Act8 Medicn Scandinevica. Vol. CXLlX, fnsc. 111, 1954.

From the Department of Medicine (Head: Erik Ask-Upmark) of the Royal University of Upsala, Sweden.

O n the ))Pulseless Discilse)) outside of Japan. BY

ERIK ASK-UPMARK, M. D.‘

(Submitted for publication November 23, 1953.)

In 1908 Takayashu described a peculiar syndrome which has since been repeatedly observed. Anatomically, we have a fair notion of its behaviour, clinically i t is ex- tremely characteristic, from the prognostical point of view it is serious and so far it seems rather inaccessible to treatment. It has been called Takayashu’s syndrome or (by Shimizu) the pulseless disease and may be briefly described as a chronic, pro- gressive and, as a rule, obliterative brachiocephalic arteritis, which deprives the upper half of the body of its due blood supply. This clinical entity has been observed particularly in Japan, where 58 cases seem to have been descxibed according to a report by Caccamise and Whitman from the Cleveland Clinic. These authors believe that the syndrome in question has not been observed outside of Japan except for their own case. This, however, is incorrect. The present paper will present two more observations of this remarkable clinical entity, and an attempt will be made to review other cases reported outside of Japan and to discuss the pathogenesis and the treatment.

Personally, I have had the opportunity to observe three cases of this disease: one case in 1946 whilst I was physician in charge of the Sahlgren Hospital in Gothen- burg, and two cases from 1949 and onwards in Upsala. The first case has already been described by Lindquist, who had seen the patient before I had. This case is denoted in the table (p. 164-165) as case 15. Briefly summarizing, the patient was a woman, aged 30, who had had symptoms for 4 years and who was admitted to our medical department because of pains in the region of the left axilla, fever and in- creased sedimentation rate (132). It was difficult to register any blood pressure in the arms and we believed we could feel what appeared to be a cord in the region of the left axillary artery. She was sent to our surgical colleagues who, on exploration, found a left brachial artery which was the seat of a periarteritis as well as of a thrombosis. For particulars of this case reference may be made to Lindquist. The other two cases were observed in Upsala (one of them also in Scania) and their rec- ords run briefly as follows. -

Presented in abbreviated form to the Swedish Society of Internal Medicine Sept. 26th, 1953.

162 ERIK ASK-UPMARK.

Case I , H . H., woman, q e d 34 (born 1915). One delivery (1936). When aged 20 she was treated in a rural hospital during 2 months for an infectious disease, characterized by fever, headaches in the right half of her head, a transitory erythema all over the body, resembling erythema multiforme, increased sedimentation rate (maximally 83) and, even- tually, transitory pains in the fingers, wrists and elbows. (Temperature-curve see fig. 1.) Nothing abnormal was registered from the lungs. A few teeth were removed and i t was presumed that the disease was a rheumatic fever. When aged 26 she was found to pre- sent corneal opacities almost as in parenchyinatous keratitis and she had pains in her arms when subjecting them to any effort. When aged 27 i t was found impossible to register the blood pressure on the arms. When aged 34 she was operated upon for a dermoid cyst of her ovary: in this cyst the arteries did present peculiar cellular cushions in the intima. Was admitted to the clinic in 1949 for the first time, mainly because of cardiac dis- turbances: dyspnoea, tachycardia, ortopnoea. No pulse was palpable in the arms and no blood pressure could be registered. In the legs, however, the pulse was recognized in the characteristic regions and the blood pressure was found to be 245/170 on the right and 240/170 on the left leg. The sedimentation rate was 55. In the right supraclavicular fossa a pronounced vascular murmur was found, similar to a machinery murmur. The pulse of the carotid arteries was less pronounced than normal. Roentgenological examination of the heart was approximately normal, as also were the electrocardiogram, the venous pressure (7.5 cm H,O), the vital capacity (3,500 ml), the basal metabolic rate (- 7 yo) and the Wassermann reaction. The cerebrospinal fluid disclosed a somewhat increased protein content (92 mg yo) but was otherwise normal. Ophthalmological examination revealed bilateral corneal opzcities, pupillary reactions normal, no pulsation of the ar- teries on compression ad modum Seide!, tension of both eyes 15.

The patient has since been repeatedly observed in the clinic as well as in the outpatient department. On one occaais- (A;xi! 1949) tmnsitory right-sicled hemiparcsis. May 1949 the right carotid artery was explored in the surgical department: i t had a much thicker wall than normal and there was only a very thin axial streaming of blood without obvious pulsations; a small thyroid artery was removed and found normal histologically. I n March 1950 she did present some tender, red infiltrations of the skin of the left leg: a small artery was removed from the foot and fourid to present pronounced, subacute inflammatory alterations throughout all layers of the wall. On that occasion the acuity of vision was but /'.' the corneal opacities prouounccd. the t,enGon of both eyes 15. The heart had by \n 1 ' ~~. -

now increased considerably in size (fig. 4) and on the whole her main complaint was the symptoms from the heart. Dec. 1959 t,hc h!cd pressure was registered in the right pop- liteal artery as 270/190, in the left popliteal artery as 250/170. The right kidney was stri- kingly small on roentgenological examination and failed to excrete any contrast on uro- graphy (fig. 5). On the whole, her symptoms are worse during spring, summer and au- tumn; they improve during the winter and she gets considerable relief from the consump- tion of alcohol. In the winter of 1952 she was i n northern Sweden and felt better than for many years.

Case II, C. S., woman, aged 5s (born 1591). This case was scrutinized by me in 1949, 1950 and 1953. Earlier in good health, one child, four miscarriages. Came t o Sweden from Germany at the end of the last war. Since the age of 48 transitory obscurations of the right eye. Intermittently during the last 6 years, sudden pains in this eye and about for the same time a certain oppressed feeling across the head, sometimes fairly far back, sometimes more in the frontal region. She has also felt a certain dizziness. These symptoms have all become worse during bad weather, such as thunderstorms, and on those occasions she has also had difficulty in speaking Swedish, which she otherwise does fluently (she is staying with her daughter and gr:tnd- children). For the last 5-6 years she has been much disturbed by a severe murmur in the left ear: its intensity may vary but occasionally i t is so pronounced as to impair her

