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Mucopolysaccharidosis type IVA (MPS IVA) is characterized by progressive skeletal dysplasia and respiratory issues with difficult airway management during anesthesia. To characterize tracheal abnormalities in children and adults with MPS IVA including interplay of the trachea, vasculature, bones and thyroid at the thoracic inlet. Computed tomography (CT) angiograms of the chest were analyzed for trachea shape, narrowing and deviation at the thoracic inlet, course of vasculature, bone alignment and thyroid location. The tracheal cross-sectional area was measured at the cervical, thoracic inlet and intrathoracic levels. Thirty-seven patients (mean age: 18.1 years) were included. The mean tracheal cross-sectional area narrowing at the thoracic inlet was 63.9% (range: −2.1–96%), with a trend for increased tracheal narrowing in older children. The trachea was commonly deviated rightward posterior (22/37, 59%). T- or W-shaped tracheas had two times greater tracheal narrowing than D- or U-shaped tracheas (P

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Children with skeletal dysplasia present unique challenges for safe anesthetic care including differences in the anatomy of the respiratory system, possibility of cervical spine instability or spinal stenosis, and a unique body habitus. Even seemly routine anesthesia can result in respiratory arrest or spinal cord injury. These complications can largely be avoided by proper planning such as appropriate techniques for the intubation of difficult airways, recognition of cervical instability, neuromonitoring for any anesthesia over an hour in patients with severe spinal stenosis, and preoperative assessment of the trachea and avoidance of neuraxial anesthesia in children with Morquio syndrome.

Achondroplasia, the most common skeletal dysplasia, is characterized by a variety of medical, functional and psychosocial challenges across the lifespan. The condition is caused by a common, recurring, gain-of-function mutation in FGFR3, the gene that encodes fibroblast growth factor receptor 3. This mutation leads to impaired endochondral ossification of the human skeleton. The clinical and radiographic hallmarks of achondroplasia make accurate diagnosis possible in most patients. However, marked variability exists in the clinical care pathways and protocols practised by clinicians who manage children and adults with this condition. A group of 55 international experts from 16 countries and 5 continents have developed consensus statements and recommendations that aim to capture the key challenges and optimal management of achondroplasia across each major life stage and sub-specialty area, using a modified Delphi process. The primary purpose of this first International Consensus Statement is to facilitate the improvement and standardization of care for children and adults with achondroplasia worldwide in order to optimize their clinical outcomes and quality of life. Achondroplasia is the most common skeletal dysplasia and is characterized by various lifelong clinical, functional and psychosocial challenges for affected individuals. This first International Consensus Statement on the care of children and adults with achondroplasia aims to facilitate the global standardization and improvement of achondroplasia clinical care.

Individuals with spastic cerebral palsy (CP) often exhibit altered sensitivities to neuromuscular blocking agents (NMBAs) used for surgical intubation. We assessed usage of the NMBA rocuronium in patients with spastic CP and evaluated potential modifiers of dosing including gross motor function classification system (GMFCS) level, birthweight, gestational age, and the use of anticonvulsant therapy. In a case-control study, surgical patients with spastic CP (n = 64) or with idiopathic or non-neuromuscular conditions (n = 73) were enrolled after informed consent/assent. Patient data, GMFCS level, anticonvulsant use, and rocuronium dosing for intubation and post-intubation neuromuscular blockade were obtained from medical records. Findings reveal participants with CP required more rocuronium per body weight for intubation than controls (1.00 ± 0.08 versus 0.64 ± 0.03 mg/kg, p &lt, 0.0001). Dosing increased with GMFCS level (Spearman’s rho = 0.323, p = 0.005), and participants with moderate to severe disability (GMFCS III-V) had elevated rocuronium with (1.21 ± 0.13 mg/kg) or without (0.86 ± 0.09 mg/kg) concurrent anticonvulsant therapy. Children born full-term or with birthweight &gt, 2.5 kg in the CP cohort required more rocuronium than preterm and low birthweight counterparts. Individuals with CP exhibited highly varied and significant resistance to neuromuscular blockade with rocuronium that was related to GMFCS and gestational age and weight at birth.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders that impair degradation of glycosaminoglycans (GAG). The specific GAGs that accumulate depend on the type of MPS, leading to unique characteristic clinical features. Development of guidelines for treatment of MPS has traditionally been multifaceted and largely based on palliative care. In the last three decades, hematopoietic stem cell transplantation and enzyme replacement therapy have been developed based on experimental and clinical studies. Guidelines have been established with the accumulation of the clinical data from natural history of the disease and therapeutic consequences, mainly sponsored by pharmaceutical companies. In recent years, committees in three countries, Australia (2015), Japan (2017), and Brazil (2018) have adopted guidelines for the treatment of MPS II, sponsored and authorized by each government. As novel treatments for MPS including substrate reduction therapy, pharmacological chaperone therapy, and gene therapy become clinically available, it is increasingly necessary to establish the optimal guideline for each type of MPS, considering multiple factors including therapeutic efficacy, adverse effects, age, disease stage, prognosis, feasibility and availability of access to treatment, and cost- performance. In this article, we discuss the historical guidelines for specific MPS types and the most recently adopted guidelines for MPS II and propose the development of future guidelines without conflict of interest and bias leading to mutual benefits to all parties including patients and families, professionals, tax payers, and governments.

