Peripheral Pathology Flashcards
Compare and contrast axonal regeneration and segmental regeneration
Axon= slow recovery
Segment =rapid recovery
Both= new myelin internodes are shorter and thinner
Compare and contrast axon injury involved in axonal and segmental degeneration
Axonal: involves distal axon and its associated myelin sheath with chromatolysis
Segmental: spares axons
compare and contrast the myofibers and nerve conduction presentation in axonal and segmental degeneration
Axonal: denervated myofibers become atrophied and there is no nerve conduction
Segmental: Muscle fibers are not affected and nerve conduction is only slowed
Define Neuropraxia and describe it with regards to its features and prognosis
Definition: compression injury causing temporary disruption of nerve conduction
Features: whole nerve remains structurally intact
Prognosis: Good chance of complete recovery of nerve function
Define Axonotmesis and describe it with regards to its features and prognosis
Definition: axon is damaged, but the perineurium and epineurium remain intact
Features: Chromatolysis and Wallerian Degeneration
Prognosis: good chance of at least partial recovery in a few months
what is chromatolysis?
reaction of a neuronal cell body in response to an axonal injury
It reflects an increase in protein synthesis in effort to restore the integrity of the damaged neurons
what does chromatolysis look like
swelling of the neuronal cell body
dispersion of Nissl Bodies
Displacement of the nucleus to the periphery
What is Wallerian Degeneration
active neuronal degeneration process in response to axonal injury to clear axonal debris and prevent scarring
Describe Wallerian Degeneration
- Initially retained electrical excitability of axonal membranes distal to the injury for up to 36 hours
- progressive degeneration of the distal segment cytoskeleton with dissolution of axonal membrane
- Degradation of residual myelin sheath by macrophages and Schwann cells
- Proximal stump stays in place, ultimately sprouting regenerative nerve fibers that ideally reinnervate the distal tissues
Define Neurotmesis and describe it with regards to its features and prognosis
Definition: complete nerve resection
Features: connective nerve sheath damage
Prognosis: Chance of recovery is poor without surgical repair
What is a traumatic neuroma
a painful, but benign nodular thickening resulting from a failure of the regenerating axons to find their distal target
Compare and contrast Wallerian degeneration in CNS and PNS with regards to its cell type, timing and likelihood of regeneration
why doesn’t regeneration occur in CNS Wallerian degeneration
persistence of myelin debris
secretion of inhibitory factors
dense glial scarring
Why does myelin debris last for so long in CNS Wallerian degeneration
macrophages and microglia are slowly recruited due to the BBB
Compare and contrast neurofibromas and schwannomas with respect to:
- location
- nerve involvement
- capsule presence
- patterns
- cell types involved
- risk of malignancy
- Associations
Describe Neurofibromas
small nodular tumors of the skin and subQ tissues, arising from small cutaneous nerves
- has no neurologic deficits
- can be isolated
- may cause local pain or bleeding
Describe the different subtypes of neurofibromas
Diffuse: large plaque-like elevations of the skin
Plexiform: multiple nodular masses affecting nerve roots, plexuses or large nerves
What causes neurofibromas
germline mutations of NF1 on chromosome 17 cause intracellular neurofibromin proteins.
