Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

Ultrasound Evaluation and Guided Injection of the Subscapularis and Serratus Anterior Muscles Between the Scapula and the Thoracic Cage: A Technical Note.

Most subscapularis and serratus anterior muscles lie between the scapula and the thoracic cage. Evaluation of this area in patients with scapulothoracic dyskinesis, snapping scapular syndrome, or interscapular pain can provide valuable information to clinicians. However, ultrasound scanning of pathologies in this area is hindered by anatomical limitations. In this study, we described a simple patient setup position and scanning method for ultrasound evaluation and guided intervention of the subscapularis and serratus anterior muscles between the scapula and thoracic cage.

Musculoskeletal injections for palliative treatment of neuromuscular hip dysplasia patients: how I do it.

This review describes our institution's standardized technique as well as potential pitfalls for therapeutic steroid injections in children with symptomatic neuromuscular hip dysplasia. Symptomatic, painful neuromuscular hip dysplasia can dramatically affect quality of life. Steroid injections are used to identify the source of perceived pain, temporarily treat pain while awaiting surgical intervention, or for therapeutic management for nonoperative hip joints.

Does the guidance method affect the doses of botulinum toxin in writer's cramp?

PURPOSE: Botulinum neurotoxin (BoNT) injections are the main medical treatment of writer's cramp. When the outcome is favourable, patients usually receive injections several times per year in the long-term. However, we know little about the course of BoNT doses and nothing about the impact of the guidance method on the clinical outcome or injection strategy. METHODS: We studied, in the long-term, the doses of BoNT and the target muscles in a group of patients with writer's cramp, according to the guidance method (electrical stimulation or ultrasound). Patients received at least three injection cycles guided by electrical stimulation, followed by at least three injection cycles guided by ultrasound. RESULTS: Twenty-four patients were included. More target muscles were injected after switching to ultrasound guidance, especially the flexor carpi ulnaris and the flexor carpi radialis. The mean dose by muscle was lower when ultrasound guidance was used. When using electrical stimulation guidance, the dose in the flexors of the fingers decreased in the long-term, but increased in the flexors of the wrist. The course of the BoNT doses and of the number of target muscles per cycle were not the same during the first period (electrical stimulation) and the second period (ultrasound). CONCLUSIONS: Switching to ultrasound guidance, the BoNT dose decreased, mainly in the flexors of the wrist. Based on the results of our study, we suggest a starting dose in several muscles (flexor carpi ulnaris, flexor carpi radialis, flexor digitorum profundus and flexor pollicis longus).

Intramuscular nerve distribution of the sternocleidomastoid muscle for the botulinum toxin injection.

PURPOSE: The aim of this study is to define the intramuscular nerve distribution of the sternocleidomastoid muscle (SCM) and the innervation zones (IZ) to describe the optimal botulinum toxin injection sites. METHODS: The cricoid cartilage (CC), laryngeal prominence (LP) and hyoid bone (HB) and angle of mandible (AM) were determined as landmarks. The length of the muscles were measured between the sternoclavicular joint and tip of the mastoid process. SCM was evaluated in two parts as anterior and posterior divided by the line where the length of the muscle was measured. Measurements were made to define the relationships of the SCM with common carotid artery, internal and external jugular veins. IZ were described according to these vessels. Afterwards, Modified Sihler's staining technique was applied to expose the intramuscular nerve distribution. RESULTS: The average length of SCM was 160,1 mm. Motor entry point of the accessory nerve fibers were between the AM-HB lines, in the range of 30-40% of the muscle length, and in the posterior part of the muscles. IZ were between the HB-CC lines in the anterior and posterior part. When this interval was examined according to the vessels, the optimal injection sites were between the LP-CC lines. CONCLUSIONS: This study shows the position of the intramuscular nerve fibers endings of the SCM according to the chosen landmarks and the relationship of the IZ with the vessels to prevent complications. These results can be used as a guide for safe and effective botulinum toxin injections with optimal quantities.

Pharmacokinetic and pharmacodynamic comparison of epinephrine, administered intranasally and intramuscularly: An integrated analysis.

