ON THE MICROSCOPIC PATHOLOGY OF CEREBRAL TRAUMAT1SM.l

By ALEXANDER MILES, M.D., F.R.C.S. Ed., Syme Surgical Fellow.

(PLATE VIII.)

IN this paper I propose to describe the inicroscopical appearances of the brain, as seen in a large series of cases, in which death was the result of severe cerebral trauma.

The different pathological conditions observed were :- 1. Colloid Bodies. 2. Miliary Sclerosis. 3. Pi,mentary Degeneration of Nerve Cells ; and 4. Minute Petechial Hwmorrhages.

I shall consider them in the above order.

1. COLLOID BODIES. Before proceeding to consider the exact pathology of these so-called

colloid bodies, I shall briefly describe the condition as presented in a large series of sections subjected by ine to inicroscopic examination. All of these, with one exception, were taken froin cases in which death was the result of, or sulmequent to, a severe blow on tho head, pro- ducing one or more of the phenoniena generically spoken of as ‘(head- symptoms.” Some of the injuries were proclucecl experimentally on rabbits, pigs, and birds, while others were clinical cases, but in all the appearances are practically the same. The non-traumatic case, to which I have referred, was one of syphilitic cerebritis, for sections of which I am indebted to I h . Batty Tuke and Alex. Bruce. It serves for coinparison with the traumatic cases.

Question as to the arti$cinl ruiture of these bodies.-As it appeared possible tliat these bodies inight have been artificially produced by one or other of the re-agents in which the specimens had been prepared, I took every precaution to eliininate all sources of fallacy in this direction by

’This paper formed part of a Graduation Thesis presented for the Degree of Doctor of Medicine in the University of Edinburgh, t o which a Gold Medal and the Syme Surgical Fellowship were awarded by the Medical Faculty. The investigations were carried out in the laboratories of the Royal College of Physicians, Edinburgh.

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preparing different portions of the same brain in different ways, hardening and embedding in various materials, and staining with varying prepara- tions of the re-agents ; but, in all, the morbid appearance persisted, and although the clearness and degree to which the bodies react to the stain varies somewhat according to the method employed, they are, in all cases, sufficiently characteristic to justify one in concluding that they are not the result of the action of re-agents. I n this connection, Bevan Lewis(’) says, “ Amyloid, colloid bodies, miliary sclerosis, have all in their turn been explained away by some, as the results of alcohol or other re-agents. Unfortunately for this theory, however, all such changes are to be found in the perfectly fresh brain, before any re-agent has been applied.” I can confirm this statement as regards the bodies of which I speak, as I have found them in specimens cut by the freezing microtome, and examined fresh or stained with aniline blue-black (Plate VIII., Fig. 3). The question as to there being artificial productions may therefore be dismissed.

Methods employed.-The majority of iny specimens were hardened in Muller’s fluid, embedded in celloidin, and stained with Ehrlich’s hzma- toxyline, aniline blue-black (one-fourth per cent. aqueous solution), and picro-carmine. Some were cut by the Cathcnrt ether-freezing microtome, and prepared after the method of Bevan Lewis. One or two were hardened in alcohol.

Bescm@tion of Colloid Bodies. In Size they vary considerably from 7 p up to 50 p, the average being

about 18 p. In some cases they are fairly uniform throughout a series of sections, while in others the greatest variety in size is found. It is observed that in the same specimen in the pia niatral meshes (0.g. P k t e VIII., Fig. l), on the surface of the brain, and in the perivascular spaces of large arteries, they assume larger dimensions than in the sub- stance of the brain. Whether this is due to their having more room for expansion, more opportunities for coalescence, or from imbibition of cerebro-spinal fluid, I am not prepared to say.

Shape.-As a rule they are more or less rounded or ovoid, never elongated. They vary greatly in their outline, some appearing swollen and tense, while others look as if their substance were shrunken, and their capsule wrinkled and crenated. Those in the meshes of the pia are, as a rule, tense and globose. I n most places the bodies occur singly and are independent, but frequently they appear in clusters, coalescing with one another, and forming rounded masses, the outline of the individual drops being still traceable.

