Clinical Efficacy of Botulinum Toxin Type A Reconstituted and Refrigerated 1 Week before Its Application in External Canthus Dynamic Lines

BACKGROUND Allergan Inc. recommends that its botulinum toxin type A (BTX-A; BOTOX) must be refrigerated and applied within 4 hours after its reconstitution to avoid losing its biologic effectiveness.
OBJECTIVE The objective was to compare clinical efficacy in treating external canthus dynamic lines with reconstituted and refrigerated toxin (BTX-A) 1 week before its application versus fresh toxin (BTX-A).
METHODS This study was a double-blind, randomized, clinical trial. A total of 30 patients aged 30 to 60 years having a minimum of one and maximum of six external canthus dynamic lines were treated in one canthus with 15 U of BTX-A reconstituted and refrigerated at 4°C 1 week before being applied and in the other with 15 U of fresh BTX-A. Patients were followed-up on Day 10 and Weeks 6, 12, and 18; assessment included a neuroconduction study of the facial nerve and the investigators' photographic evaluation of the number of external canthus dynamic lines at maximum smile.
RESULTS Outcome measurement did not show statistically significant differences between both groups.
CONCLUSION BTX-A, reconstituted and refrigerated 1 week before its application, has similar clinical efficacy in treating external canthus dynamic lines as does fresh BTX-A.     

Focal Hyperhidrosis of the Anal Fold: Successful Treatment with Botulinum Toxin A

BACKGROUND: Treatment of focal hyperhidrosis with botulinum toxin A (BTX-A) is known to be effective in the axillary, palmar, and plantar region. No studies evaluating the treatment of hyperhidrosis in the anal fold with BTX-A are available, however. OBJECTIVE: The objective was to evaluate whether or not injections with BTX-A are an effective therapy option for the treatment of focal hyperhidrosis of the anal fold. MATERIAL AND METHODS: Eleven male patients (median age, 28.3 years) with focal hyperhidrosis of the anal fold as assessed by modified iodine-starch test were enrolled. Each patient received intradermal injections with 38 U on average (30-54 U) of BTX-A (BOTOX, Allergan Inc.). Changes in sweat rates were documented by comparing the size of hyperhidrotic area in square centimeters before and 4 weeks after injection. RESULTS: The mean reduction of hyperhidrotic area was 29.9 cm(2) (range, 27-43 cm(2)), corresponding to a reduction of 78.5%. Apart from painful injections, no side effects were observed. CONCLUSION: BTX-A is an effective therapy for patients with focal hyperhidrosis of the anal fold.     

Metallic Taste: An Unusual Reaction to Botulinum Toxin A

BACKGROUND: Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides. OBJECTIVES: A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A). RESULTS: The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes. CONCLUSION: Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear. Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism. Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case.     

Dilution Volume of Botulinum Toxin Type A for the Treatment of Glabellar Rhytides: Does It Matter?

BACKGROUND Because well-controlled studies examining the efficacy and safety of various dilutions of botulinum toxin type A (BTX-A) have not been performed, dilutions used in clinical practice are chosen at the discretion of the clinician.
OBJECTIVES The objectives were to determine the most effective BTX-A dilution for the glabellar region, the relationship between dilution and duration of effect, and the side effect profile of each dilution in women with glabellar rhytides.
METHODS Eighty women with moderate-to-severe wrinkles at maximum frown were randomized to one of four dilution groups in a 48-week, single-center, double-blind, parallel-group study. Subjects received 30 U BTX-A (BOTOX, Allergan, Inc.) injected into the glabellar region at dilutions of 100, 33.3, 20, or 10 U/mL. Outcome measures included trained-observer and subject assessment of wrinkle severity at repose and at maximum muscle contraction using the Facial Wrinkle Scale (FWS) and adverse events.
RESULTS All dilutions of BTX-A effectively improved glabellar rhytides as assessed by both trained observers and subjects using the FWS. No significant differences on FWS scores were seen among the dilution groups by trained observers at any time point. Although a difference among groups was seen in subject-assessed responder rates, there was no obvious relationship between dilution and response. BTX-A treatment was well tolerated, and there were no significant differences between the four dilution groups in the number of subjects reporting adverse effects.
CONCLUSION In this study, the dilution of BTX-A was not critical to the success of treatment.     

