The Relation of the Nervous Sys- 
tem to Haemophilia, Malarial 
Haematuria, Etc. 
SECOND PAPER. 
By C. H. Hughes, M. D., St. Louis. 
Reprint from The Alienist and Neurologist, July, 1887. The Relation of the Nervous System to 
Haemophilia, Malarial Haematuria, 
etc.* 
SECOND PAPER. 
C. H. Hughes, M. D., St. Louis. 
TN a paper read before this society, in November, 1884, 
after having shown from the testimony of all observa- 
tion and the best accepted authority, that there is no 
constant capillary degeneration or microscopically discov- 
erable blood change in this affection, I characterized it as 
an hereditary or congenital neuropathic affection of the 
sympathetic system, in the following introductory lan- 
guage : 
We must look, therefore, tothe sympathetic system, of which the most 
important is the vasomotor nerves and their nerve center, for an intelligible 
explanation of the phenomena of hemorrapbilia, for under the healthy 
influence of the sympathetic fibers distributed to the arterial walls, these 
blood-vessels are kept in a state of normal tonic contraction and contracti- 
bility. The tonic contraction of the muscular coats of the arteries, even to 
the smallest arterioles, as they ramify and are lost in the minuter capillary 
system, divested of their external coat of connective tissue, and finally of 
their middle muscular coat, to the fusiform transformation of its fibers’, is 
under nervous influence; and although the terminal branches of the sym- 
pathetic nerve, like the muscular coat of the arteriole, may no longer be 
traced in the capillaries, the capillary circulation is under the influence of 
the nervous system, not only through the vis a tergo of the heart’s pulsat- 
ing impulse, which, by multiform ramifications has been modified into a 
continuous flow, but by the reciprocal contraction with propulsive power 
of the arterial walls. 
“The sympathetic nerves exert an influence on the muscular coats of 
the arteries similar to that of the cerebro-spinal nerves on the voluntary 
muscles ” They cause contraction of these vessels, a diminished flow of 
blood through them, if stimulated, and relaxation and an increased flow 
through them if divided or lowered in vital tone. 
If the flow of blood in a terminal arteriole is augmented through 
diminished contractile power and consequent dilation or dilatability of its 
walls, there will of course be a flushed capillary or distensible arteriole 
system, ready to burst or bleed profusely under slighter causes than 
* Read before the St. Louis Medical Society, Apiil 16, 18»7. 
2 Hcemophilia. 
3 
would excite bleeding in a capillary system supplied by arterioles possessed 
of greater integrity. 
In haemophilia it is the impairment or comparative paresis of the 
habitual tonic contraction of the arterioles, the diminished tone of the 
circular fibers, which are the capillary sphincters as much so as the ordi- 
nary sphincters, which keep certain outlets of the body closed without 
voluntary effort, that is at fault. It is this weakened influence of the vaso- 
motor power that permits certain other forms of hemorrhage of this kind, 
as of the stigmata. The suspended tonicity, as Dalton calls if, permits of 
the “ action of an arrest.” 
Section of the sympathetic fibers of the carotid plexus, for example, 
which go to the distributions of this artery, causes relaxation of the blood- 
vessels, increased circulation, reddening of the venous blood, and increased 
salivation, while galvanization of their peripheral extremities precisely re- 
verses results through excited contractility. 
The effect of dividing the sympathetic, then, is to paralyze the mus- 
cular coats of arteries supplied by its filaments. “Owing to the paralysis, 
the arteries no longer offer their customary resistance to the blood-pres- 
sure coming from the heart. Their relaxation admits a larger quantity to 
the capillaries of the corresponding regions, and the causes are increased 
local circulation.” Somewhere in the spinal cord and in the medulla ob- 
longata, extending perhaps a little above (Schiff and others), nearly to the 
tubercula quadrigemina, but not to include them, or more widely scattered 
in the cerebrospinal axis (Brown-Sequard, Vulpian and others), as shown 
by the influence of cross-sections upon vascular tonicity, is the nerve cen- 
ter which is probably chiefly at fault in the hemorrhagic diathesis, and this 
condition is amenable to such treatment as will impart tone and restore 
the vasomotor vigor which in this disease seems impaired.— Vide Weakly 
Medical Review, December 20tli, 1881, pp. 517, 518. 
