Postgrad Med J: first published as 10.1136/pgmj.31.353.117 on 1 March 1955. Downloaded from

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CEREBRAL ARTERIOSCLEROSIS By R. T. C. PRATT, D.M., M.R.C.P., D.P.M. Physician in Psychological Medicine, Maida Vale Hospital

The problem ofcerebral arteriosclerosis demands The clamped kidney is free from the arterial first a consideration 'of recent views on the necrosis found in many other organs of the hyper- mechanism of experimental hypertension in tensive rat, suggesting that this lesion is dependent animals and on the applicability of the proposed on the physical strain of increased intra-arterial mechanism to the clinical pictures of hypertension tension and follows on the spasm which is the and arteriosclerosis in man. response of an artery to this form of strain. This hypothesis was tested by direct observation of the Experimental hypertension in animals blood-vessels of the rat's brain through a trans- The results of his work on the pathogenesis of parent cranial window. The vessels appeared hypertensive encephalopathy in rats have recently normal in animals before the appearance of cerebral been summarised in an outstanding paper by symptoms and after their disappearance following Byrom (I954). Hypertension was induced, after removal of the clamp. With the onset of encephalo- excision of one kidney, by applying a simplified pathy there was a consistent change in the smaller Goldblatt clamp to the renal artery of the remain- cerebral arteries, a widespread sustained contrac- ing kidney. This procedure regularly leads to the tion of many of the vessels of this calibre with by copyright. development of hypertension, and has the great occasional localized areas of dilatation. advantage that the hypertension can be reversed. Byrom concluded that a state of focal but wide- by removing the clamp. Cerebral symptoms occur spread vascular spasm is the basis of severe when the blood pressure reaches a height of about experimental renal hypertension, and that the 200 mm. Hg., the most frequent manifestations effects of the spasm, depending on its intensity, being epileptic convulsions, myoclonic contrac- duration, location and extent, ' comprise in tions, focal neurological signs, and the development increasing order of severity: (i) transient dis- of coma. The symptoms are rapidly relieved with turbance of function, (2) increased capillary the fall of blood pressure resulting from removal permeability with attendant focal oedema, and (3) http://pmj.bmj.com/ of the clamp. local necrosis of the arterial wall and/or the tissue Organic brain lesions were found in only a little supplied.' more than half the rats at post-mortem, and con- sisted of focal arterial necrosis, areas of cerebral Pathology of Hypertension and Cerebral infarction, or haemorrhages arising from arteries Arteriosclerosis in Man or capillaries. The frequency of organic lesions Man, unlike the rat, is subject to atheroma, and was, therefore, not great enough to account for the the possible presence of this factor in addition to symptoms encountered, and a functional change hypertension is responsible for much of the on September 23, 2021 by guest. Protected was sought to account for this finding and for the difficulty in ascribing cerebral symptoms to their rapid return to normality following relief of the underlying pathological bases, particularly since hypertension. When the dye trypan-blue is atheroma is found more frequently in the presence injected intravenously shortly before a normal of hypertension. Haemorrhage from an artery is a animal is killed, the brain is unstained since the common complication of cerebral arteriosclerosis, dye does not pass the blood-brain barrier. How- the patient usually being found to have an accom- ever, in 87 per cent. of rats with encephalopathy, panying hypertension. Arterial thrombosis with conspicuous areas of staining of the cerebral grey resultant infarction of the corresponding part of matter were found, these areas occurring not only the brain may occur in arteriosclerotic patients in relation to organic changes, but also where the without hypertension. Cerebral embolism maygive brain appeared histologically normal or showed rise to permanent neurological signs, or to symp- only evidence of focal oedema. Byrom therefore toms and signs which are transitory and leave no suggested that increased capillary permeability deficit. From their occasional fleeting nature it with focal oedema antedated structural damage. has been argued, notably by Pickering (1951) that Postgrad Med J: first published as 10.1136/pgmj.31.353.117 on 1 March 1955. Downloaded from II8 POSTGRADUATE MEDICAL JOURNAL March 1955 a structural change such as thrombosis may well of mental and physical fatigue and a mild organic underlie also the similar clinical picture found in personality change, suggest that this clinical severe hypertension. The above-mentioned work picture can arise in benign hypertension without of Byrom makes it likely that hypertension alone the necessity of an interpretation along psycho- may eventually cause structural changes leading to pathological lines. arterial necrosis, thrombosis and haemorrhage. The clinical picture of cerebral arteriosclerosis The co-existence of atheroma may well render an with or without accompanying hypertension, is artery moresensitive in its response to raised intra- more definite. The symptoms and signs depend arterial pressure by spasm, and a more extreme on a progressive cerebral anoxia, with the general degree of atheroma may lead to focal cerebral and focal signs appropriate to the arteries involved. infarction, with or without arterial thrombosis, in In essence there is a fluctuating