Botulinum Toxin Type A Administration Research Articles

A Multicenter Phase II Study Evaluating the Safety and Efficacy of Botulax in Asian Patients with Benign Masseteric Hypertrophy.

Benign masseteric hypertrophy (BMH) is a condition in which the thickness of the masseter muscle is increased, resulting in jawline prominence with an undesirable cosmetic appearance. Botulinum toxin type A (BTA) injection is a promising treatment option, but its effective dose remains debated. Adults older than 19 diagnosed with BMH through visual examination and palpation related to a masseter muscle prominence were selected, and 80 patients were randomly assigned into five groups (placebo group and four groups with different doses of BTA: 24 U, 48 U, 72 U, or 96 U, on both sides of the jaw) and treated with placebo or BTA once at their baseline visit. During each follow-up, the treatment efficacy was evaluated with ultrasound examination of the masseter muscle, three-dimensional facial contour analysis, visual evaluation by the investigator, and patient satisfaction evaluation. The mean age of the 80 patients was 42.7 ± 9.98 years; 68.75% were women. The mean change in masseter muscle thickness during the maximum clenching state after 12 weeks of drug administration compared with baseline in the 24-U, 48-U, 72-U, and 96-U groups were -2.33 ± 0.41 mm, -3.35 ± 0.42 mm, -2.86 ± 0.42 mm, and -3.79 ± 0.42 mm, respectively. All treatment groups showed a statistically significant decrease compared with placebo. Regarding subjective satisfaction, all treatment groups, except the 24-U group at 4 weeks, showed higher satisfaction than the placebo group during all visits. No significant adverse events were noted. BTA administration of at least 48 U for BMH is more cost-effective than high-dose units and has a low risk of side effects. Therapeutic, II.

Visual evoked potential changes following Botox administration in patients with blepharospasm.

To examine visual evoked potential (VEP) changes following botulinum toxin type A (BTA) administration in patients with blepharospasm. Patients diagnosed with blepharospasm receiving BTA administration were included in the study. Three groups, a control group and two study groups (patients examined 14days after BTA administration-Study Group 1, and patients examined 28days after BTA administration-Study Group 2) were evaluated. Dilated fundus examinations were performed following detailed ophthalmological examinations and VEP tests. Keypoint (Dantec, Denmark) and ISCEV criteria were adopted for pattern VEP (PVEP) recording. BTA was applied in the form of local injections at a total 15-30 units, at 2.5-5 units per injection. A mean 19.4 ± 3.2 units of BTA was used for each eye. N70 (ms), P100 (ms), and P100 (uV) values were statistically significantly lower in both study groups following drug administrations compared to the control group (p < 0.001 for all). Significant positive correlation was observed between increased P100 amplitudes and age in the control group (p = 0.008, r = 0.200). Significant negative correlation was observed between the BTA units used and decreased P100 amplitudes in both study groups 1 and 2 following drug administrations (p = 0.017, r = - 0.180 and p = 0.043, r = - 0.153, respectively). VEP may be an important method in the diagnosis and follow-up of blepharospasm and in determining the success of drug administration and additional therapeutic requirements.

Ultrasonographic Analysis of Trapezius Muscle for Efficient Botulinum Toxin Type A Injection.

