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Prolonged intubation is known to bring on postextubation dysphagia (PED) in some patients. We have noted that there were some studies to investigate specific type and pattern of PED, which showed large variety of different swallowing abnormalities as mechanisms of PED that are multifactorial. There are several options of treatment in accordance with the management of these abnormalities. A botulinum toxin (BoT) injection into the upper esophageal sphincter (UES) can improve swallowing functions for patients with this disorder, by working to help the muscle relax. In this case, the conventional treatment was not effective in patients with PED, whereas the BoT injection made a great improvement for these patients. This study suggests that the UES pathology could be the main cause of PED.
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Neuropathic pain is usually managed pharmacologically, rather than with botulinum toxin type A (BTX-A). However, medications commonly fail to relieve pain effectively or have intolerable side effects. We present the case of a 62-year-old man diagnosed with an intracranial chondrosarcoma, which was removed surgically and treated with radiation therapy. He suffered from neuropathic pain despite combined pharmacological therapy with gabapentin, amitriptyline, tramadol, diazepam, and duloxetine because of adverse effects. BTX-A (100 units) was injected subcutaneously in the most painful area in the posterior left thigh. Immediately after the injection, his pain decreased significantly from 6/10 to 2/10 on a visual analogue scale. Pain relief lasted for 12 weeks. This case report describes intractable neuropathic pain caused by a brain tumor that was treated with subcutaneous BTX-A, which is a useful addition for the management of neuropathic pain related to a brain tumor.
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Ocular Neuropathic Pain: An Overview Focusing on Ocular Surface Pains
To compare the accuracy of ultrasound (US)-guided and non-US-guided botulinum toxin (BTX) injection into the salivary glands (parotid and submandibular glands) of cadavers.
Two rehabilitation physician injected dye into three sites in the salivary glands (two sites in the parotid gland and one site in the submandibular gland) on one side of each cadaver (one was injected on the right side, while the other was injected on the left side), using either a non-US-guided injection procedure based on superficial landmarks or a US-guided procedure. Orange dye was used for the US-guided procedure, and green dye was used for the blind procedure. Two physicians uninvolved with the injection procedures and who were blinded to the method of injection dissected the cadavers to identify whether the dye was accurately injected into each target site.
The accuracies of the blind and US-guided injections into the parotid gland were 79.17% and 95.83%, respectively. In the submandibular gland, the accuracies of the blind and US-guided injections were 50.00% and 91.67%, respectively. The difference in accuracy between the two procedures was statistically significant only in the submandibular gland (p=0.025). There were no significant differences in the accuracy of US-guided and non-US-guided injections between the two physicians for the two sites in the parotid gland (p=0.278 and p=0.146, respectively).
US-guided BTX injection into the submandibular gland offers significantly greater accuracy over blind injection. For the treatment of drooling by injecting BTX into the submandibular gland, clinicians should consider using US guidance for improved accuracy.
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To evaluate the beneficial effect of botulinum toxin A (Botox) injection into the subscapularis muscle on intractable hemiplegic shoulder pain.
Six stroke patients with intractable hemiplegic shoulder pain were included. Botulinum toxin A was injected into the subscapularis muscle. Intractable hemiplegic shoulder pain was evaluated using an 11-point numerical rating scale. Pain-free range of motion was assessed for shoulder abduction and external rotation. The spasticity of the shoulder internal rotator was measured using the modified Ashworth scale. Assessments were carried out at baseline and at 1, 2, 4, and, if possible, 8 weeks.
Intractable hemiplegic shoulder pain was improved (p=0.004) after botulinum toxin injection into the subscapularis muscle. Restricted shoulder abduction (p=0.003), external rotation (p=0.005), and spasticity of the shoulder internal rotator (p=0.005) were also improved. Improved hemiplegic shoulder pain was correlated with improved shoulder abduction (r=–1.0, p<0.001), external rotation (r=–1.0, p<0.001), and spasticity of the internal rotator (r=1.0, p<0.001).
Botulinum toxin A injection into the subscapularis muscle appears to be valuable in the management of intractable hemiplegic shoulder pain.
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Dystonia has a wide range of causes, but treatment of dystonia is limited to minimizing the symptoms as there is yet no successful treatment for its cause. One of the optimal treatment methods for dystonia is chemodenervation using botulinum toxin type A (BTX-A), alcohol injection, etc., but its success depends on how precisely the dystonic muscle is selected. Here, we reported a successful experience in a 49-year-old post-stroke female patient who showed paroxysmal repetitive contractions involving the right leg, which may be of dystonic nature. BTX-A and alcohol were injected into the muscles which were identified by dynamic polyelectromyography. After injection, the dystonic muscle spasm, cramping pain, and the range of motion of the affected lower limb improved markedly, and she was able to walk independently indoors. In such a case, dynamic polyelectromyography may be a useful method for selecting the dominant dystonic muscles.