development of an the absence of hypertension or of arterial spasm. organic intellectual and personality change. Memory for recent events is impaired whilst Hypertensive Encephalopathy in Man happenings in the distant past are well recollected. That the cerebral symptoms which may accom- There follows a more general intellectual impair- pany renal disease are not related to nitrogen ment with failure of judgment and an inability to retention but to hypertension was shown originally grasp new problems, with narrowing of the outlook by Volhard, whose term ' pseudo-uraemia' has and diminution in initiative. Insight is often been replaced by 'hypertensive encephalopathy' preserved to an extent that is not seen in senile (see Fishberg I954) and by' hypertensive cerebral dementia, and with the realisation of his failing attack' (McAlpine I933). McAlpine differentiated powers the patient becomes easily depressed. two forms of attack, the first, commoner in patients Emotional lability may develop, and the patient below the age of 40, with headache, vomiting, will then more readily than his wont be amused or drowsiness, convulsions and papilloedema, the depressed, and will, furthermore, give excessive second found in middle-aged patients and expression to these often transitory emotions, a characterized by epileptiform attacks and focal picture of emotional incontinence ultimately neurological signs in the absence of papilloedema. developing. In spite of these changes, the basicby copyright. Fishberg and McAlpine agree that the mechanism personality is often surprisingly well preserved, of the second type of attack is focal arterial spasm, although previously latent personality traits may and of the first type cerebral oedema secondary to emerge, such as irritability or suspiciousness. the rise of blood pressure from generalized Neurological symptoms and signs appear irregu- vasoconstriction, not necessarily accompanied by larly during the course of the illness. There may cerebral vasoconstriction. From the experimental be focal disturbances resulting from the underlying findings of Byrom it now seems that cerebral impairment of cerebral function; these distur- arterial spasm, generalized or localized, is the bances may be transitory or permanent and may

basis of each type of attack. take the form of minor paralyses, or disturbances http://pmj.bmj.com/ of sensation, vision or speech. Major disturbances Symptoms of Benign Hypertension and of such as a hemiparesis or a series of epileptic attacks Cerebral Arteriosclerosis in Man may follow. There are two clinical pictures which Benign hypertension in man may lead to no may result from a generalized affection of the symptoms whatsoever, the condition being found cerebral arteries; an arteriosclerotic Parkinsonism on routine examination of the blood pressure. The with marked rigidity, and a pseudo-bulbar palsy greater frequency of symptoms such as headache, with bilateral pyramidal involvement and pro- unsteadiness, and mild hypochondriasis, which nounced emotional incontinence. The most on September 23, 2021 by guest. Protected are to be found in those subjects who are aware extreme change seen in advanced cerebral that their blood pressure is raised, has led to the arteriosclerosis is of a profound organic dementia, view that many of the symptoms of uncomplicated with double incontinence and complete mental hypertension are due to a secondary anxiet state. inaccessibility. it is certain that symptoms in many hypertensive patients are aggravated or even induced by the Differential Diagnosis of Cerebral Ilowing on their awareness ofte raised Arteriosclerosis lvel of their blood rere su The differential diagnosis of cerebral arterio- the most profitable line of treatment s neof mild sclerosis resolves itself into the separation from it sedation and superficial psychotherapy, with an of other diseases causing or mimicking organic explanation of the role of emotion in causing intellectual and personality change in later life. various somatic symptoms. However, the occur- Space-occupying lesions within the skull tend rence of such symptoms in patients without to give rise to headache and vomiting with knowledge of their hypertension, and the presence papilloedema, all of which. are infrequent in Postgrad Med J: first published as 10.1136/pgmj.31.353.117 on 1 March 1955. Downloaded from March 1955 PRATT: Cerebral Arteriosclerosis 1 cerebral arteriosclerosis unless this is complicated occur in the aged, in particular by Roth (see by hypertensive encephalopathy. The most Mayer-Gross, Slater, and Roth I954) who has characteristic psychological symptom is a blunting utilized amongst other approaches, that of of the mental faculties and a lack of alertness, a Kraepelin himself in the emphasis he has placed contrast with the impairment of recent memory on the importance of prognosis in distinguishing of cerebral arteriosclerosis. An exception is the various categories of illness. pronounced memory impairment seen in lesions Roth classifies the mental diseases of old age into of the base of the brain (Williams and Smith I954). five main categories, with arteriosclerotic psychosis which is as a rule more extreme than that seen in as one group. Senile psychosis is characterized by cerebral arteriosclerosis andis often unaccompanied intellectual impairment (with memory affected by other features of organic intellectual impair- early), emotional blunting, and reduction in ment. Finally, the neurological signs in an initiative, with involvement of the personality as expanding lesion usually point to a single rather a whole, and a steady progression to death in a few than multiple lesions, and the mode of evolution years. The absence of epilepsy