Patients nowadays seek medical reduction of the upper trapezius muscle to achieve aesthetic pleasing necklines. Botulinum toxin type A (BoNT-A), a neurotoxin that reduces the force of muscle contraction, is widely used for shoulder contouring. However, detailed metrical data are lacking to guide clinical injection. Forty healthy young women were enrolled. All subjects were seated for point marking and measuring of trapezius muscle (TM) anatomical data. At marked locations, the thickness of the subcutaneous tissue, the thickness of the TM, the TM's anterior border, and the depth from the skin surface to the middle of TM were measured using a real-time ultrasound scanner. In addition, photos were taken to assess the shoulder area proportion and shoulder angle. The shoulder area size among participants was 90 ± 15.2 cm2, the average area proportion was 0.55 ± 0.1, and the shoulder angle was 23.12° ± 2.9°. Ultrasonography data reveal that the thickness of the subcutaneous tissue, the thickness of the TM, and the depth from the skin surface to the middle of TM all thickened from the anterior line to the posterior line (P < 0.001). The length of the TM extending forward was 1.47 ± 0.4 cm (range 0.51-1.31 cm). To better evaluate the appearance of the trapezius muscle, we constructed a grading system correlated to shoulder angle. In this study, ultrasonography and photos were applied to assess the TM's anatomical features. Trapezius hypertrophy was described on a scale from 0 to 2 based on the shoulder angle. The findings of the present study provide a practical clinical guidance for precise and efficient BoNT-A administration. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices

Background: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. Methods: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. Results: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). Discussion: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

Biphasic Injection for Masseter Muscle Reduction with Botulinum Toxin

Masseter Muscle Hypertrophy (MMH) is a well-known clinical benign condition that is not gender-specific and it can be monolateral or bilateral. Botulinum Toxin type A (BoNTA) injection has been widely described for MMH treatment and non-surgical facial slimming. BoNTA masseter injections have high efficacy and safety profile, but the risks of side effects remain. Muscular bulging during mastication is a complication due to the superficial overcompensation of masseteric fibers in response to neurotoxic weakening of the deep masseter. We present a biphasic-injection technique for BoNTA administration, based following anatomical concept and developed in order to prevent paradoxical bulging. A total of 98 treatments from 2015 to 2020 were performed with this technique. No remarkable complications occurred in our study. No cases of loss of full smile, difficulty in mouth opening, dizziness, headache, neurapraxia, and xerostomia were reported. A case of asymmetric smiling was self-resolved within a week. No patient claimed transient muscle weakness as distressing. No cases of paradoxical bulging were observed. Extensive knowledge of muscular anatomy and appropriate injection technique are key factors in achieving the desired result and avoiding complications. We feel that sharing this tip could be helpful for all the physicians involved in MMH treatment with BoNTA.

Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor

BackgroundSwitching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). This study aims to investigate whether botulinum toxin type A (BTX-A) regulates microglial M1/M2 polarization by inhibiting P2X7 expression in a rat model of NP.ResultsThe BTX-A administration elevated pain threshold, induced microglial polarization toward the M2 phenotype, and decreased P2X7 protein level in a rat model of NP induced by chronic compression injury (CCI). Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model and we demonstrated that BTX-A promoted microglial M2 polarization in LPS-stimulated HAPI microglial cells through suppressing P2X7.ConclusionsOur results indicate that BTX-A promotes microglial M2 polarization and suppresses CCI-induced NP through inhibiting P2X7 receptor. These findings provide new insights into the mechanism of BTX-A in relieving NP.

In vitro and in vivo studies using non-traditional bisphosphonates.

Non-traditional bisphosphonates, that is, bisphosphonates that do not inhibit osteoclast viability or function, were initially reported in the 1990s by Socrates Papapoulos' group. Originally designed to study the role of the R1 residue of aminobisphosphonates on bisphosphonate affinity for hydroxyapatite, these modified bisphosphonates retained similar affinity for mineralized bone as their parent compounds, but they lacked the potential to inhibit the mevalonate pathway or bone resorption. We found that, similar to classical bisphosphonates, these non-traditional compounds prevented osteoblast and osteocyte apoptosis in vitro through a pathway that requires the expression of the gap junction protein connexin 43, and the activation of the Src/MEK/ERK signaling pathway. Furthermore, one of those compounds named IG9402 (also known as amino-olpadronate or lidadronate), was able to inhibit osteoblast and osteocyte apoptosis, without affecting osteoclast number or bone resorption in vivo in a model of glucocorticoid-induced osteoporosis. IG9402 administration also ameliorated the decrease in bone mass and in bone mechanical properties induced by glucocorticoids. Similarly, IG9402 prevented apoptosis of osteoblastic cells in a model of immobilization due to hindlimb unloading. However, in this case, the bisphosphonate was not able to preserve the bone mass, and only partially prevented the decrease in bone mechanical properties induced by immobilization. The effect of IG9402 administration was also tested in a mouse model of masticatory hypofunction through the induction of masseter muscle atrophy by unilateral injection of botulinum toxin type A (BoNTA). IG9402 partially inhibited the loss of trabecular bone microstructure in the mandibular condyle, but not the decrease in masseter muscle mass induced by BoNTA administration. In summary, these non-traditional bisphosphonates that lack anti-resorptive activity but are able to preserve osteoblast and osteocyte viability could constitute useful tools to study the consequences of preventing apoptosis of osteoblastic cells in animal models. Furthermore, they could be used to treat conditions associated with reduced bone mass and increased bone fragility in which a reduction of bone remodeling is not desirable.