Morquio syndrome is a rare disease caused by a disorder in the storage of mucopolysaccharides that affects multiple organs, including musculoskeletal, respiratory, cardiovascular, and digestive systems. Respiratory failure is one of the leading causes of mortality in Morquio patients, thus, respiratory function testing is vital to the management of the disease. An automated respiratory assessment methodology using the pneuRIP device and a machine-learning algorithm was developed. pneuRIP is a noninvasive approach that uses differences between thoracic and abdominal movements (thoracic-abdominal asynchrony) during respiration to assess respiratory status. The technique was evaluated on 17 patients with Morquio (9 females and 8 males) between the ages of 2 and 57 years. The results of the automated technique agreed with the clinical assessment in 16 out of the 17 patients. It was found that the inverse cumulative percentage representation of the time delay between the thorax and abdomen was the most critical variable for accurate evaluation. It was demonstrated that the technique could be successfully used on patients with Morquio who have difficulty breathing with 100% compliance. This technique is highly accurate, portable, noninvasive, and easy to administer, making it suitable for a variety of settings, such as outpatient clinics, at home, and emergency rooms.

Morquio A syndrome (mucopolysaccharidosis IVA, MPS IVA) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase, resulting in systemic accumulation of the partially degraded glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. The accumulation of these GAGs leads to distinguishing features as skeletal dysplasia with disproportionate dwarfism, short neck, kyphoscoliosis, pectus carinatum, tracheal obstruction, coxa valga, genu valgum, and joint laxity. In the absence of autopsied cases and systemic analysis of multiple tissues, the pathological mechanism of the characteristic skeletal dysplasia associated with the disease largely remains a question. Here we report an autopsied case of a 23-year-old male with MPS IVA, who developed characteristic skeletal abnormalities by 4 months of age and died of severe tracheal obstruction and hypoventilation originating from respiratory muscle weakness from neurological cord deficit due to cord myelopathy at the age of 23. We analyzed postmortem tissues pathohistologically, including the thyroid, lung, lung bronchus, trachea, heart, aorta, liver, spleen, kidney, testes, humerus, knee cartilage, and knee ligament. Examination of the tissues demonstrated systemic storage materials in multiple tissues, as well as severely ballooned and vacuolated chondrocytes in the trachea, humerus, knee cartilage, and lung bronchus. This autopsied case with MPS IVA addresses the importance of tracheal obstruction for morbidity and mortality of the disease, and the pathological findings contribute to a further understanding of the pathogenesis of MPS IVA and the development of novel therapies., Highlights • Severe tracheal obstruction and respiratory failure are the leading causes of morbidity and mortality in MPS IVA patients. • The majority of chondrocytes in the examined locations were enlarged and vacuolated. • Tracheal obstruction is confirmed clinically, pathologically, and radiographically. • Risk factors and surgical intervention of tracheal obstruction should be considered to save the lives of MPS IVA patients. • MPS IVA should be evaluated in a multifaceted approach.

At a recent consensus conference, the Malignant Hyperthermia Association of the United States addressed 6 important and unresolved clinical questions concerning the optimal management of patients with malignant hyperthermia (MH) susceptibility or acute MH. They include: (1) How much dantrolene should be available in facilities where volatile agents are not available or administered, and succinylcholine is only stocked on site for emergency purposes? (2) What defines masseter muscle rigidity? What is its relationship to MH, and how should it be managed when it occurs? (3) What is the relationship between MH susceptibility and heat- or exercise-related rhabdomyolysis? (4) What evidence-based interventions should be recommended to alleviate hyperthermia associated with MH? (5) After treatment of acute MH, how much dantrolene should be administered and for how long? What criteria should be used to determine stopping treatment with dantrolene? (6) Can patients with a suspected personal or family history of MH be safely anesthetized before diagnostic testing? This report describes the consensus process and the outcomes for each of the foregoing unanswered clinical questions.

