Pathogenesis of Peripheral Nerve Disorder

7/27/2019 Pathogenesis of Peripheral Nerve Disorder

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Pathogenesis of Peripheral

NeuropathiesBasic responses of peripheral nerve fibers

to injury :

DISTAL AXONAL DEGENERATION DEGENERATION OF CELL BODY AND AXON

SEGMENTAL DEMYELINATION

REMYELINATION

REGENERATING AXON

REGENERATED NERVE FIBER


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Axonal Degeneration

Degeneration (necrosis) of the axon occurs

in many neuropathies and reflects

significant injury of the neuronal cell body

or its axon. Axonal degeneration is quicklyfollowed by breakdown of the myelin

sheath and Schwann cell proliferation.


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Axonal Degeneration

Myelin degradation is initiated by Schwann

cells and completed by macrophages,

which infiltrate the nerve within 3 days

after axonal degeneration.


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Axonal Degeneration

If the degeneration is restricted to the distal

axon, regenerating axons may sprout

within 1 week from the intact, proximal

axonal stump. There are several types ofaxonal degeneration.


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Axonal Degeneration

DISTAL AXONOPATHY: In many

neuropathies, axonal degeneration is initially

restricted to the distal ends of the larger,

longer fibers . Peripheral neuropathiescharacterized by the selective degeneration

of distal axons are known as dying-back

neuropathies (distal axonopathies)


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Axonal Degeneration

DISTAL AXONOPATHY:

The neuronal cell body and proximal axon

remain intact. Therefore, axonal regeneration

and return of nerve function may be possible

if the cause can be identified and removed.


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Axonal Degeneration

NEURONOPATHY: Axonal degeneration may

also be the result of degeneration of the

neuronal cell body, as occurs in poliomyelitis.

Neuropathies showing selectivedegeneration of the neuronal cell body are

referred to as neuronopathies and are much

less common than distal axonopathies.


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Axonal Degeneration

WALLERIAN DEGENERATION:

This term refers to the axonal degeneration

that occurs in a nerve distal to a transection

or crush of the nerve, lead to the

accumulation of supernumerary Schwann

cells around axons (onion-bulbs) and

clinically apparent nerve enlargement(hypertroplzic neuropathy).


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Segmental Demyelination

The loss of myelin from one or more

internodes (segments) along a myelinated

fiber is common in many neuropathies and

reflects Schwann cell dysfunction. Thisdysfunction may be caused by direct injury of

the Schwann cell-myelin sheath (primary

demyelination), or it may be the result ofunderlying axonal abnormalities (secondary

demyelination).


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Segmental Demyelination

Degeneration of the internodal myelin sheath is

followed sequentially by :

(1) Schwann cell proliferation

(2) remyelination of the demyelinated segments

(3) recovery of function


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PERIPHERAL NEUROPATHIES

Peripheral neuropathy is a process that

affects the function of one or more

peripheral nerves. The disease may be

restricted to the peripheral nervous system,involve both the peripheral and central

nervous systems, or affect multiple organ

systems. Peripheral neuropathies areencountered in all age groups and may be

hereditary or acquired.


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The causes of peripheral neuropathy are

diverse. Charcot-Marie-Tooth disease

(CMT) is the most common hereditary

peripheral neuropathy.

Diabetic neuropathy is the most common

acquired neuropathy in the United States.


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Pathologically, the involved nerves may

show mainly axonal degeneration (axonal

neuropathy), segmental demvelination

(lencuelinating neuropathy), or a mixture of

both. Most neuropathies are axonal.


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Clinical Features :

The major clinical manifestations of peripheral

neuropathy are muscle weakness, muscle

atrophy, alterations of sensation, and

autonomic dysfunction. Motor, sensory, and

autonomic functions may be equally or

preferentially affected.


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Clinical Features :

Sensory abnormalities may reflect

predominant involvement of largediameter

fibers (position and vibration sense) or

smalldiameter fibers (pain and

temperature).


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Inflammatory Demyelinating Neuropathy

is an acquired neuropathy that

(1) may be sporadic;(2) may follow immunization, surgery, or viral

(include HIV) and mycoplasmal infections;

(3) or may complicate cancer.


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Pathogenesis is unknown but current evidence

suggests that it may be immunologically

mediated.

Pathology : may involve all levels of the

peripheral nervous system, including spinal

roots, ganglia, craniospinal nerves, and

autonomic nerves.


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Pathology :

The involved regions show endoneurial infiltratesof lymphocytes and macrophages, segmental

demyelination, and relative sparing of axons.

The lymphoid infiltrates are often perivascular,

but there is no true vasculitis.


