An essay upon the vasomotor changes in tabes dorsalis and on the influence which is exerted by the sympathetic nervous system in that disease
From The Arthur Conan Doyle Encyclopedia
An essay upon vasomotor changes in tabes dorsalis... is the thesis written in april 1885 by Arthur Conan Doyle when he was at Bush Villas, Southsea, 4 years after being graduated as a Medical Bachelor.
An essay upon vasomotor changes in tabes dorsalis
Upon the vasomotor changes in tabes dorsalis and on the influence which is exerted by the sympathetic nervous system in that disease, being a thesis presented in the hope of obtaining the degree of the Doctorship of Medicine of the University of Edinburgh.
A. Conan Doyle. MB. CM. 
1 Bush Villas
I. The Cerebro spinal nervous system
There are few diseases which possess a more extensive literature than does tabes dorsalis, and none perhaps, considering the short time since Duchenne first draw attention to it, which has attracted the attention of so many brilliant investigators. The protean nature of its symptoms, its strange and varying course extending over lengthy periods, baffling all treatment and dragging on from one variety of torture to another until the emaciated sufferer hails the death which releases him of his pain, have excited the interest both of pathologists and of clinical observers. Yet in spite of the researchers of such men as Erb, Charcot, Leyden and a host of others, our knowledge of the initial lesion in tabes, and still more of a course of treatment which may cause permanent improvement in the patient, is scanty in the extreme.
It is with diffidence that a young medical man must approach a subject upon which so many master minds have pondered - more particularly when the views which he entertains differ in many respects from any which he has encountered in this reading.
Doubly diffident must he be when enforced residence in a provincial town cuts him off from those pathological and histological aids which might enable him to strengthen his arguments. In the preparation of a thesis upon such a subject the post-mortem room and microscope are of more value than the writing desk and the library. A workman must however work with such tools as he finds to his hand and this I have endeavoured to do to the best of my ability.
Among the many varying phases of tabes dorsalis there is one constant pathological fact. That is that in the disease the cerebrospinal system of nerves is prominently affected and that many of the most marked symptoms of the disease are dependant upon this affection. This cerebro-spinal lesion has been considered generally to be the primary morbid process in the disease. he object of this essay is to endeavour to show that it is secondary to a preceding pathological condition. In any case however the cerebrospinal system plays such an important part that a short description of it may be a fitting introduction to the subject.
The affection of this system shows itself most prominently in that portion which is set aside for the condition of sensory impressions. it is only as a secondary result, or by concurrent separate morbis processes that the motor tract is invaded. The anatomical lesion is commonly to be found in the cord itself, though in certain rare cases described by Dejerine, Vaillard, Pitres and A Hughes Bennett, the changes have been confined entirely to the peripheral sensory nerve endings. In describing the cerebro-spinal system it may be as well to start with these nerve endings and trace the sensory tract upward, indicating briefly the path taken by impressions in travelling from the periphery of the brain.
Archives de Neurologie. Paris 1883.
Four different forms of sensory nerve endings have been made out. These are the pacinian corpuscles of Kölliker, the touch corpuscles of Richard Wagner, the end organs of Krause as seen in the conjunctiva, and finally an arrangement peculiar to the cornea in which the axis cylinder and by sending out fine ramifications among the tissue elements. Through these terminal organs the cerebro spinal nervous system maintains its connection with the outer world, with the exception of those functions of hearing, smelling, sight and taste. The remainder of the sensory system has for its object the conveying of impressions so obtained to the central organ where they may be duly registered. The fibres from the and organs coalesce into trunks which pass upward to the spinal cord, and enter it by the posterior nerve roots.
When those sensory nerve fibres have entered the cord they follow two different courses, an external and an internal. The external fibres pass directly to the grey matter and continue upwards in the substantia gelatinosa of Rolando. Most of the fibres run apparently up and down just where the gelatinous substance joins the true grey substance. Some of the fibres pass horizontally into the posterior horns ending probably in the spindle cells there. Others pass across by the posterior commisure.
Of the internal fibres many pass up and down in the external part of the posterior columns, after which they penetrate the grey matter almost horizontally. Some enter the cells of the posterior horn. Some seem to join lateral cells of the anterior horns. Some pass to the cells in Clarke's column, and some decussate by the anterior commisure.
It is probable that sensory impressions travel to some extent through the grey matter of the cord as well as through the white. The postero-median columns consist of long fibres and are supposed by some to convey sensation from the legs while in the cervical region similar fibres are found in the postero-lateral columns, in connection no doubt with the arms.
There is reason to believe that various varieties of sensory impressions travel by different routes. For instance heat and pain appear to be conveyed by deeper portions of the cord than ordinary sensations of touch. The fact of the decussation of the sensory fibres shortly after joining the cord is a fact of great clinical importance. The point of decussation varies with the different varieties of sensation.
Without going deeply into the appearance of a section of the healthy cord, which would be superfluous, a few words as to its anatomical divisions are necessary before going further. The posterior column lies between the posterior median fissure or septum, and the posterior nerve roots and cornu of grey matter. It is divided by a small depression and septum into two parts, the postero-median column or column of Gall, and the postero-external column or column of Burdach, or posterior root zones of the French anatomists. For convenience sake the portion of the cord chosen for this brief sectional view is in the lower dorsal or upper lumbar region.
