MEMOIRS.

On MYELITIS, being an EXPERIMENTAL INQUIKY into the

PATHOLOGICAL APPEARANCES of the same. By D. J.

HAMILTON, Author of the " Astley Cooper Prize Essay "on " Diseases and Injuries of the Spinal Cord." (WithPlate XVI.)1

. . % • * *

So much doubt still exists as to what are the characteristicpathological appearances of inflammation of the spinal cord,and so many diverse conditions have been described as suchwhich no doubt owed their origin to entirely different patho-logical processes, that, as yet, we may be said to possess noliterature which can form a guide in telling us whether thisor that condition is an inflammatory affection, and whichclearly differentiates this from the many other pathologicalchanges to which the spinal cord and all nervous tissues areliable.

Softening, hardening, disintegration, and numerous otherstates of the organ have all been proposed as characteristic ofits inflammation without any attempt to describe the stagesor means by which these so-called pathological lesions havebeen brought about. One great source of fallacy in regardto the proper understanding of this matter is the inability todistinguish between the lesions known as " secondary de-generations " produced by failure of the trophic or nutritivenervous action exerted by the nerve-cells, on the fibres towhich they are attached, and those which are localised to acertain spot, and which are probably dependent on some dis-tinct origo malt in their neighbourhood. For, granted thatwe have degeneration of a few nerve-cells in portions of thecerebrum, it is almost a certainty that if the subject of thelesion has lived long enough, the fibres in the spinal cord incommunication with these will have also degenerated, willhave undergone fatty disintegration, and will be softened.How easy, then, in such a case to mistake this for a localaffection, instead of referring it to its true source, namely,the primary degeneration of the cerebral nerve-cells.

1 Head at the Medical Microscopical Society, May 21st, 1875.

VOL. X V . — N E W SER. Z

336 D. J. HAMUTON.

Other grave sources of error are undoubtedly post-mortemchange and the method of preparing specimens for examina-tion. I have very often found that all manner of lesions, soften-ings, areas of disintegration, varicose nerve-sheaths, &c, canbe artificially produced by merely placing the specimens,while they are being hardened, in an atmosphere with atemperature such as is generally maintained in our ordinaryhouseholds. One of the most important conditions for drawingcorrect conclusions is, especially for the first week, to keepthe temperature of the parts to be hardened as low as possible—at 32° F. or very slightly above it. In this way we canprevent decomposition until the reagent used in hardeninghas had time to penetrate into the interior of the tissue, andpartially to harden it by a process very similar to what ispursued in tanning.

If, again, we place the part in too strong a solution ofchromic acid, the outer limits become so rapidly hardened aseffectually to prevent the ingress of reagents to the interior,which accordingly undergoes decomposition. My ownmethod of preparation, described further on, is calculated todo away with these deficiencies, and to present the specimensto the eye as nearly identical with the appearances duringlife as possible.

The experiments which are about to be described wereundertaken with the object of first producing a lesion whichwe know to be an inflammatory one, and then making themost careful examination, all preconceived ideas on the sub-ject of inflammation generally being purposely laid aside.The appearances were merely carefully noted and abundantlyverified by repetition of the experiments and observations.Everything is purposely omitted which could mislead, forwant of confirmation, and only those facts which by constantrepetition were found to be invariable are here stated. I havealso been favoured with the valuable confirmatory evidenceof Professor Strieker, in whose laboratory for experimentalpathology the observations were made.

Method of experimenting.—A small animal, such as a cat,having been narcotized, the spinal cord is cut down upon inthe upper lumbar region, at the junction of the dorsal andlumbar portions. A thread is passed through it for about aninch in a longitudinal direction. The ends of the threadare then tied, the wound stitched up, and the animal left forforty-eight hours. This gives abundant time for the excite-ment of inflammation. The animal is then killed and thespinal cord cut out.

Preparation of the cord. — The dura mater having been

JAT^OLOGtCAL APPEARANCES OF MYELITIS. 33?"

removed, the cord is cut into pieces of an inch long but notentirely separated from one another, so that their relativeposition is still indicated. These are placed in the followingsolution for twenty-four hours :

Chromic acid, J ss ;Methylated spirit, gxx;Water, gx.