EUS-Guided Intragastric Injection of Botulinum Toxin A in the Preoperative Treatment of Super-Obese Patients: a Randomized Clinical Trial

Obesity is a disease that is highly prevalent in Brazil, and the associated comorbidities represent a major global public health challenge. Botulinum toxin type A (BTX-A) is a potent neurotoxin and inhibitor of gastric smooth muscle activity. In theory, BTX-A administration should promote early satiety and weight loss because it delays gastric emptying by inhibiting acetylcholine-mediated peristalsis, which is primarily responsible for gastric motility. Because results in the literature are discrepant, the efficacy of intragastric injections of BTX-A as a primary treatment for obesity remains unknown. The objective of this prospective, double-blind, single-center randomized study was to evaluate the effects of endoscopic ultrasound-guided intragastric BTX-A injections, as a bridge to bariatric surgery, in super-obese patients. Thirty-two super-obese patients were randomized to one of two groups: BTX-A, in which 200units of BTX-A were injected into the gastric antrum and body; and control, in which the same injections were performed with 0.9% saline. Weight, body mass index (BMI), and loss of excess weight were measured monthly over a 6-month period. Gastric emptying scintigraphy was performed before and after the procedure. The patients in both groups showed significant weight loss over the course of the study (p < 0.001). There were no statistically significant differences between the groups regarding weight loss, excess weight, total loss of excess weight, total weight loss, or change in BMI. Intragastric injection of BTX-A does not appear to be an effective method of achieving preoperative weight loss in super-obese patients.

Pregnancy outcomes following botulinum toxin type A exposure: A systematic review

Objective: To evaluate the available human data to-date in order to assess whether the prenatal exposure to botulinum toxin type A (BTX-A) is associated with major congenital malformations and other adverse pregnancy outcomes.&#x0D; Methods: Searches were conducted in PubMed/MEDLINE and Reprotox in November 2017. Cohort and case-control studies, case series, case reports were the primary data of interest.&#x0D; Results: No controlled studies but case series and case reports of therapeutic BTX-A administration during pregnancy were identified. Case reports regarding pregnant women with botulism were also reviewed.&#x0D; Conclusions: Limited data suggests that BTX-A exposure for therapeutic indications during pregnancy does not seem to be associated with an increase in risk of major congenital malformations. Rates of fetal loss were substantially different between prospective and retrospective data. Controlled epidemiological studies are needed to refute or support our findings.

Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity.