The lateral column is the portion of white matter which is situated between the anterior and posterior nerve roots. It has been divided by Flechsig into four areas, the most important of which is the crossed pyramidal tract, composed of the motor fibres which have decussated in the medulla. In addition to this are (a) The limiting layer of grey substance (b) The anterior mixed region of the lateral column (c) The direct cerebellar tract. The last appears in the upper part of the lumbar enlargement, and increases as it ascends to the cerebellum, constituting the restiform bodies in the medulla and entering by the inferior pedicles.
The anterior column like the posterior is subdivided into two parts. The inner or column of Türck is the direct pyramidal tract, formed by those motor fibres which do not decussate in the medulla. The function of the remainder of the anterior column has not been made out.
All these columns consist of nerve fibres, connected together by delicate connective tissue or neuroglia, with blood vessels and lymphatics.
The grey matter of each side communicates with that of the other through the posterior commisure. Each half is divided into an anterior cornu, a posterior, and a connecting body of two horns, the anterior is the larger and contains many large irregularly stellate cells, which are of great physiological and pathological importance. They are multipolar but have one long unbranched axis cylinder which in favourable sections may be traced into the anterior root fibres. The other poles divide into numerous branches which are supposed to terminate in the nerve fibrils which run through the grey matter. The nerve cells in the grey matter arrange themselves longitudinally into well marked columns. Of these the chief are (1) The anterior columns of which three may be distinguished (2) The intermedio-lateral column behind these and on the outer side (3) Clarke's column on the inner side of the head of the posterior horn, (4) The column of the posterior cornu behind, composed principally of spindle shaped cells.
After this brief sketch of the different tracts seen in a section of the cord it is easier to resume the description of the route traversed by sensory impressions. The columns of Gall and of Vurdach pass up into the funiculus gracilis and the funiculus cuneatus, which contain nuclei into which the fibres are seen to enter. The posterior horns pass up and are further continued in the formatio reticularis. Fibres pass through the interolivary fibres, formatio reticularis, fillet, tegmentum externum of crura cerebri, to the red nuclei and so through the posterior third of the internal capsule on to the optic thalami where they radiate towards the cortex.
Ferrier's researches show that the hippocampus major and gyrus hippocampus with the neighbouring inferior tempero-sphenoidal region if destroyed do away with all sensibility of the opposite side. Therefore this must be the site of the tactile centres.
All sensory fibres cannot reach the brain but many must end in centres in the cord where they subserve reflex action.
Having traced out the tract followed by sensory impressions, this short description of the cerebrospinal nervous system would be incomplete unless it ran over the course pursued by the motor impulses. The balance of evidence is in favour of their starting from the grey matter of the brain. The fibres converge as they pass down in the corona radiata and form an important part of the internal capsule, after which they pass down the crusta of the crura cerebri. In the medulla the larger portion decussate in order to form the crossed pyramidal tract, while a smaller bundle descends on the same side of the cord as Türck's column, or the direct pyramidal tract. This decussates along the whole cord through the anterior commisure with the crossed pyramidal tract of the other side. Türck's column ends by the middle of the dorsal region while the crossed tract descends as far as the third sacral. The fibres of these motor tracts pass into the grey matter and thence out as anterior nerve roots, or become connected with nerve cells in the anterior cornua.
Besides the motor and sensory conducting paths in the spinal cord there are also inhibitory, trophic, and vasomotor strands, as well as numerous centres for reflex action.
As an abeyance of reflex action owing to a break in the reflex arc caused by disease is a prominent symptom in tabes dorsalis a knowledge of the seat of the various reflex centres is of importance.
In the lumbar portion of the cord are the reflex centres for the plantar, gluteal and cremasteric reflexes, also the centres of deprecation, micturition and parturition, with the sexual centre and that for movements of the lower limbs. Somewhat higher in the cord are the centres for the abdominal and epigastric reflex. In the upper dorsal and lower cervical regions are centres for the scapular reflex and the dilator movements of the pupil (cilio spinal region). Within the dorsal region are centres connected with the stomach and intestines. In the cervical region are centres for the movement of the arms and upper part of the trunk.
Within the medulla are the respiratory vasomotor and cardio-inhibitory centres and centres for deglutition and vomiting. There is also the salivary centre and the centres for polyuria and glycosuria.
In writing this short epitome of what is known concerning the conducting paths of the motor and sensory impulses, I must acknowledge my indebtedness to the anatomical chapters at the commencement of Professor Grainger Stewart's "Introduction to the study of the nervous diseases", as well as the Turner's Anatomy, Foster's Physiology, and Byrom Bramwell's work upon spinal cord.
There is one other anatomical point about the cord which is of the highest importance in connection with this thesis. That is the origin and nature of its vascular supply. This vascular supply is carried out by slender vessels which come from the vertebral arteries within the cranium. There is one vessel in the front and two in the back of the cord. These vessels are very slender and yet have to run the whole length of the cord. No arteries so small run the same distance in any other part of the body, and pressure falls rapidly in minute arteries as the length of the pipe increases. In order to relieve the strain upon these vessels, some help is given by small reinforcing twigs which run along the nerve roots and so to the cord. Now in the cervical region where the roots are short this double supply should work well, but in the lower part where the long slender vessels have to climb up the strands of the cauda equina, the amount of blood conveyed is proportionately decreased, and that at the very spot where the supply coming from above is at a minimum.
Hence to quote Dr Moxon in his Croonian lectures of 1881 ("On the influence of the circulation on the nervous system"), "The upper parts of the cord have a better sustained supply both from above and below than the lower, and the part corresponding to the lower limbs and sphincters is the most weakly organised of all".
