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"Botulinum toxin A"

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"Botulinum toxin A"

Original Articles
The Effects of Dilution Volume of Botulinum Toxin A on the Spasticity of Children with Cerebral Palsy.
Rhim, Seung Yoon , Kim, Mi Jung , Han, Seung Hoon
J Korean Acad Rehabil Med 2008;32(3):294-299.
Objective
To evaluate the effects of the dilution volume of botulinum toxin A on spasticity of children with cerebral palsy. Method: Total 18 legs of 9 children with cerebral palsy were enrolled. 100 units of botulinum toxin were diluted with 4 cc or 2 cc of normal saline and injected to the medial and lateral heads of Gastrocnemius. Modified Ashworth scale, modified Tardieu test and range of motion (ROM) of ankle and knee were measured. Measurements were obtained before and at 1, 7, 14, 30, 60, 90, and 180 days after injection, respectively. Results: Spasticity tested by modified Ashworth scale and modified Tardieu test decreased and ROM of ankle and knee increased after 14 days since injection in both groups (p<0.05). In low dilution group, maximal ROM of ankle and knee was obtained at 30th day after injection. In high dilution group, maximal ROM of ankle and knee was achieved at 14th day after injection and maximal ROM of knee at 30th day after injection. However, there was no significant differences between high dilution group and low dilution group in different times. Conclusion: Management of spasticity with botulinum toxin in cerebral palsy was not related to dilution volume. (J Korean Acad Rehab Med 2008; 32: 294-299)
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Objective: The purpose of this study was to measure the local and distant effects of BTX-A of different dosage through the electrophysiologic study.

Method: Sixteen Sprague-Dawley rats were used and divided into four groups by the dosage of BTX-A (Botox®, Allergan Co.): 2, 4, 6, 8 U for each of the four rats. BTX-A was injected into tibialis anterior (TA) muscles. Slow rate (3 Hz) and fast rate (20 Hz) repetitive nerve stimulation test (RNST) was performed before and after BTX-A injection. The schedule of postinjection was as follows: 2 days after the injection, every seven days till 10 weeks postinjection, once a month for 4 months.

Results: In the fast rate RNST of the treated TA muscle, dose-dependent increments were seen on the 2nd day postin-

jection and thereafter dose-dependent decrements appeared and weakened over the course of time. In the slow rate RNST of the treated TA, dose-dependent decrements were observed through ten weeks postinjection in all groups. In the fast rate RNST of the untreated TA, incremental responses were produced in all groups in a dose-dependent manner. In the slow rate RNST of the untreated TA, there were no changes.

Conclusion: The BTX-A injection causes local paralysis in the treated muscles and presynaptic dysfunction of the neuromuscular junction in the distant untreated muscles in a dose- dependent manner. This study could not be differentiated between neuromuscular dysfunction, myopathy or neuropathy through these RNST studies. (J Korean Acad Rehab Med 2002; 26: 152-160)

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Neurophysiological Changes after Botulinum Toxin A Injection in Normal Adults.
Park, Gi Young , Kim, Hyun Ree , Kim, Jong Min , Lee, So Young
J Korean Acad Rehabil Med 2002;26(1):55-60.

Objecive: To evaluate the neurophysiological changes after intramuscular botulinum toxin A (BTX-A) injection in normal adults.

Method: Nine subjects were studied by electrophysiological measurements before and after the injections. BTX-A (5 IU, Botox, Allergen, USA) was injected in the extensor digitorum brevis (EDB) muscles. Thereafter, electrophysiological measurement was followed up during 6 months.

Results: The compound muscle action potential (CMAP) amplitude of injected EDB muscle decreased significantly for 8 weeks, a maximal decrement at 4 weeks after in-

jection. CMAP peak area changes over time were nearly identical to those of CMAP peak amplitudes. The first/fourth amplitude change of CMAP with 3-Hz repetitive nerve stimulation decreased significantly for 8 weeks and the amplitude following post-exercise activation increased significantly after injection. There were no significant changes in F-wave amplitude and latency.

Conclusion: Serial electrophysiological measurements after intramuscular BTX-A injection into EDB provide useful information for the neurophysiological change after injection. (J Korean Acad Rehab Med 2002; 26: 55-60)

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The Effects of Botulinum Toxin A on Upper Limb Function in Children with Cerebral Palsy.
Kim, Hyeon Sook , Hwang, Ji Hye , Lee, Peter KW , Jung, Sung Hyun , Park, Heui Dong , Cho, Eun Hee , Shim, Jong Sup , Kim, Jong Moon
J Korean Acad Rehabil Med 2001;25(4):594-600.

Objective: To evaluate the efficacy of botulinum toxin type A in the treatment of spasticitc and dystonic upper limbs in a group of cerebral palsy children

Method: Eighteen children with cerebral palsy who did not have fixed contractures in the wrist and hand were enrolled (mean age 9.0 years; range 6∼15). Measurements were obtained before and at 1 and 3 months after botulinum toxin A injections. Assessments included spasticity (modified Ashworth scale), range of motion of thumb and functional assessments including Melbourne assessment of unilateral upper limb function and Jebsen Taylor hand function test. Hand and forearm muscles were injected with 1∼3 u/kg botulinum toxin.

