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Primary diseases of the cerebral blood vessels
Primary Diseases of the Cerebral Blood Vessels By
AJAX ELI~ GEORGE,M.D.,
PULLA R. S. KISHORE,M.D.,
AND NORMAN E. CHASE, M.D.
P
RIMARY
of death
term
stroke
DISEASE of the cerebral blood vessels is the third major cause and the prime cause of disability in the United States today. The or cerebrovascular accident includes a wide range of diseases of
many different etiologies and varying degrees of prognostic significance, from a transient ischemia attack (completely reversible without residual deficit) to a fatal massive intracerebral hemorrhage. Primary diseases of the cerebral blood vessels may produce neurologic deficit with or without cerebral infarction by: 1. Stenosis or occlusion due to A. Structural changes within the arterial wall caused by (1) atherosclerosis (2) hypertension (3) arteritis: tuberculosis, syphilis, polyarteritis, giant cell arteritis, Takayasu’s disease, radiation, and others (4) miscellaneous causes: migraine, oral contraceptives, fibromuscular hyperplasia, Moya Moya’s disease (5) spasm (most commonly caused by subarachnoid hemorrhage secondary to aneurysm rupture or trauma) B. Embolization either from plaques in the extracranial vessels or from cardiac sources 2. Intracranial hemorrhage, subarachnoid or intracerebral, secondary to (1) ruptured aneurysm and its sequelae (2) hypertensive cerebrovascular disease (3) vascular malformation Among the causes listed above, atherosclerosis and hypertension are the more common causes of cerebral ischemia with or without infarction. ATHEROSCLEROSIS
During the past two decades our understanding of cerebrovascular disease has increased greatly. Pathologic as well as clinical studies now show that intracranial small vessel atherosclerosis plays a relatively insignificant role in cerebral infarction,5,” I ‘.“.P’ whereas the irregular or ulcerative atheromatous plaques at the bifurcation of the carotid arteries and other brachiocephalic vessels are now recognized as a major hazard, increasing the incidence of embolization and causing transient or permanent cerebral ischemia. Although corrective surgery may benefit some of these patients,3~8~17 its role Supported
in part by NINDS
Neuroradiology
Training
Grant NBO 5433-05.
AJAX ELIS GEORGE, M.D.: Instructor, Department of Radiology, New York Unioersity Medical Center, New York, N.Y. PULLA R. S. I&SHORE,M.D.: Instructor, Department of Radiology, New York Unioersity Medical Center, New York, N.Y. NORMAN E. CHASE, M.D.: Professor and Chairman, Department of Radiology, New York University Medical Center, New York, N.Y.
34
SEMINARSIN ROENTGENOLOGY, VOL. 6, No. 1 ( JANUARY) ,197l
PRIMARY
DISEASES
OF THE CEREBBAL
BLOOD
35
VESSELS
in the management of cerebrovascular disease is yet to be determined. Surgical treatment appears to be most beneficial to patients with unilateral carotid artery stenosis which has caused transient ischemia or moderate neurologic deficit.’ A thorough evaluation of each patient is warranted since some patients, though admittedly not a high percentage, benefit from surgical and/or medical therapy. This rather large population with stroke was previously condemned to hopelessness. Although a clinical evaluation may be adequate to localize the site of cerebral ischemia, accurate determination of the status of the intra- and extracranial vasculature is essential to surgical therapy, and this can be achieved only by cerebral angiography. By this means, the collateral circulation can be assessed and the possibility of neoplasm can be ruled out. The techniques of cerebral angiography are discussed elsewhere in this issue ( p. 7); however, a brief discussion is in order here since cerebral angiography performed to evaluate occlusive cerebrovascular disease differs somewhat in method from studies for aneurysm rupture, neoplasm, or trauma. The aim is to obtain good visualization of the entire cerebrovascular tree with minimal manipulation or trauma around the origin of the diseased brachiocephalic vessels. To achieve this, we believe bilateral, percutaneous retrograde brachial angiography followed by left carotid angiography, if necessary, to be ACA
Fig. L-Incidence and distribution of arterial lesions in the brachiocephalit vessels in patients
studied for cerebrovascular insufficiency. There is no significant difference on the two sides. Stenosisat the origin of the internal carotid and vertebral arteries (the most frequent sites of involvement) is approximately four times as common as occlusion. Intracranially, the incidence of stenosisin the posterior, anterior, and middle cerebral arteries rangesfrom 2 to 4 per cent. (Courtesv of Hass, W. K. et al.; reproduced with permission of JAMA 203:961, 1968.)