Or in other words, and this is a point upon which too great stress cannot be laid, if the whole circulatory system were subjected to some weakening influence, such as a narrowing of its arterioles or any other change tending to decrease its power of conveying nutrition, the first part to break down under the strain would be that part of the spinal cord which governs the sphincters of lower limbs.
II. The morbid anatomy and pathogenesis of the disease
Having now considered a few points in the anatomy of that portion of the human frame which is most obviously affected by the disease under consideration, we shall pass on to consider the position and nature of the pathological changes which are revealed in it after death. Having described these we can then take a more comprehensive view of the lesion as a whole and consider whether the morbid changes in question are primary in their nature or dependant upon some preceding disturbance of the general economy.
A post-mortem examination of a case of tabes shows the dura mater to be commonly normal, the arachnoid occasionally opaque, and the pia mater congested and thickened in the region of the posterior columns. The spinal fluid has been observed in some cases to be increased, and the trabeculae which traverse the subarachnoid space thicker and more numerous.
The tissue of the posterior columns is decreased in quantity and tougher than in health. In colour it is greyish, yellowish or pink. The morbid changes are most marked in those lower portions of the cord which we have endeavoured to show are most susceptible to vascular influences. As a rule morbid changes do not spread beyond the medulla, but corresponding alterations have been made out in the superficial layers of the pons varolii and the corpora quadrigemina.
For microscopic examination the cord may be hardened in Muller's fluid (one part of sodium sulphate and two and a half of potassium dichromate in a hundred of water), or in osmic acid which stains the myelin sheath of the central nerve fibre, or in ammoniacal solution of carmine as used by Vulpian and Charcot which stains the connective tissue and not the nerve tubular. It is perhaps better simply to freeze the cord in a microtome so as to avoid the possibility of all chemical alterations.
The microscopic examination of an advanced case of tabes shows that the medullary sheaths as well as the nerve tubes of the posterior columns have disappeared, their places being taken by a loose areolar tissue, which may be simply the neuroglia rendered coarser and more fibrous by irritation. Any nerve fibres which remain appear granular, varicose and narrow. Numerous amyloid bodies, the product of nerve disintegration are scattered about.
The arterioles of the posterior columns have undergone a change also. There is a thickening of the adventitia and all the coars even in the smallest capillaries are infiltrated with oil globules and compound granular corpuscles, more particularly the lymphatic space between the outer and middle coats.
A good deal of attention has been directed towards the point as to which area of the cord is primarily affected. Pierret held that the disease began in two different portions of Burdach's column, while Gall's column became affected later. This view was endorsed by Charcot and by Vulpian. It has been modified however by the researches of Strümpell of Leipzig, who has shown that the area primarily affected differs in the various regions of the cord. In the cervical region Gall's columns appear to be involved early in the lesion, while in the dorsal a similar degeneration appears on them early in the disease, but limited to their internal margin. The anterior zone of Burdach's columns remains healthy longest and in typical cases of tabes escapes altogether.
The posterior nerve roots are found to be much wasted, showing a grey or dark discolouration. The fibres may be seen to be destroyed having undergone falty and granular degeneration, the process being most marked in the axis cylinder while the medullary sheaths hold out longer.
The spinal ganglia are not as a rule affected although Luys and Pierret have reported exceptional cases in which there has been some atrophy in them. The central grey matter of the cord however, more especially the posterior cornua are frequently found affected, the sclerosis affecting the nerve tubes and the neuroglia rather than the cells. The anterior cornua are usually healthy although Leyde, has drawn attention to a peculiar tough hard condition of the anterior ganglionic cells which may be connected with those atrophies of muscle which occur in the course of the disease.
The lateral columns are occasionally affected in tabes, but only when the disease is far advanced. It occurs probably not by an extension from the posterior columns but through an entirely separate nerve lesion. Flechsig's direct cerebellar tract is the portion which usually suffers.
Much attention has not been given to the histology of the sympathetic system in cases of tabes. The researches of Raymond and Arthaud show that there are considerable changes in it, thickening of the vessels, proliferation of connective tissue, atrophy of ganglionic cells and fatty degeneration of the nuclei of Remak's fibres.
Besides the preceding changes the nuclei of the cranial nerves more particularly of the optic, the third and fifth are frequently more or less affected.
Having considered the lesion as seen in the cord it remains to be considered whether this lesion is essential to the production of the disease. Modern research has shown that it is not so. Westphal in 1878 was the first to call attention to the peripheral changes occasionally visible in tabes. He found atrophy of the cutaneous branches of the crural nerve in one of this cases. Pierret attributed lightning pains and anaesthesia to a peripheral neuritis of sensory nerves. Pitres and Vaillard have also described peripheral changes resembling Wallerian degeneration which tends to spread centripetally but usually leave the main trunk intact. Dejerine records that in two of his cases the symptoms were equally pronounced. In one after death extensive disease was found of the posterior columns, while in the other no central changes were found at all, but extensive neuritis in the peripheral expansion of the nerves.
