Cyclodextrin (CD) derivatives bearing multicharged side chains exhibit enhanced host-guest binding, with higher selectivity and affinity compared with natural CDs, due to their deep cavities, polar binding sites and electrostatic interactions. To further understand the relationship between their structures and molecular recognition, molecular dynamics simulations were performed on a series of multicharged CD hosts with per-6-substituted side chains and their oppositely charged guests. In the case of rocuronium bromide (ROC) as the guest, umbrella sampling identified glutamic acid-substituted γ-CD as the host, exhibiting the strongest host-guest binding, with a free energy of -103.1 kJ mol-1, followed in descending order by aspartic acid-substituted γ-CD, glycine-substituted γ-CD, succinic acid-substituted γ-CD, sugammadex, and adamgammadex. Meanwhile, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis showed similar rankings, suggesting that electrostatic interactions play a dominant role in binding, while hydrophobic interactions, van der Waals forces, hydrogen bonding, and host-guest geometric complementarity act synergistically to stabilize the complexes. In addition, edrophonium@succinic acid-substituted β-CD and simvastatin@ammonium-substituted β-CD complexes were also evaluated, exhibiting binding free energies of -98.42 and -59.77 kJ mol-1, respectively. These findings provide mechanistic insights into CD derivative recognition and offer theoretical guidance for the rational design and experimental screening of high-affinity hosts.

Ocular myasthenia gravis (OMG) is characterized by symptoms confined to the extraocular muscles and progresses to generalized myasthenia gravis (GMG) in approximately half of patients, most commonly within two years of onset. Several predictors of generalization have been identified, including anti-acetylcholine receptor (AChR) antibody seropositivity, abnormal repetitive nerve stimulation (RNS) findings, older age at onset, thymoma, and greater disease severity. However, the prognostic significance of early relapse frequency in OMG remains poorly defined. We report a patient with OMG marked by early, recurrent relapses who subsequently progressed to GMG. A 69-year-old male presented with a three-day history of diplopia. Neurological examination revealed no bulbar, respiratory, or limb weakness. Laboratory testing showed elevated anti-AChR antibody levels (12 nmol/L), and RNS demonstrated a significant decremental response in the trapezius and nasalis muscles. Imaging studies revealed no evidence of thymoma. Based on ocular symptoms and supportive serological and electrophysiological findings, a diagnosis of OMG was established. High-dose intravenous methylprednisolone led to complete resolution of symptoms. Despite maintenance therapy with low-dose oral prednisolone, the patient experienced relapses of diplopia and ptosis at two and four months after onset, each requiring additional courses of high-dose intravenous methylprednisolone. During this period, no generalized muscle weakness was observed, and anti-AChR antibody titers remained stable. Seven months after onset, the patient developed dyspnea and bulbar symptoms, accompanied by a marked increase in anti-AChR antibody levels (81 nmol/L). Clinical deterioration, abnormal respiratory parameters, and a positive edrophonium test confirmed progression to GMG. Plasma exchange resulted in rapid clinical improvement, and symptoms were subsequently controlled with prednisolone and tacrolimus. In this case, relapses at months two and four occurred in the absence of generalized weakness and preceded generalization at month seven, suggesting that early, frequent relapses may represent a potential predictor of generalization in OMG. These findings underscore the potential importance of relapse frequency as a clinical marker and emphasize the need for treatment strategies in OMG aimed not only at symptom control but also at preventing generalization.

Cavernous sinus dural arteriovenous fistulas (CS-DAVF) can mimic ocular myasthenia gravis (OMG), as both may present with diplopia and ptosis. Differentiating between these conditions is critical because misdiagnosis can delay appropriate vascular treatment. Herein, we present the case of a 63-year-old woman who presented with a one-month history of diplopia and left-sided ptosis. Repeated edrophonium tests were positive, leading to an initial diagnosis of OMG. Immunotherapy led to a transient improvement, with decreased Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis scores. However, persistent diplopia and a new conjunctival injection raised the suspicion of CS-DAVF. Magnetic resonance imaging and angiography revealed enlargement of the left cavernous sinus, while digital subtraction angiography confirmed a left CS-DAVF. This case demonstrates the diagnostic challenges in distinguishing OMG from CS-DAVF. Even when clinical findings and bedside tests strongly suggest OMG, atypical ocular signs, such as conjunctival injection or chemosis, should prompt consideration of CS-DAVF. Careful interpretation of edrophonium results and timely neuroimaging are essential to avoid misdiagnosis.