Asymmetrical Smiles Corrected by Botulinum Toxin Serotype A

OBJECTIVE The objective was to identify the cause of an asymmetrical smile and to ascertain whether or not it would be correctable by injections of Botulinum toxin A (BTX-A).
METHODS Five patients with asymmetrical smiles were identified and found to lower one side of their lower lip in an exaggerated fashion when smiling or laughing. After close observation, it was determined that the ipsilateral depressor labii inferioris of the lower lip was hyperkinetic and retracted that side of the lips lower than its contralateral side when smiling or laughing. Injections of low-volume and low-dose BTX-A (BOTOX, Allergan, Inc.) were placed into the depressor labii inferioris on the side where the lower lip retracted the lowest.
RESULTS All of the five patients with asymmetrical smiles presented with unilateral hyperkinetic depressor labii inferioris and responded to injections of BOTOX. Their lower lips became level and their smiles were symmetrical within 1 week of the BOTOX treatments. Their lip symmetry lasted for at least 6 months after their initial treatment. With each additional treatment, the duration of BOTOX lasted even longer, averaging approximately 7 months.
CONCLUSION BOTOX is an effective, safe, and long-lasting treatment for lower lip asymmetries caused by a hyperkinetic depressor labii inferioris.     

Botulinum neurotoxin type A in urology: Antibodies as a cause of therapy failure

Objectives:   Botulinum toxin type A (BoNT/A) proved very effective in therapy for hyperactive detrusor or sphincter dysfunction of neurogenic and non-neurogenic origin. However, therapy may fail. In a search for possible reasons, we investigated the presence of BoNT/A antibodies (BoNT/A-AB) in patients who were treated more than once and correlated the presence of antibodies with clinical findings.
Methods:   In 25 patients (aged 11–75 years; average, 48.3 years) who had experienced at least one previous BoNT/A detrusor and/or sphincter injection, BoNT/A-AB was detected with the mouse diaphragm assay before and within 3 months after the current injection. Clinically, subjective and objective outcomes of this injection session were determined on an efficacy scale.
Results:   In eight patients, BoNT/A-AB was detected; titers were clearly positive in four patients and were borderline in four patients. The subjective and objective outcomes indicated complete therapy failure in three of four patients who were positive for BoNT/A-AB. In two patients, BoNT/A-AB developed after just one injection session.
Conclusions:   Botulinum toxin type A antibodies can develop after injection of BoNT/A for urologic disorders and the antibodies can lead to therapy failure. In patients with clinically complete therapy failure in whom no obvious other causes can be determined (such as a progressive disease in a patient with multiple sclerosis), screening for BoNT/A-AB should be carried out.     

Patient-Reported Outcomes with Botulinum Toxin Type A Treatment of Glabellar Rhytids: A Double-Blind, Randomized, Placebo-Controlled Study

BACKGROUND Global patient-reported outcomes do not evaluate specific aspects of treatment that are important to patients.
OBJECTIVE The objective was to evaluate self-perception of age and specific outcomes that are important to patients receiving botulinum toxin type A or placebo for moderate to severe glabellar lines (using the Facial Line Outcomes Questionnaire to assess how much facial lines bother them, make them look older, detract from their facial appearance, prevent a smooth facial appearance, and make them look tired, stressed, or angry).
METHODS AND MATERIALS In the double-blind phase of this 12-week study, 70 patients were randomly assigned to treatment with 20 U botulinum toxin type A (BOTOX Cosmetic) or placebo. At Week 4, those still with moderate or severe glabellar lines were offered open-label 20 U botulinum toxin type A.
RESULTS Median glabellar line severity was significantly lower after botulinum toxin treatment than after placebo. Compared with placebo, botulinum toxin also resulted in significantly superior patient assessments and a greater proportion of patients considering they looked younger than their current age.
CONCLUSIONS Botulinum toxin type A can achieve specific goals of treatment that are important to patients and help them feel that they look younger than their current age.     

New indications for botulinum toxin type A in treating facial wrinkles of the mouth and neck

Botulinum toxin type A (BTX-A) is commonly used to smooth hyperkinetic lines in the periocular and forehead areas of the upper face, but has been used less frequently for indications in the lower face and neck. This study was designed to determine whether botulinum toxin treatment of the mouth and neck areas is as clinically successful as treatment of the upper face. This was a retrospective study of patients who were treated with botulinum toxin type A (BOTOX, Allergan, Inc) to soften hyperkinetic facial wrinkles. Of 100 patients randomly selected from a single clinical practice, 91 met the inclusion criteria and were divided into two groups for analysis: the 56 patients in Group 1 did not receive treatment in the mouth and neck areas, while the 35 patients in Group 2 were treated at least once in the mouth and neck areas. Patients were surveyed for periods ranging from seven to 49 months. Most patients in each group had a single BTX-A procedure during this period. Both groups of patients had comparable improvement of wrinkles both at the evaluation immediately after the neuromuscular blockade and during followup. In comparison with patients whose treatment was confined to the upper face, patients who received global treatment with BTX-A, including BTX-A injections in the mouth and neck areas, were injected in more sites per procedure and had more procedures in combination with other therapies. Patient satisfaction with botulinum toxin treatment and outcomes was high in both groups. BTX-A is an important tool within the therapeutic spectrum for the treatment of hyperkinetic facial wrinkles, including those in the areas of the mouth and neck.     

