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Disorders of peripheral nerves Disorders of peripheral nerves

Symptoms and signs of disorders of nerves • Caused by changes in axons –Increased 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

Anatomy of peripheral nerves • Peripheral nerves have different conduction velocity Anatomy of peripheral nerves • Peripheral nerves have different conduction velocity

Conduction velocity in nerves and fiber tracts • Proportional to fiber diameter • Peripheral 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)

Nerve fibers with different diameter have different conduction velocity Fig 4. 3 From: Møller: Nerve fibers with different diameter have different conduction velocity Fig 4. 3 From: Møller: Sensory Systems, 2003

From: Møller: Sensory Systems, 2003 From: Møller: Sensory Systems, 2003

Many nerves are mixed nerves • Contains nerve fibers with different conduction velocity 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 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 Organization of the dorsal horn of the spinal cord FROM BRODAL 1998

Many nerves are bipolar nerves • Examples are dorsal roots Many nerves are bipolar nerves • Examples are dorsal roots

From Brodal 1998 From Brodal 1998

Pathologies of peripheral nerves Nerves: • Neurapraxia • Axonotmesis • Neurotmesis Nuclei: • Altered 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 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 Trauma to peripheral nerves • • Interruption of nerve trunk (neurotmesis) Interruption of axons (axonotmesis) Total conduction failure (neurapraxia) Impaired conduction (no morphologic change)

Neurapraxia Neurapraxia

Total conduction failure (neurapraxia) • No function • Recovers spontaneously over days or weeks 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 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 • 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 Interruption of nerve trunk (neurotmesis) • No function • Irreversible, grafting is required

Neurotmesis • Does not regenerate spontaneously • Grafting is necessary to restore function • 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 and endoneurial sheet Interruption of Injured nerves Axon interrupted (Wallerian degeneration) Interruption of axon and endoneurial sheet Interruption of perineurial sheet Interruption of nerve trunk

Axonotmesis Type 2 Neurotmesis Type 3 Type 4 Type 5 Axonotmesis Type 2 Neurotmesis Type 3 Type 4 Type 5

Interrupted axons • Degenerate distally (away from cell body) • Wallerian degeneration • Interrupted 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 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 START 9/7/05

Remaining symptoms after nerve healing of injury • Synkinesis • Hyperactivity (Mostly caused by 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 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 Cause of neural pathologies • • Mechanical (compression, stretching) Heat Metabolic Inflammation Iatrogenic (from medical treatment) Idiopathic (unknown) Age

Trauma • Gunshot to limbs • Accidents • Surgery (iatrogenic) Trauma • Gunshot to limbs • Accidents • Surgery (iatrogenic)

Sprouting • Caused by injury • Caused by regeneration Sprouting • Caused by injury • Caused by regeneration

Formation of neuroma • Sprouting of axons at cut of a nerve • Injured Formation of neuroma • Sprouting of axons at cut of a nerve • Injured perineurium

Neuroma are mechanically sensitive Neuroma are mechanically sensitive

Compression • No known cause • Scar tissue • Changes in bone formation Compression • No known cause • Scar tissue • Changes in bone formation

Block of axoplasmatic flow Block of axoplasmatic flow

Irritation • Scar tissue • Blood vessels Irritation • Scar tissue • Blood vessels

Metabolic and chemical induced peripheral neuropathy • Diabetes • Uremic, hepatic and vitamin (B Metabolic and chemical induced peripheral neuropathy • Diabetes • Uremic, hepatic and vitamin (B 1, B 2, B 12) deficits • Alcohol • Chemical

Inflammatory (neuritis) • Guillain-Barre syndrome Inflammatory (neuritis) • Guillain-Barre syndrome

Virus • Herpes simplex (causes severe pain) Virus • Herpes simplex (causes severe pain)

Demyelination • Ephaptic transmission • Reflection of neural activity • Mechanosensitivity Demyelination • Ephaptic transmission • Reflection of neural activity • Mechanosensitivity

Injury to a peripheral nerve can cause transneural degeneration of the target cell 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: 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 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 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 • Expression of neural plasticity from injury to sensory nerves: • Deprivation of input • Overstimulation

Impaired conduction • Decreased conduction velocity • Increased refractory period • Ectopic (out of Impaired conduction • Decreased conduction velocity • Increased refractory period • Ectopic (out of place) activity

Irritation of peripheral nerves • Cause change in central processing – Pain – Hypersensitivity Irritation of peripheral nerves • Cause change in central processing – Pain – Hypersensitivity – Spasm

Irritation of nerve roots • Cause change in central processing • Transition between peripheral 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) Irritation of nerve roots • Pain • Hyperalgesia • Spasm (Expression of neural plasticity)

Start 9/12/05 Start 9/12/05

Signs of peripheral nerve disorders • Motor nerves: – Paralysis – Spasm – Electrophysiologic 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 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 Symptoms of peripheral nerve disorders • Sensory nerves – Numbness – Tingling – Pain

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

Slightly injured nerves (demyelination) • • Decreased conduction velocity Abnormal firing pattern Peripheral nerves 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 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 • 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 Increased spatial dispersion • Can decrease excitation • Can increase excitation • Can degrade temporal information

From Møller 2005 From Møller 2005

Temporal dispersion 1. Can decrease the activation of the target neuron 2. Can increase 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 Abnormal firing pattern • Burst firing

From Møller 2005 From Møller 2005

Peripheral nerves as impulse generators • Ectopic activity – After demyelination – Diabetic neuropathy Peripheral nerves as impulse generators • Ectopic activity – After demyelination – Diabetic neuropathy – Adrenergic substances facilitate impulse generation

Ectopic firing • Burst • Rhythmic • After-discharges to stimulation Ectopic firing • Burst • Rhythmic • After-discharges to stimulation