Iain Bruce

Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies.Take-home messageExpertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease.

MOMENT -- Management of Otitis Media with Effusion in Cleft Palate: protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

BackgroundCleft palate (CP) has an incidence of approximately 1 in 700. Children with CP are also susceptible to otitis media with effusion (OME), with approximately 90% experiencing nontrivial OME. There are several approaches to the management of OME in children with CP. The Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) study is a feasibility study that includes the development of a core outcome set for use in future trials of the management of OME in children with CP.Methods/DesignThe MOMENT study will include a systematic review of the literature to identify a list of outcomes that have previously been reported. This list of outcomes will be used in a Delphi study with cleft clinicians. The Delphi study is anticipated to include three rounds. The first round will ask clinicians to score the outcome list and to add any outcomes they think are relevant. The second round involves presentation of scores according to stakeholder group and the opportunity for participants to rescore outcomes. To ensure that the opinion of parents and children are sought, qualitative interviews will be completed with a purposive sample in parallel. In the final round of the Delphi process, participants will be shown the distribution of scores, for each outcome, for all stakeholder groups separately as well as a summary of the results concerning outcomes from the qualitative interviews with parents. A final consensus meeting will be held with all stakeholders, including parents and children, to review outcomes.DiscussionA core outcome set represents the minimum that should be measured in a clinical trial for a particular condition. The MOMENT study will aim to identify a core outcome set that can be used in future trials of the management of OME, improving the consistency of research in this clinical area.

Botulinum toxin is effective and safe for palatal tremor

Palatal tremor (formerly palatal myoclonus) is an extremely rare, but potentially treatable cause, of objective tinnitus. The tinnitus is thought to be secondary to rhythmic involuntary movements of the soft palate. Its aetiology is variable and it remains difficult to treat. Many different medical and surgical remedies have been tried but none have demonstrated reproducible success. Botulinum toxin has been used in sporadic cases and seems to produce good results. Ten patients with palatal tremor have presented to this department over the last three years. After discussion with the patients with regard to the management of this condition and possible complications, five opted for botulinum toxin therapy and five declined further intervention. Clinical diagnosis was made on the confirmation of soft palate movements synchronous with an audible clicking noise. Five patients underwent botulinum toxin injection into the insertion of the levator and tensor veli palatini muscles. Of the five that were treated with toxin, four showed complete resolution of symptoms after a course of treatment. Only one patient reported transient side effects. This would suggest that botulinum toxin is a safe and effective first line treatment for palatal tremor.

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.

Surgical complications of tracheo-oesophageal puncture and speech valves.

Purpose of reviewSpeech rehabilitation following total laryngectomy is central to future quality of life. Although other options exist, surgical voice restoration has emerged as the ‘gold standard’ management strategy in the majority of laryngectomees. Taking this into account, what are the complications of this technique and how should they be successfully managed? The purpose of this review is to provide a comprehensive review of the subject, with particular reference to technique, complications and outcome. Recent findingsAs with any surgical intervention, complications may occur in the early postoperative period or later. The article provides a detailed explanation of the varying problems detailed in individual reports, and in case series. Primary or secondary tracheo-oesophageal puncture is also discussed, along with complications resulting from the speech valve itself. SummaryThe positive impact of surgical voice restoration on quality of life in the alaryngeal patient considerably outweighs the complications commonly associated with the procedure. Greater knowledge of the potential problems should continue to reduce the complication rate. Primary puncture, in a patient selected and subsequently managed in a multidisciplinary environment, would appear to provide the best outcome for the patient.

Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma

Patients with adenoid cystic carcinoma of the salivary glands show over-expression of KIT in a high proportion of cases. Options for systemic treatment are limited in locally advanced and metastatic disease. We explored the efficacy of imatinib and cisplatin combined in this group of patients. A Gehans two-stage, phase II trial was conducted on 28 patients. Those with progressive, locally advanced, and metastatic disease with an over-expression of KIT were treated with single agent imatinib 800 mg daily for two months, followed by a combination of imatinib 400mg daily and cisplatin 80 mg/m(2) at four-weekly intervals for six cycles. This was followed by maintenance single agent imatinib 400mg daily until the disease progressed. Response was monitored using fluorodeoxyglucose positron emission tomography (FDG-PET) and morphological imaging using computed tomography, magnetic resonance, and chest radiographs (CT/MRI/CXR). Morphological imaging showed partial response in three of 28 patients, and five patients showed a response on FDG-PET. In addition, 19 patients had useful stabilisation of disease. The median time to progression and overall survival was 15 months (range 1-43) and 35 months (range 1-75), respectively. The combination of imatinib and cisplatin was reasonably well tolerated. This combination may provide stabilisation in locally advanced and metastatic adenoid cystic carcinoma of the salivary glands.