Wickham Legg, in his article on the subject of 
Haemophilia, in Quain’s “ Dictionary,” speaks thus of the 
anatomical characteristics, or rather of their absence, in 
this disease: “ No morbid appearances have yet been 
found with any constancy. The blood-vessels examined 
with the microscope have shown no change. The blood 
is apparently unaltered.” 
This I consider the true characteristic of haemophilia. 
Neither the vessels nor the blood show a characteristic 
change, while in all other hemorrhages there is either a 
vascular wall or a blood change to account for the mor- 
bid phenomena, and this justifies us in locating the 
disease in the only organism which can justly be held 
accountable for the abnormal phenomenon. If the agents 
are not at fault we must look for the failure in the 4 
C. H. Hughes. 
principle, and hold the power which might prevent the 
hemorrhage—the arteriole walls and blood being healthy' 
—accountable for the lapsus morbi. 
If neither the structure of the capillary walls, dissevered' 
from their nervous connection, nor the normal consistency 
of the blood is at fault, then we must find in the mech- 
anism of nervous control the true causa morbi; and we 
need not, in order to understand this disease, here 
discuss the question whether there are vaso-dilators in 
the capillaries which overcome the weakened vaso-con- 
strictors, or whether the power of contractility resides 
inherently in the arteriole walls without the necessity of 
nervous influence, as Poole, contrary to the popular view, 
maintains. 
The fact is, in haemophilia the normal contrac- 
tile capacity and arteriole tonicity in the capillary walls 
is so impaired through evidently inherent conditions of 
the ganglionic centers, which preside over vasomotor in- 
hibition, that blood exudes through the meshes of the 
capillary walls under circumstances of local irritation, or 
heart pressure or psychical influences which do not or- 
dinarily cause this phenomenon in the majority of mankind. 
The extraction of a tooth, the prick of the vaccinator’s 
lance, the lancing of a gum or an abscess, the scratch of 
a pin, the bite of a leech, the cutting of the fraenum 
linguae, or the removal of a nasal polypus, a high altitude, 
gymnastic exercise, an over-stimulating meal with wine or 
brandy, which specially strain the capillary arteries and 
weaken vasomotor control, may start a fatal hemorrhage 
in a haemophiliac whose age is an assurance that he has- 
none of those characteristic arteriole degenerations com- 
mon to later life, which dispose to sudden extravasations- 
of blood. 
The early period at which the first evidences of haemo- 
philia appear (often during the first year of life) precludes 
the reasonableness of the conjecture that the disease is- 
due to undetected and undetectable vascular disease. 
Degenerative changes are not only seldom, if ever, found1 Hemophilia. 
5 
at this age, but they would seem to be scarcely possible 
in a child not otherwise profoundly diseased. Hence, 
Legg’s conjecture, that “it is most probably the vessels 
which are at fault, as in most of the other hemorrhagic 
diseases,” about which we have the demonstrations of 
disease, is not justifiable. The fact in regard to hemo- 
philia appears to us to be just the opposite, viz., whereas 
we have in all other hemorrhagic diseases adequate path- 
ological states of the blood or arteries to account for the 
-existence of the hemorrhage, in this disease we detect, 
neither in the blood nor the arteriole wall, any sufficient 
cause. We must, therefore, look to impaired neural control 
of the arteriole caliber, through the vasomotor system, for 
the only sufficient explanation. Under this paresis of the 
sympathetic, so to speak, the arteriole caliber being with- 
out normal inhibitory neural control against dilation, the 
vis a tergo from the heart over-distends to the point of 
abnormal and often fatal exudation the arteriole capillary 
walls and the phenomena of bleeding becomes a possibility 
and a fact, without the necessity of evoking an unseen 
and undetectable disease of the coats of the vessels, or an 
impaired abnormal liquefaction of the blood, to account for it. 
