children generalized dystonia. Neurosurgery 1996;38:934-9.
spastic cerebral palsy. J Neurosurg 1998;88:1009-13.
22. Muller SG, Penn RD. Physostigmine in the treatment of 27. Becker R, Sure U, Petermeyer M, Bertalanffy H. Continuous intrathecal baclofen overdose: report of three cases. J intrathecal baclofen infusion alleviates autonomic dysfunction in patients with severe supraspinal spasticity [letter]. J Neurol 23. Saltuaria L, Baumgartner H, Kefler M, et al. Failure of physostigmine in treatment of acute severe intrathecal baclofen 28. Mason C, Gilpin P, McGowan S, Rossiter D. The effect of intoxication. N Eng J Med 1990;322:1535.
intrathecal baclofen on functional intelligibility of speech. Int 24. Azouvi P, Mane M, Thiebaut JB, Denys P, Remy-Neris O, J Lang Commun Disord 1998;33(Suppl):24S-25S.
Bussel B. Intrathecal baclofen administration for control of 29. Middel B, Kuipers-Upmeijer H, Bouma J, et al. Effect of severe spinal spasticity: functional improvement and long-term intrathecal baclofen delivered by an implanted programmable follow-up. Arch Phys Med Rehabil 1996;77:35-9.
pump on health related quality of life in patients with severe 25. Ordia JI, Fischer E, Adamski E, Spatz E. Chronic intrathecal spasticity. J Neurol Neurosurg Psychiatry 1997;63:204-9.
delivery of baclofen by a programmable pump for the treatment 30. Nance P, Schryvers O, Schmidt B, Dubo H, Loverdige B, Fewer of severe spasticity. J Neurosurg 1996;85:452-7.
D. Intrathecal baclofen therapy for adults with spinal spasticity: 26. Gerszten PC, Albright AL, Johnstone GF. Intrathecal baclofen therapeutic efficacy and effect on hospital admissions. Can J infusion and subsequent orthopedic surgery in patients with

Source: http://www.hkjpaed.org/pdf/2000;5;125-131.pdf

labogen.ch

Liebe Tierfreunde, die erst kürzlich in Kraft getretene patentrechtliche Situation beim MDR1 DNA-Test nahmen wir zum Anlass für diese neue „Nachricht“ an Sie. Auf der zweiten Seite lesen Sie außerdem mehr zu den entsprechenden Arzneistoffen, zum prcd-PRA- Test und zur Qualitätssicherung bei LABOKLIN. Wir wünschen eine geruhsame Adventszeit und viel Spaß beim Lesen Ihre MDR1-Gente

marcelo.tyszler.com.br

Voting is likely the tool most strongly associated with the idea of democratic decisions,be it at national or local elections, decisions within a parliament, committees, juries oreven at company boards. In turn, the outcomes of voting processes potentially affecta large constituency. Therefore, understanding voter behavior is of major interest in avariety of fields. In this thesis we approach vote

Copyright © 2010-2014 Medical Science