Transcript Myopathies - yeditepetip

Myopathies
The term myopathy encompasses a
heterogeneous group of disorders, both
morphologically and clinically.
PRESENT WITH WEAKNESS &/OR
WASTING OF MUSCLE
Atrophy of Muscle
Atrophic fibers loose their volume (and crosssectional area) but keep their nuclei.
Simple atrophy of muscle cells occurs when they
are
• (1) deprived of its nerve supply ("neurogenic
atrophy"),
• (2) deprived of its blood supply ("ischemic
atrophy"),
• (3) not used ("disuse atrophy"),
• (4) subjected to glucocorticoids (mostly
"iatrogenic atrophy"),
• (5) vitamin D deficient
PRIMARY MYOPATHIES
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In this broad group of disorders the abnormality is
within the muscle fiber.
A number of these disorders may microscopically
resemble one another closely, making precise
histological classification difficult.
Consequently a detailed clinical and family history is
essential.
Some of these conditions are genetically determined
(hereditary) although the exact abnormality may be
unknown.
In others, there is an identifiable metabolic abnormality.
• Unknown etiology: Occasionally they appear to
be the result of an error at some stage of muscle
development and present as congenital
disorders, while some are associated with
prominent inflammation and a disturbance of the
immune system.
• Classification of primary myopathies:
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1. Dystrophic myopathies
2. Congenital myopathies
3. Metabolic myopathies
4. Inflammatory myopathy
1. Dystrophic myopathies
• A group of genetically determined (hereditary)
myopathies,
• largely of unknown etiology,
• characterised by progressive degeneration of
muscle fibres, resulting clinically in progressive
weakness and wasting of muscle.
• The 4 major patterns are:
– a. Duchenne muscular dystrophy: males, death by 20
yrs age. Now known to be due to a genetic
abnormality resulting in a deficiency of dystrophin (a
large structural protein playing a role in maintaining
integrity of muscle fibres)
– b. Myotonic dystrophy
– c. Limb-girdle dystrophy (proximal limb muscles)
– d. Fascioscapulohumeral dystrophy.
Muscle plasma membrane (sarcolemma) and dystrophin and
the dystrophin-associated proteins (merosin, dystroglycans,
sarcoglycans, and syntrophin; merosin = α2-laminin; adhalin
= α-sarcoglycan). LGMD, Limb-girdle muscular dystophy;
MD, muscular dystrophy; SCARMD, severe childhood
autosomal recessive muscular dystrophy.
DUCHENNE DYSTROPHY
• Genetically determined (X-linked)
• Deficiency of DYSTROPHIN (normally
present in muscle cell membrane) Raised CPK
• Presents males 2-4 years
• Weakness
• Pseudohypertophy of the calves
• Die by age 20 years
DUCHENNE
MUSCULAR
DYSTROPHY
There is marked variation in
fiber size and a striking
increase in perimysial and
endomysial fibrous connective
tissue with focal fat deposition.
Scattered hyalinized fibers are
present
DYSTROPHIN STAIN
NORMAL
MUSCLE
DMD
2. Congenital myopathies
• A group of disorders which have only been
defined in recent years with the advent of
enzyme histochemistry and electron
microscopy.
• Werdnig-Hoffman disease (infantile spinal
muscle atrophy)
– present with weakness or hypotonia in infancy
(floppy baby).
3. Metabolic myopathies
• A group of diseases (genetic) with identified (or
suspected) metabolic abnormalities (inborn errors of
metabolism), generalised or confined to muscle,
involving any of the principal metabolic pathways
leading to ATP production.
• Some are recognised morphologically as vacuolar
myopathies with abnormal deposits of carbohydrates
or lipid within myofibres.
• A precise definitive diagnosis depends on the
demonstration of the exact enzyme deficiency:
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glycogen storage diseases  Pompe's, McArdles
disordered lipid metabolism  carnitine deficiency
mitochondrial myopathies  altered mitochondrial physiology
periodic paralysis  associated with potassium abnormalities.
Glycogen storage disease.
Muscle biopsy specimen from a patient with type
II glycogenosis (acid maltase deficiency, Pompe's
disease) with marked vacuolization of virtually all
muscle fibers
MITOCHONDRIAL MYOPATHY
• Mitochondrial myopathy. Ragged red fiber.
(Cryostat section, Gomori trichrome.)
• Subsarcolemmal collection of enlarged and
pleomorphic mitochondria are seen in
mitochondrial myopathy.
4. Inflammatory myopathy
• Myositis
• Any inflammatory process may involve muscle,
– the term myositis (polymyositis & dermatomyositis)
refers to an inflammatory process of muscle which is
often simply a component of a more widespread
collagen vascular disease eg. SLE.
• However, polymyositis can also be seen as part
of a paraneoplastic effect.
• Histologically :
– Non-specific lymphocyte infiltration
– Granulomatous myopathies.
Non-specific myositis
• Perimysium is
markedly widened.
