Search Results (83)

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or synkinesis and eventually improving asymmetry. This narrative review summarizes relevant literature on the use of BoNT-A for facial paralysis. It provides a summary of dosing strategies and treatment plans, discusses the use of functional scales for assessing facial paralysis and improvement after treatment, and outlines the use of electromyography (EMG) or ultrasound-guided injections to improve treatment outcomes. Finally, it discusses its potential role in the preparation for functional microsurgery. We also present the authors’ anecdotal experience, with three case reports: a woman with facial paralysis caused by Ramsay Hunt Syndrome, treated with a full-face and neck BoNT-A protocol and followed-up for 18 months with photographic documentation, to further assess the aesthetic improvement; a young woman with familiarity of facial paralysis, contralateral hyperkinesis, and synkinesis, managed with EMG-guided and landmark-guided injections; and her mother, with recurrent facial paralysis and chronic synkinesis, treated with stepwise BoNT-A sessions. All three cases demonstrated clinically meaningful improvements, as evidenced by the photographic material and functional grading scores presented. Full article

Botulinum toxin suppresses neurotransmitter release, thereby inhibiting muscle contraction and inducing flaccid paralysis. Botulinum toxin type A (BoNT/A) is widely used for neuromuscular blockade but, upon repeated administration, may cause long-lasting muscle atrophy, fibrosis, and inflammation. It is produced as a single peptide chain that becomes activated through cleavage into a heavy and light chain. BoNT/E, like BoNT/A, is produced as a single-chain polypeptide and requires cleavage to generate the active dichain form. Although BoNT/E is known to have a faster onset and shorter duration of action compared with BoNT/A, its efficacy and safety have not been thoroughly investigated. We compared BoNT/E and BoNT/A in SKH-1 hairless mice. Neuromuscular blockade, recovery pattern, and changes in muscle weight, volume, fiber size, fibrosis, mast cell infiltration, and diffusion to adjacent muscles were evaluated over time. BoNT/E induced maximal neuromuscular blockade on day 3 and fully recovered by day 35, whereas BoNT/A reached maximal effect on day 7 and showed only 20% recovery of the vehicle group by day 35. BoNT/E caused transient, dose-dependent reductions in muscle weight, volume, fiber size, and fibrosis, which largely normalized by day 35. In contrast, BoNT/A, administered at a dose of 0.5 U per injection site, induced persistent muscle atrophy, fibrosis, and significantly increased mast cell infiltration under the experimental conditions used in this study. Neither BoNT/E nor BoNT/A showed diffusion to adjacent muscles or changes in body weight. These findings suggest that BoNT/E provides rapid onset, short duration, and favorable safety, supporting its potential as an alternative therapeutic option for indications requiring temporary muscle relaxation with minimized long-term adverse effects. Full article

Botulinum neurotoxins (BoNTs) act on peripheral cholinergic nerve terminals, inducing reversible muscle paralysis and profound therapeutic effects. However, their limited cell-type specificity and narrow therapeutic window have motivated the development of engineered variants. Here, a modular strategy was employed to construct full-length chimeric BoNTs, grafting receptor-binding segments from BoNT/B or BoNT/F onto the BoNT/A framework. The novel chimeras AAAF and AAFF efficiently cleaved rSNAP-25 in cell-free assays. Firstly, both toxins showed effective cellular uptake and cleaved endogenous SNAP-25 in Neuro-2a cells, with cleavage efficiencies of approximately 46% for AAAF and 73% for AAFF, highlighting the enhanced activity of AAFF. Secondly, AAAF induced faster recovery from reversible muscle paralysis compared to rBoNT/A-WT, whereas AAFF produced more sustained paralysis, with both exhibiting reduced systemic toxicity. Despite these altered pharmacological profiles, the chimeras required higher doses than rBoNT/A-WT to induce neuromuscular effects. Collectively, this study presents the design of novel chimeric BoNT/A-F proteins, characterizes their functional activities, and provides a preliminary exploration of how domain grafting affects cellular uptake, enzymatic activity, and neuromuscular pharmacodynamics. Full article

