DMD Nelson

8/11/2019 DMD Nelson

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INTRODUCTION

term dystrophy means abnormal growth, derived fromthe

Greek trophe, meaning nourishment. A musculardystrophy is

distinguished from all other neuromuscular diseases byfour

obligatory criteria: It is a primary myopathy, it has agenetic

basis, the course is progressive, and degeneration anddeath of

muscle fi bers occur at some stage in the disease


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Dmd: most common

hereditary neuromuscular disease affecting allraces and ethnic

Groups

Gender : Male

Age of onset : symptomatic at infancy


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CLINICAL FEATURES

characteristic clinical features are progressive

weakness,

intellectual impairment, hypertrophy of the

calves, and proliferation

of connective tissue in muscle


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Clinical Manefistation

Lack of head control : 1stsign of weakness

Hip girdle weakness : 2ndyr

Early gowers sign : at 3 y/o

Fully expressed at 56 y/o

Hip waddle : 5 -6 y/ 0


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2nddecade

Continuation of relentless progressive

weakness

Distal muscles : functions are preserved ;

allowing the child to continue to use eating

utensils, using a computer keyboard and

pencil


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Respiratory muscles involvement : weak and

ineffective coughing

Pulmonary infections

Decrease respiratory reserve

Pharyngeal weakness : leads to aspiration, nasal

regurgitation of liquids, and an airy or nasal voice

quality


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The

function of the extraocular muscles remains

well preserved.

Incontinence due to anal and urethral

sphincter weakness is an

uncommon and very late event.


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Contractures most often involve the ankles, knees,hips, and

elbows. Scoliosis is common. The thoracic deformityfurther compromises

pulmonary capacity and compresses the heart.Scoliosis

usually

progresses more rapidly after the child becomesnonambulatory

and may be uncomfortable or painful. Enlargement


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Enlargement

of the calves (pseudohypertrophy) and wasting of thigh muscles

are classic features. The enlargement is caused by hypertrophy of

some muscle fi bers, infiltration of muscle by fat, and proliferation

of collagen. After the calves, the next most common site ofmuscular

hypertrophy is the tongue, followed by muscles of the

forearm.

Fasciculations of the tongue do not occur.

The voluntary sphincter

muscles rarely become involved.


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ankle contractures are severe, ankle deep tendon

reflexes remain well preserved until terminalstages. The knee

deep tendon reflexes may be present until about6 yr of age but

are less brisk than the ankle jerks and areeventually lost. In the

upper extremities, the brachioradialis reflex isusually stronger

than the biceps or triceps brachii reflexe


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Cardiomyopathy, including persistenttachycardia and myocardial

failure, is seen in 50-80% of patients with this

disease. The

severity of cardiac involvement does not

necessarily cor- relate with the degree of skeletal muscle

weakness


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Intellectual impairment occurs in all patients, althoughonly

20-30% have an IQ < 70. The majority have learningdisabilities

that still allow them to function in a regular classroom,particularly

with remedial help. A few patients are profoundlymentally

retarded, but there is no correlation with the severity of the

myopathy


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Diagnosis

Polymerase chain reaction (PCR) for the dystrophin gene mutation

is the primary test, if the clinical features and serum CK are

consistent

with the diagnosis. If the blood PCR is diagnostic,

muscle

biopsy may be deferred, but if it is normal and clinical suspicion

is high, the more specifi

c dystrophin

immunocytochemistry

performed on muscle biopsy sections detects the 30%

of

cases that do not show a PCR abnormalit


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cle biopsy is diagnostic and shows characteristic

changes ( Figs. 601-1 and 601-2 ). Myopathic changes include

endomysial connective tissue proliferation, scattered degenerating

and regenerating myofi

bers,

foci of mononuclear infl

ammatory

cell infi

ltrates

as a reaction to muscle fi

ber

necrosis, mild

architectural

changes in still-functional muscle fi

bers,

and many

dense

fi

bers.

These hypercontracted fi

bers

probably result from

segmental

necrosis at another level, allowing calcium to enter the

site

of breakdown of the sarcolemmal membrane and trigger a

contraction

of the whole length of the muscle fi

ber.


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If there is a family history of the disease, particularly in the case

of an involved brother whose diagnosis has been confirmed, a

patient with typical clinical features of DMD and high concentrations

of serum CK probably does not need to undergo biopsy.

The

result of the PCR might also infl

uence

whether to perform a

muscle

biopsy.

A fi

rst case in a family,

even if the clinical features

are

typical, should have the diagnosis confi

rmed

to ensure that

another

myopathy is not masquerading as DMD. The most

common

muscles sampled are the vastus lateralis (quadriceps

femoris)

and the gastrocnemius.


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PATHOGENESIS

Dystrophin deficiency at the sarcolemma

disrupts the

membrane cytoskeleton and leads to loss

secondarily of other

components of the cytoskeleton.


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Treatment

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


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Cardiac

decompensation often responds initially wellto digoxin.

Pulmonary

infections

should be promptly treated


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Patients should avoid

contact with children who have obvious

respiratory or other

contagious illnesses. Immunizations for infl

uenza virus and other

routine vaccinations are indicated.


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good nutritional state

Adequate calcium intake

Watchout for obesity


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Physiotherapy delays but does not always prevent contractures.

At times, contractures are actually useful in functional

rehabilitation.

If contractures prevent extension of the elbow

beyond

90 degrees and the muscles of the upper limb no longer

are

strong enough to overcome gravity,

the elbow contractures

are

functionally benefi

cial

in fi

xing

an otherwise fl

ail

arm and in

allowing

the patient to eat and writ


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Physiotherapy contributes little to muscle

strength-

ening because patients usually are already

using their entire reserve for daily function,

and exercise cannot further strengthen

involved muscles. Excessive exercise can

actually accelerate the

process of muscle fi ber degeneration.


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Other treatment of patients with DMD involves the useof

prednisone, prednisolone, deflazacort, or othersteroids. Glucocorticoids

decrease the rate of apoptosis or programmed cell death

of myotubes during ontogenesis and can deceleratethe

myofi

ber

necrosis in muscular dystrophy.


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Strength usually

improves initially, but the long-termcomplications of chronic

steroid therapy, including considerable weightgain and osteoporosis,

can offset this advantage or even result in greaterweakness

than might have occurred in the natural course of the

disease


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Nevertheless, some patients with DMD treated early with steroids

appear to have an improved long-term prognosis as well as the

short-term improvement, and steroids can help keep patients

ambulatory for more years than expected without treatment. One

protocol gives prednisone (0.75 mg/kg/day) for the fi rst 10 days

of each month to avoid chronic complications. Fluorinated steroids,

such as dexamethasone or triamcinolone, should be avoided

because

they induce myopathy by altering the myotube abundance

of ceramide.

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