Botulinum Toxin A in the Treatment of Chromhidrosis

Background. Chromhidrosis is an uncommon disorder characterized by secretion of colored sweat by apocrine glands, typically localized to the face or axilla. The current treatments available for chromhidrosis are time consuming and frequently ineffective.
Objective. Our purpose is to demonstrate a novel approach to the treatment of apocrine chromhidrosis.
Methods. We report a case of apocrine chromhidrosis successfully treated with botulinum toxin A (BTX-A; Botox).
Results. BTX-A therapy successfully controlled facial chromhidrosis, and the effects were visible at 19 weeks post-treatment. The therapeutic benefits may be attributed to its inhibitory effects on cholinergic stimulation, adrenergic stimulation, and substance P release, although further studies are necessary to elucidate the precise mechanism of action.
Conclusion. This report demonstrates a new therapeutic approach to patients suffering from chromhidrosis.     

A型肉毒毒素额部除皱后引起皮脂分泌改变的实验研究

目的：观察比较两种不同注射剂量的A型肉毒毒素（BTX-A）行额部注射除皱术后,引起局部皮脂分泌改变的情况,并研究其剂量和功效之间的关联。方法20例额部皱纹患者（中度至重度）随机分为注射总量10 U或20 U的两个治疗组。注射药物为宝妥适（BOTOX, BOTOX Cosmetic;Allergan, Irvine, CA）,使用肌肉内注射标准五点法。评价注射后2周、4周、8周、16周患者额部注射区域（注射点外围半径0.5 cm区域、注射点外围半径0.6～1.5 cm环形区域、注射点外围半径1.6～2.5 cm环形区域）皮肤油脂分泌水平。结果两种不同剂量注射2周、4周、8周后额部注射点外围半径0.5 cm区域平均皮脂分泌水平较注射前显著下降（P＜0.05）,注射16周后注射点外围半径0.5 cm区域平均油脂分泌水平于注射前相比没有显著差异。注射2周、4周、8周、16周后,注射点外围半径1.6～2.5 cm环形区域皮肤的平均油脂分泌水平显著高于注射前平均皮肤油脂分泌水平（P＜0.05）,注射点外围半径1.6～2.5 cm环形区域皮肤的平均油脂分泌水平与注射前水平相比没有显著的统计学差异。结论10 U及20 U肌肉内BTX-A注射2周、4周及8周后,能显著减少注射点外围半径0.5 cm区域的皮脂分泌,并引起注射点外围半径1.6～2.5 cm环形区域皮肤的皮脂分泌增高。     

Cervical dystonia (torticollis)

Opinion statement During the initial consultation, the patient is introduced to the five basic treatment options, acknowledging that in most cases, the choice is in the patient’s control. Th options are 1) supportive/social treatment, 2) physical therapies, 3) oral and intrathecal pharmacotherapy, 4) injection (botulinum toxin type A [BTX-A]) therapy, and 5) surgical therapy. Although a patient may be an obvious candidate for a specific intervention, the patient needs to be aware of the options, including those that he or she chooses not to use. Combination therapies are often appropriate. The option of supportive therapy is applicable in nearly all situations. All patients are encouraged to join a dystonia advocacy association. To accomplish this, literature is made available to them, and the telephone number of the local dystonia chapter is provided. For most patients with focal dystonia or symptoms limited to one region, such as those with cervical dystonia, local injections of botulinum toxin type A are core treatment. For those who cannot be treated effectively with BTX-A, or for those in whom BTX-A has failed, pharmacotherapy is instituted. Pharmacotherapy can often “take the edge off” symptoms that remain after BTX-A therapy. Physical therapies are recommended as complementary treatment for most patients receiving BTX-A in an attempt to extend the benefit from BTX-A. BTX-A may substantially change motor patterns, requiring physical therapies to help the patient relearn normal postures and functional control. In refractory cases when all other measures have failed, peripheral or brain surgery is considered. With our advancing understanding of the genetics of dystonia, it is hoped that specific therapy to either halt the progression of or bring additional relief to dystonic spasms will be available shortly.     

