Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Interventions for infantile esotropia.

BACKGROUND: Infantile esotropia (IE) is the inward deviation of the eye. Various aspects of the clinical management of IE are unclear; mainly, the most effective type of intervention and the age at intervention. OBJECTIVES: To examine the effectiveness and optimal timing of surgical and non-surgical treatment options for IE to improve ocular alignment and achieve or allow the development of binocular single vision. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers (November 2021). We did not use any date or language restrictions in the electronic searches for trials.  SELECTION CRITERIA: We included randomized trials and quasi-randomized trials comparing any surgical or non-surgical intervention for IE. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification. MAIN RESULTS: We included two studies with 234 children with IE. The first study enrolled 110 children (mean age 26.9 ± 14.5 months) with an onset of esotropia before six months of age, and large-angle IE defined as esotropia of ≥ 40 prism diopters. It was conducted between 2015 and 2018 in a tertiary care hospital in South Africa. It compared a maximum of three botulinum toxin injections with surgical intervention of bimedial rectus muscle recession, and children were followed for six months. There were limitations in study design and implementation; the risk of bias was high, or we had some concerns for most domains.  Surgery may increase the incidence of treatment success, defined as orthophoria or residual esotropia of ≤ 10 prism diopters, compared with botulinum toxin injections, but the evidence was very uncertain (risk ratio (RR) of treatment success 1.88, 95% confidence interval (CI) 1.27 to 2.77; 1 study, 101 participants; very low-certainty evidence). The results should be read with caution because 23 children with > 60 prism diopters at baseline in the surgery arm also received botulinum toxin at the time of surgery to augment the recessions. There was no evidence of an important difference between surgery and botulinum toxin injections for over-correction (> 10 prism diopters) of deviation (RR 0.29, 95% CI 0.06 to 1.37; 1 study, 101 participants; very low-certainty evidence), or additional interventions required (RR 0.66, 95% CI 0.36 to 1.19; 1 study, 101 participants; very low-certainty evidence). No major complications of surgery were observed in the surgery arm, while children experienced various complications in the botulinum toxin arm, including partial transient ptosis in 9 (16.7%) children, transient vertical deviation in 3 (5.6%) children, and consecutive exotropia in 13 (24.1%) children. No other outcome data for our prespecified outcomes were reported.  The second study enrolled 124 children with onset of esotropia before one year of age in 12 university hospitals in Germany and the Netherlands. It compared bilateral recession with unilateral recession surgeries, and followed children for three months postoperatively. Very low-certainty evidence suggested that there was no evidence of an important difference between bilateral and unilateral surgeries in the presence of binocular vision (numbers with event unclear, P = 0.35), and over-correction (RR of having exotropia 1.09, 95% CI 0.45 to 2.63; 1 study, 118 participants). Dissociated vertical deviation, latent nystagmus, or both were observed in 8% to 21% of participants. AUTHORS' CONCLUSIONS: Medial rectus recessions may increase the incidence of treatment success compared with botulinum toxin injections alone, but the evidence was very uncertain. No evidence of important difference was found between bilateral surgery and unilateral surgery.  Due to insufficient evidence, it was not possible to resolve the controversies regarding type of surgery, non-surgical intervention, or age of intervention in this review. There is clearly a need to conduct good quality trials in these areas to improve the evidence base for the management of IE.

The comparisons of different therapeutic modalities for idiopathic achalasia: A systematic review and network meta-analysis.

BACKGROUND: : Current guidelines recommend per-oral endoscopic myotomy (POEM) and laparoscopic Heller's myotomy (LHM) as first-line treatment of idiopathic achalasia, but the optimum choice between different endoscopic and surgical modalities remains inconclusive. We conducted a network meta-analysis to compare the efficacy of 8 treatments for idiopathic achalasia. MATERIALS AND METHODS: : Three major bibliographic databases were reviewed for enrollment of randomized controlled trials between January 2000 and June 2021. We included adults with idiopathic achalasia and compared two or more of eight interventions including botulinum toxin injection (BTI), pneumatic dilation (PD), BTI + PD, LHM without fundoplication, LHM followed with Dor or Toupet fundoplication, and POEM using either the anterior or posterior approach. Our focus was on clinical success rate, postsurgical acid reflux, and moderate-to-severe adverse events. RESULTS: : Twenty-four studies involved a total of 1987 participants for analysis. When compared with PD, POEM with anterior approach, POEM with posterior approach, LHM + Toupet, and LHM + Dor were all significantly superior to the other regimens in short-term efficacy, with POEM with anterior approach and LHM + Dor showing better improvement in mid-term efficacy. BTI showed a significantly lower efficacy than PD in both periods. Regarding safety, only LHM without fundoplication was significantly associated with higher acid reflux than PD, while LHM + Toupet, LHM without fundoplication, and LHM + Dor showed a non-significant increase in moderate-to-severe adverse events. CONCLUSIONS: : For idiopathic achalasia, we suggest that POEM with an anterior or posterior approach and LHM with Dor or Toupet fundoplication be initially recommended. On the contrary, both LHM without fundoplication and BTI are not recommended as definitive therapy.

