A systematic review of procedural modalities in the treatment of notalgia paresthetica.

BACKGROUND: Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP. AIMS: We sought to comprehensively evaluate the role of procedural treatments for NP. METHODS: We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included. RESULTS: Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases. CONCLUSION: Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.

Combined rehabilitation therapy with botulinum toxin to the upper limbs for acute spinal cord injury: A case report.

INTRODUCTION: Patients with spinal cord injury (SCI) and incomplete paralysis may experience muscle immobilization due to functional impairment of agonist and antagonist muscles. This can induce spasticity and pain, with the risk of contracture increasing as the period of immobilization increases. This could be aggravated by pain, which interferes with rehabilitation. There is no established treatment for pain and joint contractures caused by acute SCI. Botulinum therapy plays a role in relieving muscle tension. Here, we report a case of acute SCI in which botulinum therapy was administered. CASE PRESENTATION: The patient experienced a C5-cervical SCI due to a road traffic accident, with marked paralysis in the upper and lower limbs below the C5 level. The patient had persistent elbow flexion since the SCI and complained of excruciating pain, making adequate rehabilitation difficult. Botulinum toxin was administered to the biceps and brachialis muscles 15 days after the SCI. After administration, the patient experienced a reduction in pain with relaxation of the elbow flexor muscles, and rehabilitation treatment was resumed. This patient's contracture did not worsen, his pain decreased, and he was able to initiate self-feeding training. DISCUSSION: In this case, occupational and physical therapy was administered with botulinum therapy. Together, they successfully reduced pain. Botulinum therapy provides analgesia and muscle relaxation and may lead to functional recovery, and we believe that treatment can be considered even in the acute phase.

Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A.

More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a putative membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT), which is the most toxic protein and has paradoxically emerged as a potent reagent for therapeutic and cosmetic applications. Nevertheless, no structural analysis on AEDs and BoNT recognition by full-length SV2A has been available. Here we describe the cryo-electron microscopy structures of the full-length SV2A in complex with the BoNT receptor-binding domain, BoNT/A2 HC, and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 HC through protein-protein and protein-glycan interactions. LEV and BRV occupy the putative substrate-binding site in an outward-open conformation. A propyl group in BRV creates additional contacts with SV2A, explaining its higher binding affinity than that of LEV, which was further supported by label-free spectral shift assay. Numerous LEV derivatives have been developed as AEDs and positron emission tomography (PET) tracers for neuroimaging. Our work provides a structural framework for AEDs and BoNT recognition of SV2A and a blueprint for the rational design of additional AEDs and PET tracers.

Parietal abdominal pain with lower leg discrepancy: a case report.

BACKGROUND: This report involves the first publication describing a case of parietal abdominal pain due to lower limb length discrepancy. CASE PRESENTATION: A Caucasian male patient in his 50s was referred to our rehabilitation department with chronic abdominal pain that began in childhood. This chronic pain was associated with episodes of acute pain that were partially relieved by grade 3 analgesics. The patient was unable to sit for long periods, had recently lost his job, and was unable to participate in recreational activities with his children. Investigations revealed contracture and hypertrophy of the external oblique muscle and an limb length discrepancy of 3.8 cm (1.5 inches) in the left lower limb. The patient was effectively treated with a heel raise, physiotherapy, intramuscular injection of botulinum toxin, and lidocaine. The patient achieved the therapeutic goals of returning to work, and reducing analgesic use. CONCLUSIONS: Structural misbalances, as may be caused by lower leg discrepancy, may trigger muscular compensations and pain. Complete anamnesis and clinical examination must not be trivialized and may reveal previously ignored information leading to a proper diagnosis.

Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

INTRODUCTION: Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application. CASE PRESENTATIONS: In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application. RESULTS: The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended. CONCLUSIONS: Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.

Why do marionette lines appear? Exploring the anatomical perspectives and role of thread-based interventions.