ON THE ))PULSELESS DISEASE)) OUTSIDE OF .JAPAN. 163

ability of hearing. For some years tachycardia. For a number of years pains in her arms, if she has been working with them, so severe in recent years as to preclude her playing the piano for more than a short while. At least during the last p i i r she has, moreover, got severe pains from the neck to the chin if she has been chewing some ))tough meat)) for inore than a few minutes. Since the age of 48 she has also had a rather typical claudicatio interniittens from her legs: this symptom has become considerably less pronounced the last few years. Since 1948 she has had some few attacks of weakness of both legs, suddenly appearing and rapidly disappearing in connection with anxiety and sweating. I n 1949 she was sent to me by a very skilful and distinguished colleague, who was about to con- sider the diagnosis Acldison’s disease since i t had been found inipossiblc to register any blood pressure. On admission her general condition was good although she looked older than her age and had rather pronounced xanthelasnis. No pulse was to be felt, nor was any blood pressure to be registered in any extremity. Oscillometry revealed faint excur- sions 011 the left leg only. Roentgenological and elcctrocardiographical exaini nation of the heart was normal. A slight murmur was heard over both femoral arteries. No pulsa- tions of the right carotid artery were to be registered, on the left side, however, there was a very loud murmur from the supraclavicular fossa up to the retroinantlibular region where it reached its maximum. If she is tired or if the grandchildren are particularly disturbing and she is lying supine with her head on the pillow the head will rotate with the chin to- wards the left side for every beat of the pulse. Examination of the ears in the otological department Jan. 1950 revealed normal conditions. Examination of the eyes has been performed repeatedly by myself as well as by the ophthalmologists at the Academic Hospital and by my friend and colleague Dr. Lars Essen-Moller in Helsingborg, all of whom 1 want to thank sincerely for their experienced efforts. [n 1946 normal conditions had been registered. In 1949 Essen-Moller made the following observations.

Right eye: S = 0.4. Central scotoma. The pupil middlc-sized, itlnrost no reaction to light, slightly more to convergence and consensually. I n the anterior chamber the light can easily be trac,ed. Optic disc normal. The retinal veins wide and showing varicosities, re- minding slightly of a string of pearls. The blood flow is so slow as to be seen easily with a common ophthalmoscope in the big veins. Between the veins there are 1. rather superficial retinal haemorrhages, 2. densely scattered red points, reasonably considered as micro- aneurysms. In the macular region some greyish spots somewhat similar to those to be observed in hypertension. Arteries essentidly normal. Ocular tension 11 mm.

Left eye; S = 1. Retinal veins with alterations somewhat similar to those in the right eye, in the periphery plenty of retiual haemorrhages and also microaneurysms although not as many as in the right eye. Tension 15 mm. This was the situation in 1949. She went abroad to 13razil with her daughter and grandchildren and managed to learn Portuguese. Eventually, howel-er, they had to return to Sweden and she observed that when tired or upset she firstly lost her ability to speak Portuguese, secondly her Swedish and was able only to stick to her old German. Her eyes were examined again by Dr. Essen-Moller and myself and the following status was registered in June 1953:

Visual acuity on her right eye only light perception, on her left eye = 0 . 5 . Both eyes are congested along the lines of a caput Medusae.

Riglit. eye: :Incipient linear corucal degeneration. No light t o be traced in the anterior chamber. Pupil wide, no reactions whatsoever. Iris atrophic with basal anterior synechiac almost round the clock. Jmmediately central to these adhesions a circular venous sinus runs on the anterior surface of iris concentrically to limbus. Cataract of considerable ma- turity. No shadows on transillumination of the bulb. Tension about 15 mm.

Left eye: Cornea normal. Rather dense light trace in the anterior camera. No precipi- tations. Iris is not atrophic, nor has it any anterior adhesions, but in the periphery of the anterior surface of iris i~ similar venous sinus is seen in the nasal and in the teniporal zone. Pupil medium-sized, in its caudal border a slight contraction on light. Incipient cataract in the posterior cortex above the centrum. As to the eye-ground the optic disc is not atroph- ic nor oedematous but i t is covered by a network of recently developed capillaries which

164

Germany

USA (Mayo)

Norway . . . . . . . . Roumania

Greece Great Britain Great Britain Great Britain

Switzerland . . . . . Spain Norway Hungary Hungary Sweden Sweden France USA (Cleveland)

Norway Great Britain Great Britain Sweden

ERIK ASK-UPMARK.

- F F F F F F F F

F

F F F F F F F F

F M F F

Tab Pulseless disease - -

No. -

1 2 3 4 5 6 7 8 9

10

11 12 13 14 15 16 17

18 19 20 21

22 23 24 25

26 27 28

- - Year -

1925 1926 1936 1939 1940 1941 1942 1942 1944

1944

1946 1947 1947 1947 1947 1948 1952

1953 1953 1953 1953

1953 1953 1953 1953

1953 1953 1953

Symbols: WR SR

Author

Beneke ................ Raeder and Harbitz . . . . Marinesco and Kreindler Giffin . . . . . . . . . . . . . . . . . Kouretas and ljjacos . . . Gilmour, Case I ........ Lewis and Stokes . . . . . . Lewis and Stokes ....... Krayenbuhl and Weber,

Case I . . . . . . . . . . . . . . . Martoredc, Otzet and

Tersol ............... Frovig (1951 F. andLoken) Jobb . . . . . . . . . . . . . . . . . . Jobb . . . . . . . . . . . . . . . . . . Lindquist . . . . . . . . . . . . . . Lindquist . . . . . . . . . . . . . . Maspbtiol and Taptas ... Caccamise and Whitman

Jcrvell . . . . . . . . . . . . . . . . Skipper and Flint ...... Skipper and Flint . . . . . .

Ask-Upmark . . . . . . . . . . . Ejrup13 . . . . . . . . . . . . . . . .

Ask-Upmark ...........

E j r ~ i p ’ ~ . . . . . . . . . . . . . . . . EjrupI3 . . . . . . . . . . . . . . . . Rudbtick and Welin’3 ... Rudbiick and Welin13 ... Rudbiick and W ~ l i n ’ ~ . . . Wassermann Reaction. imentation rate.

Sweden Sweden Sweden Sweden

F F F F

Sweden F Sweden Sweden

- - Age

-- 41 37 38 19 23 23 33 45

15 :.

2 i 22 32 30 30 23 19

44 42 37 34

58 32 31 24

33 33 36

- - Dura. tion

5

7

- 1;

1; 1 -

it 2

1/3

5 3

Tears 3 5 5? 3

14 3?

O? 5? 14

10 11 1 1

11 4 3 t

- - His - tory - + +? +?

+ + +3

+ + + + + +

+ + + + + +

CS = Carotid Sinus syndrome. Sp. Cr. = Splanchrocranial symptoms. Vascular murmur = Extracardial murmur. History = Report of infection approximately a t the onset. Age = Age when first seen. Duration = lh ra t ion of symptoms prior to first examination, or, if deceased, prior to death.

1 Size somewhat enlarged. 2 Normal on phjsical examination. 3 Attack of sinfluenzaa. 4 Aorta somewhat enlarged. 6 Blitral and pericardial affection. 0 Serpiginated artery in interscapular region. 7 X-rag normal, electrocardiogram normal. * Later on claudicatio intermittens in the legs. 8 Claudicatio intermittens also in the legs.

