THE WINSTON CHURCHILL MEMORIAL TRUST OF AUSTRALIA. Dr. Manoj Menezes Churchill Fellow

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1 1 THE WINSTON CHURCHILL MEMORIAL TRUST OF AUSTRALIA Dr. Manoj Menezes 2011 Churchill Fellow CHURCHILL FELLOWSHIP to study the assessment and diagnosis of patients with inherited muscle disorders and peripheral neuropathies - UK, Slovenia, Portugal. I understand that the Churchill Trust may publish this Report, either in hard copy or on the internet or both, and consent to such a publication. I indemnify the Churchill Trust against any loss, costs or damages it may suffer rising out of any claim or proceedings made against the Trust in respect of or arising out of the publication of any Report submitted to the Trust and which the Trust places on a website for access over the internet. I also warrant that my Final Report is original and does not infringe the copyright of any person, or contain anything which is, or the incorporation of which into the Final Report is, actionable for defamation, a breach of any privacy law or obligation, breach of confidence, contempt of court, passing-off or contravention of any other private right or of any law. Signed: Manoj Menezes Dated: 22 nd January 2012

2 2 Index Introduction 3 Executive Summary 4 Fellowship Programme 5 Inherited Neuromuscular Disorders: An Overview 6 Page MRC Centre for Neuromuscular disease (London) 11 Dubowitz Neuromuscular Centre 15 Nerve conduction testing and EMG 16 The 2011 International Course on EMG, SFEMG 17 and Nerve Ultrasonography 16 th International Congress of the World 17 Muscle Society Conclusions, Recommendations, Dissemination 18 and Implementation

3 3 Introduction The last decade has seen significant progress in the management of children with muscle and nerve diseases. Some of this has been because of improved rehabilitation techniques and early and intensive management of the respiratory and cardiac complications. However, the most exciting breakthroughs have been in the understanding of the genetic basis of these diseases. These advances have provided us the ability to diagnose children with neuromuscular disease early, institute appropriate rehabilitative measures, put in place appropriate surveillance and therapy for the complications and to provide a better understanding of the prognosis to the family and the child. Achieving a genetic diagnosis also provides the family the option of genetic testing in a future pregnancy. Targeting the genetic basis of these disorders holds great promise in the development of disease-modifying therapy, and ultimately, a cure. I am a paediatric neurologist and have a clinical and research interest in the diagnosis and management of children with neuromuscular disease. I have been fortunate that my training in paediatric neuromuscular disease has occurred at a time where our ability to diagnose and manage children with muscle and nerve diseases has improved by leaps and bounds. Our next challenge is to coordinate the both the clinical care of affected children, and neuromuscular research, at the national and international level and to modify existing funding models to reflect the changes over the last decade. The Churchill Fellowship gave me the opportunity to be a part of the clinical and research programme at the National Hospital for Neurology and Neurosurgery, Queen Square and the Great Ormond Street Children s Hospital, both of which are international centres of excellence in clinical care and research in neuromuscular disease. I would like to thank the Winston Churchill Trust for this opportunity, as also the ability to establish contact with prominent researchers in the field with whom I hope to collaborate once I return to Australia. I would like to thank Prof. Kathryn North and Prof. Robert Ouvrier, for their support and encouragement as referees during the application process. I would also like to thank Prof. Mary Reilly (NHNN, Queen Square) and Prof. Francesco Muntoni (DNC, Great Ormond Street Hospital), and the staff at the MRC Center for Neuromuscular disease and the Dubowitz Neuromuscular centre who, despite their busy schedules and myriad responsibilities, helped arrange my itinerary and welcomed me into their neuromuscular clinics. Finally, I would like to thank all the patients and families that I met in clinic and from whom I learnt a great deal. My Churchill Fellowship was not only academically rewarding but also a thoroughly enjoyable experience.

