Associate Professor Andrew Kornberg April 2015 MDWA Symposium

Transcription

1 The of Neuromuscular Disease A Neurology Perspective Multifaceted and best using a multidisciplinary approach Genetic counselling begins at diagnosis issues include: Physical Emotional Social Educational Vocational A/Prof. Andrew J. Kornberg Royal Children s Hospital Melbourne, Australia One major problem in bridging the physical and educational issues is intelligence capacity 1

2 TOTAL No. OF CASES Associate Professor Andrew Kornberg Distribution Of IQ Scores In DMD Cases PMD Cases TOTAL -106 Normal IQ distribution MEAN IQ = < IQ RANGE Cohen HJ, Molnar GE, Taft LT. The genetic relationship of progressive muscular dystrophy (Duchenne type) and mental retardation. Dev Med.Child Neurol 1968; 10: Bone Health Duchenne muscular dystrophy associated with: Reduced bone mineral density Increased risk of fractures Steroids may exacerbate the reduced bone mineral density Issues: How to follow bone mineral density? Z-scores do not predict fracture risk Z-scores lower than aged matched controls throughout life Vitamin D and calcium supplementation? No data to show that risk is reduced Who should be supplemented? Are there other interventions that are useful? Quinlivan R et al. Neuromuscul Disord 2005;15: Biggar WD et al. Neuromuscul Disord 2005;15: Scoliosis Surgery Average age at surgery is about 14 years To undergo surgery Spinal curve > 25 degrees Vital capacity > 0% of predicted No active infection Cardiovascular system not compromised Rate of scoliosis surgery varies from centre to centre 2

3 Scoliosis Respiratory Predictable stages of decline Nocturnal hypoventilation and hypoxia is typical Nocturnal assisted ventilation may be helpful for symptomatic relief Respiratory failure typically occurs in the late teens or early 20 s with an insidious onset Steroids seem to preserve respiratory function Exons 48-5 deletions possibly associated with a higher incidence Dilated cardiomyopathy > hypertrophic > conduction defects Symptomatic in 57% by age 18 insidious onset Cardiac Cardiac death in 10% of cases Steroids may have long term benefit on cardiac function 1 Presymptomatic afterload reduction may be of long term benefit Markham LW et al. Pediatr Cardiol 2005;26:

4 RCH Neuromuscular Clinic u Evolution u Concept started in 2000 Joined CINRG u Initially Kate Carroll (PT) and Andrew Kornberg Added disciplines over time v Respiratory v Cardiology u Funding always a concern v MDA v Studies v IN Group The only place success comes before work is in the dictionary Vince Lombardi RCH Neuromuscular Team Quality Of Care The RCH Neuromuscular Team Monique Ryan / Eppie Yiu Dani Villano Joy Goubran Chiara Tewierik and Rachel Kennedy, Kate Carroll and Katy de Valle John Massie, Colin Robertson, Mandie Griffiths Zoe Davidson Carmel Tata Robin Forbes Maria Poppelwell Andrew Davis / Michael Cheung Michael Johnson / Paolo Selber Prakash Chidambaram Margaret Zacharin / Peter Sim RCH Education Institute Quality Of Care u Advances in the management of DMD: aggressive joint management treatment with corticosteroids early scoliosis surgery and cardiac care use of intermittent positive pressure ventilation u Have provided improvements in: function ambulation quality of life life expectancy 4

5 Clinical Trials u We must look at the learning's from the childhood leukemia experience 1970 s 5% cure rate 1980 s 25% cure rate 1990 s 70% cure rate % cure rate u What made a difference? Standards of clinical care Every child enrolled in a trial v Natural history v Drug trials v Incremental improvement in survival Monitoring in clinical trials u Functional outcome measures u Strength outcome measures u 6 Minute Walk Test u Respiratory function testing u Quality of life Functional outcome measures Strength outcome measures u Milestones of disease progression Ability to rise from floor, walk etc Require long-term follow-up/ extended lists u Timed testing Gower maneuver, stairs, walking 6MWT u Composite scores of function Hammersmith scale North Star GSGC scale u Manual muscle testing Used in most previous DMD trials Relatively quick and easy Requires careful validation in multicentre setting Different grading scales u Quantitative muscle testing May improve reliability in DMD trials Requires all centres to have same equipment and standardised training. CINRG: tests strength of KE, KF, EF, EE, WE, grip on dominant side. Quantitative muscle testing Quantitative muscle testing (QMT) is a sensitive and precise method to test muscle strength CINRG has developed a paediatric version, which includes video game-like features 5

6 Muscle testing output PFTs Neuromuscular Disease Therapy Summary u These are exciting times as there is a greater understanding of the genetic, molecular, and physiological genesis of the neuromuscular disorders The better understanding will hopefully lead to new and hopefully effective therapies u Improvement in the way we assess response to therapy in human studies, and the development of cooperative groups such as CINRG and Treat NMD will allow the rapid study of new therapies u Gold standard care of neuromuscular disease is a multidisciplinary clinic Best care Trials are part of day to day care 6

7 With thanks to.. The RCH Neuromuscular Team Monique Ryan / Eppie Yiu Dani Villano Joy Goubran Chiara Tewierik and Rachel Kennedy, Kate Carroll and Katy de Valle John Massie, Colin Robertson, Mandie Griffiths Zoe Davidson Carmel Tata Robin Forbes Maria Poppelwell Andrew Davis / Michael Cheung Michael Johnson / Paolo Selber Prakash Chidambaram Margaret Zacharin / Peter Sim RCH Education Institute 7