Staining.-They take up the heinatoxyline stain very readily, and are stained black by osmic acid ; but they are unaffected by aniline hlue- black, or picro-carmine. The smaller examples stain faintly and uni- formly, while the larger ones vary considerably in the degree to which they react.

100 ALEXANDER MILITS.

Not iinfrequently the periphery of the cell seems to be more darkly stained than the centre, and even a double outline is often to be made out (d). In the more advaiiced specimens, however, the margin is the pttler part, and in the centre of soine several dark spots appear.

Sometimes a small body is seen through a large one, giving the appearance of a nucleus (e), hut more careful focussing reveals the true condition. They have no nucleus or other cell contents, are quite hoino- geneous, and, except when deeply stained, are perfectly translucent.

Where found.-They are not confined to any one region of the brain, but are found in greater or less numbers, alike in the hemispheres, basal ganglia, cerebellum, pons, medulla, and spinal cord (Plate VIII., Fig. 2).

I n the brain substance they are found-1. All through the white matter; 2. In the most superficial area of the grey matter; and 3. In the “ lymphatic system” of the brain.

1. In the white matter they are exceedingly abundant, being found wherever inedullltted fibres exist ; in the hemispheres, basal ganglia, valve of Vieussens, pons, and in the periphery of the cord. They are here fairly uniform in size, and take up stains well, They are largest, however, and most numerous, in the immediate vicinity of punctiform hmiorrhages and lacerations of the brain tissue, where they not only invade the torn strands of nerve fibres, but also pass amongst the extravasated blood corpuscles, mid are sometimes found for some distance along the peri- vascular spaces of the blood-vessels.

In some cases they are only to be found near haemorrhages and lacerations, in others they lie near engorged vessels, and in others all through the white matter.

When near the junction of the grey and white matter, they extend only for a short distance, if a t all, into the former.

2. I n the grey nuttteT.-Here they are for the most part to be detected only in the most superficial layer-a region in which there are medul- lated fibres-and when present in this situation they are usually numerous and fairly typical. In some cases this is the only place where I have found them.

When seen deeper in the grey cortical matter it is invariably in relation to an extravasation of blood, or laceration of the brain substance, and then not unfrequently the lesion is found to pass into the white matter also. I n such cases the bodies are usually found in the yerivas- cular spaces of the blood-vessels, along which they are seen to pass beyond the area of gross damage. When apart from a blood-vessel, they are single, small, and scarce.

I n the “lymphatic system” they are met with in two positions, namely-(a) In the meshes of the pia mater-the sub-arachnoid space ; and (b) along the course of the larger intracortical blood-vessels.

(a) It may be of importance, from the point of view of their origin, to observe that when these bodies are found in the sub-arachnoid space it is always in close proximity to a laceration of the brain substance, which

MICROSCOPIC CEREBRAL T K A U&IATISM. 101

makes it probable that they are then derived from the siiperficial layer of grey matter. It is in this situation that they attain their greatest size possibly, as before suggested, because they have more room to expand here than elsewhere, or, it inay be, that they swell up by imbibition of cerebro-spinal fluid.

I n some instances they are found in the pia niatral meshes, and epicerebral space, when hmiorrhages have taken place into the brain siibstaiice, although not iniplicating the superficial layer, the probability being that they have been carried in the lymph stream in the perivascular spaces.

(b.) When in relation to intracortical blood-vessels, the colloid bodies are found in the perivascular lymph space of His, between the hyaline membrane or aclventitia a i d the brain substance. They are also present passing, for a short distance, into the brain substance, and sometimes they find their way into the space of Robin, between the tnnica adventitia and the tunica muscularis,-whether by natural or artificial openings is dafficult to determine. The vessels round which they are seen are most evident in the superficial layers of grey matter, next in the regions where the grey and white matters join-a very vascular area-and to a less degree, as we pass deeper. In all respects they resemble those described in the subarachnoid space, save that they are somewhat smaller and more compressed laterally.

Reiitnrks.--Perhaps the most interesting point brought out By these observations is the mt:treme mpidity with which the bodies are produced in the brain. I have found them in the brain of a bird which only sur- vived its injuries for a few minutes, and in it they bear similar characters to those found after much longer periods have elapsed, being only less nunierous and somewhat smaller than those found in the human subject.

These experimental cases show not only the way in which the bodies can be produced, but also throw light on their origin, because, if they appear in so short a time, they can only be derived from one element of the brain tissue, the myelin of the nerve tubules.

The clinical cases are undoubtedly of much greater interest and value, and although I have not been so fortunate as to examine a case within a few minutes of injury, I am able to show these bodies very well iiiarlred in the brain of a lad who died fourteen hours after receiving injuries by falling from the Forth Bridge ; and in another, although not so abundantly, that of a man who survived his injuries for eighteen hours. I have specimens taken from the brains of patients who have succumbed a t periods varying from twenty-seven up to two hundred and fifty-six hours after injury, exhibiting these bodies.

In this last case the appearances are undoubtedly most typical, but whether 011 account of the long duration of life after injury I cannot say. A coinparison of my sections does not warrant the statement that the longer the duration of life after injury, the more characteristic are the bodies.

102 ALEXANDER MILES.

Literntutae o n thc Sdject of Colloid Bodies.

A great deal has been written concerning so-called colloid bodies, and many diseased conditions described in which they are found, but in spite of it all we are still ignorant as to their exact pathological signifi- cance as well as to their origin and their destiny.

Morbid products which are found in such widely different diseases as acute myelitis, epilepsy, loconiotor ataxia, and general yaralysis of the insane-and, as I have shown, in cerebral coricussion and com- pression-merit a close investigation, and although we can searcelv expect thein to be important pathological factors in any m e or in all cf these dissimilar morbid states, still I think their wide distribution is ail the more reason that we should arrive at a definite conclusion as t g

their exact nature, so that in considering thc pathology of any one of the conditions in which they are found, we may be in a position to assign to them their proper dLle, or it nzny be to ignore theiii altogether.

By experiments on pigeons, Batty Tuke (z) was able to confir-n an observation of MKendrick, who found colloid bodies in the brains of these birds after injuries inflicted on their heads. He says : -<< In every case in which the injury was of ten days’ standing colloid bodies were found, and they iiicreased in number up to the seventeenth day.” They were identical with those found in the human brtiiii, only sonie- what smaller (m+&h inch).

I n May 1575, Hamilton (3) in u paper oil myelitis refers to them. The iiiyelitis was artificially produced in animals by passing a thread through the spinal cord, and after leaving it there for forty- eight hours, killing thc creature. Hamilton believes these bodies to be derixred froin the axis cylinder processes, arid that they are associated with inflaniiiiation, a d he adds that the more acute the intlaniniation is the inore marked are tlie bodies. He considers the colloid condition

In the brain of a syphilitic patient he has seen the stme appearances, and also in loconiotor ataxia and epilepsy, and in all these conditions he concludes that the colloid trensforniation is due to chronic inflamniatory action.

A similar conclusion was arrived at by Woodhead (4) as n result of a study of the same bodies found in a case of locomotor ataxia. He points out the resemblance existing betweeii the structnres he found, and those described by Hamilton, as occurring in myelitis, and also refers to papers by Stricker, Fronian, and Charcot, in which the same views were expressed as to the characters and significaiice of these bodies. This observer found that the bodies were stained black by osmic acid, in which they agree with those I have observed.

The belief that those are derived froin the axis cyliiiders seems to have been shared also by Virchow, who described them from a case of

only a stage in tlie progrcss towards pus foriii 8 t‘ 1011.

MICROSCOPIC CEREBRAL TRA UMATISM 103

congenital encephalitis, being, he said, “made by the severance of the axis cylinders of nerve tubules.”

And Moxon ( 5 ) says, they are “undoubtedly associated with an inflammatory process, and the absence of a nucleus indicates a passive breaking down, rather than an active vital multiplication.”

Bevan Lewis (6), however, in a paper contributed to Brain, in October 1879, states, that “ he regards these morbid bodies as resulting from the segmentation of the myelin ensheathing the axis cylinder.”

He bases his conclusion on (1) the close resemblance between myelin and these bodies, not only in appearance but also in reaction to dyes ; (2) to the fact that they are distributed with great regularity only in those parts of the brain and cord in which the nerve fibres have a medullary covering ; and (3) that in these regions they bear in size a direct proportion to the normal medullated nerve fibres.”