Morquio A syndrome is characterized by a unique skeletal dysplasia, leading to short neck and trunk, pectus carinatum, laxity of joints, kyphoscoliosis, and tracheal obstruction. Cervical spinal cord compression/inability, a restrictive and obstructive airway, and/or bone deformity and imbalance of growth, are life-threatening to Morquio A patients, leading to a high morbidity and mortality. It is critical to review the current therapeutic approaches with respect to their efficacy and limitations.Patients with progressive skeletal dysplasia often need to undergo orthopedic surgical interventions in the first two decades of life. Recently, we have treated four patients with a new surgery to correct progressive tracheal obstruction. Enzyme replacement therapy (ERT) has been approved clinically. Cell-based therapies such as hematopoietic stem cell therapy (HSCT) and gene therapy are typically one-time, permanent treatments for enzyme deficiencies. We report here on four Morquio A patients treated with HSCT approved in Japan and followed for at least ten years after treatment. Gene therapy is under investigation on mouse models but not yet available as a therapeutic option.ERT and HSCT in combination with surgical intervention(s) are a therapeutic option for Morquio A; however, the approach for bone and cartilage lesion remains an unmet challenge.

SummaryAim The purpose of this study was to report our experience with peripheral nerve blockade in pediatric and young adult patients with skeletal dysplasia undergoing knee arthroscopy. Background The incidence of skeletal dysplasia is 1 : 4000 live births. These patients have biomechanical predispositions to knee joint degeneration, which is often palliated by arthroscopic surgery. Regional anesthesia has been proven to improve the cost and quality of care in adults undergoing arthroscopic knee surgery. Methods This was a retrospective case series of patients with skeletal dysplasia undergoing arthroscopic knee surgery from 2012–2014 at a tertiary-care, pediatric hospital. Data pertaining to block effectiveness, technique, adjunct local anesthetic, rates of postoperative nausea/vomiting and admissions, and complications were recorded. Results Twenty patients with skeletal dysplasia underwent arthroscopic knee surgery during the study period. Ten of these patients received peripheral nerve blockade (12 procedures). All patients received femoral, femoral/sciatic, or femoral/sciatic/obturator blocks. One patient required opioid, constituting a block failure. The same patient required overnight admission for pain control. No patients suffered from PONV. There were no complications associated with any of the blocks performed. Conclusions Patients with skeletal dysplasia receiving lower extremity nerve blocks consume minimal opioid and report no major complications. Anesthesiologists should consider this mode of anesthesia in these patients. While no nerve injuries were discovered, further study is necessary to determine whether rates of nerve injury are comparable to that in the general pediatric population. Given the size of the skeletal dysplasia population, this type of study would require close to a decade of metadata from numerous institutions.

Patients with severe tracheal obstruction in Morquio A syndrome are at risk of dying of sleep apnea and related complications. Tracheal obstruction also leads to life-threatening complications during anesthesia as a result of the difficulty in managing the upper airway due to factors inherent to the Morquio A syndrome, compounded by the difficulty in intubating the trachea. A detailed description of the obstructive pathology of the trachea is not available in the literature probably due to lack of a homogenous group of Morquio A patients to study at any one particular center. We present a series of cases with significant tracheal obstruction who were unrecognized due to the difficulty in interpreting tracheal narrowing airway symptoms. Our goal is to provide the guidelines in the management of these patients that allow earlier recognition and intervention of tracheal obstruction. Sagittal MRI images of the cervical spine of 28 Morquio A patients (12±8.14years) showed that19/28 (67.9%) patients had at least 25% tracheal narrowing and that narrowing worsened with age (all 8 patients over 15years had greater than 50% narrowing). Eight out of 28 patients were categorized as severe (>75%) tracheal narrowing when images were evaluated in neutral head and neck position. Of the 19 patients with tracheal narrowing, compression by the tortuous brachiocephalic artery was the most common cause (n=15). Evidence of such tracheal narrowing was evident as early as at 2years of age. The etiology of tracheal impingement by the brachiocephalic artery in Morquio A appears to be due to a combination of the narrow thoracic inlet crowding structures and the disproportionate growth of trachea and brachiocephalic artery in relationship to the chest cavity leading to tracheal tortuosity. In conclusion, tracheal narrowing, often due to impression from the crossing tortuous brachiocephalic artery, increases with age in Morquio A patients. Greater attention to the trachea is needed when evaluating cervical spine MRIs as well as other imaging and clinical investigations, with the goal of establishing a timely treatment protocol to reduce the mortality rate in this patient population.