BACKGROUND: Manual intramuscular epinephrine injection is the standard of care for treating severe allergic reactions and anaphylaxis. Epinephrine autoinjectors were approved on the basis of the assumption that their pharmacokinetic and pharmacodynamic profiles are equivalent to manual intramuscular injection; however, although there is emerging evidence for product-related differences in pharmacokinetic profiles, very little is known about the comparative pharmacodynamic profiles. OBJECTIVE: To compare pharmacokinetic and pharmacodynamic profiles of epinephrine delivered through manual intramuscular injection, autoinjectors, and intranasal spray. METHODS: This integrated analysis was based on data from 4 randomized cross-over phase 1 trials that compared the pharmacokinetics and pharmacodynamics of epinephrine using manual intramuscular epinephrine 0.3 mg injection, epinephrine 0.3 mg autoinjectors (Symjepi and EpiPen), and epinephrine 1 mg intranasal spray (neffy). RESULTS: Data from 175 participants showed that although neffy (1.0 mg intranasal spray) resulted in a maximum concentration (258 pg/mL) that was lower than or comparable with manual epinephrine intramuscular injection (254 pg/mL), Symjepi (438 pg/mL) and EpiPen (503 pg/mL), it led to comparable increases in systolic blood pressure (maximum effect [Emax], 16.9, 10.9, 14.9, and 18.1 mm Hg, respectively). The effect of neffy on diastolic blood pressure was also markedly more pronounced than that of other products (Emax, 9.32, 5.51, 5.78, and 5.93 mm Hg, respectively). CONCLUSION: Intranasal delivery of epinephrine using neffy increases systolic blood pressure more efficiently than do manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations.

Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers.

BACKGROUND: In response to the World Health Organization call for research on alternative routes for tranexamic acid (TXA) administration in women with postpartum haemorrhage, we examined the pharmacokinetics of TXA after i.v., i.m., or oral administration. METHODS: We conducted a randomised, open-label, crossover trial in 15 healthy volunteers who received i.v. TXA 1 g, i.m. TXA 1 g, or oral TXA solution 2 g. Blood samples were drawn up to 24 h after administration. Tranexamic acid concentration was measured with liquid chromatography-mass spectrometry, and the parameters of the pharmacokinetic models were estimated using population pharmacokinetics. RESULTS: The median time to reach a concentration of 10 mg L-1 was 3.5 min for the i.m. route and 66 min for the oral route, although with the oral route the target concentration was reached in only 11 patients. Median peak concentrations were 57.5, 34.4, and 12.8 mg L-1 for i.v., i.m., and oral routes, respectively. A two-compartment open model with body weight as the main covariate best fitted the data. For a 70 kg volunteer, the population estimates were 10.1 L h-1 for elimination clearance, 15.6 L h-1 for intercompartmental clearance, 7.7 L for the volume of central compartment, and 10.8 L for the volume of the peripheral compartment. Intramuscular and oral bioavailabilities were 1.0 and 0.47, respectively, showing that i.m. absorption is fast and complete. Adverse events were mild and transient, mainly local reactions and low-intensity pain. CONCLUSIONS: The i.m. (but not oral) route appears to be an efficient alternative to i.v. tranexamic acid. Studies in pregnant women are needed to examine the impact of pregnancy on the pharmacokinetics. CLINICAL TRIAL REGISTRATION: EudraCT 2019-000285-38; NCT03777488.

Dorsogluteal intramuscular injection depth needed to reach muscle tissue according to body mass index and gender: A systematic review.

AIMS AND OBJECTIVE(S): The objective of this systematic review was to determine the needle length required to reach the dorsogluteal muscle based on body mass index and sex. Our aim was to provide evidence-based recommendations to current intramuscular injection guidelines from the result(s) of this review. BACKGROUND: Studies worldwide are documenting reduced medication effectiveness due to improperly placed dorsogluteal intramuscular injections because of incorrect needle length, wrong site selection and/or obesity. Current intramuscular injection guidelines lack specific instructions according to weight or sex. While there are similar concerns with other injectable sites, this review focuses solely on adult dorsogluteal intramuscular injections. DESIGN: A systematic review of relevant literature of dorsogluteal intramuscular injections based on body mass index and sex. METHODS: This systematic review was reported using the PRISMA checklist 2020. The review protocol was registered with Center for Open Science (OSF). We analysed 1,412 articles from nine databases. We compared twelve studies that utilised computerised tomography or ultrasonography using The Johns Hopkins Evidence-Based Practice Model and Guidelines. RESULTS: A significant number of dorsogluteal intramuscular injections are administered into subcutaneous tissue rather than muscle because needles are too short for populations with body mass indexes over 25, especially women. Poor landmarking often results in improperly placed injections. CONCLUSIONS: To prevent administering a dorsogluteal intramuscular injection into subcutaneous tissue, women with a BMI of 25 and over require needles longer than 38 mm (1.5 inches). Men have less subcutaneous tissue in the dorsogluteal area and only require longer needles if BMI is 35 and over. If skin-to-muscle depth is questionable in either sex, an ultrasound-guided intramuscular injection is warranted for accurate dorsogluteal placement. Landmarking and needle length are key to appropriately placed IM injections. RELEVANCE TO CLINICAL PRACTICE: Dorsogluteal injections are often injected into subcutaneous tissue rather than muscle because needles are not long enough to reach muscle, especially in women. Critical elements that determine placement of intramuscular injections into muscle versus subcutaneous tissue are sex, BMI, needle length and landmarking. Medications delivered into subcutaneous tissue may have reduced bioavailability.

