Peripheral Neuropathies Flashcards
what % of peripheral neuropathies are idiopathic?
10-30% are idiopathic
subtypes of neuropathy
1) axonal
2) demyelinating
3) wallerian degeneration
perineurium
surrounds each nerve fascicle
epineurium
binds all the fascicles in a nerve
blood supply of peripheral nerves
longitundinal, highly anastamosing vascular supply of arterial branches
size and myelination of touch, pressure, spindle afferents
Large, heavily myelinated
size and myelination of sharp pain, temperature
smaller, thinly myelinated
size and myelination of dull/burning/poorly localized pain
small, unmyelinated
type I PNS sensory fibers
myelinated
80-120 m/sec (fastest)
touch, pressure, spindle afferents
type II PNS sensory fibers
thinly myelinated
30-75 m/sec (medium speed)
sharp pain, temperature
type III PNS sensory fibers
unmyelinated
0.5-30 m/sec (slowest)
burning, dull, diffuse pain
PNS Motor: large myelinated fibers terminate on _____
PNS Motor: large myelinated fibers terminate on MUSCLE
PNS Motor: small unmyelinated fibers terminate on _____
PNS Motor: small unmyelinated fibers terminate on parasympathetic/sympathetic ganglia
alpha motor unit
80-120 m/sec (fast)
large, myelinated
main movers of skeletal muscle
gamma motor unit
4-25 m/sec (kinda slow)
large, myelinated
terminate on muscle spindles, maintain tension
preganglionic autonomic
3-15 m/sec (slow)
small, unmyelinated
postganglionic autonomic
.5-2 m/sec (super slow)
small, unmyelinated
axonal transport runs along __________
axonal transport runs along MICROTUBULES
anterograde transportation
away from cell body
retrograde transportation
towards cell body
T or F: axonal transport does not require energy
F.
Axonal transport requires energy – ox phos in mitochondria
effects of vincristin/vinblastine (chemotherapeutic drugs) on axons
Disrupt neurotubule organiation.
Results in neuropathy.
________ transport is necessary to maintain the axon itself
ANTEROGRADE transport is necessary to maintain the axon itself (and thus the muscle too since denervated muscles atrophy)
what happens to denervated muscle?
atrophy
what is transported with rapid axonal transport?
synaptic vesicles,
membrane bound proteins
what is required to link proteins to microtubules in anterograde axonal transport?
kinesin
what is transported with slow axonal transport?
soluble enzymes,
tubulin (used in making microtubules)
100x slower
what determines the rate of recovery from nerve injury?
slow axonal transport
-bc it is needed to transport the structural components
what is transported with retrograde transport?
Signal of nerve injury
-induces chromatolysis
neurotropic viruses and axonal transport
Neurotropic viruses: polio, herpes, rabies.
- enter peripheral nerve endings
- use retrograde transport to ascend to nerve body
what protein is required with retrograde axonal transport?
dynein (instead of kinesin)
Wallerian degeneration
“dying forward”
- axonal injury occurs
- axon dies from site of injury to the end of the axon (peripherally)
- chromatolysis
- muscle atrophy
axonal degeneration
“dying back”
- metabolic derangement
- distal part dies first (due to lack of nutrients etc)
- proximal direction
- chromatolysis
- muscle atrophy
segmental demyelination
- myelin is stripped off in some places
- AP dies out
- axon is still intact, just missing myelin
- NO chromatolysis
- NO muscle atrophy
nerve conduction studies
- used to diagnose peripheral neuropathies
- measure nerve function
- measure evoked action potentials (either motor or sensory)
does NOT look at overall nerve function
-just between cell body and end organ
-helps distinguish between types of lesions
Peripheral nerve injury: appearance on nerve conduction studies
Motor: abnormal
Sensory: abnormal
- lesion distal to dorsal root ganglion
- both axons are cut between cell body and muscle
- neither trigger an AP
nerve root injury: appearance on nerve conduction studies
Motor: abnormal
Sensory: normal
- axon bringing sensory info to cell body is still intact; still transmits AP
- motor axon is cut between anterior horn cells and muscle; degenerates; no AP
patterns involved in diagnosis of peripheral neuropathies
- Focal v. Systemic
- Motor v. Sensory v. Autonomic v. Mixed
- Chronic v. Acute
- Axonal v. Demyelinating
- weakness: myotomal or peripheral nerve pattern
- atrophy?