4 4 Executive Summary Dr. Manoj Menezes Paediatric Neurologist Institute for Neuroscience and Muscle Research Children s Hospital at Westmead Cnr Hawkesbury Rd and Hainsworth St, Westmead, Sydney, N.S.W. Tel: CHURCHILL FELLOWSHIP to study the assessment and diagnosis of patients with inherited muscle disorders and peripheral neuropathies. During the fellowship I visited the MRC Centre for Neuromuscular Disease and Dubowitz Neuromuscular Centre in London. I also attended the SFEMG course in Llubljana, Slovenia and the WMS 2011 Conference in Portugal. Recommendations 1. Establishment of a nationally funded centre of excellence for care of children with neuromuscular disease. 2. Coordination of genetic testing and research into neuromuscular disease at a national level. 3. Change in traditional models of funding for genetic testing, so that testing for rarer genetic testing and newer gene testing modalities are more widely accessible. Dissemination and implementation 1. I will have the opportunity to apply my improved skill and knowledge in the diagnosis and management of children with neuromuscular disease into my clinical practice as a neuromuscular physician, and to present the knowledge I have gained at clinical and scientific meetings. 2. I plan to collaborate with many of the scientists and researchers I have met through the Churchill Fellowship in order to provide access to our patients to newer genetic tests and genetic research techniques not currently available in Australia. 3. I plan to advocate and work towards the establishment of a centre of clinical and research excellence in neuromuscular medicine, particularly peripheral nerve medicine, in Australia.

5 5 Fellowship Programme 11 th September 22 nd October 2011 National Hospital for Neurology and Neurosurgery and MRC Centre for Neuromuscular Disease, Queen Square, London, UK Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, UK 23 rd 25 th September 2011 The 2011 International Course on Electromyography (EMG), Single Fibre EMG (SFEMG) and Nerve Ultrasonography The Institute of Clinical Neurophysiology University Medical Centre Ljubljana, Slovenia 3 rd 5 th October 2011 Improving the use of electromyography in paediatrics: Paediatric EMG and SFEMG course UCL Institute of Child Health London, UK 18 th 22 nd October th International Congress of the World Muscle Society Ria Park Hotels, Resort and Spa Almancil, Algarve, Portugal

6 6 Inherited Neuromuscular Disorders: An Overview Coordinated movement requires the efficient transmission of an impulse, generated in neurons in the cerebral cortex, down the spinal cord and then along the peripheral nerve and neuromuscular junction to activate the contractile apparatus within the muscle. Abnormalities in the function of the peripheral nerve, the neuromuscular junction or the muscle result in weakness and wasting of the muscle and are classified together as neuromuscular disorders. Neuromuscular disorders include both inherited and acquired disorders of the nerve and muscle. They may be considered to be relatively uncommon in the general population with inherited muscle disorders having a population prevalence of 37.0/ , while Charcot- Marie-Tooth disease (CMT), the commonest inherited nerve disease, has a population prevalence of 40/ However, most of these disorders have an onset in childhood and are a common cause of childhood presentation to hospital, attendances at outpatient clinics, inpatient admissions and presentations to the emergency department. The common inherited neuromuscular disorders are listed in table 1. Table 1. Common neuromuscular disorders 1 Level of lesion Anterior horn cell Peripheral nerve Neuromuscular junction Muscle Common disorders Spinal muscular atrophy Charcot-Marie-Tooth disease Congenital myasthenic syndromes Juvenile myasthenia gravis Duchenne and Becker muscular dystrophy Other limb-girdle dystrophies Congenital myopathies Congenital muscular dystrophies Myotonic dystrophy Living with a neuromuscular disorder can present significant challenges to the affected child and their family. They cause a progressive loss of strength, loss of sensation, wasting of the affected muscles and loss of ambulation. The severe neuromuscular disorders can affect cardiac and respiratory muscles and, unfortunately, sometimes be life-limiting. They can also have a devastating impact on the rest of the family with the significant emotional and financial costs of caring for an affected child. The effective diagnosis and management of children with neuromuscular disorders requires physicians trained to recognise and evaluate affected children, specialists skilled in performing and interpreting intricate diagnostic tests and allied