A 44-year-old man with spinal and bulbar muscular atrophy (SBMA) and an anterior mediastinal tumor presented with ptosis and diplopia with diurnal variation. Dysarthria, dysphagia, and limb weakness deteriorated acutely, and developed respiratory failure. Repetitive nerve stimulation resulted in a decremental response. Ice pack and edrophonium tests were positive. Myasthenia gravis (MG) was diagnosed based on the presence of anti-acetylcholine receptor (AChR) antibodies. Immunotherapy improved the myasthenic symptoms. Although a few cases of SBMA exhibiting myasthenic symptoms have been reported, none of these patients had anti-AChR antibodies. This is the first report of seropositive MG with comorbid SBMA.

Acetylcholinesterase (AChE) is a cholinergic enzyme called acetylcholine acetylhydrolase. Acetylcholinesterase inhibition is one of the prominent methods in studies on pest control management. In this study, AChE was purified 103.7-fold from Loxostege sticticalis (L.) using an Edrophonium-Sepharose 6B affinity column, and some kinetic properties were investigated. The molecular weight of the purified enzyme was determined by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). Inhibition studies of AChE were realized with tacrine, edrophonium chloride, and cypermethrin, which are known inhibitors of AChE, as well as aqueous extracts of certain plant leaves. The subunit molecular weight of purified AChE was estimated to be approximately 56 kDa by SDS-PAGE analysis. The maximum activity of Loxostege sticticalis AChE was specified at 40.0 °C and pH 8.0. Vmax, Km, and kcat values of the AChE were determined as 243.9 ± 15.7 EU/mg protein, 0.122 ± 0.06 mM, and 13.7 ± 2.7 min[-1], respectively. In the inhibition studies, the IC50 values of tacrine, edrophonium chloride and cypermethrin were found to be 3.4 ± 0.5, 0.08 ± 0.006 and 85.0 ± 4.1 μM, respectively. Besides, the IC50 values of aqueous extracts of olive leaf, alder leaf, walnut leaf, cherry laurel leaf, and plane leaf were as 12.0 ± 0.6, 15.2± 1.3, 32.1 ± 1.5, 58.3 ± 1.9, and 75.2 ± 2.8 µg dry matter/mL, respectively. In addition, the oleuropein and phenolic substance amounts of these plant extracts were determined and correlated with the IC50 values. Consequently, the plant extracts used in this study may be recommended as an alternative biopesticide source to control such pests via AChE inhibition.

Anti-GQ1b antibody syndrome is a spectrum of autoimmune neurological disorders that includes Miller Fisher syndrome, Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis, and acute ophthalmoplegia without ataxia. These conditions are characterized by the presence of immunoglobulin G (IgG) antibodies targeting GQ1b gangliosides. The coexistence of anti-GQ1b antibody syndrome and myasthenia gravis (MG) is rare and presents diagnostic and therapeutic challenges. We report the case of an 84-year-old Japanese man with overlapping features of both disorders, describing his clinical course and response to add-on treatment with the neonatal Fc receptor antagonist efgartigimod. He presented with fever and diarrhea, followed by acute limb weakness. He was initially suspected of having had a stroke but was later diagnosed with GBS based on areflexia, anti-ganglioside antibody positivity, and nerve conduction abnormalities. Intravenous immunoglobulin therapy was initiated but his condition worsened, leading to respiratory failure and mechanical ventilation. Subsequently, bilateral ptosis and eye movement dysfunction emerged, prompting the consideration of MG. Anti-acetylcholine receptor antibodies and tensilon test results were positive and high-dose methylprednisolone was administered, resulting in partial improvement. Plasmapheresis was performed, but profound limb weakness and respiratory failure persisted; intravenous efgartigimod was thus introduced. Remarkably, the patient's respiratory function improved within 7 days, leading to ventilator weaning, and his limb weakness showed notable recovery. After a second cycle of efgartigimod, the patient regained speech and independent mobility, allowing transfer to a rehabilitation facility. His case underscores the diagnostic complexity of overlapping anti-GQ1b antibody syndrome and MG, and it highlights the therapeutic potential of efgartigimod in treating refractory cases of overlapping autoimmune neuromuscular syndromes. Given the rapid efficacy of efgartigimod for improving both respiratory and motor functions in this case, it is apparent that efgartigimod can be a valuable therapeutic option in complex neuromuscular autoimmune conditions.