We present the novel case report of a child with hypotonia and dysmorphic features who developed malignant hyperthermia (MH) intraoperatively. Neurology workup revealed the presence of a known causative ryanodine receptor (RYR1) mutation for MH, c.7522C>T; p.R2508C. Furthermore, the neurology workup diagnosed the child with King-Denborough syndrome (KDS). This particular mutation has never been documented in a patient with KDS. Atypical presentation of MH is more likely in patients with RYR1-related myopathy. A high index of suspicion for MH in children with myopathy is important. The MH hotline was helpful in the management of this patient when it was called after the initial dose of dantrolene. A neurology consult was essential for the diagnosis of KDS and future care.

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.

Background One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury. Objective We hypothesized that a single 2-mg·kg−1 dose of methylprednisolone given 45–60 min prior to lung collapse would minimize injury from OLV and improve physiological stability. Methods Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg−1 methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for inflammatory markers related to lung injury at timed intervals related to administration of methylprednisolone. Results Three children in the placebo group experienced clinically significant intraoperative and postoperative respiratory complications. Respiratory resistance was lower (P = 0.04) in the methylprednisolone group. Pro-inflammatory cytokine IL-6 was lower (P = 0.01), and anti-inflammatory cytokine IL-10 was higher (P = 0.001) in the methylprednisolone group. Tryptase, measured before and after OLV, was lower (P = 0.03) in the methylprednisolone group while increased levels of tryptase were seen in placebo group after OLV (did not achieve significance). There were no side effects observed that could be attributed to methylprednisolone in this study. Conclusions Methylprednisolone at 2 mg·kg−1 given as a single dose prior to OLV provides physiological stability to children undergoing OLV. In addition, methylprednisolone results in lower pro-inflammatory markers and higher anti-inflammatory markers in the children's plasma.

We describe an instance in which complete paraplegia was evident immediately postoperatively after apparently uneventful lumbar epidural-general anesthesia in a patient with Morquio Type A syndrome (Morquio A) with moderate thoracic spinal stenosis.A 16-yr-old male with Morquio A received lumbar epidural-general anesthesia for bilateral distal femoral osteotomies. Preoperative imaging had revealed a stable cervical spine and moderate thoracic spinal stenosis with a mild degree of spinal cord compression. Systolic blood pressure (BP) was maintained within 20% of the pre-anesthetic baseline value. The patient sustained a severe thoracic spinal cord infarction. The epidural anesthetic contributed to considerable delay in the recognition of the diagnosis of paraplegia.This experience leads us to suggest that, in patients with Morquio A, it may be prudent to avoid the use of epidural anesthesia without very firm indication, to support BP at or near baseline levels in the presence of even moderate spinal stenosis, and to avoid flexion or extension of the spinal column in intraoperative positioning. If the spinal cord/column status is unknown or if the patient is known to have any degree of spinal stenosis, we suggest that the same rigorous BP support practices that are typically applied in other patients with severe spinal stenosis, especially stenosis with myelomalacia, should apply to patients with Morquio A and that spinal cord neurophysiological monitoring should be employed. In the event that cord imaging is not available, e.g., emergency procedures, it would be prudent to assume the presence of spinal stenosis.

There are 3 surgical procedures that patients with cerebral palsy (CP) undergo that may be considered major procedures: femoral osteotomies combined with pelvic osteotomies, spine fusion, and intrathecal baclofen pump implant for the treatment of spasticity. Many complications are known to occur at a higher rate in this population, and some may be avoided with prior awareness of the preoperative pathophysiology of the patient with CP.