An interesting case was quoted at a meeting of the Clinical Society of London on March 7th 1885 by John Hughes Bennett which is worth transcribing here in greater detail. The patient presented during life all the prominent symptoms of tabes, including incoordination of movement, an ataxic gait, Romberg's symptoms, impaired sensibility of the lower limbs, lancinating pains and loss of the knee-jerk. After death the cord itself was found to be perfectly healthy. Outside the membranes however the spinal nerves in the dorsal and lumbar regions were involved in a sarcomatous mass. This was a pathological conformation of the experiments of Von Deen and Claude Bernard who by dividing the posterior roots induced incoordination without motor paralysis. A similar conclusion was pointed at by the researchers of [Virrodt] and [Hegel] who showed that by freezing the soles of the feet all power of coordination was lost.
On the other hand Langerhans has examined the touch corpuscles in several cases of anaesthesia without detecting any alteration in them. The evidence however is conclusive that cases resembling tabes dorsalis in every particular may occur without their being any central lesion to account for the symptoms.
Duchenne, the original investigator of the disease and more recently Neftel of New York have asserted that tabes is a lesion of the brain, or rather of the cerebellum. All pathological research and clinical experience is against this view however so that it may be put to one side.
Another theory of the disease which has been hazarded is that its starting point lies in the sympathetic system. This view is supported by no great name, and is somewhat disparagingly alluded to by Dr Julius Althaus in his recent work upon diseases of the spinal cord. "Even supposing" he remarks “that there should be a constant and well demonstrated change in the sympathetic system, it would be impossible to explain why this should lead only to the posterior columns of the cord and no other portion of it". The object of this essay is to attempt this "impossibility" and to show that given a certain condition of the sympathetic system it is just exactly in the posterior columns of the cord that we should expect to find the very changes which we do find there.
Tacász and others have thought the primary lesion was a degeneration of the posterior nerve roots which ascends until it implicates the cord itself. Many observers however have observed well marked disease of the columns before any degeneration of the roots, which negatives this view.
Herbert Page (Brain Oct 1883) has endeavoured to trace a connection between corns and tabes. In this view he thinks he is supported by the researches of Pitres and Vaillard already mentioned. It is a fact that corns are often conspicuous in tabid patients and that the seat of corn is frequently the starting point of a perforating ulcer. It is more probable however that the corns are the result of the tabes than that the tabes springs from the corn. In any case in the majority of cases of tabes no such exciting cause can be shown, so that even granting that in exceptional case the peripheral irritation of a corn might give rise to central disturbance, it cannot be quoted as a theory of the pathogenesis of tabes.
Some observers have thought that the original lesion might be lepto-meningitis, the inflammation spreading from the posterior as part of the pia spinalis to the posterior columns. This has been disproved by careful investigations of Strümpell and Tuczek who have shown conclusively that in early stages of the disease the columns are affected and not the membrane. No relation has been proved either between the amount of inflammation in the membranes and that in the columns.
On the supposition that tabes is primarily a disease of the posterior columns of the spinal cord, considerable differences of opinion have arisen as to which element of the cord is first affected.
Ordoñez has put forward a theory that the blood vessels are the starting point of the disease. He pointed out that in tabes it was common to find the arterioles thickened and blocked up with oil globules and granular corpuscles in such a manner as must interfere with the nutritive functions of the vessels. On the other hand Vaillard and others have asserted that these changes are by no means constant and that considering the effect upon vessels of the experimental section of nerves as done by Waller, the changes in the vessels are more likely to be an effect than a cause.
Bevan Lewis has recently published an account of his microscopical examination of one of Buzzard's cases which appears to hear out the veins of Ordoñez. In this case he found ample evidence of periarteritis in the spinal vessels. These vessels were numerous and dilated, with thickened and diseased coats, each one of them being the centre of a patch of sclerosis. In vertical section ampullar enlargements were seen along the course of the vessels and groups of large nucleated cells seen in their perivascular sheaths. In this case it was evident that arterial changes had played a prominent part in the disease.
Another theory with which Adamkiewicz has identified himself considers that the primary lesion is a degeneration of the interstitial connective tissue and subsequent atrophy of the nerve tissue fibres. In this case the lesion would be analogous to cirrhosis of the liver, and the supposition would accord with the syphilitic theory of the disease.
An objection to this theory is that in certain forms of interstitial inflammation of peripheral nerves where the connective tissue is undoubtedly affected there is no wholesale destruction of nerve fibres as we find in the cord in tabes. The balance of pathological evidence is also opposed to the theory of an interstitial origin of tabes.
The theory usually accepted is that the primary lesion occurs in the nerve fibres themselves. The axis cylinder appears to be the first to suffer. It atrophies, the nuclei of the nerve fibres swell and multiply while the myelin sheath becomes segmented and eventually degenerates entirely. The irritation extends to the surrounding connective tissue which exhibits a multiplication of the cells and a proliferation of its fibres. It is at this stage that the coats of the blood vessels are supposed to participate in the disease.
This theory of the initial lesion in the disease may be applicable to the changes which occur in the spinal cord and which interrupt the current of sensation and by doing so interrupt threw the reflex mechanism out of fear and do away with the co-ordination of movement. It may also explain, by the irritating changes occurring around the posterior roots, those terrible pains which are such a distinctive feature of the disease. No light is thrown however upon the strange evanescent paralyses occurring often years before the appearance of any spinal disease. Neither does it helps us to understand the lesions in the nerves of special sensation, nor the gastric and other crises which also occur frequently in the malady. Above all it does not help us to explain why the posterior columns of the cord, especially in its lower segments should be the principal seat of morbid changes. On all these points we are as ignorant as when Duchenne a quarter of century ago first picked the disease out of the chaos when then existed among all things nervous and gave it an individuality of its own.
