Pathology of the Peripheral Nervous System Flashcards
What are the main responses of peripheral nerves by the following?
Schwann cells
Axons
Schwann cells - “segmental demyelination”; primary involvement of Schwann cell and loss of myelin.
Axons - axonal DEgeneration; primary involvement of neuron and its axon. Axonal DEgeneration may be followed by axonal REgeneration and REinnervation.
What are the 2 principle pathologic processes seen in muscle (denervation atrophy vs. myopathy)?
- Denervation atrophy: follows loss of axon.
2. Myopathy: primary abnormality of the muscle itself.
What processes may cause segmental demyelination? (2)
What remains unaffected during the process?
What happens to the damaged myelin?
It occurs with dysfunction of Schwann cells (heredity motor and sensory neuropathy) OR damage to the myelin sheath (Guillan-Barre).
No primary abnormality of the axon and does not affect the Schwann cells. Myocytes are also unaffected.
Disintegrating myelin gets engulfed by Schwann cells then macrophages.
What is the stimulus for remyelination?
What happens to the size of newly myelinated internodes?
Denuded axon.
They tend to be shorter than normal.
What is the histological finding in segmental demyelination?
“Onion bulbs” - concentric layers of Schwann cell cytoplasm and redundant BM surrounding the thinly myelinated axon.
What produces a “traumatic neuroma”?
What is seen on histology? (2)
How does it present clinically?
A failure of the outgrowing axons to find their distal can produce a “pseudotumor” - traumatic neuroma.
Non-neoplastic haphazardly whorled proliferation of axonal processes and associated Schwann cells. It’s all “misaligned”.
CT - “Parallel fibers”.
A painful nodule.
Axonal degeneration occurs as a result of… (2)
What causes axonal damage? (focal, neuronopathy, axonopathy)
What occurs to the axon with a focal lesion?
What occurs to the axon distal to the lesion?
What produces myelin ovoids?
Destruction of the axon + secondary disintegration of myelin sheath.
Focal damage (trauma, ischemia), generalized affect of whole neuron body (neuronopathy) or its axon (axonopathy).
Focal lesion: traumatic transection of axon.
Distal portion: undergoes Wallerian degeneration.
They are produced by Schwann cells that catabolize myelin and later engulf axon fragments and produce small oval compartments.
What is denervation atrophy?
What are “angulated” fibers?
What are the target fibers?
Muscle fibers in the motor unit that lose neural input and undergo denervation atrophy.
Angulated fibers: atrophic fibers that are smaller and triangular in shape when undergoing denervation atrophy.
Target fibers: rounded zone of disorganized myofibers in center of the fiber itself.
What is a regenerated cluster?
What occurs are collateral damage of reinnervation of skeletal muscle?
What determines the fiber type?
What is meant by the “checkerboard pattern”?
A cluster of closely aggregated and thinly myelinated small-caliber axons.
Changed composition of skeletal muscle - altering distribution of the 2 major fiber types.
Motor neuron determines fiber types; all muscle fibers of a single unit are the same type.
Fibers of a single unit that are distributed across the muscle.
What is the role of unaffected neighboring motor neurons of denervated myocytes?
What is type grouping?
What occurs in group atrophy/.
The unaffected neighboring motor neuron unit extend sprouts to reinnervate the denervated myocytes.
A patch of contiguous myocytes that have the same histochemical type.
The type group becomes denervated.
What are the two major causes of type 2 fiber atrophy?
- Inactivity or disuse (limb fx, pyramidal tract degenration, neurodegenrative disease).
- Glucocorticoid therapy - “steroid myopathy”.
What occurs in “segmental necrosis” of muscle fibers?
What other changes occur within myocytes in response to injury? (3)
Destruction of a portion of myocytes, followed by myophagoctosis. This leads to deposition of collagen and fat.
- Vacuolization, changes in structural proteins or organelles and intracytoplasmic deposits.
- Regeneration.
- Hypertrophy: muscle fiber splitting.
What histological feature is seen in regenerating muscle fibers?
What stain is used?
Large, internalized and centrally located nuclei with prominent nucleoli.
Trichrome stain - makes the RNA red!
Mononeuropathy =
Polyneuropathy =
Mononeuropathy = affects a single nerve and deficits are in a single distrubution (causes: trauma, entrapment, infection, etc.).
Polyneuropathy = multiple nerves, usually symmetric. Deficits begin at the feet and ascend with disease progression. Hands become affected at same time as the knees - “stocking and glove” distribution.
What occurs in mononeuritis multiplex?
What are common causes of this pattern? (2)
Several nerves are damaged in a haphazard fashion.
Vasculitis - PAN.
HIV.
Polyradiculopathies suggest involvement of…
What is the distribution of the radiculopathy?
Nerve roots + peripheral nerves.
Diffuse and symmetric in proximal and distal parts of the body.
Bell’s Palsy is described as…
What is the progression?
What age range does it usually onset?
What is the cardinal symptom?
It is associated with what? (2)
A mononeuropathy affecting CN VII leading to facial muscle paralysis.
Generally resolves spontaneously.
15-60 y/o.
Unilateral facial droop within 2-3 days of initial symptoms: tingling, HA, neck pain, weakness, confusion, etc.
URI and DM.
What is “neurogenic bladder”?
What causes the nerve damage?
Patients with what other condition may have this kind of bladder problem?
A number of urinary conditions in people who lack bladder control due to a CNS or PNS problem.
MS, PD or DM.
Patients with spinal cord abnormalities like spina bifida.
What is Guillan-Barre?
What are the symptoms/progression of it? (3)
“Acute inflammatory demyelinating polyneuropathy”; also considered an “acute onset immune-mediated demyelinating neuropathy”.
- Weakness beginning in the distal limbs, but rapidly progressing to proximal muscles - “ascending paralysis”.
- Absent DTRs.
- Acute inflammation and demyelination of spinal nerve roots and peripheral nerves - radiculopathy.
What is the cause of Guillan-Barre in 2/3 of cases?
What is seen histologically?
What is found in serum?
What change is seen in the CSF?
What is the treatment?
Preceding acute flu-like illness (C. jejuni most often).
Perivenular and endoneurial inflammation by WBCs.
Segmental demyelination affecting peripheral nerves (primary lesion).
Anti-myelin anitbodies.
Increased CSF protein, but no change in WBCs as they remain in the roots.
Plasmaphoresis + IVIg.
What is needed for the diagnosis of Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy?
What occurs molecularly?
What is seen on sural n. biopsy?
Symmetrical mixed sensorimotor polyneuropathy persisting for > 2 mo. May have relapsing/remitting phases of time course.
Complement fixing IgG and IgM on the myelin sheath.
Onion bulbs.
What are the 3 bugs that can cause infectious polyneuropathy?
Leprosy (Hansen disease)
Diphtheria
VZV (HZV)
What is infected in Leprosy?
What occurs molecularly? (2)
How is the neuropathy described?
What is the major contribution to the injury?
What is seen grossly on the patient?
Schwann cells are invaded by Mycobacterium leprae.
Segmental demyelination, remyelination and loss of both myelinated and unmyelinated axons.
Endoneurial fibrosis and multilayered thickening of perineural sheaths.
Symmetric polyneuropathy affecting cool extremities (low temp. favors Mycobacterium growth).
Involvement of pain fibers and loss of sensation.
Large traumatic ulcers.
What is meant by Tuberculoid leprosy?
What the major features? (2)
There is an active cell-mediated response.
Granulomatous nodules in the dermis.
Localized nerve involvement.