I n his Text-Book of Mental Discmes, 1890 (l), he adheres to his previously expressed opinion as to their nature, and confirms it by the result of eleven years’ further experience in the investigation of hseased brains. He, however, still believes that they are associated with a ‘( chronic degenerative affection of the medullated nerve fibres of the cortical nerve system,” . . . “the real origin of the affection is in the severance of the fibre from its trophic cells,” . . . ‘ I the cell is the priinary seat of disease.”

Obersteiner (7) holds that “ the presence of these colloid bodies indicates a retrogressive atrophic process” . . . “they always appear where nerve substance is slowly disintegrating, and may possibly re- present the last phase of a series of chemical changes associated with atrophy of nerve fibres.” He quotes Rindfleisch in support of his own view, that they are not derived from cells. He believes that chemically they are related to albumen, although a satisfactory explanation of that relationship has not yet been given.

That these bodies consist of altered myelin is also believed by Joffroy, Gombault, and Ceci (*), the last named pointing out the fact that, in their relations to staining agents, they closely resemble that substance.

Writer’s Opiniolz.-A careful study of these colloid bodies as they occur in my specimens, leads me to agree with Bevan Lewis in his opinion that they are derived from the myelin of the medullated nerve fibres.

With myelin droplets they agree closely, not only in shape, structure, and general appearance, but also in the way in which they take up, or reject, the various re-agents to which they have been subjected.

Speaking generally, they are only found in those positions where, normally, medullated fibres exist. It is true that in some specimens they are found in the substance of the grey cortex, but then they are not far froiii some torn portion of white tissue, close to blood-vessels,

104 ALEXANDER MILES.

and oftenest in their sheaths, so that the probability is that, when in these channels, they have been carried thither, having their origin in the damaged nerve tubules.

Such an explanation would also account for their abundance in the epicerebral space and meshes of the pia mater, should the snperficial layer of white nerve fibres he deemed insufficient to produce the large numbers found in some specimens.

I n addition, the time which elapsed between the infliction of injury and death, in many cases renders it highly improbable that they could be derived from any other element, such as axis cylinder process, neuroglia, or nerve cell, from which they diff'er so much in every way. 111 addition, the changes through which they seem subsequently to pass, lends additional support to the view that those found in cases rapidly fatal, are very little altered from the naturd condition of the element from which they are derived, whatever it may be.

Applying Duret's (") cerebro-spinal fluid theory of the mechanism of cerebral concussion, I would explain the presence of colloid bodies in this way.

On the receipt of the blow, part of the fluid displaced by the " cone of depression " rushes along the perivascular spaces of the intracortical vessels, dilating them to their ultimate ramifications, even to those SUP

rounding the nerve-cells. The increased tension compresses the nerve fibres, and the semi-fluid inyelin so pressed upon, escapes, either through the slits shewn by Lantermann to exist in the capsule surrounding it, or by bursting that capsule.

Of course, when gross lacerations of, and haemorrhage into, the nervous tissues take place, the tearing of the nerve fibres amply accounts for the escape of niyelin, and as a inatter of fact we find such conditions in a great majority of these cases.

If such be their nature, and if they are so produced, we can no longer look upoil colloid bodies as necessarily an evidence of " chronic degenera- tive aEection of medullated nerve fibres," as has hitherto been held by almost all who have written on the subject. That they may, in a vast majority of cases, be so, I am unable to deny, but the fact that they can be demonstrated to have been produced in the space of half an hour, or even less, with all the characters of those described in chronic cases, is sufficient to prove that their presence in any given condition is no guide as to the probable duratioii of the morbid process, and clearly shows that they are pathologically much less significant than has gener- ally been supposed.

2.-MILIAHY SCLEROSIS.

The morbid condition o l the tissues of the central nervous system, known as Miliary Sclerosis, is also one which is as yet imperfectly ex- plained, and whose true pathological significance is undetermined. It

MICROSCOPIC CEREBRAL TRA UiWATISM 105

seems not improbable that some relationship may exist between it and the colloid changes which we have already considered, and as one of my cases seems to throw a little light on the subject, I propose to deal with it in some detail.

Miliary sclerosis was originally described in a paper written con- jointly by Rutherford and Batty Tuke (”) in the Edinburgh Medico1 Joumnl of September 1868. These observers a t first were of opinion that the diseased elements were the nuclei of the neuroglia, which underwent changes divisible into three stages.

I n the year following the publication of the above paper, Kesteven (10) described what appears to have been a case of d i a r y sclerosis, although not so called by him. There was no clinical history forth- coming.

Bevan Lewis (1) while regretting that the name is not more in accord- ance with the exact pathological nature of these bodies, agrees in the main with Batty Tiike’s description. “ At first sight,” says he, “ under a low power of the microscope, they look like a number of unequal sized droplets of fluid, of a dense unctuous consistence, incompletely fused with one another.” I n longitudinal section “ the appearance a t once suggests to the mind the forcible extravasatioii a t numerous points of a coagulable material, which has driven the textural elements asunder before it, a suggestion further favoured by the almost invariable presence of a blood-vessel (often of considerable magnitude) running in close proximity to, or even appearing to lose itself in, the morbid focus.”

This writer believes that these bodies uldo~1btedly consist of altered myelin which has exuded in droplets from the medullated tubes, and coalesced more or less completely.

I n sections of the brain of one of my patients who died 256 hours after receiving his injuries, I have found large numbers of bodies, which, in appearance, exactly resemble those of miliary sclerosis, as described by Batty Tuke and Bevan Lewis (Plate VIII., Fig. 4).

An examination of these bodies shows that, like colloid bodies, they are to be found only in regions of the brain where niedullated nerve fibres normally exist, and in their reactions to staining agents, as well as in their general appearance, they are very similar to these colloid struc- tures. The patches are well seen in the anterior pyramids of the medulla, in the pons, and in the white matter of the hemispheres, and look as if they were formed by the coalescence of several of the colloid bodies so abundant there. The constituent droplets of a miliary patch seem larger than the single colloid bodies in the vicinity, and although the outline is more evident, the contents are less darkly stained, having a somewhat yellowish tinge, evidently having undergone some chemical or structural change. Some of the drops are only in apposition, the outline of each being still distinct, while others have coalesced corn- yletely, and all the degrees between these two stages may be traced. None of my specimens have reached the stage described by Lewis,

106 ALEXANDER MILES.

where the miliary patches shrink from the brain tissue, so that they fall out in the process of mounting, leaving irregular holes in the section. Some specimens do present a peat many holes, but they are regular in outline, a i d represent perivascular spaces from which the blood-vessels have dropped.

All the varieties of colloid body are to be fonnd in the vicinity of these patches, some being homogeneous, some with a dark periphery, and others with the centre becoining dark and the periphery lighter.

There is usually a blood-vessel running close to, soinetiiiies through, the patches.

These, and other considerations, lead one to suppose that niiliary sclerosis is closely related to the colloid change, in fact, that it is simply a further development of it ; and this view is strengthened by the fact that ainoiig my cases the former appearances are oiily to be detected in the one instance in which life wits prolonged for a considerable period after injury, the inore rapidly fatal cases presenting the various stages, from the single iiiyelin droplets up to the colloid body in its niost typical form, the complete evolutioii being traceable in a series of sections.

Bevan Lewis (I), page 464, regards “ these multiple lesions, not as a primary sclerotic change, but as cwcidents occnrring in the course of n sub-acute i?zja?nnzcttoyy OT clcgcnemtivc chnnge in the inedullated nerve tracts ; ’) and at page 469 he says, “ We regard both the ‘ niiliary ’ and ‘colloid’ change as represeiitiiig stages in the progress of a chronic degenerative affection of the ineclullated fihres of the centric nervous system, an affection which is of inore freqiient occurreiice in the brain of the insane, aud not of most vital import.”

While I am quite convinced as to the close relationship existing between these two morbid appearances, I cannot, in the face of iny observations, admit that either of them is evidence of chronic mischief, both being found in comparatively acute conditions.

3.-pIGIMENTARY DEGENERATION OF NERVE CELLS.

