PERIPHERAL NERVE (incl CRPS; ) Flashcards
CLASSIFY AND LIST AND OUTLINE FACTORS THAT MODIFY (POSITIVE, NEGATIVE) NERVE HEALING AND REPAIR
Patient factors:
- Age
- Comorbidities: DM, alcoholism (vit def), malnutrition (vit def), Gout (colchicine inhibit tubulin)
- Cellular and humoral immune mechanisms
- Compliance w/ rehab
Nerve factors:
- Mixed motor and sensory worse than isolated/pure motor or sensory
- Proximal vs. distal nerve injury
- Nerve gap
- Neurotropic and neurotrophic factors
- neurotropism: factors produced by target to promote distal growth to target
- neurotrophism: influences that promote ‘maturation and nutrition’ of regenerating axons, includes growth factors, extracellular matrix components and hormones (neuronal growth factor (NGF), IGF, FGF, IL-1
Injury factors:
- Time since injury
- Mechanism: crush/avulsion/stretch/contusion vs. clean laceration
- Open vs. closed; contamination
- Multi-level injury
- Associated skeletal, vascular, soft tissue injury overlying/adjacent to nerve injury; devascularization
Repair factors:
- Delayed repair
- Tension on repair
- Nerve gap and graft required
WHAT ARE THE PRINCIPLES OF NERVE REPAIR?
- Mircrosurgical technique including Careful handling of tissues & dissection
- Limited devascularization of nerve
- Resection of neuroma & glioma (*can be difficult to ascertain in crush mechanism – can use frozen sections)
- Primary repair when possible
- Tension free repair / avoidance of nerve gaps
- Use of interpositional nerve graft (or alternative) if tension free primary repair not possible
- Epineural repair (not better than perineurial repair; use perineurial if grouped motor/sensory fascicles are known)
- Avoid postural movement to diminish tension
- Timing – earlier = better (<3/12 for sensory, no motor recovery >1 year)
DISCUSS THE TYPES OF NERVE REPAIR
Direct primary repair – best results within 3 wks
o Ends:
§ End-to-end (preferred)
§ End-to-side (push, recipient is in continuity, babysitter principle) - to preserve motor end-plates while await more proximal regeneration (ex: AIN to ulnar nerve after direct repair of proximal ulnar nerve injury)
§ end to side (pull, donor is in continuity) - neurotization for sensory re-innervation (ex: corneal neurotization with supraorbital n end-to-side with sural nerve graft directly onto cornea)
o Epineural repair equivalent to grouped fasicular repair – align fascicles anatomically if possible, based on topographic vascular anatomy on nerve surface
o Fascicular (perineural) –technically challenging – no proven benefit; if nerve topography known then may be advisable
o Fibrin glue
o Laser
Delayed primary repair – excise neuroma/glioma formed w/I 3 wks; then direct repair
Graft across gap
Nerve Transfer
Neurotization (placement directly on muscle fibres; least desirable)
DESCRIBE TECHNIQUES USED TO AID IN FASICULAR MATCHING
· Anatomic landmarks – fascicle size, position, epineural vessels
· Knowledge of internal topography
· Electrical stimulation – sensory for proximal and motor for distal stump (< 3 days post injury)
· Histochemical staining – stain for acetylcholinesterase, choline transferase (motor) and carbonic anhydrase (sensory) – <9d
LIST MECHANISMS TO INCREASE LENGTH TO FACILITATE PRIMARY REPAIR
· mobilization - affords 1-2cm
· transposition - ie ulnar nerve anterior transposition
· bone shortening
(+neurotization)
DISCUSS INTERNAL TOPOGRAPHY OF PERIPHERAL NERVES IN UPPER EXTREMITY
Radial
- at / above elbow: sensory bundle is fairly discrete from motor and generally more lateral, although should be nerve tested (exclude from repair to direct regenerating axons to motor end-plates)
Median - more complex because more fascicles
- forearm: AIN radial / posterior
- Distal: RMB radial and sensory are ulnar; ** in carpal tunnel the most superficial fascicle is sensory branch to long
Ulnar
- at mid-distal 1/3 becomes clear
- ulnar dorsal sensory fasicle bundle - branches from main nerve ~ 8-10cm proximal to wrist
- radial volar sesnory fasicle group
- ulnar volar motor fasicle group
- at Guyon’s canal
- Motor group passes dorsally and radially
- Sensory group becomes superficial and ulnar
DESCRIBE NERVE GRAFT HEALING
· Plasmatic imbibition (diffusion) for 3 days
· Inosculation (vascular reconnection) from proximal and distal stumps begins at 3 days
· Revascularization from surrounding tissue begins by 6 days
· Blood flow exceeds normal nerves after 6 days
CLASSIFY TYPES OF NERVE GRAFTS REPAIR
· Trunk (historical) - cross-section of a whole nerve segment interposed btwn the two ends (central fibrosis impairs growth)
· Cable – Multiple strands of nerve graft, interposed under minimal tensions, to repair a single larger nerve
· Interfascicular graft – fascicles dissected proximal and distal, neuroma excised, grafts placed btwn fascicles (use <6cm)
· Free vascularized ‘graft’ – Controversial, possible improved # axons vs non-vacularized
· Nerve conduit – gaps up to 3cm
DESCRIBE SOURCES OF NON VASCULARIZED AND VASCULARIZED AUTOGENOUS NERVE GRAFT
· Non-vascularized
- Leg: sural n., medial or lateral n. of thigh,
- Arm: MABC, LABC, PIN (good for digital nerve graft),
- Neck: cervical plexus
- Other: cutaneous portion of a nerve that has been injured proximally
· Vascularized (radial nerve-artery, sural nerve-artery, ulnar nerve + superior ulnar collateral artery, deep peroneal nerve-dorsalis pedis artery)
DESCRIBE SOURCES OF GRAFT MATERIAL FOR NERVE GAP
Nerve graft (autologous) - best results overall and for gaps > 5cm
- non-vascularized, vascularized
Nerve graft (alloplastic)
- gaps < 30-50mm
- scaffold for nerve regeneration
- processed (requires immunosuppression until renervation across coaptation) vs. decellularized
Autogenous conduit: Vein graft
- gaps < 30-50mm
Synthetic conduit
- gaps < 30mm
- polyglycolic, collagen, caprolactone
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 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 (
- Regeneration rate: initial lag phase of ~ 30 days (to cross coaptation and clear cellular debris) then ~ 1mm/d
Describe axonal regeneration to distal target
- 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
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, TENS (transcutaneous nerve stimulation), medications (gabapentin, pregabalin, TCA/lyrica)
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
what is the etiology of brachial plexopathy?
Congenital
- Congenital anomaly of the cervical rib
- Scalene anticus syndrome (Naffziger’s syndrome)
Acquired (vitamin)
Vascular
- Aneurysm of subclavian artery
Infectious
- ?viral Parsonage-Turner
Inflammatory
- Multiple neuritis, post-radiation
Trauma (most common)
- Closed (Traction or compression) – MVA, pedestrian, sports, falls, #/dislocation of shoulder, neck, clavicle
- Open – knife, GSW, glass
Toxic
Allergic
- Allergic plexopathy
Metabolic
Idiopathic
- Plexopathy of unknown origin
Iatrogenic
- Open: Intra-op injuries,
- Closed: positioning (post-anaesthetic), Radiation
Immunologic
- Post Vaccination
Neoplastic
- Benign – plexiform neuroma, benign schwannomas
- Malignant – tumours of neck, malignant schwannomas, pancoast tumour