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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