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To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection.
As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications.
International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%–30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome.
In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.
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Paroxysmal autonomic instability with dystonia (PAID) is a rare complication of brain injury. Symptoms of PAID include diaphoresis, hyperthermia, hypertension, tachycardia, and tachypnea accompanied by hypertonic movement. Herein, we present the case of a 44-year-old female patient, who was diagnosed with paraneoplastic limbic encephalopathy caused by thyroid papillary cancer. The patient exhibited all the symptoms of PAID. On the basis that the symptoms were unresponsive to antispastic medication and her liver function test was elevated, we performed alcohol neurolysis of the musculocutaneous nerve followed by botulinum toxin type A (BNT-A) injection into the biceps brachii and brachialis. Unstable vital signs and hypertonia were relieved after chemodenervation. Accordingly, alcohol neurolysis and BNT-A injection are proposed as a treatment option for intractable PAID.
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Spontaneous opening and closing of both eyes usually occurs in the normal awake state, unless a deliberate and voluntary attempt is made to open only one eye. We present a rare case of a male patient who was unable to open both eyes simultaneously after bilateral posterior cerebral artery infarction. He was able to close both eyes voluntarily. However, he was unable to keep both eyes open simultaneously and either the right or left eye remained closed. Upon a verbal command to open both eyes, the opened eye closed and the contralateral eye opened. When the closed eye was forced open, the opened eye closed. We thus presented a case of right-left dissociation of voluntary eyelid opening following bilateral posterior cerebral artery infarction, which was treated with botulinum toxin type A injection. Differential diagnosis to other movement disorders of the eyelids was discussed.
To determine the optimal injection site in the flexor digitorum longus (FDL) muscle for effective botulinum toxin injection.
Fourteen specimens from eight adult Korean cadavers were used in this study. The most proximal medial point of the tibia plateau was defined as the proximal reference point; the most distal tip of the medial malleolus was defined as the distal reference point. The distance of a line connecting the proximal and distal reference points was defined as the reference length. The X-coordinate was the distance from the proximal reference point to the intramuscular motor endpoint (IME), or motor entry point (MEP) on the reference line, and the Y-coordinate was the distance from the nearest point from MEP on the medial border of the tibia to the MEP. IME and MEP distances from the proximal reference point were evaluated using the raw value and the X-coordinate to reference length ratio was determined as a percentage.
The majority of IMEs were located within 30%-60% of the reference length from the proximal reference point. The majority of the MEPs were located within 40%-60% of the reference length from the proximal reference point.
We recommend the anatomical site for a botulinum toxin injection in the FDL to be within a region 30%-60% of the reference length from the proximal reference point.
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To evaluate the therapeutic effect of botulinum toxin A (BTX-A) injection on spastic gastrocnemius (GCM) and tibialis posterior muscles (TPo) by using the foot pressure measurement system (FPMS).
Eighteen ambulatory CP patients were recruited in this study. BTX-A was injected into the GCM at a dose of 6-12 units/kg and TPo at a dose of 4-9 units/kg according to the severity of equinus and varus deformity. Foot contact pattern, pressure time integral (PTI), coronal index using the FPMS and Modified Ashworth Scale (MAS), and visual inspection of gait pattern were used for evaluation of the therapeutic effect of BTX-A injection. Clinical and FPMS data were statistically analyzed according to the muscle group.
A significant decrease in the MAS score of the GCM and TPo was observed, and spastic equinovarus pattern during gait showed improvement after injection. The GCM+TPo injection group showed a significant decrease in forefoot, lateral forefoot pad, and lateral column PTI, and a significant increase in hindfoot PTI and coronal index. In the GCM only injection group, forefoot PTI and lateral column PTI were significantly decreased and hindfoot PTI was significantly increased. The TPo only injection group showed a significant decrease in lateral column PTI and a significant increase in the coronal index. Change in PTI in the hindfoot showed a significant correlation with the change in MAS score of the GCM. Change in PTI of the lateral column and coronal index showed a significant correlation with the change in MAS score of the TPo.
The FPMS demonstrated the quantitative therapeutic effect of BTX-A on abnormal pressure distribution in equinovarus foot in detail. The FPMS can be a useful additional tool for evaluation of the effect of BTX-A injection.