Dissolve the chromic acid in the water and then addthe spirit. Place in an extremely cool situation, or if possiblein an ice chamber. Change the fluid every second day forthe first week, and at the beginning of the second weekplace it in the following solution:

Chromic acid, Jss;Methylated spirit, %x;Water, Jxx.

Allow it to lie in this for another week, changing if aprecipitate is thrown down. At the beginning of the thirdweek change to the following :

Chromic acid, Jss;Water, Jxxx.

Change this every week until the end of the fifth or sixth,when the parts will be ready for cutting. This process isinfinitely superior for all nervous tissues to anything'that Ihave used, as the consistence of the tissue so hardened istough instead of being brittle as in the old chromic acidmethod. For very large animals the solutions used aresomewhat stronger. Cut extremely thin sections with a micro-meter screw apparatus, fixing the cord in the hollow cylinderby a piece of carrot, punched out by means of graduated corkcutters. Stain with the following :

Carmine, J j ;Liq. Ammonise fort., 5 j ;Water, Jiv.

Allow the sections to lie from five to ten minutes in thissolution and then wash them in the following:

Acetic acid, iT|vj;Water, giv.1

After this, wash them in pure water and place them inmethylated spirit. Render them transparent with oil ofcloves, and then mount them permanently in the following :

Gum Dammar, Jj;Chloroform, 3iss;Oil of cloves, Jj.

1 For all chromic acid preparations of the nervous centres it will befound that, the specimens stain much more rapidly and thoroughly if thewater in which they are washed is slightly acidulated.

§38 •• b. i. HAMILTON.

Examination of the parts.—At the exact seat of the lesioncaused by the thread the tissue was mechanically brokenclown and numbers of blood-extravasations were seen. Thetrue inflammatory area, however, was not here, but at somedistance from this in the surrounding parts, generally mostmarked in the deepest portion of the anterior columns, closeby the commissure, and in the commissure itself. In someinstances the whole extent of atransverse section wasinflamed.

Changes in the Nerve-tubes.By far the most remarkable change was that which had

taken place in the axis-cylinders of the nerve-tubes (seePI. XVI. fig. 1). On looking at a transverse section, numberslarge round translucent bodies deeply stained were seenoccupying the distended and attenuated nerve-sheaths.These bodies were usually five to ten times as largeas the normal transverse section of an axis-cylinder, but,in many instances, reached even greater dimensions.Their formation was most beautifully seen in longitudinalsections. At regular intervals large oval tumours could beseen on the course of the axis-cylinders,1 with attenuatedportions of the original axis-cylinder still uniting themtogether (fig. 3). In many cases the axis-cylinder had quitegiven way, so that these large new formations came to have aseparate existence, an existence as we shall see not calculatedto end here, but to proceed to still further development. Thiscondition was so remarkable as at once to arrest the attention,and in certain instances, it was seen all over the section;in others it was localised to the most inflamed part. In some ofthe swellings concentric rings could be noticed, but, generallyspeaking, they had a translucent homogeneous aspect. Onstill closer examination one was struck with the remarkablefissiparous division which large numbers of them had under-gone, producing little depots of similar round translucentbodies of smaller size (fig. 2). These lay at first closely to-gether in aggregated clusters, but soon spread themselves outand invaded the surrounding tissues, leaving in their formersite nothing but an empty distended nerve-sheath. In thisstage they were exactly identical with the so-named colloidbodies so abundantly found in chronic nervous affections ofthe cord. Their size, shape, translucency, and especiallytheir adaptability for being deeply coloured with staining re-agents, were exactly similar to what every one must have

1 Leyden ('Klinik dcr Riickeumarks Krankheilen') describes a similarlesion,

PATHOLOGICAL APPEARANCES OF MYELITIS, 3 3 9

noticed in regard to colloid bodies generally, while theoccasional appearance of faintly marked concentric rings wasnot inconsistent with their being identical. A little closerexamination, however, enabled one to see a still further andmore remarkable development which they underwent,especially in the neighbourhood of greatest inflammation,namely, that they lost their translucency, became transparentand granular, and that several nuclei formed in their interior.In fig. 4 is shown the formation of one of these large granularcorpuscles. It is seen separating from the parent mass, i.e.from the contracted axis-cylinder, which latter shows a hollowspace corresponding to the portion which has been lost.

