Guirish Solanki

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management

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.

Anaesthesia and airway management in mucopolysaccharidosis

This paper provides a detailed overview and discussion of anaesthesia in patients with mucopolysaccharidosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical manifestations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardiovascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation difficulties or failure [can’t intubate, can’t ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS should always be balanced against the associated risks. Therefore, careful evaluation of anaesthetic risk factors should be made before the procedure, involving evaluation of airways and cardiorespiratory and cervical spine problems. In addition, information on the specific type of MPS, prior history of anaesthesia, presence of cervical instability and range of motion of the temporomandibular joint are important and may be pivotal to prevent complications during anaesthesia. Knowledge of these risk factors allows the anaesthetist to anticipate potential problems that may arise during or after the procedure. Anaesthesia in MPS patients should be preferably done by an experienced (paediatric) anaesthetist, supported by a multidisciplinary team (ear, nose, throat surgeon and intensive care team), with access to all necessary equipment and support.

A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II

Purpose:Approximately two-thirds of patients with the lysosomal storage disease mucopolysaccharidosis II have progressive cognitive impairment. Intravenous (i.v.) enzyme replacement therapy does not affect cognitive impairment because recombinant iduronate-2-sulfatase (idursulfase) does not penetrate the blood–brain barrier at therapeutic concentrations. We examined the safety of idursulfase formulated for intrathecal administration (idursulfase-IT) via intrathecal drug delivery device (IDDD). A secondary endpoint was change in concentration of glycosaminoglycans in cerebrospinal fluid.Methods:Sixteen cognitively impaired males with mucopolysaccharidosis II who were previously treated with weekly i.v. idursulfase 0.5 mg/kg for ≥6 months were enrolled. Patients were randomized to no treatment or 10-mg, 30-mg, or 1-mg idursulfase-IT monthly for 6 months (four patients per group) while continuing i.v. idursulfase weekly.Results:No serious adverse events related to idursulfase-IT were observed. Surgical revision/removal of the IDDD was required in 6 of 12 patients. Twelve total doses were administrated by lumbar puncture. Mean cerebrospinal fluid glycosaminoglycan concentration was reduced by approximately 90% in the 10-mg and 30-mg groups and approximately 80% in the 1-mg group after 6 months.Conclusions:These preliminary data support further development of investigational idursulfase-IT in MPS II patients with the severe phenotype who have progressed only to a mild-to-moderate level of cognitive impairment.Genet Med 18 1, 73–81.

Predictors of blood loss in fronto-orbital advancement and remodeling.

Fronto-orbital advancement and remodeling for craniosynostosis is extensive surgery and is associated with potential risks; the most significant of these is blood loss. We prospectively studied 116 consecutive patients undergoing fronto-orbital advancement by the same surgical team for a 5-year 6-month period to determine what factors are associated with blood loss and transfusion of blood products. The data collected on the calvarial sutures involved were whether the patient had a diagnosed syndrome, the age at operation, the length of the operation, the estimated blood volume lost during the perioperative course, the number of units of packed cells transfused (donor exposures), and the use of other blood products. The mean (SD) total blood volume lost was 116% (5.4) of the estimated preoperative volume. The median number of whole units of packed cells transfused was 2 units. Other blood products were given in 28% of the cases. There was significantly greater blood loss in those patients with recognized craniofacial syndromes, pansynostosis, an operating time longer than 5 hours, and an age of 18 months or younger at operation. The use of other blood products was associated with those patients losing a blood volume higher than the mean.

A multinational, multidisciplinary consensus for the diagnosis and management of spinal cord compression among patients with mucopolysaccharidosis VI

Cervical cord compression is a sequela of mucopolysaccharidosis VI, a rare lysosomal storage disorder, and has devastating consequences. An international panel of orthopedic surgeons, neurosurgeons, anesthesiologists, neuroradiologists, metabolic pediatricians, and geneticists pooled their clinical expertise to codify recommendations for diagnosing, monitoring, and managing cervical cord compression; for surgical intervention criteria; and for best airway management practices during imaging or anesthesia. The recommendations offer ideal best practices but also attempt to recognize the worldwide spectrum of resource availability. Functional assessments and clinical neurological examinations remain the cornerstone for identification of early signs of myelopathy, but magnetic resonance imaging is the gold standard for identification of cervical cord compression. Difficult airways of MPS VI patients complicate the anesthetic and, thus, the surgical management of cervical cord compression. All patients with MPS VI require expert airway management during any surgical procedure. Neurophysiological monitoring of the MPS VI patient during complex spine or head and neck surgery is considered standard practice but should also be considered for other procedures performed with the patient under general anesthesia, depending on the length and type of the procedure. Surgical interventions may include cervical decompression, stabilization, or both. Specific techniques vary widely among surgeons. The onset, presentation, and rate of progression of cervical cord compression vary among patients with MPS VI. The availability of medical resources, the expertise and experience of members of the treatment team, and the standard treatment practices vary among centers of expertise. Referral to specialized, experienced MPS treatment centers should be considered for high-risk patients and those requiring complex procedures. Therefore, the key to optimal patient care is to implement best practices through meaningful communication among treatment team members at each center and among MPS VI specialists worldwide.