Results: Spasticity measured by modified Ashworth scale decreased by 1 month and diminished spasticity continued for 3 months. Range of motion of thumb increased by 1 and 3 months. In Jebsen hand function test, patients showed functional improvements in item 6 (lifting light weight object) and item 7 (lifting heavy object). Melbourne assessment of unilateral upper limb function scores improved from a mean value of 92 at baseline to a mean value of 101 at 1 month and a mean value of 105 at 3 months.

Conclusion: Botulinum toxin A would be helpful in some selected cerebral palsy patients with upper limb dysfunction. But further research including randomized controlled study is needed on the use of botulinum toxin A to improve function.

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Objective: The purpose of this study was to investigate the dose-dependent responses to botulinum toxin A (BTX-A) injection on compound muscle action potential (CMAP) amplitude and needle electromyography (EMG) in local and distant muscles.

Method: The BTX-A (Botox®, Allergan Co.) was injected to the left tibialis anterior (TA): 2, 4, 6, 8 U for each 4 Sprague-Dawley rats; 5, 10, 15, 20 U for each 2 rats. The sciatic nerve conduction and needle EMG were performed in the right and left TA immediately before BTX-A injection, on 2 days after injection, weekly for 1 to 10 weeks, and then monthly for 4 months.

Results: The range of dose-dependent maximal paralysis of the injected muscle was from 94% to 99.2% on 7 days after injection. With the lapse of time, the amplitudes in the left sciatic nerve conduction recovered, the abnormal spontaneous activities disappeared, and the power in spectral analysis of motor unit action potential increased. The range of dose-dependent reductions of the CMAP amplitude of the right TA was from 41.8% to 69.9% in the distant muscle, but there was no abnormal spontaneous activity in needle EMG study. As higher doses of BTX-A were injected, the degree of amplitude reduction became larger and the duration of amplitude reduction became longer in both local and distant TA muscles.

Conclusion: We observed the dose-dependent muscle paralysis with injection of BTX-A. The systemic effects by local injection were induced and the durations of local and systemic effects were proportional to the BTX-A dosage.

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We report the case of a 40-year-old hypoxic encephalopathy patient who suffered from dry mouth and frequent poor oral hygiene secondary to a prominent nasolabial fold and elevated upper lip, exposing the canine teeth at rest. This expression was confirmed secondary to persistent contraction of the levator labii superioris muscle with electromyography (EMG) study. We have injected 6 units of Botulinum toxin A in levator labii superioris muscle with electromyographic guidance. Elevation of upper lip at rest causing exposure of canine teeth has been nearly disappeared 3 days after the injection. We suggest that chemical weakening of the levator labii superioris muscle using Botulinum toxin A could be possibly responsible for the dramatic reduction of elevated upper lip exposing canine teeth in patients with hypoxic encephalopathy.

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Botulinum Toxin A Treatment for the Improvement of Hand Function in Spastic Hemiplegia.
Park, Gi Young
J Korean Acad Rehabil Med 1999;23(2):240-246.

Objective: The purpose of this study is to evaluate the effects of intramuscular botulinum toxin A injection for the improvement of hand function in spastic hemiplegia.

Method: We have studied 8 patients with spastic hemiplegia. Botulinum toxin A was injected into target muscles with electromyographic guidance. Before injection, muscle activity patterns were evaluated by dynamic electromyography. Follow-up assessments were performed at three months after injection.

Results: There were continuous activity patterns in all dynamic electromyography of target muscles. Dynamic electromyography of antagonist muscles in five patients showed normal phasic activity pattern but it showed absent pattern in other three patients. Mean modified Ashworth scale decreased significantly after injection. There were an improvement in functional classification and a significant increase of mean scores of unilateral hand skills after injection in patients with normal phasic pattern of antagonist muscles.

Conclusion: Botulinum toxin A can improve the impaired hand movement and function in spastic hemiplegia by reducing spasticity and contracture of the target muscles in cases of normal phasic activity in antagonist muscles and continuous activity in target muscles.

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Measuring Compound Muscle Action Potentials after Botulinum Toxin A Injection for the Quantification of Effects.
Seo, Jeong Hwan , Kim, Sang Su , Kim, Nam Kyun , Lee, Ju Hong
J Korean Acad Rehabil Med 1998;22(6):1225-1231.

Objective: To quantify the effect of botulinum toxin A injection, by the compound muscle action potential (CMAP) measure from the gastrocnemius muscles (GCM) and to compare them with the clinical data.

Methods: Seventeen legs of 10 cerebral palsy (CP) children were studied with botulinum toxin A injection on the motor points of their GCM. Each GCM was injected up to 6 units of the botulium toxin A per kilogram of the body weight. The CMAP were measured at the motor points of GCM with the surface electrodes on the post-injection day 1, day 3, day 7, 2 weeks and at 1 month then monthly thereafter for 6 months. Physician rating scale (PRS) and the angle of passive ankle dorsiflexion were evaluated at the same time.

