Peripheral Nervous System Disorders

Question 1

contrast negative vs positive PNS lesion

Answer 1

• negative: loss of normal function
  
  • muscle weakness
  • loss of tendon reflexes
  • autonomic deficits (anhydrosis)
  • impaired sensation (anesthesia)
• positive: emergent or exaggerated phenomena
  
  • paresthesias (numbness, pins and needles, tingling) possibly reflecting ephatic transmission between adjacent damaged sensory nerve fibers that have become hyperexcitable
  • pain cuased by compression of nerves leading to hyperexcitability (carpal tunnel)

Question 2

what is the equation for conduction velocity?

Answer 2

= D2 /(T2-T1)

Question 3

describe how lesions affect mean conduction velocities

Answer 3

• lesion in motor neuron soma: slight or no change in motor
  
  • no change in sensory
• demyelination of peripheral nerve: marked reduction in motor + sens. CV
• compression of periph. nerve: slowing of motor + sens. at site
• axonal degeneration of periph. n.: no or slight reduction
• NMJ: no change in motor + sensory
• muscle: no change in motor + sensory

Question 4

the ____ is the most vulnerable part of the peripheral nerve, whereas the tough _____ is the most damage resistant

Answer 4

the axon is the most vulnerable part of the peripheral nerve, whereas the tough epineurium is the most damage resistant

Question 5

describe chromatolysis

Answer 5

dilution of somatic organelles with enlargement and displacement of the nucleus/nucleolus (often precedes apoptosis)

Question 6

describe Wallerian degeneration

Answer 6

degeneraton of the distal part of the transected axon

Question 7

describe anterograde transneural degeneration

Answer 7

degeneration of downstream nerve cells

Question 8

describe retrograde transneural degeneration

Answer 8

degeneration of upstream nerve cells

Question 9

describe the degeneration seen here

Answer 9

Question 10

describe the degeneration seen here

Answer 10

Question 11

describe the degeneration seen here

Answer 11

Question 12

describe the regeneration and regrowth in the PNS

Answer 12

• after transection of a peripheral nerve, axonal sprouting may occur
• the sprouts use the lingering Schwann cells of the Wallerian-degenerated axons as guide tubes for regrowth (~1mm/day)
• functional axonal regrowth is facilitated by “nerve growth factor” (which is released by the Schwann cells), laminins and adhesion molecules
• later, Schwann cells may remyelinate axons, restoring conduction velocities

Question 13

describe why regeneration doesn’t occur in the CNS

Answer 13

• oligodendrocytes neither release nerve growth factor nor guide regenerating axonal sprouts (unlike Schwann cells)
• gliosis occurs, where astrocytes proliferate in traumatized regions and form glial scars that act as mechanical barriers to sprouting axons
• an inhibitory chemical messenger accumulates within the CNS to oppose axonal regeneratio in adults

Question 14

describe reinnervation of denervated skeletal muscle

Answer 14

• the regenerating axons differentiate into nerve terminals when they contact the basal lamina
• certain components of the basal lamina facilitate reinnervation of synaptic sites and trigger the differentiation of axonal grwoth cones into presynaptic nerve terminals

Question 15

describe what is seen

Answer 15

• when the muscle is injured (including the basal lamina), there is an absence/decreased amount of receptors, so function is difficult to regain in those patients where basal lamina is not injured

Question 16

describe the different laminin isoforms

Answer 16

different laminin isoforms exist in synaptic and extrasynaptic basal lamina

• laminin 11 is present int he synaptic basal lamina
• laminin 2 arises in the extrasynaptic basal lamina

Question 17

describe Guillain-Barre syndrome

Answer 17

refulects progressive (often ascending) muscle weakness and paralysis that may follow an infectious illness (often respiratory or GI)

• causes: acute inflammation damages the myelin sheath
  
  • as a result, the conduction of impulses through the nerve slow or ceases

Question 18

describe what is seen in the tests of Guillian-Barre patients

Answer 18

• lumbar puncture: elevated protein in CSF (100-300 mg/dL)
• nerve conduction velocity decreased
• EMG: diminished nervous input

Question 19

describe treatment of Guillain-Barre

Answer 19

• intravenous immune globulin
• plasmapheresis (plasma exchange)
• ventilatory support

Question 20

describe leprosy (Hansen disease)

Answer 20

chornic infection that affects the skin and the peripheral nerves; one of the commonest treatable neuropathy

• etiology: infection of skin and peripheral nerves by myobacterium leprae, usually after a long incubation or slow multiplication
  
  • bacterial multiplication causes compression and ischemia of peripheral axons which result in profound sensory losses (pain and temp.)
• bacterial entry proceeds through a cutaneous lesion, often following contact with nasal secretions from infected persons

Question 21

describe lead poisoning

Answer 21

• children younger than 6 years are vulnerable to lead toxicity
• relatively low blood levels of lead may lead to encephalopathy with diminished IQ, attention problems, and learning disabilities
• in adults, lead poisoning may cause memory and concetration problems and peripheral motor neuropathy, often preferentially targeting extensor muscles (wrist drop is seen)​

Question 22

describe alcoholic peripheral neuropathy

Answer 22

• reflects the neurotoxic effects of alcohol or associated nutritional (thiamin) deficiencies in persons consuming more than 80-100 g alc/day
• sensory and motor losses, both symmetrical
  
  • starts with sensory neuropathy from distal (foot, leg, etc)
  • motor losses follow
• nerve conduction velocity normal in most cases

Question 23

describe diabetes mellitus (in peripheral neuropathy)

Answer 23

• many diabetics (type I and type II) eventually develop polyneuropathy
• types: sensory (usually symmetric in the distal extremities), motor (usually asymmetric) and autonomic neuropathy
• begins in the extremities (usually legs) with abnormalities of unmyelinated axons carrying pain and temp. in a “stocking and glove” distribution
• may originate in failure of the cell body to supply its distal parts with nutrients and essential cytoskeletal proteins
  
  • accompanying vasculopathy may also be implicated