7 7 health professionals experienced in rehabilitation. With the genetic cause of a large number of these disorders remaining undiscovered, and effective disease-modifying or curative therapy available for only a small fraction, there also need to be an investment of resources into research into these disorders. A cost and resource effective way to accomplish this would be to establish a single or a network of centralised tertiary-care clinical and research facilities that can provide advice, clinical and diagnostic services and rehabilitation support to the neurologists, paediatricians and allied health professionals involved in the care of these children throughout the country, while supporting scientists involved in research and providing access to clinical trials to affected children. Identifying the genetic basis of neuromuscular disorders Children with inherited neuromuscular disorders usually have an early onset and a progressive course, often without rapid deterioration or improvement in their clinical function. The progress of the difficulties varies among the different neuromuscular disorders but most affected children will have delayed motor milestones or difficulties with their motor abilities. Some never learn to walk while others lose the ability to ambulate with progress of the disease. While the presence of a known pathogenic mutation confirms the genetic basis of a neuromuscular disorder, this is possible in only around 67% of those with CMT and 75% of those with an inherited muscle disorder 2, 3. In the rest, a genetic etiology is presumed on the basis of the family history and careful delineation of clinical features, supported by histological and immunohistochemical testing. The number of genes identified to cause neuromuscular disorders has increased exponentially over the last 2 decades. The first gene causing inherited neuropathy was identified only in 1991; a century after the disorder was described by Jean-Martin Charcot and Pierre Marie in France and by Howard Henry Tooth in London in We now know of more than 40 genes causing inherited neuropathy, and genes causing neuropathy have been identified on each of the 23 chromosomes.

8 8 Figure 1. Genes causing inherited neuropathy. (Courtesy Prof. Mary Reilly, MRC Centre for Neuromuscular disorders, Queen Square, London) Similarly, the gene for Duchenne Muscular dystrophy, the most common form of inherited muscle disease, was identified in We now know of more than 50 genes that cause inherited muscle disease and the list continues to expand rapidly. Figure 2. Components of the muscle sarcolemmal membrane and contractile apparatus. Mutations have been found in almost genes encoding almost every protein in this system (From Muntoni F. Neuromuscular Disorders 2004)

9 9 Why do we need to identify the underlying genetic mutation? The genetic basis of a child s neuromuscular disorder can be confirmed only by testing for mutations in a suspected gene by a process called gene sequencing. While the clinical features and diagnostic tests that may suggest a particular gene, many genetic diseases have a broad clinical phenotype. The cost of sequencing a single gene usually ranges from a few hundred to a few thousand dollars (for rare and large genes). For the rarer muscle and nerve disorders, this adds significantly to cost as the number of genes sequenced to identify a particular child s genetic mutation increases. Most health services and hospitals, including those in Australia, have limitations on the amount of money that can be allocated for genetic testing. Over the last two decades, the number of diseases for which a genetic diagnosis is available has increased exponentially. There has been no cure identified for any neuromuscular disorder, and disease-modifying therapy is available for only a couple. In the remaining therapy is mainly rehabilitative and aimed at preserving function or limiting complications, but can improve quality of life and even the life-span, often significantly. It has been the convention to limit genetic testing, especially where testing is costly, to those genes where a treatment is available for the disease or to those families where identifying a genetic basis helps in planning and managing a subsequent pregnancy. However in addition to these, achieving a genetic diagnosis can have a number of benefits for the affected child, the family and towards research into that disorder For the child - identifying a genetic mutation confirms the diagnosis, and helps the child and the family understand the progress, complications and prognosis of that particular disorder - limits further unnecessary, costly, and sometimes invasive, diagnostic tests - enables the physician to monitor of the complications specific to that disorder and institute appropriate therapy early - enables the physician to commence disease-modifying therapy, where available For the family - enables the parents to understand the inheritance of the disorder with the option of testing a future pregnancy

