Peripheral Nerve & Skeletal Muscle Pathology Flashcards
There are 2 main responses of peripheral nerves to injury, determined by their target.
_______ _______ occurs with primary involvement of the Schwann cell and loss of myelin.
____ _____ occurs with involvement of the neuron and its axon, which may be followed by ________ _______ and ________ of muscle
Segmental demyelination
Axonal degeneration; axonal regeneration; reinnervation
There are 2 principle pathologic processes seen in muscle:
_______ _______ follows loss of axon
_______ is a primary abnormality of muscle fiber itself
Denervation atrophy
Myopathy
Segmental demyelination occurs with dysfunction of _____ cells or damage to the ______ sheath. There is no primary abnormality of axons and not all cells are affected.
Schwann; myelin
[disintigrating myelin is engulfed by schwann cells then macrophages; random internodes of myelin are remyelinated by multiple schwann cells, while the axon and myocytes remain intact]
In the case of segmental demyelination, a ______ axon is the stimulus for remyelination. Precursor cells inside the endoneurium have the capacity to replace injured schwann cells. Newly myelinated internodes are shorter than normal. Histologically appear as “______ _____”, which are formed by concentric layers of schwann cytoplasm and redundant basement membrane surrounding thinly myelinated axon
Denuded
Onion bulbs
A failure of the outgrowing axons to find their distal target can produce a “pseudotumor” called ______ _______: a non-neoplastic haphazard whorled proliferation of axonal processes and associated schwann cells that results in a painful nodule
Traumatic neuroma
Axonal degeneration is the result of 1. Primary destruction of axon, and 2. Secondary disintigration of myelin sheath. Axon damage may be focal (trauma, ischemia) or generalized affecting whole neuron body (neuronopathy) or its axon (axonopathy).
With a focal lesion — traumatic transection of axon, the distal portion undergoes __________ _________
Wallerian degeneration
______ ______ = small ovoid compartments produced when cells catabolize myelin and later engulf axon fragments
Myelin ovoids
[macrophages are then recruited for cleanup; proximal stump of severed nerve shows degenerative changes in most distal 2-3 internodes, then undergoes regeneration]
When axonal degeneration occurs, muscle fibers in the motor unit lose neural input and undergo _______ ________.
Features of this process include _________ fibers —atrophic fibers that are smaller and triangular in shape, and _______ fibers which are a rounded zone of disorganized myofiebrs in the center
Denervation atrophy
“Angulated”; target
In terms of nerve regeneration and reinnervation of muscle, schwann cells vacated by degenerating axons provide the guide for growth cone of regenerating fibers. A regenerating cluster consists of multiple closely aggregated, thinly myelinated, small-caliber axons.
Reinnervation of skeletal muscle changes its composition, altering distribution of the 2 major fiber types. The _____ ______ determines fiber type, and all muscle fibers of a single unit are the same type. Fibers of a single unit are distributed across the muscle in a _______ pattern
Motor neuron; checkerboard
Type ____ fiber atrophy occurs with inactivity or disuse (limb fracture, pyramidal tract degeneration, neurodegenerative disease, etc), as well as with glucocorticoid therapy
Type 2
Many diseases affect muscle, but myocytes only have a few pathologic reactions:
What are some of these reactions?
Segmental necrosis: destruction of portion of myoctye, followed by myophagocytosis
Loss of fiber leads to deposition of collagen and fat
Vacuolization, alterations in structural proteins or organelles, and accumulation of intracytoplasmic deposits
Regeneration
Hypertrophy (and muscle fiber splitting)
Describe regeneration of muscle fiber
Satellite precursor cells proliferate and reconstitute the destroyed portion of the fiber; regenerating portion has large internalized nuclei in central location and prominent nucleoli; cytoplasm is laden with RNA
Describe hypertrophy and muscle fiber splitting that occur with damage to muscle
Hypertrophy is a response to increased load either due to exercise or pathologic condition (fibers injured)
Muscle fiber splitting — large fibers may divide longitudinally
4 general types of peripheral neuropathy
Mononeuropathy — affects single nerve with deficits in restricted distribution
Polyneuropathy — multiple nerves, usually symmetric; deficits start at the feet and ascend with disease progression (“stocking and glove”)
Mononeuritis multiplex — several nerves damaged in haphazard fashion; common cause is vasculitis (polyarteritis nodosum)
Polyradiculoneuropathies — nerve ROOTS as well as peripheral nerves
Bell’s palsy is a type of _________ of CN VII leading to facial muscle paralysis that generally resolves spontaneously. It is characterized by one-sided facial droop and is associated with conditions like _____ and _______
Mononeuropathy; URI; DM
What is a neurogenic bladder and what are some associated conditions?
Neurogenic bladder = urinary condition in people who lack bladder control due to a brain, spinal cord, or nerve problem
May be result of MS, parkinsons, diabetes, infection, heavy metal poisoning, stroke, spinal cord injury, major pelvic surgery, spina bifida
Acute onset immune-mediated inflammatory demyelinating polyneuropathy in which weakness begins in distal limbs, but rapidly advances to proximal muscles as “ascending paralysis”; DTRs disappear, there is inflammation and demyelination of spinal nerve ROOTS and peripheral nerves (radiculoneuropathy)
Guillain-barre
2/3 of cases of guillain barre are preceded by an acute influenza-like illness caused by C.jejuni, CMV, EBV, M.pneumoniae, or prior vaccination. Inflammation of the peripheral nerve includes ______ and _______ infiltration by lymphocytes, macrophages, and few plasma cells. This inflammation and demyelination is widely distributed throughout the PNS.
