An X linked neuromuscular disease characterised by rapidly progressing muscle weakness and wasting, (WHO, 2013). Four phases Early phase (<6 yrs): clumsy, fall frequently, difficulty jumping or running, enlarged muscles, contractures. Transitional Phase (ages 6-9): Trunk weakness (Gowers manouvre), muscle weakness, heart problems, fatigue. Loss of ambulation (ages 10-14): by 12 yrs most boys use a powered wheelchair. Scoliosis due to constant sitting and back weakness, UL weakness make ADL’s difficult (retain use of fingers). Late stage (15+): life threatening heart and respiratory problems more prevalent, dyspnea, oedema of the LL’s. Average age of death is 19 yrs in untreated DMD but due to improvements in clinical care in many centres the average age of death is the late twenties or beyond, (Bushby et al, 2005).
Sex linked: X-linked genetic recessive disorder Inherited by the carrier mother/sporadic mutation in the mothers egg cell (1/3 of cases). Results in an abnormality in the genetic code for the protein dystrophin resulting in lack of dystrophin. (Nowak and Davies, 2004)
The dystrophin gene is the largest in the human genome and is prone to mutation. 60% of dystrophin mutations are large insertions or deletions that lead to frame shift errors downstream, whereas approximately 40% are point mutations/duplications or small frame shifts/ rearrangements (Hoffman, 2001).
Dystrophin links the muscle cells to the extracellular matrix stabilising the membrane and protecting the sarcolemma from the stresses that develop during muscle contraction. Mechanically induced damage through eccentric contractions puts a high stress on fragile membranes and provokes micro-lesions that could eventually lead to loss of calcium homeostasis, and cell death. Imbalance between necrotic and regenerative processes: early phase of disease. Later phases the regenerative capacity of muscle fibers are exhausted and fibers are gradually replaced by connective tissue and adipose tissue. (Deconinck and Dan, 2007)
Incidence: 1 in 3600-6000 (Emery, 1991), (Bushby et al, 2010), Bradley & Parsons, 1998) Between 1 February 1993 to 30 June 1994 – DMD incidence was 1 in 12,200 in Northern Ireland (Hughes et al, 1996). 1 in 4200 – The Netherlands (Essen et al, 1992). 1 in 5,600 to 1 in 7,700 DBMD males through 5-24 years in four states in the U.S.A. 1982-2002. (Ciafoloni et al, 2009) First symptoms noticed on average at 3.6 years (MDSTARnet, 2007)
Mean age of diagnosis in cases without family hx is >4 ½ years (bushby et al, 2005). Delay in diagnosis of 2 ½ yrs (Bushby et al, 2005), (Parsons et al, 2004) (Bushby et al, 2010)
Family support is NB at this time: provide contact with a named member of staff and provide details of parental support groups . http://www.parentprojectmd.org www.dfsg.org.uk http://www.mdi.ie/index.html http://www.informingfamilies.ie/
Age: 5 ½ years. PC: rare Xp21 mutation with Point mutation of exon 7 of the dystrophin gene resulting in complete absence of dystrophin. Presentation: (Early ambulatory stage ) - Ambulant, weight – 50th %, hypertrophy of the calves, +ve Gowers sign, mild lordosis. Problem List: Poor attention, Speech delay (uses pecs), ?hyperactivity(reported by mother), proximal weakness of lower and upper limbs and neck flexors, epistaxis, poor balance, gait- waddle/flat footed, muscle spasm of calves. PMHX: Initially presented with developmental delays before he was diagnosed.
Corticosteroids: prednisolone 20 mg daily. Splinting for prevention of contractures at night time. Check ups with neurologist every 6 months. PhysiotherapyLTG’s Improve upper limb strength Improve lower limb strength Improve balance Improve participation in playSTG’s Increase throwing distance of bean bag from 1 meter to 1 ¼ meters in 3 weeks. Increase kicking distance of soccer ball while on gym matt from 1 meter to 1 ½ meter in 3 weeks. Improve one legged stance to 2 seconds in 3 weeks. OtherFamily Support and servicesSLTPsychologyOT
Management of muscle extensibility and joint contractures: stretching and positioning, assistive devices for MSK MGT (orthoses, standing devices), surgical mgt for LL contractures (Triple arthrodesis). Improvement, maintenance and support of muscle strength and function: Recommendations for physical activity - regular submaximum (gentle) functional strengthening/activity, including a combination of swimming-pool exercises and recreation-based exercises in the community. Steroid prescription and management(Fowler et al 2002), (Fowler, 1982), (Bushby et al 2010)
Currently best treatment available Improve Muscle Strength and function Significantly slow the progression of muscle weakness Prolong ambulation Delsy the onset of respiratory and/or cardiac dysfunction Use with caution as side effects include weight gain, reduced bone density, hyperactivity, failure to gain height. Pednisone/prednisolone – 0.75 mg/kg/day Deﬂazacort – 0.9 mg/kg/day
90 % of boys with DMD are likely to develop a clinically signiﬁcant scoliosis. Surgery has shown to be effective in correcting scoliosis and Success rates are likely to be highest and complication rates lowest if surgery is performed when the spine is still mobile at a Cobb angle of 20–40% (Cervellati et al, 2004) . Spinal bracing for those unable for surgery. Triple arthrodesis may be required Bone health: Fractures (long bone and vertebral)Osteopenia, Osteoporosis Kyphoscoliosis, Bone pain, Reduced QOL – DEXA scans, serum/urine tests, spine readiograph – Vit D, Calcium, Biphosphonates.