Ultrasound-Guided BoNT-A (Botulinum Toxin A) Injection Into the Subscapularis for Hemiplegic Shoulder Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND AND PURPOSE: This study aimed to assess the efficacy of an ultrasound-guided lateral approach for BoNT-A (botulinum toxin A) injections into the subscapularis in patients with hemiplegic shoulder pain. METHODS: This single-center trial used a randomized, double-blind, placebo-controlled design. The key inclusion criteria were a visual analogue scale score of ≥4 cm and a modified Ashworth scale score of ≥1+. The patients were randomized to receive either BoNT-A injections or a placebo. The outcomes included the visual analogue scale score, modified Ashworth scale score, pain-free passive range of motion of the hemiplegic shoulder, Fugl-Meyer assessment score for the upper extremities, and Stroke-Specific Quality-of-Life score. RESULTS: A total of 49 hemiplegic shoulder pain patients were screened, and 36 were included. The participants receiving the BoNT-A injection reported a significant decrease in pain (visual analogue scale, -1.39 [95% CI, -2.41 to -0.36]; P=0.002) and spasticity (modified Ashworth scale score for shoulder internal rotation, -0.72 [95% CI, -1.10 to -0.35]; P=0.001; modified Ashworth scale score for shoulder abduction, -0.44 [95% CI, -0.90 to -0.01]; P=0.026) and improved pain-free passive shoulder internal rotation range of motion (14.56 [95% CI, 6.70-21.41]; P<0.001) and quality of life (Stroke-Specific Quality-of-Life upper extremity subscale, P=0.025) compared with those receiving the placebo at the end point. The shoulder abduction range of motion did not significantly improve after the BoNT-A injection at the end point (P=0.127). In addition, the patients in the BoNT-A group showed significant improvements in the visual analogue scale score and shoulder external rotation range of motion at the 12-week follow-up. No injection-related adverse events were observed during or after the interventions in either group. CONCLUSIONS: The ultrasound-guided lateral approach for BoNT-A injections into the subscapularis is a precise and reliable method for reducing pain and spasticity and improving quality of life in stroke survivors with hemiplegic shoulder pain. Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900023513.

Effectiveness and Predictors of Discontinuation of Aripiprazole Long-acting Injection: A 12-Month Naturalistic Cohort Study.

PURPOSE/BACKGROUND: This study aimed to explore the discontinuation rate of aripiprazole long-acting injection (LAI) in a naturalistic clinical setting. METHODS/PROCEDURES: A retrospective cohort study of 1 year duration was conducted on the first 200 patients registered to receive aripiprazole LAI in Sussex, UK. Rate of discontinuation and the association of robustly recorded clinical variables with discontinuation or a new acute care episode were explored. FINDINGS/RESULTS: Of 200 registered, 173 patients initiated aripiprazole LAI and 40% discontinued this by 1 year. Mean discontinuation time was 18 weeks. The commonest discontinuation reason was "patient choice," independent of efficacy or adverse effects. Not having a diagnosis of schizophrenia spectrum was the only variable significantly associated with treatment continuation after 1 year. No single diagnostic group accounted for this, although a greater continuation rate was observed in those with bipolar disorder. Illness severity factors at baseline, including apparent treatment resistance, had no impact on later aripiprazole LAI discontinuation or on acute service use over the year. Medication-related variables had no identified impact on acute service use. IMPLICATIONS/CONCLUSIONS: This study supports the clinical utility of aripiprazole LAI for its licensed indications. The 1-year discontinuation rate is equivalent to that in reports of similarly designed studies of paliperidone LAI. Further exploration of nonmedication factors influencing LAI discontinuation is required. Preferential use of aripiprazole LAI over other medications may be supported due to fewer associated metabolic adverse effects.