Background/Objectives: Perioperative neurocognitive disorders (PND), including postoperative delirium and cognitive dysfunction (POCD), represent significant complications in elderly surgical patients undergoing general anesthesia. The choice of neuromuscular blockade reversal agent may influence POCD risk through different mechanisms and side effects. This systematic review and meta-analysis evaluated the comparative effect of neostigmine versus sugammadex on POCD incidence in elderly patients. Methods: A systematic search of PubMed, Web of Science, Scopus, and Google Scholar was conducted from database inception to September 2025, following PRISMA 2020 guidelines with PROSPERO registration (CRD420251058187). Randomized controlled trials involving elderly patients (≥60 years) undergoing general anesthesia with neuromuscular blockade were included, comparing neostigmine and sugammadex for reversal. Primary outcomes included POCD incidence, assessed using validated cognitive tools, including the Mini-Mental State Examination and Montreal Cognitive Assessment. Meta-analysis was performed using Review Manager 5.4.1, with results expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Six randomized controlled trials involving 795 elderly patients published between 2017 and 2024 met the inclusion criteria. Studies encompassed non-cardiac surgery, robotic-assisted radical cystectomy, and pars plana vitrectomy. Pooled meta-analysis showed neostigmine was associated with a higher risk of POCD than sugammadex (OR 1.74, 95% CI 1.00–3.02, p = 0.05), with low heterogeneity (I² = 39%). Secondary outcomes, including prevention of POCD, management strategies, and related complications, were inconsistently reported and unavailable across all six RCTs. Subgroup analysis stratified by neostigmine dosage demonstrated that administration of a higher dose (≥0.04 mg/kg) was associated with reduced POCD incidence compared to a lower dose (<0.04 mg/kg) (OR 0.31, 95% CI 0.15–0.63, p = 0.001), with negligible heterogeneity (I² = 0%). Conclusions: This meta-analysis suggests that sugammadex may be associated with reduced early postoperative neurocognitive disorders compared to neostigmine in elderly patients, likely through rapid neuromuscular blockade reversal that minimizes residual paralysis and respiratory complications. Full article

Background: Variants in the ryanodine receptor 1 (RYR1) gene have been linked to a range of disorders, from congenital myopathy to adult-onset manifestations, with phenotypes varying from mild to severe. Methods: A retrospective review was conducted on an Israeli cohort of 36 individuals with RYR1 variants, identified through genetic testing as part of a national collaboration among multiple pediatric and adult neuromuscular clinics. Clinical features, molecular data, laboratory results, electromyographic findings, and muscle histology were analyzed. Each variant was classified according to its respective domain within the RYR1 gene. Results: Thirty-six cases were included in the analysis; 31 were from 11 unrelated families, and 5 were sporadic. Nine individuals were asymptomatic with normal CK levels. Most of the 27 affected patients presented with variable degrees of perinatal weakness, often accompanied by respiratory impairment or arthrogryposis. Weakness was predominantly proximal, with clinical courses that included deterioration, improvement, or stabilization. Three cases of King–Denborough syndrome were identified. Additional presentations included malignant hyperthermia and, in isolated cases, periodic paralysis. Muscle biopsies demonstrated considerable histologic heterogeneity, including fiber-size variation, internal nuclei, multiminicores, and fibrosis or dystrophic features. The pathogenic RYR1 variants included five compound-heterozygous genotypes, two homozygous variants, and two heterozygous variants. There was a positive correlation between variants located in the Bsol domain and disease severity. Conclusions: This cohort confirms and expands the clinical and histological diversity associated with RYR1 variants in Israel. Variants in the Bsol domain appear to be indicative of disease severity. Full article

Background: Cobras (Naja sp.) are medically important snakes in Thailand. Envenoming by the monocled cobra (N. kaouthia) often causes neurotoxicity, most notably ptosis, ophthalmoplegia, local tissue necrosis and progressive paralysis leading to respiratory failure. Early antivenom administration and respiratory support are medically significant for effective treatment. Methods: In this study, we determined the association between the time course of cobra envenoming and related neurotoxic outcomes using the clinical profiles of cobra envenomed patients. We also demonstrated histopathological changes in the neuromuscular junction of the diaphragm in experimentally envenomed rats. Results: A retrospective study of 69 cases of cobra envenoming in Central and Southern Thailand shows that delayed arrival beyond one hour at hospital was common among younger adults (47.0% aged 10–29) and associated with more severe neurotoxicity, including higher rates of ptosis (41.2%, p = 0.032) and referrals (41.2% vs. 15.4%, p = 0.040). Antivenoms (22 Monovalent and 1 Polyvalent) were administered to 23 (33.3%) envenomed victims and caused adverse reactions in 9 cases (39.1%). Neurotoxicity following cobra envenoming in the clinical section correlated with histopathological examination of envenomed rat diaphragms. Transmission electron microscopy (TEM) revealed degeneration of the neuromuscular junction and diaphragm within 1 h following experimental cobra envenomation, which worsened by 4 h. Intravenous administration of antivenom at recommended doses reduced diaphragmatic damage but failed to prevent presynaptic degeneration after 90 min of envenoming. Conclusions: Clinically, extraocular muscle paralysis was the earliest manifestation. Early monitoring and prompt administration of antivenom are essential to reduce neurotoxicity and relevant complications. Full article

