Neuromuscular Junction + Disorders

Question 1

Motor Unit

Answer 1

A single axon and all of the muscle fibers innervated by that muscle fiber; size varies from a few to thousands of muscle fibers per motor unit

Question 2

Miniature End Plate Potential (MEPP)

Answer 2

~1mV depolarizations of skeletal muscle representing spontaneous release of single vesicles of ACh, each containing 5,000-10,000 ACh molecules

Question 3

Safety factor for synaptic transmission

Answer 3

Refers to the fact that the motor nerve terminal secretes the contents of a few times more than the minimum number of synaptic vesicles needed to initiate a muscular action potential

Question 4

Synaptic Facilitation

Answer 4

During repetitive, high frequency stimulation, Ca2+ accumulates in the nerve terminal due to the inability of the Ca2+ pumps to keep pace with Ca2+ influx; residual calcium increases the number of quanta released with subsequent stimulation

Question 5

Synaptic depression

Answer 5

Caused by depletion of synaptic vesicles during repetitive stimulation; after a single action potential, quantal release is reduced by about 10% and recovers over 5 seconds

Question 6

Myasthenia Gravis

Answer 6

An autoimmune diseases caused by inappropriate antibody production to the acetylcholine receptor; antibodies block the receptors causing a reduction in EPP amplitude

Greater quantal release is needed to reach the same EPP amplitude; therefore these patients are prone to synaptic depression as vesicles are depleted

Question 7

Myasthenic Syndrome

Answer 7

Autoantibody production to the pre-synaptic Ca2+ channel; antibodies block the Ca2+ channel so that fewer quanta are released and less ACh is released

Synaptic facilitation during exercise increases Ca2+ within the nerve terminal and is beneficial

Question 8

Clinical features of ALS

Answer 8

Asymmetric, progressive weakening and wasting of the limbs, often with fasciculations and foot drop; upper motor neuron signs (hyperreflexia, spasticity, Babinski sign) as well as lower motor neuron sign (flaccid paralysis) are seen

Cognitive defects seen in up to 30%

Diaphragm weakness and impaired swallowing increase risk of fatal aspiration pneumonia; mean mortality is 3.5 years

Question 9

CMT Type 1

Answer 9

Demyelinating

NCV < 38m/s

Question 10

CMT Type 2

Answer 10

Axonal degeneration (NCV > 38m/s)

Question 11

Clinical features of diabetic neuropathy

Answer 11

Distal sensory/sensorimotor polyneuropathy seen in 50-60% of diabetics; characterized by “stocking glove” distribution of numbness and burning in feet and hands

May also present with weakness of dorsiflexor muscles causing slapping foot drop gait, diminished grip strength and fine hand dexterity

Question 12

2 patterns of diabetic neuropathy

Answer 12

Large fiber - loss of position, vibration, light touch sensation, and decreased reflexes

Small fiber - loss of pain and temperature

Question 13

Clinical features of Myasthenia Gravis

Answer 13

Rapidly developing weakness often affecting cranial muscles; presents as droopy eyelids (ptosis), double vision, slurred speech, difficulty swallowing

Difficulty swallowing and respiratory muscle weakness increases risk of choking and aspiration

Question 14

Clinical features of DMD

Answer 14

Clumsy, waddling gate
Pseudohypertrophy of the calves with tendency for toe walking
Difficulty rising from the floor (Gower’s maneuver)

Question 15

Pathologic changes of ALS

Answer 15

Degeneration of UMNs, brainstem, and spinal cord LMNs

Vast majority of cases are sporadic; only 5-10% are familial

Question 16

Pathologic changes of CMT - Types I and II

Answer 16

CMT I - Slow nerve conduction velocity (demyelinating)

CMT II - Normal nerve conduction velocity (axonal degeneration)

Question 17

Pathologic changes of MG

Answer 17

Thymic hyperplasia; autoimmune

Question 18

Pathologic changes of DMD

Answer 18

Dystrophin mutation

Question 19

Genetic defect of CMT1A

Answer 19

Duplication of PMP22 gene on chromosome 17

Question 20

Genetic defect of DMD

Answer 20

X-linked mutation of dystrophin, which links actin to dystroglycan in the sarcolemma

Question 21

Immune-pathogenesis of MG

Answer 21

Production of auto-antibodies against the AChR; diagnosis is confirmed by the presence of AChR antibodies in the serum and by repetitive nerve stimulation, which produces a decremental response in the train of muscle twitches that can be restored with edrophonium

Question 22

Treatment - MG

Answer 22

Oral cholinesterase inhibitors (pyridostimine)
Corticosteroids (prednisone)
Thymectomy
Plasma exchange

Question 23

Treatment of ALS

Answer 23

Riluzole extends life 3-6 months

Question 24

Pseudobulbar affect in ALS

Answer 24

Inappropriate laughing and/or crying; caused by demyelination of fibers that project from the cortex to the brainstem

Question 25

Genetic defect of hereditary neuropathy with pressure palsy (HNPP)

Answer 25

Deletion of PMP22 gene on chromosome 17

Question 26

Upper motor neuron signs

Answer 26

Spasticity
Hyperactive tendon reflexes
Pathological reflexes (Babinski)
Emotional lability

Question 27

Lower motor neuron sign

Answer 27

Muscle atrophy
Fasciculations
Diminished tone
Reduced/absent reflexes