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Holmes' tremor is a low-frequency rest and intentional tremor secondary to various insults, including cerebral ischemia, hemorrhage, trauma, or neoplasm. Pharmacologic treatment is usually unsuccessful, and some cases require surgical intervention. We report a rare case of Holmes' tremor secondary to left pontine hemorrhage in a 29-year-old Asian male patient who developed 1.6-Hz postural and rest tremor of the right hand. He responded markedly to ultrasonography-guided botulinum toxin type A injection. To our knowledge, this is the first report of Homes' tremor treated with ultrasonography-guided botulinum toxin type A injection with favorable results.
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To evaluate whether age influences a change in the spasticity of the ankle plantar flexor after botulinum toxin type A (BTA) injection in children with spastic cerebral palsy (CP).
Sixteen children with spastic CP were enrolled in the study. Seven children (group 1) were under 5 years of age, and nine (group 2) were over 5 years of age. They all received BTA injection in the gastrocnemius muscle (GCM) under ultrasound guidance. Passive range of motion (PROM) of ankle dorsiflexion, Modified Ashworth Scale (MAS) of the ankle plantar flexor, Gross Motor Function Measure (GMFM) and median red pixel intensity (RPI) of the medial GCM on real-time sonoelastography were measured at baseline (pre-injection) and 1-, 3-, and 6-month post-injection.
In both groups, the mean PROM, MAS, and RPI were significantly improved after injection until 6-month post-injection. The change of PROM of ankle dorsiflexion in group 1 was significantly greater than that in group 2, until 6-month post-injection. The change in the MAS and GMFM between baseline and 6-month post-injection in group 1 was greater than that in group 2. The changes in the median RPI between baseline and 3- and 6-month post-injections were greater in group 1 than in group 2.
Our pilot study demonstrated the different changes in spasticity of the ankle plantar flexor after BTA injection based on age. Therefore, age may be considered when establishing a treatment plan using BTA injection for children with spastic CP.
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Birth brachial plexus palsy (BBPP) is usually caused by plexus traction during difficult delivery. Although the possibility of complete recovery is relatively high, 5% to 25% of BBPP cases result in prolonged and persistent disability. In particular, muscle imbalance and co-contraction around the shoulder and elbow cause abnormal motor performance, osseous deformities, and joint contracture. Physical and occupational therapies have most commonly been used, but these conventional therapeutic strategies have often been inadequate, in managing the residual muscle imbalance and muscle co-contraction. Therefore, we attempted to improve the functional movements, by using botulinum toxin type A, to reduce the abnormal co-contraction of the antagonist muscles.
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To investigate the effect of botulinum toxin type A (BTA) injection into the salivary gland and to evaluate the changes of drooling in varied postures in tetraplegic patients with brain injury.
Eight tetraplegic patients with brain injury were enrolled. BTA was injected into each parotid and submandibular gland of both sides under ultrasonographic guidance. Drooling was measured by a questionnaire-based scoring system for drooling severity and frequency, and the sialorrhea was measured by a modified Schirmer test for the patients before the injection, 3 weeks and 3 months after the injection. Drooling was evaluated in each posture, such as supine, sitting, and tilt table standing, and during involuntary mastication, before and after the injection.
The severity and frequency of drooling and the modified Schirmer test improved significantly at 3 weeks and 3 months after the injection (p<0.05). Drooling was more severe and frequent in tilt table standing than in the sitting position and in sitting versus supine position (p<0.05). The severity of drooling was significantly increased in the patients with involuntary mastication (p<0.05).
Salivary gland injection of BTA in patients with tetraplegia resulting from brain injury who had drooling and sialorrhea could improve the symptoms for 3 months without complications. The severity and frequency of drooling were dependent on posture and involuntary mastication. Proper posture and involuntary mastication of the patients should be taken into account in planning drooling treatment.
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To evaluate the short-term clinical effects of the intra-articular injection of botulinum toxin type A (BoNT-A) for the treatment of adhesive capsulitis.
A prospective, controlled trial compared the effects of intra-articular BoNT-A (Dysport; 200 IU, n=15) with the steroid triamcinolone acetate (TA; 20 mg, n=13) in patients suffering from adhesive capsulitis of the shoulder. All patients were evaluated using a Numeric Rating Scale (NRS) of the pain intensity and a measurement of the range of motion (ROM) at baseline (before treatment) and at 2, 4, and 8 weeks post-treatment.
The NRS at 2 weeks (BoNT-A vs. TA; 5.0 vs. 5.2), 4 weeks (4.1 vs. 4.9) and 8 weeks (3.8 vs. 4.6) of both treatment groups were significantly lower than that measured at baseline (7.4 vs. 7.6). The ROM of patients' shoulders increased significantly from baseline in both treatment groups. There was no significant difference in the NRS of pain intensity or the ROM between the two groups. Reduction in the pain intensity score was maintained for 8 weeks post-injection in both groups. There were no significant adverse events in either treatment group.
