MUSCULAR DYSTROPHY

Goodluck AugustineJohn Moteswa

Rochius Modest

Course Outline• Introduction• Epidemiology• Classification• Genetic etiology and pathogenesis• Clinical presentation• Diagnosis• Differential diagnosis• Treatment• Complications• Prognosis

Introduction• Muscular Dystrophy (MD) is a group of inherited diseases in

which the voluntary muscles progressively weaken overtime. • The term dystrophy means abnormal growth,• A muscular dystrophy is distinguished from all other

neuromuscular diseases by four obligatory criteria: – It is a primary myopathy– it has a genetic basis– the course is progressive – and degeneration and death of muscle fibers occur at some stage in

the disease

• Heart and other organs can also be affected.

Epidemiology

• It is estimated that between 50,000 -250,000 are affected annually. 1 per 3500 live male births.

• Can occur at any age• Most common in young males.• Type depends on how severe the disease is,

which muscles it affects, rate of progression

Classification

• Sex-linked: – Duchenne muscular dystrophy– Becker muscular dystrophy– Emery-dreifuss muscular dystrophy

• Autosomal recessive: – Limb girdle muscular dystrophy– Fascio scapulo humeral muscular dystrophy

• Autosomal dominant: – ocular.pharyngeal muscular dystrophy

Duchenne and Becker Muscular Dystrophy

DMD • Is the most common hereditary neuromuscular disease

affecting all races and ethnic groups. • Its characteristic clinical features are progressive

weakness, intellectual impairment, hypertrophy of the calves, and proliferation of connective tissue in muscle

BMD• Is a fundamentally similar disease as DMD, with a

genetic defect at the same locus, but clinically it follows a milder and more protracted course.

Genetic Etiology and Pathogenesis:

• DMD and BMD are inherited as an X-linked recessive trait. The abnormal gene is at the Xp21 locus and is one of the largest genes.

• Despite the X-linked recessive inheritance, about 30% of cases are new mutations, and the mother is not a carrier

• The female carrier usually shows no clinical signs, but occasionally there are girls who show mild muscle weakness; where the normal X chromosome becomes inactive and the one with gene deletion is active

• A cytoskeletal protein known as dystrophin is encoded by the gene at the Xp21.

• Dystrophin links muscle cells to extracellular matrix stabilising the membrane and protecting the sarcolemma from the stresses that develop during muscle contraction.

• Mechanical damage through eccentric contractions puts high stress on fragile membranes, provoke micro lesions that eventually lead to loss of calcium homeostatis and cell death

Clinical features in DMD

Early phase• In infants:

rarely symptomatic at birth or in early infancy, although some are mildly hypotonic,other gross motor skills(sitting, standing) maybe mildly delayedPoor head control is usually the first sign, walking is usually at normal age(12mo)

Transitional phase• Toddler:

– By the 2nd year have hip girdle weakness– Delayed walking, falling, toe walking and trouble

running or walking upstairs– Developmental delay – Lordotic posture when standing to compensate for

gluteal weakness

Transitional phase:• In 3-9yrs:

– Early Gowers sign-hands pushing on legs to stand – Trendelenburg gait/hip waddle– Pseudohypertrophy of calf muscles– Contractures mostly of ankles, knees hips and

elbows

Loss of ambulation• In 10-14yrs:

– Children are using wheelchair– Scoliosis due to sitting and back weakness– Upper limb weakness and difficult to retain use of

fingers makes daily activities difficult

Though in Beckers children remain ambulatory until early adult life

Late stage• 15yrs+:

– Cardiomyopathies ; peristent tachycardia, dyspnea and LL edema– Respiratory problems; ineffective cough, frequent pulmonary

infections and decreasing respiratory reserve

– Pharyngeal weakness; ep of aspiration, nasal regurgitation of liquids and nasal voice quality

– CNS; learning disability but can fxn in regular classroom(20-30% have an IQ of <70)(less common in Becker), ep of epilepsy

Pseudohypertrhophy of calf muscle,Tip toe gaitforward tilt of pelvis, compensatory lordosis

Diagnosis

• History taking• Physical examination• Investigations

Physical examination• Involves examination of all systems:

– CNS– CVS– RS– Per Abdomen

• Special tests:– Thomas test:

• Test for hip flexor contracture/shortness• Pt lies supine and one of the hips is fully flexed if the opposite leg lifts of the examination table

then it is a posiive test

– Obers test:• Test for iliotibial band tightness• With the pt lying in the lateral position, support the the knee and flex it to 90 degrees then

extend and abduct the hip and then release the knee support• Failure of the to abduct is a positive test

Investigations

Primary investigations:Serum CK

– usually greatly elevated in DMD– (15,000-35000IU/L),norm(<160IU/L)– But can be low in terminal stage

Cardiac assesment:– ECHO,ECG,chest x-ray done periodically

Invx…Secondary investigationsPCR

– for the dystrophin gene mutation– Done if serum CK and CF are consistent with Dx

done as confirmatory

Invx…MUSCLE BIOPSY

• Diagnostic & its done when PCR is normal but clinical suspicion is high.

• Immunohistochemical staining of frozen sections of muscle biopsy tissue is done.

