WELCOME TO CPD

2 Part
nd

Dr. Mohammad Helal Uddin

MD (Phase-B), ICMH
Date: 08/01/2024
MUSCULAR DYSTROPHY
 INTRODUCTION
• Dystrophy means abnormal growth, derived from
greek trophe, meaning ’’Nourishment”.
• Muscular dystrophy is distinguished from all
neuromuscular disease by 4 criteria-
1) It’s a primary myopathy
2) It has genetic basis
3) The course is progressive
4) degeneration & death of muscle fibers occur
at some stage.
 TYPES OF MUSCLE DYSTROPHY

• There are over 20 types of genetic muscular

disorders, each differing in their symptoms and
severity.
1. Sex linked-
• Duchenne muscular dystrophy(DMD)
• Becker muscular dystrophy(BMD)
 TYPES OF MUSCLE DYSTROPHY
2. Autosomal dominant-
• Facioscapulohumeral muscular
dystrophy(FSHD)
• Distal MD
• Ocular MD
3. Autosomal recessive-
• Limb-girdle muscular dystrophy (LGMD)
• Infantile FSHD
DUCHENNE MUSCULAR DYSTROPHY
 DUCHENNE MUSCULAR DYSTROPHY

• DMD is named after the 19th century French

neurologist Guillaume Benjamin Amand
Duchenne (1806-1875).
• Aulternative name: Pseudohypertrophic
Muscular Dystrophy
• The most common muscular dystrophies,
X-linked recessive disorder
• onset is generally before age 6 years.
• Incidence rate 1 in every 3600 live born
infant boy( In our ICMH we found yearly 2
to 3 patients)
 Genetics and Pathogenesis
• Caused by mutations of the dystrophin gene
located on chromosome Xp21 and it is one of
the largest gene.
 Deletions
• Around 65% of patient
 Partial gene duplications
• 10% of patients
 Point mutations
• 10% patients
 New mutation
• 30% cases
 Dystrophin

• Dystrophin is located on the cytoplasmic face of

the plasma membrane of muscle fibers,
functioning as a component of large, tightly
associated glycoprotein complex.
Pathogenesis
 Pathogenesis
Dystrophin provide mechanical stability to myofiber
and cell membrane during muscle contraction

Absence of dystrophin

Small membrane tear

Influx of calcium

Triggering events that cause myofiber degeneration

CLINICAL FEATURES
 Clinical features cont’d
• Rarely symptomatic at birth or in early infancy,
may be mildly hypotonic.
• Early gross motor skills(rolling over, sitting,
standing) are usually achieved at the
appropriate ages or may be mildly delayed.
• Transverse or horizontal smile- in later
childhood.
• Walking is often accomplished at the normal
age 12 month but hip girdle weakness as early
2nd year
 Clinical features cont’d
• Gowers’ sign may be seen by age 3 yr, but
nearly always is evident by age 5 or 6 yr.
• Trendelenburg (waddling) gait frequently
appears at this time.
• In toddlers- delayed walking, frequent falling,
toe walking and trouble running or walking up
stairs, developmental delay.
• Unable to support body wt when suspended
by axilla(slipping sign)
 Clinical features cont’d
• Pseudohypertrophy of calf muscles, due to fat
infiltration in muscle, hypertrophy of muscle fiber
and collagen proliferation. After calves
hypertrophy occurs in tongue and forearm.
Wasting of thigh muscle occurs.
 Clinical features cont’d
• Male sex
• Age of onset is early
• Frequent fall while walking, difficulty in standing
• Rapidly progressive in nature
• On examination:
– Wasting of thigh muscles
– Calf muscles hypertrophy
– Power decreased in both lower limbs
– Winging of scapula present
– Wower’s sign positive
– Wadling gait
EXAMINATION FINDINGS
GOWERS MANEUVER
Winging of Scapula
 Complications
• Cardiomyopathy
• Respiratory failure
• Deformities
• Permanent, progressive disability
• Decreased mobility
• Decreased ability to care for self
• Mental impairment
 Cardiac complication

• Primary dilated cardiomyopathy

• Conduction abnormalities
• Intra-atrial and inter-artial conduction defects
• Arrhythmias, primarily supraventricular
tachycardia.
 Cardiomyopathy
• Characterized by extensive fibrosis of the
posterobasal left ventricular wall
• As the disease progresses, fibrosis can spread to
the lateral free wall of the left ventricle.
• Significant mitral regurgitation due to involvement
of posterior papillary muscle.
 Cardiomyopathy cont’d
• Incidence
• By 14 years: One –third of patients
• By 18 years: One half of patients
• Older than 18 years: All patients
• Heart failure and arrhythmias may develop in the
later stages of the disease.
 Respiratory complications

• Chronic respiratory insufficiency due to restrictive

lung disease in all patients.
– Obstructive sleep apnea
1st decade
– Hypoventilation
2nd decade
• Pharyngeal weakness cause aspiration, nasal
regurgitation of liquids and nasal voice.
 Intellectual disability
• In around 30% of patients
• Average IQ is 85, 20%-30% have <70
• Verbal IQ is more impaired than performance IQ
• Intellectual disability is not correlated with the
severity of weakness
 Orthopedic Complications
• Contracture involve ankle, knee, hip, elbow, neck
lateral rotation, shoulder and fingers.
• Long bone fractures
• 21% of DMD patients had experienced fractures.
• Most common mechanism was falling
• About half of the fractures occurred among
patients who were ambulatory
 Orthopedic Complications