Background Metatropic dysplasia is a rare form of skeletal dysplasia requiring multiple anesthetics for surgical and imaging procedures, most of which are orthopedic procedures. We provide centralized care to patients with skeletal dysplasia at our tertiary care pediatric hospital, and we were able to collect the largest number of metatropic dysplasia patients reported to date. Aim The aim of this retrospective study was to describe and characterize the anesthetic difficulties in this high-risk population. Methods Medical charts of all patients with metatropic dysplasia were reviewed to collect data, including anesthetics performed, difficulties, and complications related to the anesthetic care, co-morbid conditions, and related events. Results Twenty-three patients with metatropic dysplasia underwent 188 anesthetics with 61% of the anesthetics having been administered for orthopedic procedures. Fourteen of 23 (60.8%) progressively became difficult to intubate over the course of their care, with 12 out of 14 having undergone cervical spine fusion. These 14 patients had a total of 133 procedures. Sixty procedures (45.1%) had an airway described as difficult. Glidescope was the difficult airway tool most commonly used (68%) with flexible fiberoptic scope used 12% and Miller or Macintosh blade used 18% of the time. In addition to the airway difficulties, spinal canal narrowing or stenosis was widely prevalent, and no neuraxial anesthetic was performed in any of our patients. Conclusion Difficult airway is the most common co-morbid condition present in patients with metatropic dysplasia, especially if their cervical spine has been fused. Familiarity with the difficulties involving the airway and its management is critical in safe and successful management of anesthesia in this high-risk population.

Mucopolysaccharidosis IVA (OMIM 253000; also known as Morquio A syndrome) is associated with skeletal, airway, and hearing abnormalities. Cochlear implantation is an effective intervention for patients with severe-to-profound hearing loss. Patients can gain substantial improvement in auditory performance, speech perception, and their quality of life from cochlear implantation. Although severe progressive sensorineural hearing loss is a common feature of mucopolysaccharidosis IVA, no detailed description of cochlear implantation for mucopolysaccharidosis IVA has been reported. To review the effectiveness and special considerations associated with cochlear implantation in patients with mucopolysaccharidosis IVA, we here report the case of cochlear implantation in mucopolysaccharidosis IVA by a multidisciplinary team. A retrospective chart review was conducted on a 34-year-old female with mucopolysaccharidosis IVA, who received a cochlear implant. Audiometric thresholds, speech perception scores, and cochlear implant processor mapping information were reviewed during the first 12 months following cochlear implantation. The results of audiological tests indicate improved hearing thresholds as well as remarkable enhancement of speech perception skills over 12 months of cochlear implant use. Cochlear implantation improved auditory performance in a mucopolysaccharidosis IVA patient with postlingually severe-to-profound sensorineural hearing loss. The benefits of cochlear implantation could be meaningful for other Morquio patients with progressive hearing loss, although the risks of surgery and anesthesia should be carefully considered by a multidisciplinary team of experts during the cochlear implant candidacy process.

Summary The core myopathies are a subset of myopathies that present in infancy with hypotonia and muscle weakness. They were formerly considered a rare type of congenital myopathy but are now recognized as being more prevalent. Due to their genetic linkage to mutations in the ryanodine receptor gene (RYR1), core myopathies (in particular, central core disease) carry a high risk of malignant hyperthermia susceptibility. In this review article, we describe the phenotypical, genetic, and histopathological characteristics of core myopathies and further describe the currently understood nature of their risk of malignant hyperthermia. We also review the level of suspicion a clinician should exhibit with a child who has a possible core myopathy or other congenital myopathy presenting for an anesthetic prior to a definitive genetic analysis. For this review article, we performed literature searches using the key words anesthesiology, core myopathies, pediatric neurology, malignant hyperthermia, genetics, ryanodine receptor, and molecular biology. We also relied on literature accumulated by the two authors, who served as hotline consultants for the Malignant Hyperthermia Hotline of the Malignant Hyperthermia Association of the United States (MHAUS) for the past 12 years.

Patients with skeletal dysplasia frequently require surgery. This patient population has an increased risk for peri-operative complications related to the anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and function; deformity of their chest wall; abnormal mobility of their upper cervical spine; and associated issues with general health and body habitus. Utilizing evidence analysis and expert opinion, this study aims to describe best practices regarding the peri-operative management of patients with skeletal dysplasia. A panel of 13 multidisciplinary international experts participated in a Delphi process that included a thorough literature review; a list of 22 possible care recommendations; two rounds of anonymous voting; and a face to face meeting. Those recommendations with more than 80% agreement were considered as consensual. Consensus was reached to support 19 recommendations for best pre-operative management of patients with skeletal dysplasia. These recommendations include pre-operative pulmonary, polysomnography; cardiac, and neurological evaluations; imaging of the cervical spine; and anesthetic management of patients with a difficult airway for intubation and extubation. The goals of this consensus based best practice guideline are to provide a minimum of standardized care, reduce perioperative complications, and improve clinical outcomes for patients with skeletal dysplasia.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA.

The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of "Movement" and "Movement with cognition." Patients, who underwent HSCT and were followed up for over 10years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5years follow-up on average) were similar with the-age-matched controls below 10years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls.

