Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions.

OBJECTIVE: To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. METHODS: This retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. RESULTS: The median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8-15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. CONCLUSIONS: Ketamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

[Pathophysiology of Respiratory Failure in Neuromuscular Diseases].

Based on a recent review by Krohn et al, the respiratory center and its regulatory mechanisms are described. Although the respiratory control centers in the medulla and pons ensure rhythmic respiration, maintaining and regulating respiration involves a complex network of peripheral chemoreceptors, vagal nerves, and central chemoreceptors. This review discusses the pathophysiology of respiratory disorders in neuromuscular diseases and evaluation and treatment methods based on the anatomy of the respiratory network.

"De Novo" Hypercapnic Respiratory Failure Unmasking Neuromuscular Disorders: Experiences From a Tertiary Care Center and Review of Literature.

OBJECTIVES: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario. METHODS: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed. RESULTS: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms. DISCUSSION: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.

Multidisciplinary Treatment in Patients with Craniofacial, Neurocognitive, and Neuromuscular Disorders with Obstructive Sleep Apnea: A Systematic Review of the Literature.

Obstructive sleep apnea (OSA) is a respiratory disorder that has a high prevalence in patients with craniofacial, neurocognitive, and neuromuscular disorders. Currently, the treatments for this population are diverse and depend on the individual conditions of the patient and the severity of the case. However, there are no multidisciplinary dental treatment guidelines. The aim of the present study was to determine the multidisciplinary dental treatment alternatives in patients with craniofacial, neurocognitive, and neuromuscular disorders with a diagnosis of OSA through evidence-based medicine. A systematic review of the literature has been performed by searching scientific articles in the PubMed, Cochrane, Ovid, ScienceDirect and Scopus databases, through controlled and uncontrolled language. Articles were classified according to the level of evidence and grades of recommendation through the Scottish Intercollegiate Guidelines Network. A total of 19,439 references were identified, of which 15 articles met the predetermined requirements to be included in the investigation. The articles included for this systematic review showed that mandibular distraction osteogenesis and adenotonsilectomy are the first-choice therapies for craniofacial and neurocognitive disorders. However, for neuromuscular disorders, the findings reported were not enough to provide information about surgical or nonsurgical alternatives. Despite the reported high frequency of OSA in those children with craniofacial, neurocognitive, and neuromuscular disorders, the evidence on the surgical and nonsurgical therapeutic success for OSA in these patients is scarce. It is necessary to perform future studies to investigate successful therapies for OSA in children. [Pediatr Ann. 2024;53(2):e62-e69.].

Living with Dysphagia: A Survey Exploring the Experiences of Adults Living with Neuromuscular Disease and their Caregivers in the United Kingdom.

Background: Dysphagia is common in adults living with neuromuscular disease (NMD). Increased life expectancy, secondary to improvements in standards of care, requires the recognition and treatment of dysphagia with an increased priority. Evidence to support the establishment of healthcare pathways is, however, lacking. The experiences of people living with NMD (pplwNMD) and their caregivers are valuable to guide targeted, value-based healthcare. Objective: To generate preliminary considerations for neuromuscular dysphagia care and future research in the United Kingdom, based on the experiences of those living with, or caring for, people with NMD. Methods: Two surveys (one for adults living with NMD and dysphagia, and a second for caregivers) were co-designed with an advisory group of people living with NMD. Surveys were electronically distributed to adults living with NMD and their caregivers between 18th May and 26th July 2020. Distribution was through UK disease registries, charity websites, newsletters, and social media. Results: Adults living with NMD receive little information or education that they are likely to develop swallowing difficulties. Most respondents report wanting this information prior to developing these difficulties. Difficulties with swallowing food and medication are common in this group, and instrumental assessment is considered a helpful assessment tool. Both adults living with NMD and caregivers want earlier access to neuromuscular swallowing specialists and training in how best to manage their difficulties. Conclusions: Improvement is needed in the dysphagia healthcare pathway for adults living with NMD to help mitigate any profound physical and psychological consequences that may be caused by dysphagia. Education about swallowing difficulties and early referral to a neuromuscular swallowing specialist are important to pplwNMD and their caregivers. Further research is required to better understand the experiences of pplwNMD and their caregivers to inform the development of dysphagia healthcare pathways.