and of focal is more steadily progressive. neurological signs, and the steady course of the General paralysis of the insane is differentiated disease, serve to distinguish it from cerebral by its occurrence at a younger age, by the physical arteriosclerosis. Delirious states in old age may signs of this disorder, and by the positive Wasser- depend on an intercurrent infection or on toxic mann reaction. In this condition there is an early or vitamin-deficiency states, the latter often without change in the patient's personality, with the any of the more characteristic signs of vitamin frequent emergence of latent personality traits such deficiency. When delirious states are due to any of as depression, grandiosity and suspiciousness. The these causes, the primary state may be detectable, presenile dementias comprising Pick's disease, and the confusion will have appeared somewhat Alzheimer's disease and a larger undifferentiated suddenly in a person who was previously well. group may be distinguished by the earlier age of Delirium, however, is not uncommon as a com- onset, the occasional positive family history, the plicating factor in cerebral arteriosclerosis, and absence of and be to one causes other signs of arteriosclerosis, by may due of the above-mentioned by copyright. the more steadily progressive course of the illness. or may be dependent directly on further arterio- A relatively uncommon cause of an illness which sclerotic lesions, the effect of which is more likely may be taken for cerebral arteriosclerosis is to be permanent than transient. The group of late myxoedema: the importance of considering this paraphrenia is distinguished from cerebral arterio- condition in the diagnosis of any psychiatric illness sclerosis by the consistency and systematization in later life lies, of course, in the frequency of a of the delusions, in contrast to their fleeting nature favourable response to thyroid medication. A and poor hold on the personality when they occur single one of the following features, coarseningof in cerebral arteriosclerosis. the face, dryness of the skin, a slowpulse, mental The final group in Roth's classification of the andhpsica1torpor or excessive sensitivitto psychoses of the aged is the affective psychoses; http://pmj.bmj.com/ cd, may e the only outstanding evidence of their differentiation from cerebral arteriosclerosis hypothyroidism, and should prompt investigation is of outstanding importance in view of their of the serum cholesterol and basal metabolic rate. excellent response to electro-convulsive treatment. The final conditions to be considered in the The most important feature in the illness of a differential diagnosis of cerebral arteriosclerosis are patient with endogenous depression is that the the mental diseases of the aged. Kraepelin (I904) history will show that there was little or no impair- stated: ' We must, that the ment of intellect or before the fairly however, recognize personality on September 23, 2021 by guest. Protected interpretation of those cases of disease which sudden onset of an illness with reduction of occur at the beginning of old age is often very psychomotor activity and a predominantly de- difficult.' He pointed out one criterion thus: ' The pressive colouring. Often the classical features of great prominence of this inability to retain im- an endogenous depression will be present, with pressions in the rtore severe forms of the insanity retardation or agitation, insomnia with early of old age seems to me to justify the view that those waking, and a lifting of the depressive mood states of depression and excitement in which it is a towards the evening. Such features, even in the leading feature . . . are also to be considered as presence of hypertension or cerebral arterio- varieties of senile insanity. If further experience. sclerosis, should call forthe consideration ofelectro- shows that this view is correct, we may perhaps convulsive treatment. (Partridge, 1954). have found a criterion for the distinction of melancholia . . . from real senile imbecility.' In Future Treatment recent years consideratle progress has been made The present treatment of cerebral arterio- in the distinction of the various psychoses which sclerosis is entirely non-specific, and consists Postgrad Med J: first published as 10.1136/pgmj.31.353.117 on 1 March 1955. Downloaded from I 20 POSTGRADUATE MEDICAL JOURNAL March 1955 largely of general management of the everyday BIBLIOGRAPHY routine of life, and appropriate measures for the BYROM, F. B. (I954), Lancet ii, 201. various complications that may ensue. The success FISHBERG, A. M. (1954), 'Hypertension' and, Nephritis,' 5th and of hexamethonium in the Edition, Bailliere, Tindall & Cox, London. ·of sympathectomy KRAEPELIN, E. (1904), (English Translation, edited by T. treatment of severe hypertension (see Rosenheim, Johnstone), Lectures on Clinical Psychiatry, W. Wood, New I954) indicates that similar measures may well be York. of help in the management of cerebral arterio- McALPINE, D. (I933), Quart. J. Med. N.S., 2, 463. sclerosis to the extent that this condition is MAYER-GROSS, W., SLATER, E., and ROTH, M. (1954), accompanied by cerebral arterial spasm secondary 'Clinical Psychiatry,' Cassell, London. to the stress of intra-arterial tension: the answer PARTRIDGE, M..(I954), Postgrad. med. J, 30, I76. to this problem and to that of the value of anti- PICKERING, G. W. (195I), Lancet, ii, 845. in treatmen on a controlled ROSENHEIM, M. L. (1954), Brit. med. J., ii, Ix8i. coagulants depends WILLIAMS, M. and SMITH, H. V. (I954), J. Neurol. Neurosurg. comparison of treated and untreated patients. Psychiat. N.S., 17, 173.

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