Summary Objectives: Our objective was to make recommendations based on our experience and findings from this study regarding the anesthetic care of children with Morquio syndrome (MS). We emphasize information not readily available in the Anesthesiology literature. Aim: To describe the unique nature of difficulties, especially the relationship of the head and neck to airway patency. In addition, we aim to examine 83 intubations performed in 28 patients and report on observed preferences. Background: Much of the available literature in Anesthesiology consists of case reports of single or small groups of cases, many describing a nonhomogenous population inclusive of many mucopolysaccharidoses. Methods/Materials: We retrospectively studied 28 children with MS who underwent 108 surgical procedures at our pediatric hospital, which provides multidisciplinary, comprehensive care to children with skeletal dysplasia. Results: Cervical fusion was performed in 22 of 28 patients in our study. Eight children after cervical fusion became difficult to intubate for subsequent surgical procedures. In addition, we found airway abnormalities including tortuous appearance of the trachea and bronchi, evident on chest radiograph, as a result of the abnormalities in the hyaline cartilage and deposits of glycosaminoglycans. Conclusion: Morquio syndrome results in abnormalities of not only upper airway but also of large airways. Information from 83 intubations of 108 anesthetics (in 28 patients) shows a preference for Glidescope when intubating children with MS. Displacing the tongue anteriorly prior to intubation by manual retraction using a ring forceps or a piece of gauze helps to access the larynx in children with MS.

Objectives To test the hypothesis that surfactant, when given prophylactically during one lung ventilation, improves physiological stability and reduces inflammation.

BACKGROUND The specific aim of this study was to examine the efficacy of a low dose of methylprednisolone in minimizing inflammatory response in juvenile piglets when given 45-60 min prior to onset of one-lung ventilation. METHODS Twenty piglets aged 3 weeks were assigned to either the control group (n = 10) or methylprednisolone group (n = 10). The animals were anesthetized and after 30 min of ventilation, they had their left lung blocked. Ventilation was continued via right lung for 3 h. The left lung was then unblocked. Following another 30 min of bilateral ventilation, the animals were euthanized and both lungs were harvested. The methylprednisolone group had a single dose (2 mg x kg(-1)) of methylprednisolone given i.v. 45-60 min prior to onset of one-lung ventilation. Physiological parameters (PaO2, resistance, and compliance) and markers of inflammation (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) were measured at baseline and every 30 min thereafter. Lung tissue homogenates from both collapsed and ventilated lungs were analyzed for TNF-alpha, IL-1beta, IL-6, and IL-8. RESULTS The methylprednisolone group had higher partial pressure of oxygen (P = 0.01), lower plasma levels of TNF-alpha (P = 0.03) and IL-6 (P = 0.001) when compared with control group. Lung tissue homogenate in the methylprednisolone group had lower levels of TNF-alpha (P < 0.05), IL-1beta (P < 0.05), and IL-8 (P < 0.05) in both the collapsed and the ventilated lungs. CONCLUSIONS In a piglet model of one-lung ventilation, use of prophylactic methylprednisolone prior to collapse of the lung improves lung function and decreases systemic pro-inflammatory response. In addition, in the piglets who received methylprednisolone, there were reduced levels of inflammatory mediators in both the collapsed and ventilated lungs.

Summary Background: Our objective was to better understand neuromuscular junction (NMJ) morphology in children with Duchenne muscular dystrophy (DMD). Methods: We examined the NMJs of four children, age 6–13 years, who were diagnosed with DMD. Using our previously established staining technique, we examined the gross appearance of the NMJs in patients with DMD and evaluated the spread of acetylcholine receptors (AChRs) in relationship to the NMJs. We used a computerized algorithm to measure the area of staining corresponding to AChRs and NMJ. Results: Abnormal shape and morphological appearance of some of the NMJs was clearly evident. The spread of AChRs in DMD patients is comparable with the spread of AChRs in nonDMD patients. Conclusions: The distribution of AChRs in relationship to the boundaries of NMJs in DMD children is similar to the distribution of NMJs in the erector spinae muscles of idiopathic scoliosis patients.

