Actn l edicn Scandinnvica. Pol. CHI, fast. VI, 1956.

From the Medical Department (Head: Professor E. Ask-Upmark) of the Royal Academic Hospital of the University of Upsala, Sweden.

Oil the Laterality of Cerebral Embolies. BY

ERIK ASK-UPMARK, M. D.

(Submitted for publication May 12, 1955.)

Divergent opinions have been expressed as to the laterality, if any, of the vascular lesions of the brain, not least so with regard to arterial embolies. On the one hand several authors have maintained that the left hemisphere is more often involved than the right (Saveliew, Hultquist, Boyd, Cappell), ))because the left carotid is more directly in the line of the blood stream of the aorta)), as Cappell puts the matter. On the other hand the same preponderance has been claimed for the right hemisphere, for instance by Daley and co-workers. Murphy seems to base his agreement with Daley on this matter mainly upon the paper of Daley. In support of the last mentioned opinion may be mentioned the fact that symptoms from the left hemisphere are apt to be more apparent than from the right (aphasia, for instance). Since the brain scarcely is examined a t every necropsy a certain selection of the material, favouring the left hemisphere, might possibly occur'. Biorck and co-workers investigated the occurrence of cerebral arterial embolies in 240 cases of rheumatic valvular disease, as observed post mortem; they reported that out of 26 necropsies presenting cerebral embolies, the right hemisphere was affected in 15 instances, the left in 14, and thus that no conclusive difference was established.

In order to study this question the necropsies carried out in the Department of Pathology during the years 1946-1954 were reviewed.' It turned out that, if subarachnoid haemorrhages and subdural haematomas were excluded, altogether 306 cases with vascular lesions of the brain could be assembled. The various lesions are to be seen in Table 1.

The reason why I have selected a 9-year material is because those years cor- respond to my presence in Upsala. If a 10-year material, including 1945 as well, is picked out 3 more embolic cases are to be registered, two left-sided and one right-sided.

I am obliged to my friends in the Department of Pathology and particularly to its head Professor Robin F&hraeus for the kind permission to use the material. The vast majority of the cmes have been observed in the Medical Clinic, only some 10-20 cases being derived from other departments (Clinic of Surgery f. ex.).

434 E R I K ASK-UPMARK.

Tnblo 1.

Vascular lesions of the brain 1946--19~2.

I 163 haemorrhages 30(i representing ................ 115 ramollitions

28 embolies I Right Left Mid- Right and left side side line side

{ - 163 hemorrhages ................. 62 73 28

115 ramollitions ................. 54 43 13 5 28 embolies .................... 6 17 3 2

))Mid-linen generally refers to the brain stem, occasionally to the cerebellum if no laterality could be discerned. With regard to the brain stem the 28 haemor- rhages here considered were to be regarded as the main vascular lesions; minor haemorrhages in the brain stem were quite frequently observed in connection with, particularly, the haemorrhages of the hemisphere. With regard to the 3 embolic mid-line cases one was located in the basilar artery, one in the left vertebral and one in the right vertebral artery immediately before their confluence. The embolus of the right vertebral artery was, incidentally, the only paradox embolus of the material. With regard to the ramollitions of the mid-line a t least 5 belonged to the left vertebral artery and one more to the left half of the cerebellum, whereas the other instances were true mid-line cases.

It will be seen that whereas no conclusive difference is evident with regard to the laterality of cerebral haemorrhages and encephalomalacias, there is an out- standing difference between the embolies, being represented on the right side by 6 cases, on the left side by 17. If the three embolic cases from 1945 are allowed to be included the corresponding figures will become 7 and 19. In one case, ob- served before my arrival in Upsala in 1946, the embolus was lodging in the left art. cerebri media whereas the right carotid was entirely obstructed. It was felt by the pathologists that this embolus might have been derived from the right carotid and eventually managed, by means of the anterior communicating artery, to enter the left side of the circle. If, however, this had been the case i t is difficult to see how the embolus could have managed to enter art. cerebri media, against the direction of the arterial blood flow. Personally I am inclined to believe i t had arrived by means of the left internal carotid. Since, however, this case repre- sents a handicap with regard to the right hemisphere - the carotid on the right side being obstructed - i t will be discarded in this connection. We then have 7 right-sided and 18 left-sided embolies. The seat of the embolus was in most instances art. cerebri media (3 right-sided, 13 left-sided), in 5 cases art. cerebri posterior (2 right-sided, one of whom had also an embolus in the art. cerebri media), in 2 cases art. cerebri ant. (both left-sided, in one of whom the art. cerebri media waR also involved), in one case the carotid artery (right side). The basal nuclei were involved on the right side in one, on both sides in 3 cases. The mid-line cases have already been described. The source of the emboli was in most instances a valvular lesion of the heart, in some few instances infarctions or thrombosis of the left atrium present without any obvious valvular affection.

