Chapter 27: Diseases of Peripheral Nerves Flashcards
Which painful nodule composed of non-neoplastic haphazard whorled proliferation of axonal processes and assoc. Schwann cells results from failure of axons to find their distal target during regeneration ?
Traumatic neuroma aka “pseudotumor”
In cases of toxic and metabolic insults, axons often degenerate in what type of fashion?
What does this result in?
in a length-dependent fashion with the longest axons being most susceptible
-Results in a “dying-back” type of pattern progression
What is the electrophysiologic hallmark of axonal neuropathies vs. demyelinating neuropathies?
- Axonal neuropthay = a reduction in signal strength
- Demyelinating neuropathy = slowed nerve conduction velocity
What are the primary targets of damage in demyelinating neuropathies?
Schwann cells w/ their myelin sheaths
Why is the peripheral nerve dysfunction caused by neuronopathies equally likely to affect proximal and distal parts of the body?
Damage at the level of neuronal cell body
-leads to a secondary degeneration of axonal processes
What are two examples of insults that can leads to neuronopathies?
Infections (herpes zoster) and toxins (platinum compounds)
Mononeuritis multiplex describes a disease process that damages several nerves in a haphazard fashion and is commonly due to what?
Vasculitis i.e., polyarteritis nodosum
Characteristic “stocking and glove” distribution of sensory deficits is seen with what anatomic pattern of peripheral neuropathies?
Polyneuropathies
What are the 4 categories of inflammatory neuropathies?
- guillain-barre
- chronic inflammatory demyelinating poly(radiculo)neuropathy
- neuropathy associated with systemic autoimmune diseases
- neuropathy associated with vasculitis
Histologic features of Guillain-Barre Syndrome are characterized by what?
Inflammation** and **demyelination of spinal nerve roots and peripheral nerves = radiculoneuropathy
-inflammation of peripheral nerve: perivenular and endoneurial infiltration by lymphs, macrophages, and few plasma cells
2/3’s of Guillain-Barre Syndrome cases are preceded by what; which etiologies have been implicated?
- Acute, influenza-like illness
- Campylobacter, CMV, EBV, and Mycoplasma penumoniae, or prior vaccination
Morphologically what is the most prominent lesion (primary lesion) seen in Guillain-Barre Syndrome?
Segmental demyelination affecting peripheral nerves
Clinical presentation of Guillain-Barre Syndrome is dominated by what signs/sx’s; what characteristic CSF finding will there be?
- Ascending paralysis and areflexia
- DTR’s lost early in the process
- ↑ CSF protein levels w/ little or no CSF pleocytosis (inflammatory cells remain confined to the roots
What antibodies are present in Guillain-Barre?
anti-myelin antibodies
How is Guillain-Barre Syndrome managed clinically?
Plasmapheresis and IV Ig
What is the most common acquired inflammatory peripheral neuropathy?
Chronic inflammatory Demyelinating Poly(radiculo)neuropathy
Chronic inflammatory Demyelinating Poly(radiculo)neuropathy is characterized by what type of neuropathy?
Symmetrical mixed sensorimotor polyneuropathy that persists for 2 months or more
-relapses and remissions evolve over years
Which 2 features of Chronic inflammatory Demyelinating Poly(radiculo)neuropathy distinguish it from Guillain-Barre?
Time course (presence at least 2 months) and response to steroids
How is Chronic inflammatory Demyelinating Poly(radiculo)neuropathy treated?
Glucocorticoids + IVIg + plasmapheresis
Upon sural nerve biopsy in patient with Chronic inflammatory Demyelinating Poly(radiculo)neuropathy what is a characteristic finding?
Onion-bulbs: excessive proliferation –> multiple layers of Schwann cells wrap around an axon like the layers of an onion
What is implicated in the inflammatory process of chronic inflammatory demyelinating poly(radiculo)neuropathy?
T cells, as well as antibodies
what leads to the recruitment of macrophages that strip myelin from axons in Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy?
complement-fixing immunoglobulin G (IgG) and IgM can be found on the myelin sheaths and the deposition of these opsonins leads to recruitment of macrophages that strip myelin from axons
Which systemic autoimmune diseases are often associated with peripheral neuropathies?
RA, Sjogren syndrome, or SLE
How does neuropathy associated with systemic autoimmune diseases present?
they often take the form of distal sensory or sensorimotor polyneuropathies
how does vasculitis often present?
as mononeuritis multiplex
what are some examples of vasulitides associated with neuropathy? (anca associated)
- MPO-ANCA associated vasculitides
- polyarteritis nodosa
- PR3-ANCA
what is the most common form of vasculitis associated with peripheral neuropathy?
a localized form referred to as nonsystemic vasculitic neuropathy, which is not associated with ANCAs
what are the histologic characteristics of neuropathy associated with vasculitis?
peripheral nerves typically show patchy axonal degeneration and loss, some fascicles more severely affected than others
-(perivascular inflammatory infiltrates often present)
In lepromatous leprosy (Hansen Disease) Schwann cells are invaded by Mycobacterium leprae and what pattern of peripheral nerve damage will be seen?
Segmental demyelination and remyelination + loss of both myelinated and unmyelinated axons
What are the histologic features associated with Leprosy associated neuropathy?
endoneurial fibrosis** and **multilayered thickening of perineural sheaths
Which type of neuropathy is seen with lepromatous leprosy (Hansen Disease) and which sensory fibers will be lost?