One-lung ventilation (OLV) is the intentional collapse of one lung during surgical procedures in the chest. The objective of this report is to demonstrate that a piglet model of pediatric OLV mimics the clinical sequelae, and thus is valid to study lung protective interventions. Pediatric pigs (n = 7; 21 ± 1 d old; 7.7 ± 0.5 kg) were instrumented and ex- posed to OLV (left lung collapsed) for 3 hrs, followed by 30 min of bilateral lung ventilation (BLV) before sacrifice and tissue harvest. Pulmonary compliance (Cp) and resistance (Rp) were measured half-hourly and plasma samples were drawn hourly for inflammatory cytokine analysis. Cp dropped to 86% and Rp rose to 148% of baseline with OLV, which is consistent with clinical observations given the anatomical differences of the pig thorax. Plasma levels of TNF-� and IL- 6 rose throughout the protocol, consistent with clinical observations. Lung histology showed greater atelectasis in the col- lapsed lungs following 30 min of BLV. The piglet model is valid for the study of OLV-induced lung injury and may be useful for the study of potential therapies to improve outcomes in the pediatric population.

Progressive tracheal obstruction is commonly seen in Morquio A syndrome and can lead to life-threatening complications. Although tracheostomy can address severe upper airway obstruction, lower airway obstruction, commonly associated with a narrow thoracic inlet and vascular compression, requires an alternative approach. We describe the case of a 16-year-old patient with Morquio A syndrome whose near-fatal tracheal obstruction was relieved by timely surgical tracheal vascular reconstruction with dramatic resolution of his respiratory symptoms.

article i nfo In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary end- points and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory induc- tanceplethysmographyinconjunctionwithconventionalspirometrywereevaluatedintwenty-twoMorquiopa- tients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 to 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with the exception of IOS (81.8%-18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including N95% oxygen saturation, end tidal CO2 (38-44 mm Hg), and age-appropriate heart rate (mean = 98.3, standard deviation = 19) (two patients were deviated). All patients preserved normal values in the impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, al- though predicted forced expiratory total (72.8 ± 6.9 SE%) decreased with age and was below normal; phase angle (35.5 ± 16.5°), %rib cage (41.6 ± 12.7%), resonant frequency, and forced expiratory volume in 1 s/forced expiratory volume total (110.0 ± 3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young pa- tients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function inMorquio syndrome which inmany casesmay bedifficult to evaluate. Morquio patients studied herein demon- strated no clinical or functional signs of restrictive and/or obstructive lung disease.

Summary Background Spinal deformity is one of the secondary musculoskeletal problems that occur with cerebral palsy (CP). Of the co morbidities associated with CP and spinal deformity, cardiac function is of theoretical concern. Objective The goal of our study was to determine the clinical relevance of routine preoperative cardiology evaluation via echocardiogram for patients with CP presenting for posterior spine fusion (PSF) surgery. Methods A retrospective chart review was performed of CP patients presenting for scoliosis surgery. The data collected for each patient included: age, sex, height, weight, Cobb angle, and medical history. All patients had a preoperative cardiac evaluation. Results Seventy-two patients were included. The mean age was 13.6 ± 3.4 years. Left ventricular systolic function was normal in all patients; the mean shortening fraction was 39.3 ± 6.2%. No patient had more than mild insufficiency of either the semilunar or atrioventricular valve. One patient was diagnosed with aortic root dilation as well as aortic valve insufficiency. All patients had PSF surgery without changes in anesthetic or surgical plans, and no patient experienced complications attributable to a cardiac origin. Conclusion The results suggest that routine preoperative cardiology evaluation via echocardiogram for children with CP in the absence of clinical history or physical examination findings suggestive of cardiac disease is not necessary.

Mucopolysaccharidosis IVA is an autosomal recessive condition caused by mutations in the GALNS gene, which encodes N-acetylgalactosamine-6-sulfatase, also called galactosamine-6-sulfatase (GALNS). A reduction in or absence of effective GALNS leads to faulty catabolism of keratan sulfate and chondroitin-6-sulfate within the lysosome; their accumulation causes cell, tissue, and organ dysfunction. The connective tissue, cartilage, ligaments, and bone of patients with Morquio A syndrome are particularly affected. Patients with Morquio A syndrome are at high risk of neurological complications because of their skeletal abnormalities; many patients are in danger of cervical myelopathy due to odontoid hypoplasia and ligamentous laxity leading to atlantoaxial subluxation. The multisystemic involvement of patients with Morquio A syndrome requires treatment by multidisciplinary teams; not all members of these teams may be aware of the potential for subluxation and quadriparesis. A multinational, multidisciplinary panel of 10 skeletal dysplasia or Morquio A syndrome specialists convened in Miami, FL on December 7 and 8, 2012 to develop consensus recommendations for early identification and effective management of spinal cord compression, for anesthesia and surgical best practices, and for effectual cardiac and respiratory management in patients with Morquio A syndrome. The target audience for these recommendations includes any physician who may encounter a patient with Morquio A syndrome, however doctors who do not have access to the full spectrum of specialists and resources needed to support patients with Morquio A syndrome should attempt to refer patients to a center that does. Physicians who manage Morquio A syndrome or comorbid conditions within specialty centers should review these expert panel recommendations and fully understand the implications of spinal cord instability for their own practices. © 2014.