ON THE LATERALITY OF CEREBRAL EMBOLIES. 435

The material presented above represents a post mortem material. It should readily be admitted that several instances of cerebral vascular lesions and, hence, also embolies are apt to leave the hospital alive and eventually recover or die a t home or in old people’s homes. There is, under present circumstances, no reason why left-sided lesions should be retained in hospital more than right-sided lesions. Such might have been the case if they could be offered a reasonable chance of rehabilitation with speech lessons, etc., but since, so far, our depart- ment has no accomodation for this, it might be presumed that the figures already quoted are reasonably representative of the clinical material. Moreover, the dif- ference is outstanding between the obvious laterality of the emboli and the ab- sence of any apparent laterality with the other vascular lesions. The brain is, in our department of Pathology, examined as a routine in every case where symp- toms from the nervous system have been noticed during life or where the character of the disease makes a post mortem study of the brain desirable.

No attempt has been made to collect the material of apoplexy, as observed clinically, since it was felt that it might prove difficult to distinguish in every case a cerebral haemorrhage from a cerebral ramollition, and although the em- bolies ought to be more feasible from a diagnostic point of view I have refrained from entering upon this more clinical side of the subject. Recently, however, Dalsgaard-Nielsen has published an admirable survey of 1,000 cases of apoplexy, observed a t the Frederiksbergs Hospital in Copenhagen. The question of laterality was not entered upon in Dalsgaard-Nielsen’s paper, but he has had the kindness personally to inform me about this matter. Out of 68 cases of arterial embolies to the brain a laterality was to be made out in 56 cases. Out of these 56 cqses 32 had symptoms from the extremities on the right side (hence reasonably left- sided embolies) whereas the converse was found with 24 cases. Although not striking the difference seems to be fairly obvious.

There are four other series of observations which may or may not substantiate the presumption about the predilection of arterial embolies for the left hemisphere.

1. In valvular lesions of the heart i t may sometimes be observed that the patient himself is able to listen to the murmur in question. Such has been the case, for instance, with doctors who have been treated in the clinic. More often than not they have reported the loudest murmur to be heard in their left ear; so far I have not encountered any doctor with a valvular lesion and an audible murmur, who heard this murmur more with his right ear. This observation may perhaps be correlated with the proneness of the left ear to otosclerosis, since there are reasons to believe that this disorder involves a vascular factor.

2. Parasitic emboli, arriving a t the nervous system with the arterial blood, are apt to lodge more often in the left than in the right eye. Such is the case a t least with the intraocular manifestation of cysticercus cellulosae (Graefe; for references see the thesis of Ask). It may be objected that the sub-conjunctival localization seems to be more frequent a t the right side, as will be seen in the material collected by Ask, but as Ask rightly has emphasized the intraocular localization of these parasites is much more frequent than the subconjunctival (Graefe gives the proportion as 16: 1).

436 ERIK ASK-UPMARK.

3. Neoplastic metastases have been studied with regard to the laterality of their cerebral localization by several authors (for instance Kaufmann, Krasting, Of- fergeld, Kikuth, Maxwell, Brunner, Willis; in the valuable study of Lesse and Netsky nothing is mentioned about the laterality). Although the size of the individual materials generally is rather limited, and the opinions hence necessarily are some- what divergent the bulk of evidence seems to favour a certain although hardly overwhelming predilection for the left hemisphere (Table 2). On the other hand metastatic choriodal carcinoma - a rare condition per se - seems to affect both eyes equally. Usher gives an excellent survey of the literature and has it than when only one eye was affected (i. e. in 2 cases out of every 3) the left and the right eye were involved in exactly the same number of cases (34). With Storte- becker, tho incidence of metastasis to the brain was also about equal in both hemi3phere.s.

TsbJe 2.

Kaufmann 1906: Left hemisphere involved twice as often as the right. Krasting 1900: 62 solitary metastases: left only, 30; right only, 13. 142 metastatic nodes in all: left

Offergeld 1908: Cancer of uterus only. Right hemisphere 11, left 5 cases. Kikuth 1925: 31 cases of metastases from pulmonary carcinoma. Left hemisphere involved 5 times

Maxwell 1930: Bronohial Carcinoma. Right hemisphere only, 4 cases; left only, 3 cases; both, 9 cases. Brunner 1936: 74 instances of brain metastases, 66 % left-sided. Walther 1948: 41 solitary metastases: left only in 19, right only in 17. Willis 1952: Collected material 30 left, 24 right cerebral hemisphere. Corresponding figures for core-

only, 70; right only, 50.

as often as right.

hellum wore 13 and 9.

