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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 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 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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