Background/Objectives: Rapid sequence intubation (RSI) involves nearly simultaneous administration of a rapid-acting induction agent and a neuromuscular blocking agent (NMBA) to facilitate ideal intubation conditions. The NMBAs most commonly used for RSI are succinylcholine and rocuronium, which cause paralysis for 5–15 min and 45–70 min, respectively. Awareness with paralysis can occur in patients who are given longer-acting NMBAs with delayed initiation of post-intubation sedation or insufficient sedation depth. The previous literature has associated the use of rocuronium with a significantly longer time to sedation and analgesia. However, a recent study found no difference. The purpose of this study was to assess the association between paralytic agent choice and time to initiation of analgesia and/or sedation after RSI in the emergency department (ED) of a large tertiary care hospital. Methods: This study was an institutional review board (IRB)-approved, single-center, retrospective cohort evaluation of adult patients (≥18 years of age) who received succinylcholine or rocuronium following administration of an induction agent in the ED for RSI during the study time period. The primary outcome was time to initiation of post-intubation analgesia and/or sedation. Continuous data were analyzed by using Mann–Whitney U or Student’s t-test, and categorical data were analyzed using the Chi Square test or Fisher’s Exact test. Results: A total of 400 patients were included in this study. The median time to sedation with succinylcholine was 9 min compared to 14 min with rocuronium (p < 0.01). No significant differences were identified in the baseline characteristics or secondary outcomes related to induction agent choice or ED length of stay. Conclusions: The results of this study further support that the use of rocuronium for RSI is associated with a significantly longer time to sedation and/or analgesia, making emergency medicine provider awareness essential for minimizing the risks associated with inadequate post-intubation sedation. Full article

Objectives: Facial paralysis is a devastating yet frequent complication of skull base surgery, significantly impacting quality of life through functional impairments and psychosocial consequences. Management is complex and requires an individualized approach based on duration of paralysis, etiology and extent of nerve injury, overall prognosis, and rehabilitative goals. This review provides a comprehensive overview of current strategies for managing post-skull base surgery facial paralysis. Methods: A narrative review of the literature was performed, analyzing surgical reanimation techniques (nerve grafting, nerve transfers, regional and free muscle transfers), static procedures for facial symmetry and ocular protection, and non-surgical interventions such as physical therapy, botulinum toxin injections, and psychological support. Key criteria guiding treatment selection, including muscle viability and timing since injury, were examined. Results: Dynamic surgical approaches remain central to restoring movement. Nerve grafting and transfers are effective when viable musculature is present, whereas regional or free muscle transfers are required in long-standing paralysis with irreversible atrophy. Static procedures provide adjunctive improvements in resting symmetry and eye protection. Non-surgical strategies, including rehabilitation therapy and botulinum toxin, enhance functional outcomes and reduce synkinesis. Psychological counseling addresses the profound emotional burden associated with facial disfigurement. Across modalities, individualized treatment planning is crucial. Conclusions: Management of facial paralysis after skull base surgery demands a multidisciplinary, patient-centered approach. Combining surgical and non-surgical interventions optimizes functional and aesthetic outcomes, helping restore both facial movement and psychosocial well-being. Full article

The common krait (Bungarus caeruleus) and the endemic Sri Lankan krait (B. ceylonicus) are two species of krait responsible for envenomings in Sri Lanka that result in progressive neuromuscular paralysis. We characterised the in vitro neurotoxicity of B. ceylonicus and B. caeruleus venoms and studied their neutralisation by two commercially available Indian polyvalent antivenoms (i.e., VINS and BHARAT), Thai banded krait antivenom and Australian polyvalent antivenom using the chick biventer cervicis nerve-muscle preparation. Both venoms displayed concentration-dependent neurotoxicity, showing equipotent pre-synaptic neurotoxicity at 0.03 μg/mL. At a higher concentration (1 μg/mL), both venoms showed post-synaptic neurotoxicity, with B. ceylonicus venom being more potent. VINS was unable to neutralise the neurotoxicity of B. ceylonicus venom, but neutralised both pre- and post-synaptic neurotoxicity of B. caeruleus venom. BHARAT neutralised in vitro pre- and post-synaptic activity of both B. ceylonicus and B. caeruleus venoms. Banded krait antivenom and Australian polyvalent antivenoms were unable to fully neutralise the neurotoxicity of either venom at tested concentrations. In conclusion, B. ceylonicus venom shows pre- and post-synaptic neurotoxicity similar to B. caeruleus venom. BHARAT effectively neutralises both pre- and post-synaptic neurotoxicity of B. ceylonicus venom. Both Indian polyvalent antivenoms effectively neutralise neurotoxicity induced by B. caeruleus venom. Full article

