Tracheal Narrowing and Its Impact on Anesthesia Care in Patients With Morquio A (Mucopolysaccharidosis Type IVA): An Observational Study.

BACKGROUND: Recently, tracheal narrowing has been recognized as a significant comorbid condition in patients with Morquio A, also known as mucopolysaccharidosis IVA. We studied a large cohort of patients with Morquio A to describe the extent of their tracheal narrowing and its relationship to airway management during anesthesia care. METHODS: This is an observational study, collecting data retrospectively, of a cohort of patients with Morquio A. Ninety-two patients with Morquio A syndrome were enrolled, among whom 44 patients had their airway evaluated by computed tomography angiography and had undergone an anesthetic within a year of the evaluation. Our hypothesis was that the tracheal narrowing as evaluated by computed tomography angiography increases with age in patients with Morquio A. The primary aim of the study was to examine the degree of tracheal narrowing in patients with Morquio A and describe the difficulties encountered during airway management, thus increasing awareness of both the tracheal narrowing and airway management difficulties in this patient population. In addition, the degree of tracheal narrowing was evaluated for its association with age or spirometry parameters using Spearman's rank correlation. Analysis of variance followed by the Bonferroni test was used to further examine the age-based differences in tracheal narrowing for the 3 age groups: 1 to 10 years, 11 to 20 years, and >21 years. RESULTS: Patient age showed a positive correlation with tracheal narrowing ( rs= 0.415; 95% confidence interval [95% CI], 0.138-0.691; P = .005) with older patients having greater narrowing of the trachea. Among spirometry parameters, FEF25%-75% showed an inverse correlation with tracheal narrowing as follows: FEF25%-75% versus tracheal narrowing: ( rs = -0.467; 95% CI, -0.877 to -0.057; P = .007). During anesthetic care, significant airway management difficulties were encountered, including cancelation of surgical procedures, awake intubation using flexible bronchoscope, and failed video laryngoscopy attempts. CONCLUSIONS: Clinically significant tracheal narrowing was present in patients with Morquio A, and the degree of such narrowing likely contributed to the difficulty with airway management during their anesthetic care. Tracheal narrowing worsens with age, but the progression appears to slow down after 20 years of age. In addition to tracheal narrowing, spirometry values of FEF25%-75% may be helpful in the overall evaluation of the airway in patients with Morquio A.

Tracheal narrowing in children and adults with mucopolysaccharidosis type IVA: evaluation with computed tomography angiography.

BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA) is characterized by progressive skeletal dysplasia and respiratory issues with difficult airway management during anesthesia. OBJECTIVE: To characterize tracheal abnormalities in children and adults with MPS IVA including interplay of the trachea, vasculature, bones and thyroid at the thoracic inlet. MATERIALS AND METHODS: 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. RESULTS: 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<0.05). The brachiocephalic artery was tortuous in 35/37 (95%) with direct impingement on the trachea in 24/37 (65%). No correlation was observed between bony thoracic inlet diameter and tracheal narrowing. The thyroid was located in the thoracic inlet in 28/37 (76%) cases, significantly associated with tracheal narrowing (P=0.016). CONCLUSION: Narrowing, deviation and abnormal shape of the trachea at the thoracic inlet are common in children and adults with MPS IVA, with a trend toward increased narrowing with advancing age in children. A W- or T-shaped trachea is associated with focal tracheal narrowing. Crowding of the thoracic inlet, due to vascular tortuosity and thyroid position, appears to play a major role.

Pediatric Airway Management in COVID-19 Patients: Consensus Guidelines From the Society for Pediatric Anesthesia's Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society.

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.

Critical review of current MPS guidelines and management.

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.

Consensus Statement of the Malignant Hyperthermia Association of the United States on Unresolved Clinical Questions Concerning the Management of Patients With Malignant Hyperthermia.

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.

Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA.

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.

Mucopolysaccharidosis IVA and glycosaminoglycans.

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.

Best practices in peri-operative management of patients with skeletal dysplasias.

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.

Metatropic dysplasia-a skeletal dysplasia with challenging airway and other anesthetic concerns.

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.

Obstructive airway in Morquio A syndrome, the past, the present and the future.

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.

Activity of daily living for Morquio A syndrome.

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.

A case series of peripheral nerve blocks in pediatrics and young adults with skeletal dysplasia.