36
GEORGE,
KISHORE
AND
CHASE
the best method.? Using this approach, visualization of the extracranial portions of the four great vessels and the intracranial circulation is obtained and dislodgment of plaques and embolization may be avoided. In instances where a left carotid angiogram is indicated because of failure to fill the artery on right brachial injection, the needle is placed well below the carotid bifurcation. Angiograph y Although occlusion and stenosis may occur anywhere, the sites of vascular branching are the most frequently involved (Fig. 1). Careful evaluation of the lesion, preferably in more than one projection, is important because irregular or ulcerated plaques may signify cerebral embolismk.D~li (Fig, 2). Arterial kinks, seen more commonly with vascular disease, may also cause considerable narrowing of the lumen, compromising the blood flow. Recognition of branch occlusion is important and is based on ( 1) the absence of a branch at an expected anatomic site, (2) collaterals to the area, (3) stasis in the vessel, and (4) capillary blush. Cerebral edema and infarction are diagnosed by their mass effect, and occasionally distinction from a neoplasm may be difficult, especially when there is early venous drainage from the area. In such circumstances, follow-up studies coupled with brain scanning are helpful. The value of collateral circulation cannot be overemphasized because the degree of neurologic deficit and the ability to recover from it depend upon
Fig. 2.-Ulcerated plaque (horizontal arrow) at the bifurcation of the common carotid and internal carotid arteries. Right
brachial angiogram. Identification of irregularities and ulcerations in plaques is essentialbecauseof embolic implications. There is stenosisof the external carotid artery (vertical arrow) an unusual site of involvement.
PBIhXAFiY
DISEASES
OF THE CEREBRAL
BLOOD
VESSELS
Fig. X-Collateral circulation. A. Absence of filling of the middle cerebral artery on the initial film of a serial left carotid angiogram. Note marked stenosis at the junction of the cavernous and supraclinoid segments of the internal carotid artery (arrow). B. Middle cerebral branches (horizontal arrows) are filled in retrograde fashion via pial collaterals (vertical arrows). Intermediate arterial phase.
38
GEORGE,
KISHORE
AND
CHASE
PFUMARYDISEASESOF'JXECEl3EBFiALBLOOD!'ESSELS
Fig. 5.-Occlusion of tbe left vertebral artery at origin. Filling of the distal intraos-
seous segment of the vertebral artery (arrows)via collateralsfrom branches(arrowhead) of thyrocervical and ascendingcervical trunks. Left retrograde brachial angiogram at 3 seconds. the collateral channels as well as such physiologic factors as cardiac output, systemic blood pressure, blood viscosity, and oxygenation. It is not uncommon to see patients with complete occlusion of three of the four major vessels who have no significant neurologic deficit because of good collateral circulation. Development of effective collaterals depends upon the status of the circle of Willis. The most frequent anastomotic pathways are the anterior and posterior communicating arteries. Pial collaterals occur most commonly between the anterior, middle, and posterior cerebral, and between the superior and inferior cerebellar arteries (Fig. 3). Collaterals are also seen between the internal and external carotid arteries via ophthalmic or meningeal branches in cases of internal carotid artery occlusion; between the external carotid and vertebral arteries in common carotid occlusion; and between cervical and vertebral arteries in occlusion of the origin of the vertebral artery (Figs. 4 and 5). Detailed discussion of collateral circulation is beyond the scope of this communication and the reader is referred to the excellent monograph by Fields et al.’ HYPERTENSIVECEREBROVASCXJLARDISEASE (WITH ORWITHOUTINTRACRANIALHEMORRHAGE) The association of arteriosclerotic cerebrovascular disease and hypertension is not uncommon, increasing the severity of cerebrovascular insufficiency. A necrotizing arteriopathy of diffuse or focal nature occurs in the brain in hypertension. The basic process is one of hyaline and fibrinous changes (rarely with evidence of inflammation) and frequent microaneurysm formation. The arterial lesion occurs in the brain stem and deep nuclei and not in the subarachnoid vessels. The common sites are the gangliothalamic areas, including the internal
40
GEORGE,
KISHORE
AND
CHASE
Fig. 6.-Arteritis in a 24 year old man with a history of tuberculous meningitis.
Left carotid angiogram shows irregularity of the internal carotid (horizontal arrows), proximal middle cerebral (vertical arrows). and anterior cerebral arteries (arrowhead). and external capsule and pons. When bleeding occurs, the angiographic findings are essentially those of intracerebral hemorrhage. ARTERITIS
Arteritis is a less common cause of cerebral vascular insufficiency. Inflammation of cerebral vesselscan be conveniently divided into infectious, collagen, and nonspecific forms. In the infectious group are included syphilis, tuberculosis, hemophilus influenza, and more rarely salmonella. Irregular narrowing of the lumen of the large vessels of the circle of Willis in a patient with a previous history of one of these diseasessuggests the diagnosis (Fig. 6). Infectious arteritis may be associated with mycotic aneurysm, or with epidural, subdural, or intracerebral abscess. Polyarteritis is by far the commonest collagen disease to affect cerebral blood vessels. Lupus erythematosus and rarely rheumatoid arteritis and scleroderma are also known to involve the intracranial vessels. Giant cell arteritis and Takayasu’s disease, the latter by involvement of the aortic arch and its major branches, may rarely produce cerebral ischemia. MISCELLANEOUS
CAUSES
Angiography should be avoided in cases of migraine for fear of increasing spasm. When performed, the angiograms may be completely normal or may show evidence of spasm or branch occlusion. An increased incidence of thromboembolic disorders leading to cerebral ischemia in women using oral contraceptives has been reported.?
PRIXIARY
DISEASES
OF THE CEREBRAL
BtOOb
VESSELS
41
Several reports have described fibromuscular hyperplasia of the internal carotid artery, especially in women, based on the corrugated appearance at angiography. However, the close resemblance to stationary waves, a flow phenomenon, makes this diagnosis questionable unless proved by biopsy. Fibromuscular hyperplasia can be suspected, however, if the possibility of spasm due to needle trauma and stationary waves is ruled out and if the carotid bifurcation is spared.“’ A syndrome consisting of multiple progressive intracranial arterial occlusions in children, originally thought to occur only in Japanese ( Moya Maya’s disease) has recently been reported in this country.“’ This disease is characterized by rapidly progressive stenosing lesions of the major arterial channels along the circle of Willis leading to total occlusion of these vessels. Peculiarly, the process stops once total occlusion has taken place, so that if collaterial circulation is adequate most patients are able to lead a fairly normal life. Characteristically, the branches of the anterior, middle, and posterior cerebral arteries are not involved. The pathogenesis of this syndrome is unknown.““ INTRACRANIAL
ANEURYSM
Intracranial aneurysm is usually congenital or developmental ( berry), arteriosclerotic, or mycotic. Traumatic, luetic, and venous aneurysms are comparatively iare. Berry aneurysms are by far the commonest and their incidence in the general population has been variously estimated from 0.5 per cent to as high as 5.0 per cent. The age incidence varies from 20 to 70 years; it is rare below the age of 10.” Approximately 80 per cent of berry aneurysms occur on the carotid circulation, the remaining 20 per cent occurring on the vertebrobasilar circulation. About 15 to 20 per cent are multiple. An analysis of over 6000 aneurysms showed the following distribution: anterior communicating artery, 30 per cent; internal carotid artery at the origin of the posterior communicating, 24 per cent; and bifurcation of the middle cerebral artery, 13 per cent; only 5.5 per cent of single bleeding aneurysms occurred in the vertebrobasilar system.” Aneurysms account for 50 to 80 per cent of nontraumatized patients with blood in the cerebrospinal fluid. Occasionally, a large aneurysm may present as an intracranial mass. This is more frequent around the base of the brain where a large aneurysm of the internal carotid artery or basilar artery manifests as a para- or suprasellar mass. It is this feature that necessitates angiography to avoid a possible catastrophe when surgery is planned for a suprasellar mass. Angiography Although the diagnosis of bleeding aneurysm can be made clinically with some degree of accuracy, angiography is the only method for accurately localizing and evaluating the aneurysm. The purpose of angiography is to demonstrate the presence and location of the aneurysm, to localize a hematoma that may warrant immediate surgical intervention, and to rule out other causes of intracranial hemorrhage. A follow-up angiographic study in postoperative patients may be a useful prognostic tool.