Sleep disordered breathing assessment in patient with slowly progressive neuromuscular disease.

BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with neuromuscular diseases (NMD). Focusing on hypercapnia may lead to the neglect of other SDB such as obstructive and/or central sleep apnea syndrome (SAS). Our objectives were to assess the risk of inappropriate SDB management according to different screening strategies and to evaluate the prevalence and determinants of isolated and overlapping sleep apnea in patients with slowly progressive NMD. METHODS: This monocentric, cross-sectional, retrospective study analyzed medical records of adult NMD patients referred to a sleep department. Diagnostic strategies, including respiratory polygraphy (RP), nocturnal transcutaneous capnography (tcCO2), and blood gases (BG), were assessed for their performance in diagnosing SDB. Demographics and pulmonary function test results were compared between patients with or without SDB to identify predictors. RESULTS: Among the 149 patients who underwent a full diagnostic panel (RP + tcCO2 + BG), 109 were diagnosed with SDB. Of these, 33% had isolated SAS, and central apneas were predominant. Using single diagnostic strategies would lead to inappropriate SDB management in two thirds of patients. A combination of 2 diagnostic tools resulted respectively in 21.1, 22.9 and 42.2 % of inappropriate SDB management for RP + tcCO2, RP + BG and tcCO2 + BG. CONCLUSION: The significant prevalence of sleep apnea syndrome in patients with slowly progressive NMD highlights the need for increased awareness among clinicians. Improved diagnostics involve a systematic approach addressing both sleep apnea and diurnal and nocturnal alveolar hypoventilation to avoid inappropriate management and limit the consequences of SDB.

Sound-based cough peak flow estimation in patients with neuromuscular disorders.

INTRODUCTION/AIMS: Cough impairment is common in individuals with neuromuscular disorders and is associated with respiratory infections and shorter survival. Cough strength is assessed by measuring cough peak flow (CPF) using a flow meter, but this method requires a complex device setup and trained staff. The aim of the study is to evaluate the reliability of a smartphone app to estimate CPF based on cough sounds in a cohort of individuals with neuromuscular disorders. METHODS: Individuals with neuromuscular disorders underwent CPF measurement with a flow meter and a smartphone app. A CPF <270 L/min was considered abnormal. RESULTS: Of the 50 patients studied, 26 had amyotrophic lateral sclerosis (52%), 15 had hereditary myopathies (30%), and 9 had myasthenia gravis (18%). The intraclass correlation coefficient (ICC) between the CPF measured with a flow meter and CPF estimated with cough sounds was 0.774 (p < .001) even if the patients had orofacial weakness (ICC = 0.806, p < .001). The smartphone app had 94.4% sensitivity and 100% specificity to detect patients with CPF of less than 270 L/min. DISCUSSION: Our findings suggest that sounds measured with a smartphone app provide a reliable estimate of CPF in patients with neuromuscular disorders, even in the presence of with orofacial weakness. This may be a convenient way to monitor respiratory involvement in patients with neuromuscular disorders, but larger studies of more diverse patient cohorts are needed.

Back pain and disability according to early onset scoliosis etiology in children younger than 10 years.

PURPOSE: To determine caregiver-reported back pain prevalence, disability, pain interference, and associations with curve magnitude in early onset scoliosis (EOS) using the Oswestry Disability Index (ODI) and Patient Reported Outcome Measurement Information Systems (PROMIS) measures. METHODS: A single-center, retrospective review was performed in children below 10 years of age according to EOS etiology. Caregiver-reported back pain prevalence, ODI, PROMIS Pain Interference, Mobility, and Anxiety measures, and curve magnitude were recorded as part of routine clinic appointments. RESULTS: A total of 1212 patients with EOS (588 idiopathic, 295 congenital, 217 neuromuscular, 112 syndromic) ages 6.6 ± 2.7 were included; 23% had caregiver-reported back pain. Neuromuscular EOS patients had the highest prevalence of back pain (29%). ODI scores were higher in neuromuscular (48%) and syndromic (35%) patients than congenital (20%, p < 0.05) and idiopathic (16%, p < 0.01) patients. Neuromuscular patients also had higher PROMIS Pain Interference scores (53.3) compared to idiopathic (41.6, p < 0.001) and syndromic (45.0, p = 0.016) patients. A higher curve was associated with the presence of back pain (39° vs. 30°, p < 0.001) and had positive correlations with ODI scores (r = 0.38, p < 0.001) and PROMIS Pain Interference scores (r = 0.34, p < 0.001). CONCLUSION: Approximately one in five children with EOS under the age of 10 have caregiver-reported back pain, with the neuromuscular EOS type exhibiting higher pain prevalence, interference, and disability scores. Larger curve magnitude is associated with an increased prevalence of caregiver-reported back pain, increased disability, and increased pain interference. LEVEL OF EVIDENCE: 3 - case-control study.

Long-term outcomes and complications of isolated anterior thoracolumbar fusion for neuromuscular scoliosis associated with myelomeningocele.

PURPOSE: Neuromuscular scoliosis associated with myelomeningocele is a difficult clinical dilemma for the treating surgeon. The traditional surgical treatment consists of a posterior spinal instrumented fusion with or without a combined anterior procedure, but this has been associated with high complication rates, mostly related to deep infection. An anterior thoracolumbar fusion is not able to address the entirety of the deformity in many cases but could potentially avoid the devastating infection risks from the posterior approach by avoiding compromised skin. This study aims to evaluate the long-term outcomes and complications associated with isolated anterior thoracolumbar fusion in this high-risk group. METHODS: This study is a retrospective analysis of patients with myelomeningocele-associated scoliosis treated with an isolated anterior spinal fusion over a 20-year time period at a single center. Surgical details, demographics, curve characteristics and complications were recorded. Comparisons were made between patients who required revision surgery and those who did not. RESULTS: Sixteen patients were enrolled with an average age of 12.7 years at the time of surgery and average follow-up of 5.5 years. Patients had on average 7.4 levels fused anteriorly with the most common levels being T10-L4. There were no deep wound infections associated with the anterior surgery. Overall, nine patients (56%) had to be revised posteriorly due to adding-on or junctional deformity at an average of 3.7 years after index procedure. Four patients were revised due to proximal adding-on, while 1 was extended distally. Four additional patients were extended both proximally and distally. Of the posterior revisions, 2 patients developed deep wound infections, and both of these were in patients extended distally. Preoperative lumbar lordosis was higher in patients who required distal extension (100 vs. 69 degrees; p = 0.035). CONCLUSIONS: Patients undergoing isolated anterior fusion for scoliosis associated with myelomeningocele have low infection rates but often require posterior revision. The majority of patients can avoid the deep infection risk associated with distal posterior surgery at long-term follow-up. LEVEL OF EVIDENCE: IV.

Identification and Management of Acute Neuromuscular Respiratory Failure in the ICU.

Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder.

Sleep in pediatric neuromuscular disorders.

Sleep disordered breathing (SDB) is prevalent among children with neuromuscular disorders (NMD). The combination of respiratory muscle weakness, altered drive, and chest wall distortion due to scoliosis make sleep a stressful state in this population. Symptomatology can range from absent to snoring, nocturnal awakenings, morning headaches, and excessive daytime sleepiness. Sequelae of untreated SDB includes cardiovascular effects, metabolic derangements, and neurocognitive concerns which can be compounded by those innate to the NMD. The clinician should have a low threshold for obtaining polysomnography and recognize the nuances of individual disorders due to disproportionately impacted muscle groups such as hypoventilation in ambulating patients from diaphragm weakness. Non-invasive or invasive ventilation are the mainstay of treatment. In this review we explore the diagnosis and treatment of SDB in children with various NMD.

