Botulinum Toxins in Clinical Practice

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 34020

Special Issue Editors


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Guest Editor
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
Special Issues, Collections and Topics in MDPI journals

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Co-Guest Editor
Department of Dermatology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, KOREA

Special Issue Information

Dear Colleagues,

The study of botulinum neurotoxin (BoNT) extends beyond the treatment of neurologic disorders and facial wrinkles to include many off-label uses in clinical practice. With more and more studies being published, it is crucial for researchers to collect up-to-date scientific achievements in the emerging clinical applications of BoNT. In fact, what we still lack is the scientific evidence of less-investigated clinical applications of BoNT, particularly for aesthetic medicine and surgery. Providing clinicians and researchers with relevant scientific data will support a better understanding of the clinical efficacy of BoNT in medicine and surgery.

To this end, this Special Issue of Toxins on BoNT has been carefully compiled to provide scientific data on various clinical indications including facial aesthetic medicine and cosmetic surgery, non-surgical body contouring, hypertrophic scars and keloids, pain control, and rehabilitation medicine. Active uses of BoNT for treating common dermatological conditions such as acne and rosacea will also be reviewed. A discussion of the current practice patterns and over-the-edge uses of BoNT will be included.

The advances seen in clinical uses of BoNT over the past 30 years are in large part owing to the investigations in the field. Through these studies, clinical results have been further optimized and complications are reduced. Appreciation should go to every researcher and clinician in this rapidly growing field who continue to expand our collective knowledge.

Prof. Hee-Jin Kim
Dr. Nark-Kyoung Rho
Guest Editors

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Keywords

  • botulinum toxins
  • clinical studies
  • dermatology
  • off-label use
  • pain
  • plastic surgery
  • practice patterns
  • regional anatomy
  • rehabilitation medicine

Published Papers (7 papers)