10 10 For researchers - helps understand the prognosis of a known genetic disorder by observing a large number of children with the same genetic cause for their neuromuscular difficulties - a genetic diagnosis is a requirement for enrollment in clinical trials that may lead to useful rehabilitative and curative therapy, as therapies are often disease and gene specific However, a careful clinical assessment of the patient and accurate evaluation of appropriate investigations are required in order to select the appropriate gene or group of genes to tests. Recent advances have led to the development of new techniques that can sequence multiple genes at the same time, thereby saving time and money, and techniques that help identify new genes causing muscle disease. References 1. Menezes MP, North KN. Inherited neuromuscular disorders: Pathway to diagnosis. Journal of Paediatrics and Child Health 2011:no-no. 2. Norwood FLM, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain;132: Saporta ASD, Sottile SL, Miller LJ, Feely SME, Siskind CE, Shy ME. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Annals of Neurology;69:22-33.

11 11 MRC Centre for Neuromuscular disease (London) Funded by the Medical Research Council (MRC), a government funded body, and located at the National Hospital for Neurology and Neurosurgery, Queen Square, UCLH-Bloomsbury, the MRC Centre for Neuromuscular disease is a multidisciplinary translational research centre involved in the care of both adults and children with neuromuscular disease. The centre aims to deliver the highest quality patient care through a coordinated multidisciplinary approach, to translate research findings into clinical trials and new treatments for patients and to act as a national and international centre of excellence in clinical/research training and education in neuromuscular diseases. The centre treated over 5000 adults with neuromuscular disease in and works closely with the Dubowitz Neuromuscular Centre at Great Ormond Street Children s Hospital (GOSH) for the diagnosis and management of children with neuromuscular disease and their transition to adult services. The peripheral nerve service of the MRC Centre is led by Prof. Mary Reilly and consists of 6 consultants. During my Churchill Fellowship, and while continuing my research in the postfellowship period, I was part of the peripheral nerve service as an honorary clinical research fellow and attended the following clinics and meetings; Peripheral Neuropathy Clinic (0900 to 1300 Tuesday and Thursday) Prof. Reilly runs a tertiary referral peripheral neuropathy clinic twice a week with patients being referred by neurologists and GP s from around London and the rest of the UK. The clinic has a mix of new patients and patients being followed-up after having been seen there previously. Patients undergo a thorough evaluation with nerve conduction studies and EMG being performed at the same visit so that a provisional diagnosis can be formulated during the initial visit. The clinic is also supported by a visiting neurophysiologist (Dr. Julian Blake), a clinical nurse specialist (Ms. Karen Bull), physiotherapist (Dr. Gita Ramdharry) and the clinical research fellows. As Prof. Reilly is a renowned authority on inherited neuropathies, her clinic follows up patients with rare genetic neuropathies that affect only a few families or patients worldwide, and I was fortunate to have the opportunity to review these patients while in clinic. It was also a great learning experience to see how Prof. Reilly uses clues in the clinical history and examination and the results of investigations that include blood tests, nerve conduction tests and EMG and imaging studies like MRI, to formulate an opinion on whether the neuropathy is genetic or acquired and if genetic, to decide on a set of genes to test for. The clinic also reviews patients with acquired (non-genetic) neuropathies and some of these patients are on immunosuppressant medications for treatment. Patients who need complex and multiple