10 Right arm 160/130-220/130. Aneurysm of right subciavim artery. 11 Blood pressure of the arms llO/90. 12 Reduced pulsations right leg. 13 I am indebted to my colleagues Ejrup, Rudbiick and Welin for personal information about

the cases 23-28. The cases of Ejrup were demonstrated to the Swedish SOC. of Internal Medicine in the go’ties, the cascs of Rudback and Welin to the Mcdical Soc. of Gothenburg in 1952.

** Right arm 215/130, lcft arm 150/130. Left carotid reduced pulsations. Hypertension a t delivery 11 years ago.

16 I am indebted to Sir Harry Himsworth and Dr. Glynn for their kindness of scnding me details about the post-mortcm of this case.

ON THE #PULSELESS DISEASED OUTSIDE OF JAPAN. 165

- - : I : + - - . - - - -

- ’ 33i-EO : - 40 +

134 - 100 - 132 - - . - 30-80 -t + - 55 1 - 20 - 4’3-136’ .

52-102 . I 7 40--00 I - 53

. I 43

- . + + __ . Necropsy + + 4 470 g . Necropsy

a + + + + + i 40po . . Necropsy + + + + 175/90 - + + I + + . + 150-180/80 +’ + . + + Hypertension + + Necropsy . + . + + + 230/130 -’ + Necropsyls . + + + 130-150 -* +

I1 + - _ -

. + + + 230/150 350 g . Necropsy

. + f‘ + O Necropsy

. + 125

- + + . -

. + + l40/80 . AST 700 E

. + - + + 110/40 - . Necropsy + + + - + 180/130 - . Ecg low ampti- tude

. + - + 250/00 + . Aortic insuff.

. + . + 240/140 -’ + . + l50/90* + +

+ + + + 245170 + + One kidney small

- . + + + + f0 . + + I ’ . + . + . Biopsy: pcriar- teritis nodosa?

-

. + 1901130, + + 210/140 (+) +?

i . + . + 1 4 260,1501 . +

Occurrence. As already mentioned Takayashu’s syndrome has been described mainly by

Japanese authors, 58 cases being collected by Caccamise a,nd Whitman. Outside

166 ERIK ASK-UPMARK.

of Japan the observations have been scanty but including my own two cases reports are available on a t least 28 cases, 2 of which have been observe’d in America and 26 in Europe, with England, Norway aiid Sweden furnishing the majority. The occur- rence around the North Sea and the obviously bad influence of moist weather conditions remind us of the Japanese cases and may or may not be of some impor- tance. The Norwegian cases deserve particular mention: on the one hand one of the very first cases described outside of Japan was Norwegian (Raeder aiid Harbitz), on the other hand 110 less than two out of three cases have been examined post Inortem in a commendable way (Raeder and Harlitz, Frovig aiid Loken). It will be seen that whereas only 2 cases were reported in the 20’s aiid 2 cases in the ~ O ’ S , no less than 12 cases were described in the 40’s and SO far 12 cases in the 50’s. \Vithout doubt more cases will be observed in the future.l As to the sex 39 out of 44 Japanese cases were females; in this study 27 out of 28 were females. The age is remarkable: in the main i t is young women that are affected, about 30 years of age, the youngest case being reported by Giffin (19 years) the oldest by myself (case TI above = case 22 in table). The correlation with the years of genital ac- tivity is unmistakable and reminds us of quite another enigmatic disease, lupus erythematosns disseminatus (vide infra p. 175).

An at o in y.

Anatomically, Takayashu‘s syndrome is characterized, firstly, by an obliteratiiig arteritis particularly of the brachiocephalic arteries, secondly, by the development of an arterial collateral system for the supply of the upper half of the body. Necrop- sies have been reported in 8 instances: Beiieke (1925), Raeder and Harbitz (1926), Marinesco and Kreindler (1936), Gilmours case I (1941), Lewis and Stokes’s first case, examined by Himsworth arid Glynn (1949), Jo6b’s second case (1947), MaspBtiol and Taptas (1948) and Frovig and Loken (1951 = same case as reported by Frovig in 1946). As pointed out by the two authors last mentioned i t should be emphasized that a necropsy intended to elucidate the eiitaiigled derangements of the circulation in such cases has to be combined with a complete and detailed arteriography post mortem. I t seems to me that this examination should include the pulmonary circulation as well.

1. The brachiocephalic arteritis doniiiiates the anatomical as well as the cliiiical picture. It is localized to the innominate artery, the carotid arteries and the sub- clavian arteries. It has the character of a panarteritis, involving all layers of the arterial wall and, as a rule, sooner or later resulting in an obliteration. The artery will hence be transfornied from a canal with soft, functionally efficient walls iiito a solid cord; a certain recanalization may occur. The extension of the pathological tissue may be variable. It may start immediately a t the origin from the aortic arch, where the orifices of the three large arteries from the convexity hence may become obliterated but i t may also start some few centimeters from the origin. It may end completely in the carotid sinus but also extend itself until immediately below the base of the skull (the left carotid artery in the case of Frovig and Loken) or even in the middle of the carotid canal (the right carotid artery in the same case). _ _ _ _

See Addendum.

c

, '

ON THE IPULSELESS DISEASE)) OUTSIDE OF JAPAN. I67

The iiivolvement of the carotid sinus is of particular clinical importance (vide infra). As to the subclavian arteries the pathological alteration as a rule seems to end a t the level of the origin of the vertebral artery, although i t sometimes may proceed beyond this point. The proximal part of the vertebral arteries was more dense than iiornial in the case of Frovig and Loken. It should be particularly em- phasized that the pathological alteration does not seem to involve the intracranial vessels, which are entirely normal except for a dilatation of art.. commuiiicans posterior which could reasonably be considered compensatory (Frovig and Loken). In Harbitz‘s case, however, an incipient thrombosis was to lie registered in the left art . fossae Sylvii and also in the longitudinal sinus. The brachial and the radial arteries were normal in the case of Frovig and Loken as were also the femoral and the dorsalis pedis arteries, with the exception that crescent- or pillow-shaped fi- brotic proliferations of the intima were to be registered; the same was the case with art . centralis retinae and, in Harbitz and Raeder’s case, with i,he right brachial ar- tery. My own case I seems to be the only one where inflammatory alterations of the same character as in the big arteries involved were to lie observed in an artery of the foot (dorsum); i t is instructive to note the occurrence of proliferations of the intima also in the arteries of the dermoid cyst in the same case. With regard to the aorta the occiirreiice of an infiltration of its wall almost so dense as to suggest car- tilaginous structure was observed by Harbitz and Raeder particularly in the de- scending thoracic and the abdominal part, by Frovig and Lijken more so in the ascending aorta and the arch, by Oota in the thoracic aorta and by nlarinesco and Kreindler also particularly in the arch. The pathological tissue has accordingly a definite affinity for the proxinial par t of the aorta, particularly thc arch, but may also extend itself into the abdominal aorta towards the region of the bifurcation. In such instances the big abdominal arteries may be involved at least as far as their origin from the aorta is concerned: with Raeder and Harbitz such was the case with art . coeliaca and art . mesenterica inferior, with Frovig and Loken more so with art . mesenterica superior. It is obvious that also the origins of some intercostal arteries may become involved (constricted or obliterated) and this alteration may extend itself to the first few centimeters of these arteries. With regard to the renal arteries they have been described only in the two Norwegian necropsies. They were normal except for some narrowing of their origin (the case of Raeder and Harbitz). In my own case I there was a strikingly small rightsided kidney, the function of which was seriously impaired as judged by the urogra,phy. It is perfectly obvious tha t an obstructioii of the renal artery with a subsequent infarction and organisation of the kidney may be considered but the possibility is not to be exclu- ded that there may be a primary hypoplasia of this kidney, as described by our- selves in another paper (Ask-Upniark 1929). Jo6b’s case 11 is not recognized by Liiidquist as identical with the disorder here in question. This, however, may be disputed. On the one hand i t may be admitted that the details are scanty and tha t the evidence presented is suggestive of arteriosclerosis. On the other hand the ex- tremely high sedimentation rate in a young woman with seriously affected big arteries and the presence of extra thoracic collateral arteries are facts hardly com- patible with arteriosclerosis as the only cause. Also in this case one of the kidneys