4. The predilection of xanthelasms for the left eye is a phenomenon well- known to all physicians. There are reasons to believe in a vascular factor, facili- tating the occurrence of this affection on the left side. On the other hand no conclusive difference seems to be present between the occurrence of subarachnoid aneurysms of the circle of Willis on the left and on the right side. Gowers had it that left-sided aneurysms should prevail in a proportion of 4 : 3, but considering the materials brought together by Fearnsides, Mc Donald & Korb, Poppen, Jaeger, Hamby, Ask-Upmark & Ingvar, one cannot but realize that the localiza- tion of these aneurysms is about 50 : 50 as between the two sides (mid-line ex- cluded).

It will hence be seen that arterial embolies, brainwards bound, seem to have a certain predilection for the left hemisphere. This is in accordance with the generally more common involvement of the left internal carotid in carotid ob- structions, most frequently derived from the carotid sinus (Hultquist).l On the other hand Takayashu’s disease seems t o involve the right side more often than the left, at least as far as could be judged from a material published elsewhere (Ask-Upmark). While this holds for the carotid system the limited size of our material does not permit any conclusions as to the laterality of the embolies

1 Perlow and coworkers (1955) have i t that the left carotid should be affected in 6 cases out of 7. This figure exceeds by far that from our own (modest) experience.

ON THE LATERALITY OF CEREBRAL EMBOLIES. 437

arriving a t the brain within the vertebral arteries. It seems reasonable, however, t o presume a considerable predilection for the left side. Firstly, the Wallenberg syndrome does affect the left vertebral artery much more frequently than it affects the right. Hulth-Gyllensten had i t that in 11 out of 12 cases the left vertebral was concerned. Secondly, ever since the important investigations of Radner i t has been well known that the right vertebral artery tends to leave the subclavian artery in a recurrent direction, hence facilitating the introduction of a catheter from the radial artery (Radner 1951). It is perfectly obvious that embolic material from the heart as well as the impetus of the pressure wave is much more likely to affect the left vertebral artery.

Summary and Conclusions.

The laterality of arterial embolies to the brain was examined on a post-mortem material for the years 1945-54. During this period 31 cases of embolies to the brain were to be registered, representing some 10 yo of all cases of vascular lesions of the brain in whom necropsy had been performed. If only one-sided lesions are concerned 7 cases were found in the right and 18 cases in the left hemisphere. This predilection for the left side is briefly discussed.

Referenoes.

Ask, F.: 1902, Cysticercus cellulosae subconjunctivalis. Thesis. University of Lund. - Ask-Upmark, E.: 1954, Acta Med. Scand. 149: 161. - Biorck, G. et al.: 1952, Am. Heart J. 44: 600. - Boyd, W.: 1945, Pathology of Internal Diseases, Lea and Febiger. - Brunner, W.: 1936, Zschr. ges. Neurol. u. Psych. 154: 793. - Cap- pell, D. F.: 1951, Muir’s Textbook of Pathology, Arnold, London. - Daley, R. et al.: 1951, Am. Heart J. 42: 566. - Dalsgaard-Nielsen, T.: 1955, Personal communica- tion. - Dalsgaard-Nielsen, T.: 1955, Acta Psych. Neur. Scand. 30: 168. - HultBn- Gyllensten, Inga-Lisa: 1954, Acta Psych. et Neurol. Scand. 29: 79. - Hultquist, G. T.: 1942, uber Thrombose und.Embolie der Arteria carotis, Fischer, Jena. - Kaufmann: 1906, Korr. bl. Schweitz. Artz. Nr 8, p. 255. - Kikuth, W.: 1925, Virshows Archiv 255: 107. - Krasting, K.: 1906, 2. Krebsforsch. 4: 315. - Maxwell, J.: 1930, J. Path. and Bact. 32: 233. - Murphy, J. P.: 1954, Cerebrovascular Disease, Year Book Publ. - Offergeld, H.: 1908, 2. Geburtsh. u. Gyn. 63: 1. - Perlow, S., Daniels, J. L. and Sloan, N. S.: 1955, Angiology 6: 32. - Radner, Stig: 1951, Vertebral sngiography by catheteri- sation. A new method employed in 221 cases. Acta Radiolog. Suppl. 87. - Saveliew, N.: 1894, Virschows Archiev 135: 112. - Stortebecker, T. P.: 1954, J. of Neurosurg. 11: 84. - Usher, C. H.: 1923, Brit. J. Ophthalm. 7: 10. - Walther, H. E.: 1948, Krebsmetastasen, Schwabe, Basel. - Willis, Rupert: 1952, The Spread of Tumours in the Human Body, Butterworth and Co. Publ., London.