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Research

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8 pages, 2216 KiB  
Article
Anatomical Injection Guidelines for Glabellar Frown Lines Based on Ultrasonographic Evaluation
by Soo-Bin Kim, Hyoung-Moon Kim, Haeryun Ahn, You-Jin Choi, Kyung-Seok Hu, Wook Oh and Hee-Jin Kim
Toxins 2022, 14(1), 17; https://doi.org/10.3390/toxins14010017 - 25 Dec 2021
Cited by 6 | Viewed by 6601
Abstract
When botulinum neurotoxin (BoNT) is injected to treat glabellar frown lines, the corrugator supercilia muscle (CSM) and procerus muscles are the main targets. Although there have been many studies on the treatment of glabellar frown lines, no study has confirmed the dynamic movement [...] Read more.
When botulinum neurotoxin (BoNT) is injected to treat glabellar frown lines, the corrugator supercilia muscle (CSM) and procerus muscles are the main targets. Although there have been many studies on the treatment of glabellar frown lines, no study has confirmed the dynamic movement under ultrasonography (US). This study examined and evaluated dynamic muscle movements under US, thereby providing more effective BoNT injection guidelines for glabellar frowning. Glabellar frowning was categorized as either Type A or B. Type A is the general frowning pattern in which vertical wrinkles are made by contracting the CSM and procerus muscles (81%, n = 13). On US images, the procerus muscle thickens and the bilateral CSMs contract. Type B is an upward frowning pattern demonstrating upward elevation of vertical wrinkles due to hyperactive contraction of the frontalis muscle during frowning (19%, n = 3). On US images, the hypoechoic frontalis muscle thickens, forming horizontal forehead lines. After BoNT injection into the CSM and frontalis muscle but not the procerus muscle, Type B patterns showed improvements in the vertical crease and horizontal forehead line. Both types showed improvement in glabellar frown lines after conventional injection, but the horizontal forehead line did not improve in Type B. Type B wrinkles improved after additional injections into the frontalis muscle. This study provided novel anatomical findings related to the injection of glabellar frown lines with BoNT. Preliminary analysis and optimized procedures using US will enable more effective and safer injections. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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10 pages, 1707 KiB  
Article
Practical Application of Novel Test Methods to Evaluate the Potency of Botulinum Toxin: A Comparison Analysis among Widely Used Products in Korea
by Ji-Yeon Hong, Jong-Hee Kim, Jung-Eun Jin, Sun-Hye Shin and Kui-Young Park
Toxins 2021, 13(12), 833; https://doi.org/10.3390/toxins13120833 - 23 Nov 2021
Cited by 2 | Viewed by 3385
Abstract
The safe and effective dosing of botulinum neurotoxins (BoNTs) requires accurate and reliable methods to measure their potency. Several novel methods have been introduced over the past decade; however, only few studies have compared the potency of BoNT products with that of the [...] Read more.
The safe and effective dosing of botulinum neurotoxins (BoNTs) requires accurate and reliable methods to measure their potency. Several novel methods have been introduced over the past decade; however, only few studies have compared the potency of BoNT products with that of the LD50 and other alternative assays. Therefore, the objective of this study was to comparatively evaluate widely used BoNT products using various test methods. Four types of BoNTs (prabotulinumtoxin A, onabotulinumtoxin A, neubotulinumtoxin A, and letibotulinumtoxin A) were used in this study. The estimated potency was assessed using the LD50 assay, and the total BoNT type A protein levels were measured using the enzyme-linked immunosorbent assay (ELISA). The in vitro efficacy of the BoNTs was determined using fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) assays. The results showed differences in the total amount of BoNT protein and the cleavage activity of SNAP-25 within all types of BoNTs. The SPR study seemed to be useful for evaluating the potency by specifically measuring intact 19S neurotoxin, and these results provide new insights for assessing different BoNT products. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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14 pages, 1629 KiB  
Article
The Impact of the Course of Disease before Botulinum Toxin Therapy on the Course of Treatment and Long-Term Outcome in Cervical Dystonia
by Harald Hefter, Isabelle Schomaecker, Max Schomaecker, Dietmar Rosenthal and Sara Samadzadeh
Toxins 2021, 13(7), 493; https://doi.org/10.3390/toxins13070493 - 16 Jul 2021
Cited by 3 | Viewed by 2370
Abstract
This study analyses the influence of the course of the disease of idiopathic cervical dystonia (CD) before botulinum toxin (BoNT) therapy on long-term outcomes. 74 CD-patients who were treated on a regular basis in the botulinum toxin outpatient department of the University of [...] Read more.