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Pathology :

Macrophages are frequently found adjacent todegenerating myelin sheaths and have been

observed to strip off and phagocytose the

superficial myelin lamellae.


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Dorsal Root Ganglionitis

(Sensory Ganglionitis)

Dorsal root ganglionitis is a sensoryneuronopathy that may occur independently,

as a remote effect of cancer (paraneoplastic

neuropathy), or in association with Sjogrensyndrome.


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Dorsal Root Ganglionitis

(Sensory Ganglionitis)

The neuronopathy typically is seen as asubacute or chronic sensory polyneuropathy

with sensory ataxia. The pathogenesis of the

ganglionitis is unknown, but an immunemechanism is likely.


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Diabetic Neuropathy

The neuropathy may manifest as a distal sensory

or sensorimotor polyneuropathy, autonomic

neuropathy, mononeuropathy, or

mononeuropathy multiplex. DistaL

predominantly sensory, polyneuropathy is the

most common form of diabetic neuropathy.


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Diabetic Neuropathy

The pathogenesis of the nerve fiber injury in

diabetes is unknown. It has long been held

that the metabolic alterations of diabetes are

responsible for the distal symmetric

polyneuropathy and that nerve ischemia

caused by the small-vessel disease isresponsible for the mononeuropathies.


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Diabetic Neuropathy

The distal symmetric polyneuropathy of diabetes

is characterized pathologically by a mixture of

axonal degeneration and segmental

demyelination, with axonal degeneration

predominating.


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Uremic Neuropathy

Uremic neuropathy is a distal sensorimotor

axonal polyneuropathy that may complicate

chronic renal failure.The pathogenesis of the nerve fiber damage is

not known, but the disease usually stabilizes

or improves with chronic dialysis.


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Uremic Neuropathy

Characterized pathologically by both distal

axonal degeneration and segmental

demyelination, with axonal degeneration

predominating and preferentially involving

large-diameter fibers. The neuropathy

resolves after renal transplantation


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Alcoholic Neuropathy

Alcoholic neuropathy is a distal sensorimotor

axonal polyneuropathy that is generally

attributed to nutritional deficiencies, rather

than to a direct toxic effect of ethanol on the

peripheral nervous system


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Alcoholic Neuropathy

Peripheral nerves show loss of nerve fibers

from axonal degeneration of the dying-

back type. Axonal neuropathy is also

associated with a lack of vitamins B1, B6,

B12, or E, but is much less common than

alcoholic neuropathy.


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Vasculitic Neuropathy

Vasculitis may involve the nutrient arteries ofnerves and produce ischemic nerve injury

(ischemic neuropathy). Vasculitis-inducedischemic neuropathy may complicatepolyarteritis nodosa and other systemicvasculitidies, rheumatoid arthritis, othercollagen-vascular diseases,cryoglobulinemia, and HIV infection.


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Vasculitic Neuropathy

Vasculitic neuropathy is characterized

pathologically by axonal degeneration and

typically is seen as a mononeuropathy or

mononeuropathy multiplex.


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Toxic Neuropathy

A wide variety of drugs, environmentalagents, and industrial compounds cause

peripheral neuropathy. The majority oftoxic neuropathies are iatrogenic (i.e.,they are caused by drugs). Most toxic

neuropathies are characterized by axonaldegeneration, usually of the dying-backtype.


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Paraneoplastic Neuropathy

Several clinicopathological types :

* Chronic axonal polyneuropathy* Dorsal root ganglionitis (subacute sensory

polyneuropathy, sensory ganglionitis)

* Subacute motor polyneuropathy* Inflammatory demyelinating neuropathy


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Hereditary NeuropathyHereditary neuropathy is the most common form of

chronic neuropathy in children and an often

unrecognized cause in adults.

CHARCOT-MARIE-TOOTH DISEASE: CMT is a

slowly progressive form of hereditary motor and

sensory neuropathy (HMSN), which is seen inlate childhood or adolescence as a distal

sensorimotor polyneuropathy.


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Cryptogenic Neuropathy

In at least 10% of patients who have

peripheral neuropathy, no etiology is

apparent, despite careful and extensive

investigations. These cryptogenic

neuropathies are usually axonal and are

seen as a chronic, distal, sensorimotorpolyneuropathy.


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NERVE TRAUMA Traumatic Neuroma

Traumatic neuroma is a mass of regeneratingaxons and scar tissue thatforms at the end

of the proximal stump ofa nerve that hasbeen disrupted physically.After thetransection of a peripheral nerve,regenerating axonal sprouts arise within 1week from the distal ends of the intactaxons in the proximal nerve stump.


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Pathogenesis of Peripheral Nerve Disorder

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