III. The clinical symptoms of Tabes
Having now discussed briefly the region of the human frame in which the effects of tabes are most visible and having described the morbid changes which are visible in this region, and given a short summary of the various views put forward to account for the disease, it may be as well to run over the clinical symptoms visible in an ideal case of tabes.
The sufferer is commonly a man of between five and twenty and fifty. In many cases he is of that swarthy neurotic type which furnishes the world with an undue proportion of poets, musicians and madmen. In nine cases out of ten he has had syphilis, possibly a year ago, more probably four, eight, twelve or even twenty years before.
Eye symptoms are very commonly the first to drive the patient to seek medical advice. His wife calls his attention to the fact that he has developed a squint, or he finds a dimness come over his sight and the lines of his morning paper become blurred and blotted. Very commonly one of his eyelids drop and he finds he cannot raise it. His medical adviser on examining his eye sight finds that the visual angle is contracted, that scotomata or blurred patches occur in the circle of vision, and that the pupil which has perhaps been mydriatic is now myotic. Examination shows him also perhaps that this pupil while accommodating itself for distance, does not answer to the stimulus of light. Atropia may not cause it to dilate. An ophthalmoscopic examination may show atrophy of the optic nerve, the arteries being reduced in size and the disc grey and diminished.
There are no more constant symptoms in tabes than the pupillary ones. Vincent found them in 47 cases out of 51.
The patient returns home after this examination and may notice little or no change in his condition for years. Various little symptoms show him however that the demon which has seized him has not relaxed its grip. He may have fleeting attacks of facial neuralgia and even of facial paralysis. Strange flashes come over him and he perspires profusely without obvious cause. Numbness and pricklings alternate in different parts of his frame. His sexual desire which has possibly for some time back been inordinate begins to wane. Vague pains which have been flitting about his lower limbs and which he has probably ascribed to rheumatism, become more intense and sudden in their character until he can only compare them to electric shocks.
The sufferer's appetite has been probably capricious for sometime back and his digestion uncertain. Suddenly some day after a meal he is seized by an irresistible attack of nausea. He vomits for hours, throwing up not only all that he has eaten but also many pints of a clear mucoid fluid, occasionally stained with blood or mixed with bile. The attack continues until he is utterly exhausted. This is a gastric crisis. Or it may be a violent attack of diarrhea with tenesmus and innumerable watery stolls. Or it may be a sudden cough with difficulty of breathing, simulating whooping cough and going to such a length that the sufferer becomes black in the face and may even expire of apnea in the paroxysms. These latter are the intestinal and laryngeal crises.
For some time the friends of the patient have observed an uncertainty in his gait, which continues until walking becomes a matter of difficulty. He himself makes the discovery some night that without a light he is helpless, and falls to the ground. With this fresh budget of symptoms he seeks his medical man once more.
On examination the latter finds that the knee-jerk is gone, and possibly the cremasteric and gluteal reflexes as well. On being asked to shut his eyes the patient lotters. There is no loss of muscular power, beyond that which is inevitable in a long illness.
After this, presuming the disease continues to run its course without check the foregoing symptoms increase in severity while others gradually develop themselves. A feeling of constant constriction round the waist or under the armpits is a common phenomenon. Renal crisis in which great quantities of pale urine of low specific gravity is passed are rarer. The victim seldom escapes vesical troubles however, with cystitis and a constant desire to micturate, or the bladder may be sluggish so that there is no desire to micturate, or there may be vesical crises causing intolerable agony during many hours.
Occasionally stranger symptoms may come upon the sufferer. A small raw spot upon the plantar aspect of his foot may deepen and enlarge until a perforating ulcer is established. Or certain of his joints may become flooded by a sudden copious effusion, which rapidly bursts the ligaments, destroys the joint and causes atrophy of the articular ends of the bones. Or there may be changes in the shafts of the bones themselves by which they are rendered brittle and liable to fracture.
The skin during this time has been pallid dry and cold, and subject to various eruptions, to herpes, pemphigus, erythema, and a condition resembling ichthyosis.
As the disease progresses the sufferer gets some relief from pain, the sudden shocks dying away and being replaced by analgesia and anesthesia. Motor paralysis and acute muscular atrophy may supervene. Slowly the unfortunate victim sinks from one gradation of misery to another and can only look forward to the death which may reach him from pure exhaustion or may come from the involvement of the vital centres in the medulla. Here are the words of Heine the great German Jewish port when after seven years of this torture he saw the shades of death gather round his couch. They are interesting as showing the thoughts evolved by a great brain when linked to what was practically a dead body.
"Do I really exist" he writes "My body is so shrunken than I am hardly anything but a voice. In my mattress grace in the great city I hear early and late nothing but the noise of vehicles, hammering, quarrelling and piano-strumming. A grave without repose, death without the privileges of the dead who at least need not spend any money nor write letters or books - that is indeed a pitiful condition. Long ago the measure has been taken for my coffin and my obituary, but I die so slowly that the process is tedious for myself as well as my friends. Whats avails me that youths and maidens crown my marble bust with laurel when the withered hands of an aged hag are putting blisters behind my ears. What avails me the incense of the roses of Shiraz when in the wearisome loneliness of my sick room I get no perfume but the smell of hot towels? But patience, everything has an end! You will one day find the booth closed where the puppet show of my humour has so often delighted you."
