peripheral nervous system and nerve regeneration

endoneurium

connective tissue separating individual axons

perineurium

connective tissue that bundles multiple axons together
continuous with arachnoid, can be open at NMJ

epineurium

entire bundle, visible nerves in the body (ex median or ulnar nerve)
continuous with dura

large myelinated axons

fastest conduction
efferent: A-alpha fibers to extrafusal muscle fibers
afferent: Ia to spindles, Ib to GTOs

medium myelinated axons

efferent: A-gamma fibers to intrafusal muscle fibers
afferent: II to spindles, A-beta for touch, vibration, skin stretch, pressure receptors

small myelinated axons

efferent: B to presynaptic autonomic structures
afferent: A-delta to nociceptive, temp, visceral receptors

unmyelinated axons

slowest conduction rate
efferent: C to postsynaptic autonomic structures
afferent: C to nociceptive, temp, visceral receptors

mechanical nerve injury initial response

axoplasm leaks out distal and proximal segments, ends seal by fusion and become swollen

distal segment degeneration

wallerian degeneration
distal axon and schwann cells die off within 3-5 days, macrophages come and clean up debris

chromatolysis

cell body does not receive messages from distal component, swells and nucleus shifts
how you can tell which nerve is damage

regeneration of axons

proximal axonal segment grows via slow axonal transport, schwann cells rapidly proliferate and let off chemicals to promote regeneration
basal membrane from schwann cells may stay intact, helps nerve to regrow in correct place

neuron growth chemicals

neurotrophins and neuron growth factors

transneuronal or transsynaptic degeneration

degenerative changes in cells with synaptic contact with injured neuron, retrograde (presynaptic) or anterograde (postsynaptic)
retrograde axonal transport tells cell body if distal components healthy, target gives off chemicals that are transported
in injured neuron, presynaptic neuron withdraws due to lack of input

CNS regeneration

little to none
basal lamina not available, astrocytes hypertrophy and proliferate to obstruct sprouting, adequate growth factor not available, oligodendrocytes myelin may inhibit regrowth via glycoproteins

muscle reinnervation from partial deinnervation

leads to functional overloading of remaining innervated fibers
collateral reinnervation increases size of motor unit which stresses neurons
regrouping of fiber types based on nerve innervating, changes proportions of types in muscle

peripheral nerve dysfunction sensory changes

hyperalgesia: increased sensitivity to painful stimuli
hypesthesia: decrease sensitivity to stimulus
dysesthesia: decreased sensation, abnormal sensation in absence of stimulus
allodynia: noxious response to normally non-painful stimulus
parethesia: abnormal sensation, prickling/tingling
anesthesia

peripheral nerve dysfunction autonomic changes

single nerve involvement: may be insignificant, lack of sweating, loss sympathetic control smooth muscle in arterial wall
multiple nerve involvement: more significant, difficulty regulating BP/HR, sweating, B/B, impotence

peripheral nerve dysfunction motor changes

paresis and paralysis

trophic changes in denervated muscle

no EMG activity after 7 days, increase fibrous tissue and fat, severe muscle fiber atrophy, histochemical changes

histochemical changes

increase Ach sensitivity, formation extra-junctional receptors (leads to fibrillation), increase intracellular Ca, selective fiber type atrophy

trophic changes in denervated tissue

skin shiny, nails brittle, subcutaneous thickening, ulceration of cutaneous and subcutaneous tissue, poor healing of wounds, infection, neurogenic joint damage

neuromuscular junction

interdigitated, folds in postsynaptic membrane
AP coming down nerve causes muscle to fire off always, always enough Ach/receptors to generate

mini endplate potentials

presynaptic leaks Ach at rest to signal muscle connection still there but not enough to depolarize

myasthenia gravis

impaired transmission due to decrease in Ach receptors, increase width of postsynaptic cleft, decrease number postsynaptic folds, variable muscle activity that worsens with activity

myasthenia gravis initial symptoms

extraocular eye muscle weakness causing diplopia from difficulty coordinating, bulbar phenomena

myasthenia gravis pathology

thymus gland plays crucial role, serum antibodies to AchR often found, autoimmune response

myasthenia gravis treatment

responds well to anticholinesterases (inhibit breakdown Ach), plasmapheresis, removal thymus gland, immunosuppressive drugs

NCV testing

differentiate demyelinating (slowing in NCV) vs axonal (reduced amplitude and slowing)
differentiate UMN and LMN (abnormal NCV)
identify conduction block and wallerian degeneration

EMG studies

denervation/trauma/LMN lesions: muscle fibers hypersensitive to Ach - fibrillations at rest, reinnervation leads to larger number muscle fibers per motor unit (larger amp response)
primary disease of muscle: small amplitude potentials (smaller number fibers), short duration low amp potentials with voluntary contraction, lack spontaneous muscle activity, absence sensory involvement

mononeuropathy

single nerve involvement, focal dysfunction

class I (neuropraxia)

focal compression (entrapment or pressure), axon still intact but decreased blood supply, prolonged compression leads to local demyelination

class I signs

lost or decrease function large diameter axons (motor, DT, proprioception, phasic stretch reflex), intact autonomics
commonly peroneal, ulnar, radial, median nerve

carpal tunnel syndrome

compression between carpal bones and flexor retinaculum from repetitive finger movement, gripping, vibrating tools
lead to pain, numbness, can cause lack of sweating in median nerve distribution

class II (axonotmesis)

crushing injuries/trauma, connective tissue and myelin sheath intact, all sizes of axons, reflexes reduce or absent, muscle atrophy, wallerian degeneration with slow regeneration, nerve conduction returns

class III (neurotmesis)

nerve physically severed by laceration or excessive stretch, immediate loss sensation and/or paralysis, wallerian degeneration
proximal end sprouting: some reach original targets, some meet obstacles, tangles mass (traumatic neuroma)
nerve conduction may not recover

multiple mononeuropathy

several nerves involved, slow regrowth axons
multifocal dysfunction: random asymmetrical involvement of individual nerves
from nerve ischemia from diabetes or blood vessel inflammation

polyneuropathies

diabetic neuropathy or GBS, many nerves involved, trophic changes occur
generalized dysfunction: starts distal and is symmetrical progresses to proximal

polyneuropathy etiology

metabolic: diabetes, nutritional deficits secondary to alcohol
toxic: therapeutic drugs and industrial toxins
autoimmune: GBS

diabetic polyneuropathy

all sizes axons and myelin sheaths damaged, stocking glove distribution, decreased sensation/paresthesia/dysesthesias
secondary joint involvement and ulcerations, autonomic dysfunction

GBS

acquired inflammatory demyelinating disease, motor > sensory, distal to proximal progression
increase in severity leads to: diaphragm, intercostal, CN, autonomic dysfunction

other neuromuscular disorders

duchenne muscular dystrophy: weakness starts more proximally
poliomyelitis: LMN disease, enlarged motor units
ALS: UMN and LMN
all only affect motor