Quantitative laryngeal electromyography parameters may correlate with improved outcomes following botulinum toxin injection for spasmodic dysphonia.

BACKGROUND: Despite use of qualitative laryngeal electromyography (LEMG) guided botulinum toxin A (BoNT-A) injection for treatment of adductor spasmodic dysphonia (AdSD), unsatisfactory injections and complete "misses" remain problematic. We aimed to determine if the quantitative LEMG measure of number of small segments (NSS) correlates with voice outcomes following (BoNT-A injection for AdSD. METHODS: Automated quantitative LEMG analysis was performed during electromyography (EMG) -guided BoNT-A injection into the thyroarytenoid-lateral cricoarytenoid muscle complex for treatment of AdSD. Pre-injection phonatory NSS values were correlated with clinical voice outcomes and patient reported injection results. RESULTS: Quantitative LEMG measures were obtained for 45 AdSD patients (28 female, mean age 60.8 ± 12.8 years) during EMG-guided BoNT-A injection. Mean sampled NSS during phonation immediately prior to BoNT-A injection was 524 ± 323 (range: 2-904). Mean follow up was 36.5 ± 9.4 days; one patient was lost to follow-up. In comparison to their previous BoNT-A injection, the current injection was rated as worse, same, and better by 13 (29.5%), 25 (56.8%), and 6 (13.6%) patients, respectively. All 4 (9.1%) patients with NSS < 200 rated their BoNT-A injection result as worse than previous, and change in Voice Handicap Index-10 (VHI-10) scores were worse or without change. CONCLUSIONS: Aiming for an NSS value greater than 200 during phonation prior to BoNT-A toxin injection for AdSD may reduce unfavorable voice outcomes.

A Cadaveric Study of Dye Spreading: Determining the Ideal Injection Pattern for Masseter Hypertrophy.

BACKGROUND: Masseter hypertrophy is the main cause of an asymmetrical and squared lower facial contour in the Asian community. Botulinum toxin injection technique is crucial to treat this condition. OBJECTIVE: To improve injection techniques for masseter hypertrophy by elucidating the distribution of the injections within the masseter. METHODS: Thirty masseter muscles were divided into 6 groups of 5 muscles each. Each group received one 0.2- or 0.3-mL injection at Point A, B, or C according to a three-point technique. Muscle dimensions and dye of the primary and secondary dye spreading were measured. RESULTS: The average muscle length, width, and thickness were 69.87, 33.50, and 11.23 mm, respectively. The average primary longitudinal and horizontal spreading was 36.56 and 15.60 mm, respectively. No statistically significant difference was found between 0.2- and 0.3-mL injections at each point. CONCLUSION: The three-point technique best fits in the safe zone and should be the standard injection technique for masseter hypertrophy. Injection at Points B and C may create secondary spreading that affect the risorius muscle and the parotid gland which are the cause of asymmetrical smiling and xerostomia, respectively. The dosage should be adjusted according to the muscle volume and not only the thickness.

Aesthetic ONE21 Technique for Injecting IncobotulinumtoxinA into the Forehead: Initial Experience With 86 Patients.

BACKGROUND: Treatment of upper facial lines is a common aesthetic practice; however, there is limited information on systematic tailored approaches for the treatment of forehead wrinkles using botulinum toxin A. OBJECTIVE: To describe the safety and efficacy of the ONE21 technique using incobotulinumtoxinA (INCO) for the treatment of forehead wrinkles. METHODS: Single-center, retrospective study with 86 females presenting a baseline Merz Aesthetic Scale (MAS) score ≥2 for dynamic forehead lines who had been treated with INCO using the ONE21 technique. Assessment was performed by two independent blinded raters using MAS for forehead lines (dynamic and at rest), and eyebrow positioning, based on standardized pictures taken before (baseline) and 4 (±2) weeks after treatment injection. The primary outcome was the percentage of subjects with a MAS improvement ≥2 points for dynamic forehead lines at week 4 (±2). Secondary outcomes were MAS scores for resting forehead lines and for eyebrow positioning. RESULTS: The mean age was 46.2 years, and mean total dose of INCO, 20.3 U. Most (97.7%) subjects had a MAS improvement of ≥2 points for dynamic forehead lines at week 4 (±2); 100% improved ≥1 point. MAS scores for resting and dynamic lines, and eyebrow positioning were significantly improved (P<0.001). Eyebrow positioning MAS improved ≥1 point in 56.9% of subjects, and 39.5% maintained the original shape. CONCLUSION: INCO injection using the ONE21 technique is effective and safe in treating forehead wrinkles, providing a natural result, with a customized treatment and a predictable eyebrow shape. J Drugs Dermatol. 2021;20(1):31-37. doi:10.36849/JDD.5617.