Is there a relationship between the severity of metopic synostosis and speech and language impairments

The occurrence of cognitive impairment and behavioral problems in patients with metopic synostosis has been described. The relationship between the severity of metopic synostosis and the incidence of speech and language delays has not been established. Twenty patients with nonsyndromic isolated metopic synostosis were evaluated. Five different preoperative measurements (metopic angle at the roof of the orbit, angle of lateral orbital wall at the sella, cranial indices, and distances between medial orbital walls and lateral orbital walls) were taken from computed tomography and compared with results from postoperative speech and language assessments. Frontal orbital advancement and remodeling were carried out by the same surgical team at a mean age of 1 year 4 months. Speech and language were assessed at 3 and 5 years. Six of the 20 patients had delayed speech and language developments. No consistent trend was observed linking the severity of frontal stenosis using the measured parameters with speech and language delays. Speech and language impairments in these patients cannot be explained by a physical concept, causing mechanical compression of the frontal lobes.

Clinical significance of medication reconciliation in children admitted to a UK pediatric hospital: observational study of neurosurgical patients.

BackgroundIn December 2007, the National Institute for Health and Clinical Excellence and the National Patient Safety Agency in the UK (NICE-NPSA) published guidance that recommends all adults admitted to hospital receive medication reconciliation, usually by pharmacy staff. A costing and report tool was provided indicating a resource requirement of £12.9 million for England per year. Pediatric patients are excluded from this guidance.ObjectiveTo determine the clinical significance of medication reconciliation in children on admission to hospital.MethodsA prospective observational study included pediatric patients admitted to a neurosurgical ward at Birmingham Children’s Hospital, Birmingham, England, between September 2006 and March 2007. Medication reconciliation was conducted by a pharmacist after the admission of each of 100 consecutive eligible patients aged 4 months to 16 years. The clinical significance of prescribing disparities between pre-admission medications and initial admission medication orders was determined by an expert multidisciplinary panel and quantified using an analog scale. The main outcome measure was the clinical significance of unintentional variations between hospital admission medication orders and physician-prescribed pre-admission medication for repeat (continuing) medications.ResultsInitial admission medication orders for children differed from prescribed pre-admission medication in 39% of cases. Half of all resulting prescribing variations in this setting had the potential to cause moderate or severe discomfort or clinical deterioration. These results mirror findings for adults.ConclusionsThe introduction of medication reconciliation in children on admission to hospital has the potential to reduce discomfort or clinical deterioration by reducing unintentional changes to repeat prescribed medication. Consequently, there is no justification for the omission of children from the NICE-NPSA guidance concerning medication reconciliation in hospitals, and costing tools should include pediatric patients.

Changing referral patterns to a designated craniofacial centre over a four-year period.

Craniofacial conditions are mainly treated within England by four supra-regional centres. Due to a continuous increase in the number of cases referred to our service we audited the source and nature of these referrals. Data was prospectively collected over a four-year period from April 2004 to March 2008. The speciality of the referring clinicians was recorded, along with the diagnosis. A year-by-year increase in the number of referrals from 138 in 2004-2005 to 253 in 2007-2008 was seen. There was a 214% increase in the number of patients referred with single suture craniosynostosis, a 520% increase in patients with benign hyperplastic conditions such as fibrous dysplasia, neurofibromatosis and vascular anomalies and a 220% increase in patients treated elsewhere but now needing revision surgery. A 407% increase in referrals for positional plagiocephaly was recorded. Our referral pattern reflects the internationally accepted increase in the incidence of metopic synostosis and positional plagiocephaly. Due to the skill mix and experience present in a designated craniofacial service other benign hyperplastic and hypoplastic conditions are increasingly being referred. Additional referrals have come from a change in the referral pathway. To manage the increased workload we have established separate clinics to manage vascular anomalies and have adopted a policy of not reviewing patients with positional plagiocephaly.

Infantile clivus chordoma without clivus involvement: case report and review of the literature

BackgroundWe present a giant clival chordoma with disseminated disease but without involvement of the clivus. To our knowledge, this is the youngest child and only the second case, presenting without base of skull involvement, in paediatric literature and the fourth reported case of a chordoma in a patient with tuberous sclerosis.DiscussionWe discuss the subtle presentation, difficulties in diagnosis and management and also review the literature.

Normal Fusion of the Metopic Suture

AbstractThere is some uncertainty as to when normal fusion of the metopic suture occurs. Existing studies have included relatively small numbers and have not used a statistical model to represent any variation in normality. In this study, a total of 337 head computed tomographic scans performed between 2006 and 2009 were retrospectively reviewed after strict exclusion criteria were met. Only patients aged younger than 18 months were included. Assessment was performed by analyzing axial slices of the bony window of the computed tomographic scan by 2 independent investigators. Two separate probit analyses were carried out to estimate the proportion of patients in whom the fusion process would have started and completed. Of 337 patients, 204 (60.5%) were male and 133 were female (39.5%). All patients older than 15 months and 23 days had completely fused metopic sutures. The estimated median age for the start of the fusion process was 4.96 months (95% confidence interval, 3.54–6.76 months), and the estimated median age for the completion of fusion was 8.24 months (95% confidence interval, 7.37–9.22 months). The fusion process completed between 2.05 and 14.43 months of age in 95% of the normal population. The difference between sexes was not significant. In conclusion, there was wide variation in the timing of normal fusion that can complete as early as 2 months of age.