168 ERIK ASK-UPMARK.

(the left) was very much reduced in size (weight 40 gm). An involvement of the orifices of also the coronary arteries has been described by Frovig and Loken .and the same authors describe an alteration of the proximal part of the pulmonary artery of about the same character as in aorta.

2. The brachiocephalic arteritis implies the presence of ischaemia in the struc- tures of the head and the arms. In order to compensate for this deficient blood supply a collateral system is being developed so that blood is carried from the de- scending aorta by means of intercostal and/or diaphragmatic arteries to the subcla- vian system, firstly art. thoracodorsalis but also art. mamm. interna and further on by means of the vertebral arteries to the head. The condition may accordingly be compared with an inverted coarctation, as emphasized by Giffin and Dill, Lewis and Stokes, Frovig. Even crenations of the lower borders of the ribs, as induced by serpiginous and ectatic intercostal arteries, have been observed (Lewis and Stokes, Frovig and Loken). Superficial arteries, palpable through the skin, have been registered by Lewis and Stokes in their first case (on the abdominal wall and a t the dorsal surface of thorax), by Jobb in his second case (interscapular region) and by Skipper and Flint in their second case; i t seems likely that this feature might have been observed more frequently if only properly looked for. Frovig made the instructive observation that on puncture of the vertebral artery the blood did not spurt out, as is usual from an arterial vessel, but appeared in a .continuous stream. In this case the arteriography post mortem was able to dem- onstrate the presence of an entangled network of fine arteries a t the level of the convexity of the aortic arch.

3. With regard to other anatomical observations the reduced size of one of the kidneys in my own first case and in Jobb’s second case should be recalled as might also the origin of the left carotid artery from the anonymous artery in Frovig and Loken’s case. It is impossible not to remember the importance of certain mal- formations as disposing factors in various diseases. Such is the case, for instance, with the occurrence of two aortic cusps instead of three, which invites a valvulitis. Such is the case also with the peculiar type of renal hypoplasia which invites the appearance of malignant nephrosclerosis. Whether the small kidney in the two instances here concerned should be ascribed to hypoplasia or to arterial obstruction need not be further discussed. The heart did present a pericarditis and endocar- ditis in Jobb’s case 11, a certain enlargement in the cases described by Raeder and Harbitz, by Kouretas and Djacos, by Frovig and by Jervell (where aortic insuffi- ciency was presumed), and a most considerable enlargement in my own case I . When judging the size of the heart it is necessary to remember on the one hand the fact that an arterial hypertension, as judged from the observations of the legs, was present in several of the cases here concerned, on the other hand the fact, empha- sized by ourselves in a paper on aortic coarctation in 1942, that the heart does not respond to an arterial hypertension with enlargement to the same degree in females as in males. Finally, as far as the endocrine organs were concerned, no constant or characteristic changes seem to have been registered although the description is slightly different in the various cases; i t should be particularly emphasized that when the pituitary gland is described no necrosis seems to have been found. That

ON THE LPULSELESS DISEASE0 OUTSIDE OF JAPAN. 169

no Sheehan syndrome is present, in spite of the malnutrition of the head, is easily t o be seen from the fact that the periods do not seem to be seriously affected.

CI it1 icnl S yti d 1.0 ti1 e. The symptoms in Takayashu’s disease may be briefly summarized under five

1. The ischaemia of the upper half of the hody. 2. The development of a collateral circulation. 3. The carotid sinus syncope. 4. The cardiac symptoms. 5. The general symptoms.

aspects

1. Ischaemia in the craiaial part of the body. These symptoms are found in the arms and the head and might be compared with

a claudicatio intermittens, where the arterial insufficiency gets progressively worse. A. With regard to the arms the characteristic symptoms are rapid exhaustion

and pains, particularly if working with the arms elevated (e. g. when hanging washing) but also in other connections, such as scrubbing, milking cows, playing the piano. The radial pulse is not to be felt, and no blood pressure can be registered; the oscillations are poor or absent. The necessity to register the blood pressure on all four extremities should be emphasized. One may get the information that the nails grow but slowly or that the arms turn white when elevated and bluish if hanging down. Case (25) had pains in her nipples if exposed to cold.

B. As to the head, symptoms are to be registered from the splanchnocranium, from the brain and from the eyes.

The splanchnocranium may present claudicatio intermittens with regard to the masticatory functions. Thus, when chewing, these patients are apt to get easily exhausted and to feel pains in the jaws, for instance in my case I1 but also in the cases described by Raeder and Harbitz and by Giffin. A pronounced atrophy of the alveolar processes with loss of the teeth has been repeatedly registered and adds to the thin, pigmented skin in giving an aged appearance to the face, such as would become a very old woman. Sometimes perforation of the nasal septum has been described (Marinesco arid Kreindler, Kouretas and Djacos, Caccaiiiise and Whitman), sonietimes also ulcerations of the palate or of the concha media (Masp[tiol and Taptas) or a t the upper margin of the ears (Kouretas and Djacos).