______ ______ affecting peripheral nerves is the primary lesion
Overall characterized by presence of ________ antibodies
Perivenular; endoneurial
Segmental demyelination
Anti-myelin
Describe the role macrophages play in demylination that occurs with GBS
Cytoplasmic processes of macrophages penetrate basement membrane of Schwann cells, particularly in vicinity of Nodes of Ranvier, and extend between myelin lamellae, stripping myelin sheath away from axon
CSF changes in GBS
Increased CSF protein d/t altered permeability of microcirculation of spinal roots
[inflammatory cells remain confined the roots so there is little or no CSF pleocytosis]
Most common acquired inflammatory peripheral neuropathy and how it is distinguished from GBS
Chronic inflammatory demyelinating polyradiculoneuropathy = symmetrical mixed sensorimotor polyneuropathy persisting >2 months
Distinguished from GBS based on time course and response to steroids
[dx also involves complement fixing IgG and IgM found on myelin sheath as well as sural nerve bx showing onion bulbs]
Describe peripheral neuropathy caused by lepromatous leprosy
Schwann cells invaded by M.leprae; bacteria proliferates and infects other cells
Segmental demyelination and remyelination and loss of both myelinated and unmyelinated axons
Endoneurial fibrosis and multilayered thickening of perineural sheaths
Overall it is a symmetric polyneuropathy affecting cool extremities; tends to involve pain fibers leading to loss of sensation
Describe peripheral neuropathy caused by tuberculoid leprosy
Active cell-mediated response resulting in grannulomatous nodules in derms, LOCALIZED nerve involvement, injury to cutaneous nerves, axons+schwann cells+myelin are lost, as well as fibrosis of perineurium and endoneurium
How does diphtheria infection lead to peripheral neuropathy?
Diphtheria exotoxin affects peripheral nerves and begins with paresthesias and weakness
Affects sensory ganglia with early loss of proprioception and vibratory sensation
Selective demyelination of axons that extend into adjacent anterior and posterior roots, and into mixed sensorimotor nerves
Most common viral infection of PNS, affecting sensory ganglia of spinal cord and brainstem leading to neuronal destruction and loss of affected ganglia, regional necrosis and hemorrhage, axonal degeneration, and focal destruction of large motor neurons in anterior horns or CN motor nuclei
Varicella-zoster virus
Infectious disease resulting in polyradiculoneuropathy in second and third stages, manifestations include unilateral or bilateral facial nerve palsies
Lyme disease
What type of peripheral neuropathy is caused by HIV?
Mononeuritis multiplex
[later stages of HIV are associated with distal sensory neuropathy]
Most common cause of peripheral neuropathy
Diabetes
What is the most common pattern of peripheral neuropathy in diabetic pts?
Ascending distal symmetric sensorimotor polyneuropathy
Pathogenesis of the neuropathy caused by DM
Segmental demyelination: decreased number of axons as well as degeneration of myelin sheaths and regenerative axonal clusters
There is a relative loss of small myelinated fibers and unmyelinated fibers, but large fibers are also affected
Endoneurial arterioles show thickening, hyalinization, and intense PAS positivity
Types of neuropathy associated with uremia
Distal symmetric neuropathy — may be asymptomatic, muscle cramps, distal dysesthesias, decreased DTRs
Axonal degeneration is usually primary event; regeneration and recovery common after dialysis
Types of neuropathy associated with thyroid dysfunction
Hypothyroid —> compression mononeuropathies (carpal tunnel), distal symmetric predominantly sensory polyneuropathy
Rarely, hypERthyroidism is associated with syndrome resembling GBS
Neuropathies are often associated with malignancies due to local effects, complications of tx, paraneoplastic syndromes, or tumor derived Ig. This may occur due to direct infiltration as in brachial plexopathy with apical lung neoplasm or obturator palsy with pelvic tumor.
In terms of paraneoplastic neuropathy, sensorimotor neuronopathy is most common and is seen in ______________
Small cell lung cancer
Neuropathy associated with monoclonal gammopathy (B-cell neoplasms)
POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
Compression neuropathy affecting median nerve due to entrapment by transverse carpal ligament, leads to numbness and paresthesias of tip of thumb and first 2 digits
Carpal tunnel syndrome
Compression neuropathy affecting radial nerve of upper arm, often due to sleeping in an awkward position
Saturday night palsy
Compression neuropathy manifesting as metatarsalgia due to interdigital nerve entrapment; histological lesion is perineural fibrosis
Morton neuroma
Most common inherited peripheral neuropathy
Charcot-Marie-Tooth (CMT)
[genes involved include CMT1 or CMT2 which are autosomal dominant forms, or CMTX which is X-linked]
Inherited peripheral neuropathy resulting in amyloid deposition within peripheral nerves
Familial amyloid polyneuropathy
