Lecture 49
Skeletal Muscle Diseases
Dr zeenat
DR ZEENAT NASEER
• HISTOPATHOLOGIST
• College of Medicine
• Majmaah
Lecture Objectives
• Enlist and classify muscular dystrophies.
– Describe their pathogenesis
– Describe their morphology
– Discuss their clinical features and management.
• Enlist common diseases of neuromuscular
junctions.
– Describe their pathogenesis.
– Describe their morphology.
– Describe their clinical features, diagnosis and
complications.
Classification
• X-linked:
• Duchenne muscular dystrophy (DMD)
Most
• Becker muscular dystrophy (BMD)
Common
• Emery-Dreifuss muscular dystrophy (EDMD)
• Autosomal recessive:
• Limb-girdle muscular dystrophy (LGMD)
• Autosomal dominant:
•
•
•
•
Less
Facioscapulohumeral muscular dystrophy (FSHD) Common
Distal muscular dystrophy
Ocular muscular dystrophy
Oculopharyngeal muscular dystrophy
Reference: UpToDate, 2014
Pathogenesis
Reference: UpToDate, 2014
Duchenne
Muscular
Dystrophy
(DMD)
Becker
Muscular
Dystrophy
(BMD)
Role of Dystrophin
α2- chain
Cytoplasmic actin
Reference: Robbins Basic
Pathology. 8th Ed.
The relationship between
the cell membrane
(sarcolemma) and the
sarcolemmal associated
proteins. Dystrophin, an
intracellular protein, forms
an interface between the
cytoskeletal proteins and a
group of transmembrane
proteins, the dystroglycans
and the sarcoglycans. These
transmembrane proteins
interact with the ECM,
including the laminin
proteins. Mutations in
dystrophin are associated
with the X-linked muscular
dystrophies, mutations in
caveolin and the
sarcoglycan proteins with
the autosomal limb girdle
muscular dystrophies, and
mutations in the α2-laminin
(merosin) with a form of
congenital muscular
dystrophy.
• Histology is similar in DMD
& BMD
• Marked variation in muscle
fiber size
• Residual muscle fibers show
a range of degenerative changes
• Other fibers show regeneration
• Connective tissue is increased throughout the muscle
• Definitive diagnosis – abnormal immunohistochemical staining for
dystrophin or by western blot of skeletal muscle
Clinical Features
References:
-Robbins Basic Pathology. 8th Ed.
-UpToDate, 2014
• Death due to:
- Respiratory insufficiency
- Pulmonary infection
- Cardiac decompensation
Management
• Steroids – main treatment option
• Vaccination to prevent Pneumonia & Influenza
• Screening (by Echo/MRI) at around 6 years
age, and treatment of Cardiomyopathy
• Lung function testing at around 9-10 years age
and assisted ventilation if needed
• Periodic monitoring of Vitamin D levels & diet
rich in Calcium & Vit D
• Physical therapy, leg braces
• Surgery for correction of contractures &
scoliotic deformities
Reference: UpToDate, 2014
Diseases of the Neuromuscular junction
Myasthenia gravis
• Pathogenesis Autoantibodies to
AChRs (Acetylcholine Receptors)
• Associated conditions Thymic
hyperplasia (65%)
Thymoma (15%)
• Electrophysiologic studies
decreased motor responses after
repeated stimulation
• Morphology
Electron Microscopyloss of AChRs
from region of synapse
• Clinical features
weakness starts in extraocular
muscles or generalized
clinical improvement with anticholinesterase drugs
• Complication Respiratory
compromise, no autonomic
dysfunction
Lambert-Eaton Myasthenic
Syndrome
•
•
•
•
•
•
Reference: Robbins & Cotran
Pathologic Basis of Disease. 8th Ed.
Pathogenesis Autoantibodies to
presynaptic Calcium channels
Associated conditions paraneoplastic
process with Small cell lung carcinoma60%
Electrophysiologic studies increased
motor responses after repeated
stimulation
Morphology
Electron Microscopynormal AChRs in
region of synapse
Clinical features
weakness starts in proximal muscles
no clinical improvement with
anticholinesterase drugs
Complication  Autonomic
dysfunction present
Summary
• Duchenne & Becker are the most common
Muscular Dystrophies
• Inheritance is X-linked recessive
• Dystrophin, an important skeletal muscle
intracellular protein, is either absent (DMD) or
decreased (BMD)
• Progressive weakness of the pelvic girdle
followed by the shoulder girdle occurs; symptoms
being less severe in BMD
• Management mainly involves use of steroids
along with good supportive course
Summary
• Myasthenia gravis & Lambert-Eaton
Myasthenic Syndrome are the two main
diseases of the Neuromuscular Junction; the
former being differentiated from the latter by:
– Presence of Autoantibodies to AChRs
– No autonomic dysfunction
– Decreased motor responses after repeated
stimulation in Electrophysiologic studies
– Clinical improvement with use of
Anticholinesterase drugs
Thank you