second week. In peripheral nerves the changes seem to progress from the lesion to the periphery, but within the central nervous system they are said to begin at the same time in all parts of the fibre. It is uncertain to what extent the difference is real or apparent, being simultaneous in the whole extent of the separated portion of the nerve. They progress more rapidly at its peripheral extremity than elsewhere. At the end of the second day, in the rabbit, stimulation of the nerve by electricity no longer causes muscular contraction. Thus the disappearance of the electrical excitability coincides in time with the first complete segmentation of the myelin and axis-cylinder. This interruption explains what is termed the "loss of excitability." It must be remembered that the loss of continuity is not the only cause of loss of excitability. (See p. 52.) If the ends of a divided nerve are brought quickly into perfect apposition secondary degeneration does not occur in animals, and probably not in man. Simple division appears to be a less serious injury than the extensive displacement of myelin in a contusion.

Thus the process is the result of an active growth of the nuclei and protoplasm of the nerve, i. e. of the cellular elements of which the nerve is composed. Why does this occur? The determining cause is the interruption of the axis-cylinder-its separation from the cell of which it is a process. It follows equally destruction of the nervecell. Ranvier points out that the destructive growth of the protoplasm, which follows loss of function in the axis-cylinder, suggests that normally its function restrains the vital energy of the cellelements. But it is possible that changes in the nutrition of the axiscylinder precede the segmentation.

A process of destructive cell-activity suggests the idea of inflammation. The degeneration may be regarded as a process of parenchy matous inflammation. Several observers have described other indications of inflammation outside the fibres, especially increase of nuclei, and accumulation of leucocytes in the interstitial connective tissue, and even in the nerve-sheath, and also dilatation of the blood-vessels. Such changes are intense at the primary lesion. Their degree in the nerve below the lesion is very variable, and seems to be proportioned to that in the primary process. This is another mode of stating the important fact that the irritative character of the secondary process is determined by the irritative nature of the primary disease.

The process of secondary degeneration occurs more slowly in the rabbit than in a bird, and seems to be still slower in man, in whom it is probable that complete segmentation does not occur until between the fourth and eighth days. It is certain that an identical process occurs in man. Changes in peripheral nerves near bedsores and in the fifth nerve, found by Pitres and Vaillard, are shown in Fig. 34, a comparison of which with Fig. 33 will show the identity of the process. It is highly probable that after complete division of a nerve in man the See Bowlby, Injuries and Diseases of Nerves,' p. 32.

changes are the same as in animals. But the most common lesion in man is neuritis, and in this the process of degeneration is probably greatly modified by the severity of the primary lesion; in some cases it occurs rapidly, in others very slowly. In the latter cases, which are chiefly those of focal neuritis, the process cannot be the same as that which follows division of a nerve. The change in irritability, which will be more fully described in the account of the symptoms, is a slow depression, sometimes moderate in degree. The depression may be preceded by an increase in irritability. In such cases there can be no complete segmentation of the nerve-fibres. There must be a gradual alteration in the molecular nutrition of the axis-cylinder, changing its excitability. Even in severe cases there is not usually a sudden loss of irritability; the current necessary for stimulation has to be made stronger, until at last in seven or eight days the strongest endurable current fails to cause muscular contraction. But we cannot infer, from this alone, that there is an actual interruption of the axis-cylinder. A stronger current might still excite the nerve, because, as we shall presently see, when a nerve is being regenerated, an axis-cylinder may conduct, and still not be excitable by currents of ordinary strength.

All severe changes in the nutrition of the fibres involve the intramuscular nerve-endings in the same degree. The evidence of this is that the faradic irritability of the muscles (which depends on the nerves within them) presents changes quite similar to that of the nerve-trunk. But this is not always true in slight changes of nutrition of the nerve. We shall presently see that the slight alterations of irritability in the nerve and muscle do not always correspond. The nerves terminate in structures of special nature, and these may well have some slight degree of nutritional independence.

Regeneration may occur in the nerve after the degeneration is over. It is a slow process, occupying the second, third, and fourth month after division. According to Ranvier, it occurs always by the growth of new axis-cylinders from the central end of the nerve (see Fig. 33, K and L), which ultimately become covered with myelin. One or more new fibres may spring from each central fibre, and these may subdivide. All are enclosed in a sheath which is continuous with that of the central end (Fig. 33, K, 8.). We must assume that only some of these axis-cylinders persist and achieve functional permanence. Sometimes these fibres twist about, and even turn back and grow upwards, probably in the direction of least resistance. In animals, new fibres may grow through a considerable extent of cicatricial tissue between the divided ends of a nerve, but in man it is doubtful whether regene ration of a divided nerve occurs unless the extremities are brought in contact, or at least close proximity. Some investigators believe that there is a formation of fibres in the peripheral extremity independently of the growth of new fibres from the central end.* In cases

E. g. by Neumann, Mayer, &c. A full abstract of their observations is given

of slight injury, regeneration occurs more readily; in these it is probable, as we have just seen, that degeneration has been incomplete. The regenerated nerve-fibres regain some conducting power while they are still much narrower than normal, and before they can be excited by electricity.

Muscles. The degeneration of the motor nerves is attended by changes in the nutrition of the muscles. These commence in or after the second week. The muscular fibres become narrower, and may be reduced, ultimately, to one-third of their former width. An increase in width has been said to precede the narrowing for a few days. The transverse striation becomes less distinct, and the striæ seem to be nearer together than in health. The fibres may become cloudy or granular, but do not present actual fatty degeneration except in some very acute cases. If no regeneration of the nerve takes place, the transverse siriation gradually disappears, and may be replaced by a longitudinal striation, or the fibres may undergo certain chemical changes, and present a peculiar glassy appearance, which has been called "vitreous degeneration." During the progress of the changes in the fibres, the nuclei of the sarcolemma and of the interstitial tissue are increased in number, and cellular elements, either newly formed, or migrated from the vessels, develop into fibres, so that ultimately the muscular fibres are separated by considerable tracts of connective tissue, and a state of cirrhosis results. If regeneration of the nerve occurs, the muscular changes are arrested, and the normal condition of the fibres is slowly restored. The amount of connective tissue in the muscle is often permanently increased, but the fibres are narrowed out of proportion to the increase in the connective tissue, and this undergoes contraction so that the muscle is for a long time smaller than normal, and its natural bulk may never be regained. If no regeneration of the nerve occurs, the muscular fibres gradually disappear; fibrous tissue takes their place, and, slowly contracting, permanent shortening may result. Similar shortening sometimes occurs when there is partial recovery of the nerve and muscle. In most lesions of nerves, other than actual division, some fibres recover, even though others are permanently

by Bowlby (loc. cit.), and also by Allen Starr in the Middleton Goldsmith Lectures for 1887 (New York Med. Record,' February, 1887). By some the new axiscylinders are said to be formed by elongation of the fragments of the old axis; by others from the nuclei of the sheath of Schwann, and appearances have been seen by Bowlby (loc. cit.) in man which seemed to him to bear this interpretation. But Rauvier's careful investigations have been fully confirmed by the minute researches of Vanlair (Arch. de Biologie,' 1885), and it is difficult to understand that perfect axis-cylinders should be formed and remain unexcitable, as the peripheral segment certainly does. Structures may be formed resembling axis-cylinders that are not really capable of the proper function. The weight of Ranvier's undisproved and confirmed observations is very great. It is possible that the process, in the peripheral part of a nerve, is influenced by the connection with other nerves and the recurrent influence of anastomosing fibres.

Steinert, Verh. Phys. Ges. Wurzburg,' 1858, No. 10.

destroyed. The muscular degeneration is the result of that of the motor nerves, as described at p. 22.

