upper extremity and peripheral nerve Flashcards
WHAT ARE THE THREE COMPONENTS OF A PERIPHERAL NERVE CELL?
- Cell body – contains nucleus & cytoplasm, located in dorsal root ganglion (sensory) or anterior horn of spinal cord (motor)
- Axon – column of neuronal cytoplasm (axoplasm) enclosed by a cell membrane (axolemma) – transports material to and from cell body via fast (200-400mm/d) or slow (1-4mm/d) transport
- Dendrites – receive electrochemical signals intended for cell body
what is a schwann cell and what is its role?
· glial cells that act to support neurons (production of trophic factors, development/regeneration, antigen presentation)
DESCRIBE THE STRUCTURAL ORGANIZATION OF A PERIPHERAL NERVE
Axon - Endoneurium - Fascicles - Perineurium - Grouped Fascicles/Peripheral nerve - Epineurium (internal, external) - Mesoneurium
-
Axon:
- unmyelinated: wrapped in Schwann-cell derived double membrane –> slower transduction of action potential
- myelinated: multi-laminated laminin-rich myelin with stacks of individual Schwann cells –> rapid nerve conduction as action potential jumps between nodes of ranvier (gap junction btwn schwann cells)
- Endoneurium: encases the axon & its glial cells; contains mesh-like layer of capillaries for axonal support
-
Fascicles: grouped axons; smalled unit that can be coapted surgically
- can be adjacent fascicular groups of similar target (motor/sensory)
- Perineurium: connective tissue that encircles each fascicle and grouped fascicles; provides selective permeability (blood-nerve barrier)
- Epineurium: structural framework supporting the fasicles
- Epifasicular (internal) epineurium: epineurial septae between fasicles
- Peripheral nerve: terminal end; groups of fasicles
- Epineurial (external) epineurium: epineurium surrounding the nerve trunk
- Mesoneurium: external loose areolar layer that permits gliding/excursion and conveys blood vessels to the nerve trunk
-
Blood supply and axonal transport:
- vasa vasorum travel longitudinally along peripheral nerve within epineurium; supplied by regional vessels; extensive alloweing for bipedicle L:W ratio of mobilization of 64:1
- axonal transport is bidirectional of neurotransmitters and neurotrophic factors
how do you classify nerve injury?
· Anatomic location: supraclavicular (roots, trunks); retroclavicular (divisions); infraclavicular (cords, branches)
o Supraclavicular can be grouped as: pre-ganglionic (avulsed roots, complete motor & sensory deficit, preclude spontaneous recovery; tend to be lower roots) vs. post-ganglionic (may retain cell body within ventral horn, rupture, tend to be upper roots)
· Mechanism: open (penetrating, gunshot, missile, avulsion) vs. closed (blunt, traction, crush)
· Degree of nerve injury: Seddon/Sunderland classification
what features are UNCOMMON in neurapraxia/conduction block?
§ Complete nerve palsy
§ Wound over course of nerve
§ Vasomotor or sudomotor paralysis in territory
§ Tinel sign
§ Neuropathic pain
DESCRIBE CLASSIFICATION BY DEGREE OF NERVE INJURY
Seddon
Sunder-land
Description
Tinel sign
NCS (fibrillation)
EMG (MUPs)
Rate of Recovery
Prognosis and treatment
Neurapraxia
I
Localized conduction block and segmental demyelination
Negative
-
Normal
fast, within 3 months
Favorable with complete recovery, no surgery
Axonotmesis
II
Axon injury; distal segment Wallerian degeneration; variable proximal degeneration or to next node of Ranvier
Positive
progresses
+
+
slow, 1mm / day
Favorable with complete recovery, rare surgery
III
Axon injury, endoneurium injury & fibrosis
Positive
progresses
+
+
slow, 1mm/day
Favorable with incomplete recovery, occasional surgery
(Neuroma-in-continuity)
IV
Nerve in continuity but axon, endo and perineurium injury with complete scar block
Positive
No progress
+
-
none
Unfavorable,requires surgery, incomplete recovery
Neurotmesis
V
completely divided nerve
Positive
No progress
+
-
none
Unfavorable,requires surgery, incomplete recovery
Mixed
VI
combination of levels I-V
+/-
+/-
variable
Variable (level I/II/III), may require surgery
define wallerian degeneration
· axon distal to the site of injury will degenerate, leaving behind a scaffold of schwann cells for nerve regeneration. Proximally, the amount of Wallerian degeneration varies with degree of nerve injury, but rarely exceeds 1-2cm
Describe what happens to cell body, proximal stump, distal stump, motor endplate, nerve ending after nerve injury
Cell Body
- Nucleus and cell body swells as the cell undergoes metabolic changes to help rebuild the damaged axon
- Neurotransmitter synthesis diminishes
Proximal Stump = chromatolysis
- Limited Wallerian degeneration, variable distance (unmyelinated) or to adjacent node of Ranvier (myelinated)
Distal Stump = Wallerian degeneration
- Increased cytoplasmic Ca++ –> Myelin phagocytosed –> End result is a hollow endoneurial sheath –> scaffold of schwann cells & macrophages for new neuronal growth (band-like appearance under EM, called Bands of Bunger)
- Endoneurial sheath shrinks approx. 1 month after injury if no axon grows into it
Motor End-Plate
- muscle fibre atrophy within weeks of injury —> eventually fibrosis; irreversible fibrosis at 12-18mos
- initially increased ACh receptors along the cell membrane (not just NMJ) leading to denervation super sensitivity with stimulation (fibrillations)
Nerve End-Organ
- Pacinian corpuscle and Merkel cells degenerate but regain function with re-innervation
- Meissner corpuscle degeneration permanent > 6 months
- Re-innervation of receptors may not correlate with functional recovery, regeneration up to 20yrs
- 2PD lost after 6-12mo delay in re-innervation; but protective sensation is possible even after years
WHAT HAPPENS IN THE PROXIMAL STUMP DURING NERVE HEALING?