IV. Vascular and vasomotor peculiarities in tabes
In a previous portion of this thesis the fact has been pointed out that given a general derangement of the whole vascular system by which its nourishing qualities should be impaired all over the body, the point at which this morbid condition would first show itself would probably be in the lower dorsal and lumbar portion of the cord. The reason for this is, as has been shown, that the vascular supply of that region is carried on under exceptional disadvantages, the vessels from above being longer and more slender than any others in the body, while from below the reinforcing branches which accompany the nerve roots are much longer and therefore weaker than those of the superior segments of the cord.
Not only might it be predicted that a vascular derangement would show itself in that region, but the posterior portion of the cord might be foretold to be the area in which such changes would first appear. The reason if this is that that the vascular supply of the front of the cord is furnished from above by a single larger artery, while the posterior portion is nourished by two smaller ones, the total supply of which is not greater than that conveyed through the single anterior vessel. Now presuming that a vasomotor influence was at work (as I hope to show there is, through another chain of reasoning) it would tell more upon the part which is nourished by the two small arteries than that which depends upon the single larger one, for the smaller vessels are more susceptible to vasomotor influence and their contraction would therefore reduce the blood supply in the posterior portion of the cord more than it would be reduced in the anterior part, even though the artery there had responded also to the vasomotor stimulus.
Now looking at the fact that the vascular arrangement of the cord is such that its weakest portion is in the posterior part of the lower dorsal and lumbar regions, and that this is the very spot which is most frequently and most obviously the seat of the morbid changes in tabes dorsalis, then it is so very wild flight of fancy to as surmise that there may be an intimate connection between vascular derangement and the disease in question.
If however we can prove that by the use of a drug the main action of which is to contract small arteries both clinical symptoms and pathological appearances can be produced by no means discernible from tabes dorsalis than I think that our surmise becomes almost a certainty. On the one hand we have anatomical reasoning to show that this portion of the cord is the one which is most susceptible to vascular changes. On the other we should have proved that a substance producing vascular changes does affect that portion of the cord, and affect it in an exactly similar manner to the disease with which we have to deal. If the second proposition be established the double chain of reasoning which links tabes and vascular derangement together appears to me to be irresistible.
The peculiar influence exercised by ergot upon the spinal cord has been long recognised. When bread contaminated with ergot of rye is taken for sometime either gangrene of the extremities may set in, or a peculiar disease identical with tabes. Tuezek has had opportunities as recently as 1879 of studying an outbreak of this disease in Frankenberg in Hesse when as much as ten per cent of the flour was found to consist of ergot of rye.
In the majority of these cases the clinical symptoms were numbness, pins and needles, lightning pains, girdle pain, analgesia, staggering on closing the eyes (Bauch-Romberg's symptom) and loss of the patellar reflex (Wiesberg's / Westphal's symptom). The pupils were usually dilated. This the symptoms were identical with those of ordinary tabes dorsalis.
A histological examination of the cord proved that the pathological lesion was what might have been expected. Burdach's columns were found to be sclerosed and in some cases Gall's were also slightly affected. The lateral and anterior columns were normal. There were numerous corpora amylacea. The principal changes in the cord appeared to be atrophy of the nerve fibres and overgrowth of the neuroglia.
Dr. R. Robert of Strasburg has within the last few months published in the "archiv für experimentalle Pathologie und Pharmakologie" some researches of his upon the active principles of ergot which throw some light upon which of them it is which has this remarkable effect upon the human spinal cord. He has obtained three bodies from ergot, ergotinic acid, cornutin and sphacelinic acid.
Ergotinic acid appears to be a powerful depressant, causing narcosis, paralysis of the cord, and stoppage of respiration. Being a glucoside however it is split up into sugar and an inert base in the alimentary canal, so that its action unless it is injected is of no practical importance.
Sphacelinic acid to the constituent of ergot which gives rise to the characteristic gangrene. Locks when dosed with it rapidly lost their combs which turned black and dropped off. Intestinal derangement and profuse watery diarrhea was a frequent result of a dose.
Sphacelinic acid, according to Dr. Robert by its action on the vasomotor centre causes a spasmodic contraction of the arterioles and raises the blood pressure. He found that continuous small doses of the acid caused changes in the spinal cord with the result that the animal showed an ataxic gait and lost all power of coordination.
Thus we arrive at the fact a substance which causes excitement of the sympathetic system and consequent constriction of vessels will also have the effect of causing changes in the spinal cord leading to ataxic symptoms.
Cornutin is a new alkaloid which was discovered by Dr. Robert in the course of his researches. It is a poison causing tonic and clonic spasms and epileptiform convulsions. It's presence explains the epileptic attacks which have been constantly observed as concomitants of every epidermic of ergotism.
It is still an open question whether ergot acts directly upon the vascular walls or whether it acts through the nervous system. The balance of evidence is rather in favour of its acting through the vasomotor system, when the power of the drug over involuntary muscular fibres is considered. In any case the undeniable fact remains that however produced it's action is to cause spasm and of the arterioles and to raise pressure, and that this physiological action brings about among other changes, a morbid condition of the posterior columns of the spinal cord.
Looking at the matter from two entirely different points of view then, an anatomical and a therapeutic we find ourselves led to the same conclusion, namely that an exciting influence in the system which shall act upon the vasomotor centre and produce constriction of the small arterioles, will produce all the symptoms of tabes dorsalis. Considering that no other influence as far as we know will have this effect, and that there is no other feasible explanation for the particular seat of this lesion, we may take the converse of the foregoing statement and formulate the opinion
that tabes dorsalis is produced by some influence in the human frame which excites the sympathetic system and so causes constriction of the small arterioles.