The pathogenesis of marionette lines involves a complex interplay of anatomical, physiological, and age-related factors leading to the development of wrinkles around the oral commissures. This exploration delves into the distinct anatomical predispositions observed among different ethnicities, emphasizing the role of compact modiolus structures and muscle compositions. Notably, individuals of East Asian descent exhibit inherent facial structures that predispose them to pronounced sagging around the oral commissures during aging. The emergence of distinct facial lines, such as the commissural line and the melolabial fold, contributes to the formation of marionette lines. This specific wrinkle pattern, resembling a marionette puppet's mouth contours, is influenced by various factors like bone resorption, gravitational forces, fat compartment variations, muscle compression, ligament tethering, and skin aging. Treatment strategies for marionette lines encompass diverse interventions, including filler injections, botulinum neurotoxin, surgeries targeting fat reduction, thread lifting, and volumizing fillers. These approaches aim to address the underlying causes and mitigate the appearance of marionette lines. Botulinum neurotoxin injections, for instance, weaken specific facial muscles, reducing downward strain and aiding in tissue retraction. Anatomical considerations during procedures are crucial to avoid nerve or vascular damage. Delicate manipulation and precise entry points are essential to prevent inadvertent injuries, particularly concerning blood vessels like the facial artery and nerves like the mental nerve. Technical guidelines for procedures targeting marionette lines involve specific techniques like cogged thread reverse methods and volumizing thread placements. Attention to entry points, tissue engagement, and the direction of threads is crucial for effective treatment outcomes, minimizing complications, and ensuring patient safety.

[Achalasia cardiae causing megaesophagus: "From the beginnings to the resolution"]. / Megaoesophagust okozó achalasia cardiae: "a kezdetektol a megoldásig".

Achalasia cardiae miatt az elso oesophago-cardia myotomiát több mint száz évvel ezelott Ernst Heller német sebész végezte. Az achalasiás betegek a mai napig ettol a beavatkozástól várják panaszaik megszunését. Az achalasia napjainkban is chronikus, progresszív betegség, aminek oki kezelését nem ismerjük, a gyógyítására, a panaszok enyhítésére gyógyszeres (calcium csatorna blokkolók stb.), endoscopos (botulinum toxin inj., ballonos tágítás, per oralis endoscopos myotomiát [POEM]) és sebészi (laparoscopos, thoracoscopos myotomia) kezeléseket váltakozó sikerrel alkalmazunk.A betegség progresszivitása miatt a betegek 5%-ánál a nyelésképtelenségig fokozódó dysphagia, megaoesophagus alakul ki, megoldására mutéti beavatkozás válik szükségessé. A muködésképtelen nyelocso eltávolítása és pótlása kiterjedt, nem elhanyagolható morbiditással és mortalitással járó beavatkozás. Közleményünkben egy 45 éves nobeteg kórtörténetét, az általunk alkalmazott mutéti beavatkozást ismertetjük. A beteg a mutét óta panaszmentes.

Recent Developments in Engineering Non-Paralytic Botulinum Molecules for Therapeutic Applications.

This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic forms of botulinum neurotoxin due to concerns about muscle function loss. We highlight the research findings that confirm not only the effectiveness of these molecules but also their reduced paralytic effect. We also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the spatial parameters of the new botulinum molecules. In summary, this article reviews the current research that enhances our understanding of the application of new botulinum neurotoxins in the context of common conditions and suggests new avenues for developing more efficient molecules.

Sequelae Treatment Needs Following Peripheral Facial Palsy: Retrospective Analysis of 525 Patients.

OBJECTIVE: This study uses retrospective longitudinal data from a large unselected cohort of patients with peripheral facial paralysis to determine the prevalence and patient characteristic predictors of sequelae receiving intervention. STUDY DESIGN: Retrospective case review. SETTING: Karolinska University Hospital in Stockholm Sweden serves as the only tertiary facial palsy center in the region. Here, patients are diagnosed, are followed up, and undergo all major interventions. PATIENTS: All adult patients presenting with peripheral facial palsy due to idiopathic, zoster, or Borrelia origin at Karolinska, January 1, 2010 to December 31, 2011 with follow-up until December 2022. INTERVENTIONS: Patient charts were studied to identify patient characteristics, etiology, initial treatment, severity of palsy, and treatments targeting sequelae. MAIN OUTCOME MEASURES: Types of initial and late treatments were noted. Sunnybrook and/or House-Brackmann scales were used for palsy grading. RESULTS: Five hundred twenty-five patients were included. Thirty-three patients (6.3%) received botulinum toxin injections and/or surgical treatment. In this subgroup, 67% received corticosteroids compared to 85% of all patients ( p = 0.005), cardiovascular disease prevalence was higher (23 and 42%, respectively, p = 0.009). For 81 patients (15%), follow-up was discontinued although the last measurement was Sunnybrook less than 70 or House-Brackmann 3 to 6. CONCLUSIONS: Of patients with peripheral facial palsy, 6.3% underwent injections and/or surgical treatment within 12 years. However, due to a rather large proportion not presenting for follow-up, this might be an underestimation. Patients receiving late injections and/or surgical treatment had more comorbidities and received corticosteroid treatment to a significantly lower extent in the acute phase of disease.

Musician's dystonia in a percussionist - clinical video analysis and botulinum toxin intervention: a case report.

OBJECTIVE: Musician's focal hand dystonia is a painless task-specific focal dystonia, which presents with involuntary movements, abnormal postures, and loss of fine motor dexterity. We report here the case of a 63-year-old male, percussionist, with african ethnicity, with musician's focal hand dystonia who was treated with botulinum toxin, and describe the results at 4-weeks follow up. METHODS: Clinical examination and video analysis revealed abnormal flexion of the 3rd finger, followed by flexion of the 4th and 5th fingers while playing the congas. Based on these findings, a diagnosis of musician's focal hand dystonia was established. Ten units of botulinum toxin were injected into the muscle fibres of the flexor digitorum superficialis corresponding to the 4th finger using electromyography and ultrasound guidance. Four weeks later, the patient reported a subjective 60% improvement in his performance. He emphasized the effect of botulinum toxin on performance speed and tension over the forearm and hand. CONCLUSION: Botulinum toxin is not a definitive treatment for musician's focal hand dystonia, but it may potentiate other definitive rehabilitation techniques. More research is needed to determine the long-term effects of botulinum toxin on function enhancement in musician's focal hand dystonia.

Impact of Botulinum Toxin Injections on Quality of Life of Patients with Long-Standing Peripheral Facial Palsy.

(1) Background: Sequels of facial palsy lead to major psychosocial repercussions, disrupting patients' quality of life (QoL). Botulinum toxin (BoNT) injections can permit us to treat long-standing facial palsy, improving facial symmetry and functional signs including synkinesis and contractures. (2) Methods: The main aim of this study was to assess the evolution of the QoL for patients with long-standing facial palsy before, at 1 month, and at 4 months after BoNT injections by using three questionnaires (HFS-30, FaCE, and HAD). The other goals were to find clinical factors associated with the improvement in the QoL and to assess the HFS-30 questionnaire for patients with unilateral facial palsy (3) Results: Eighty-eight patients were included in this study. There was a statistically significant improvement in QoL at 1 month after injections, assessed using the three questionnaires. This improvement was sustained at 4 months after the injections, with a statistically significant difference for the HFS-30 and FaCE questionnaires. (4) Conclusions: This study showed that the BoNT injections lead to a significant increase in the QoL of patients with unilateral facial palsy. This improvement is sustained 4 months after the injections.

Botulinum Toxin Injections to Manage Sequelae of Peripheral Facial Palsy.

Long-standing facial palsy sequelae cause functional, aesthetic, and psychological problems in patients. Botulinum toxin is an effective way to manage them, but no standardized recommendations exist. Through this non-systematic review, we aimed to guide any practitioner willing to master the ins and outs of this activity. We reviewed the existing literature and completed, with our experience as a reference center, different strategies of botulinum toxin injections used in facial palsy patients, including history, physiopathology, facial analysis, dosages, injection sites, and techniques, as well as time intervals between injections. The reader will find all the theorical information needed to best guide injections according to the patient's complaint, which is the most important information to consider.

The state of the art in therapeutic administration of botulinum toxin in children with cerebral palsy: an integrative review.

OBJECTIVE: To describe the current state of the art in the therapeutic administration of botulinum toxin with indications, efficacy, and safety profile for children and adolescents with cerebral palsy. DATA SOURCE: An integrative review was conducted. The MEDLINE/PubMed database was searched twice within the last decade using distinct terms, and only studies written in the English language were included. The study population was limited to those aged 0-18 years. Articles that were duplicates or lacked sufficient methodology information were excluded. DATA SYNTHESIS: We found 256 articles, of which 105 were included. Among the included studies, most were conducted in developed countries. Botulinum toxin demonstrated good safety and efficacy in reducing spasticity, particularly when administered by a multidisciplinary rehabilitation team. It is primarily utilized to improve gait and upper limb function, facilitate hygiene care, reduce pain, prevent musculoskeletal deformities, and even decrease sialorrhea in patients without a functional prognosis for walking. CONCLUSIONS: The administration of botulinum toxin is safe and efficacious, especially when combined with a multi-professional rehabilitation team approach, which increases the probability of functional improvement. It can also be beneficial for patients with significant functional impairments to help with daily care tasks, such as hygiene, dressing, and reducing sialorrhea. Pediatricians must be familiar with this treatment and its indications to attend to and refer patients promptly when necessary, and to exploit their neuroplasticity. Further research on this topic is required in developing countries.

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle.

The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A recent structural study of the translocation domain of BoNTs suggests that the interaction with the membrane is driven by the transition of an α helical switch towards a ß hairpin. Atomistic simulations in conjunction with the mesoscopic Twister model are used to investigate the consequences of this proposition for the toxin-membrane interaction. The conformational mobilities of the domain, as well as the effect of the membrane, implicitly examined by comparing water and water-ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central two α helices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using the Twister model, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit an origin for the mechanism opening the membrane to be proposed.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review.  Results: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses.  Conclusions: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties.  J Drugs Dermatol. 2024;23(3):173-186. doi:10.36849/JDD.7243e.

Intensive Voice Treatment following Botulinum Neurotoxin Injection for a Speaker with Abductor Laryngeal Dystonia: An Exploratory Case Study.

Abductor laryngeal dystonia (ABLD) is a rare neurological voice disorder which results in sporadic opening of the vocal folds during speech. Etiology is unknown, and to date there is no identified effective behavioral treatment for it. It is hypothesized that LSVT LOUD®, which was developed to treat dysphonia secondary to Parkinson's disease, may have application to speakers with ABLD to improve outcomes beyond that with botulinum neurotoxin (BoNT) treatment alone. The participant received one injection of BoNT in each vocal fold 2 to 3 months prior to initiating intensive voice therapy via teletherapy. Objective measures of vocal loudness (dB sound pressure level), maximum phonation time, and high/low pitch frequency (Hz) were recorded in all treatment sessions and follow-up sessions. Over the course of treatment, the participant showed steady gains in phonation time, volume, pitch range, and vocal quality with a substantial reduction in aphonic voice breaks by the end of the treatment program. Perceptual symptoms of ABLD were nearly undetectable by the participant and the clinicians up to 12 months posttreatment, with no additional BoNT injections. The results suggest that LSVT LOUD® following BoNT was effective, with long-lasting improvement in vocal function, for this speaker with ABLD.