This study analyses the influence of the course of the disease of idiopathic cervical dystonia (CD) before botulinum toxin (BoNT) therapy on long-term outcomes. 74 CD-patients who were treated on a regular basis in the botulinum toxin outpatient department of the University of Düsseldorf and had received at least 3 injections were consecutively recruited after written informed consent. Patients were asked to rate the amount of change of CD in relation to the severity of CD at begin of BoNT therapy (IMPQ). Then they had to draw the course of disease of CD from onset of symptoms until initiation of BoNT therapy (CoDB-graph) on a sheet of paper into a square of 10 × 10 cm2 size. Remaining severity of CD was estimated by the treating physician using the TSUI-score. Demographical and treatment related data were extracted from the charts of the patients. Depending on the curvature four different types of CoDB-graphs could be distinguished. Time to BoNT therapy, increase of dose and improvement during BoNT treatment were significantly (p < 0.05) different when patients were split up according to CoDB-graph types. The lower the age at onset of symptoms, the shorter was the time to therapy (p < 0.02). Initial dose (p < 0.04) and actual dose (p < 0.009) were negatively correlated with the age of the patients at recruitment. The course of disease of CD before BoNT therapy has influence on long-term outcome. This has implications on patient management and information on the efficacy of BoNT treatment. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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8 pages, 1454 KiB  
Article
Application of Botulinum Neurotoxin Injections in TRAM Flap for Breast Reconstruction: Intramuscular Neural Arborization of the Rectus Abdominis Muscle
by Kyu-Ho Yi, Hyung-Jin Lee, Ji-Hyun Lee, Kyle K. Seo and Hee-Jin Kim
Toxins 2021, 13(4), 269; https://doi.org/10.3390/toxins13040269 - 9 Apr 2021
Cited by 18 | Viewed by 2071
Abstract
Breast reconstruction after mastectomy is commonly performed using transverse rectus abdominis myocutaneous (TRAM) flap. Previous studies have demonstrated that botulinum neurotoxin injections in TRAM flap surgeries lower the risk of necrosis and allow further expansion of arterial cross-sectional diameters. The study was designed [...] Read more.
Breast reconstruction after mastectomy is commonly performed using transverse rectus abdominis myocutaneous (TRAM) flap. Previous studies have demonstrated that botulinum neurotoxin injections in TRAM flap surgeries lower the risk of necrosis and allow further expansion of arterial cross-sectional diameters. The study was designed to determine the ideal injection points for botulinum neurotoxin injection by exploring the arborization patterns of the intramuscular nerves of the rectus abdominis muscle. A modified Sihler’s method was performed on 16 rectus abdominis muscle specimens. Arborization of the intramuscular nerves was determined based on the most prominent point of the xyphoid process to the pubic crest. All 16 rectus abdominis muscle specimens were divided into four muscle bellies by the tendinous portion. The arborized portions of the muscles were located on the 5–15%, 25–35%, 45–55%, and 70–80% sections of the 1st, 2nd, 3rd, and 4th muscle bellies, respectively. The tendinous portion was located at the 15–20%, 35–40%, 55–60%, and 90–100% sections. These results suggest that botulinum neurotoxin injections into the rectus abdominis muscles should be performed in specific sections. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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11 pages, 2637 KiB  
Article
Effective Locations for Injecting Botulinum Toxin into the Mentalis Muscle; Cadaveric and Ultrasonographic Study
by Da-Yae Choi, Hyungkyu Bae, Jung-Hee Bae, Hee-Jin Kim and Kyung-Seok Hu
Toxins 2021, 13(2), 96; https://doi.org/10.3390/toxins13020096 - 27 Jan 2021
Cited by 14 | Viewed by 9229
Abstract
The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed [...] Read more.
The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed to rejuvenate the lower face. Forty-four adult hemifaces from five Thai cadavers and 21 Korean cadavers were dissected to identify the locations of the mentalis muscle. Sixty-six hemifaces from 33 healthy young Korean subjects were included in an ultrasonographic study. The depth of the mentalis muscle below the skin surface, the thickness of the mentalis muscle, and the distance from the bone to the mentalis muscle were measured at the two points that were 5 mm lateral to the most-prominent point of the chin. The mentalis muscle was classified into two types based to its shape: in type A (86.4%, 38 of the 44 cases) it was dome shaped in three dimensions, while in type B (13.6%, 6 of the 44 cases) it was flat. The mentalis muscle was present mostly at the area 5–10 mm from the midsagittal line and 20–30 mm from a horizontal line connecting the mouth corners. The mentalis muscle was present between depths of 6.7 to 10.7 mm below the skin. This new information about the location of the mentalis muscle may help when identifying the most effective and safe botulinum toxin injection points and depths during esthetic procedures for weakened facial rhytides on the lower face. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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Review

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13 pages, 1138 KiB  
Review
Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan
by Masamitsu Hyodo, Kento Asano, Asuka Nagao, Kahori Hirose, Maya Nakahira, Saori Yanagida and Noriko Nishizawa
Toxins 2021, 13(12), 840; https://doi.org/10.3390/toxins13120840 - 25 Nov 2021
Cited by 9 | Viewed by 2431
Abstract
Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that [...] Read more.
Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90–95% of all cases; 3.5–7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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12 pages, 2233 KiB  
Review
Botulinum Neurotoxin Type A in the Treatment of Facial Seborrhea and Acne: Evidence and a Proposed Mechanism
by Nark-Kyoung Rho and Young-Chun Gil
Toxins 2021, 13(11), 817; https://doi.org/10.3390/toxins13110817 - 19 Nov 2021
Cited by 14 | Viewed by 6945
Abstract
Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing [...] Read more.
Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of facial seborrhea and acne with botulinum neurotoxin type A. Full article
(This article belongs to the Special Issue Botulinum Toxins in Clinical Practice)
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