Botulinum toxins for facial wrinkles: beyond glabellar lines

Botulinum toxin type A (BTX-A) has been used for years with excellent results for upper facial cosmetic applications. Because of this success, the use of BOX-A for facial aesthetics has expanded to the lower facial and neck regions. BTX-A, especially when used in combination with fillers, has generally proven to be safe and efficacious in these areas. For optimal results, however, several issues must be taken into considerations, including dosing differences versus upper facial applications, the specific type of botulinum toxin used and the importance of precise placement and injection technique. In this article, the authors present their experience with BTX-A in the lower face and neck, and compare and contrast their current practices with those reported by others.     

Ice Minimizes Discomfort Associated with Injection of Botulinum Toxin Type A for the Treatment of Palmar and Plantar Hyperhidrosis

BACKGROUND The value of botulinum toxin type A (BTX-A) for treatment of palmar and plantar hyperhidrosis (HH) has been limited by injection pain, which in the past has generally required administration of a nerve block. We describe the successful use of ice applied to the intended injection point followed immediately by application of either ice or vibration to skin adjacent to the injection point to reduce discomfort associated with injection of BTX-A for the treatment of palmar and plantar HH.
RESULTS During needle insertion and injection of BTX-A, both the application of ice to the intended injection point followed by application of ice adjacent to the injection point (ice+ice) and the application of ice to the intended injection point followed by application of vibration adjacent to the injection point have been preferred by our patients to nerve block. These two techniques allow efficient treatment of both hands and/or both feet in a single session.
CONCLUSION By eliminating the need for nerve blocks, the techniques described here will enlarge the pool of physicians who can administer BTX-A for palmar and plantar HH, and will enlarge the pool of patients who are willing to have this treatment.     

A Randomized Pilot Study Comparing the Action Halos of Two Commercial Preparations of Botulinum Toxin Type A

BACKGROUND The determination of the action halos of botulinum toxin type A aids in targeting specific muscles and/or sweat glands, thereby preventing the occurrence of side effects.
OBJECTIVES The objective of this study was to compare the action halos of two commercial preparations of botulinum toxin type A, Dysport (Ipsen, Slough, UK) and BOTOX (Allergan, Irvine, CA).
MATERIAL AND METHODS Eighteen volunteers received applications of both products into randomized sides of the frontalis muscle. Equivalent doses of 5U of Dysport and 2U of BOTOX were injected using the same technique, in the same volume (0.02mL), and at a controlled depth. Twenty-eight days later, clinical and photographic assessments were performed.
RESULTS All the areas around the injected points were regular, round, or slightly oval and showed similar effects in the muscles and sweat glands. No statistically significant differences were observed between the mean sizes of the diameters of the halos produced by the two products.
CONCLUSION Injections of Dysport and BOTOX at an equivalence ratio of 2.5:1U, respectively, applied at the same volume and depth, using the same technique resulted in similar action halos with regard to muscular and sweat gland activity. Both products seem to be safe and very predictable.     

Effect of Robot-assisted Rehabilitation to Botulinum Toxin A Injection for Upper Limb Disability in Patients with Chronic Stroke: A Case Series and Systematic Review

Combining single-joint hybrid assistive limb (HAL-SJ) with botulinum toxin A (BTX-A) therapy is novel and has great therapeutic potential for the rehabilitation of stroke patients with upper limb paralysis. The purpose of this observational case series study was to evaluate the effect of BTX-A and HAL-SJ combination therapy on different exoskeleton robots used for treating upper limb paralysis. The HAL-SJ combination received a BTX-A injection followed by HAL-SJ-assisted rehabilitation for 60 min per session, 10 times per week, during 2 weeks of hospitalization. Clinical evaluations to assess motor function, limb functions used during daily activities, and spasticity were performed prior to injection, at 2-week post-treatment intervention, and at the 4-month follow-up visit. The total Fugl-Meyer assessment-upper limb (FMA-UE), proximal FMA-UE, action research arm test (ARAT), Motor Activity Log (MAL), and Disability Assessment Scale (DAS) showed a statistically significant difference, and a large effect size. However, the FMA distal assessment at 2-week post-treatment intervention showed no significant difference and a moderate effect size. The FMA-UE scores of the extracted systematic review articles showed that our design improved upper limb function. The change in the total FMA-UE score in this study showed that, compared to previous reports in the exoskeletal robotic therapy group, our combination therapy had a higher score than five of the seven references. Our results suggest that BTX-A therapy and HAL-SJ combination therapy may improve upper limb function, similar to other treatment methods in the literature.     