¿Se puede utilizar la determinación del pico flujo de tos para valorar la capacidad tusígena en enfermedades respiratorias obstructivas graves? / Can cough peak flow be used to assess cough capacity in severe obstructive respiratory diseases?

Introducción: La valoración de la capacidad tusígena se realiza con la medición del flujo espiratorio máximo durante la tos (peak-flow tos [PFT]). Sin embargo, esta valoración podría alterarse por enfermedades con obstrucción espiratoria de la vía aérea. El objetivo fue valorar la medición de la capacidad tusígena mediante PFT en pacientes con enfermedad pulmonar obstructiva crónica (EPOC), así como las correlaciones con la función pulmonar, muscular respiratoria y orofaríngea. Métodos: Se seleccionaron los pacientes con EPOC y con enfermedad neuromuscular, así como los sujetos sanos a los que se había realizado una medición de la fuerza de los músculos respiratorios de forma asistencial. De esta población, se analizaron los valores de la función respiratoria, así como la fuerza muscular orofaríngea. En un subgrupo de pacientes con EPOC se realizó el estudio de deglución por videofluoroscopia. Resultados: Se incluyeron 307 sujetos (59,3% EPOC, 38,4% enfermedades neuromusculares y 2,3% sanos). En el grupo EPOC, el PFT se encontraba disminuido de forma estadísticamente significativa comparado tanto con el grupo de los sanos como con los enfermos neuromusculares. El 70% de los EPOC tenían una disminución patológica del PFT. Solamente, existía una correlación directa entre el PFT con el grado de obstrucción bronquial y la fuerza de los músculos espiratorios. No se encontró alteración de la función de los músculos inspiratorios ni orofaríngeos. Conclusiones: La utilización del PFT en los pacientes con EPOC no refleja la capacidad tusígena ya que se ve influenciada por el grado de obstrucción bronquial. Por tanto, se deberían valorar nuevas pruebas diagnósticas para la medición de la capacidad tusígena, fundamentalmente, en los pacientes que coexistan enfermedades neuromusculares y patología obstructiva bronquial grave.(AU)

Introduction: Cough capacity is assessed by measuring cough peak flow (CPF). However, this assessment could be altered by obstructive airway diseases. The aim was to assess measurement of cough capacity by CPF in patients with chronic obstructive pulmonary disease (COPD), as well as correlations with pulmonary, respiratory muscle, and oropharyngeal function. Methods: Patients with COPD, and with neuromuscular disease, were selected as well as healthy subjects who had undergone respiratory muscle strength measurement in a healthcare setting. From this population, respiratory function values and lung and oropharyngeal muscle function were analysed. A subgroup of COPD patients underwent a videofluoroscopic swallow study. Results: Three hundred and seven subjects were included (59.3% COPD, 38.4% neuromuscular diseases, and 2.3% healthy). CPF was found to be statistically significantly decreased in the COPD group compared to both the healthy and neuromuscular disease groups. Of the COPD patients, 70% had a pathological decrease in CPF. There was only a direct correlation between CPF with the degree of bronchial obstruction and expiratory muscle strength. No alteration of inspiratory or oropharyngeal muscle function was found. Conclusions: The use of CPF in COPD patients does not reflect cough capacity as it is influenced by the degree of bronchial obstruction. Therefore, new diagnostic tests to measure cough capacity should be considered, especially in patients with coexisting neuromuscular diseases and severe bronchial obstructive disease.(AU)

Ventilatory failure in chronic neuromuscular disease.

Patients with neuromuscular diseases (NMD) can present to the neurologist with symptoms and signs of respiratory failure, either acutely or as an insidious process in the outpatient setting. Since the advent of non-invasive ventilation, the outcomes of patients with ventilatory failure due to NMD have dramatically improved. However, the natural history of different NMDs requires a nuanced approach to respiratory investigation and management. Respiratory failure dictates the prognosis of many NMDs and timing the most appropriate investigation and referral to ventilation services is crucial in optimising care.

Recurrent atraumatic compartment syndrome as a manifestation of genetic neuromuscular disease.