The results suggest that there are no significant short-term differences between the intra-articular injections of BoNT-A and TA. Although BoNT-A has a high cost, it may be used as a safe alternative of TA to avoid the steroid-induced side effects or as a second-line agent, for patients who have failed to respond to the current treatments.
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To observe the changes in protein expression induced by botulinum toxin A (BoNT-A) injection and to characterize the molecular and cellular action of mechanisms of BoNT-A injection on skeletal muscles using proteomic elements as biomarkers.
BoNT-A was injected into left gastrocnemius muscles of 12 Sprague-Dawley rats (2 months of age) at a dosage of 5 units/kg body weight. For the controls same volume of normal saline was injected to right gastrocnemius muscle of each rat. Muscle samples were obtained at 4 time points (3 rats per time point): 3, 7, 14, and 56 day post-injection. To reveal the alterations in muscle protein, we performed 2-dimensional electrophoresis (2DE) and compared Botox group and normal saline group at each time point. Altered protein spots in 2DE were identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometer (MALDI-TOF MS) proteomics analysis.
Compared with normal saline group, 46 protein spots showed changed protein expression. Twelve protein spots demonstrated increased volume and 34 protein spots demonstrated decreased volume. Among spots of decreased volume, 17 spots showed statistically significant differences. Thirty-eight identified proteins were associated with alterations in energy metabolism, muscle contractile function, transcription, translation, cell proliferation, and cellular stress response.
BoNT-A gives influences on muscle contractile function and energy metabolism directly or indirectly besides neurotoxic effects. Proteomic expression provides better understanding about the effect of BoNT-A on skeletal muscle.
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To investigate Botulinum toxin type B (BNT-B) injection's effect and duration depending on dose for patients with brain lesion.
Twenty one patients with brain lesion and severe drooling were included and divided into three groups. All patients received conventional dysphagia therapy. Group A patients (n=7) received an injection of 1,500 units and group B patients (n=7) received an injection of 2,500 units of BNT-B in submandibular gland under ultrasound guidance. Group C patients (n=7) received conventional dysphagia therapy. Saliva secretion was assessed quantitatively at baseline and at weeks 1, 2, 4, 8, and 12. The severity and frequency of drooling was assessed using the Drooling Quotient (DQ) by patients and/or caregivers.
Group A and B reported a distinct improvement of the symptoms within 2 weeks after BNT-B injection. Compared to the baseline, the mean amount of saliva decreased significantly throughout the study. However, there was no meaningful difference between the two groups. The greatest reductions were achieved at 2 weeks and lasted up to 8 weeks after BNT-B injection. Group C did not show any differences.
Local injection of 1,500 units of BNT-B into salivary glands under ultrasonic guidance proved to be a safe and effective dose for drooling in patient with brain lesion, as did 2,500 units.
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To evaluate the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the management of cervical dystonia (CD) with botulinum toxin type A (BoNT-A) injection.
Thirty two subjects with CD were included. A BoNT-A injection was provided either by clinically targeting method (group 1) or by 18F-FDG PET/CT-assisted, clinically targeting method (group 2). In group 2, selection of target muscles and dosage of BoNT-A were determined according to the increased 18F-FDG uptake, in addition to physical examination and functional anatomy. The outcomes of BoNT-A injection was compared between the two groups, in terms of the number of subjects who had reinjection before and after 6 months, the number of reinjections, the interval of reinjections, the duration to the minimal Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the number of adverse events, the reduction rate of TWSTRS at 1-3 months and 3-6 months after injection, and the probability of reinjection-free living.
The number of subjects who had reinjection within 6 months was significantly lower in group 2 than in group 1 (10 in group 1 vs. 3 in group 2). The reduction rate of TWSTRS after 3-6 months (37.8±15.7% of group 1 vs. 63.3±28.0% of group 2) and the probability of reinjection-free living were significantly higher in group 2 than in group 1.
These findings suggest that 18F-FDG PET/CT study could be useful in management of CD in terms of the identification of dystonic muscles if there is an increase in the 18F-FDG uptake in the cervical muscle of the images.
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To determine the 9 month period effect of botulinum toxin A (BoNT-A) injection into the salivary gland in children with neurologic disorders and sialorrhea by qualified parent/caregiver-administered questionnaires.