- Symmetric polyneuropathy affected cool distal extremities and face
- Involves pain fibers, loss of sensation = injury; since pt’s are rendered unaware of injurious stimuli –> large traumatic ulcers
More localized nerve involvement associated with granulomatous nodules in the dermis is characteristic of what form of leprosy?
Tuberculoid leprosy = TH1 (cell-mediated) response
What are the features of tuberculoid leprosy?
granulomatous nodules in dermis
localized nerve involvement
injures cutaneous nerves
axons, schwann cells, & myelin lost
What is the histology associated with Tuberculoid leprosy?
fibrosis of perineurium and endoneurium
What stain should you use if you suspect leprosy?
acid fast bacilli (AFB)
lyme disease causes what type of neuropathy?
polyradiculoneuropathy
early stage HIV infection causes what type of neuropathy?
mononeuritis multiplex
Peripheral nerve dysfunction as a result of Diptheria is due to what; what are the early sx’s and later findings?
- Result of diptheria exotoxin
-begins with paresthesias and weakness
- Early** loss of **proprioception** and **vibratory sensation
- Acute peripheral neuropathy assoc. w/ prominent bulbar and respiratory m. dysf.
If VZV is reactivated it travels along sensory nerves and leads to what?
Painful, vesicular skin eruption (shingles) in a sensory dermatomal distribution
Which dermatomes are commonly affected by VZV reactivation; what kind of damage is seen?
- Thoracic or trigeminal nerve dermatomes
- Neuronal destruction and loss of affected ganglia
_-_regional necrosis and hemorrhage may be found
- Axonal degeneration of periphral nerves after death of sensory neurons
Focal destruction of which neuronal structures may be seen with reactivation of VZV?
Large motor neurons in anterior horn or cranial nerve nuclei
What is the most common pattern of peripheral neuropathy seen with Diabetes?
Ascending distal symmetric sensorimotor polyneuropathy
how does diabetic neuropathy present?
numbness, loss of pain sensation, difficulty with balance
-paresthesias or dysesthesias
Prevalence of peripheral neuropathy associated with diabetes is dependent on what?
Duration of the disease
Biopsies of the affected peripheral nerves/arterioles in diabetes will show what finding and with what stain?
Endoneurial arterioles show thickening, hyalinization, and intense PAS-(+) of their walls + extensive reduplication of basement membranes
Diabetic peripheral neuropathy is characterized by a relative loss of which size and type of nerve fibers?
Small myelinated and unmyelinated fibers
What are “positive sx’s” associated with diabetic peripheral neuropathy?
Paresthesias and dyesthesias = painful sensations
what is believed to contribute to the damage of axons and Schwann cells in cases of DM neuropathy?
both metabolic and secondary vascular changes
Other than peripheral neuropathy, what is another manifestation of diabetic nervous system dysfunction that is often seen?
Autonomic dysfunction: postural hypotension, incomplete bladder emptying (↑ infections) and sexual dysfunction
Uremic neuropathy seen in setting of renal failure is a distal, symmetric neuropathy often associated w/ what signs and sx’s?
Muscle cramps + distal dysesthesias + ↓ DTRs
what is the primary event occurring in uremic neuropathy?
axonal degeneration is usually the primary event
-regeneration and recovery common after dialysis
what type of neuropathy is associated with hypothyroidism?
compression mononeuropathies (carpel tunnel) or distal symmetric predominantly sensory polyneuropathy
what type of neuropathy is associated with hyperthyroidism?
-rare, associated with syndrome resembling Guillain-Barre
What type of neuropathy is associated with vitamin b12 (cyanocobalamin) deficiency?
subacute combined degeneration with damage to long tracts in the spinal cord and peripheral nerves
Besides vitamin B12, what other vitamin deficiencies are associated with peripheral neuropathy?
vitamin B1 (thiamine), vitamin B6 (pyridoxine), folate, copper, and zinc
Which type of neuropathy is the most common paraneoplastic form and which malignancy is it most commonly associated with?
Sensorimotor neuronopathy in setting of Small cell lung cancer = most common
What is a a distinctive presentation of neuropathy associated with monoclonal gammopathies?
POEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes
“Saturday night palsy” is due to compression of which nerve?
Radial nerve in the upper arm
Which nerve is affected in Morton neuroma and what histologic finding is seen?
- Interdigital nerve at intermetatarsal sites –> foot pain; “walking on a marble”
- Histologically = perineural fibrosis
Demyelinating forms of Charcot-Marie-Tooth (CMT) disease are associated with what morphological features?
- Demyelination and remyelination including Schwann cell hyperplasia —> Onion-bulb formation
- Hyperplasia may be so severe that involved nerve is palpably enlarged
What is the most common subtype of hereditary motor and sensory neuropathy (CMT) disease, what is the inheritance pattern, when and how does it present?
- CMT1 = group of autosomal dominant disorders
- Presents in 2nd decade w/ slowly progressive distal demyelinating motor and sensory neuropathy
Which structures are injured in the CMT2 variant of CMT disease and when does it present?
Axonal injury; typically severe w/ early childhood onset
Familial amyloid polyneuropathies are mainly due to germline mutations in which gene?
Transthyretin gene
how does diabetic neuropathy present?
numbness, loss of pain sensation, difficulty with balance
-paresthesias or dysesthesias
