THE PERIPHERAL NERVOUS SYSTEM

1. INTRODUCTION

Arbitrarily the nervous system is divided into peripheral and central systems. Essentially the Central Nervous System(CNS) consists of the brain and spinal cord.

The peripheral nervous system (PNS) consists of those structures outside the CNS: motor, sensory and autonomic. These structures typically consist of (a) cell body, (b) nerve, (c) junction, and (d) end organ.

Motor:
Cell body (anterior horn cell) lies in the CNS.
Nerve consists of myelinated and unmyelinated axons.
Junction is the neuromuscular junction.
End organ is muscle (and also the muscle spindle).

Sensory:
End organ is the sensory receptor.
Junction is the connection between receptor and nerve.
Nerve consists of myelinated and unmyelinated axons passing to the cell body (dorsal root ganglion cell), from which nerve passes into the Spinal Cord and the CNS.

Autonomic:
This has fibers leading from and back to the cord, which effect motor functions (like emptying bladder) and sensory functions (like bladder sensation).

Two features make the peripheral nervous system unique: its simplicity, both anatomically and functionally compared with the CNS, and its accessibility to investigation: electrophysiology and biopsy.


2. GROSS ANATOMY

2.1
The motor neuron leaves the anterior horn cell via the ventral rootlets, links up with the dorsal (sensory) rootlets and thereby forms the mixed spinal nerve. Related to the development of the limbs, the mixed spinal nerves form the brachial (C5678&T1), lumbar (L234) and sacral (L45&S12) plexi. From these plexi are derived the major mixed peripheral nerves of the arm and leg. These may be purely motor (musculocutaneous), purely sensory (cutaneous nerve of arm) or, usually, mixed (radial, median, ulnar, femoral, and sciatic).

Note the difference between a myotome and a dermatome:

The myotome refers to all those muscles innervated from a particular segment of the cord eg. 5th cervical segment (C5) has its anterior horn cells sending axons to the deltoid (from C5); biceps (from C5 & C6) and brachioradialis (from C5 & C6). However, these muscles are all supplied by different peripheral nerves, which arise from different parts of the brachial plexus.

The dermatome refers to an area of sensory innervation to the skin from a particular cord segment or mixed spinal nerve; it is overlapped by other dermatomes and does not correspond to the same area of distribution of the myotome.

2.2 Major Peripheral Nerves

ARM
 
Nerve
Muscle  Roots
Axillary Deltoid C5
Musculocutaneous  Biceps C5,6
Radial  Triceps C6,7,8
Radial Brachioradialis C5,6
Radial Wrist extensors  C6,7
Radial Finger extensors  C7,8
Median  Wrist Flexor C6,7
Median  Abduct Poll Brev C8,1
Ulnar  Finger ABD/ADD  C8,1
 

LEG
 
Nerve Muscle  Roots
  Hip Extension L2,3,4
Femoral Knee Extension  L2,3,4
Obturator Thigh Adduction L2,3,4
Sciatic  Knee Flexion L5 S1
Sciatic Branches:
Peroneal Ankle dorsiflex L4,5
Tibial Plantarflex  S1,2
peroneal nerve everts the foot; tibial inverts it.

3. HISTOLOGY

Mixed peripheral nerves (eg. Radial) are composed of individual motor, sensory and autonomic fibers. Each of these fibers is surrounded by endoneurium. The fibers are grouped into fascicles surrounded by the perineurium. The entire nerve (eg. Radial) is surrounded by epineurium.

Regional arteries send penetrating branches (vasa nervorum) into the nerve.

The axons are variable in size and are myelinated or unmyelinated.

Schwann cells surround either groups of unmyelinated axons or single myelinated axons: the myelin consists of alternating lipid and protein formed by the fusion of the Schwann cell plasma membrane as it wraps round the axon. As the axon enters into the CNS, it is again myelinated but from a different cell, the Oligodendrocyte (a glial cell).


4. DISORDERS OF PERIPHERAL SYSTEM

4.1 Basic mechanisms of nerve injury

Diseases of peripheral nerves are of two types:

1. Symmetric polyneuropathies, usually distal and due to a disturbance involving many nerves.
2. Localized Mononeuropathies involving a single or a few isolated peripheral nerves with motor and sensory loss in the distribution of the specific (eg. named) peripheral nerve (eg. Ulnar).

The mechanisms of trauma (neurotmesis, axonotmesis and neuropraxia) apply here.

Neurotmesis: Separation of the two stumps of nerve. Note that the distal stump degenerates after the separation.

Axonotmesis: Disruption of the axon with preservation of the surrounding connective tissue sheath.

Conduction block: failure of transmission of the action potential down the nerve, usually due to focal demyelination from compression: this is neuropraxia.

Following disruption of the axon the terminal stump dies: Wallerian degeneration. Thereafter if the connective tissue sheath is intact the axon may grow back at the rate of 1-3 mm/day; if there is no connective tissue sheath the axonal sprouts are misdirected and a neuroma forms. Also if axonal sprouts are misdirected, synkinesis will occur: eg. in facial nerve lesions when attempting to smile the eye will close. Generally disruption higher up (eg. brachial plexus) will have a poor outcome, whereas a good outcome follows on distal nerve injury. Neuropraxia will tend to recover quickly (minutes to days).

4.2 Specific mechanisms of nerve injury

4.2.1 TRAUMA (acute, subacute and chronic)

The major peripheral nerves are frequently damaged by trauma, compression against underlying bone or entrapment in a fibro-osseous tunnel. Typically the lesion is either:

(a) Acute: following a stab, generally with complete loss.
(b) Gradual onset of pain, tingling and with neglect of the problem, progressive weakness, which may be irreversible.

Traumatic lesions and peripheral nerve disease result in Neurotmesis, Axonotmesis and Neuropraxia, discussed above.


SPECIFIC NERVE INJURIES

Radial Nerve: (Saturday Night Palsy) injury in the Spiral Groove of Humerus; Wrist drop and weakness of finger extension

Median Nerve: Carpal Tunnel Syndrome: injury in Carpal Tunnel at the wrist; Pain in the hand and arm, sensory loss in thumb, index and middle finger and weakness & atrophy of thenar muscles

Ulnar Nerve: In the Cubital Tunnel at the elbow: nerve is compressed by the heads of flexor carpi ulnaris. Produces pain in the forearm, sensory loss of little and ring fingers and weakness of the intrinsic muscles of the hand.

Peroneal Nerve: Compressed at the level of the fibular head; Foot drop and numbness of the anterolateral aspect of the lower leg

Note: in lesions of the median, ulnar and radial nerves, the sensory loss is restricted to the hand and never found above the level of the wrist.

The plexi and roots are also subject to damage. Trauma and tumor are the commonest: birth trauma, avulsion injuries in motor vehicle accidents and bronchial carcinoma of the lung apex the best known. Typically there is involvement of several roots or trunks or cords: this gives rise to widespread weakness, sensory loss and autonomic dysfunction. It is worth noting that avulsion of the nerve roots, as commonly occurs with brachial plexus injuries, often causes a Horner's syndrome due to damage to C8T1 Roots.

4.2.2 DISORDERS OF THE AXON

The average cell length of axons is immense - up to 1.5 metres. The cell body and axon has an energy dependant process, axonal transport, which enables the protein products of the cell body to be transported distally (eg. synaptic membrane, acetylcholine), and for degraded products to be brought back to the cell body: this is anterograde and retrograde transport.

Since axonal transport is energy dependant it is sensitive to drugs, toxins and metabolic (including inherited metabolic) disturbances. Cell products may pile up in the axon; the axon swells and dies off distally beyond the point of swelling (a form of Wallerian degeneration). Clinically this is seen as the impairment of function in the furthest part of the nerve, which then slowly advances in the direction of the cell body: "dying back neuropathy".

Retrograde transport is the major mechanism by which neurotropic viruses enter the CNS: rabies, polio and herpes.

4.2.3 DISORDERSOFTHE MYELIN SHEATH

The typical lesion is segmental demyelination where there is demyelination in some areas, and sparing others. Recalling that the insulating effect of myelin prevents the dissipation of the action potential and therefore increases speed of nerve conduction by the process of saltatory conduction, it is obvious that myelin loss will result in slowing, and if severe, conduction block of the nerve impulse. Note that if there is a random loss of myelin it is statistically more likely that the most distal parts of the nerve will have the greatest number of demyelinating lesions between distal region and cell body. Therefore the clinical disturbance also tends to be distal in these conditions.

Genetic disorders can be associated with lack of myelin (hypomyelination).


5. NEUROMUSCULAR JUNCTION

See lecture on Muscle and Neuromuscular Junction.

Essentially in response to a nerve impulse, quanta of acetylcholine are released from the nerve terminal and bind with specific receptors on the post Functional membrane. An excitatory post synaptic potential (EPSP) is produced, and if of sufficient magnitude, the muscle contracts.

If there is failure of neuromuscular transmission then the end plate potential (EPP) does not exceed threshold and the muscle fiber action potential is not triggered. The result is weakness of the muscle.


6. MUSCLE

See lecture on Muscle and Neuromuscular Junction.

A single anterior horn cell sends its axon to muscle and this innervates a number of muscle fibers. This whole functional unit is the motor unit. If there is injury to a nerve, then the muscle fibers innervated by that nerve are no longer in communication with the anterior horn cell: the fibers are "orphaned" and they become smaller: "neurogenic atrophy". However, other nerves send collateral sprouts from their tips which reinnervate these muscle fibers. Also, later on the original "parent" nerve may grow back and reinnervate the fibers.


7. INVESTIGATION OF THE PERIPHERAL NERVOUS SYSTEM

1) General tests for systemic diseases cg. glucose, kidney function.

2) Nerve conduction:
Basically one stimulates either a motor or sensory nerve and further along the course of the nerve a pick-up will detect the response. In motor nerves the pick-up is on the muscle innervated by that nerve, on sensory nerves the pick-up is placed over the nerve itself. One can determine the speed of the nerve conduction and the size of the response.Lesions of myelin reduce the speed of conduction. Lesions of the axons reduce the number of nerves carrying the stimulus and therefore the size of response decreases.

One can detect local areas of slowing or areas where the proximal stimulation results in a smaller response than the distal: a typical example would be at the level of the elbow in an ulnar nerve lesion.

3) Electromyography:
A needle in the muscle may show changes which help to distinguish between diseases of the nerve or of the muscle.


8. SYMPTOMS OF NERVE AND ROOT DISORDERS

8.1 Motor and sensory loss:

This can be due to axonal interruption or blockage of conduction by demyelination. In axonal neuropathies, symptoms begin distally in the feet and progress proximally. Larger fibers are often damaged before smaller fibers: larger fibers carry joint position and vibration; smaller fibers carry pain and temperature.

8.2 Reflex loss:

This follows axonal lesions: eg. damage to sensory nerve leads to interruption of the reflex arc.

It occurs early in large fiber demyelination: the afferent signal is dispersed and therefore a distorted signal is presented to the spinal cord, and the corresponding anterior horn cell does not fire. If large fibers are preserved, but there is damage of smaller myelinated and unmyelinated afferent fibers, reflexes may be normal.

8.3 Atrophy:

Motor nerves have chemically mediated trophic influences on muscle fibers and interruption of the axons will therefore lead to atrophy. Atrophy also follows on disuse.

8.4 Spontaneous motor unit activity:

Fasciculations are brief twitches of muscle visible to the eye.

8.5 Ataxia:

This may be seen in neuropathies causing severe loss of joint position sense.

8.6 Positive symptoms:

In damaged fibers impulses may arise from an area of damage spontaneously or after normal transmission of a sensory impulse. A number of phenonema may be produced: paresthesia (tingling & pins and needles) dysesthesias (spontaneous painful sensations) and pain.

8.7 Autonomic dysfunction:

This is a feature of small fiber neuropathies eg. diabetes. Also seen in demyelinating lesions of the afferent fibers which arise from the baroreceptors (which are the receptors responsible for detecting blood pressure).


9. CORRELATION OF SIGNS WITH ANATOMICAL LEVEL

MUSCLE DISEASE:

  • Weakness (often proximal)

  • Reflexes normal; fasciculations absent
    Atrophy: often mild, but in the case of muscle dystrophies may be severe and typically involves a specific and particular group of muscles.
    Sensation is normal
    NEUROMUSCULAR JUNCTION:
  • Weakness (proximal, ocular muscles, face, bulbar muscles); no atrophy.

  • reflexes normal; fasciculations absent.
    Sensation is normal.
    PERIPHERAL NERVE:
  • (including damage to anterior horn cell and dorsal root ganglion cell)

  • Weakness: distal and symmetrical in the case of neuropathies
    Atrophy: - distal and symmetrical in the case of neuropathies ("glove and stocking type")
    Atrophy - in a myotomal distribution in the case of damage to the anterior horn cell or roots.
    Reflexes lost in distribution of damaged nerves, roots or segments of cord.
    Fasciculations may be present
    Sensory loss in distribution of damaged nerves, roots or segments of cord.
    Loss of sympathetic fibers in distribution of damaged nerves.
    These changes will be seen in distal nerves in most metabolic-toxic neuropathies; will be seen in the distribution of individual nerve if a single serve is damaged (mononeuritis) or more than one peripheral nerve distribution if several isolated nerves damaged (mononeuritis multiplex).
     
     
     
    Anterior Horn Cell
    Motor Nerve
    Junction
    Muscle
    Fasciculations
    ++
    +
    -
    -
    Atrophy
    +++
    ++
    -
    Often late, mild-"Pattern specific"
    Weakness
    Often distal
    Usually distal
    Proximal
    Proximal
    Reflexes
    -
    -
    +
    +
      SPINAL CORD INVOLVED
    SENSORY NERVE MAY BE INVOLVED
     
    MUSCLE ENZYMES RAISED
      eg:

    Motor Neuron Disease

    Poliomyelitis

    Syrinx

    eg:

    Cervical Spondylosis

    Motor Neuropathies( Porphyria, GBS, hereditary)

    eg:

    Myasthenia Gravis

    Eaton Lambert

    eg:

    Inflammatory Myositis

    Metabolic

    Dystrophy (AD, AR, X-linked)

    Disorders of fate and

    carbohydrate usage