12 12 investigations that cannot be arranged during a single clinic visit or those that are on regular immunosuppressant medication are admitted to the day-stay or inpatient wards. There is also a joint neuropathy clinic with the Dubowitz Neuromuscular Centre where children with undiagnosed genetic neuropathies are reviewed by Prof. Reilly along with the GOSH neuromuscular team. CMT Management Clinic ( Thursday) The CMT management clinic is run by a consultant (Dr. Laura) and a physiotherapist (Dr. Ramdharry) and reviews patients who have been previously seen in the peripheral neuropathy clinic, with the focus on interventions (splints, mobility aids, exercise regimen) to improve their quality of life. Nerve Biopsy Review Meeting ( Wednesday) Occasionally it is necessary to perform a biopsy of a peripheral nerve and to perform various immunostaining and immunohistochemical techniques on the nerve section to look for microscopic abnormalities and signs of inflammation. The meeting is attended by the peripheral nerve consultants and pathologists skilled in the evaluating nerve biopsies. The MRC Centre performs approximately 150 peripheral nerve biopsies a year. MRI meeting (weekly) and Muscle MRI meeting (monthly) MRI s of the brain, spinal cord and muscles performed on patients with neuromuscular disease are reviewed under the supervision of a radiologist skilled in their interpretation. Genetics Meeting (1300 Tuesday once monthly) Results of genetic testing on patients with presumed inherited neuropathies are discussed at this meeting that is attended by the peripheral nerve consultants, geneticists and laboratory scientists. Often the results of genetic testing need to be evaluated depending on the clinical profile, and complex modelling using specialised software is required to determine if a particular gene abnormality does actually cause a disease. Plans for setting up new genetic tests and ongoing genetics research are also discussed. Peripheral Neuropathy Service and Research Laboratory The MRC Centre has a large laboratory with scientists performing genetic testing, and researchers involved in cutting-edge research that includes looking for genetic mutations, identifying new genes that cause neuromuscular disease and understanding how different genetic mutations cause peripheral neuropathies. I had the opportunity to meet and interact

13 13 with a number of these researchers with the aim of collaborating with them, especially for genetic tests that are not available yet in Australia. Databases and Clinical Trials Every patient who is reviewed in by the peripheral neuropathy service and presumed to have a genetic neuropathy is entered in a database that records their clinical profile, nerve conduction study result and the result of genetic testing. This allows easy access to patient data for research studies, for genetic testing when new genes are discovered, and for recruitment in clinical trials. Summary It was a wonderful learning experience to review patients with both common and rare genetic neuropathies and understand how to use the clinical review and the results of investigations to direct genetic testing. Despite being a large service which cares for complex patients referred from distant parts of the UK, the concentration of skilled physicians, allied health professionals and scientists working in a focussed area at one location enables the neuropathy service at the MRC Centre to provide comprehensive and holistic care to its patients. The consultants focus on patients with peripheral nerve disorders, allowing them to concentrate their skills and keep up-to-date with the latest advances in peripheral nerve research and the ever increasing number of genes that cause peripheral neuropathy. Even among themselves, the consultants have developed subspecialty interests in genetic, inflammatory and infectious neuropathies and lead research in their chosen field. Similarly, the service is backed by histopathologists and radiologists who are skilled at evaluating nerve and muscle biopsies and neuromuscular MRI s. The service is also supported by a service and research laboratory concentrating on peripheral nerve research and genetic testing. We have attempted to provide a similar service at the Children s Hospital at Westmead, Sydney, Australia for children with peripheral neuropathies, though many components of the service are still being developed. The aim will be to have children referred from all over Australia to the Neuropathy Diagnostic Clinic (already established) for an opinion on the cause and treatment of their peripheral neuropathy and to have them followed up at the Peripheral Neuropathy Management Clinic (already established) while sharing follow-up responsibilities with the referring physician. All children with a peripheral neuropathy will be part of the neuropathy database (being developed) and eligible for enrolment in clinical trials via the clinical trials arm (being developed). We hope to develop our expertise with neuromuscular MRI at the Children s Hospital at Westmead and our skill with interpreting nerve biopsies at the Sydney Nerve laboratory, University of Sydney. We also hope to develop our collaboration with

14 the Concord Hospital Molecular Medicine Laboratory, NSW, Australia and the MRC Centre for Neuromuscular Disease for genetic testing and research. 14

