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A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 43971

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Prof. Dr. Hee-Jin Kim

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Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Interests: botulinum; neurotoxin; clinical studies
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Dear Colleagues,

Despite not only the safety but also the reversible clinical procedures of botulinum toxin injections in the fields of therapeutics or cosmetics, various clinical side effects have been reported. The background of these side effects includes not only inappropriate injection techniques but also a lack of anatomical knowledge, contrary to clinical experience.

Recently, clinical practices, such as ultrasonography-guided injection, have been used to prevent the side effects known to be associated with botulinum toxin injection. This enables precise injection with accurate doses of toxins, but recently, clinical anatomical knowledge has been lacking in the clinical use of botulinum toxins, making further clinical development impossible.

This Special Issue includes safety guidelines for the most desired outcome related to botulinum toxin injection, as well as an introduction to new injection techniques using supplementary equipment.

Prof. Dr. Hee-Jin Kim
Guest Editor

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Keywords

botulinum neurotoxin
injection
anatomy
clinical guideline
ultrasonography
safety

Published Papers (10 papers)

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10 pages, 3013 KiB

Open AccessArticle

Comparison between Conventional Blind Injections and Ultrasound-Guided Injections of Botulinum Toxin Type A into the Masseter: A Clinical Trial

by Hyungkyu Bae, Jisoo Kim, Kyle K. Seo, Kyung-Seok Hu, Seong-Taek Kim and Hee-Jin Kim

Toxins 2020, 12(9), 588; https://doi.org/10.3390/toxins12090588 - 11 Sep 2020

Cited by 16 | Viewed by 4510

Abstract

The aim of the study was to propose a more efficient and safer botulinum toxin type A (BoNT-A) injection method for the masseter by comparing the conventional blind injection and a novel ultrasonography (US)-guided injection technique in a clinical trial. The 40 masseters from 20 healthy young Korean volunteers (10 males and 10 females with a mean age of 25.6 years) were included in this prospective clinical trial. The BoNT-A (24 U) was injected into the masseter of each volunteer using the conventional blind and US-guided injection techniques on the left and right sides, respectively, and analyzed by US and three-dimensional (3D) facial scanning. One case of PMB (paradoxical masseteric bulging) was observed on the side where a conventional blind injection was performed, which disappeared after the compensational injection. The reduction in the thickness of the masseter in the resting state differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 12.38 ± 7.59% and 17.98 ± 9.65%, respectively (t(19) = 3.059, p = 0.007). The reduction in the facial contour also differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 1.95 ± 0.74 mm and 2.22 ± 0.84 mm, respectively (t(19) = 2.908, p = 0.009). The results of the study showed that the US-guided injection method that considers the deep inferior tendon by visualizing the masseter can prevent the PMB that can occur during a blind injection, and is also more effective. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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10 pages, 787 KiB

Open AccessArticle

Rectus Femoris Characteristics in Post Stroke Spasticity: Clinical Implications from Ultrasonographic Evaluation

by Lucia Cosenza, Alessandro Picelli, Danila Azzolina, Marco Alessandro Minetto, Marco Invernizzi, Michele Bertoni, Andrea Santamato and Alessio Baricich

Toxins 2020, 12(8), 490; https://doi.org/10.3390/toxins12080490 - 31 Jul 2020

Cited by 5 | Viewed by 3174

Abstract

In stroke survivors, rectus femoris (RF) spasticity is often implicated in gait pattern alterations such as stiff knee gait (SKG). Botulinum toxin type A (BoNT-A) is considered the gold standard for focal spasticity treatment. However—even if the accuracy of injection is crucial for BoNT-A efficacy—instrumented guidance for BoNT-A injection is not routinely applied in clinical settings. In order to investigate the possible implications of an inadequate BoNT-A injection on patients’ clinical outcome, we evaluated the ultrasound-derived RF characteristics (muscle depth, muscle thickness, cross-sectional area and mean echo intensity) in 47 stroke survivors. In our sample, we observed wide variability of RF depth in both hemiparetic and unaffected side of included patients (0.44 and 3.54 cm and between 0.25 and 3.16 cm, respectively). Moreover, our analysis did not show significant differences between treated and non-treated RF in stroke survivors. These results suggest that considering the inter-individual variability in RF muscle depth and thickness, injection guidance should be considered for BoNT-A treatment in order to optimize the clinical outcome of treated patients. In particular, ultrasound guidance may help the clinicians in the long-term follow-up of muscle quality. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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9 pages, 248 KiB