• Progressive scoliosis in
nearly all patients
• Scoliosis, in combination with
progressive weakness,
results in impaired pulmonary
function and eventually,
respiratory failure
DIAGNOSIS
 Investigation
• Suspected dystrophinopathy diagnosed on the
basis of :
1. Serum muscle enzymes
-CPK, Aldolase, Aspartate aminotransferase
2. X-ray
3. ECG
4. Echo
5. Muscle biopsy
6. MRI of muscle
7. LFT
8. Immunohistochemistry
9. Genetic analysis
 Serum muscle enzymes
• Markedly raised serum CK level, 10-20 times the
upper limit of normal (may elevated 15000-35000
IU/L, normal<160IU/L)
• Levels peak at 2-3 years of age and then decline
with increasing age, due to progressive loss of
dystrophic muscle fibres.
• Serum creatinine decrease because of decrease
muscle mass.
 Electromyography

An electromyography (EMG) shows that

weakness is caused by destruction of muscle
tissue rather than by damage to nerve. Motor
and sensory nerve conduction velocities are
normal.
 Muscle biopsy
Gold standard for diagnosis.
Muscle biopsy shows :
• Endomysial connective tissue proliferation
• Scattered degenerating and regenerating myofibers
• Foci of mononuclear cell infiltration due to muscle
fiber necrosis.
• Extensive replacement of muscle fibres by Adipose
cells.
Histopathology of Gastrocnemious muscle, cross
section shows extensive replacement of muscle
fibres by Adipose cells:
 Genetic Analysis
• Molecular genetic testing is indicated for patients
with an elevated serum CK level and clinical
findings suggestive of a dystrophinopathy.
• Deletion/duplication/point mutations of one or
more exons of DMD gene
 Muscle MRI

• Muscle MRI is usually not performed in DMD for

diagnosis, but may be a useful noninvasive tool to
evaluate progression of muscle involvement over
time.
 CARRIER DETECTION
• Asymtomatic carrier has increased S.CPK in
80% cases.
• In prepubertal carrier girl, CPK is highest at
8-12 years of age. In 20% cases, there is
normal CPK level
• Muscle biopsy of suspected female carrier
may detect an additional 10% in whom S.CPK
is normal
MANAGEMENT
 Multidisciplinary Approach
 There is no medical cure for this diseases. Much can be done to
treat complication and improve quality of life.
• Counselling
• Dietary Management
• Drug treatment:
 Corticosteroid Therapy:
 Prednisolone
 Deflazacort
• Physical therapy
• Cardiac management
• Respiratory management
• Orthopedic management
 Corticosteroid Therapy
• Prednisolone and deflazacort have been the
drugs shown to be effective to date in DMD
• Prednisolone
• 0.75mg/kg/day
or
• Deflazacort
• 0.9mg/kg/day
(Weekend- only dosing, alternate- day regimens
or 10-day-on/ 10-day-off regimens.)
 Prednisolone- Merits and
Demerits
Average muscle strength increased by 11% with
prednisone treatment compared with placebo
• Strength increases significantly by 10 days
reached a maximum at 3 months and was
maintained at 6 and 18 months.
• Forced vital capacity improved significantly
(10.5% higher) after 6 months of daily prednisone.
 Prednisolone- Merits and
Demerits cont’d
• Mechanism unknown but postulate effects
include-
1. Membrane stabilization
2. Decrease fibrosis
3. Inflammatory response.
• Cataract, Acne, Weight gain, diabetes,
Osteoporosis, hypertension and Growth or
puberty delay are side effects.
 Cardiac disease
• Cardiac surveillance with ECG and
echocardiogram recommended at diagnosis or by
6 yrs of age then yearly.

• Early treatment of dilated cardiomyopathy with

ACE inhibitors or beta blockers or angiotensin
receptor blocker.
 Respiratory disease
• Baseline pulmonary function tests and
respiratory evaluations beginning at age 8 to 9
years.
• Pneumococcal vaccine and annual flu
vaccination.
• Promt Treatment of Pulmonary infection.
 Orthopedic problems
• Physiotherapy
• Passive stretching
• Surveillance radiographs for scoliosis
• Maintenance of bone density
• Monitoring of vitamin D levels and
supplementing calcium and vitamin D.
 ORTHOPEDIC APPLIANCES:

• Braces,
• Wheel chairs
 Newer Treatment
• Exon 51 skipping antisense oligonucleotide -
weekly IV infusion.
 Follow Up

• At 6 monthly interval observe:

– progression of weakness in skeletal muscle,
– drug side effect
– cardiac status
– development of deformities.
 PROGNOSIS
• Affects all voluntary muscles and involves the
heart & respiratory muscles.

• Death in boys occurs in late teens to 20s.With

current standard of care many patients expect of
live into 4th decade.
 PROGNOSIS cont’d

• Studies have shown median life expectancy

with ventilatory support 21yrs-40 yrs & without
ventilatory support 14-27 yrs.

• The common causes of death are respiratory

failure, intractable heart failure, pneumonia or
occasionally aspiration and airway obstruction