These proteins increase the RAS signalling cascade
Describe the morphology of a neurofibroma
heterogenous composition of Schwann cells, admixed with perineural-like cells, fibroblasts and CD34+ spindle cells
Complications of neurofibromas
Malignant peripheral nerve sheath tumors
What are Malignant peripheral nerve sheath tumors and where do you usually find them
poorly defined tumor masses that frequently infiltrate along the axis of the parent nerve and invade soft tissues
Usually found on the:
- chest
- abdomen
- pelvis
- neck
- limb girdle
how are most Malignant peripheral nerve sheath tumors formed
from transformation of a plexiform neurofibroma
Describe the morphology of Malignant peripheral nerve sheath tumors
fasciculated arrangements of spindle cells, commonly seen with mitoses, necrosis and nuclear aplasia
S-100 +
Describe a schwannoma with regards to symptoms, location, and appearance
symptoms resemble local compression of involved nerves or adjacent structures
Cranial vault: occurs at the cerebellopontine angle, where they are attached to the vestibular branch of CN8
Dura: involves sensory nerves
Extradural: can arise in association with large nerve trunks or soft tissue lesions without an identifiable associated nerve
What causes schwannomas
germline mutations of NF2 on chromosome 22, causes loss of function mutations to merlin protein. In its absence, cells hyperproliferate in response to uninhibited growth factors like EGFR
Describe spinal muscular atrophy with respect to clinical features, subtyping, and prognosis
symptoms: muscle weakness, hypotonia, bulbar symptoms, preserved sensations, Preserved eye movement and continence
Type 1: non-sitters
Type 2: sitters
Type 3: Walkers
Prognosis improves with later onset
what causes spinal muscular atrophy
Autosomal recessive inherited mutation of SMN1 gene on chromosome 5q causes apoptosis of LMN in late stages of fetal development and postnatal period
Diagnostics of spinal atrophy
normal or mildly elevated Creatine kinase
spontaneous large-amplitude, low frequency electrical activity with rarified interface pattern
Morphology of spinal muscular atrophy
atrophy to groups of motor units interspersed with normal or hypertrophies motors skills
what causes carpal tunnel syndrome and what contributes to it
cause: compression of the median nerve causes impaired blood flow and altered vascular structuring, leading to edema, hypoxia and axonal degeneration
Contributions:
prior wrist trauma
manual work
pregnancy
hypothyroidism
DM
Rheumatoid arthritis
dialysis associated amyloidosis
clinical presentation of carpal tunnel syndrome
sensory impairment and motor weakness in medial nerve distribution
thenar atrophy and motor weakness during thumb abduction and opposition
weakened pinch grip
wrist flexion and tapping over the flexor surface exacerbate symptoms
presentation of Guillain Barre
ascending flaccid paralysis about 1-4 weeks post infection
Pathology of Guillan Barre
autoantibodies against gangliosides or other known antigens of Schwann cells cause immune-mediated segmental demyelination and axonal degeneration
Describe diagnostics seen in Guillain Barre
elevated proteins, but normal cells in CSF
reduced nerve conduction velocity due to demyelination eith increased F wave frequency
common pathogens in association with Guillain Barre
C. jejuni
EBV
CMV
HIV
Influenza
Mycoplasm
How do you differentiate from Guillain Barre and Chronic Inflammatory Demyelinating Polyradiculopathy
Chronic Inflammatory Demyelinating Polyradiculopathy’s symptoms last for at least 2 months with subacute or chronic course relapses and remissions
Pertaining to morphology: Chronic Inflammatory Demyelinating Polyradiculopathy displays onion bulb changes on biopsy
What does Charcot-Marie Tooth Disease Look like
calf muscle atrophy (stork legs)
symmetric distal sensorimotor polyneuropathy
claw foot
intrinsic hand musculature may become involved after several years
What causes Charcot-Marie Tooth Disease
mutations of peripheral myelin protein PMP22 causes unstable myelin, which causes decreased impulse conduction velocity
Describe the morphology of Charcot-Marie Tooth Disease
segmental demyelination and remyelination with onion bulb formations
Associations of Charcot-Marie Tooth Disease
sleep apnea
features of Leprosy polyneuropathy
segmental demyelination, remyelination
loss of myelinated and demyelinated axons
Describe the pathogenesis of Diptheria polyneuropathy and discuss its features
Pathogenesis: Diptheria toxin inhibits protein synthesis by deactivation of EF-2 and ADP ribosylation, leading to nerve demyelination
Features: prominent bulbar and respiratory dysfunction
describe the pathogenesis of VZV polyneuropathy and discuss its features
Pathogenesis: reactivation of latent virus within neurons of the sensory ganglia
Features: shingles
What is the most common cause of peripheral neuropathy and how does it occur
Diabetes Mellitus
- hyperglycemia causes glycalation of proteins, lipids and amino acids
- Glycation causes activation of inflammatory signaling through AGE receptors
- Inflammatory signaling causes Endoneural arteriole hyalinization
- Arterial hyalinization causes polyneuropathy
Metabolic factors that cause polyneuropathy
uremia
Vitamin B1 deficiency
Vitamin B6 deficiency
Vitamin B12 deficiency
Vitamin E deficiency
Chronic liver disease
Chronic respiratory disease
Per powerpoint, the following malignancies are associated with which neuropathies?
Lung apex neoplasms
Malignant pelvic neoplasms
meningeal carcinomatosis
small cell lung cancer
Lung apex neoplasms= brachial plexopathy
Malignant pelvic neoplasms= obturator palsy
meningeal carcinomatosis causes cauda equina syndrome, yielding lower extremity polyradiculopathy
small cell lung cancer= sensorimotor neuropathy