- Quiescent period
- Elongate as growth-cone (regenerating unit) with single axon sprouting multiple daughter axons (filopodia, rich in actin) 5 - 24 hours after injury
- Growth cone preferentially target appropriate end-organ receptors from distal stump via contact guidance and neurotrophic factors (neurotrophins)
- Functional synapse is made and remaining daughter sprouts degenerate / are pruned back (neuroma = poor pruning)
- Rate limiting step of neuroregeneration is axonal transport of actin, tubulin and neurofilaments (< 30mm/d)
- Regeneration rate: initial lag phase of ~ 30 days (to cross coaptation and clear cellular debris) then ~ 1mm/d
WHAT HAPPENS AT THE DISTAL STUMP DURING NERVE HEALING?
- Axonal regeneration to distal target end-plate promoted via neurotropism and neurotrophism
- Neurotropism: regenerating fibres demonstrate tissue and end-organ specificity (factors produced by distal target that promote regenerating fibres get to the distal target)
-
Neurotrophism - enhanced elongation and maturation of regenerating nerve fibres to correct distal stump via autocrine / paracrine secretion of neurotrophic / nutritional factors (food for nerves)
- Neurotrophic factors expressed by Schwann cells, fibroblasts, myocytes, injured axons
- Ex: nerve growth factor, glial growth factor, epidermal growth facto, insulin-like growth factor I/II
DEFINE NEUROTROPISM
o Neurotropism: regenerating fibres demonstrate tissue and end-organ specificity (factors produced by distal target that promote regenerating fibres get to the distal target)
DEFINE NEUROTROPHISM
o Neurotrophism - enhanced elongation and maturation of regenerating nerve fibres to correct distal stump via autocrine / paracrine secretion of neurotrophic / nutritional factors (food for nerves)
§ Neurotrophic factors expressed by Schwann cells, fibroblasts, myocytes, injured axons
§ Ex: nerve growth factor, glial growth factor, epidermal growth facto, insulin-like growth factor I/II
HOW DO YOU DEFINE NEUROMA?
· Defined as the process that occurs to the proximal stump of an injured peripheral nerve when regenerating axon sprouts / growth cones do not enter the distal stump and instead grow into the surrounding mesoneurial tissue
o Schwann cells and fibroblasts produce disorganized collagen, forms encapsulated firm scar;
§ more proximal injury = bigger neuroma
WHAT IS THE HISTOPATHOLOGY OF A NEUROMA?
schwann cells, fibroblasts, disorganized collagen, blood vessels, partial/unmyelinated axons
DESCRIBE CLINICAL PRESENTATION OF NEUROMA
-
Triad of symptoms: discrete area of pain (in scar), altered sensation in peripheral nerve distribution, stagnant tinel
- Only nerves w/ sensory components are symptomatic (i.e. motor nerves will not form a symptomatic neuroma)
- Pain relieve by local anaesthetic block is helpful for diagnosis (ie compare w/ saline infiltration)
- Cause pain by:
- a) persistent mechanical or chemical irritation of axons or
- b) persistent spontaneous activation of axons leading to activity in DRG
LIST NON OPERATIVE TREATMENTS OF NEUROMA
OT/PT, desensitization, medications (gabapentin, pregabalin, TCA/lyrica – if not useful response in < 6 months unlikely to respond ever)
CLASSIFY NEUROMA
o Neuroma in continuity – neuroma in a nerve that has not been completely divided
§ Spindle = connective tissue can constrict nerve = irritation
§ Lateral neuroma – partial transection
§ Neuroma following repair
o Neuroma in completely severed nerve
DESCRIBE OPERATIVE TREATMENT OF NEUROMA
o prevention; excision of neuroma (and glioma) and:
§ direct repair / grafting of nerve (direction for axons to go, even if reinnervation not the goal);
§ transposition into muscle/vein/bone/well - vascularized soft tissue
§ relocation away from mechanical stress/pressure point
§ closure of epineurium w/ glue
§ silicone cap (poor results)
§ not useful: crushing, cauterizing, ligating, multiple sectioning
WHAT IS A GLIOMA
o no regeneration in distal stump therefore neuroma does not form
o glioma is the minor fibroblast and schwann cell response
draw the brachial plexus, label nerves, muscles innervated, and actions.