(Eagle et al, 2007) Kaplan–Meier survival plot to show the impact of spinal surgery and ventilation on survival. Survival curves are significantly different p = 0.0001.
Death is due to cardiac dysfunction in 10% of cases (Gulatie et al, 2005). Dilated cardiomyopathy: A condition in which the heart becomes weakened and enlarged. As a result, the heart cannot pump enough blood to the rest of the body. Death due to cardiomyopathy is expected to rise now that life expectancy increases, (Bushby et al, 2003). It is estimated that 20–30% of DMD boys have left ventricular impairment on echocardiography by age 10 years (Bushby et al, 2005). Cardiac mgt should be implemented at diagnosis as clinical symptoms appear later than initial cardiac dysfunction, echocardiogram & electrocardioram – at 6 yrs, every 2 yrs up to age 10 and annually after 10 yrs +. ACE and beta blockers(American academy of Paediatrics, 2005)
Panel 1: Respiratory interventions indicated in patients with Step 3: nocturnal ventilationDuchenne Nocturnal ventilation† is indicated in patients who havemuscular dystrophy any of the following:Step 1: volume recruitment/deep lung inﬂ ation technique • Signs or symptoms of hypoventilation (patients with FVCVolume recruitment/deep lung inﬂ ation technique (by self-inﬂ ating <30% predicted are atmanual ventilation bag especially high risk)or mechanical insuﬄ ation–exsuﬄ ation) when FVC <40% predicted • A baseline SpO2Step 2: manual and mechanically assisted cough tech <95% and/or blood or end-tidal CO2• Respiratory infection present and baseline peak cough ﬂ ow <270 >45 mm Hg while awakeL/min* • An apnoea–hypopnoea index >10 per hour on• Baseline peak cough ﬂ ow <160 L/min or maximum expiratory polysomnography or four or morepressure <40 cm water episodes of SpO2• Baseline FVC <40% predicted or <1·25 L in older teenager/adult <92% or drops in SpO2 of at least 4% per hour of sleep Optimally, use of lung volume recruitment and assisted cough techniques should always precede initiation of non-invasive ventilationStep 4: daytime ventilation Step 5: tracheostomyIn patients already using nocturnally assisted ventilation, daytime Indications for tracheostomy include:ventilation‡ is • Patient and clinician preference§indicated for: • Patient cannot successfully use non-invasive ventilation• Self extension of nocturnal ventilation into waking hours • Inability of the local medical infrastructure to support• Abnormal deglutition due to dyspnoea, which is relieved by non-invasive ventilationventilatory assistance • Three failures to achieve extubation during critical illness• Inability to speak a full sentence without breathlessness, and/or despite optimum use of• Symptoms of hypoventilation with baseline SpO2 non-invasive ventilation and mechanically assisted cough <95% and/or blood or end-tidal CO2 • The failure of non-invasive methods of cough assistance>45 mm Hg while awake to prevent aspiration ofContinuous non-invasive assisted ventilation (with mechanically secretions into the lung and drops in oxygen saturationassisted cough) can below 95% or the patient’sfacilitate endotracheal extubation for patients who were intubated baseline, necessitating frequent direct tracheal suctioningduring acute via tracheostomyillness or during anaesthesia, followed by weaning to nocturnal non-invasive assistedventilation, if applicable
Nutritionist/dietician: to guide the patient to maintain good nutritional status to prevent both under nutrition/malnutrition and being overweight/obese, and to provide a well- balanced, nutrient-complete diet. SLT: To monitor and treat swallowing problems, to prevent aspiration and weight loss, and to assess and treat delayed speech and language problems. Clinical Nurse specialist: Family Support and Services OT: Continue previous measures Provision of appropriate wheelchair and seating, and aids and adaptations to allow maximum independence in ADL, function, and participation.
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(Parsons et al, 2004) Milestone Late/never Median age achieved (range (%) case achieved) numbers (months) Walking alone (89%) 16/18 16 (13–27) Sitting alone (67%) 12/18 8 (5–16) Meaningful (53%) 9/17 29 (20–43) sentences Single words (47%) 8/17 13 (9–24)