The adverse events (AEs) with botulinum toxin type-A (BoNTA), used for indications other than spasticity, are widely reported in the literature. However, the site, dose, and frequency of injections are different for spasticity when compared to the treatment for other conditions and hence the AEs may be different as well. The objective of this study was to summarize the AEs reported in Canada and systematically review the AEs with intramuscular botulinum toxin injections to treat focal spasticity. Data were gathered from Health Canada (2009-2013) and major electronic databases. In a 4 year period, 285 AEs were reported. OnabotulinumtoxinA (n=272 events): 68% females, 53% serious, 18% hospitalization, and 8% fatalities. The type of AEs reported were - muscle weakness (19%), oropharyngeal (14%), respiratory (14%), eye related (8%), bowel/bladder related (8%), and infection (5%). IncobotulinumtoxinA (n=13): 38% females, 62% serious, and 54% hospitalization. The type of AEs reported were - muscle weakness (15%), oropharyngeal (15%), respiratory (38%), eye related (23%), bowel/bladder related (15%), and infection (15%). Commonly reported AEs in the literature were muscle weakness, pain, oropharyngeal, bowel/bladder, blood circulation, neurological, gait, and respiratory problems. While BoNTA is useful in managing spasticity, future studies need to investigate the factors that can minimize AEs. A better understanding of the underlying mechanisms of the AEs can also improve guidelines for BoNTA administration and enhance outcomes.

Treatment of allergic rhinitis with intranasal infusion of botulinum toxin type A in mice

AimsTo determine whether intranasal infusion of botulinum toxin type A (BTX-A) relieves symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) and reduces nasal inflammation in mice. Main methodsAR was induced via intraperitoneal injection of OVA followed by daily intranasal challenge with OVA. Five weeks after the initiation of OVA sensitization, nasal cavities were exposed to a single intranasal infusion of BTX-A. The behavior of mice was observed before and 1, 3, 5, 7, 14, 21, and 28days after infusion. Mice were sacrificed after 28days and late histological findings were examined. PBS was administered to control mice. ResultsOn Day 3, the frequency of typical AR symptoms, including sneezing and nose scratching, significantly decreased in the BTX-A-treated group (n=6) compared to the control group (n=6). Although the AR-inhibiting effects of BTX-A persisted until Day 21, AR symptoms re-appeared in response to daily OVA stimulation. Histological findings of the nasal mucosa also improved following BTX-A administration. Although capillary dilatation and eosinophil infiltration decreased by Day 3, these effects disappeared by Day 28. In contrast, the number and size of the secretary glands in the nasal mucosa did not change following BTX-A administration. PBS had no effect on nasal symptoms or histology. ConclusionsTopical treatment with BTX-A efficiently and temporarily ameliorates AR symptoms. Intranasal infusion does not cause pain or bleeding, and the effects of a single infusion of BTX-A last for at least three weeks. This treatment might be a promising therapeutic strategy for the treatment of AR.

Effects of botulinum toxin type A on non‐injected bi‐articular muscle include a narrower length range of force exertion and increased passive force

The goal of this study was to test the hypothesis that botulinum toxin type A (BTX-A) injection in rat tibialis anterior (TA) muscle affects the mechanics of its bi-articular synergist, both actively and passively. Two groups of Wistar rats were tested: control (no BTX-A) and BTX (0.1 U of BTX-A) animals were injected exclusively to the mid-belly of TA. Extensor digitorum longus (EDL) muscle isometric forces were measured after proximal and distal lengthening. Five days after injection, BTX-A administration changed EDL mechanics: (1) active forces decreased (proximal muscle length dependently); (2) length range of active force exertion decreased both proximally and distally; and (3) passive muscle forces increased. Effects of BTX-A appear to not be limited to decreased active muscle tone, but may cause also a narrower active range of movement and increased passive resistance. Through spread of BTX-A to a bi-articular muscle, such effects are plausible for both joints spanned.

The effects of botulinum toxin type A on improvement and dynamic spastic equinus correction in children with cerebral palsy - preliminary results.

IntroductionWe evaluated the effects of botulinum toxin type A (BTA) with physical therapy on dynamic foot equinus correction and higher motor functional outcome in children with spastic type of cerebral palsy (CP).Material and methodsAnkle joint active and passive movement, gastrocnemial muscle spasticity levels (Modified Ashworth Scale (MAS)), and higher motor functional status (Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM) (GMFM-D – standing and GMFM-E – walking) were assessed before treatment and 3, 8, 16 weeks and 6 months after BTA administration in 12 children.ResultsThere was a significant improvement of active (initial – (–)13.07 ±5.78; 6 months – (–)10.64 ±4.77; p < 0.001) and passive (initial – 4.21 ±2.29; 6 months – 4.71 ±2.16; p < 0.05) ankle joint foot dorsiflexion. GMFM-D and GMFM-E were significantly higher after 3, 8, 16 weeks (p < 0.001) and GMFM-D after 6 months (p < 0.001).ConclusionsBotulinum toxin type A administration and physical therapy in patients with spastic CP improves the motion range of dynamic foot equinus after 3 weeks and higher motor functional outcome (standing and walking).