The brain with its well-known susceptibility to reduction of the blood supply will in advanced cases have to rely upon the scanty supply offered by means of collateral systems. The circle of \Villis represents a certain safety arrangement although of limited value since, in these cases, the blood has to be supplied mainly by means of the vertebral artery. The posterior communicating arteries may, of course, become elaborated and enlarged but they do represent the weakest and most fragile link in the arterial circle. It is hence entirely understandable that neurologi- cal symptoms are common. They may be represented by more or less transitory

170 ERIK ASK-UPMARK.

hemiplegias or hemipareses but also in other syndromes such as aphasia or epilep- tiform seizures or a mental impairment with increased irritability, emotional incontinence, reduced memorising ability and bad temper. My last case was a German woman who had been living in Sweden for 5 or 6 years and then for one year in Brazil. She had learned to speak Swedish as well as Portuguese, which a t her age and with her vascular handicap must be considered rather an admirable performance. It was quite characteristic that during bouts of her disease she firstly lost the ability to speak Portuguese, then her ability to speak Swedish whereas the German language was being preserved.l

It is only natural that fits of unconsciousness may appear in these patients even so as to dominate the clinical picture (for instance in Lewis and Stokes’s first case). In this case, however, a contributory factor seems to be represented by an increased susceptibility of the carotid sinus (vide infra).

The blood supply of the eye2 is apt to become particularly impaired, on the one hand because it belongs to the vascular province of the carotid artery, which is the main vessel involved, on the other hand possibly also because of the peculiar haemodynamic conditions to be encountered in the eye: even in healthy aviators the black-out phenomenon precedes the unconsciousness when turning the machine abruptly upwards from a steep dive. In the great majority of the cases here assem- bled ocular symptoms were accordingly evident. Four different signs may be encount- ered, frequently in various combinations: retinal changes, atrophy of iris, cataract and corneal opacities. Thus corneal opacities were to be met with in both of my own cases and in one case of Skipper and Flint; i t seems more often to be a late than an early symptom. When studying the tension of the eye Kouretas and Djacos obtained a corneal oedema around the tonometer. The retinal pathology is domina- ted by the vascular disorders: the arteries may be narrow and are easily compressi- ble, the veins are dilated but for local constrictions so that their appearance may remind of a string of pearls or perhaps more of the legs of a crab. In the veins the blood stream is frequently so slow as to be easily observed (sludged blood). Nu- merous microaneurysms may be seen, being of the same type as in diabetes, occa- sionalIy also retinal haeinorrhages and sometimes the formation of new vessels across and around the optic disc, somewhat like a network or a wreath. Consider- able interest attaches to the valuable observation of Kouretas and Djacos on the correlation between the retinal alterations and the posture: they were more pro- nounced in erect or sitting position and least pronounced in Trendelenburg position. The occurrence of cataract seems as a rule to be later than the retinal pathology (cf. the cases of Skipper and Flint and my own last case): with regard to case (22) i t was instructive to observe the considerable progression of the cataract of the left eye during only one week of a rather moderate cortisone treatment. The cataract

A similar observation on the astacking up? of various languages was the following observation of ours. A man had emigrated from Sweden t o the United States when aged 15 and had been living in a region and under conditions where only English was being spoken. When aged 75 he got a vascular lesion of his brain with aphasia. On recovery he was able to speak only Swedish and had t o emigrate back t o the old country again.

It is instructive that involvement of the hearing is only rarely mentioned in these cases ( e . 9. case Beneke and case Raeder and Harbitz). This may depend upon the principal nutrition of the ear being from the vertebral part of the arterial circle.

ON THE ))PUI,SELESS DISEASE)) OUTSIDE OF JAPAN. 171

]nay otherwise vary from incipient opacities in the lens to total, mature cataract. ‘The cataract as well as the alterations of the retina and the cornea are obviously to be ascribed to the arterial malnutrition of the eye. The same applies to the atrophy of the iris: one gets the impression of a quite unusually thin, mydriatic iris, which obviously appears to invite to adherences in the angular region of the anterior chamber, hence presenting a disposition towards a glaucoma. As a matter of fact the eye may present evidences of a caput Medusae (as in my last case) although the tension of the eye, when registered, always has been found to be low, for obvious reasons. On the whole the ocular affection in this disease seems likely to elucidate several questions of ophthalmological importance. Frovig’s shrewd observation of the reduction of visual acuity on walking should be particularly remembered: the same phenonienon may occasionally be observed in dissemiiiated sclerosis. In one case only (the first case of Lewis and Stokes) the ophthalmological .observations are described as a primary optic atrophy: since the acuity of vision had already become diminished with every f i t suffered by the patient some corre- lation with the disorder in question must be presumed. In 8 out of 10 cases where the description allows a comparison between the eyes the right eye was the one earlier and inore severely e1igaged.l

2. Xigns of collateral circulation.

These signs are represented by palpable superficial arteries, by crenations of the ribs and by vascular murmurs. Palpable superficial arteries on the outside of the thorax were registered by Lewis and Stokes, by Jo6b and by Skipper and Flint. Such arteries should be systematically looked for and palpated for. Creiiations of the ribs were noted by Frovig and Loketi and also by Lewis and Stokes. In such instances the question of the presence or absence of such crenatiotis should be raised with our roentgenological colleagues. As to the vascular murmur it is rather similar to a machinery murmur although i t is more pronounced in systole. In the material here collected i t has been observed by Giffin, by Kouretas and Djacos, by GiImour in his case I, by Lewis and Stokes in both their cases, by Skipper and Flint in their case I1 atid in both of my own cases. The localisation was in most instances in the angle between the clavicle and the sternocleido-mastoid niuscle (on the right side in my own case I and in Lewis and Stokes’s first case -in the latter it was audible .over a considerable area of the body; on the left side with Skipper and Flint and in my own case I1 - in the latter i t extended up towards the mastoid region and very much annoyed the patient in her left ear). In Giffin’s case i t was heard to the right .of the cricoid cartilage and with Kouretas and Djacos in the interscapular and supra- scapular region. The murmur should without doubt be amscribed to the elaborated .collaterals and to the haemodyiiamic conditions implied by them. In Beneke’s

’ I n the cme of Frovig and Loken the cataract of one of the cyes was opcratcd upon one mont,h before thc cleat11 of the patient. There is no information about t h c cffcct. on the visiial acuity. On the ,one hand the probability seems considcrable that retinal changcs were ap t to reduce the benefit of the opcration since they generally seem to preccde the cataract. On thc otlier hand the technical conditions seem to be re:tsonable: in my own case I1 (22 ) i t was spontaneously reportcd tha t wounds in the fingers wcre a p t to heal qiiitc easily and there are some observations of ocular transplantation experiments in fish, made several years ago by Fritz Ask, letc professor of Ophthalmology at the University of Lund, where i t \VRS found that. t h e healing was being facilitated hy a certain malnutrition of the fish.

172 ERIK ASK-UPMARK.

case the murmur was maximal along the carotids and over the abdominal aorta and the femoral arteries: in this case no collateral vessels seem to have been reported, the vascular pathology being confined to alterations of the walls of the big arteries.

