Peripheral Nerve and Skeletal Muscle Pathology

Question 1

Guillain-Barre Syndrome

Answer 1

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

Question 2

Hereditary Motor and Sensory Neuropathy Type I (Charcot Marie Tooth Disease)

Answer 2

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

Question 3

Diabetes Mellitus Peripheral Neuropathy

Answer 3

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

Question 4

Spinal Muscular Atrophy

Answer 4

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)

Question 5

Duchenne Muscular Dystrophy

Answer 5

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

Question 6

Becker Muscular Dystrophy

Answer 6

Less severe form similar to DMD

Question 7

Myotonic Dystrophy

Answer 7

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

Question 8

Fascioscapulohumeral muscular dystrophy

Answer 8

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

Question 9

Oculopharyngeal muscular dystrophy

Answer 9

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

Question 10

Limb-girdle dystrophies

Answer 10

Inheritance: auto dom or auto recessive
Sx: myopathy

Question 11

Child Dermatomyositis

Answer 11

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

Question 12

Adult Dermatomyositis

Answer 12

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

Question 13

Polymyositis

Answer 13

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

Question 14

Inclusion body myositis

Answer 14

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

Question 15

Lipid storage myopathy

Answer 15

Carnitine deficiency
- fatty acid cannot enter mitochondria, fat accumulates in muscle fibers
Tx: steroids/carnitine replacement therapy

Question 16

Kern-Sayre disease

Answer 16

Mitochondrial myopathy

Sx: ophthalmoplegia, heart block, retinitis pigmentosa, numerous fibers with abnormal mitochondrial accumulations

Question 17

Steroid myopathy

Answer 17

Severe Type II fiber atrophy seen in cachexia and in patients with systemic cancer

Question 18

Myasthenia Gravis

Answer 18

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

Question 19

Lambert-Eaton Myasthenic Syndrome

Answer 19

Disease of NMJ paraneoplastic process associated with small cell carcinoma of lung
Sx: proximal muscle weakness and autonomic dysfunction