BTX-A Administration to the Target Muscle Affects Forces of All Muscles Within an Intact Compartment and Epimuscular Myofascial Force Transmission

Measurement of forces of mono- and bi-articular muscles of an entire intact muscle compartment can allow for a comprehensive assessment of the effects of Botulinum toxin type A (BTX-A) both at and beyond the injection site, and in conditions close to those in vivo. The goal was to test the hypotheses that BTX-A affects (1) the forces of not only the injected but also the noninjected muscles of the compartment, and (2) epimuscular myofascial force transmission (EMFT). Two groups of Wistar rats were tested: Control (no BTX-A injected) and BTX (0.1 units of BTX-A were injected exclusively to the mid-belly of TA). Isometric forces were measured simultaneously at the distal tendons of the tibialis anterior (TA) at different lengths, the restrained extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles and at the proximal tendon of EDL. Five days post-injection, BTX-A did affect the total forces of all muscles significantly: (1) The TA force decreased differentially (by 46.6%-55.9%) for most lengths such that a significant negative correlation was found between force reductions and increased muscle length. The maximum TA force decreased by 47.3%. However, the muscle's length range of force production did not change significantly. (2) Distal and proximal EDL forces decreased (on average by 67.8% and 62.9%, respectively). (3) The EHL force also decreased (on average by 9.2%). The passive forces of only the TA showed a significant increase at higher lengths. EMFT effects were shown for the control group: (1) at the shortest TA lengths, the EDL proximo-distal force differences were in favor of the distal force, which was reversed at higher lengths. (2) the EHL force measured at the shortest TA length decreased (by 34%) as a function of TA lengthening. After BTX-A exposure, such EMFT effects disappeared for the EDL, whereas they remained as profound for the EHL. Exposure to BTX-A does affect forces of all muscles operating in an intact compartment. For the BTX-A injected muscle, the reduction in muscle force becomes less pronounced at higher muscle lengths. BTX-A also has effects on EMFT, however, these effects are not uniform within the anterior crural compartment. Decreased forces of the noninjected synergistic muscles suggest the presence of unintended additional effects of BTX-A both for the targeted distal joint and for the nontargeted proximal joint.

Intravesical Electromotive Botulinum Toxin Type A Administration: Part I—Experimental Study

To evaluate the depth and pattern of botulinum toxin type A (BTX-A) distribution throughout the rabbit bladder wall by intravesical electromotive drug administration (EMDA). In an experimental study, 15 male healthy New Zealand white rabbits were allocated in 3 groups of BTX-A injection into the bladder wall, intravesical electromotive BTX-A administration (BTX-A/EMDA), and electromotive saline administration. In BTX-A injection group, a total dose of 10 IU/kg of BTX-A (Dysport) was injected into 10 sites of bladder detrusor muscle using a 6-Fr rigid cystoscope. In BTX-A/EMDA group, a current generator delivered a total of 2-2.4 mA with a frequency of 2.5 kHz to a fully distended bladder containing 10 IU/kg BTX-A for 15 minutes. In electromotive saline administration group, electrical current with the same characteristics was delivered to a saline-filled bladder. Three different specimens from the bladder dome, posterior, and anterior bladder walls were obtained and submitted for pathologic evaluation. Pattern of immunohistochemical staining in bladder specimens from BTX-A injection group was weak and heterogeneous in the urothelium, interstitium, and muscular layers. However, in BTX-A/EMDA group the staining was uniform in urothelium, interstitial and muscular layers in all submitted specimens. In electromotive saline administration group, the urothelium, interstitium, and muscular layers were intact. There is no clinical or experimental report of intravesical BTX-A/EMDA in the literature. This method demonstrated deep and homogenous penetration of the toxin throughout the urinary bladder layers compared with the intravesical BTX-A injection.

The biomechanical effects of limb lengthening and botulinum toxin type A on rabbit tendon

Numerous studies have examined the effects of distraction osteogenesis (DO) on bone, but relatively fewer have explored muscle adaptation, and even less have addressed the concomitant alterations that occur in the tendon. The purpose herein was to characterize the biomechanical properties of normal and elongated rabbit ( N=20) tendons with and without prophylactic botulinum toxin type A (BTX-A) treatment. Elastic and viscoelastic properties of Achilles and Tibialis anterior (TA) tendons were evaluated through pull to failure and stress relaxation tests. All TA tendons displayed nonlinear viscoelastic responses that were strain dependent. A power law formulation was used to model tendon viscoelastic responses and tendon elastic responses were fit with a microstructural model. Distraction-elongated tendons displayed increases in compliance and stress relaxation rates over undistracted tendons; BTX-A administration offset this result. The elastic moduli of distraction-lengthened TA tendons were diminished ( p=0.010) when distraction was combined with gastrocnemius (GA) BTX-A administration, elastic moduli were further decreased ( p=0.004) and distraction following TA BTX-A administration resulted in TA tendons with moduli not different from contralateral control ( p>0.05). Compared to contralateral control, distraction and GA BTX-A administration displayed shortened toe regions, ( p=0.031 and 0.038, respectively), while tendons receiving BTX-A in the TA had no differences in the toe region ( p>0.05). Ultimate tensile stress was unaltered by DO, but stress at the transition from the toe to the linear region of the stress–stretch curve was diminished in all distraction-elongated TA tendons ( p<0.05). The data suggest that prophylactic BTX-A treatment to the TA protects some tendon biomechanical properties.

Retrograde Dissemination Through Sacral Neural Pathways: Mechanism of Action for Botulinum Toxin Type A in Concomitant Neuropathic Bladder and Bowel Dysfunction

Purpose In our two previous studies with intravesical botulinum toxin type A (BTX-A) injection and electromotive BTX-A administration in children with myelomeningocele and neurogenic detrusor overactivity, notable improvement in concomitant bowel dysfunction occurred. The exact mechanism for this observation is still unclear but the effect of toxin on common neural pathways for urinary and bowel function and the diffusion of toxin to bladder's contiguous structures are existing hypotheses. This experimental model aimed at determining the validity of current hypotheses. Material and Methods Ten male white New Zealand rabbits were divided in two equal groups: the first group received intravesical 10 IU/kg BTX-A through a specific catheter for electromotive drug administration. A maximum current of 4 mA for 15 min was delivered to the drug solution. In another group, the electrical current with similar characteristics was delivered to the saline-filled bladder. Then, biopsies from the bladder wall and bladder's contiguous structures including intestinal wall lying posterior to the bladder, pelvic floor muscles, sacral neural plexus, and anal sphincter were taken and then submitted for immunohistochemical analysis. Results Botulinum toxin penetrated through muscularis layer of the bladder wall in BTX-A group. The toxin was not present in pelvic floor muscles, intestinal wall, and anal sphincter. The toxin was detected in sacral neural plexus in BTX-A group. Conclusions Botulinum toxin type A acts on neuromuscular junction. Current study suggests that retrograde dissemination of toxin through upper neural pathways which also control bowel motor function can justify simultaneously improved bladder and bowel function.

Improvement in Both Raynaud Disease and Hyperhidrosis in Response to Botulinum Toxin Type a Treatment.