Results: The amplitude and the area of the CMAP decreased from post-injection day 1 to 3 months. The most pronounced decrement was seen at 2 weeks post-injection (p<0.05). The most pronounced increase of the dorsiflexion angle and PRS were seen at 1 and 2 months post-injection, respectively (p<0.05).

Conclusion: The compound muscle action potential measure can be used for the neurophysiological quantification of the effect of botulinum toxin A, especially for the superficial muscles of extremities.

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Treatment Effects of Botulinum Toxin A in Cerebral Palsy with Foot Deformities.
Park, Gi Young , Jang, Sung Koo
J Korean Acad Rehabil Med 1998;22(1):21-26.

The purpose of this study is to evaluate the effectiveness of intramuscular botulinum toxin A injection in cerebral palsy with foot deformities using roentgenogram. We have studied 26 children with cerebral palsy(age 3 to 13 years old). They were twenty spastic diplegias, three hemiplegias and three mixed types(spasticity and athetosis). The botulinum toxin A was injected into gastrocnemius or peroneous muscles with an electromyographic guidance. Before injections, passive joint angles of the ankle were assessed by the goniometric measurements. A plantar-flexion angle of talus, dorsiflexion angle of calcaneous, and talar-calcaneal divergence angle were measured using the lateral and anterior-posterior roentgenograms of the foot with weight- bearing for the assessment of equinovalgus of ankle. Follow-up assessments were performed at 1 and 3 months after the injection. At 1 month after the injection into gastrocnemius muscle, there was an increased range of passive ankle joint motion, decreased plantar-flexion angle of talus, and increased dorsiflexion angle of calcaneous. These changes were still significant at 3 months after the injection. After the injection into peroneous muscle, the talar-calcaneal divergence angle was significantly decreased. This study provides the evidence that the treatment with botulinum toxin A improves the ankle joint motion in cerebral palsy with feet deformities by reducing hypertonicity, spasticity and dynamic contracture. In addition, the lateral and anterior- posterior roentgenograms of the foot with weight bearing seems to be the simple and objective methods to evaluate the effectiveness of intramuscular botulinum toxin A injection in cerebral palsy with foot deformities.

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Botulinum toxin develops muscular paralysis through the inhibition of acetylcholine release from presynaptic membrane in neuromuscular junction. It has been used clinically to treat strabismus, blepharospasm and spasmodic dysphonia. Recently it was introduced for the treatment of limb spasticity as well. Serial compound muscle action potential(CMAP) amplitudes were measured and repetitive nerve stimulation test(RNST) was performed with 2Hz and 30Hz on the rat gastrocnemius muscle to observe the effect of muscle paralysis. Also, Periodic acid Schiff (PAS) staining sections of the muscle for glycogen was studied to quantify the degree of muscular paralysis.

Thirty Sprague-Dawley rats, 10 for control and 20 for experimental group were studied for 12 weeks. Normal saline 0.025 ml and 0.125 ml was injected into gastrocnemius muscle in cotrol group 1 and 2, respectively. Botulinum toxin type A(Botox) was injected 5.0U/0.025 ml in experimental group 1, 2.5U/0.025 ml in group 2, 2.5U/0.125 ml in group 3, and 0.5U/0.025 ml in group 4. The amplitudes of CMAP declined markedly by 81.1% to 96.5% of basal amplitudes on the first week after Botox injection, but slightly recovered on 12th week by 20.8% to 42.2% with greater recovery in lower dose group. RNST with 2Hz produced no remarkable 1 : 5 amplitude change in experimental group. RNST with 30Hz produced marked increment in 1 : 5 amplitude up to 24.4%. PAS staining for muscle sections showed residual glycogen after tetanic stimulation due to neuromuscular block by Botox.

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Effects of Botulinum Toxin A Treatment in Cerebral Palsy.
Park, Gi Young
J Korean Acad Rehabil Med 1997;21(2):390-398.

The purpose of this study is to evaluate the effects of intramuscular botulinum toxin A injection in cerebral palsy. We studied 25 children with cerebral palsy(age 3 to 20 years old). Among them, 14 children were spastic diplegia; 5 were athetoid quadriplegia; 3 were spastic hemiplegia; and 3 were mixed type(spasticity and athetosis). Botulinum toxin A was injected into the target muscle groups with electromyographic guidance. The dose was calculated in unit/body weight basis. Followup assessments were performed at 1 and 3 months after injection. After injection, 11 out of 16 children(68.8%) had a one-level improvement in ambulatory status. The passive range of joint motion increased significantly after injection. Modified Ashworth scale decreased significantly after injection. In 23 out of 25 children, there were a significant increase of the mean GMFM(gross motor function measure) total score and mean GMFM scores for all dimensions at three months after injection. There were the distant effects after injection in spastic diplegia. In conclusion, botulinum toxin A tretment would improve the motor function and ambulatory status in cerebral palsy by reducing hypertonicity, spasticity, dynamic contracture and athetoid movement.

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