3. Carotid sinus syncope.

An increased sensibility of the carotid sinus with ensuing affinity for syncope was described by Shimizu (1948) as characteristic for Takayashu’s syndrome. Cases outside of Japan as collected in this paper did present positive supporting information with Marinesco and Kreindler, Kouretas and Djacos, Lewis and Stokes’s first case, Jobb’s first case, Caccamise and Whitman, Jervell, and Skipper and Flint’s first case, that is in altogether 7 instances. It is very likely that the real number should be considerably greater, only the syndrome is not generally known. It is certainly familiar to me and yet I failed to test my patients on this point, a n instructive example of human fallibility. The attacks have the character of s p - cope and are particularly apt t o occur on postural alterations of the head, for in- stance if it is being raised or bent forwards or if the patient suddenly is changing her position from recumbent to sitting, but also if pressure with the finger or by a stiff collar is exerted towards the sinus region. It is extremely instructive to note the remarkable observation of Kouretas and Djacos that the sensibility of the sinus varied with the female period: it was most pronounced immediately before, during and immediately after the menstrual period. This observation is entirely compatible with our knowledge about the lowered threshold of irritation during these periods (Ask-Upmark 1945) but has to the best of my knowledge not been previously described in connection with the carotid sinus syncope. In connection with the sinus reaction there has also been described a ))spasm)) of the retinal vessels and this observation has been considered as evidence for a nervous correlation between the sinus and the cerebral circulation. That a correlation does exist has been conclusively demonstrated elsewhere (Ask-Upmark 1935), only it is the other way round: a stimulation of the sinus nerve gives a slight dilatation of the cerebral arteries, which, however, is entirely neutralized and overcompensated by the fall occurring in the systemic blood pressure. For the word nspasmo, as used by Kou- retas and Djacos, there should be substituted an arterial collapse of the vessels. That such is the case may be seen also from their own beautiful demonstration of the bilateral collapse of the retinal arteries on the administration of amylnitrite. It seems reasonable to assume that the arterial systems of the brain and the retina are particularly apt to follow the variations of the blood pressure if the blood supply is scanty and the observations in this disorder may hence be considered as a clinical confirmation of the experimental investigations on animals that were pub- lished in 1935 by Ask-Upmark. It may be presumed that the essential factor in the carotid sinus syncope in these cases is of cardial (vagal) or vascular (hypotensive) character although i t is not to be excluded that a cephalic factor may be involved as well (cf. Weiss and Baker and particularly Pistocchi). Electroencephalographic studies in these instances are highly desirable. The cicatricial tissue around the carotid sinus seems to represent the susceptible basis for the increased reflex sensi- tivity -possibly the carotid artery is less movable in the tissues of the neck and

ON THE >>PULSELESS DISEASE)) OUTSIDE OF JAPAIi. 173.

hence more apt to exert a traction on the carotid sinus nerve when the position of the head is changed.

4. Cardiac symptoms.

Tachycardia seems to be common in Takayashu’s disease. It is mentioned by Marinesco and Kreindler, Raeder and Harbitz, Kouretas and Djacos, Lewis and Stokes, Caccamise and Whitman, Serve11 and in one of my own cases. Whether i t has anything to do with the elimination of the normal buffer nerve mechanism or if it depends upon other factors remains to be settled. The phenomenon is obviously not constant.

Arterial hypertension has repeatedly been registered in the arteries of the lower limbs although this phenomenon is not constant either. It has been recorded by Gilmour in his case I , by Lewis and Stokes in their first case, by Frovig, by Caccamise and Whitman, by Jervell, by Skipper and Flint in their first case and by myself in my case I. A fairly normal blood pressure in the legs has on the other hand been noted by Giffin, by Kouretas and Djacos, by Lindquist, by MaspBtiol and Taptas and by Skipper and Flint in their second case. In my own case I1 claudicatio intermittens was to be encountered also in the legs, where no blood pressure could be elicited. In Jobb’s case I1 the blood pressure on the left arm was 2251120, on the right arm 150/110. Considering the age of the cases here in question i t may be considered quite remarkable that arterial hypertension was present in 11 out of 18. cases thus examined. Several factors may be involved in this hypertension, which as a matter of fact seems to illustrate the multitudiness of the pathophysiological mechanisms in hypertension:

1. ,The blockade of the buffer nerves. 2. The decreased elasticity of the arterial ,wind kettle)). 3. The involvement of the origin of the renal arteries. 4. Possibly also the presence of unilateral renal hypoplasia (cf. p. 167).

As emphasized by us in a paper in 1942 on aortic coarctation, the female heart will not react to arterial hypertension with the same hypertrophy as will the male heart. Nevertheless, the heart was registered as enlarged in Raeder and Harbitz’s case (470 g), in Kouretas and Djacos’s case (where no definite hypertension seems to have been present), in Sobb’s case I1 (where, howev,er, there was also a mitral and pericardial involvement) and in one of my own cases, where the cardiac symptoms dominated the whole clinical scene. Jervell’s case, finally, was considered to present aortic incompetence.

5 . General signs. Fever was registered in the initial stage of my own case I, by Kouretas and Djacos

and by MaspBtiol and Taptas. The most conclusive evidence as to an activity of the disease here in question is furnished by the increased sedimentation rate, which has been observed in every case thus examined. It may reach considerabIe levels: in Lindquist’s second case it was 132 mm/l hour, in Jobb’s case I1 134. The mini- mum level was registered as 20, in my case 11. No obvious alteration of the blood

174 E R I K ASK-UPMARK.

morphology has been registered. In all cases examined in this regard (21 in the present material) the Wassermann reaction was negative. The tachycardia has already been mentioned.

Aetio 1 ogy :tiid Pibt 11 ogcbn esis. Not only the aetiology but also the pathogenesis is unknown. There can be no

doubt but that the character of the disease is an arteritis.’ Convergent evidence to this effect is represented by

1. The histological appearance of the arterial wall. 2. The increased sedimentation rate and 3. The history of the individual cases.

M7ith regard to the history it will appear as if some sort of reumatic ( 2 ) infection may be traced in the cases (l), (8), (12), (13), (15), (16), (19), (21, (27). The antistrep- tolysin titre was increased in case (14). The cases (16) and (21) had some outstanding dermatological signs in connection with their being taken ill (erythema multiforme? nodosum?). The cases (7) and (15) started their history with fever. The case (23) had had a tonsillar abscess twice; case (25) had frequently had a sore throat. About the rest of the cases no information is available, only that case ( 2 ) had scarlet fever when aged 26 and case (11) had had infectious hepatitis half a year before the first symptoms appeared. Nevertheless, from the anamnestical point of view there is strikingly often an infectious disease, frequently of rheumatic character, heralding the manifestation of Takayashu’s disease. It may or may not be coincidental that no less than 18 of the cases here in question were observed in the countries around the North Sea (Great Britain, Norway, Sweden) which is a region predis- posing to rheumatic infections.

The arteritis in question has two quite characteristic features: firstly, the predi- lection for young women, secondly, the localization mainly to the thoracic part of the aorta and the branches derived from the convexity of the aortic arch. Case (22) in the present study demonstrates that the first of these rules is not without exception. Case (21) in this study represents an elaboration of the second point, in as much as the artery of the skin of the foot did present the characteristic altera- tions as well.

