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
How do you classify BPI?
- Congenital vs. acquired
- By level
- Root/trunk/division/cord/branches
- Supraclavicular (pre-ganglionic vs. post-ganglionic)
- Retroclavicular
- Infraclavicular
- By mechanism:
- Open: penetrating (clean, contused), avulsion, gunshot, missile
- Closed: crush, traction, fall, mvc
List findings that differentiate a pre-ganglionic injury (infer avulsion)
- On history:
- Nerve pain / deafferentiation pain
- On physical:
- proximal motor weakness (levator, rhomboids, paraspinals)
- anaesthesia at/above the glenohumeral joint
- Horner’s syndrome (miosis, anhydrosis, ptosis, enophthalmos)
- No or weak Tinel in supraclavicular neck
- On investigations:
- C-spine fracture
- Elevation hemi-diaphragm (phrenic nerve palsy)
- CT myelogram shows pseudomeningocele +/- absent ventral root
- EDS show proximal muscle denervation
- NCS show present SNAP in anesthetic limb
- On special tests:
- negative SSEP intraoperative
- positive histamine triple response (vasodilation, wheal, flare) in anaesthetic limb
what to know on history for acquired BPI?
- Rule out life or limb threatening injuries; LOC / altered level of consciousness – head injury
- ID: age, hand dominance, occupation, hobbies
- Mechanism of injury: timing, open (penetration, knife edges, gsw, missile, etc) vs closed (traction, fall, MVC) vs other mechanism; low vs. high velocity
- Arm position at time of injury
- Arm pulled down – C5 & C6 roots injuries
- Arm abducted to 90o – middle plexus injured, especially C7 (iatrogenic intraop injuries)
- Arm abducted > 90o – lower plexus injured, C8 & T1 are more severely injured
- Symptoms: ispilateral motor/sensory deficits, pain (quality, quantity etc); Presence of paresthesia / weakness in other extremities – head or C-spine (complete and incomplete) injuries
what to do on physical / how do you approach physical for acquired BPI?
- ABCs, vitals, general examination, vascular exam/pulses
- Ideal to remove shirt; examine entire forequarter (extremity, back, chest, neck) of ipsi & contra-lateral
- Assess for Horner’s (present 3-4 days post injury) – strongly correlates with avulsion C8/T1 or traction injury very close to cord (sympathetic fibres divide from the spinal nerve and emerge from T1 & T2 foramen), poor prognostic sign of recovery
- Motor
- Inspection – fasciculations, atrophy, position (waiter tip [upper plexus] - shoulder adduction, internal rotation; elbow extension; forearm pronation; wrist flexion)
- All muscle groups tests in detailed & objective manner (MRC 0-5)
- Proximal to distal following organization of plexus in terms of MOVEMENTS (for plexus) and MUSCLES (for peripheral nerves) and including trapezius, paraspinal muscles (head position)
- AROM/PROM – look for glenohumeral joint stability (axillary nerve)
- Reflexes
- Sensory (each dermatome and terminal branches)
- MRC scale in all distributions (S0-S4)
- Innervation density (S2PD, D2PD) & threshold (monofilament/vibration)
- Tinel
- Histamine triple response test
- Histamine injected dermally à vasodilation, wheal, flare
- Response = axonal reflex involving the sympathetic ganglion & DRG
- Skin denervation + intact triple response à pre-ganglionic lesion
- Serial exams over time
describe classic patterns of BPI (by cervical root) muscles affected, and motor functions /sensory loss
Roots
Muscles Affected
Functional Loss
Sensory Loss
C 5-6
Erb-Duchenne palsy
- Deltoid, supraspinatus & infraspinatus, biceps, brachialis, coracobrachialis, brachioradialis ± radial wrist extensors, clavicular pectoralis major
- Shoulder ext/int rotation, abduction & forward flexion, elbow flexion ± wrist extension, supination
- Shoulder, lateral arm + thumb & index finger
C5-7
Erb’s Plus deformity
- As above, plus triceps, ECRL & ECRB, FCR, EDC, EPL, EPB, APL
- As above plus elbow, wrist, finger & thumb extensors
- As above, plus middle finger
C(7), 8, T1 Klumpke’s palsy
- (EDC, EPL) FDS, FDP, FPL, Lumbricals & interossei, thenars & hypothenars
- (Finger extension) Finger & thumb flexion, median & ulnar intrinsics
- Anterior and medial arm, (middle finger), Little & ring fingers
C5 - T1
- All above
- All above (flail arm)
- Anaesthesia
discuss when, how and why diagnostic imaging is used in acquired BPI?
- Plain X-rays
- Cervical spine, chest, clavicle, shoulder girdle & humerus
- CXR – inspiration / expiration AP – to assess diaphragm activity: elevation hemi-diaphragam = upper roots & phrenic n
- Arteriogram
- Penetrating injury to region of brachial plexus
- Abnormal pulses associated with blunt or penetrating trauma
- Normal initial exam followed by ↑ brachial plexus neurologic deficit that may be due to an expanding haematoma
- CT / myelogram
- Perform at 3-4 weeks to r/o pseudomeningocele: dye extrudes thru rupture of root/meningeal tear
- Absence of 1 or both ventral/dorsal rootlets seen with a pseudomeningocele increases the specificity for root avulsion
- Sensitivity 74-95 %, specificity – 90-98% [institution dependent]
- MRI
- High field strength MRI with mutliplanar views for distal plexus lesions; gold standard for non-traumatic BP palsy
- 3D MR myelography – intradural rootlets
- Both sensitivity and specificity lower than that reported for CT/Myelogram
discuss use of EMG in BPI
- Useful to assess muscles which are difficult to assess clinically (rhomboids, serratus anterior, paraspinal muscles)
- Denervation paraspinals = strong indicator of root avulsion
- First few days: no change
- 5-7 days: reduced recruitment - fewer MUPS;
- 6-12 weeks
- Denervation: Fibrillations indicate axonal injury (2nd – 5th) – present at > 6 wks; absent MUPs w/ volunt. effort @ 12 wks
- Signs of spontaneous recovery/reinnervation @ 12 wk assessment (2nd, 3rd degree injury): MUPS, nascent units, giant MUPS ( higher amplitude and longer duration)
discuss use of NCS in BPI
· Sensory Nerve Action Potentials (SNAPs) most helpful to determine pre/postganglionic level of injury
o preganglionic injuries à DRG separated from the CNS causing anaesthesia, however the cell body of the peripheral nerve which is located within the DRG is intact so Wallerian degeneration does not occur and the SNAP is maintained
o Positive SNAP in the presence of anaesthesia is pathognomonic of preganglionic injury (= root avulsion)
