Peripheral Nerve and Skeletal Muscle Pathology Flashcards
Guillain-Barre Syndrome
Immune mediated neuropathy
Sx: weakness beginning in distal limbs advancing to proximal muscle function with inflammation and demyelination of spinal nerve roots and peripheral nerves
- DTR disappear early on
Path: Possibly associated with infections or T cell lymphocytes issues
Morph: inflammation of peripheral nerve
- perivenular and endoneurial infiltration by lymph, macro, plasma
- worst inflammatory reaction associated with spinal and cranial motor roots
- remnants of myelin sheats engulfed by macro, noted in nodes of Ranvier
CSF: elevation of protein, infl cells
Hereditary Motor and Sensory Neuropathy Type I (Charcot Marie Tooth Disease)
Age: childhood or early adulthood
Inheritance: autosomal dominant
Sx: progressive muscular atrophy of leg below knee, distal muscle weakness, secondary orthopedic problems of the foot
Path: duplication of a large region of 17p11.2, involves PMP22
Morph: demyelination and remyelination with onion bulbs more pronounced in distal nerves than in proximal nerves
- hypertrophic neuropathy
Diabetes Mellitus Peripheral Neuropathy
Segmental demyelination, relative loss of small myelinated and unmyelinated fibers
- endoneurial arterioles show thickening, hyalinization, intense PAS positive walls
Sx: distal sensory and motor nerves neuropathy
- loss of pain sensation
- dysfunction of autonomic nervous system
Spinal Muscular Atrophy
Motor neuron diseases with progressive neurologic illnesses selectively destroying anterior horn cells in spinal cord and CN motor neurons
Inheritance: autosomal recessive
Age: childhood or adolescence
Molecular: SMN1 mutations
Morph: Large numbers of atrophic fibers
Sx: SMA 1 (Werdnig-Hoffmann Disease) - onset at birth with severe hypotonia, death first 3 yeras of life
- SMA 2 and SMA 3 present at later ages (after 2)
Duchenne Muscular Dystrophy
Sex: male children
Inheritance: x-linked recessive inheritance
Age: onset at 2, death by 18
Labs: high serum CK
Path: abnormal dystrophin gene which connects intracellular and extracellular CT matrix
Morph: variation in fiber size, increased numbers of inernalized nuclei, degeneration with necrosis and phago of muscle fibers, regeneration of muscle fibers, proliferation of endomysial CT
- muscles are lost with progressive collagen tissue and fat replacement of muscle tissue
Sx: pseudohypertrophy of lower leg muscles, clumsiness and weakness of lower extremities
Becker Muscular Dystrophy
Less severe form similar to DMD
Myotonic Dystrophy
Inheritance: Autosomal dominant
Age: adult
Sx: muscle weakness, inability to relax their muscles, frontal baldness, cataracts
- atrophy of face and ptosis
Path: CTG repeat expansion
Morph: skeletal muscle may show variation in fiber size, ring fiber, ring fiber associated with irregular mass of sarcoplasm
Fascioscapulohumeral muscular dystrophy
Inheritance: autosomal dominant
- mild muscle disease
Age: 10-30 years
Sx: weakness of muscles of face, neck, and shoulder girdle
Path: dystrophic myopathy associated with inflammatory infiltrates in muslce
Oculopharyngeal muscular dystrophy
Inheritance: autosomal dominant
Molecular: polya binding protein 2 gene
Age: mid-adult life
Sx: ptosis and weakness of extraocular muscles, difficulty in swallowing
Path: dystrophic myopathy, but often including rimmed vacuoles in type I fibers
Limb-girdle dystrophies
Inheritance: auto dom or auto recessive
Sx: myopathy
Child Dermatomyositis
Sx: skin rash, heliotrope rash around eyes, muscle weakness and pain on exertion, periorbital edema
- proximal muscles affected first
Path: capillary angiopathy manifested as loss of capillaries in muscle
- inflammation in CT septa
- no malignancy
Tx: steroids or azathioprine
Adult Dermatomyositis
Sx: extensive rash and muscle weakness main clinical features
- capillary loss in muscle
- variable inflammation
- regenerating and necrotic muscle fibers
- associated with malignancy
- proximal muscles affected first
Tx: steroids
Polymyositis
Age: adulthood disease Morph: necrosis, regeneration, lymph infiltration in and around muscle fibers - capillary angiopathy - no rash Path: cell mediated injury of myocytes Tx: steroids
Inclusion body myositis
Age: adults
Sx: diffuse muscle weakness that is slowly progressive
- begins with distal muscles, especially extensors of knees and flexors of wrist and fingers
- may be asymmetric
Path: vacuolar myopathy with filamentous inclusions on EM
Tx: not respond to steroids
Lipid storage myopathy
Carnitine deficiency
- fatty acid cannot enter mitochondria, fat accumulates in muscle fibers
Tx: steroids/carnitine replacement therapy
Kern-Sayre disease
Mitochondrial myopathy
Sx: ophthalmoplegia, heart block, retinitis pigmentosa, numerous fibers with abnormal mitochondrial accumulations
Steroid myopathy
Severe Type II fiber atrophy seen in cachexia and in patients with systemic cancer
Myasthenia Gravis
Immune mediated loss of ACh receptor
Age: women under 40, both sexes above 40
Associated: thymic hyperplasia and thymoma
Path: Autoantibodies against AChR with loss of functional AChRs at NMJ
- fixing complement and causing direct injury to post syn membrane
- increasing internalization and degradation of receptors
- inhibiting binding of ACh
Sx: weakness begins with extraocular muscles, drooping eyelids (ptosis) and double vision (diplopia), generalized weakness
Lambert-Eaton Myasthenic Syndrome
Disease of NMJ paraneoplastic process associated with small cell carcinoma of lung
Sx: proximal muscle weakness and autonomic dysfunction