42
GEORGE,
KISHORE
AND
CHASE
Fig. 7.-Severe spasm of proximal middle cerebral (vertical arrows), anterior cerebral (arrowheads), and internal carotid (horizontal arrow) arteries in a patient
with ruptured internal carotid aneurysm at bifurcation. Note normal size of distal middle cerebral and anterior cerebral branches. Identification of bleeding aneurysm can be difficult. A vascular loop may mimic an aneurysm and sometimes requires examination in multiple projections. Usually it is relatively denser than an aneurysm of the same diameter. The so-called junctional dilatation seen frequently at the origin of the posterior communicating artery and less commonly at the origin of the anterior choroidal artery should not be mistaken for aneurysm. It can be distinguished by its triangular shape, with the branch vessel arising from the apex of the triangle rather than adjacent to it as in aneurysm. Usually it measures less than 3 mm. at the base. It is essential to opacify the entire intracranial circulation in subarachnoid hemorrhage, in view of the significant incidence of multiple aneurysms. With multiple aneurysms, it may be possible to identify the bleeding aneurysm on the basis of the neurologic deficit. However, certain angiographic findings, such as a clot in the aneurysm, arterial spasm, intracerebral or subdural hematoma, or extravasation are helpful in pinpointing the bleeding site. In the absence of any of these signs, it is more likely that the largest aneurysm bled.” The phenomenon of spasm may represent a defensive mechanism to prevent further bleeding. Spasm is usually seen between 2 and 14 days after the onset of subarachnoid hemorrhage and may last for several weeks. A high percentage of patients with ruptured aneurysm have spasm, and this may lead to cerebral infarction. Spasm is diagnosed by a smooth narrowing of the vessel adjacent to the ruptured aneurysm, Arteriosclerotic narrowing is usually more irregular and involves vessels in many areas. One should not mistake a hypoplastic origin of the anterior cerebral artery for spasm. Narrowing of the proximal part
PRIMARY
DISEASES
OF THE CEREBRAL
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VESSELS
43
of the pericallosal or callosal marginal arteries with normal caliber distally is essential for a diagnosis of spasm (Fig. 7). The extent of spasm is variable and may occasionally involve the entire hemisphere and rarely even the contralateral side. It is extremely unusual, however, to see the spasm extend extradurally. Rarely, spasm may prevent the filling of the aneurysm. A repeat examination is required, preferably after a delay of a week or tw0.l’ A space occupying lesion is not infrequent with aneurysmal rupture and is helpful in identifying the site of bleeding (Fig. 8). It may be due to diffuse cerebral edema associated with spasm or to localized intracerebral or subdural clot. Intracerebral hematoma indicates a grave prognosis and may warrant immediate surgical intervention. Hematoma from aneurysm rupture is usually cortical in location, in contrast to the deep capsular lesion seen in hypertensive cerebral hemorrhage. Occasionally, intraventricular clots are visible after subarachnoid hemorrhage. Extravasation of contrast material in the proximity of an aneurysm is rare and also implies grave prognosis. Irregularity secondary to clot formation is often seen in the bleeding aneurysm (Fig. 8). Occasionally, an intraluminal clot may be seen as a filling defect surrounded by contrast material. A tentlikc projection in the dome of the aneurysm is presumptive of the actual bleeding site.
Fig. 8.-Temporal hematoma from ruptured aneurysm. The
large middle cerebral aneurysm has irregular margins due to clot (arrows). Note the elevation and medial displacement of the middle cerebral artery (arrowheads).
44
GEORGE,KISHOREANDCHASE
As with any other large intracranial mass, transtentorial herniation may result from subarachnoid hemorrhage. Hydrocephalus is a frequent complication of subarachnoid hemorrhage and is usually seen about two weeks after the hemorrhage. This delayed ventricular enlargement is apparently due to incisural block secondary to arachnoidal adhesions, in contrast to the hydrocephalus occurring within hours of the bleeding, which is due to obstruction of the ventricular system by an intraventricular clot or posterior fossa hemorrhage. Failure to demonstrate the aneurysm in subarachnoid hemorrhage after adequate examination (including multiple projections and films of good technical quality) is rare. The prognosis of such patients on conservative management is considered to be much better than those with demonstrable lesions.” As mentioned earlier, angiographic evaluation of an aneurysm is not considered complete unless the neck of the aneurysm is demonstrated. Multiple projections are often necessary for this purpose. Finally, the patency of the anastomotic channels around the circle of Willis, particularly the anterior communicating artery, should be evaluated by compressing the carotid artery on the side of lesion with contralateral injection when carotid artery ligation is contemplated. Cross-filling of the involved side by such a maneuver suggests that the patient can tolerate carotid ligation. Aneurysm of the vein of Galen is exceedingly rare and presents as a posterior third ventricular mass on pneumoencephalography. It has a characteristic calcification and angiographic features.* VASCULARMALFORMATIONS
These relatively rare lesions may be divided into arteriovenous malformation ( the most common), capillary telangiectasia, and cavernous vascular malformation on the basis of the angiographic appearance. Vascular malformations constitute 4 per cent of brain lesions initially diagnosed as tumor” and 6 per cent of the lesions causing subarachnoid hemorrhage.‘” In the second decade of life, vascular malformations and intracranial aneurysms are equally probable as the cause of subarachnoid hem0rrhage.l’ By shunting blood away from normal tissues, vascular malformations may be the cause of epileptic seizures, mental deterioration, underdevelopment and weakness of one or more extremity, and an audible bruit. Hemorrhage occurs in 40 to 60 per cent.l’ They may occasionally produce hydrocephalus by obstructing the ventricular system. Arteriovenous
Malformation
Pathophysiologically, arteriovenous malformation represents the persistence of embryonic arteriovenous shunts. It may be composed in varied proportion of dilated, tortuous, venous and arterial structures and shunts. Krayenbiihl’s review of 800 cases shows the distribution of lesions to be extracranial in 3.1 per cent, supratentorial in 85.7 per cent, and infratentorial in 6.2 per cent.” The site of greatest predilection is the region of the sylvian fissure (36.1 per cent) where it obtains its main blood supply from the middle cerebral artery. The arteriovenous malformation is usually localized in the pial region in the shape
PRIMARY
DISEASES
OF THE CEREBRAL
BLOOD
VESSELS
Fig. 9.-Arteriovenous malformation. A. Fine curvilinear calcihca-
tion on the right. The patient had subarachnoid hemorrhage and history of previous seizures. B. Right carotid angiogram of same patient showsa large A-V malformation in the right cerebral hemisphere. C. Different patient. Enlarged corkscrew middle meningeal groove (arrows), indicating external carotid artery supply to the arteriovenous malformation. of a broad-based cone whose apex is directed toward the deep structures of the brain. Radiologic findings include fine curvilinear calcifications, seen in about 25 per cent of the patients (Fig. 9A), and dilated vascular channels, evident in the skull when meningeal vessels are involved (Fig. SC). Angiography (Fig. 9B) usually reveals more than one major vessel supplying the arteriovenous malformation. Not uncommonly, the full extent of the malformation is not demonstrated until all of the intracranial vesselsare studied. Occasionally, blood is supplied from the external carotid artery. The caliber of the feeding vessels increases as the malformation is approached. Large draining veins are evident usually on the first or second film of serial angiography. This
46
GEORGE,
KISHORE
AND
CHASE
finding and the lack of mass effect (unless associated with hemorrhage) help in distinguishing an arteriovenous malformation from a highly vascular neoplastic lesion. Neurosurgical excision, when feasible, offers the best results. In selected patients, embolization with small plastic fragments via the carotid artery may prove beneficial. Ligation of feeding vessels may result in temporary decrease in the size of the anomaly but will frequently be followed by enlargement of other feeding arteries. In terms of prognosis, the arteriovenous malformation has no neoplastic potential but may expand in response to the increased blood ilow over a span of many years. Capillary
Telangiectasia
This is a local collection of vessels histologically similar to dilated capillaries, separated by normal brain parenchyma. These lesions are extremely rare, are usually located in the brain stem, and are seldom demonstrable on routine angiography. Sturge-Weber
Disease (Capillary-Venous
Calcifying
Angioma)
This condition can be classified either as a variant of arteriovenous malformation or of capillary telangiectasia. Cutaneous nevi along the course of the first branch of the trigeminal nerve are almost invariably associated with this condition. Plain films reveal characteristic “railroad track” calcifications in the cerebral cortical layers (not in blood vessels, as is sometimes thought). These parallel lines are usually limited to the occipitoparietal area. At angiography, a diffuse increase in density of the involved area may be seen as well as small arterial thrombosis. Cavernous
Vascular Malformation
Since this is not a neoplasm, the term cauernous angioma should be avoided. The malformation is extremely rare and consists of closely packed sinusoidal vascular channels resembling large hollow spaces (cavernous), not arteries or veins, and has no interposed cerebral tissue.” It may occasionally calcify. Cerebral circulation time in these patients is only slightly altered, if at all. REFERENCES 1. Bauer, R. B., Meyer, J. S., Fields, W. S., Remington, R., Mcdonald, M. C., and Callen, P.: Joint study of extracranial arterial occlusion: III. Progress report of controlled study of long-term survival in patients with and without operation. JAMA 208:509, 1969. 2. Chase, N. E.: Radiology of cerebrovascular disease. Bull. N.Y. Acad. Med. 39:790, 1963. 3. Ehrenfeld, W. K., Hoyt, W. F., and Wylie, E. J.: Embolization and transient
blindness from carotid atheroma: surgical considerations. Arch. Surg. 93:787, 1966. 4. Fields, W. S., Bruetman, M. E., and Weibel, J.: Collateral Circulation of the Brain. Baltimore, Williams & Wilkins Co., 1965. 5. Fisher, C. M.: Observations of the fundus oculi in transient monocular blindness. Neurology 9:333, 1959. 6. Gunning, A. J., Pickering, G. W., RobbSmith, A. H. I., and Russell, R. R.: Mural
muhmw
DI~EASESOFTHECEREBRAL
BLOODVESSELS
thrombosis of the internal carotid artery and subsequent embolization. Quart. J. Med. 33: 155, 1964. 7. Inman, W. H. W., and Vessey, M. P.: Investigation of deaths from pulmonary coronary, and cerebral thrombosis and embolism in women of child-bearing age. Brit. Med. J. 2:193. 1968. 8. Julian, 0. C., Dye, W. S., Javid, H., and Hunter. J, A.: Ulcerative lesions of the carotid artery bifurcation. Arch. Surg. 86:803, 1963. 9. Kishore, P. R. S., Chase, N. E., and Kricheff, I. I.: Carotid stenosis and intracranial emboli. Unpublished. 10. Kishore, P. II. S., Lin, J. P., and Krichcff, I. I.: Fibromuscular hyperplasia of internal carotid artery and stationary waves. Acta Radiol. ( Diag. ) ( in press). 11. Krayenbiihl, II. A., and Yasargil, hl. Angiography. Philadelphia, C.: Cerebral Lippincott, 1968. 12. Kricheff, I. I., Chase, N. E., and Ransohoff, J. R.: The angiographic investigation of ruptured intracranial aneurysms. Radiology 83:1016, 1964. 13. Kudo, T.: Spontaneous occlusion of the circle of Willis: a disease apparently confined to Japanese. Neurology 18:485, 1968. 14. Lhermitte, F., Gautier, J, C., and Derouesne, C.: Nature of occlusions of the middle cerebral artery. Neurology 20: 82, 1970. 15. Locksley, H. B.: Report on the cooperative study of intracranial aneurysms and subarnchnoid hemorrhage. Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations: based on 6368 cases in the cooperative study. J. Neurosurg. 253219, 1966.
47
16. Millikan, C. H.: The pathogenesis of transient focal cerebral ischemia. Circulation 32:438, 1965. 17. hloore, W. S., and Hall, A. D.: Ulcerated atheroma of the carotid artery: a cause of transient cerebral ischemia. Amer. J. Surg. 116:237,1968. 18. hloosy, J.: Morphology, Sites and Epidemiology of Cerebral Atherosclerosis in Cerebrovascular Disease. Association for Research in Nervous and Mental Disease. Baltimore, Williams & Wilkins, 1966. 19. Pool, J. L., and Potts, D. G.: Aneurysms and Arteriovenous Anomalies of the Brain. New York, Hoeber Med. Division, Harper and Row, 1965. 20. Taveras, J. XI.: Multiple progressive intracranial arterial occlusions: a syndrome of children and young adults. Amer. J. Roentgen. 106:235, 1969. 21. Taveras, J. M., and Wood, E. H.: Diagnostic Neuroradiology. Baltimore, Wdliams & Wilkins Co., 1964. 22. Walsh, L. S.: Results of treatment of spontaneous subarachnoid hemorrhage. In Williams, D. (Ed.): Modern Trends in Neurology. London, Butterworth, 1957, pp. 119-129. 23. Wilson, C. B.. and Roy, M.: Calcification within congenital aneurysms of vein of Galen. Amer. J. Roentgen. 91:1319, 1969. 24. Wood, E. H.: Angiographic identification of the ruptured lesion in patients with multiple cerebral aneurysms. J. Neurosurg. 21:182,1964. 25. Yates, P. O., and Hutchinson, E. C.: Cerebral infarction: the role of stenosis of the extracranial cerebral arteries. hledicnl Research Council Special Report Series No. 300. London, Her Majesty’s Stationery Office, 1961.
AJAX ELI~ GEORGE,M.D.,
PULLA R. S. KISHORE,M.D.,
AND NORMAN E. CHASE, M.D.
P
RIMARY
of death
term
stroke
DISEASE of the cerebral blood vessels is the third major cause and the prime cause of disability in the United States today. The or cerebrovascular accident includes a wide range of diseases of
many different etiologies and varying degrees of prognostic significance, from a transient ischemia attack (completely reversible without residual deficit) to a fatal massive intracerebral hemorrhage. Primary diseases of the cerebral blood vessels may produce neurologic deficit with or without cerebral infarction by: 1. Stenosis or occlusion due to A. Structural changes within the arterial wall caused by (1) atherosclerosis (2) hypertension (3) arteritis: tuberculosis, syphilis, polyarteritis, giant cell arteritis, Takayasu’s disease, radiation, and others (4) miscellaneous causes: migraine, oral contraceptives, fibromuscular hyperplasia, Moya Moya’s disease (5) spasm (most commonly caused by subarachnoid hemorrhage secondary to aneurysm rupture or trauma) B. Embolization either from plaques in the extracranial vessels or from cardiac sources 2. Intracranial hemorrhage, subarachnoid or intracerebral, secondary to (1) ruptured aneurysm and its sequelae (2) hypertensive cerebrovascular disease (3) vascular malformation Among the causes listed above, atherosclerosis and hypertension are the more common causes of cerebral ischemia with or without infarction. ATHEROSCLEROSIS
During the past two decades our understanding of cerebrovascular disease has increased greatly. Pathologic as well as clinical studies now show that intracranial small vessel atherosclerosis plays a relatively insignificant role in cerebral infarction,5,” I ‘.“.P’ whereas the irregular or ulcerative atheromatous plaques at the bifurcation of the carotid arteries and other brachiocephalic vessels are now recognized as a major hazard, increasing the incidence of embolization and causing transient or permanent cerebral ischemia. Although corrective surgery may benefit some of these patients,3~8~17 its role Supported
in part by NINDS
Neuroradiology
Training
Grant NBO 5433-05.