Looking at the symptoms of tabes dorsalis from this new standpoint two very distinct stages can be made out, corresponding roughly with the first and second stages of Duchenne. The first is the stage of sympathetic excitement, the second the stage of sympathetic paralysis. The first might be called the stage of the dilated pupil and the second the stage of the contracted pupil.
Let us take this theory of the diseases and follow the sequence of events implied by it and one how it tallies with the actual facts of the disease.
Presuming the existence of an exciting influence in the human frame, this influence being probably the syphilitic poison in the case of tabes, it may be very long before it shows its influence upon the arterioles. In the case of ergot it was not uncommon for the ergotinic tabes to become developed long after the diseased rye had been eaten. During all that time no doubt nutrition had been to some extent impaired but so gradually that it took months or years for the system to break down under it.
This malnutrition would show itself first as has been already explained in the lower part of the spinal cord, that being the weakest point of the vascular system. It would not confine itself to that point however but being a general process would show itself more or less in every part, the most susceptible suffering first. Thus the whole of the spinal cord would in time show traces of the morbid action, the process travelling from below upwards so fresh segments found the effect of a curtailed blood supply. Why the posterior column should be most sensitive to vascular changes it is impossible in the present state of our knowledge to say. The action of ergot indicates that it is so. Possibly the reason already put forward that its nutrition depends upon two small vessels instead of the one larger one in front, may have something to do with it.
While these changes are going in the cord we should expect to have symptoms of vasomotor derangement in other parts of the body. More particularly we should imagine that the nerve centres would be highly sensitive to any interference with their blood supply, and would either show signs of deranged action or become entirely paralyzed. Accordingly in the early stages of tabes we find many signs of derangement of the nervous centres. The first is more rarely affected than some others, but anosmia is not a very uncommon symptom. In the optic nerve various conditions have been observed some pointing to central and some to peripheral changes. These peripheral changes when they take the shape of amblyopia, or atrophy of the optic nerve are most important to our argument. Here through the ophthalmoscope we can actually see those changes going on the existence of which we have been endeavouring to establish by reasoning an deduction. What could throw more light upon the general condition which leads to tabes than the examination of the disc of a tabid patient? Here the very process is going on which is occurring in his spinal cord. There are no traces of inflammatory changes. The edges of the disc are clean-cut and well defined with none of that blurred appearance which characterizes optic neuritis. The arterioles however are notably lessened in calibre, with the result of giving the disc a whitish greyish appearance. On account of the diminished blood supply the nerve fibrils degenerate and break down, while the neuroglia being a less sensitive element than the actual nerve tissue shows the impairment of its nutrition by changing its character and becoming coarser and more fibrous. At the same time the attenuated arteries of the retina show that this contraction of vessels is not confined to the trunk of the nerve but is a general condition.
The third nerve is frequently involved early in the disease, as is shown by ptosis resulting from paralysis of its branch which supplies the levator palpebrae superiosis. Recent experiments of Bechterew have shown that the reflectory centres for the nerve fibres which contract the pupils are situated in the nucleus of the third nerve. It is probable therefore that the myosis so common in the later stages of tabes depends upon excitement of this nucleus as well as upon sympathetic paralysis.
Signs of changes in the nuclei of the fourth and sixth nerves are not uncommon, as shown by paresis or paralysis of the recti externi or interni and the appearance of a convergent squint.
The fifth nerve shows signs of derangement early in the course of the disease. Lightning pains frequently occur along its course. Anesthesia of the head and face is also a common symptom.
The auditory centre is frequently affected, tinnitus aurium and complete deafness being not uncommon.
The partis dura and the glosso-pharyngeal are not involved so frequently as the others, nor to the spinal accessory. The pneumogastric however shows signs of excitement along all its branches — which signs may however be due to other causes.
Now in the case of all these derangements of nervous mechanism, many of which are temporary, passing away and then recurring again, what possible explanation can account for them except that of vasomotor changes in the nuclei. From what we know of the vasomotor centre and system we know that it acts spasmodically rather than continuously. The variations of the blood supply in the nerve nuclei brought about by these sympathetic influences would fully account for these sudden fleeting paralyses of motor nerves, and shocks of pain in sensory ones. This, the only explanation which appears to cover the facts, will tally exactly with the view which we have arrived at as to the nature of the changes going on in the spinal cord and also with the appearances which we actually observed in the ophthalmoscopic examination of the optic disc.
The brain is so vascular an organ that a general contraction of arterioles would not affect it to any great extent, beyond rendering it sluggish and impairing its general efficacy. Nevertheless in many cases temporary aphasia, monophagia and hemiplegia which can only be due to vasomotor changes show that it participates in the general condition. Lecoq dwells upon peculiar apoplectiform attacks which he has observed in the course of the disease and which are due no doubt to the same cause.
Thus the condition of the brain and of all the cranial nerves support the view of tabes which is founded upon the study of the anatomy of the cord and upon the action of ergot as a poison. There is another test we may apply. In addition to malnutrition of the nervous centres as a consequence of the constriction of arterioles, we should expect to find signs of impaired vitality in the body itself. Such changes would naturally be looked for in the foot as being the portion furthest removed from the circulatory centre.