Open AccessArticle

by Lorenzo Pietro Roncoroni, Daniel Weiss, Leonhard Hieber, Justine Sturm, Axel Börtlein, Ingo Mayr, Matthias Appy, Benedicta Kühnler, Joachim Buchthal, Christian Dippon, Guy Arnold and Tobias Wächter

Toxins 2020, 12(5), 292; https://doi.org/10.3390/toxins12050292 - 4 May 2020

Cited by 4 | Viewed by 2231

Abstract

Objective: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment. Methods: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed. Results: BoNT improved the EQ visual analog scale (EQ VAS). In addition, state of health and pain maxima improved. The EQ VAS improvement correlated with pre-injection characteristics of the EQ VAS and life satisfaction in the “movement disorders” domain. Conclusion: EQ VAS is sensitive for monitoring HR-QoL outcomes in an unselected real life observational cohort. This study may inform future studies intended to validate prediction variables that could inform on HR-QoL effects of BoNT treatment in spasticity. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

9 pages, 1568 KiB

Open AccessArticle

Intramuscular Neural Distribution of Rhomboid Muscles: Evaluation for Botulinum Toxin Injection Using Modified Sihler’s Method

by Kyu-Ho Yi, Hyung-Jin Lee, You-Jin Choi, Ji-Hyun Lee, Kyung-Seok Hu and Hee-Jin Kim

Toxins 2020, 12(5), 289; https://doi.org/10.3390/toxins12050289 - 3 May 2020

Cited by 24 | Viewed by 5224

Abstract

This study describes the nerve entry point and intramuscular nerve branching of the rhomboid major and minor, providing essential information for improved performance of botulinum toxin injections and electromyography. A modified Sihler method was performed on the rhomboid major and minor muscles (10 specimens each). The nerve entry point and intramuscular arborization areas were identified in terms of the spinous processes and medial and lateral angles of the scapula. The nerve entry point for both the rhomboid major and minor was found in the middle muscular area between levels C7 and T1. The intramuscular neural distribution for the rhomboid minor had the largest arborization patterns in the medial and lateral sections between levels C7 and T1. The rhomboid major muscle had the largest arborization area in the middle section between levels T1 and T5. In conclusion, botulinum neurotoxin injection and electromyography should be administered in the medial and lateral sections of C7−T1 for the rhomboid minor and the middle section of T1−T7 for the rhomboid major. Injections in the middle section of C7−T1 should also be avoided to prevent mechanical injury to the nerve trunk. Clinicians can administer safe and effective treatments with botulinum toxin injections and other types of injections by following the methods in our study. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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10 pages, 720 KiB

Open AccessArticle

Botulinum Toxin Effects on Sensorimotor Integration in Focal Dystonias

by Maria Ilenia De Bartolo, Nicoletta Manzo, Gina Ferrazzano, Viola Baione, Daniele Belvisi, Giovanni Fabbrini, Alfredo Berardelli and Antonella Conte

Toxins 2020, 12(5), 277; https://doi.org/10.3390/toxins12050277 - 25 Apr 2020

Cited by 4 | Viewed by 2384

Abstract

(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD); and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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14 pages, 1631 KiB

Open AccessArticle

Comparative Effectiveness of Botulinum Toxin Injection for Chronic Shoulder Pain: A Meta-Analysis of Randomized Controlled Trials

by Po-Cheng Hsu, Wei-Ting Wu, Der-Sheng Han and Ke-Vin Chang

Toxins 2020, 12(4), 251; https://doi.org/10.3390/toxins12040251 - 12 Apr 2020

Cited by 12 | Viewed by 4998

Abstract

Botulinum toxin (BoNT) injection is regarded as a promising treatment for musculoskeletal pain. However, its efficacy for treating chronic shoulder pain remains unclear. We investigated the effectiveness of BoNT injections for chronic shoulder pain by conducting a systematic search of electronic databases up to March 2020 for randomized control trials (RCTs) that used BoNT injections for chronic shoulder pain treatment. The primary outcome was the between-group comparison of pain reduction, quantified by the standardized mean difference (SMD). Nine RCTs comprising 666 patients were included and divided into two groups: one group with shoulder joint pain (n = 182) and the other group with shoulder myofascial pain (n = 484). Regarding shoulder joint pain, the efficacy of BoNT injections was similar to that of the reference treatment (SMD: −0.605, 95% confidence level [CI]: −1.242 to 0.032 versus saline; SMD: −0.180, 95% CI: −0.514 to 0.153 versus corticosteroids) at one month post-intervention, and was superior (SMD: −0.648, 95% CI: −0.1071 to −0.225 versus corticosteroids) between one and three months. Likewise, in terms of shoulder myofascial pain, the effectiveness of BoNT injections did not differ from the reference treatment (SMD: −0.212, 95% CI: −0.551 to 0.127 versus saline; SMD: 0.665, 95% CI: −0.260 to 1.590 versus dry needling and SMD: 1.093; 95% CI: 0.128 to 2.058 versus lidocaine) at one month post- intervention, and appeared superior (SMD: −0.314, 95% CI: −0.516 to −0.111 versus saline) between one and three months. Our meta-analysis revealed that BoNT injections could be a safe and effective alternative for patients with chronic shoulder pain. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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7 pages, 1396 KiB

Open AccessArticle

A Proposal for Botulinum Toxin Type A Injection Into the Temporal Region in Chronic Migraine Headache

by Young-gun Kim, Jung-Hee Bae, Hyeyun Kim, Shuu-Jiun Wang and Seong Taek Kim

Toxins 2020, 12(4), 214; https://doi.org/10.3390/toxins12040214 - 28 Mar 2020

Cited by 9 | Viewed by 4191

Abstract

Botulinum toxin type-A (BTX-A) injection for treating chronic migraine (CM) has developed into a new technique covering distinct injection points in the head and neck regions. The postulated analgesic mechanism implies that the injection should be administered to sensory nerves rather than to muscles. This study aimed to determine the topographical site of the auriculotemporal nerve (ATN) and to propose the effective injection points for treating CM. ATNs were investigated on 36 sides of 25 Korean cadavers. The anatomical structures of the ATN were investigated focusing on the temporal region. A right-angle ruler was positioned based on two clearly identifiable orthogonal reference lines based on the canthus and tragus as landmarks, and photographs were taken. The ATN appeared superficially in the anterosuperior region of the tragus. The nerve is located deeper than the superficial temporal artery. And it runs between the artery and the superficial temporal vein. In the superficial layer, it is divided into anterior and posterior divisions. The anterior division runs in a superior direction, while the posterior division runs in front of the ear and the several branches are distributed to the skin. We suggest that the optimal BTX-A injection points for CM are in the temporal region. The first point is about 2 cm anterior and 3 cm superior to two orthogonal reference lines defined based on the tragus and canthus, and the second point is about 4 cm superior to the first point. The third and fourth points are recommended about 2 cm superior to the first point, but respectively 1 cm anterior and posterior to it. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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10 pages, 3349 KiB

Open AccessArticle

Anatomical Considerations When Treating Compensatory Hypertrophy of the Upper Part of the Masseter after Long-Term Botulinum Neurotoxin Type A Injections

by Kyu-Lim Lee, Hyun Jin Cho, Hyungkyu Bae, Hyun Jin Park, Min Sun Park and Hee-Jin Kim

Toxins 2020, 12(3), 202; https://doi.org/10.3390/toxins12030202 - 22 Mar 2020

Cited by 6 | Viewed by 4814

Abstract

The masseter is the most targeted muscle when treating hypertrophy to produce a smooth face shape. Compensatory hypertrophy is a well known clinical sequela that occurs in botulinum neurotoxin (BoNT) treatments and is limited to the lower part of the masseter. Based on the masseteric hypertrophy procedure, which targets a confined area, we predicted the possibility of compensatory hypertrophy occurring in the upper part of the masseter. If the patient complains about an unexpected result, additional injections must be performed, but the involved anatomical structures have not been revealed yet. The aim of this study was to identify the morphological patterns of the masseter. Deep tendons were observed in most specimens of the upper part of the masseter and mostly appeared in a continuous pattern (69.7%). The superficial and deep tendons could be classified into a simply connected form and forms surrounding part of the muscle. In 45.5% of cases there were tendon capsules that completely enclosed the muscle, which can interfere with how the injected toxin spreads. Interdigitation patterns in which the tendons could be identified independently between the muscles were present in 9.1% of cases. The present findings provide anatomical knowledge for use when injecting BoNT into the masseter. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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10 pages, 1033 KiB

Open AccessArticle

Botulinum Toxin Therapy for Managing Sleep Bruxism: A Randomized and Placebo—Controlled Trial

by Young Joo Shim, Hee Jin Lee, Keun Jeong Park, Hyung Tack Kim, Il Hee Hong and Seong Taek Kim

Toxins 2020, 12(3), 168; https://doi.org/10.3390/toxins12030168 - 9 Mar 2020

Cited by 20 | Viewed by 8319

Abstract

The purpose of this study is to evaluate the effects of botulinum toxin type A (BoNT-A) for managing sleep bruxism (SB) in a randomized, placebo-controlled trial. Thirty SB subjects were randomly assigned into two groups evenly. The placebo group received saline injections into each masseter muscle, and the treatment group received BoNT-A injections into each masseter muscle. Audio–video–polysomnographic recordings in the sleep laboratory were made before, at four weeks after, and at 12 weeks after injection. Sleep and SB parameters were scored according to the diagnostic and coding manual of American Academy of Sleep Medicine. The change of sleep and SB parameters were investigated using repeated measures analysis of variance (RM-ANOVA). Twenty-three subjects completed the study (placebo group 10, treatment group 13). None of the SB episode variables showed a significant time and group interaction (p > 0.05) except for electromyography (EMG) variables. The peak amplitude of EMG bursts during SB showed a significant time and group interaction (p = 0.001). The injection decreased the peak amplitude of EMG bursts during SB only in the treatment group for 12 weeks (p < 0.0001). A single BoNT-A injection cannot reduce the genesis of SB. However, it can be an effective management option for SB by reducing the intensity of the masseter muscle. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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15 pages, 2667 KiB

Open AccessPerspective

Clinical Implications of Difference in Antigenicity of Different Botulinum Neurotoxin Type A Preparations: Clinical Take-Home Messages from Our Research Pool and Literature

by Sara Samadzadeh, Beyza Ürer, Raphaela Brauns, Dietmar Rosenthal, John-Ih Lee, Philipp Albrecht and Harald Hefter

Toxins 2020, 12(8), 499; https://doi.org/10.3390/toxins12080499 - 4 Aug 2020

Cited by 19 | Viewed by 3423

Abstract

The three different botulinum toxin type A (BoNT/A) preparations being licensed in Europe and the U.S. differ in protein content, which seems to be a major factor influencing the antigenicity of BoNT/A. In the present study, several arguments out of our research pool were collected to demonstrate that the clinical response and antigenicity were different for the three BoNT/A preparations: some results of (1) a cross-sectional study on clinical outcome and antibody formation of 212 patients with cervical dystonia (CD) being treated between 2 and 22 years; (2) another cross-sectional study on the clinical aspects and neutralizing antibody (NAB) induction of 63 patients having developed partial secondary treatment under abobotulinum (aboBoNT/A) onabotulinumtoxin (onaBoNT/A) who were switched to incobotulinumtoxin (incoBoNT/A) in comparison to 32 patients being exclusively treated with incoBoNT/A. These results imply that (1) the presence of NAB cannot be concluded from the course of treatment, that (2) an increase in the dose and variability of outcome with treatment duration indicates the ongoing induction of NABs over time, that (3) the higher protein load of BoNT/A goes along with a higher incidence and prevalence of NAB induction and that (4) the best response to a BoNT/A is also dependent on the protein load of the preparation. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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