Disorders of peripheral nerves

Symptoms and signs of disorders of nerves

• Caused by changes in axons–Increased conduction time–Increased temporal dispersion

• Expression of neural plasticity causing changes in the function of CNS structures

Anatomy of peripheral nerves

Anatomy of peripheral nerves

• Peripheral nerves have different conduction velocity

Conduction velocity in nerves and fiber tracts

• Proportional to fiber diameter• Peripheral nerves: ~50 meter/sec

(5 cm/msec)• Spinal descending tracts: ~70-100 m/sec • Cranial nerves: varies

(Auditory nerve: 20 m/sec)

Fig 4.3From: Møller: Sensory Systems, 2003

Nerve fibers with different diameter have different conduction velocity

Epineurium

Perineurium

Endoneurium

Fascicles

Nerve fiber

Node of Ranvier

Schwann cell

Myelin

Axon

From: Møller: Sensory Systems, 2003

Many nerves are mixed nerves

• Contains nerve fibers with different conduction velocity

Recording from a long nerve composed of fibers with different diameter thus different conduction velocity

Organization of the dorsal horn of the spinal cord

FROM BRODAL 1998

Many nerves are bipolar nerves

• Examples are dorsal roots

From Brodal 1998

Pathologies of peripheral nerves

Nerves:• Neurapraxia• Axonotmesis • Neurotmesis Nuclei:• Altered discharge pattern (burst activity)

Causes of injury to peripheral nerves

• Trauma• Compression (entrapment)• Irritation• Metabolic disorders• Inflammatory (neuritis)• Virus• Age related changes

Trauma to peripheral nerves

• Interruption of nerve trunk (neurotmesis)

• Interruption of axons (axonotmesis)

• Total conduction failure (neurapraxia)

• Impaired conduction (no morphologic change)

Normal

Central portion Peripheral portion

Stretched

Axon

EpineuriumPerineuriumEndoneurium

Neurapraxia

Total conduction failure (neurapraxia)

• No function

• Recovers spontaneously over days or weeks (when the cause is resolved)

• Results of spontaneous recovery are almost always good

Interruption of axons (axonotmesis)

• No function

• New axon grows from cell body (spontaneously)

Axonotmesis

• Nerve may regenerate from injured location away from the cell body

• Regeneration: 1 mm per day (approx. 1 inch per month)

• Results of spontaneous recovery are good to moderate depending on distance

Interruption of nerve trunk (neurotmesis)

• No function

• Irreversible, grafting is required

Neurotmesis

• Does not regenerate spontaneously

• Grafting is necessary to restore function

• Results of grating are good to moderate to failures

Injured nerves

Axon interrupted(Wallerian degeneration)

Interruption of axon andendoneurial sheet

Interruption ofperineurial sheet

Interruption of nerve trunk

Axon

EpineuriumPerineuriumEndoneurium

Type 2

Type 3

Type 4

Type 5

Axonotmesis

Neurotmesis

Interrupted axons

• Degenerate distally (away from cell body)

• Wallerian degeneration

• Interrupted axons regenerate from injury, provided that endoneural tube is intact

Wallerian degeneration means:

The degenerative changes the distal segment of a peripheral nerve fiber (axon and myelin) undergoes when its continuity with its cell body is interrupted by a focal lesion. Syn: orthograde degeneration, secondary degeneration.

START 9/7/05

Remaining symptoms after nerve healing of injury

• Synkinesis

• Hyperactivity

(Mostly caused by effect on central nervous system structures)

Electrophysiological manifestations of pathologies of peripheral nerves

Nerves:• Increased conduction times • Increased or decreased discharge activity• Dispersion of neural activity • Altered discharge pattern (burst activity)

Cause of neural pathologies

• Mechanical (compression, stretching)• Heat• Metabolic• Inflammation• Iatrogenic (from medical treatment)• Idiopathic (unknown)• Age

Trauma

• Gunshot to limbs

• Accidents

• Surgery (iatrogenic)

Sprouting

• Caused by injury

• Caused by regeneration

Formation of neuroma

• Sprouting of axons at cut of a nerve

• Injured perineurium

Neuroma are mechanically sensitive

Compression

• No known cause

• Scar tissue

• Changes in bone formation

Block of axoplasmatic flow

Irritation

• Scar tissue

• Blood vessels

Metabolic and chemical induced peripheral neuropathy

• Diabetes

• Uremic, hepatic and vitamin (B1,B2,B12) deficits

• Alcohol

• Chemical

Inflammatory (neuritis)

• Guillain-Barre syndrome

Virus

• Herpes simplex (causes severe pain)

Demyelination

• Ephaptic transmission

• Reflection of neural activity

• Mechanosensitivity

Injury to a peripheral nerve can cause transneural degeneration of the target cell

Functional implications of neural injuries

• Change the function of the target central neurons:– May cause expression of neural plasticity

Abnormal activity in a peripheral nerve can cause changes in the

function of the target cells

Cause of synkinesis and hyperactivity

• Plastic changes in target neurons induced by the injury

Expression of neural plasticity from injury to sensory nerves:

• Deprivation of input

• Overstimulation

Impaired conduction

• Decreased conduction velocity

• Increased refractory period

• Ectopic (out of place) activity

Irritation of peripheral nerves

• Cause change in central processing

– Pain

– Hypersensitivity

– Spasm

Irritation of nerve roots

• Cause change in central processing

• Transition between peripheral and central myelin is especially sensitive

Irritation of nerve roots

• Pain

• Hyperalgesia

• Spasm

(Expression of neural plasticity)

Start 9/12/05

Signs of peripheral nerve disorders

• Motor nerves:– Paralysis– Spasm– Electrophysiologic changes

Explanation

A sign is any abnormality indicative of disease, discoverable on examination of the patient.

Symptoms of peripheral nerve disorders

• Sensory nerves– Numbness– Tingling– Pain

A symptom is any morbid phenomenon or departure from the normal in structure, function, or sensation, experienced by the patient and indicative of disease.

Explanation

Slightly injured nerves (demyelination)

• Decreased conduction velocity

• Abnormal firing pattern

• Peripheral nerves as impulse generators

• Possible ephaptic*) transmission

*) Direct transfer of impulse activity from one nerve fiber to another

Decreased conduction velocity

• Temporal dispersion of neural activity

• Change in neural coding of sensory stimuli

Decreased conduction velocity

• The decrease is not the same for all fibers

• Temporal dispersion of neural activity

Increased spatial dispersion

• Can decrease excitation

• Can increase excitation

• Can degrade temporal information

Action potential

Threshold

Threshold

EPSP

EPSP

From Møller 2005

Temporal dispersion

1. Can decrease the activation of the target neuron

2. Can increase the duration of firing of the target neuron, which can increase or decrease activation of the following neuron.

3. Increased temporal dispersion may prevent activation of the next neuron in a chain, or it may make it possible to activate neurons that are not normally activated.

4. Increased temporal dispersion may degrade information when temporal coding is important such as in sensory systems, most pronounced in hearing

Abnormal firing pattern

• Burst firing

Threshold

Resting potential

Incoming nerve impulses

Action potential

From Møller 2005

Peripheral nerves as impulse generators

• Ectopic activity– After demyelination– Diabetic neuropathy– Adrenergic substances facilitate impulse

generation

Ectopic firing

• Burst

• Rhythmic

• After-discharges to stimulation