These corpuscles now presented the appearance of "mother-cells," with numerous young cells in their interior (fig. 5).Last of all, in places where the inflammation had gone on tosuppuration, these " mother-cells " were broken down, andthe younger cells in their interior were set free as pus-cor-puscles (fig. 5). Where the inflammation was not so acute thedivided portions of the original axis-cylinders evidentlyremained as colloid-looking bodies resembling those seen inlocomotor ataxia and other chronic nervous affections.

Changes in the Nerve-cells.

The most common occurrence which was noticed in thesewas a swelling or molecular transformation of the cellsubstance, by which its outline became indistinct. Itwas soon converted into a molecular mass, in which thenucleus usually remained for some time, finally, however,undergoing a similar degeneration. This is a conditionwhich has been frequently described, and has been'called byMeynert an oedematous affection of the nerve-cell. In noinstance was fissiparous division of the nerve-cell noticed,but almost invariably the degeneration above describedwas present. In one instance there was a defined areaabout a line in length at a certain spot in the grey substancein which all the nerve-cells were so affected, and at the outerpart of this area, where the degeneration was more advanced,their granular debris had disappeared, leaving a coarse net-work produced by the empty spaces, blood-vessels, and neur-oglia. Swellings were seen on the processes of certain of thenerve-cells similar to what were seen in the medullary nerve-tubes.1

1 Meynert lias noticed such a lesion in syphilitic brains,

3 4 0 D. J. HAMILTON.

Changes in the Neuroglia.'This was not so markedly altered as one would a priori

have expected; still in many instances its protoplasmic nucleiwere much more abundant than in sections taken from normalportions of the same cord. The manner in which the newcorpuscles were produced could not be made out with satis-faction, but the probability is, from what was seen, that theyalso resulted from fissiparous division.

Changes in the Blood-vessels.In the neighbourhood of the ligature numerous and large

extravasations were noticed, probably mechanically broughtabout in operating on the cord. In the pia mater surround-ing the cord, and in the processes which run into it, immensenumbers of round clear corpuscles were observed in theperivascular spaces and tunica adventitia of the vessels.They were also abundantly seen within the vessels, adheringto the inner coat, and many of them could be actuallynoticed in the wall. What these corpuscles were I think canhardly be a matter of doubt. They were the leucocytes ofthe blood, which, after adhering to the inner wall of thevessel in greater abundance than under normal conditions,made their way through its coats, passing into the perivas-cular space and adventitia, and there constituting pus-cor-puscles. Throughout the grey substance numbers of similarcorpuscles could be seen scattered indiscriminately, and thereis every probability that these were also leucocytes whichhad wandered from the neighbouring vessels.

Having thus summed up the characteristic alterations inthe individual tissues, their consideration shows us that theinflammatory condition in the spinal cord, like inflammationin other organs, is not one simple process, but is a combina-tion of phenomena dependent on the individual characteris-tics of the histological elements entering into the constructionof the part. The formation of colloid bodies from the axiscylinders, and their subsequent transformation into pus-cor-puscles, were so clearly demonstrated as to leave little or nodoubt on the subject, and it was a somewhat remarkable fact,in confirmation, that at the seat of greatest inflammation thedivision of the swollen axis-cylinders was most abundant, thesegments becoming rapidly round, transparent, and granular,and further subdividing into pus-corpuscles. Where theirritation was not so great, the divided parts became roundand translucent, but remained as colloid bodies, i. e. bodieswhich had a colloid-looking aspect. Much has been written

