A STUDY OF MENTAL DISEASES ASSOCIATED WITH CEREBRAL ARTERIO-SCLEROSIS.'

BY ALBERT M. BARRETT, M. D.,

Pathologist and Assistant Physician, Danvers Insane Hospital, and Assistant in Neuropathology in the Harvard University Medical School. (From the Pathological Laboratory of the Danvers Insane Hospital.) At the present time there are three forms of mental disease which seem to be associated with characteristic changes in the central nervous system; these are general paralysis, arterio-sclerotic dementia and less certainly senile dementia. The better understanding of the pathological anatomy of general paralysis and the importance which plasma cell infiltration of the vessel wall is known to play, has cleared the way for the separation of the arterio-sclerotic brain diseases. In the same way the recognition of a senile brain atrophy without arterio-sclerosis shows an independence of two processes, often associated in the brain in the senile period.

Difficulty in the interpretation of the importance of the arteriosclerotic process occurs from the fact that arterio-sclerosis of the cerebral vessels is not uncommon in various forms of mental disease, especially of the later years of life, and that undoubtedly arterio-sclerosis of the cerebral vessels may be present without recognizable mental disease. There are however certain forms of mental disturbance which clinically show such a prominence of symptoms referable to focal or diffuse vascular brain disease, and which anatomically are associated with destructive lesions of the brain due to diseased vessels that they may be grouped among the psychoses due to organic brain disease as a special group of arterio-sclerotic dementia.

The dementia associated with coarse vascular lesions such as hæmorrhage and softening has long been a familiar type and these cases have been described in the text-books as post-paralytic dementia, post-apoplectic dementia and as arterio-sclerotic

'Read before the Boston Society of Psychiatry and Neurology.

dementia. After separating out from this type of cases those in which the disease is of embolic origin and no arterio-sclerotic brain disease demonstrable, it will be found that most cases of coarse lesion at the same time are associated with arterio-sclerosis of the finer vessels and with greater or less destruction of the cortical nervous elements. This supports the view that the mental disturbance of these cases may be due more to the finer changes in the cortex than to the coarser deeper-lying lesions. In addition to these cases there have been more recently described other varieties of arterio-sclerotic brain disease. Alzheimer' in 1902, described four groups of cases in which the mental process is associated with arterio-sclerotic brain disease. All of these groups are, however, but varieties of one arterio-sclerotic process.

I. Arterio-sclerotic brain atrophy which clinically may course. in two ways; there may be what he calls minor nervous symptoms in which the process lacks the progressive character of the other type. The symptoms are less severe, there is a pronounced increase of mental fatigue and there occurs memory weakness, headache, and dizzy attacks. Anatomically there is present a severe sclerosis of the arteries with very slight gross changes in the brain. Microscopically there is an absence of marked focal disintegration of nervous tissue, little more than pigment atrophy of the ganglion cells, with scattered proliferative phenomena in the glia cells of the cortex and an increase of glia fibers about the vessels.

The second type is that of a severe progressive arterio-sclerotic brain degeneration, which in its beginning may resemble the first form, but there develops rapidly severe psychical phenomena, with gradually progressive deep dementia, incidentally there are "attacks" of different nature such as fainting, apoplectiform shocks, or epileptiform convulsions, with more or less well-defined focal symptoms.

II. Subcortical encephalitis; this is a group described by Binzwanger, in which there is an atrophy of the deep-lying white substance due to arterio-sclerosis of the long medullary arteries.

* Alzheimer: Die Seelenstörungen auf arteriosclerotischer Grundlage. Allg. Zeitschr. f. Psych., Vol. 59, p. 695.

Binzwanger: Die Begrenzung der allgemeinen Paralyse. Allg. Zeitschr. f. Psych., Vol. 51, p. 804.

Clinically, difficulty in the association processes is the first and most striking symptom; speech is early affected. Often there are varieties of aphasic disturbances, apoplectiform and epileptiform attacks with periods of excitement and confusion. There sometimes develops, suddenly or gradually without psychical involvement, articulatory speech disturbance or hemiparesis. Anatomically there is an absence of the focal softenings expected. The pia is moderately hazy, the convolutions are a little narrowed and deeply depressed. The cortex is well preserved, but the hemisphere white substance is greatly atrophied. Often in these cases there are arterio-sclerotic foci in the internal capsule, lenticular nucleus, thalamus, and quite regularly in the pyramid tract of the pons.

III. Perivascular gliosis is a process in which there is an atrophy of the nervous elements and a proliferation of glia in the field of distribution of vessels which by reason of arteriosclerotic disease furnish less nutrition. The nervous elements easily reacting to such disturbance gradually atrophy and give place for a glia overgrowth.

IV. Senile cortical devastation, is an arterio-sclerotic disease occurring in senile years and associated with senile brain atrophy. In this process there occurs an arterio-sclerotic degeneration of the smaller vessels of the cortex with disintegration of the nervous elements in peculiar wedge-shaped foci or in streaks.

Pure types of these groups of Alzheimer's are not common, as often the focal lesions, where of any considerable size or important location, modify the clinical and anatomical picture.

Anatomically arterio-sclerotic brain disease must be considered as two processes, viz., that present in the vessels and the reactions in the nervous tissue. As it affects the vessels at the base of the brain, in the meninges and the largest vessels of the brain substance, the process presents the same features as in other arteries of the same size. The intima is chiefly involved; its cells proliferate, increasing the thickness of the coat, usually unsymmetrically. The elastica increases and new-formed fibers pass in among proliferated intimal cells, later necrotic degenerative processes occur in the new tissue, the so-called atheromatous degeneration; often calcareous salts are deposited in the degenerated area. The wall instead of becoming atheromatous may more rarely undergo hya

line transformation. In the finer vessels, such as occur in the cortex and white substance of the convolutions, there occurs proliferation of the endothelial layer and increase or splitting up of the elastic fibers. Later the endothelium may lose its staining qualities. The elastica or intima may degenerate into a hyaline or colloid substance. As a result of these changes there occur peculiar arrangements of the vessels. Often there are clusters of rings due to vessels cut in cross-section, or long chains of rings, possibly produced by tortuosities in the vessel wall. Various other kinds. of irregularities in the vessel wall may occur. As a result of the proliferation of the intima and elastica the original lumen may be obstructed and new channels formed through the vessel. In one instance four channels ran through the intimal proliferation. The adventitia commonly contains phagocytes with pigment; true infiltration of the vessel wall does not occur. As hyaline change there occurs a transformation of the arterio-sclerotic wall into a hyaline-like substance. More rarely the vessel may degenerate into a substance giving a reaction different from hyaline and which Alzheimer' has described as colloid degeneration.

As a result of these changes there may occur focal softenings, where the shutting off of nutrition is sudden, or if gradual, the softening is incomplete and there occurs a degeneration of the least resistive elements and proliferative changes of the glia in the involved region. This may be of large extent where arteries of wide distribution are affected, or small where the fine cortical vessels are changed. As another result of arterio-sclerosis, especially of the hyaline degeneration of vessels there may occur, as described by Weber, fine miliary hæmorrhages. Further, the degenerative changes may lead to weakening of the walls and the formation of miliary aneurisms, the rupture of these giving origin to the larger brain hæmorrhages.

The changes in the nervous tissue cannot be regarded as specific, yet they are quite characteristic in their peculiar distribution. As a result of the disturbance of nutrition there occur necrotic

*Alzheimer: Die Kolloidentartung des Gehirns. Arch. f. Psychiatrie, Vol. 30.

"Weber: Hyaline Gefässentartung als Ursache miliarer Gehirnblutung. Arch. f. Psychiatrie, Vol. 35, p. 159.

changes in the nerve cells which are of a variety of types; ultimately the diseased cells may disappear or persist as severely altered forms.

The glia elements as a rule show focal proliferative phenomena such as swelling and production of fibers; occasionally glia nuclei mitoses are observed. When the injury is very severe or recent the glia elements may show only regressive changes. Other forms of cellular elements occur with greater or less frequency. Chief of these is the epithelioid cell, which is rarely absent from the arterio-sclerotic foci, another is the long rod-shaped "Stäbchenzelle" whose origin is less certain.

The characteristic feature of the arterio-sclerotic process in the cortex is its focal occurrence. These focal lesions may vary from small fields visible only under the immersion to larger patches of devastation seen with the unaided eye. Histologically arterio-sclerotic brain disease is to be chiefly differentiated from that of general paralysis. This is to be made from the less diffuse character of the process and above all by the absence of lymphoid and plasma cell infiltration of the vessel wall. From the senile brain atrophy it is differentiated by its focal character and the relation of the nervous tissue degenerations to vessel changes; the appearance of the cortex being that of a patch-like degeneration, while in senile dementia the disappearance of the nerve cells is more diffuse and general. In both general paralysis and senile brain atrophy arterio-sclerosis with its secondary degenerations may also be present, yet is purely associative.

Out of a number of cases of arterio-sclerotic brain atrophy we have collected the following: The first four cases correspond to Alzheimer's first group. The fifth case is that of an arteriosclerosis in which the coarse lesions are especially marked.

For the clinical records of all of the cases described I am indebted to my associates on the medical staff of the Danvers Hospital.

CASE R.: Arterio-sclerotic brain atrophy with minor focal symptoms.-At 62 becoming irritable and developing mild delusional ideas; marked forgetfulness; gradual improvement; stationary course for three years, then return of ideas of suspicion; rapidly progressing deterioration; profound memory disturbance; defect