LAMB2 gene disorders present with different phenotypes. Pierson syndrome (PS) is a common phenotype associated with LAMB2 variants. Neuromuscular phenotype has been reported including hypotonia and developmental delay. However, neuromuscular junction abnormalities represented as congenital myasthenic syndrome (CMS) was reported in one adult patient only. Here, in this paper, we present two pediatric cases with a severe presentation of PS and have CMS so expanding the knowledge of LAMB2 related phenotypes. The first patient had hypotonia and global developmental delay. Targeted genetic testing panel demonstrated homozygous pathogenic variant in the LAMB2 gene (c.5182C>T, pGln1728*) which was reported by Maselli et al. 2009. Repetitive nerve stimulation (RNS) showed a decremental response at low frequency of 3 Hz. On the other hand, the second patient had profound weakness since birth. Tri-Whole exome sequencing showed homozygous pathogenic variant in the LAMB2 gene c.2890C>T, pArg964*. A trial of salbutamol did not improve the symptoms. Both patients passed away from sequala of PS. The spectrum of phenotypic changes associated with LAMB2 mutations is still expanding, and further investigation into the various clinical and morphologic presentations associated with these mutations is important to better identify and manage affected individuals.

Background: Failure in early diagnosis of myasthenia gravis (MG) and the risks of taking certain medications and undergoing surgery and anesthesia can lead to severe respiratory disorders and death. However, there are therapeutic measures that significantly control the disease and improve individual\'s functionality. Methods: First, an expert panel was formed, and a needs assessment questionnaire was prepared for the information elements and the capabilities required for the application and provided to neurologists with a subspecialty fellowship in neuromuscular diseases. Then, based on the analyzed results, the application was designed and created in 2 versions (physician and patient), and in 2 languages (Persian and English). Eventually, a questionnaire for user interaction and satisfaction was provided to 5 relevant physicians to evaluate the application. Results: The results showed that neurologists considered all items of the needs assessment questionnaire to be 100% essential. The capabilities of the application included registering the medication name and dose, recording symptoms and complaints by the patient, completing standard questionnaires, online chat, medication reminder, sending alerts to the doctor when the patient is unwell, and providing a variety of reports. The usability evaluation showed that neurologists evaluated the application at a good level with the average score of 8.23 ± 0.47 (out of 9 points). Conclusion: In the long run, using this technology can reduce costs, improve patients\' quality of life (QOL) and health care, change health behaviors, and ultimately, improve individual\'s health.

Bovine spastic paresis (BSP) is a neuromuscular disorder characterized by hypertension and stiffness of hindlimb. Two Korean native cattle (Hanwoo) calves developed BSP or BSP-like symptoms, and a tenotomy of superficial tendon of medial head and deep tendon of lateral head of gastrocnemius muscle was performed for treatment. A cast was applied postoperatively to prevent muscle rupture and was removed three weeks later. The prognosis was evaluated at 3 weeks, 6 and 18 months postoperatively. Neither calf showed any other postoperative sequelae. This is the first case study to report the diagnosis, treatment, and prognosis of BSP in Hanwoo.

Located between skeletal muscle fibers and motoneurons, the neuromuscular junction is a chemical synapse essential for the transmission of information from nervous system to skeletal muscle. There are many diseases related to neuromuscular junction dysfunction, including myasthenia gravis, Lambert‑Eaton myasthenic syndrome, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and spinal muscular atrophy. The pathophysiological mechanisms of these diseases have been investigated using many animal models. Among them, mouse models are the most commonly used and have provided the majority of current data. Moreover, advances in human induced pluripotent stem cell technology has resulted in new opportunities to study neuromuscular junction disorders from both patients and healthy individuals. Currently, patient‑specific induced pluripotent stem cells derived from motor neurons have begun to be studied. These studies will help us achieve a more comprehensive understanding of diseases related to neuromuscular junction disorders. We will describe the research models of neuromuscular junction disorders and provide an overview of recent key findings.

BACKGROUND: Rarely, hyperthyroidism will initially present with chronic myopathy characterized by progressive and sometimes fluctuating proximal muscle weakness, along with elevated creatine kinase and myopathic pattern in the electromyogram, mimicking other muscle and neuromuscular junction disorders with poorer prognosis.
METHODS: Here, we present 2 young patients who complained of 1-4 months duration of chronic proximal muscle lower extremity weakness, supported by elevated creatine kinase and myopathic pattern in electromyogram, who later found to have markedly low thyroid-stimulating hormone, high free T3 and free T4, enlarged thyroid gland on ultrasound, and elevated anti-thyroid-stimulating hormone receptor antibody, characteristic of Grave disease.
CONCLUSIONS: Although rare, thyrotoxicosis should always be ruled out in a patient with chronic myopathy because this has better prognosis than other primary muscle conditions presenting similarly.

In amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome (GBS), and neuromuscular junction disorders, three mechanisms may lead, singly or together, to respiratory emergencies and increase the disease burden and mortality: (i) reduced strength of diaphragm and accessory muscles; (ii) oropharyngeal dysfunction with possible aspiration of saliva/bronchial secretions/drink/food; and (iii) inefficient cough due to weakness of abdominal muscles. Breathing deficits may occur at onset or more often along the chronic course of the disease. Symptoms and signs are dyspnea on minor exertion, orthopnea, nocturnal awakenings, excessive daytime sleepiness, fatigue, morning headache, poor concentration, and difficulty in clearing bronchial secretions. The \"20/30/40 rule\" has been proposed to early identify GBS patients at risk for respiratory failure. The mechanical in-exsufflator is a device that assists ALS patients in clearing bronchial secretions. Noninvasive ventilation is a safe and helpful support, especially in ALS, but has some contraindications. Myasthenic crisis is a clinical challenge and is associated with substantial morbidity including prolonged mechanical ventilation and 5%-12% mortality. Emergency room physicians and consultant pulmonologists and neurologists must know such respiratory risks, be able to recognize early signs, and treat properly.

Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders.
International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process.
A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies.
This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

The neuromuscular junction (NMJ), which is a synapse for signal transmission from motor neurons to muscle cells, has emerged as an important region because of its association with several peripheral neuropathies. In particular, mutations in GARS that affect the formation of NMJ result in Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. These disorders are mainly considered to be caused by neuronal axon abnormalities; however, no treatment is currently available. Therefore, in order to determine whether the NMJ could be targeted to treat neurodegenerative disorders, we investigated the NMJ recovery effect of HDAC6 inhibitors, which have been used in the treatment of several peripheral neuropathies. In the present study, we demonstrated that HDAC6 inhibition was sufficient to enhance movement by restoring NMJ impairments observed in a zebrafish disease model. We found that CKD-504, a novel HDAC6 inhibitor, was effective in repairing NMJ defects, suggesting that treatment of neurodegenerative diseases via NMJ targeting is possible.

We used α-Latrotoxin (α-LTx), the main neurotoxic component of the black widow spider venom, which causes degeneration of the neuromuscular junction (NMJ) followed by a rapid and complete regeneration, as a molecular tool to identify by RNA transcriptomics factors contributing to the structural and functional recovery of the NMJ. We found that Urocortin 2 (UCN2), a neuropeptide involved in the stress response, is rapidly expressed at the NMJ after acute damage and that inhibition of CRHR2, the specific receptor of UCN2, delays neuromuscular transmission rescue. Experiments in neuronal cultures show that CRHR2 localises at the axonal tips of growing spinal motor neurons and that its expression inversely correlates with synaptic maturation. Moreover, exogenous UCN2 enhances the growth of axonal sprouts in cultured neurons in a CRHR2-dependent manner, pointing to a role of the UCN2-CRHR2 axis in the regulation of axonal growth and synaptogenesis. Consistently, exogenous administration of UCN2 strongly accelerates the regrowth of motor axon terminals degenerated by α-LTx, thereby contributing to the functional recovery of neuromuscular transmission after damage. Taken together, our results posit a novel role for UCN2 and CRHR2 as a signalling axis involved in NMJ regeneration.

Myasthenia gravis and Lambert-Eaton myasthenic syndrome are antibody-mediated autoimmune diseases of the neuromuscular junction that usually present with weakness in ocular muscles and in proximal muscles of the limb and trunk. Prognosis regarding muscle strength, functional abilities, quality of life, and survival is generally good. However, some patients do not respond to treatment. Symptomatic drugs, corticosteroids, and steroid-sparing immunosuppressive drugs remain the cornerstone of treatment. In the past few years, new biological agents against complement, the FcRn receptor, or B-cell antigens have been tested in clinical trials. These new therapies extend the possibilities for targeted immunotherapies and promise exciting new options with a relatively rapid mode of action. Challenges in their use might occur, with barriers due to an increase in cost of care and additional considerations in the choice of drugs, and potential consequences of infection and vaccination due to the COVID-19 pandemic.