With regard to the predilection for females, substantiated also by the Japanese material, one is reminded of a similar predilection in the temporal arteritis, a disease without doubt of infectious origin. This temporal arteritis, however, is ap t to occur mainly in old women and the prognosis is as a rule generally good, whereas Takayashu’s syndrome deals with young women and has a poor prognosis. The question may be raised whether the female body has some peculiar qualities, ap t to influence the reaction towards an infection. Such is without doubt the case. Thus, i t is well known that erythema nodosum in males almost always will appear before puberty; i t is, essentially a disease of male childhood, whereas in females --

1 Reneke’s case should without doubt be assigned to this disease. The same is probably true also for Jo6b’s case 11: against the doubts expressed by Lindquist may be argued that the prescncc of such a scvere arterial disease in a young woman with superficial arterial collaterals and a scdimentation rate of 134 makes it compatible with tho present group.

ON THE ))PULSELESS DISEASE)) OUTSIDE OF JAPAN. 175

erythema nodosum not infrequently is encountered also after puberty. The peculiar disease represented by lupus erythematosus disseminatus has a predilection for females about the age of 30 that very much reminds us of Takayashu’s syndrome. There are sometimes virus pneumonias exclusively affecting the female members of the family, whereas the males escape although they are just as much exposed: Reimann has published an instructive example of this observation. In thrombangi- tis obliterans (Buerger) the disease favours the lower limbs of males, in Takayashu’s syndrome the upper limbs of females without, a t least in most cases, affecting the legs. Periarteritis nodosa has a predilection for middle-sized arteries, it is apt to give more localized symptoms and it will readily run a course with eosinophilia which is not characteristic for Takayashu’s disease. It is impossible not to get the impression that Takayashu’s disease involves a specific reaction of the body towards an infection, whether or not one chooses to call i t an allergic-hyperergic reaction. It is not entirely unbelievable that pregnancy may prepare thc soil: on the one hand the disease has occasionally taken its apparent origin during pregnancy (ease 20), 011 the other hand 10 out of 11 females where information pertaining to this matter was available had been pregnant and, finally, i t is wcll known that the ar- terial system is influenced by pregnancy (cf. the aneurysms of the splenic ar- tery, the vascular spiders of the skin etc).

As to the localization to the aorta and to the big arteries derived from its arch it should be emphasized that this localization, although dominating, is riot exclu- sive. The pulmonary artery may also become engaged and branches from the ab- dominal aorta such as the art. coeliaca, the art. mesenterica cranialis and the art. mesent. caudalis may present alterations, a t least a t their origin from aorta. Nev- ertheless, the localization to the thoracic aorta and its brachiocephalic branches represents the outstanding topographical predilection. Only hypotheses may be ventured to explain this fact. On the one hand i t would be reasonable to consider an exogenous infection, which may be derived from the respiratory tract, the mammary glands (females!) or the abdominal organs (cf. the observation of the infradiaphragmatic tuberculosis in lfarinesco and Kreindler’s case) and which may engage the arterial structures of the mediastinum (cf. the abdominal lymphatic stream towards and through the diaphragm to the mediastinum). On the other hand one has to realize that this very region of the arterial system occupies a uni- que position from the hydrodynamic point of view in as much as it represents the important first part of the ))wind-kettle)). That structures subjected to effort are apt to become the seat of allergic reactions is well known and has been dealt with elsewhere ( Ask-Upmark 1943). One might perhaps, finally, remember that not least in this very region of the arterial system obliteration and involution are part and parceI of the normal evolution: the disappearance of the carotid duct, the in- volution of the right aortic arch in mammals, the obliteration of the Botallic duct may be quoted as examples, which easily may become extended into the teratology (for instance aortic coarctation) or the comparative anatomy (cf. the peculiar blood supply of the brain in snakes!). The factor of sex is involved in those mechanisms as well: why coarctation is so much more common in males is thus just as enigmatic as why the Botallic duct is inore frequently left open in females or why the glomus

11-5411G7. Actn nied. Scnndinciu. 1’01. C S L I S .

176 ERIK ASK-UPMARK.

tumours of promontorium tympani - the old province of the stapedian artery - are ten times as common in women as in men. In case (11) of the present material an obvious malformation was present in that the left carotid artery was derived from the innominate trunk. More information along these lines is t o be obtained from the Japanese cases: thus, Sat0 (1938) mentions one case with open Botallic duct and another case with pulmonal stenosis.

Prognosis and Treatment.

The prognosis in Takayashu’s syndrome has so far to be considered as fatal quoad vitam as well as quoad valetudinem. Death will apparently as a rule result through cerebral ischaemia, although in cases with hypertension also cardiac fa- talities may have to be considered. Even the kidneys may become the atrium mortis partly as a consequence of the arterial hypertension and partly through oblitera- tion of the origin of the renal artery from the aorta. I n these unfortunate cases it is perfectly obvious that complications may ensue and eventually become fatal. The course, however, is chronic, not infrequently through several years: the ex- tremes seem to be represented by Raeder and Harbitz’s case ( year) and Jervell’s case as well as one of my own cases (more than 14 years and still alive).

With regard to the treatment one may distinguish between general hygiene, med- ical treatment and surgical therapy. As to the general hygiene of these patients tlie paramount thing to remember is not to overstress the ischaemic structures. I n two instances (case 15 and 21) the patients have emphatically maintained that they do better in a dry and cold climate (reduction of metabolic function as in the treatment of incipient gangrene?) and one case (21) was firmly convinced that the consumption of alcohol was apt to improve her condition. This may well be true since hardly any other substance is so active in dilating the cerebral arteries (ob- servations of C. Bedell with the window technique of Forbes). There can be no doubt but that these patients should, when recumbent, have their head low down and the observations of Kouretas and Djacos tend to suggest special precautions during the periods (bed during those days, possibly with a slight elevation of the foot end of the bed). Some prophylactic Buerger gymnastics with the upper end of the body in the r61e otherwise given to the legs may be attempted. Exhaustion, however, should by all means be avoided and the observation of Frovig on the decrease of the visual acuity during walking seems to contain a sound warning.