We report a case of perioperative management of a toddler with plastic bronchitis complicated by tracheal obstruction. We discuss our management of this case as well as the diverse group of patients who may present with this disease. We also reviewed the literature regarding medical management of cast bronchitis.

Background Cerebral palsy (CP) is the most prevalent neurologic disease in children. A primary deficit in CP is neuromuscular dysfunction; however, neuromuscular junctions in children with CP have not been studied. Evidence exists that up-regulation of acetylcholine receptors (AChRs) may be present in children with CP, and the current study was undertaken to examine this possibility. Methods Thirty-nine children with spastic CP and 25 neurologically normal children were enrolled in the study. Paraspinal muscles underwent biopsy during scheduled spinal fusion surgery. Two sets of assessments were performed on the biopsy specimens: (1) reverse-transcription polymerase chain reaction and Western blotting to evaluate the expression of the gamma subunit of the AChR; and (2) histologic evaluation using a double-stain technique for AChR and acetylcholinesterase, wherein acetylcholinesterase staining defined the limits of the neuromuscular junction, and AChR staining that appeared outside of these limits indicated an abnormal distribution of AChRs. Results Reverse-transcription polymerase chain reaction and Western blot analyses showed that neither the CP nor non-CP samples had detectable gamma-AChR subunit. Histologic analysis indicated that 11 of 39 children with CP and none of 20 children with idiopathic scoliosis scored positive for the presence of AChR outside of the neuromuscular junction (P = 0.0085). Conclusion A subset of children with CP have an abnormal distribution of AChR relative to the acetylcholinesterase found at the neuromuscular junction. The altered distribution of AChR in CP was not associated with a detectable presence of the gamma-AChR subunit, suggesting that the nonjunctional AChRs in CP does not contain the gamma subunit.

We describe three children ages 20 to 33 months who presented for surgical resection of their laryngeal papillomata. Their anaesthetic management revealed the severity of obstruction which these children presented and the obstacles that faced the anaesthesiologist trying to secure the airway and provide adequate ventilation. The airway obstruction had both a fixed and a dynamic component to it. This was evidenced by the ability of the children to maintain ventilation when spontaneously breathing. But, they exhibited total obstruction when ventilation was attempted via mask using positive pressure. It is possible to encounter obstruction to ventilation after the trachea has been intubated because of papillomata that were 'shaved off,' filling the tracheal tube lumen.

Background Studies examining the use of desmopressin acetate (DDAVP) have shown variable results in DDAVP's efficacy for reducing blood loss. Studies of adults having cardiac surgery and of children having spinal fusion have suggested that patients with complicated medical histories and complex surgical procedures may benefit from use of DDAVP. Therefore, this study was designed to examine the homeostatic effects of DDAVP in children with severe cerebral palsy undergoing spinal fusion. Methods A randomized, double-blinded, and placebo-controlled trial of DDAVP was designed to enroll 40 patients. However, termination of the study was advised by the Institutional Review Board after 21 patients were enrolled. All patients had spastic quadriplegic-type cerebral palsy and were randomly assigned to one of two groups. The DDAVP group received 0.3 microg/kg DDAVP in 100 ml normal saline, and the placebo group received normal saline alone. All patients were anesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl. Factor VIIIC and von Willebrand's factor (vWF) concentrations were measured in blood drawn before DDAVP infusion and 1 h after infusion. Blood pressure was maintained at a systolic pressure of less than 100 mmHg. Use of crystalloids, packed erythrocytes, platelets, and fresh frozen plasma were based on criteria established by protocol. Estimated blood loss was assessed by weighing sponges and measuring suctioned blood from canisters. Results Estimated blood loss (intraoperative and postoperative) and amount of packed erythrocytes transfused were similar for the DDAVP and placebo groups. Concentrations of both factor VIIIC and vWF were significantly greater after DDAVP infusion when compared with concentrations after placebo infusion. Conclusions In the children who had complex spinal fusion, there was no difference in estimated blood loss between those who received DDAVP and those who received a placebo. Administration of DDAVP significantly increased factor VIIIC and vWF levels.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed.