말초신경 손상의 병리와 회복에 대하여

[문형철]

말초신경이 손상 회복에 대해서

신경손상의 세가지 기전

1. Stretch-related injury - 가장 흔한 형태. 

2. Lacerations such as those created by a knife blade are another common PNI type

3. Compression is a third common type of PNI

panic bird...

Peripheral nerve injuries associated with anaesthesia.pdf

Pathophysiology of peripheral nerve injury.pdf

Pathology and pathophysiology

Peripheral nerves comprise an extruded portion of the nerve cell body, the axon, encased by a series of Schwann cells, which form myelin segments. Each nerve is enclosed within three layers of connective tissue, the inner endoneurium, the perineurium and the outer epineurium.

The relatively simple structure of peripheral nerve results in a relatively small repertoire of responses to injury. These are focal conduction block, with or without detectable minor structural change, demyelination, and degeneration.

Focal conduction block

This is thought to be due to ischaemic anoxia. In animal experiments, modest degrees of tourniquet pressure to a nerve cause conduction block initially and, if the pressure is maintained, conduction block associated with oedema of the nerve. At either of these stages, cessation of pressure will reverse the block, either in a matter of minutes or hours, or over a period of days or weeks, respectively[33, 37].

Demyelination

In acute or chronic compression, Schwann cells underneath the compressing force are damaged leading to loss of the associated myelin segments. This process is referred to as segmental demyelination [38]. At the edges of the cuff in tourniquet compression, mechanical changes corresponding to displacement of soft tissue cause intussusception of internodes leading to paranodal demyelination [39].

If the pressure is high enough and prolonged, degeneration of the nerve distal to the compressing force occurs, producing axonal or Wallerian degeneration [38]. The degree of damage is proportional to the degree and duration of pressure applied [38, 39].

Degeneration

If a nerve is severely damaged, whether by compression, stretch or other means, there is distal degeneration of the axon and, with it, the myelin, over a period of 2±7 days [40]. In crush injuries which spare the endoneurium, the residue of macrophage activity on Schwann cells and other debris forms the so-called bands of Bungner.

Remyelination and regeneration

Remyelination is achieved by Schwann cells wrapping around an axon. Each cell produces a segment of myelin. The segments of myelin, or internodes, formed by this process are shorter than normal internodes [41±43]. Compared with regeneration, remyelination is a faster process and, in general, a more effective one.

In regeneration after lesions such as severe crush or nerve section, several neurofibrils emerge from the normal proximal portion of the nerve to form a growth cone. Eventually one axon predominates and, if there has been no disruption of the endoneurium, it may grow down the endoneurial tube to the end organ, the process being guided by the bands of Bungner. The regenerated nerve is usually smaller in diameter than normal [44, 45].

Regeneration after section is less effective than when continuity of the nerve has been preserved. The gap contains exudate and fibroblasts which interfere with the attempts of regenerating axons to find a way through, and there may be severe malalignment between the opposing nerve ends. It has been estimated that in these conditions only one in seven axon sprouts will reach an end organ [46]. These features are often expressed  clinically in the form of a neuroma at the site of the growth cone.

The rate of regeneration varies from 1 to 4 mm.day21  [47]. It is slower over distal than proximal segments because of the increasing burden on axoplasmic flow as the distance of the growth cone from the cell body becomes greater [44]. Regeneration across scar tissue is about a tenth of this speed [46]. Remyelination of the regenerated axons lags behind by 9±20 days [48±50]. It also proceeds in a proximal to distal direction.

If no regeneration occurs within 1±1.5 years the prognosis is poor because Schwann cells tend to become replaced by fibrous tissue [44]. Regeneration also tends to be less effective as the age of the patient increases. When there is less severe degeneration of motor nerves, particularly in chronic cases, a process of collateral regeneration frequently coexists. In this, nerve sprouts from a normal motor unit grow across to innervate muscle fibres which have lost their nerve supply. As a result they are incorporated into the donor's motor unit. This has important implications in diagnosis (see below, `Electromyography and nerve conduction studies').

Classification of nerve injury

 The degree to which a nerve is damaged has implicatons with respect to its function and potential recovery. There are essentially two general classification systems. Seddon's classification of nerve injuries describes three groups: neurapraxia, axonotmesis and neurotmesis [48]. Sunderland's classification describes five types of injury and depends exclusively upon which connective tissue components are disrupted [44].

1. Neurapraxia  describes a mild degree of neural insult that results in impulse conduction failure across the affected segment. It is reversible. 

2. Axontomesis  occurs when only the axon is physically disrupted with preservation of the endoneurial and other supporting connective tissue structures. Recovery of function depends upon time for the process of Wallerian degeneration and neural regeneration to occur. 

3. Neurotmesis  is the greatest degree of disruption a nerve can incur and is complete disruption of all supporting connective tissue structures. The nerve is completely severed and there is no continuity and this carries a very poor prognosis for complete functional recovery. Table 1 succinctly compares Seddon's and Sunderland's classifications.

Clinically, the prognosis for spontaneous recovery is good in Sunderland's Type 1 and fairly good in Type 2 injuries. In the remaining groups the prognosis is poor, and surgery will usually be required in Type 4 or 5 nerve injuries.