We should find no difficulty in seeing this matter in 
this light were we not too prone to look always to the 
direct seat of a morbid phenomenon for its sole causative 
.explanation. 
This was universal in the medical mind till the phys- 
iological neural phenomena of reflex transmission of symp- 
toms became an accepted fact and had one of its earliest, 
if not its earliest, applications to disease in the knee 
pain symptom of hip-joint disease, followed up by the 
knee phenomena of antero-iateral and posterior spinal 
sclerosis, and in the reflected cardiac and utero-ganglio- 
pathias, and in the gastric and. laryngeal symptoms of 
affections of the medulla and pons. 
Neither the deficiency of fibrin theory, as accepted by 
Wood, Flint, Tanner, and others, nor the “delicate construc- 
tion and vulnerability of the vessels and watery condition 6 
C. H. Hughes. 
of the blood ” idea of Rokitansky are now tenable be- 
cause they have been disproved, and the blood coagulates 
well after being drawn from these patients, especially in 
the early bleeding. It would not be strange, however, if, 
as the period of exhaustion after a prolonged and fatal 
bleeding is reached, the blood should be thinner in 
fibrin; and this may explain why in some cases the 
fibrin has been found deficient. 
After the long continuance of the bleeding and con- 
sequent central nerve exhaustion it would not be strange 
to find the consistency of the blood altered as to the 
normal proportions of fibrin, and even of other essential 
ingredients, and it has so been found in some cases. 
In death from lightning and other violent shock, and 
after section of the pneumogastric nerves, the blood has 
been found to have lost its power of coagulability. 
On October 2ist, 1884, while haemophilia and pur- 
pura were under discussion before the Pathological So- 
ciety of London, Dr. Acland showed some specimens 
taken from a case of haemophilia in a boy aged seven, 
and from a case of purpura in a girl aged thirteen. In 
none of the organs or tissues of the former case which 
were examined were any lesions of the blood-vessels 
found such as have been described, either as regards 
their distribution or structure. No abnormal relation was 
found to exist between the blood supply and the size of 
the vessels; but the blood, which was examined after 
much hemorrhage had taken place, was found to be more 
watery than natural, and the white corpuscles were greatly 
in excess. The tissues round the wound from which the 
fatal hemorrhage took place were healthy. 
At the same meeting, Dr. Wickham Legg said that 
he had read a paper before the society three years ago, 
stating that the examination of the tissues from a case of 
haemophilia had revealed nothing differing from the nat- 
ural state (British Medical Journal, p. 938, Vol. II., 1881). 
The specimens he now showed had been prepared and 
examined by Dr. Klein, who was unable to discover any Hcemophilia. 
7 
change, either in the vessels or tissues. The specimens were 
obtained from the body of a boy who died of epistaxis ; 
diagnosis of haemophilia in this case was very clear, and the 
the family history to some extent characteristic. The ex- 
amination of the tissues had now been made in six cases; 
in four of these cases no change at all had been found ; 
one in which changes were found was a case of exten- 
sive ichthyosis; the other was the case recorded by Dr. 
Percy Kidd, in which extensive changes in vessels were 
observed. Dr. Wickham Legg also showed specimens of 
joints from a case of haemophilia. The condition of the 
joints had previously been observed in one case by Pon- 
cet, in one case by Sir William Jenner, and in one by 
himself; the same appearance was observed in all the 
cases. The first stage consisted in the extravasation 
of blood into the joint without any change in the 
structures of the joint. In the second stage, the synovial 
membrane was of a russet color, and there was slight 
erosion of the cartilage. In the third stage, the synovial 
membrane was deeply dyed and the cartilages exten- 
sively eroded and destroyed, so that the disease of the 
joint would seem to have its origin in the extravasation. 
There is no question about the consequences of ex- 
travasation, but they are simply sequelae; nor need we 
doubt the existence in exceptional cases of accompany- 
ing vascular disease or blood change. It would not be 
unreasonable to expect these at certain times and in cer- 
tain stages, but the general absence of the local evi- 
dences of morbid change is the chief distinctive evidence 
to differentiate haemophilia from purpura haemorrhagica. 
The British Medical Journal, while discussing the 
malady of Prince Leopold, thus candidly states the case, 
.as follows: “We do not know what is the malformation 
or disease which predisposes to such an easy escape of 
,blood from its proper channels. The chemical con- 
stitution of the blood has been thought by some to be 
at fault, the smaller blood-vessels by others; but no 
■chemical or microscopical investigations that have been 8 
C. H. Hughes. 
conducted as yet have been anything but satisfactory, 
and, therefore, have been without result. One curious 
fact, however, has been elicited from various observations 
that have been made, and this is, that it is hereditary 
to a marked degree, and that it is transmitted along the 
male much oftener than along the female line.” 
Let us now again recur to the physiology of our sub 
ject. A little over a century and a half ago (1727) Pour- 
four du Petit, after cutting out the ophthalmic ganglion of 
a dog, observed an increased vascular turgescence to follow 
in the vessels of the eye. The later similar experiments 
of Claude Bernard, Brown-Sequard, and others on the 
cervical sympathetic have so fully confirmed the discovery 
of Petit that the phenomenon has become an accepted 
fact of modern physiology. 
If the ischiatic nerve of a frog be divided the relax- 
ation of the muscular coat of the arteries, on which the dila- 
tation of their caliber by distention with blood depends 
appears to be an effect of a section of special vaso-con- 
strictors, derived from the sympathetic, bound up in the 
ischiatic trunk, and not of fibrils derived from the spinal 
cord. Thus T. Wharton Jones, in a paper on “ The 
State of the Blood and the Blood-vessels in Inflammation,” 
showed, in a communication to the Royal Medical 
and Chirurgical Society, in May, 1883, in the “Medico- 
Chirurgical Transactions,” Vol. XXXV., and “ Guy’s Hos- 
pital Reports,” October, 1853, that if we lay open the lower 
part of the vertebral canal of a frog, and remove the 
roots of the ischiatic nerves with the corresponding por- 
tion of the spinal cord, so that all sensation, voluntary 
motion, and spinal reflex action in the posterior extreme- 
ties are abolished, the walls of the arteries are neverthe- 
less seen, on examination of the webs under the micro- 
scope, to retain their contractility ; nay, they appear even 
more disposed to become contracted, so as to keep up 
greater than ordinary constriction of the caliber of these 
vessels. 
When, now, the trunk itself of the ischiatic nerve in Hmnophilia. 
9 
the thigh, which comprises not only the spinal fibrils,, 
sensitive and motor, the roots of which were with the cor- 
responding portion of the spinal cord destroyed, but also 
fibrils from the sympathetic nerve in the pelvis as yet unin- 
jured, was divided on one side, the skin of the extremity 
subjected to this part of the experiment was seen by the* 
naked eye to become redder from general vascular fulness 
than that of the opposite extremity, and on microscopical 
examination of the web the arteries were observed to be 
relaxed and dilated by distention with full and rapid 
streams of blood injecting the capillaries and venous rad- 
icles. In the web of the opposite extremity, in which the 
trunk of the ischiatic nerve in the thigh was left uninjured, 
the arteries were, on the contrary, seen much constricted, 
some even to closure. This remarkable fact would appear 
to indicate something like the operation of inhibitory nerv- 
ous influence having been arrested by the destruction of 
the spinal roots of the ischiatic nerve and the correspond- 
ing portion of the spinal cord whence they originate, 
leaving the vaso-constrictors derived from the sympathetic 
in uncontrolled action. 
The electric irritation of the chorda tympani nerve 
gives a phenomenon different from that which immediately 
follows the peripheral stimulation of other nerves presiding 
over vascular and glandular supply. In this experiment, 
first performed by Claude Bernard, when the nerve is 
excited by electricity, the arteriole walls of the blood- 
vessels dilate, the submaxillary secretion is accelerated and 
profuse. This is exceptional and may be explained on 
the hypothesis of speedier exhaustion of central inhibition 
than we see elsewhere. 
The effect of a smart blow on the skin or of a sudden 
scald is something like it, but here there is more or less of 
capillary destruction. The action of a blister in its primary 
stimulation and final exhaustion of vasomotor tonicity, fol- 
lowed by relaxation and exudation of serum, is a thera- 
peutic illustration. 
But whatever view we take of the modus operandi of 10 
C. H. Hughes. 
peripheral irritation on the capillary circulation, the fact- 
remains that the movements of the blood current are 
presided over by a central nervous system mainly located 
in the sympathetic chain of ganglia and its fibrils, and 
that whether there be vaso-dilator as well as vaso-con- 
strictor fibers, or only vaso-constrictor fibers, and prob- 
ably inhibitory fibrils going beyond the vasomotor ganglia, 
and if arterioles permit the blood to extrude through their 
walls without our being able to detect appreciable struc- 
tural disease in them or in the blood current, the 
condition that permits this is disease, and this disease- 
can only be in the nervous system. Since the pub- 
lication of my first paper on the subject, and since 
this paper was written (May, 1886), though it is only 
just now given to the medical press, papers have 
appeared accepting this view in part as the proper ex- 
planatory view of its pathology; among them a paper by 
Thomas Oliver, M. R. C. P., in the London Lancet. 
Whatever other pathological co-existences may be 
found, neuropathic or otherwise, in any case, I believe 
the essential pathology of this disease is in defective 
central action on the part of the vasomotor center,, 
a view which Oliver accepts only in part. A defect- 
ive blood condition as to its fibrinous constituents 
and coagulability may precede or follow haemophilia; 
but this is certainly not an invariable or even a common 
causative condition. 
What is true of hsemorrhaphilia is true, in part at least, 
and in the chief part we think, of haemorrhagic malarial 
fever, of purpura haemorrhagica and certain erythemas, 
the two latter, according to E. Wagner, being closely 
related. 
In simple purpura and urticaria, hemorrhage takes 
place in the skin only. In malarial haematuria the san- 
guineous exudate is chiefly into the stroma of the kid- 
neys, the malpighian tufts, and the tubuli uriniferi; but, 
wherever it is, though the more remote cause be malarial Hemophilia. 
11 
toxaemia, the immediate is in the lost vasomotor control 
that allows arterial dilatations and permits of the fatal 
pressure of passive congestion and sanguinuric excretion. 
Dr. W. Allen Jamieson, lecturer on Diseases of the 
Skin, in the Edinburgh School of Medicine, in a review 
discussion of purpura and erythema in the Edinburgh 
Medical Journal for March, expresses the common feeling 
on these subjects when he asks, Why in certain cases of 
tubercular erythema hemorrhage occurs so constantly, so 
quickly, and so severely? and answers, that it cannot be 
explained by the youth of the patients, nor from their 
anaemic conditions; and concludes that, some hitherto 
unknown cause exists, as in haemorrhagic smallpox. That 
hitherto unexplained cause is in the paralysis of vaso- 
.motor control. 
A thoughtful and observant writer in the Texas 
Courier-Record of Medicine, Dr. Jas. A. Abney, of Tufkin, 
Texas, writing on malarial haematuria, strikes the true 
pathology in his second proposition, that, following the 
pre-existing toxaemia, “ the resulting pathological con- 
dition is one of vasomotor depression, with consequent 
'vascular expansion.” 
A survey of other fields of clinical observation, for 
iwhich we have here neither time nor space, serves to 
.-confirm the conviction enunciated by us years ago, that 
the neural pathology is destined to .reign pre-eminent in 
.medical thought.