AIM: 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.

Non-invasive pulmonary function test on Morquio patients.

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 endpoints 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 inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (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 >95% oxygen saturation, end tidal CO2 (38-44 mmHg), 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, although 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 patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs of restrictive and/or obstructive lung disease.

Diagnostic evaluation, monitoring, and perioperative management of spinal cord compression in patients with Morquio syndrome.

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.

Paraplegia after epidural-general anesthesia in a Morquio patient with moderate thoracic spinal stenosis.

PURPOSE: 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. CLINICAL FEATURES: 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. CONCLUSION: 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.

Clinical relevance of echocardiogram in patients with cerebral palsy undergoing posterior spinal fusion.

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.

Prophylactic methylprednisolone to reduce inflammation and improve outcomes from one lung ventilation in children: a randomized clinical trial.

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.

Morquio A syndrome: diagnosis and current and future therapies.

Morquio A syndrome is an autosomal recessive disorder, one of 50 lysosomal storage diseases (LSDs), and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme causes specific glycosaminoglycan (GAG) accumulation: keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced in the cartilage, therefore, the undegraded substrates accumulate mainly in cartilage and in its extracelluar matrix (ECM), causing direct leads to direct impact on cartilage and bone development and leading to the resultant systemic skeletal spondyloepiphyseal dysplasia. Chondrogenesis ,the earliest phase of skeletal formation that leads to cartilage and bone formation is controlled by cellular interactions with the ECM, growth and differentiation factors and other molecules that affect signaling pathways and transcription factors in a temporal-spatial manner. In Morquio A patients, in early childhood or even at birth, the cartilage is disrupted presumably as a result of abnormal chondrogenesis and/ or endochondral ossification. The unique clinical features are characterized by a marked short stature, odontoid hypoplasia, protrusion of the chest, kyphoscoliosis, platyspondyly, coxa valga, abnormal gait, and laxity of joints. In spite of many descriptions of the unique clinical manifestations, diagnosis delay still occurs. The pathogenesis of systemic skeletal dysplasia in Morquio A syndrome remains an enigmatic challenge. In this review article, screening, diagnosis, pathogenesis and current and future therapies of Morquio A are discussed.

Severe Multilevel Tracheal Stenosis with Significant Twisting in a Patient with Spondylometaphyseal Dysplasia: A Case Report.

Spondylometaphyseal dysplasia (SMD) is a rare genetic disorder affecting skeletal growth and development presenting anesthesiologists with many perioperative challenges. We present a case of a patient found to have multilevel tracheal stenosis due to twisting and folding of his trachea. This was discovered on imaging during a research review of SMD cases at our institution. Structural and functional abnormalities of the trachea have not been reported in SMD. This is the first description of a patient with SMD with severe multilevel tracheal disease requiring tracheal reconstructive surgery.

Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase, which results in systemic accumulation of glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. Accumulation of these GAGs causes characteristic features as disproportionate dwarfism associated with skeletal deformities, genu valgum, pigeon chest, joint laxity, and kyphoscoliosis. However, the pathological mechanism of systemic skeletal dysplasia and involvement of other tissues remain unanswered in the paucity of availability of an autopsied case and successive systemic analyses of multiple tissues. We report here a 20-year-old male autopsied case with MPS IVA, who developed characteristic skeletal features by the age of 1.5 years and died of acute respiratory distress syndrome five days later after occipito-C1-C2 cervical fusion. We pathohistologically analyzed postmortem tissues including trachea, lung, thyroid, humerus, aorta, heart, liver, spleen, kidney, testes, bone marrow, and lumbar vertebrae. The postmortem tissues relevant with clinical findings demonstrated 1) systemic storage materials in multiple tissues beyond cartilage, 2) severely vacuolated and ballooned chondrocytes in trachea, humerus, vertebrae, and thyroid cartilage with disorganized extracellular matrix and poor ossification, 3) appearance of foam cells and macrophages in lung, aorta, heart valves, heart muscle, trachea, visceral organs, and bone marrow, and 4) storage of chondrotin-6-sulfate in aorta. This is the first autopsied case with MPS IVA whose multiple tissues have been analyzed pathohistologically and these pathological findings should provide a new insight into pathogenesis of MPS IVA.