As for medical remedies there may be an understandable desire to give anticoag- ulant drugs to these patients. Opinions diverge, however, as to the effect; drugs like heparin or dicoumarol are apt to get the patient laboratory-ridden and whether these drugs are safe in instances with retinal haemorrhages may be disputed, although their use in thrombosis of the retinal veins tends to suggest that such may be the case. Yasodilating agents may apparently be justified but one must never forget that a drop of the blood pressure, if thus induced, may be fatal for the already hampered cerebral and ocular circulation (cf. the observation of Kouretas and Djacos about amyl nitrite). It is possible that alcohol may be an exception and that i t might be used in moderate doses in suitable cases (vide supra). Antibiotics do not seem to have yielded any effect whatsoever as far as can be judged from the

ON THE OPULSELESS DISEASE)) OUTSIDE OF JAPAN. 177

limited material so far available. Yet, since we know that a systematic use of antibiotics in infections of the upper respiratory tract (angina etc.) is apt to reduce the occurrence of rheumatic fever, the possibility should not bc, denied that such a treatment may give some degree of prevention also against such complications of the rheumatic infections as the pulseless disease may conceivably represent. It seems entirely reasonable to attempt treatment with ACTH or cortisone if no contraindications exist: but the obvious progress of the cataract during the mod- erate treatment with cortisone (2 x 25 mg for one week) in case 22 represents a warning. An attempt may be made to treat these cases with male hormones: no harm can reasonably be done and the predilection of the disease for the female sex makes it tempting to t ry this. It is an important truism in these cases that the bowels should be kept moving in order to avoid straining when a t stool. If cardiac failure should appear it is evidently necessary to use strophantine or digitalis. This, however, is a serious step to take if the case should have a susceptible carotid sinus, since the sensitivity of the sinus becomes enhanced by digitalis and thus a deterio- ration of the cerebral blood supply may ensue. Tachycardia in itself will not justify the use of digitalis in such a case. On the other hand an attempt to prevent the carotid sinus syncope by giving atropine may be considered, provided that the syncope is of the vagal type. A point to be remembered is that atropine will always increase the danger of glaucoma, which anyhow is imminent in these cases.

Surgical treatment can so far be offered only against certain complications. It may be justified to make an attempt surgically to denervate the carotid sinus, should this be very susceptible with resulting syncope and subsequent further impairment of cranial blood supply. A cataract may be operated upon, as done by Takayashu, but the retinopathy may well precede the cataract so the expectations should be judged with due precaution. The ideal operation would be the substitu- tion of the carotid arteries but whether such an intervention will be feasible in the future remains to be seen (use of jugular vein?). Sympathectomy in the neck may or may not favour a cerebral vasodilatation: no influence on the severe organic disease of the carotid artery is to be expected anyway.

Siininiary and Conclusions.

1. A survey is given of the cases of opulseless disease)) observed outside of Japan, in Europe and America. In all 28 cases have been assembled, including two hitherto unpublished cases of my own. 27 out of 28 were females, the average age being 30 years. The disease is apparently somewhat less uncommon than generally assumed.

2. The anatomy is briefly reviewed. Although the thoracic part of the aorta and the brachiocephalic arteries represent the main province of the disease, alterations may be found also in other arteries, thus in one of my cases in an artery of the foot. The collateral system is discussed and the possibility of certain malformations briefly mentioned. The behaviour of the heart is reviewed, one of my own cases possessing a most considerable cardiac enlargement.

3. The clinical syndrome of Takayashu’s disease is represented by 1. the ischae- mia of the upper half of the body (arms, face, brain, eyes), 2. the development of the collateral system, 3. the increased sensitivity of the carotid sinus, 4. sometimes

178 ERIK ASK-UPMARK.

cardiac symptoms, 5. general symptoms, mainly an increased sedimentation rate. 4. The aetiology and pathogenesis are discussed. There are some few pertinent

features to be considered: the character of a n arteritis, the predilection for females, the localization of the pathological tissue.

5. The prognosis is poor in the long run but there is some evidence tha t treat- ment may be a t least of some avail. This treatment consists of general hygiene, certain medicatioii and, occasionally, surgical interventions. Research on the aetiology may well yield a preventive treatment and some questioiis pertaining t o this matter are outlined.

Bibli o gr sp h y.

Ask-Upmark, E.: 1. Acta Psych. e t Neurol. Scand. Suppl. VI, 1935; 2. Acta Pathol. et Microbiol. Scand. 1929: 6: 383; 3. Acta Medica Scand. 1942: 112: 7; 4. Svenska Lakar- tidn. 1945, nr 9; 5. Svenska Lakartidn. 1943, nr 10; 6. Unpublished observ a t‘ ions. - Beneke, R.: Virschows Archiv 1925: 254: 722. - Caccaniise, W. C. and Whitnian, J. F.: Am. Heart J. 1952: 44: 629. - Frovig, A.: Acta Psych. et Neurol. Scand. Suppl. XXXIX, 1946. - Frovig, A. and Loken, A.: Acta Psych. e t Neurol. Scand. 1951: 26: 313. - Giffin, H. M.: Proc. Staff Meet. Mayo Clin. 1939: 14: 561. - Jervell, A.: Nord. Med. 1953: 50: 1272. - Jo6b, A.: Schweitz. Med. Wochenschr. 1947: 77: 431. - Kouretas, D. and Djacos, C.: Ann. d’0cul. 1940: 177: 161. - Lewis, T. and Stokes, Joan: Brit. Heart J. 1942: 4: 57. - Lindquist, T.: Nord. Med. 1948: 37: 321. - Marinesco, G. and Kreindler, A.: Presse Mkdicale 1936: 44: 1: 833. - Martorell Otzet, F. and Fabre Tersol, J.: Med. Clin. Barcelona 1944: 2: 26. - Masp6tio1, R. and Taptas, J. N.: Semaine d’H6p. Paris 1948, Nr. 84, 10 nov. - Pistocchi, G.: Bull. d. Scient. mkd. Bologna 1932: 104: 256. - Raeder, J. G. and Harbitz, F.: Norsk Magas. f. Laegevidensk. 1926: 87: 529. - Sato, T.: Klin. Wochenschr. 1938: 17: 1154. - Shimizu, K.: Clin. Surg. 1948. - Skipper, E. and Flint, F. J.: Brit. Med. J. 1952: 2: 9. - Takahashi, K.: Arch. f. Psych. u. Nervenkrankh. 1940: 111: 619. - Takayashu, M.: Acta SOC. Opht. Jap. 1908: 12: 554. - Weiss, S. and Baker, J.: Medicine 1933: 12: 297.

Addendum.

Since this paper was written two more cases have been observed in Sweden. One was presented a t a medical meeting in Gavle by our friend and colleague Lublin: it dealt with a woman, aged 62 (!), who since 8 months ago had symptoms of reduced arterial supply t o her arms, increased sedimentation rate (about 60) and obstruction of the distal par t of the axillary and the proximal par t of the brachial artery on both sides, as demonstrated b y arteriography. The other case was a girl, aged 16, who has been observed in our clinic for months: she has, briefly summarized, symptoms of thrombosis of the left internal carotid artery, as evidenced by arteriography and substantiated by surgical intervention. I n this case the sedimentation rate was also considerably increased (about 60) and the temperature as well. Whether these cases should be considered as Takayashus syndrome seems so far uncertain: the age of Lublin’s case seems t o be rather high and the localization of the pathological process was confined, in Lublin’s case, to the axillary-brachial arteries, and in my own case, t o the internal carotid on one side.