This link in the chain of evidence is supplied by the perforating ulcer of the foot, a symptom which often appears early in the disease and in one case quoted by Althaus was the first thing to draw attention to the patient's condition. It is a symptom analogous to those gangrenes of the extremities which appear in ergot poisoning. The constriction of the arterioles upon which we have founded our argument is sufficient to cause functional and eventually organic change in sensitive nerve centres, but is not as a rule enough to cause the coarser tissues of the body to undergo any marked change. In the case of the aged however or in those whose circulation is naturally weak the condition of affairs is different and the extremities of the body may lose their vitality to such an extent as to become gangrenous. It is in the aged usually the t the symptom of perforating ulcer is seen and it is associated often with a tendency to acute bedsores which shows that it depends upon a general rather than a local condition.
There is a case which was read by Mr. Pepper before the Clinical Society of London which illustrates this view of perforating ulcer. The woman complained of 'stinging sensations' all over her body. There was anaesthesia of both feet and loss of the patellar reflex, with partial ptosis of both eyes. A sinus in one of her feet led through a mass of heaped-up epithelium down towards the second metatarsal bone. Shortly after her entrance into hospital there was gangrene and sloughing of the skin upon the dorsum of the foot, which went so far that the foot had to be amputated. For four days after that all went well, then the heel flap sloughed away, bedsores formed rapidly over the sacrum, the lower part of the stump became black and the patient died exhausted. After death extensive degeneration of the posterior columns was found, proving the case to have been a genuine one of tabes dorsalis. The patient was sixty years of age.
In this case it was evident that the perforating ulcer and the subsequent gangrene did not depend upon any lesion of the local trophic nerves, because similar changes were going on in the back, producing acute bedsores. The result can only be attributed to impaired circulation, and the sequence of events in the foot was exactly what would have been expected in a case of senile gangrene with atheromatous arteries.
In the cord, the nerve nuclei, the brains, the peripheral end of the optic nerve and in the foot we have symptoms all of which are consistent with the idea of excitement of the sympathetic nerve and consequent contraction of arterioles. Apart however from the vasomotor action we have other indications of sympathetic irritation.
One of the chief of these is the dilation of the pupil which almost invariably ushers in the disease. The radiating fibres of the iris are supplied by sympathetic branches from the lenticular ganglion. By their irritation the pupil is widely dilated, an effect which is encreased if there is any accompanying paresis of the third nerve which supplies the circular fibres. Later on in the second stage the sympathetic nerve becomes paralyzed and the third nerve acting unopposed produces the myosis which is characteristic. The same effect is to be observed in ergotinic tabes the pupil being largely dilated at first and afterwards myotic. The condition of the pupil may be taken as an index of the state of the sympathetic nervous system.
It has frequently been remarked that in tabes the pulse rate is frequently permanently encreased, averaging from a hundred to a hundred and twenty per minute. This has been ascribed to a paralysis of the inhibitory branch of the vagus. It is quite as probable however and more in consonance with the train of symptoms cited already that the encrease in the pulse rate is due to the stimulation of the accelerans branch from the cervical sympathetic ganglia. This seems the more probable as it has been recorded that at the period of gastric and other crises the pulse rate slows down, sometimes to the extent of thirty a minute. How the phenomena of gastric crises can only be due, according to the theory of the sympathetic origin of tabes, from a sudden paralysis of the vasomotor nerves supervening upon their excited condition. Thus the membrane of the alimentary tract which had been anaemic from the contraction of its arterioles, becomes in a moment extremely vascular and congested, gastric juice is poured out in great quantities, the organ becomes irritable owing to the sudden change, and there is persistent reaching, during which great quantities of the acid juice are thrown up. What we may see upon the surface in some of those rare cases in which there are crises of perspiration bears out this view of the cause of these phenomena. The skin in some cases of Pitres' which I hope to refer to afterwards was intensely hyperaemic in the perspiring region, showing every symptom of the condition being caused by vascular change. What better confirmation could there be of this view than the sudden change from an abnormally high to an abnormally low pulse rate. The former testified to the accelerating influence of the excited sympathetic system upon the heart, and just at the moment when other symptoms lead us to suppose that stimulating influence to be paralyzed we find the pulse change its character completely exactly as we should expect to do were the heart under the unopposed inhibitory influence of the vagus.
In accordance with this theory of the disease the first stage of tabes is marked by a contraction of all the systemic arterioles and a consequent impairment of nutrition. In the second stage the vasomotor system is paralyzed and the vessels are dilated. There have been however such morbid changes by that time in the vascular coats, owing to the vasa vasorum being involved in the general attenuation of vessels, that the passage of nutrient serum is interfered with and the parts around are no better off than when the vessels were constricted.
Taking the cord as being the part which is most affected by vascular change we may trace the sequence of events in it. For a long time the vessels become gradually narrower and smaller, with perhaps occasional short returns to their original calibre, for nervous influences seldom act continuously. This prolonged malnutrition tells first upon the highly-organised nervous elements in the posterior column — that being, as has been shown by studying the action of ergot, the part of the cord which is most sensitive to vascular influences. The nerve fibres begin to atrophy, to break up and to disintegrate as they do in Wallerian degeneration. In the meantime the delicate neuroglia alas feels the effect of impaired nutrition. It becomes coarse and fibrous, and takes the place to some extent of the atrophied nerve tissues.
- Medical Bachelor, Chirurgiae Magistrum