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1. DISEASES OF THE NEUROMUSCULAR
JUNCTION
• Regardless of cause, patients with disorders
that impair the function of neuromuscular
junctions complain of painless weakness and
fatigue

2. Myasthenia Gravis
• is an autoimmune disease that is usually associated with
autoantibodies directed against Ach receptors
• Pathogenesis
– About 85% of patients have autoantibodies against postsynaptic
ACh receptors
– most of the remaining patients have antibodies against the
sarcolemmal protein musclespecific receptor tyrosine kinase
• There is a strong association between pathogenic anti–ACh
receptor autoantibodies and thymic abnormalities
• Patients with anti–ACh receptor antibodies typically
present with fluctuating weakness that worsens with
exertion and often over the course of the day.

3. • Diplopia and ptosis due to involvement of
extraocular muscles are common and distinguish
myasthenia gravis from myopathies
• Cases with antibodies against muscle-specific
receptor tyrosine kinase differ from typical cases
by exhibiting more focal muscle involvement
• Diagnosis is based on clinical history, physical
findings, identification of autoantibodies, and
electrophysiologic studies

4. DISEASES OF SKELETAL MUSCLE

5. Skeletal Muscle Atrophy
• Causes: Loss of innervation, disuse, cachexia, old
age, and primary myopathies
• Clusters or groups of atrophic fibers -neurogenic
disease.
• Perifascicular atrophy - in dermatomyositis
• Type II fiber atrophy with sparing of type I fibers is
seen with prolonged corticosteroid therapy or
disuse

7. Inflammatory Myopathies
• Historically, dermatomyositis, polymyositis,
and inclusion body myositis have been
considered the three main primary
inflammatory myopathies

8. Dermatomyositis
• is a systemic autoimmune disease that typically
presents with proximal muscle weakness and skin
changes.
• Pathogenesis
– is an immunologic disease in which damage to small blood
vessels contributes to muscle injury
– Biopsies of muscle and skin may show deposition of the
complement membrane attack complex (C5b-9) within
capillary beds
• may occur in adults or in children(av=7yr)
• Dermatomyositis is the most common inflammatory
myopathy in children

9. C/F
• Muscle weakness is slow in onset, symmetric,
and often accompanied by myalgias.
• It typically affects the proximal muscles first
• heliotrope rash associated with periorbital
edema
• a scaling erythematous eruption or dusky red
patches over the knuckles, elbows, and knees
(Gottron papules)

11. •Morphology
•perimysial mononuclear inflammatory
infiltrates
•perifascicular atrophy

12. Polymyositis
• is an adult-onset inflammatory myopathy that
shares myalgia and weakness with
dermatomyositis but lacks its distinctive
cutaneous feature
• vascular injury does not have a major role in
the pathogenesis

13. Inclusion Body Myositis
• is a disease of late adulthood that typically affects
patients older than 50 years
• is the most common inflammatory myopathy in
patients older than age 65 years
• present with slowly progressive muscle weakness
that tends to be most severe in the quadriceps
and the distal upper extremity muscles
• Abnormal cytoplasmic inclusions described as
“rimmed vacuoles”

14. Toxic Myopathies
• can be caused by prescription or recreational
drugs or by certain hormonal imbalances
• Eg statins, thyroid dysfunction, alcohol etc..

15. Muscular Dystrophies
• include many inherited disorders of skeletal muscle
that have in common progressive muscle damage that
typically manifests between childhood and adulthood
• with the exception of congenital muscular dystrophies,
these diseases do not present in infancy
• The most common muscular dystrophies are X-linked
and stem from mutations that disrupt the function of a
large structural protein called dystrophin

16. Duchenne and Becker Muscular
Dystrophy
• The most common early-onset form is referred to
as Duchenne muscular dystrophy
– has a severe progressive phenotype
• Becker muscular dystrophy is a second relatively
common dystrophinopathy that is characterized
by later disease onset and a milder phenotype
• are caused by loss-of-function mutations in the
dystrophin gene on the X chromosome
• Dystrophin is thought to provide mechanical
stability to the myofiber and its cell membrane
during muscle contraction

17. • C/F of duchenne MD
– Boys with Duchenne muscular dystrophy appear normal at
birth.
– Very early motor milestones are met, but walking is often
delayed
– Despite supportive care, the mean age of death is 25 to 30 years
of age
• Dystrophin is also expressed in the heart and the CNS
• in contrast Becker md , typically presents in later childhood,
adolescence, or adult life; has slower progression; and may
have a near-normal life expectancy

18. • morphologic changes that muscular dystrophies elicit in skeletal muscle
tissue may differ in severity but do not discriminate between different
forms of dystrophy

19. END