Guidelines for botulinum neurotoxin injections in piriformis syndrome.

BACKGROUND: The piriformis muscle is normally involved in piriformis syndrome and can be treated with botulinum neurotoxin using several different injection methods. However, definitive injection guidelines for the muscle have not been reported previously. AIMS: This study aimed to determine the ideal area for injections based on the intramuscular nerve distribution as obtained using a modified Sihler's staining technique. MATERIALS AND METHODS: A modified Sihler's method was applied to the piriformis muscle in 15 specimens. The intramuscular arborization areas were identified based on two anatomical landmarks: (a) the lateral border of the sacrum bone and (b) the greater trochanter. RESULTS: The nerve entry point for both piriformis muscles was found in the area between the lateral border of the sacrum and one-fifth of the distance toward the greater trochanter. The intramuscular nerve distribution for the piriformis muscle had the largest arborization patterns between one-fifth and two-fifths of the distance from the sacrum to the greater trochanter. The piriformis muscle was tendinous from two-fifths of the distance to the greater trochanter. DISCUSSION: This study has yielded suggested optimal injection locations for the piriformis muscle relative to external anatomical landmarks. CONCLUSION: Clinicians can use these guidelines to ensure the effectiveness of not only botulinum neurotoxin injections but also other agents such as steroids, anesthetics, and normal saline. These guidelines will also help to avoid adverse outcomes of injection treatments.

Anatomical guide for botulinum neurotoxin injection: Application to cosmetic shoulder contouring, pain syndromes, and cervical dystonia.

INTRODUCTION: This study proposes an ideal botulinum toxin injection point of the trapezius muscle for shoulder line contouring, pain management, and functional impairment. This study describes the intramuscular nerve branching in the trapezius muscle, providing essential information for botulinum neurotoxin injection. METHOD: A modified Sihler's method was performed on the trapezius muscles (16 specimens). The intramuscular arborization areas were elucidated regarding the external occipital protuberance superiorly, spinous process of the 12th thoracic vertebra inferiorly and acromion of the scapula. RESULT: The intramuscular neural distribution for the superior, middle, and inferior regions of the trapezius muscle had the greatest arborized patterns in the horizontal 1/5-2/5 and vertical 2/10-4/10 sections, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections, and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections, respectively. DISCUSSION: We propose that BoNT treatments should be directed to the horizontal 1/5-2/5 and vertical 2/10-4/10 sections of the superior trapezius, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections of the middle trapezius and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections of the inferior trapezius. Additionally, injective treatment at the horizontal 2/5-3/5 and vertical 2/10-4/10 nerve entry points should be avoided to prevent nerve trunk damage causing paralysis. According to our guidelines, clinicians can ensure minimal dose injections and fewer adverse effects in botulinum neurotoxin injective treatment.

Morphological characteristics of the posterior neck muscles and anatomical landmarks for botulinum toxin injections.

PURPOSE: Cervical dystonia is a common movement disorder for which botulinum toxin (BoNT) is the first choice treatment. Injecting the specific neck muscles can be challenging because of their thin morphology and deep locations. We, therefore, designed a study to investigate the locations of the posterior neck muscles to help the physician predict the locations of the targeted neck muscles and to protect the vertebral vessels from injury during deep injections. METHODS: The posterior neck region was divided into four quadrants by imaginary lines passing vertically and transversely through the spinous process of C2 vertebra (C2sp). The thicknesses and depth of the posterior neck muscles were measured in ten formaldehyde-fixed adult male cadavers. These muscles were located and a projection of them was drawn on the neck. Using the measurements, colored latex in place of BoNT was injected into them in one cadaver. The cadaver was dissected to investigate whether the muscles were colored. RESULTS: 2 cm above the C2sp, trapezius, splenius capitis (SPC) and semispinalis capitis (SSC) were colored at depths of 10.70 mm, 11.88 mm and 15.91 mm, respectively. 2 cm below the C2sp, the trapezius, SPC and SSC were colored at depths of 20.89 mm, 23.25 mm and 27.63 mm, respectively. The posterior neck muscles were had taken up their assigned colors when they were injected according to the results obtained in this study. The vertebral vessels were not colored. CONCLUSIONS: Although BoNT injection into the posterior neck muscles is challenging, we think that it can be practically and safely applied using the measurements obtained in this study.