PATHOLOGICAL APPEARANCES OF MYELITIS. 3 4 1

about these so-called colloid bodies, but, so far as I am aware,their true nature has always been a matter of the gravestdoubt, the current idea being that they result from acolloid transformation of previously existing protoplasm.This has always seemed a most indefinite and unscientificway of speaking of such matters, as the stages by which theyarrived at this development have never been described, andwhy these, and none of the other tissues, should undergocolloid transformation has always remained unexplained.Wherever they occur, as in locomotor ataxia, the medullarysheaths of the nevve-tubes ave generally distended, and theiraxis-cylinders are absent. This I have seen typically inseveral instances of the above-mentioned disease, similarlesions having also been described by many writers; and inan instance of syphilitic inflammation of the brain which Iexamined some time before making the above experiments,the appearances were so entirely similar that I beg to offerhere a short account of them. The patient had sufferedfrom a chronic cerebral affection accompanied with greatpain, and was one day suddenly seized with hemiplegia, anddied shortly afterwards. He had a distinct chronic syphilitichistory, and there was every reason to suppose that the cere-bral lesion was also dependent upon this diathesis. At thepost-mortem examination every part of the brain was foundcomparatively healthy except the vessels at the base and aportion of the pes pedunculi on one side. In this lattersituation was a dirty red softened mass with a small extra-vasation in the centre, extending through the middle of thepes pedunculi, and for some distance into the tegmentum. Onhardening the entire nervous centres and examining them withthe utmost care, it was found that at the situation of the lesiondescribed the vessels were greatly distended and their coatscovered with thick translucent exudation composed of roundcorpuscles. In the centre of the pes pedunculi were seen blood-extravasations and broken-down nervous tissue,but around thisnumerous large colloid bodies of an oval or rounded form wereseen arranged in a linear manner according to the direction ofthe fibres. They were very abundant, and, in many places, hadundergone minute subdivision, the divided portions assuminga round and translucent aspect and constructing small depdts.Throughout the grey matter of the convolutions in manyplaces, and in the region of the nucleus lentiformis on the leftside, were scattered round transparentcorpuscles distributed inan exactly similar manner to those seen in the grey substance ofthe spinal cord in many of the animals experimented Upon.We may therefore conclude that this condition was a somewhat

3 4 2 DR. W. R. M'NAB.

chronic inflammation of certain parts of the brain, and thatin the pes pedunculi on one side, where it Avas mostadvanced, appearances were seen which were identical withthose artificially produced in the above-mentioned experi-ments. In the medulla oblongata of epileptics I have alsomet with lesions which I now feel convinced were due to achronic inflammation of the part, and in locomotor ataxiathe absence of axis-cylinders, the distended nerve-sheaths,and the presence of large numbers of colloid bodies, all tendto confirm the hypothesis that we have here also to do witha chronic inflammatory affection.

The LIFE-HISTORY O/PENICILLIUM. Translated and abridgedfrom Dr. OSCAII BREFELTJ'S ' Botanische UntersuchungenTiber Schmimelpilze,' Heft II. By W. R. M'Nab, M.D.Edin.; Professor of Botany, Royal College of Science forIreland. (With Plates XVII and XVIII.)

AMONG moulds Penicillium glaucum is the one of mostfrequent occurrence. "With unparalleled obtrusiveness thelittle plant forces its troublesome and unwelcome acquaint-ance alike on the learned and unlearned. Its pre-eminenceamong moulds depends less upon its size than upon itsabundance, commonness, and highly characteristic pale bluecolour. The fungus exists everywhere, and it is not,possible by any observations to fix the limits of its geo-graphical distribution. Its occurrence is dependent on noaccident; it is the natural and necessary consequenceof the ubiquitousness of its excessively minute conidia(asexually developed spores), which reproduce it with thegreatest ease. The spores are scattered through the atmo-sphere, settling down when the air is still as a constituent ofthe dust; and they are then carried to the ground by rain,&c,from whence, on becoming dry, they are again lifted andcarried by the faintest atmospheric current, if the placewhere they were first deposited was unsuitable for theirgermination. Thus the fungus obtains access everywhere;it is as unavoidable as the air by which it is carried. Out ofdoors it is to be found on all organic substances in a state ofdecomposition, more especially on the larger fungi. In ourdwellings it is a real plague. Raw and prepared articles offood are exposed to its destructive influences. It moulds