15 15 Dubowitz Neuromuscular Centre The Dubowitz Neuromuscular Centre (DNC) is part of the University Colleges London (UCL) Institute of Child Health and the Great Ormond Street Children s Hospital (GOSH), and a member of the MRC Centre for Neuromuscular disease. The DNC provides clinical assessment, diagnostic services and therapeutic and rehabilitative interventions for children with neuromuscular disease. Research at DNC focuses on understanding the cause of pediatric neuromuscular disease and developing novel therapies. The DNC is a centre of clinical and research excellence and has been designated by the National Commissioning Group (NCG) to provide a national specialist diagnostic and assessment service for congenital muscle disorders. The DNC team is led by Professor Francesco Muntoni and is composed of other consultants and clinical and research fellows and trainees who focus on pediatric neuromuscular disorders. In addition to my role at the MRC Centre, I also attended the following clinics at the DNC as an honorary clinical fellow; Muscle Biopsy Meeting ( Monday) The muscle biopsy meeting takes place prior to the neuromuscular clinic and all recent muscle biopsies, especially those from patients attending clinic that week, are viewed and discussed. The meeting is attended by clinicians from the DNC and histopathologists who focus primarily on paediatric muscle biopsies. It provides the clinician the unique opportunity to put together the clinical data with the results of microscopy and immunostaining of the muscle biopsies to formulate a diagnosis. Neuromuscular Clinic ( Monday) There are a number of neuromuscular clinics scheduled through the week at GOSH. I used to attend the Monday clinic that was to review new patients and also follow-up children with neuromuscular diseases. Other clinics during the week usually focused on a particular group of muscle diseases or a specific complication (for e.g. curvature of the spine (scoliosis), orthopaedic management, complications from long term steroid therapy). The Monday clinic is run by the neuromuscular consultants with the clinical and research fellows, and is supported by a clinic coordinator, social worker and physiotherapists. Children with undiagnosed neuromuscular diseases are referred from paediatricians throughout the UK, and it was again a wonderful learning experience to see how the clinical profile, results from the muscle biopsy and other investigations like muscle MRI were used to narrow the diagnostic possibilities and suggest a set of genes to test. The children are reviewed by physiotherapists during the same clinic visit and this is useful for documenting the muscle weakness and to measure change during a follow-up visit.

16 16 Nerve conduction testing and EMG Nerve conduction tests are a method by which the integrity of the peripheral nerves is evaluated by stimulating a nerve and recording the electrical impulse on the muscle it supplies. The stimulation and recording is done by electrodes on the skin surface and the tiny responses (in mv or µv) is amplified and displayed on a computer screen and this requires sophisticated equipment and software. On the days that I was not attending clinic at the MRC centre or GOSH (usually Wednesday and Friday), I would spend the day at the Neurophysiology laboratory at GOSH. The paediatric nerve conduction tests are performed by Dr. Matthew Pitt who is considered the foremost expert on nerve conduction studies and EMG in children. He continues to be one of the few neurophysiologists worldwide who perform testing solely on children, performing around 80 tests a month. Because of his expertise and association with the Dubowitz Neuromuscular Centre and Great Ormond Street Children s Hospital, Dr. Pitt is referred children with complex neurological and neuromuscular problems and those with undiagnosed or rare genetic mutations. Dr. Pitt routinely performs bulbar EMG, to aid in the diagnosis of children with motor weakness and swallowing disorders, and single-fibre EMG (SFEMG) for diagnosis of children with possible myasthenia (a disorder of the neuromuscular junction between the nerve and muscle), two modalities that we do not routinely perform in children in Australia. In addition to attending the nerve conduction studies scheduled for the days I was at the lab, I was also able to go over nerve conduction and EMG results from interesting and informative cases that Dr. Pitt had collected over the years. The other difference between his practice and our protocols in Australia is that while we sedate children before performing nerve conduction studies, Dr. Pitt performs them unsedated, and this is usually tolerated well by the children who attend the clinic. Improving the use of electromyography in paediatrics: paediatric EMG and SFEMG course This biennial course is formulated specifically for physicians who perform nerve conductions studies and EMG in children, and was held this year at the Institute of Child Health, GOSH from 3 rd 5 th October There were talks spanning both clinical and research areas, and interesting case presentations by expert neurophysiologists including Dr. Pitt, Prof. Royden Jones from Boston, Dr. Monique Ryan from Melbourne and experts from the Mayo Clinic. The course included an interactive hands-on workshop on performing SFEMG in children.