The challenge of treating of Myasthenia Gravis (MG) stems from the multiple underlying mechanisms, the varied presentations, the need for chronic immunotherapy, and the long-term consequences of treatment. The disease itself is varied with clinical presentations ranging from droopy eyes to respiratory failure. The underlying etiology may be paraneoplastic or one of several identified antibodies that affect the post-synaptic neuromuscular junction. Treatment strategies vary depending on all of these factors. There are limited medications available for symptomatic treatment of the neuromuscular junction while most treatment focuses on immunotherapy to limit the immune response. Thymectomy is beneficial for most patients with thymoma and many with antibody positive disease. Choosing the right treatments to maximize benefits and limit adverse effects of the medicines is crucial in this chronic disease.

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder primarily characterized by fluctuating skeletal muscle weakness. While it typically presents with ocular or generalized symptoms, vocal cord paralysis (VCP) as an initial manifestation is exceedingly rare and often leads to diagnostic delays. We report the case of an 86-year-old Japanese woman who developed progressive hoarseness, dysphagia, and respiratory distress approximately one week after receiving the inactivated herpes zoster vaccine (Shingrix®). Initial evaluation revealed unilateral VCP, which progressed to bilateral paralysis, requiring emergency intubation and subsequent tracheostomy. Despite extensive imaging and laboratory investigations, the etiology remained unclear until the patient developed diplopia and ptosis around hospital day 25. Although both anti-acetylcholine receptor (AChR) and anti-muscle-specific kinase (MuSK) antibodies were negative, the diagnosis of MG was confirmed through positive edrophonium and ice pack tests. Treatment included pyridostigmine, plasma exchange, and immunosuppressive therapy with tacrolimus and prednisolone. While ptosis improved, bilateral VCP and diplopia persisted at one year, and the patient remained tracheostomy-dependent but functionally independent. This case adds to the limited literature on laryngeal-type MG, a focal subtype marked by bulbar symptoms and often negative for AChR antibodies. Our review of post-2000 literature identified 13 cases of MG with VCP, 10 of which presented with VCP initially. Notably, nine required airway management, underscoring the potential for rapid respiratory compromise. This is the first reported case of MG development temporally associated with herpes zoster vaccination. Although a definitive causal link cannot be established, the close temporal sequence - fever and systemic immune activation shortly after vaccination, followed by MG onset - raises the possibility of an immune-mediated trigger. Previous reports have described MG onset after various other vaccines, including HPV, HBV, influenza, and COVID-19, suggesting that vaccination may rarely unmask or precipitate MG in susceptible individuals. Nonetheless, large-scale studies have not demonstrated a significant increase in autoimmune disease following vaccination, supporting the overall safety of immunization programs. This case highlights the importance of recognizing atypical MG presentations such as isolated VCP, particularly in the context of recent immune stimulation. Early diagnosis and appropriate treatment are critical for improving outcomes and preventing life-threatening complications such as airway obstruction. Heightened clinical suspicion is warranted in similar scenarios to facilitate timely intervention.

Pembrolizumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death protein 1 (PD-1) receptor on T cells, enhances the immune system's ability to recognize and attack cancer cells. However, immune-related adverse events (irAEs) may arise, necessitating careful monitoring during treatment. Here, we present the case of a 47-year-old woman who developed multiple irAEs following pembrolizumab therapy. Initially diagnosed with Stage IIIB non-small cell lung cancer, she underwent chemotherapy followed by concurrent chemoradiotherapy. After two years of monitoring, progression of disease was observed, and pembrolizumab was initiated as second-line chemotherapy. Shortly thereafter, she presented with left-sided ptosis and weakness in both upper and lower extremities. Diagnostic evaluation, including a tensilon test and laboratory findings, confirmed with myositis, hepatitis, and myasthenia gravis. Treatment with steroids and neostigmine led to marked clinical improvement. Two months later, the patient developed additional dermatological symptoms, including rash and pruritus. Skin biopsy confirmed a diagnosis of pityriasis lichenoides. She is currently receiving antihistamines therapy, with no further exacerbation. This case underscores the importance of recognizing and promptly managing irAEs associated with ICIs to ensure patient safety and treatment efficacy.

No information is available on the use of edrophonium during breastfeeding. However, because of its short half-life and quaternary ammonium structure, it is unlikely to be excreted into breastmilk or orally absorbed by the infant. Administering the drug just after breastfeeding and waiting 2 to 3 hours before breastfeeding again should avoid any adverse reactions in the infant.