The importance of integration of stakeholder views in core outcome set development : otitis media with effusion in children with cleft palate

Background Approximately 75% of children with cleft palate (CP) have Otitis Media with Effusion (OME) histories. Evidence for the effective management of OME in these children is lacking. The inconsistency in outcome measurement in previous studies has led to a call for the development of a Core Outcome Set (COS). Despite the increase in the number of published COS, involvement of patients in the COS development process, and methods to integrate the views of patients and health professionals, to date have been limited. Methods and Findings A list of outcomes measured in previous research was identified through reviewing the literature. Opinion on the importance of each of these outcomes was then sought from key stakeholders: Ear, Nose and Throat (ENT) surgeons, audiologists, cleft surgeons, speech and language therapists, specialist cleft nurses, psychologists, parents and children. The opinion of health professionals was sought in a three round Delphi survey where participants were asked to score each outcome using a bespoke online system. Parents and children were also asked to score outcomes in a survey and provided an in-depth insight into having OME through semi-structured interviews. The results of the Delphi survey, interviews and parent/patient survey were brought together in a final consensus meeting with representation from all stakeholders. A final set of eleven outcomes reached the definition of “consensus in” to form the recommended COS: hearing; chronic otitis media (COM); OME; receptive language skills; speech development; psycho social development; acute otitis media (AOM); cholesteatoma; side effects of treatment; listening skills; otalgia. Conclusions We have produced a recommendation about the outcomes that should be measured, as a minimum, in studies of the management of OME in children with CP. The development process included input from key stakeholders and used novel methodology to integrate the opinion of healthcare professionals, parents and children.

A selective approach to histopathology of the gallbladder is justifiable.

BACKGROUND Recent changes in the NHS have led to a considerably increased workload for histopathologists prompting the publication of guidelines from the Royal College of Pathologists regarding specimen analysis. In most hospitals, cholecystectomy specimens are routinely sent for histology regardless of whether or not there is any visible macroscopic abnormality suggestive of malignancy. Our aim was to assess whether it would be safe to adopt a policy of processing only suspicious gallbladders without compromising patient management and outcome. METHODS A retrospective analysis of all cholecystectomies performed between 1995 and 1999 was conducted using computerised histopathology records and patient notes. The histopathology department has a standardised procedure for the evaluation of cholecystectomy specimens and all gallbladders had been processed in this manner. RESULTS 1308 patients had undergone cholecystectomy (mean 262/year). All specimens had been sent for histology: 1249 of the specimens showed chronic cholecystitis, 38 acute cholecystitis or empyema and 16 were removed as part of another procedure. In five gallbladders there was evidence of primary carcinoma. In all cases the gallbladder was opened at the time of surgery (as commented upon in the operation notes) and all showed macroscopic evidence suggestive of carcinoma. Pre-operative ultrasound scanning identified probable carcinoma in three of the five cases. CONCLUSIONS All cases of gallbladder carcinoma were diagnosed pre-operatively or intra-operatively and a histological diagnosis did not alter the management or outcome of any of these patients. Selective histopathology of the gallbladder is safe and may be a more measured approach saving histolopathology departments time and money.

The role of magnetic resonance imaging in the assessment of suspected extrinsic tracheobronchial compression due to vascular anomalies

Aims: To evaluate the role of magnetic resonance imaging (MRI) in the assessment of children with suspected extrinsic tracheobronchial compression due to vascular anomalies. Methods: Retrospective case note review in a tertiary referral centre. Twenty nine children who underwent dynamic laryngotracheobronchoscopy (DLTB) and were found to have a clinical suspicion of extrinsic tracheobronchial compression were evaluated. All subsequently underwent thoracic MRI within 10 days. The findings on endoscopy were compared to those of MRI, and where performed, echocardiography, aortography, and surgery. Results: There were 17 males and 12 females (mean age 5 months, range 28 weeks gestation to 60 months). The most common presenting features were stridor and cyanotic episodes. MRI showed abnormalities in 21 patients. There were five vascular rings (three double aortic arches and two right aortic arches) and 11 cases of innominate artery compression. Other vascular anomalies noted included aberrant right subclavian artery and aneurysmal left pulmonary artery. Echocardiography was generally found to be unhelpful in the diagnosis of extra-cardiac vascular abnormalities. Angiography was subsequently conducted in eight children; findings agreed with those shown on MRI. Surgery was performed on all five vascular rings, one innominate artery compression, and one aneurysmal left pulmonary artery. Surgical findings were also compatible with the preoperative MRI. Conclusions: This study shows the successful use of MRI as the initial imaging modality in endoscopically suspected extrinsic vascular compression of the upper airway. It enables accurate delineation of vascular anomalies and, unlike aortography, is non-invasive and does not require the use of contrast media.

Cochlear implantation in children with cerebral palsy

OBJECTIVE Few studies have looked at the outcomes of children with complex needs following cochlear implantation. Increasing evidence supports the case for implantation in these children. To date there is very little evidence available evaluating the role of cochlear implantation in children with cerebral palsy. In this paper we look at the Manchester Cochlear Implant Programmes experience of implantation in 36 children with cerebral palsy. METHODS A retrospective review of prospectively collected data for all children with cerebral palsy was undertaken. Cognitive and physical disability was scored by members of the cochlear implant team. A modified version of Geers and Moogs 1987 Speech Reception Score was used to assess outcome. Data was analysed looking at the relationship between cognitive and physical impairment, age at implantation and the SRS outcomes. RESULTS This study demonstrated that children with cerebral palsy and a mild cognitive impairment do significantly better following implantation than those with a severe impairment (p=0.008). Children with mild physical impairment did not appear to do significantly better than those with moderate or severe impairments (mild versus severe p=0.13). Age at implantation was not a significant prognostic factor in this study group. CONCLUSIONS Children with complex needs are increasingly being referred for consideration of cochlear implantation. Further research is required to help guide candidacy, but each case must be considered individually. Higher functioning does appear to be the most important prognostic indicator regarding outcome but the effect of modest improvement in sound perception should not be underestimated.