Background/Objectives: Guillain–Barré syndrome (GBS) is a rare autoimmune peripheral neuropathy that affects both the myelin sheaths and axons of the peripheral nervous system. It is the leading cause of acute neuromuscular paralysis worldwide, with an annual incidence of less than two cases per 100,000 people. Although most patients recover, a small proportion do not regain mobility and even remain dependent on mechanical ventilation. In this study, we refer to the analysis of samples collected from GBS patients at different defined time points during hospital recovery and performed by a medical or research group. Methods: The conditions for whole blood collection, peripheral blood mononuclear cell isolation, and serum collection from GBS patients and volunteer donors are explained. Aliquots of these human samples have been used for red blood cell phenotyping, transcriptomic and proteomic analyses, and serum biochemical parameter studies. Results: The initial sporadic preservation of human samples from GBS patients and control volunteers enabled the creation of a biobank collection for current and future studies related to the diagnosis and treatment of GBS. Conclusions: In this article, we describe the laboratory procedures and the integration of a GBS biobank collection, local medical services, and academic institutions collaborating in its respective field. The report establishes the intra-disciplinary and inter-institutional network to conduct long-term longitudinal studies on GBS. Full article

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive disease that degeneratively damages both upper and lower motor neurons, eventually resulting in muscular paralysis and death. Although ALS is broad in scope and commonly thought of as a motor neuron disease, more active research sheds light on the that role skeletal muscle plays in the development and progression of the disease. Muscle tissue in ALS patients and in animal models demonstrates severe regenerative deficits, including impaired myogenesis and impaired myoblast fusion. In ALS, muscle stem cells, known as satellite cells, show poor performance in activation, proliferation, and differentiation and thus contribute to ALS muscle wasting. Moreover, the pathological tissue environment that inhibits myoblast fusion is made up of proinflammatory cytokines, oxidative stress, and a lack of trophic signals from the neuromuscular junction, which greatly disrupts homeostatic regulation. It is likely that skeletal muscle is instead a dynamic player, fueling neuromuscular degeneration as opposed to a passive responder to denervation. One must appreciate the cellular and molecular changes that complicate muscle regeneration in ALS for effective treatment to be developed, permitting simultaneous interventions with both muscle and neurons. Full article

Background/Objectives: Non-invasive spinal cord transcutaneous stimulation (scTS) has expanded the therapeutic landscape of spinal cord injury (SCI) rehabilitation, offering potential benefits beyond compensatory approaches to paralysis. Children with SCI are particularly susceptible to developing neuromuscular scoliosis due to trunk muscle paralysis and ongoing skeletal growth, making targeted interventions crucial. As demonstrated in adults and pediatrics with SCI, the ability of scTS to acutely and safely enable an upright posture and trunk control could be leveraged as a therapeutic adjunct. Activity-based locomotor training (AB-LT) alone significantly improves trunk control in children with SCIs; combining it with scTS may enhance outcomes. This pilot study evaluated the safety, feasibility, and cumulative effects of AB-LT combined with scTS on trunk control in children with SCI. Methods: Three children with SCI completed 19 to 64 sessions of combined AB-LT and scTS. Adverse effects were monitored session to session, and trunk control was assessed pre- and post-intervention. Results: Across 130 interventions in three participants, 88.5% of sessions were free from adverse effects. Reported adverse events included autonomic dysreflexia (5.4%), skin redness at electrode sites (4.6%), and headaches (1.5%). No significant impact of scTS on fatigue or central hemodynamic parameters was observed. Post-intervention, all participants demonstrated improved trunk control during quiet and perturbed sitting. Conclusions: These findings provide the first evidence supporting the safety and feasibility of this combinatorial approach in pediatric SCI rehabilitation while emphasizing the importance of monitoring skin integrity and signs of autonomic dysreflexia. This intervention shows potential synergistic benefits, warranting further research to confirm efficacy and optimize therapeutic protocols. Full article

Sugammadex represents a significant advancement in neuromuscular blockade management, enabling rapid, predictable, and highly effective reversal of steroidal neuromuscular blockers such as rocuronium and vecuronium. This review critically examines recent advances in sugammadex research, particularly over the last decade, detailing its pharmacological profile, clinical efficacy, and safety compared to traditional reversal agents, like neostigmine. Its expanding clinical applications across operating rooms, critical care units, and emergency medicine are discussed, emphasizing dosing recommendations and clinical utility in special patient populations, including individuals with renal impairment, pediatric, obstetric, and obese patients. Economic considerations are explored, highlighting sugammadex’s cost-effectiveness through reduced postoperative complications and enhanced operational efficiency, despite higher initial costs. Finally, the review outlines ongoing research directions, including emerging reversal agents, advanced neuromuscular monitoring technologies, and potential future clinical applications, underscoring sugammadex’s evolving role in improving patient safety and anesthetic practice. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS. Full article