This document summarizes several neuromuscular diseases. It first describes myasthenia gravis as an autoimmune disorder causing weakness that worsens with exertion, often involving extraocular muscles. It is diagnosed through clinical exams, autoantibody identification, and electrophysiology. Dermatomyositis is then covered as a systemic autoimmune disease causing muscle weakness and skin changes, often affecting children. Inflammatory myopathies like polymyositis and inclusion body myositis are discussed alongside toxic and muscular dystrophies like Duchenne muscular dystrophy. Duchenne is severe and early-onset while Becker is milder with later onset; both involve mutations disrupting the dystrophin

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