Complications of botulinum toxin type A

Introduced over 30 years ago for the treatment of strabismus and blepharospasm, botulinum toxin type A (BTX-A) now has established uses for various therapeutic and cosmetic purposes. Although remarkably safe and effective, BTX-A is a potent toxin. Complications can occur, particularly when used by the inexperienced injectors. Through knowledge of its mechanism of action and effect and careful attention to dosing and technique can minimize the risk of more serious adverse events.     

Antibodies against botulinum neurotoxin type A as a cause of treatment failure after the first detrusor injection

Botulinum neurotoxins are increasingly used in treatment for hyperactive detrusor and sphincter function. Although reported results are promising, conditions in some patients are refractory. We report what we believe to be the first urologic case of therapy failure possibly induced by botulinum toxin antibodies after just one injection and discuss treatment alternatives based on experience in other fields.     

GaAs laser treatment of bilateral eyelid ptosis due to complication of botulinum toxin type A injection

The widespread use of botulinum toxin type A (BTX-A) for aesthetic procedures in recent years has brought about some unwanted side effects that, though they are self-limited, cause inconvenience for patients. Injection of this paralytic toxin inactivates target muscle(s) for many months and unwanted facial movements will thus be prevented. Spreading of the toxin beyond the target muscles sometimes involves muscles necessary for other facial movements, such as the levator palpebrae, inactivation of which causes upper eyelid ptosis. Mild cases resolve after 2-3 wk, but in severe cases the complication may last as long as the cosmetic results persist (3-4 mo), and until now there has been no medical intervention to accelerate healing. In an effort to achieve more rapid recovery from eyelid ptosis due to overdose of BTX-A in the glabella, laser therapy was used in a 46-year-old woman with bilateral eyelid ptosis (partial on the right side and complete on the left) 12 d after injection. A GaAs laser was used and the protocol consisted of irradiation of three points on the upper lid just above the levator, and one point on the corrugator muscle on each side in contact mode, with three sessions per week (wavelength 890 nm, peak power 94 W, output power 28 mW, pulse duration 200 ns, spot size 3 mm, pulse repetition rate 3000 Hz, duration of irradiation 40 sec per point, energy per point 1.1 J, total energy per session 8.8 J, dose 16 J/cm2). The result was complete recovery from ptosis after 10 sessions, but the cosmetic results persisted for several months. It appears that if this procedure has similar results in other case series, it will be an effective therapeutic option to treat this complication.     

A preliminary report of the use of botulinum toxin type A in infants with clubfoot: four case studies

This report describes the use of botulinum toxin type A (BTX-A) in four infants with very severe clubfoot deformity. The gastrocnemius and posterior tibial muscles were injected with BTX-A after the patients reached a treatment plateau in physical therapy. Significant improvement in foot dorsiflexion and foot flexibility was seen in two patients, and surgery was not required. Surgical intervention was necessary in the remaining two patients, both of whom were ultimately diagnosed with a demyelinating neuropathy. The use of botulinum toxin as an adjunct to conservative care in infants with clubfoot is discussed.     

Topically Applied Botulinum Toxin Type A for the Treatment of Primary Axillary Hyperhidrosis: Results of a Randomized, Blinded, Vehicle-Controlled Study

OBJECTIVE The objective was to demonstrate that botulinum toxin type A (BTX-A) can be delivered to targeted skin sites with topical application for the treatment of primary axillary hyperhidrosis.
METHODS This randomized, blinded, vehicle-controlled study enrolled 12 patients with primary axillary hyperhidrosis with greater than 50 mg of sweat produced per 5 minutes. BTX-A (200 U), combined with a proprietary transport peptide molecule to bind the toxin in a noncovalent manner, was topically applied to one axilla; vehicle without BTX-A was applied to the other axilla. Rates of sweat production were measured and imaged at baseline and 4 weeks after application.
RESULTS Two patients were excluded from analyses. At 4 weeks, 10 axillae treated topically with BTX-A demonstrated a 65.3±21.5% mean reduction in sweating relative to the same-patient, vehicle-control axillae, which had a 25.3±66.2% mean reduction. The 40% difference in mean sweat reduction between groups was statistically significant ( p< .05). Quantitative image analysis of the results of the Minor's iodine starch test confirmed the reduction of sweat production in the BTX-A–treated versus the vehicle-treated axillae.
CONCLUSION Topically applied BTX-A appears to be safe and may prove to be effective for the treatment of axillary hyperhidrosis.