Compartment syndrome (CS) is a medical emergency that occurs secondary to excessively high pressures within a confined fibro-osseous space, resulting in reduced perfusion and subsequent tissue injury. CS can be divided into acute forms, most commonly due to trauma and considered an orthopaedic emergency, and chronic forms, most commonly presenting in athletes with recurrent exercise-induced pain. Downstream pathophysiological mechanisms are complex but do share commonalities with mechanisms implicated in genetic neuromuscular disorders. Here we present 3 patients with recurrent CS in the context of a RYR1-related disorder (n = 1) and PYGM-related McArdle disease (n = 2), two of whom presented many years before the diagnosis of an underlying neuromuscular disorder was suspected. We also summarize the literature on previously published cases with CS in the context of a genetically confirmed neuromuscular disorder and outline how the calcium signalling alterations in RYR1-related disorders and the metabolic abnormalities in McArdle disease may feed into CS-causative mechanisms. These findings expand the phenotypical spectrum of RYR1-related disorders and McArdle disease; whilst most forms of recurrent CS will be sporadic, above and other genetic backgrounds ought to be considered in particular in patients where other suggestive clinical features are present.

Respiratory Insufficiency in Neuromuscular Disease (RIND): A Delphi Study to Establish Consensus Criteria to Define and Diagnose Hypoventilation in Pediatric Neuromuscular Disease.

Chronic respiratory failure is a common endpoint in the loss of respiratory muscle function in patients with progressive neuromuscular disease (NMD). Identifying the onset of hypoventilation is critical to allow for the timely introduction of ventilator support and effectively manage respiratory failure [1-3]. While there are accepted criteria governing the diagnosis of hypoventilation during polysomnography (PSG) [4], there is concern that criteria are insufficient for identifying hypoventilation in the earlier stages of respiratory insufficiency related to NMD. The purpose of this project was to identify more sensitive criteria for identifying hypoventilation. METHODS: Fifteen pediatric pulmonologists with broad experience in managing patients with NMD, 10 of whom were board certified in and practice sleep medicine, were assembled and performed a review of the pertinent literature and a two-round Delphi process with 6 domains (Table 1). RESULTS: Within the 6 domains there were three pertinent items per domain (Table 2). There was clear agreement on findings on history (morning headaches) and pulmonary function testing (FVC < 50% or awake TcCO2 > 45 mmHg) indicating a high concern for nocturnal hypoventilation. There was close agreement on the definitions for nocturnal hypercapnia and hypoxemia. PSG criteria were identified that indicate a patient is likely in the transitional phase from adequate ventilation to hypoventilation. DISCUSSION: We identified a set of clinical criteria that may allow for more sensitive diagnosis of hypoventilation in NMD and earlier initiation of non-invasive ventilation leading to a reduction in the respiratory morbidity in progressive NMD. These criteria need to be further and more broadly validated prospectively to confirm their utility.

Multi-rod posterior correction only with halo-femoral traction for the management of adult neuromuscular scoliosis (> 100°) with severe pelvic obliquity: a minimum 5-year follow-up.

BACKGROUND: Many patients with neuromuscular scoliosis (NMS) experience a variety of difficult medical problems that aggravate the development effects of progressive scoliosis and pelvic obliquity (PO). The objective of the current study was to assess the safety and effectiveness of multi-rod posterior correction only (MRPCO) with halo-femoral traction (HFT) for the management of adult NMS (> 100°) with severe PO. METHODS: From 2012 to 2017, 13 adult patients who suffered from NMS (> 100°) with severe PO underwent MRPCO with HFT. The radiography parameters in a sitting position, such as the coronal Cobb angle of the main curve, the PO and the trunk shift (TS), were measured at the preoperative, postoperative and final follow-up stages. The preoperative and final follow-up assessment of the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was taken. RESULTS: The average follow-up span was 68.15 ± 6.78 months. There was decreased postoperative coronal Cobb angle with an average mean of 125.24° ± 11.78° to 47.55° ± 12.10°, with a correction rate of 62.43%; the PO was reduced to 6.25° ± 1.63° from 36.93° ± 4.25° with a correction rate of 83.07%; the TS was reduced to 2.41 cm ± 1.40 cm from 9.19 cm ± 3.07 cm. There was significant improvement in all parameters compared to the preoperative data. The VAS score reduced from 4.77 ± 0.93 to 0.69 ± 0.75, and the ODI score reduced from 65.38 ± 16.80 to 28.62 ± 12.29 at the final follow-up. CONCLUSIONS: Treatment of adult NMS (> 100°) with severe PO could be safe and effective with MRPCO with HFT. In order to obtain the optimum sitting balance, this could reduce the prevalence of complications and rectify the curvature and the correction of PO.