• Shows myopathic changes such as; connective tissue proliferation, scattered degenerating and regenerating myofibres

• Common muscles sampled are the vastus lateralis (quadriceps femoris ) and the gastrocnemius

NORMAL ABNORMAL

• Scattered degenerating muscle fibres in a 4yr old with DMD

Differential Diagnosis

Neurogenic Non hereditary Non progressive-non necrotizing

Hereditary –non progressive

Spinal muscular atrophy

Dermatomyositis congenital muscle fiber-type disproportion (CMFTD

Metabolic myopathies

Standards of care for Duchenne muscular dystrophy

• There is neither a medical cure for this disease nor a method of slowing its progression

• Much can be done to treat complications and to improve the quality of life of affected children

• So it is multidisciplinary approach involves:– Neurologist or pediatric neurologist.– Rehabilitation specialist– Pediatricians– Primary care physician.

Neurology

The use of corticosteroids in DMD: prednisone, prednisolone, deflazacort, or other steroids.

– Decrease the rate of apoptosis of myotubes during ontogenesis and can decelerate the myofiber necrosis

• Timing- Physical performance of the child plateaus (4-6yrs),– Less functional when initiated close to the loss of

ambulation.

Neuro…

• Regimen: – 0.75 mg/kg/day prednisone/prednisolone and 0.9

mg/kg/day deflazacort (less effect of weight gain).– Alternating day dosing to reduce steroid-associated side-

effects.– Dose reduction even withdrawal if severe and/or

unacceptable side effects occur in a tapering manner– Continuation of steroids beyond the loss of ambulation is

common practice in some centres for the possible protective effect on spinal alignment, respiratory and cardiac function.

GI-Nutrition

• Adequate dietary advice should be offered from a young age with specific focus on weight control using(BMI)

• focused especially at:– Initiation of steroids– loss of ambulation – Adequate calcium and vitamin D intake– Controlled sodium intake

GI…

• Overweight- aim for a weight loss of 0.5 kg per month.

• Undernutrition are most likely after the boy starts using a wheelchair (approximately 12-13 years of age) and may be multifactorial.

• The first step is to evaluate intake and to optimize if necessary the existing diet with energy and protein.

• The next step with more severe malnutrition is enteral nutrition during night time.

GI…

Esp. in steroid users: if the diet is not adequate in supply of calcium and vitamin D, these should be added separately to reach a recommended intake:

• calcium(4-8 years: 800 mg/d; 9-18 years: 1300 mg/d) &• vitamin D (400 IU)

Later stages of the disease there can be difficulty swallowing and where this leads to aspiration and/or undernutrition:

• feeding by tube or • percutaneous endoscopic gastrostomy (PEG) is indicated

RESPIRATORY CARE

• Respiratory surveillance: Serial measurement of forced vital capacity(FVC) to detect progression of respiratory muscle weakness.

• FVC <40% predicted value serial measurement of overnight oximetry allows the recognition of the development of nocturnal respiratory failure.

• Cough effectiveness: Peak cough flow (PCF)• Cough assist machine should be considered when the PCF is

below 270 l/ min in non-ambulant boys and introduced before PCF is less than 160 l/min

Resp…

• Prophylaxis and management of chest infections: • Through vaccinations and antibiotics should be provided

promptly.• Chest physiotherapy such as postural drainage and assisted

coughing should be taught when coughing is ineffective

• Management of nocturnal hypoventilation Elective non-invasive nocturnal ventilation (NIV)

CARDIAC CARE

• Surveillance: Cardiac investigation (echocardiogram and ECG)- 2yrly/10years then annually and prior to GA at any age.

• Prophylaxis: ACE-inhibitors should be started at a subclinical deterioration of cardiac function as detected by echocardiography.

• Early prophylactic treatment with ACE-inhibitors at a pre-clinical stage is recommended from 5-10 years of age.

Cardiac…

• Treatment: Dependent on type and stage of cardiomyopathy. DCM is the most common form. – ACE-inhibition and beta-blocker both or ACEI starts– Add diuretics and other with onset of heart failure.– Anticoagulation therapy in severe cardiac dysfunction to

prevent systemic thromboembolic events

• Arrhythmias: Occur in late stage hence antiarrhytmic treatment should be introduced, bearing in mind the possible negative inotropic effect of agent chosen

ORTHOPEDIC CARE

• Splinting: In ambulant children night splints should be provided when there is loss of dorsiflexion at the ankle and before the foot can only achieve plantagrade.

• AFOs(ankle-foot orthosis)/brace & Standing frames can delay contracture development in non-ambulant children.

AFOs night splint

ORTHO…

• DMD spine deformity A fusion surgery can be recommended as soon as there is clear progression and the Cobb angle passes 25 – 30 degrees

PSYCHOLOGICAL CARE

• Social (information, advocacy and advice) and psychological support should be offered at times of changing needs and crisis.

• Learning difficulties/ autism spectrum disorders should be identified early and recommendations given to parents and educators about managing these difficulties.

REHABILITATION• Annual neurological, respiratory and cardiological

assessments should ideally be co-ordinated.• Physiotherapist and occupational therapist are to

encourage activity (i.e. self hygiene care) and promote function.

• Exercise: Resisted exercises may accelerate muscle damage. Moderate levels of active exercise is recommended.

• Wheelchairs: to improve mobility and independence.

Complications

• Mental impairment• Cardiomyopathy• Lung failure• Contractures• Decreased self-independence and mobility

Prognosis

• Most of these patients have a poor prognosis• Patients with DMD have the worst prognosis;

death occurs usually at about 18-20yrs of age. The causes of death are: – respiratory failure in sleep– intractable heart failure– pneumonia– aspiration – airway obstruction.

THANK YOU!

• http://www.youtube.com/watch?v=JnDVRB1DIUA