Anatomo-sonographic identification of the longissimus capitis and splenius cervicis muscles: principles for possible application to ultrasound-guided botulinum toxin injections in cervical dystonia.

OBJECTIVE: The main objective of this study was to define and verify anatomo-sonographic landmarks for ultrasound-guided injection of botulinum toxin into the longissimus capitis (LC) and splenius cervicis (SC) muscles. METHODS AND RESULTS: After a preliminary work of anatomical description of the LC and SC muscles, we identified these muscles on two cadavers and then on a healthy volunteer using ultrasound and magnetic resonance imaging (MRI) to establish a radio-anatomical correlation. We defined an anatomo-sonographic landmark for the injection of each of these muscles. The correct positioning of vascular glue into the LC muscle and a metal clip into the SC muscle of a fresh cadaver as verified by dissection confirmed the utility of the selected landmarks. DISCUSSION: For the LC muscle, the intramuscular tendon of the cranial part of the muscle appears to be a reliable anatomical landmark. The ultrasound-guided injection can be performed within the cranial portion of the muscle, between the intra-muscular tendon and insertion into the mastoid process at dens of the axis level. For the SC muscle, the surface topographic landmarks of the spinous processes of the C4-C5 vertebrae and the muscle body of the levator scapulae muscle seem to be reliable landmarks. From these, the ultrasound-guided injection can be carried out laterally by transfixing the body of the levator scapulae. CONCLUSION: The study defined two cervical anatomo-sonographic landmarks for injecting the LC and SC muscles.

PHYSIOLOGICAL AND ANESTHETIC EFFECTS OF HAND INJECTION VERSUS DARTING TO INDUCE ANESTHESIA IN CHIMPANZEES (PAN TROGLODYTES).

Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO2, oxygen saturation (SpO2), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO2, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia.

Consensus recommendations for botulinum toxin injections in the spasticity management of children with cerebral palsy during COVID-19 outbreak

Spasticity is the most common motor disturbance in cerebral palsy (CP). Lockdown in the COVID-19 outbreak has profoundly changed daily routines, and similarly caused the suspension of spasticity treatment plans. Besides, the delay in botulinum toxin (BoNT) injection, which is important in the management of focal spasticity, led to some problems in children. This consensus report includes BoNT injection recommendations in the management of spasticity during the COVID-19 pandemic in children with CP. In order to develop the consensus report, physical medicine and rehabilitation (PMR) specialists experienced in the field of pediatric rehabilitation and BoNT injections were invited by Pediatric Rehabilitation Association. Items were prepared and adapted to the Delphi technique by PMR specialists. Then they were asked to the physicians experienced in BoNT injections (PMR specialist, pediatric orthopedists, and pediatric neurologists) or COVID-19 (pediatric infectious disease, adult infectious disease). In conclusion, the experts agree that conservative management approaches for spasticity may be the initial steps before BoNT injections. BoNT injections can be administered to children with CP with appropriate indications and with necessary precautions during the pandemic.

Distinct transduction of muscle tissue in mice after systemic delivery of AAVpo1 vectors.

The human musculature is a promising and pivotal target for human gene therapy, owing to numerous diseases that affect this tissue and that are often monogenic, making them amenable to treatment and potentially cure on the genetic level. Particularly attractive would be the possibility to deliver clinically relevant DNA to muscle tissue from a minimally invasive, intravenous vector delivery. To date, this aim has been approximated by the use of Adeno-associated viruses (AAV) of different serotypes (rh.74, 8, 9) that are effective, but unfortunately not specific to the muscle and hence not ideal for use in patients. Here, we have thus studied the muscle tropism and activity of another AAV serotype, AAVpo1, that was previously isolated from pigs and found to efficiently transduce muscle following direct intramuscular injection in mice. The new data reported here substantiate the usefulness of AAVpo1 for muscle gene therapies by showing, for the first time, its ability to robustly transduce all major muscle tissues, including heart and diaphragm, from peripheral infusion. Importantly, in stark contrast to AAV9 that forms the basis for ongoing clinical gene therapy trials in the muscle, AAVpo1 is nearly completely detargeted from the liver, making it a very attractive and potentially safer option.