• Perimysium is
populated by
lymphocytes
• Necrotic fibers .
• Polymyositis. Muscle biopsy specimen has myopathic
features with fiber size variation, degenerating and split
fibers, and internal nuclei. A focal mononuclear
inflammatory cell infiltrate is present
• Dermatomyositis. This muscle exhibits striking
perifascicular atrophy and focal lymphocytic infiltrates
Granulomatous myopathies
• Clinical features
– Dysphagia
– Muscle hypertrophy
– Post-menopausal females.
• Pathology
– Granulomas
• Non-caseating
• Location in muscle.
SECONDARY MYOPATHIES
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The muscle is secondarily affected by
disease processes outside the neuromuscular system:
– 1. Cachetic atrophy - seen in many wasting
conditions eg. chronic infection, cancer,
malabsorption, old age.
– 2. Endocrine disorders - eg. acromegaly, hyper
and hypothyroidism, hyperaldosteronism (K+),
hyperparathyroidism, corticosteroid excess.
– 3. Alcohol and other drugs - may produce a
"necrotising, inflammatory myopathy".
– 4. Vit D deficiency.
MYASTHENIA GRAVIS
• A disorder of the neuromuscular strength that
occurs during sustained or repetitive muscle
contraction.
• In obtaining the history it is essential to
document that loss of muscle power occurs in
association with continuous effort.
• It is also necessary to inquire about common
signs and symptoms, such as ptosis, diplopia,
dysarthria or dysphagia.
• Improvement with rest is an important
feature of the disease.
• Young women
• Polyclonal antibodies attack the
acetylcholine receptor of the post-synaptic
membrane of the neuromuscular junction.
• This is not an anatomic pathologist's
disease.
– In a minority of patients clusters of
lymphocytes ("lymphorrhages") appear
around the motor end plates.
Anti-skeletal muscle antibody titer: Elevated in
95% of patients with thymoma.
NORMAL
MYASTHENIA GRAVIS
Lymphorrhages
Types of MG
• 1. Autoimmune ocular: Many patients present
with ocular involvement. Some have disease
restricted to ocular musculature and never have
generalized MG.
• 2. Autoimmune generalized:
– a. Many patients present with ocular symptoms.
– b. Most patients have generalized weakness within
13 months of clinical onset.
– c. 40% improve.
– d. 15% develop irreversible weakness and atrophy.
• 3. Transient neonatal MG: is produced by passive
transfer of maternal antibodies from a mother with MG.
• 4. Congenital MG: Multiple forms occur with different
pathophysiological mechanisms such as structural
and/or electrophysiologic defects of the neuromuscular
junction. These are congenital syndromes and not
related to autoimmunity.
• 5. Drug Induced MG: Antibody mediated MG is
sometimes caused by the drug Penicillamine.
• 6. Neuromuscular Junction Blockade (NJM):
Gentamicin and other Aminoglycoside antibiotics can
cause a pharmacologic block of the NJM which has
clinical features similar to MG without autoimmunity.
Autoimmune diseases associated with
MG
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Autoimmune Thyroid Diseases
Systemic Lupus Erythematosus (SLE)
Rheumatoid arthritis
Pernicious anemia
Pemphigus vulgaris (an autoimmune skin
disease)
MYASTHENIC SYNDROMES
• CONGENITAL MYASTHENIC
SYNDROMES
– not associated with antibody or autoimmunity
• LAMBERT-EATON MYASTHENIC
SYNDROME
– Weakness and fatigue of proximal muscles
– relative sparing of ocular and bulbar muscles.
– common association with carcinoma
• specifically oat cell carcinoma of the lung.
BOTULISM
• A food-borne illness caused by the
exotoxin of clostridium botulinum.
• Canned vegetables are the most frequent
source of poisoning.
• Symptoms frequently begin 12 to 36 hours
after ingestion of the contaminated food.
Symptoms and clinical findings of
Botulism
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Blurred vision and diplopia
Ptosis
Extraocular muscle palsies
Dysarthria and dysphagia
Progressive generalized weakness with
respiratory failure.
6. Dilated pupils
7. Constipation
AMYOTROPHIC LATERAL
SCLEROSIS
• A progressive disorder involving lower and
upper motor systems.
• Clinical features: Wasting and weakness
of muscles with visible fasciculations in
scattered muscles.
– The disease frequently presents in the upper
extremities but may initially involve lower
extremities or bulbar muscles.
– Hyper-reflexia and spasticity may be
observed.
• Pathology:
– Shrinkage with sclerosis in the corticospinal
tracts
– Degeneration of the large anterior horn
neurons noted in spinal cord and brainstem
– Degeneration of the large Betz cells of the
motor cortex.
MUSCLE BIOPSY
MUSCLE BIOPSY REQUIRES SPECIAL
TECHNIQUES.
SAMPLE MUST NOT BE PUT INTO
FORMALDEHYDE!!!
THUS PRIOR PATHOLGY
CONSULTATION IS ESSENTIAL!!!