SYMPTOMS OF NERVE-INJURY AND DEGENERATION.-The symptoms that attend the lesions of motor nerves and the consequent degeneration are of great importance. The lesion of the nerve causes paralysis of the muscles supplied by it, due to, and in proportion to, the interference with the conducting power of the nerve. The muscles at once become flabby from loss of tone, and to this atony actual wasting is added in the course of a few weeks. The wasting is due to the reduction in size of the muscular fibres. If the sensory nerve-fibres are not interrupted, the muscles become tender to the touch, and pain is caused by their strong contraction, due probably

FIG. 35.-Type of degenerative reaction in a case of nerve-injury of mode-
rate severity. (After Erb.) Muscle irritability lowered from middle of
first week; faradic, extinct in middle of third, reappearing in ninth;
voltaic, increased from middle of second week until tenth, then de-
pressed until fourteenth. Nerve irritability (changed alike to both cur-
rents) is lowered from middle of first week, lost at end of second,
reappearing at seventh. Power lost until end of fifth week.
In this and the following figures the normal degree of irritability (ascer-
tained from the healthy side) is represented by the finely dotted
horizontal line (n.l.); faradic irritability, F, by a line of larger dots;
voltaic irritability, V, by a broken line; M, muscle; N, nerve; P,
power of voluntary contraction, its degree shown by the vertical lines;
the asterisk marks the occurrence of the lesion. The vertical divisions
represent time intervals. (Many of these indicating letters are given only
in subsequent figures.)

to the effect of interstitial inflammation on the sensory nerves, which end in the connective tissue.

The most important symptoms are those that are afforded by elec trical examination of the muscles and nerves, since they enable the degenerative changes to be ascertained and followed during life. The alterations in the electrical reaction, consequent on this degeneration, have been already briefly mentioned (p. 24), but must now be described in greater detail. The rapid degeneration of a nerve, which follows a severe lesion, is attended by a loss of irritability on electrical stimulation, the loss being the same to faradism and voltaism. After such lesions as are common in man, neuritis for instance, there is no sudden loss, such as occurs after injury of a nerve in an animal, when the nerve becomes segmented, but there is a more or less rapid diminution

of excitability, and this goes on until no stimulation can be produced, even by a strong current. The progressive changes in irritability may be conveniently represented on a chart. Fig. 35 shows the typical course of the changes of irritability in a case of moderate severity. In the muscle (M) a fall of irritability (due to the degeneration in the rerve-endings) occurs simultaneously with that in the nerve trunk (N), and the faradic excitability becomes extinct at the same time in both nerve and muscle. The fall in voltaic irritability is quickly arrested by the change in the muscular fibres, through which they soon become more excitable than normal to the voltaic current. This change usually occurs during the second week, and the irritability continues to increase during the third and fourth weeks. At its maximum it may amount to three, four, or five cells of the battery i e. contraction can be obtained in the paralysed muscles with a current weaker, by so many cells, than is necessary to cause contraction in a corresponding unaffected part. The further course of the changes in irritability depends on the severity of the lesion and the intensity of the degeneration. In a case of moderate degree, such as is shown on the chart, nerve irritability reappears about the end of the second month, usually after some voluntary power is regained. It is at first low, so that a strong current is required. It gradually increases, but for a long time continues a little below the normal degree. This return of nerve irritability is accompanied by a corresponding return of faradic irritability in the muscles (i. e. in the intra-muscular nerves). The increase of voltaic irritability often persists long after recovery of power, but it lessens as faradic irritability returns, and, as shown in the chart, it may fall below the normal before it ultimately regains its original degree.

Slight changes in irritability can be ascertained only by a comparison with the corresponding part on the other side in the same individual. Moreover, when we speak of excitability being "lost," we mean that we can obtain no stimulation by any strength of current that can be borne. This strength varies in different persons and in different parts. The more sensitive the part, the earlier irritability seems to be lost, and the later it seems to return; and the greater the resistance of the skin, the stronger must be the strength of current.* In many cases, if we could use very strong currents, the irritability would be found to be merely much lowered, although it seems to be extinct when we can only test it with currents of moderate strength.

If the lesion is very severe, so that there is no recovery, and no regeneration of the nerve, the loss of nerve irritability, and of the faradic muscular irritability, is permanent. The increase in voltaic irritability persists for months, and then gradually falls as the muscular fibres waste, and becomes lower and lower (see Fig. 36)

⚫ Hence the importance of ascertaining what current is actually passing by the use of a galvanometer, which may be thus used when the comparison with the other ide is made by a number of cells, to spare the patient the longer and more painful process which the more exact comparison by absolute current strength involves.