I n a number of cases in which there has been some degree of com- pression of the brain substance, by blood-clot extravasated on to its sixrface or into its tissues, I have observed that the nerve-cells exhihit varying degrees of pigmentatioii in excess of that found normally. We know that a small quantity of golden yellow pigment exists as a normal histological condition, varying in amount in the different laminae of nerve-cells, and probably affording an index of the functional activity of these cells, the pigment being, as it wcre, the evidence of the wear and tear of the cell in which it is found.

In the case of a wonian who died from the effects of a severe blow to her head, as a result of which a lnrge clot was extravasated over the right hemisphere, this excessive pigmentation of cells was very evident.

MICROSCOPIC CEREBRAL TRA UMATISM. 107

Freshly prepared sections of the cortex of the injured side showed a considerable increase of pigment in the motor cells. The p i p e n t , instead of being collected into a small heap at the base of the cell or around the nucleus, was scattered promiscuously all through the proto- plasm. I n some of the cells (Plate VIII., Fig. 5 ) the normal appearance persisted (a) ; in others the only change evident was an increase in the amount of pigment, and its wider distribution, the nucleus appearing normal in size, position, and reactions (a). I n other cells again, the great excess of pigment obscured the protoplasm, and the iiucleus was seen to be displaced and lying against the cell wall (c). A still further stage in the degenerative process exhibited the nucleus less darkly stained and with a clear spot in the centre, and the protoplasm of the cell entirely replaced by a mass of pigment (d). I n the most advanced stage the cell and its contents were represented by a small mass of pigment apparently lying free in the brain substance (e) .

I n some of the cells, pigment could be seen for a considerable dis- tance along the axis cylinder process (f) ; and in others large vacuoles were to be made out in the protoplasm and nuclear substance (9).

I n another clinical case, in which there was also extensive extra- vasation on to the surface of the brain, the sections of the motor cortex exhibited similar appearances. I n the fresh specimens the condition was exactly like that of the last case described, although not so ad- vanced ; and, in the hardened ones also, the increased pigmentation could be detected, all the stages from the normal cell, down to the mass of granular dtfbiis, being traceable. The pericellular sacs appeared very large from the shrinking of the contained cells, and the perivas- cular and pericellular nuclei mere well seen. Exactly similar appear- ances were observed in other cases.

I imagine that this pigmentary degeneration is the result of the pressure exerted by the clot on the brain substance interfering with the supply of nourishment to the nerve-cell. If the piementation found normally be the evidence of physiological activity, it means that the demand on the nerve-cell has been greater than the nutritive supply could meet ; and, for the same reason, obstruction of the vascular supply to a particular area of the brain will produce a similar result.

It is interesting to observe how rapidly the degeneration took place in the cases I have mentioned-fifty and twenty-five hours respectively elapsing between the infliction of the injury and death.

Like the presence of colloid bodies, this form of degeneration is usually associated with more or less chroriic conditions, but these obser- vations show that it is by no means necessarily so. That nerve-cells rridy be very quickly depressed is abundantly evident from the fact that a short exposure to the action of certain vapours, such as carbonic acid gas, nitrous oxide, or chloroform, materially affects their functional activity. This can only be the result of chemical changes tak- ing place in the nerve-cells, which chemical action implies change

108 ALEXANDER MILES.

in the constitution of the cell protoplasm. Now if the cause of this chemical change, whether it be a poisonous gas, a physical obstruc- tion to the circulation, or excessive functional activity, be kept up for a sufficient tinie, the degeneration may go so far i - 1 ~ to be beyond repair, or to be inconsistent with life.

Such changes, taking place in the cells constituting the vital centres a t the base of the brain, would account for the fatal termination of cases where the pressure interferes with the nutrition of these parts; and when affecting the cortical centres would explain the permanent sym- toms of nerve impairment which so often follow head injuries. We have it, on the authority of Bevan Lewis (l), that nerve-cells which are depressed to a certain extent, even by hyper-activity, never regain their previous condition. How much inore then should we expect such a result from a physical barrier to nutrition, such as we get in head in- juries with compression ?