17 17 The 2011 International Course on EMG, SFEMG and Nerve Ultrasonography This course was held at the Institute of Clinical Neurophysiology of the University Medical Centre Ljubljana from 23 rd 25 th September Single-fibre EMG (SFEMG) is a method of diagnosing disorders of the neuromuscular junction by measuring the jitter i.e. the variation or difference in the onset or peak of the action potential recorded from 2 separate muscle fibres. Normal muscle fibres will have only a small difference or jitter, and the jitter is abnormally increased in individuals with myasthenia, even if their disease is mild or they are on treatment. SFEMG also has a higher sensitivity when compared to conventional tests (Repetitive Nerve Stimulation) and is the ideal screening test. While the conventional forms of SFEMG require sustained patient cooperation and are difficult to perform in young children, stimulated SFEMG using conventional EMG electrodes has a high success rate and can be performed without sedation, using only a topical anaesthetic cream. The course included lectures, demonstrations and hands-on workshops led by Jože Trontelj, Donald B. Sanders and Erik Stålberg, all regarded as the foremost experts in the field of SFEMG with Prof. Stålberg being responsible for inventing the technique. 16 th International Congress of the World Muscle Society WMS 2011 was held from October 18 th 22 nd, 2011 at Algarve in Portugal. The World Muscle Society aims to bring together clinicians and scientists who share an interest in neuromuscular disease. The focus of this year s conference was on Duchenne and Becker muscular dystrophy and associated dystrophinopathies, new developments in spinal muscular atrophies and hereditary neuropathies and advances in therapy of neuromuscular disorders. The format consisted of lectures by eminent researchers and selected oral presentations by scientists of the recent advances in our understanding of the causes of neuromuscular disease and novel therapies that are being developed. In addition, there were a vast number of posters that detailed the research of individual scientists and laboratories involved in the conference. This conference gave me the opportunity not only to familiarise myself with the latest neuromuscular research, but also to meet and develop collaborations with researchers around the world.

18 18 Conclusions Our knowledge of the genetic causes of neuromuscular disease and the pathophysiological processes that underlie these disease processes continues to grow rapidly. Because of this complexity, it is essential that physicians and allied health care professionals caring for children with neuromuscular disease have specialised training in paediatric neuromuscular disease. Similarly, histopathologists and radiologists are required to be specifically skilled in the interpretation of diagnostic tests for neuromuscular disease. During my Churchill Fellowship, I not only had the opportunity to improve my knowledge and skill in paediatric neuromuscular disease, but also realised that we are fortunate in Australia to possess both the skill base and the resources to provide an effective neuromuscular service. Recommendations 1. Establishment of a nationally funded centre of excellence for the care of children with neuromuscular disease that includes specialist clinical tertiary referral and review, specialised diagnostic services for muscle and nerve disease including neurophysiology and specialist rehabilitative services including physiotherapy and occupational therapy. Linked and funded by the centre would be research groups focused on neuromuscular disease in children. 2. Coordination of genetic testing and research into neuromuscular disease at a nationally level to avoid duplication of services and to promote laboratories and research groups to develop an expertise in a specific area of neuromuscular medicine. 3. Change in traditional models of funding for genetic testing, so that testing for rarer genetic diseases and newer gene testing modalities are more widely accessible. Dissemination and implementation 1. I will have the opportunity to apply my improved skill and knowledge in the diagnosis and management of children with neuromuscular disease into my clinical practice as a neuromuscular physician, and to present the knowledge I have gained at clinical and scientific meetings. 2. I plan to collaborate with many of the scientists and researchers I have met through the Churchill Fellowship in order to provide access to our patients to newer genetic tests and genetic research techniques not currently available in Australia. 3. I plan to advocate and work towards the establishment of a centre of clinical and research excellence in neuromuscular medicine, particularly peripheral nerve medicine, in Australia.