- distal weakness (axonal) or proximal weakness (demyelinating)?
patellar reflex tests
L4
achilles reflex tests
S1
how to measure conduction velocity
Stimulate nerve at two spots
Subtract the time between the two
slower in demyelinated nerve
pattern of root damage v. peripheral n damage
ROOT
- dermatomes overlap
- difficult to pinpoint
PERIPHERAL N
- do not overlap
- easier to pin point
muscles atrophy suggests
axonal damage
no atrophy suggests
demyelinating damage
distal weakness suggests
axonal damage
proximal weakness suggests
demyelinating damage
OR myopathy
symptoms of axonal neuropathy
- slow, chronic
- stocking glove distribution
- loss of reflexes distally
- muscle wasting distally
- low amplitude CMAPs (muscle AP)
- absent SNAPs (sensory AP)
causes of axonal neuropathy
- metabolic: diabetes, uremia, endocrine, porphyria
- toxic: environmental or pharmalogical agents
- deficiency: thiamine, pyridoxine, vit E
- genetic: HSMN II
- paraneoplastic: tumors make antibodies that injure nerves
Guillian-Barre Syndrome
- acute demyelinating polyneuropathy
- segmental demyelination
- primarily motor (some sensory)
- rapidly progressive
- no reflexes (afferent pathology)
- ataxia (afferent pathology)
- conduction block
- treatment: immune modulating therapy (IVIg)
if reflexes are lost, it is most likely due to a ______ injury
sensory/afferent
what part of the nerve is most susceptible to injury?
myelin
- may degenerate as part of primary disease process
- or as secondary effect of axonal disruption
causes of demylinating polyneuropathy
- autoimmune: Guillain-Barre, CIDP (chronic inflammatory demyelinating neuropathy), certain antibodies
- genetic: Charcot-Marie-Tooth I, metachromatic leukodystrophy
causes of chronic demyelinating neuropathy
- hereditary: Charcot-Marie-Tooth I
- chronic inflammatory demyelinating neuropathy (CIDP)
histological sign of chronic demyelinating neuropathy
onion bulb sign
-myelin grows, dies, grows, dies…
ischemic mononeuritis multiplex
- commonly seen in polyarteritis nodosa (vasculitis)
- fascicular injury –> individual fascicles are injured by interruption of microcirculation of nerve
- confluent mononeuritis makes it look like generalized neuropathy
- biopsy: arteritis, fascicular injury
-tx: steroids (vasculitis), cyclophosphamide (immune modulating drug)
fascicular injury
- Individual fascicles are injured, not the whole nerve.
- Due to interruption of the microcirculation of the nerve.
types of focal neuropathies
- Compressive/traumatic
- Ischemic: diabetic or vasculitic – fascicular injury
- autoimmune; brachial plexopathy
-Injury: wallerian degeneration
injury associated with focal neuropathies
wallerian degeneration
- disruption of anterograde transport so axon dies backward
- retrograde transport starts chromatolysis, increases metabolic activity for axonal regeneration
- axonal sprouting occurs
- regeneration depends on if schwann cell sheaths are disrupted or not
traumatic nerve injury classification
CLASS 1: Neurapraxia
- compression with focal demyelination
- no denervation (no atrophy)
- quick recovery
CLASS 2: Axonotmesis
- axonal damage
- intact nerve sheath for sprouting to occur through
- slower recovery (sometimes incomplete)
CLASS 3: Neurotmesis
- scarred/disrupted nerve sheath
- no recovery
neurotmesis
- scarred/disrupted nerve sheath
- no recovery
Axonotmesis
- axonal damage
- intact nerve sheath for sprouting to occur through
- slower recovery (sometimes incomplete)
Neurapraxia
- compression with focal demyelination
- no denervation (no atrophy)
- quick recovery
involvement of feet before hands is seen in ______ neuropathy
involvement of feet before hands is seen in AXONAL neuropathy
slowed conduction characterizes a ________ neuropathy
slowed conduction characterizes a DEMYELINATING neuropathy
nerve disease in general (w/ exception of ____________) usually leads to atrophy
nerve disease in general (w/ exception of SEGMENTAL DEMYELINATION) usually leads to atrophy