Comprehensive Assessment of the Time Course of Biomechanical, Electrophysiological and Neuro-Motor Effects after Botulinum Toxin Injections in Elbow Flexors of Chronic Stroke Survivors with Spastic Hemiplegia: A Cross Sectional Observation Study.

Botulinum neurotoxin (BoNT) is commonly used to manage focal spasticity in stroke survivors. This study aimed to a perform comprehensive assessment of the effects of BoNT injection. Twelve stroke subjects with spastic hemiplegia (age: 52.0 ± 10.1 year; 5 females) received 100 units of BoNT to the spastic biceps brachii muscles. Clinical, biomechanical, electrophysiological, and neuro-motor assessments were performed one week (wk) before (pre-injection), 3 weeks (wks) after, and 3 months (mons) after BoNT injection. BoNT injection significantly reduced spasticity, muscle strength, reflex torque, and compound muscle action potential (CMAP) amplitude of spastic elbow flexors (all p < 0.05) during the 3-wks visit, and these values return to the pre-injection level during the 3-mons visit. Furthermore, the degree of reflex torque change was negatively correlated to the amount of non-reflex component of elbow flexor resistance torque. However, voluntary force control and non-reflex resistance torque remained unchanged throughout. Our results revealed parallel changes in clinical, neurophysiological and biomechanical assessment after BoNT injection; BoNT injection would be more effective if hypertonia was mainly mediated by underlying neural mechanisms. BoNT did not affect voluntary force control of spastic muscles.

Safety and Efficacy of Botulinum Toxin in the Treatment of Self-Biting Behavior in Lesch-Nyhan Disease.

BACKGROUND: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting. METHODS: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. We retrospectively analyzed six patients with LND who were treated with BoNT to prevent automutilatory behavior. RESULTS: The patient ages when started on treatment with BoNT were 4, 4.5, 6.6, 7.9, 13.9, and 32.3 years. Patients received a mean number of injections of 20, ranging from 3 to 29, over a period that ranged from 1.5 to 7.1 years. The maximum total dose of Botox was 21.3 units/kg mean and the maximum total dose of Dysport was 37.5 units/kg mean. A total of 119 injections were performed. Of these 113 (95%) were partially or completely effective. Only three of 119 injections (2.5%) produced adverse effects. CONCLUSIONS: Botulinum toxin is useful and safe for the treatment of self-biting behavior in patients with LND.

Forehead Movement Discrepancies After Botulinum Toxin Injections: A Review of Etiology, Correction, and Prevention.

BACKGROUND: Forehead rhytides are a popular target for botulinum toxin injections, but neuromodulation of the frontalis can be fraught with complications because of its anatomic complexity and integral role in brow position and expressivity. OBJECTIVE: This article explores common forehead movement discrepancies that can occur after neuromodulation of the frontalis, as well as how to correct and prevent them. METHODS: A review of the literature was conducted and combined with clinical experience to examine underlying forehead anatomy, etiology and correction of forehead movement discrepancies, and important factors to consider before injecting the frontalis with botulinum toxin. RESULTS AND CONCLUSION: Variable anatomy from person to person necessitates an individualized treatment approach to achieve the best cosmetic results and prevent the occurrence of forehead movement discrepancies.

Safety and efficacy of botulinum neurotoxin in the treatment of erectile dysfunction refractory to phosphodiesterase inhibitors: Results of a randomized controlled trial.

BACKGROUND: There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. OBJECTIVES: To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). PATIENTS AND METHODS: A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment. RESULTS: Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p < 0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. CONCLUSION: BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy.

Techniques to Relieve Pain Associated With Botulinum Injections for Palmar and Plantar Hyperhidrosis.

BACKGROUND: Palmar and plantar hyperhidrosis (HH) is a common condition characterized by excessive sweating of the palms and soles. Botulinum neurotoxin (BTX) is a very effective and safe treatment. However, the associated intense injection pain is a major limiting factor deterring patients from selecting this treatment. OBJECTIVE: The aim of this study was to review the numerous techniques used to minimize pain accompanying injections for palmoplantar HH. Additionally, the advantages and limitations of each modality will be discussed. MATERIALS AND METHODS: The authors performed a comprehensive literature search in PubMed/MEDLINE, Embase, Cochrane Central, and Google Scholar on randomized controlled trials, cohort studies, and case series on techniques to relieve pain of BTX injections for treatment of palmar and plantar HH. RESULTS: Current available techniques in reducing botulinum injection with merits and drawbacks are nerve blocks, Bier blocks, cryoanalgesia, needle-free anesthesia, topical anesthetics, and vibration anesthesia. CONCLUSION: Topical anesthesia, ice, and vibration are the safest and most convenient noninvasive available methods to relieve pain associated with botulinum injection. Nerve blocks, Bier block, and needle-free anesthesia provide better anesthesia but are limited by the need for training and equipment.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

In vivo non-invasive near-infrared spectroscopy distinguishes normal, post-stroke, and botulinum toxin treated human muscles.

In post-stroke hemiparesis, neural impairment alters muscle control, causing abnormal movement and posture in the affected limbs. A decrease in voluntary use of the paretic arm and flexed posture during rest also induce secondary tissue transformation in the upper limb muscles. To obtain a specific, accurate, and reproducible marker of the current biological status of muscles, we collected visible (VIS) and short-wave Infrared (SWIR) reflectance spectra in vivo using a portable spectroradiometer (350-2500 nm), which provided the spectral fingerprints of the elbow flexors and extensors. We compared the spectra for the affected and unaffected sides in 23 patients with post-stroke hemiparesis (25-87 years, 8 women) and eight healthy controls (33-87 years, 5 women). In eight patients, spectra were collected before and after botulinum toxin injection. Spectra underwent off-line preprocessing, principal component analysis, and partial least-squares discriminant analysis. Spectral fingerprints discriminated the muscle (biceps vs. triceps), neurological condition (normal vs. affected vs. unaffected), and effect of botulinum toxin treatment (before vs. 30 to 40 days vs. 110 to 120 days after injection). VIS-SWIR spectroscopy proved valuable for non-invasive assessment of optical properties in muscles, enabled more comprehensive evaluation of hemiparetic muscles, and provided optimal monitoring of the effectiveness of medication.

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.

Botulinum Toxin Services for Neurorehabiliation: Recommendations for Challenges and Opportunities during the COVID-19 Pandemic.

The COVID-19 pandemic severely impacted the function of medical facilities and rehabilitation services worldwide, including toxin services delivering Botulinum toxin treatments for neuromuscular conditions such as spasticity, dystonia, and sialorrhea. The aim of this paper is to understand how toxin services have dealt with the situation and what strategies have been adopted to continue services. The recommendations are based on a virtual round table held with toxin services experts from different European countries who shared their experiences and discussed the best practices. The challenges for toxin services were reviewed based on the experts' experiences and on relevant literature from 2020 and 2021. A set of recommendations and best practices were compiled, focusing firstly on guidance for clinical practice, including assessing patients' health and risk status and the urgency of their treatment. Secondly, it was discussed how patients on botulinum toxin therapy can be cared for and supported during the pandemic, and how modern technology and tele-medicine platforms can be generally used to optimize effectiveness and safety of toxin treatments. The technological advances prompted by the COVID-19 crisis can result in better and more modern patient care in the future.

Anatomical locations of the motor endplates of sartorius muscle for botulinum toxin injections in treatment of muscle spasticity.

PURPOSE: This study aimed to detect the idyllic locations for botulinum neurotoxin injection by analyzing the intramuscular neural distributions of the sartorius muscles. METHODS: An altered Sihler's staining was conducted on sartorius muscles (15 specimens). The nerve entry points and intramuscular arborization areas were measured as a percentage of the total distance from the most prominent point of the anterior superior iliac spine (0%) to the medial femoral epicondyle (100%). RESULTS: Intramuscular neural distribution were densely detected at 20-40% and 60-80% for the sartorius muscles. The result suggests that the treatment of sartorius muscle spasticity requires botulinum neurotoxin injections in particular locations. CONCLUSIONS: These locations, corresponding to the locations of maximum arborization, are suggested as the most suggestive points for botulinum neurotoxin injection.

The auditory startle response in relation to outcome in functional movement disorders.

BACKGROUND: The auditory startle reflex (ASR) is enlarged in patients with functional movement disorders (FMD). OBJECTIVES: To study whether the ASR relates to symptom reduction in FMD patients, who participated in a placebo controlled double blind treatment trial with Botulinum Neurotoxin (BoNT). METHODS: Response to treatment in the BoNT study was assessed using the Clinical Global Impression - Improvement scale (CGI-I). The electromyography (EMG) muscle activity of 7 muscles following 110 dB tones was measured in 14 FMD patients before and after one-year treatment and compared to 11 matched controls. The early and a late (behaviorally affected) component of the ASR and the sympathetic skin response (SSR) were assessed. RESULTS: 10 of 14 patients (71.4%) showed symptom improvement, which was believed to be mainly caused by placebo effects. The early total response probability of the ASR at baseline tended to be larger in patients compared to controls (p = 0.08), but normalized at follow-up (p = 0.84). The late total response probability was larger in patients vs. controls at baseline (p < 0.05), a trend that still was present at follow-up (p = 0.08). The SSR was higher in patients vs. controls at baseline (p < 0.01), and normalized at follow-up (p = 0.71). CONCLUSIONS: On a group level 71.4% of the patients showed clinical symptom improvement after treatment. The early part of the ASR, most likely reflecting anxiety and hyperarousal, normalized in line with the clinical improvement. Interestingly, the augmented late component of the ASR remained enlarged suggesting persistent altered behavioral processing in functional patients despite motor improvement.

The Role of Ultrasound for the Personalized Botulinum Toxin Treatment of Cervical Dystonia.

The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among experts that some of the most relevant muscles in this indication can be safely injected under visual US guidance. This review will explore the method from basic technical considerations, current evidence to conceptual developments of the phenomenology of cervical dystonia. We will review the implications of introducing US to our understanding of muscle function and anatomy of common cervical dystonic patterns. We suggest a flow chart for the use of US to achieve a personalized treatment of people with CD. Thus, we hope to contribute a resource that is useful in clinical practice and that stimulates the ongoing development of this valuable technique.

Nonlinear Changes in Botulinum Toxin Treatment of Task-Specific Dystonia during Long-Term Treatment.

Botulinum toxin (BoTX) is the standard treatment for task-specific dystonias (TSDs) such as musician's dystonia (MD). Our aim was to assess the long-term changes in BoTX treatment in a highly homogeneous and, to our knowledge, largest group of MD patients with respect to the following parameters: (1) absolute and (2) relative BoTX dosage, (3) number of treated muscles, and (4) inter-injection interval. We retrospectively assessed a treatment period of 20 years in 233 patients, who had received a cumulative dose of 68,540 MU of BoTX in 1819 treatment sessions, performed by two neurologists. Nonlinear correlation was used to analyze changes in the parameters over the course of repeated treatments. Post-hoc we applied a median-split to classify two subgroups (high-BoTX, low-BoTX) depending on the total amount of BoTX needed during treatment. Across all patients, we found a decrease of dosage for the first approximately 25 treatments with an increase afterwards. The number of muscles and inter-injection intervals increased with time with a discrete decrease of inter-injection intervals after about 35 treatments. Subgroup differences were observed in the amount of BoTX and inter-injection intervals, with continuously increasing inter-injection intervals and decreasing BoTX dosage in the low-BTX group. Both groups showed a continuously increasing number of injected muscles. In summary, we found nonlinear changes of BoTX dosage and inter-injection intervals and a continuously increasing number of injected muscles with treatment duration in TSD-patients. Furthermore, we, for the first time, identified two subgroups with distinct differences. Increasing inter-injection intervals and decreasing BoTX dosages in the low-BoTX group indicated improvement of symptoms with continued treatment. Continually increasing BoTX dosages with unchanged inter-injection intervals in the high-BoTX group indicated deterioration.