A total of 17 patients (age 7.6±4.24 years) were enrolled in this study. The degree of sialorrhea was assessed at the baseline, 2 weeks, 1, 2, 4, 6 and 9 months after injection. The Drooling Count (DC) was assessed as an objective measurement. The Drooling Frequency and Severity Scale (DFS) and the Teacher Drooling Scale (TDS) were evaluated as a subjective measurement. BoNT-A (0.5 unit/kg) was injected into each submandibular and parotid gland under ultrasonography-guidance.
DC, DFS and TDS showed significant improvement at 2 weeks, 1, 2, 4, 6, and 9 months follow-up (p<0.05). Twelve of 17 cases (70.5%) showed more than 50% reduction in DC from the baseline value.
Ultrasonography-guided BoNT-A injection into the submandibular and parotid gland was a safe and effective method to treat sialorrhea in children with neurologic disorders.
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To localize the site of motor points within human biceps brachii muscles through surface mapping using electrophysiological method.
We recorded the compound muscle action potentials of each lattice of the biceps brachii in 40 healthy subjects. Standardized reference lines were made as the following: 1) a horizontal reference line (elbow crease) and 2) a vertical reference line connecting coracoid process and mid-point of the horizontal reference line. The Compound muscle action potentials were mapped in reference to the standardized reference lines. The locations of motor points were mapped to the skin surface, in the ratio to the length of the vertical and the half of the horizontal reference lines.
The motor point of the short head of biceps was located at 69.0±4.9% distal and 19.1±9.5% medial to the mid-point of horizontal reference line. The location of the motor point of the long head of the biceps was 67.3±4.3% distal and 21.4±8.7% lateral. The motor point of the short head of the biceps was located more medially and distally in the male subjects compared to that in the female (p<0.05).
This study showed electrophysiological motor points of the biceps brachii muscles through surface mapping. This data might improve the clinical efficacy and the feasibility of motor point targeting, when injecting botulinum neurotoxin in biceps brachii.
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A 62-year-old female patient diagnosed with left brain stem stroke 2 months ago was admitted to our clinic for rehabilitation. She had no generalized spasticity on both extremities, but could open her mouth only approximately 2 mm between her upper and lower teeth due to severe trismus. On needle electromyography, the left masseter muscle showed paradoxically increased muscle activity during mouth opening. We injected 50 units of type A botulinum toxin (Botox®) into the left masseter muscle, and 20 units into the left temporalis muscle with guidance of ultrasonography. The interincisal distance increased to 8 mm on the 3rd day after injection, and 9 mm on the 4th day. One month later, the interincisal distance increased to 14 mm. The increased interincisal distance was maintained for 13 months after injection, and the quality of hygienic care and compliance of oral stimulation therapy also improved.
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To investigate the effect of botulinum toxin type A (BTXA) on drooling and the morphologic change of the salivary gland in patients with cerebral palsy.
Eight cerebral palsy patients suffering from severe drooling participated in this study. BTXA was injected into both submandibular and parotid glands under intravenous sedation and with ultrasound guidance (1 unit/gland/kg: maximum 100 units) in an outpatient or inpatient procedure. The severity of drooling was measured before injection and 3 weeks after injection using the Teacher Drooling Scale, the Drooling Score-severity, frequency and the Visual Analog Scale. To investigate the morphologic change of the salivary glands, the size of salivary glands were measured before injection and 3 weeks after injection using computed tomography of the neck. The measurement values were analyzed by Wilcoxon signed rank test.
Statistically significant improvements were shown in all three parameters for assessing the severity of drooling after BTXA injections (p<0.05). Size of the salivary glands were significantly decreased at 3 weeks after BTXA injection (p<0.05).
Salivary gland injection with BTXA could be a useful treatment method to reduce drooling in patients with cerebral palsy and decreased size of salivary glands may partially explain the mechanism.
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To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot.
Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed weekly for 3 times. Spasticity of the ankle joint was evaluated using the modified Ashworth scale (MAS), and the modified Tardieu scale (MTS). Gait pattern was measured using the physician's rating scale (PRS).
The degree of ankle dorsiflexion and the MAS improved significantly until 12 weeks following the BTX-A injection in the serial casting group (p<0.001), while the BTX-A injection-only group improved until 6 weeks following injection (p<0.05). The combined group showed a significantly greater increase in the degree of dorsiflexion compared to the BTX-A injection-only group at post-injection weeks 6 and 12 (p<0.05). Three children (11.5%) suffered from foot ulcers as a complication caused by the serial casting.
Our study demonstrated that the effect of BTX-A injection with serial casting was superior and lasted longer than the effect of BTX-A injection only in patients with spastic equinus foot. We therefore recommend BTX-A injection with serial casting for the treatment of equinus foot. However, physicians must also consider the possible complications associated with serial casting.
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