In vitro and in vivo models for the study of EV-D68 infection.

Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States in 2014 aroused widespread concern among the public and health authorities. The infection was found to be associated with increased surveillance of acute flaccid myelitis, a neurological condition that causes limb paralysis in conjunction with spinal cord inflammation. In vitro studies utilising two-dimensional (2D) and three-dimensional (3D) culture systems have been employed to elucidate the pathogenic mechanism of EV-D68. Various animal models have also been developed to investigate viral tropism and distribution, pathogenesis, and immune responses during EV-D68 infection. EV-D68 infections have primarily been investigated in respiratory, intestinal and neural cell lines/tissues, as well as in small-size immunocompetent rodent models that were limited to a young age. Some studies have implemented strategies to overcome the barriers by using immunodeficient mice or virus adaptation. Although the existing models may not fully recapitulate both respiratory and neurological disease observed in human EV-D68 infection, they have been valuable for studying pathogenesis and evaluating potential vaccine or therapeutic candidates. In this review, we summarise the methodologies and findings from each experimental model and discuss their applications and limitations.

The impact of SARS-CoV-2 on neuromuscular disorders.

The emergence of SARS-CoV-2 has profoundly impacted global society and various aspects of human life. While the pandemic has resulted in disruptions and challenges, it has also accelerated scientific research on viruses and immunology, leading to remarkable progress in vaccine technology and immunization strategies. This review examines the impact of SARS-CoV-2 on pre-existing neuromuscular disorders, and neuromuscular events following SARS-CoV-2 infection, including immune-mediated and critical illness status-related disorders. Furthermore, the review discusses the relationship between SARSCoV- 2 vaccination and neuromuscular complications. The findings highlight the need for further research and understanding to improve patient outcomes. Keywords: SARS-CoV-2, neuromuscular diseases, vaccine.

The indication of fusion to the pelvis in neuromuscular scoliosis is based on the underlying disease rather than on pelvic obliquity.

INTRODUCTION: The decision to instrument to L5 or ilium, in NMS, is usually based on radiologic factors, including pelvic obliquity (PO) > 15°, apex of curvature < L3, and Cobb angle > 60°. Since scoliosis in these patients is caused by a neurologic disease, we based our decision to stop at L5 on the presence of spasticity or flaccidity. PATIENTS & METHODS: The senior author did 109 primary fusions in NMS. Of those with DMD or SMA only 16% were instrumented to the ilium. The main factor for our decision was the correction potential of the truncal shift and PO in the supine traction radiographs and the absence of severe spasticity. RESULTS: The 57 patients with DMD/SMA had a mean preoperative curvature of 68°, PO of 17°, and truncal shift of 20°. 74% should have been instrumented to the pelvis, but only 16% were. Those instrumented shorter as the rule, were corrected from 74° to 26° and had a postoperative PO of 8°. There was no significant difference in postoperative correction and PO compared to those instrumented to L5 on standard protocol. Subsequent extension to the pelvis was needed in 1 CP patient. There were no significant changes after 2 years. Of the 20 patients instrumented to the pelvis 11 had cerebral palsy and a preop curvature of 89°, a PO of 21° and a truncal shift of 25°. DISCUSSION: The decision on instrumentation length should take flexibility and disease into consideration. If the trunk is centred over the pelvis, deterioration will not occur in absence of spasticity.