I n the same way may be explained those cases of syphilitic herni- plegia which are, according to Hutchinson, almost en tirely curable by potassium iodide, and mercury. The specific lesion, probably endar- teritis, interferes with the blood supply of a particular part of the brain, the nerve - cells degenerate in consequence, and hemiplegia results. Specific remedies remove the cause-the endarteritis ; but some of the nerve-cells have gone beyond the possibility of recovery, and so some residual symptoms are exhibited. So in head injuries, the blood-clot is eventually absorbed, but not until some of the nerve centres are so far degenerated as to be rendered permanently fanetionless.

4.-MINUTE FETECHIAL HIEMORRIIAGES.

I do not intend here to deal with those large, gross extravasations of blood, so often seen on the surface of different parts of the brain after severe head injuries. These I have elsewhere (I2) referred to in de- scribing individual clinical, and experimental cases, specifying their exact position, and probable clinical and pathological significance.

I am now concerned rather with the minute petechial hsernorrhages found scattered throughout the brain, most of them too sinall to be seen by the naked eye, and all of them invisible without cutting into the cere- bral substance. Many of these are a t points altogether remote from the seats of gross effusions on to the surface; some are situated under, but not in direct continuity with such, a portion of healthy tissue inter- vening between the two blood masses.

The brain of a youth, aged 16, who fell from a scaffold eighteen feet high, exhibited to the naked eye numerous small haeniorrhages into its substance. One of these near the surface, but not seen until the brain was cut into, was about lidf the size of a threepenny piece, situated for the niost part in the white matter, but infiltrating also the deeper layers of the grey; it had ploughed up the strands of

MICROSCOPIC CEKEBRAL TRA UMd TISM 109

white fibres, a considerable area being quite disintegrated. On micro- scopic exaniination it was found that the hemorrhagic area was made up of a number of separate small extravasations of blood corpuscles, divided from one another by septa of nerve fibres, and in each mass could be detected the outline of a small blood-vessel, sometimes intact, sometimes ruptured, doubtless the source of the blood among which it lay.

At a deeper level in the white matter the vessels were contracted, and for the most part empty, possibly from their contents having escaped into the brain tissue. I n the vicinity of the htEmorrhages, colloid bodies were numerous. The other petechize found throughout the brain agreed with the one described.

Tn the brain of another patient, who died from injuries sustained in fiilling backwards down a stair, these petechial hxmorrhages were very numerous. Many of the clots have fallen out in the process of mounting, leaving small round holes, of fairly equal size and regular outline studded throughout the section. The holes evidently represent the perivascular spaces into which the blood had been effused, many of them, indeed, still retaining blood-vessels and others, blood corpuscles. I n some cases a blood-vessel could be traced up to the edge of these spaces, and then was seen t o end abruptly, not unfrequently dilating before doing so.

I n several other clinical, as well as in almost all my experimental cases, exactly similar appearances are to be made out-in the cortex, basal ganglia, pons, and medulla, the seat of the petechiae bearing no definite or constant relation to the seat of injury or of gross lesion, but seeming rather to be due to some general, universal disturbance of the brain tissues, such as the cerebro-spinal fluid wave would amply account for.

Condition of Blood-vessck-The blood-vessels in a majority of my cases were seen to be in a state of congestion, varying in degree, in some cases being extreme. They were distended and packed full of corpuscles, the perivascular space being much diminished in size, sometimes even occluded. The number of sections of blood-vessels seen in a given area was above the normal.

I n a few cases the vessels were widely open, but empty, while in a few others they w-ere contracted.

Condition of Perivasculnr Spnees.-The state of these varied, of course, with the degree of congestion of the continued blood-vessel, being com- pletely occlnded wheii this wits extreme. Not unfrequently they were observed to be the seat of small masses of blood-corpuscles, effused be- tween the vessel wall and the limits of the space, in some instances these even filling the space, Often the contents fall out in the manipulations, leaving small round holes in the section ; and it is interesting to observe how the size and numbers of these holes vary in different parts of the same brain. I n the clinical case last mentioned, for example, as many as thirty spaces could be counted in one field of the microscope,

110 ALEXANDER MILES.

near the surface of the brain, while deeper, only six or eight could be seen.

Codition of Perieellu.lnr Snes.-In a few specimens, blood-corpuscles, and in some others, blood pigment could be detected in these spaces in which the ultimate nerve-cells lie. New to the area in which this occurred, a small ruptured blood-vessel was seen, clnd it is not improbable that the corpuscles or pigment was carried hither by the lymph stream.

