Muscular Pathology

Duchenne muscular dystrophy (DMD) DMD: XR; absence of

a. Epidemiology dystrophin

(1) X-linked recessive (XR)

(2) Incidence 1 : 3500 male births

b. Pathogenesis
(1) Absence of dystrophin due to frameshift mutation of the dystrophin gene on the X chromosome
(a) Dystrophin normally anchors actin to membrane glycoprotein.
DMD:
(b) Becker type has deficiency/defective dystrophin. pseudohypertrophy of
(2) Most common childhood muscular dystrophy calf muscles

(3) Progressive degeneration of type I and II fibers

(4) Fibrosis and infiltration of muscle tissue by fatty tissue
Produces pseudohypertrophy of calf muscles

c. Clinical findings
DMD: waddling gait due
(1) Symptoms occur between 2 and 5 years of age. to weakness of pelvic
(2) Weakness and wasting of pelvic muscles muscles
(a) Child places hands on the knees for help in standing (Gower maneuver)
(b) Waddling gait (duck-like)
(3) Cardiac involvement is present and causes a cardiomyopathy leading to heart failure and arrhythmias.
(4) Respiratory muscle weakness eventually leads to respiratory failure.
(5) Death usually occurs by 20 years of age.

d. Laboratory findings
DMD: serum CK at
(1) Serum creatine kinase (CK) is increased at birth (20 to 100 times greater).
birth; as muscles
It progressively declines as the muscle degenerates over time.
degenerate
(2) Female carriers have increased levels of serum CK.

e. Diagnosis
(1) Muscle biopsy, electromyography (EMG)
(2) DNA testing is available (Western blot)
Diagnosed prenatally via chorionic villous sampling

f. Treatment
Mainly supportive
Myasthenia gravis (MG)

a. Epidemiology
(1) Afflicts men in sixth and seventh decades of life MG: autonomic disorder
of postsynaptic
(2) Afflicts women in second and third decades of life neuromuscular
transmission
b. Pathogenesis
(1) Definitionautonomic disorder of postsynaptic neuromuscular transmission
MG: antibodies block
(2) Autoantibody against acetylcholine (ACh) receptors and/or destroy
(a) Type II hypersensitivity reaction
(b) Antibodies inhibit and/or destroy the receptors.
(c) Decrease in functional ACh receptors MG: autoantibodies
(3) Antibody is synthesized in the thymus. against ACh receptors;
synthesized in thymus
Thymic hyperplasia with germinal follicles (85% of cases)

c. Clinical findings
(1) Fluctuating muscle weakness
Worsened with exercise, improved with rest MG: ptosis MC initial
finding; diplopia
(2) Ptosis most common initial finding (see Fig. 24-12G, left). common
Diplopia is also common and is due to eye muscle weakness.
(3) Weakness in proximal muscles, diaphragm, neck extension and flexion (85% of cases)
(4) Dysphagia for solids and liquids MG: oropharyngeal
Occurs in the upper esophagus (striated muscle) dysphagia for solids/
liquids
(5) Normal reflexes, sensation, and coordination
(6) Increased risk for developing a thymoma (15% of cases)

d. Diagnosis
(1) Tensilon (edrophonium) test Tensilon: inhibits
acetylcholinesterase
(a) Inhibits acetylcholinesterase
(b) Increase in acetylcholine reverses muscle weakness (see Fig. 24-12G, right)
(2) Single-fiber electromyography (abnormal in 95% of MG)
e. Treatment
(1) Avoid certain medications
-Blockers, aminoglycosides, quinolone antibiotics, class 1 antiarrhythmics
(2) Pyridostigmine (acetylcholinesterase inhibitor)
(3) Immunosuppressive drugs
Corticosteroids; azathioprine; mycophenolate mofetil; cyclosporine
(4) Plasmapheresis (short-term treatment; removes antibodies)
(5) Thymectomy (removes site for antibody production)
Polymyositis (PM)
Epidemiology
Female dominant disease with an increased incidence in the black population.
Primarily occurs in persons aged 40 to 60 years.
Increased risk of malignant neoplasms (15% 20% of cases), particularly lung and bladder cancer, and non-Hodgkin
malignant lymphomas.
Etiology and pathogenesis
Cytotoxic CD8 T cells (predominant cell) and CD4 TH1 subset cells that activate macrophages damage unidentified
antigens in myocyte fibers in skeletal muscle.
Triggers for the T cell response may be associated with viruses including human retroviruses (HIV, human T-cell
lymphotropic virus 1 [HTLV-1]) and coxsackievirus B.
The viruses just mentioned damage skeletal muscle, leading to altered class I and II MHC antigens.
Clinical findings
Constitutional signs
Symmetrical, proximal muscle weakness (with or without pain) in both the upper and lower extremities, trunk,
shoulders, and hips
Symmetrical, proximal muscle weakness (with or without pain) in both the upper and lower extremities, trunk,
shoulders, and hips
Respiratory difficulties are related to interstitial lung disease
Laboratory findings
Serum creatine kinase (CK) and aldolase are markedly increased.
Antibody findings
Electromyography shows myopathic dysfunction.
Muscle biopsies show necrotic and regenerating muscle and a lymphocytic and macrophage infiltrate: Muscle atrophy is
not a prominent feature.
Treatment and Prognosis
corticosteroids first-line treatment

Dermatomyositis (DM)
Epidemiology of DM is similar to PM, including the increased risk for malignancies.
Etiology and pathogenesis
Clinical Findings
Muscle complaints are similar to those in PM.
Cutaneous findings are key.
Gottrons Papules

LambertEaton Syndrome
Pathophysiology
Disorder of the presynaptic neuromuscular transmission
Mediated by autoantibodies
Secondary to a underlying malignancy (small cell CA) in 60% of cases
Usually occurs after the age of 40
Associated with proximal muscle weakness of the arms and legs
Muscle weakness is more of the lower extremeties
Mixed Connective Tissue Disease (MCTD)
Definition
signs and symptoms similar to SLE, systemic sclerosis, and PM.
Epidemiology
female dominant, renal disease uncommon
Etiology and pathogenesis
B/ T cell activation; antibodies against ribonucleoprotein
Clinical findings
Vascular findings: Raynaud phenomenon (> 95% of cases) and sclerodactyly (50% of cases), similar to systemic sclerosis
Musculoskeletal findings: Arthralgia and arthritis involving the hands (> 95% of cases)
Gastrointestinal findings: Esophageal dysmotility similar to systemic sclerosis (65% of cases)
Clinical findings
Respiratory findings: Pulmonary hypertension, pleuritis, High association with antiphospholipid antibodies if pulmonary
hypertension is present
Cardiovascular findings: Pericarditis (40% of cases)
CNS findings: Trigeminal neuralgia is common.
Laboratory findings
Positive serum ANA (95% to 99% of cases)
Anti-ribonucleoprotein antibodies (U1-RNP; 100% of cases)
Other antibodies frequently found in MCTD include antiphospholipid antibodies, rheumatoid factor, anti dsDNA (similar
to SLE), and antiDNA topoisomerase (similar to systemic sclerosis).