A patient with concurrent Raynaud disease presented for hyperhidrosis of the axillae and palms. After a positive response to botulinum toxin type A (BoNTA) for axillary hyperhidrosis, she returned requesting palmar treatment. Our goal was to investigate the effect of BoNTA on Raynaud disease in concurrent hyperhidrosis with respect to color change, swelling, and digital pain. The patient had treatment with 100 units of BoNTA to one hand at first, with the other being a negative control, followed by treatment of the second hand 1 week later. After the injection into the first palm, the patient demonstrated an 85% reduction in palmar hyperhidrosis and a significant improvement in her Raynaud symptoms. Specifically, the BoNTA-treated hand had reduced swelling, color change, and pain, whereas the untreated control hand remained affected. After the second hand was treated, it, too, demonstrated the same positive results. Our case report of concurrent Raynaud disease and palmar hyperhidrosis shows significant improvement in both conditions to BoNTA administration. The physiology is multifactorial and relates to BoNTA's effect on acetylcholine, noradrenaline, substance P, calcitonin gene-related peptide, and glutamate release from nerve terminals. These results present an encouraging novel treatment option in dermatology for patients with Raynaud disease.

Optimising effects of botulinum toxin by post-injection activity

Recent studies indicate that increased motor activity can increase presentation of SV2-specific botulinum toxin type A (BTX-A) receptor. This might result in higher efficacy of BTX-A injected. The aim of the present study was to investigate whether post-injection activation program may increase the duration of clinical benefit in cervical dystonia (CD). A total of 27 patients (17 female and 10 male, age range 26–63 years, disease duration >2 years) who had improved significantly to BTX-A injections during the previous year were enrolled into this single-centre, single-blind, crossover study. Each patient was injected with previously used effective dose of BTX-A (100–200 U of BOTOX, Allergan). CD was assessed using validated scales for dystonia (TWSTRS, ADL) every 2 weeks. In addition, patients were asked to contact their doctor immediately when they deemed the effect of BTX-A. Only after the second BTX-A injection activation and physical therapy, with the help of a physiotherapist, were performed 15 min before and immediately after BTX-A administration (60 min daily during 2 weeks). Physical activity protocol included biofeedback training and active stretching to increase specific muscle activity. Our results showed that BTX-A was effective in improving CD symptoms during both treatment periods. But the duration of clinical improvement was significantly longer (10–15 days) when the same dose of BTX-A was administered in combination with activation physiotherapy.

Botulinum Toxin Therapy in the Ovalbumin-Sensitized Rat

Objective: The aim of this study was to determine whether intranasal administration of botulinum toxin type A (BTX-A) could relieve the typical symptoms of allergic rhinitis (AR) and alter substance P (SP)- and vasoactive intestinal peptide (VIP)-immunoreactive (IR) expression in nasal mucosa of AR animals sensitized with ovalbumin (OVA). Methods: AR was induced by intraperitoneal injection of OVA followed by its repeated intranasal instillation in female Wistar rats. Some AR animals were intranasally treated with a cotton strip containing BTX-A (10 U per nostril) for 1 h. After BTX-A treatment, OVA was repeatedly instilled in AR and AR + BTX-A groups every 2 days for 10 days. Subsequently, nasal symptoms were evaluated, and nasal secretions collected. Finally, the nasal mucosae of all animals were prepared for histological and immunohistochemical assessment. Results: BTX-A administration alleviated typical AR symptoms including rhinorrhea, nasal itching and sneezing, and subsequent intranasal repeated challenge with OVA did not trigger AR symptoms. After BTX-A treatment, inflammatory histological characteristics within the nasal mucosa of AR animals were absent, but atrophy of serous glands was observed. BTX-A decreased dense SP-IR and VIP-IR cells and fibers within and beneath the epithelium, around blood vessels and close to serous glands in AR animals. Conclusion: Local BTX-A treatment is an effective method to reduce AR symptoms. BTX-A decreased the excessive SP-IR and VIP-IR expression induced by OVA. Therefore, BTX-A may affect the nasal mucosa via the suppression of neuropeptides, playing a major role in autonomous mucosal innervation in the pathophysiology of AR.