The B?nin Tissue surrouncling the congested vessels and hmnorrhages has, as one would have expected, taken on the stain more deeply, as if cornpressed and condensed by the increased vascular tension.

All these appearances are, I think, readily explicable on the cerebro- spinal fluid wave theory. The flow of the wave would dilate the peri- vascular spaces, and forcibly coniprcss their contained blood-vessels, while, during the ebb these latter would for the moment be left unsup- ported, and in a condition in which riipture would be extremely likely to take place. On such a theory as this, not only the large numbers of these ruptures, but also their wide diffusion through the brain, and the condition of the perivascular and pericellnlar spaces, and the adjacent brain tissue, are quite intelligible.

1. REVAN LEWIS, . 2. J. BATTY TUKE, 3. HAMILTON, . . 4. WOODHEAD, . 5. MOXON, . . . 6. BEVAN LEWIS,. 7. (JBERSTEINER, . 8. CECI, . . . 9. RJJTHERFORD AND

10. KESTEVEN, . . 11. DURET, . . . 12. MILES, . . .

REFERENCES.

. , Text-book of Mental Diseases, 1889.

. . Brit. For. Med.-Chir. Rev., July 1873.

. . Microscopical Jour., vol. xv. 1875.

. . Jour. dnat. Physiol., vol. xiv. April 1884.

. . Med. Times and Gazette, Dec. 1870.

. . Brain, Oct. 1879.

. . Anat. Centr. Nerv. Sys. (Hill), 1890.

. . (Quoted by Ziegler), Path. Anat.

. . Grit. For. Mod.-Chir. Rev., vol. xliii. April 1869.

. . Etudes sur les traumatisnies cdrdbraux, t. i. 1878.

. . Lab. Rep. Roy. Coll. Phys. Edin. vol. iv.

TUKE, Edin. Med. Jour., Sept. 1869.

MICROSCOPIC CEREBEAL TRA UMATISM 111

PLATE VIII.

FIG. 1.-Colloid bodies as found in the meshes of the pia mater of the occipital lobe. Stained with haematoxylin ( x 600).

a. Vessel of pia distended with blood. b. Blood in meshes of pia. c. Colloid bodies amongst blood corpuscles. d. Colloid body focused to show double contour. e. Small colloid body, seen through larger one (apparent nucleus). f. Vessel of pia (transverse). 8. ,f ,, (longitudinal). h. Superficial layer of grey matter of cortex. i. White blood corpuscles.

FIG. 2.-Colloid bodies as found in cervical portion of spinal cord (Column of Turck). Stained with hematoxylin ( x 300).

a. Large vessel of pia filled with blood. b. Superficial neuroglia of cord. c. Transverse section of nerve fibre. d. Neuroglia cell. e. Small vessel in transverse section. f. Colloid bodies.

FIG. 3.--Colloid bodies as found in parietal cortex. Cut fresh. Stained with aniline blue black ( x 300).

a. Superficial layer of grey matter. b. Nerve cells showing excessive pigmentation. c. Blood vessel. d. Colloid bodies.

PIG. 4.-kfiliary Sclerosis as seen in transverse section of medulla oblongata (anterior pyramid). Stained with haematoxylin ( x 300).

a. Neuroglia. b. Blood veasel in perivascular space. c. Colloid bodies. d. Colloid body showing dark centre and light periphery. e. Maases of colloid bodies assuming the appearance of miliary sclerosis. f. Tissue around these, condensed.

FIG. 5.-Pigmentary Degeneration of Nerve Cells. Parietal Cortex. Cut fresh. Stained with aniline blue black ( x 300).

a. Normal nerve cell, with pigment in small heap near to nucleus. b. Increase in quantity and wider distribution of pigment. c. Protoplasm obscured by pigment, and nucleus displaced against cell wall.

e. Mass of pigment lying free in brain substance. f. Pigment along axis cylinder of nerve cell. g. Vacuolation of nerve cell. h. Small blood vessel with much pigment along its courcle.

d.d. Clear space in centre of nucleus. Great increase in amount of pigment.

JL. O F PATH.-VOL. 1. 8