AJAX ELIS GEORGE, M.D.: Instructor, Department of Radiology, New York Unioersity Medical Center, New York, N.Y. PULLA R. S. I&SHORE,M.D.: Instructor, Department of Radiology, New York Unioersity Medical Center, New York, N.Y. NORMAN E. CHASE, M.D.: Professor and Chairman, Department of Radiology, New York University Medical Center, New York, N.Y.
34
SEMINARSIN ROENTGENOLOGY, VOL. 6, No. 1 ( JANUARY) ,197l
PRIMARY
DISEASES
OF THE CEREBBAL
BLOOD
35
VESSELS
in the management of cerebrovascular disease is yet to be determined. Surgical treatment appears to be most beneficial to patients with unilateral carotid artery stenosis which has caused transient ischemia or moderate neurologic deficit.’ A thorough evaluation of each patient is warranted since some patients, though admittedly not a high percentage, benefit from surgical and/or medical therapy. This rather large population with stroke was previously condemned to hopelessness. Although a clinical evaluation may be adequate to localize the site of cerebral ischemia, accurate determination of the status of the intra- and extracranial vasculature is essential to surgical therapy, and this can be achieved only by cerebral angiography. By this means, the collateral circulation can be assessed and the possibility of neoplasm can be ruled out. The techniques of cerebral angiography are discussed elsewhere in this issue ( p. 7); however, a brief discussion is in order here since cerebral angiography performed to evaluate occlusive cerebrovascular disease differs somewhat in method from studies for aneurysm rupture, neoplasm, or trauma. The aim is to obtain good visualization of the entire cerebrovascular tree with minimal manipulation or trauma around the origin of the diseased brachiocephalic vessels. To achieve this, we believe bilateral, percutaneous retrograde brachial angiography followed by left carotid angiography, if necessary, to be ACA
Fig. L-Incidence and distribution of arterial lesions in the brachiocephalit vessels in patients
studied for cerebrovascular insufficiency. There is no significant difference on the two sides. Stenosisat the origin of the internal carotid and vertebral arteries (the most frequent sites of involvement) is approximately four times as common as occlusion. Intracranially, the incidence of stenosisin the posterior, anterior, and middle cerebral arteries rangesfrom 2 to 4 per cent. (Courtesv of Hass, W. K. et al.; reproduced with permission of JAMA 203:961, 1968.)
36
GEORGE,
KISHORE
AND
CHASE
the best method.? Using this approach, visualization of the extracranial portions of the four great vessels and the intracranial circulation is obtained and dislodgment of plaques and embolization may be avoided. In instances where a left carotid angiogram is indicated because of failure to fill the artery on right brachial injection, the needle is placed well below the carotid bifurcation. Angiograph y Although occlusion and stenosis may occur anywhere, the sites of vascular branching are the most frequently involved (Fig. 1). Careful evaluation of the lesion, preferably in more than one projection, is important because irregular or ulcerated plaques may signify cerebral embolismk.D~li (Fig, 2). Arterial kinks, seen more commonly with vascular disease, may also cause considerable narrowing of the lumen, compromising the blood flow. Recognition of branch occlusion is important and is based on ( 1) the absence of a branch at an expected anatomic site, (2) collaterals to the area, (3) stasis in the vessel, and (4) capillary blush. Cerebral edema and infarction are diagnosed by their mass effect, and occasionally distinction from a neoplasm may be difficult, especially when there is early venous drainage from the area. In such circumstances, follow-up studies coupled with brain scanning are helpful. The value of collateral circulation cannot be overemphasized because the degree of neurologic deficit and the ability to recover from it depend upon
Fig. 2.-Ulcerated plaque (horizontal arrow) at the bifurcation of the common carotid and internal carotid arteries. Right
brachial angiogram. Identification of irregularities and ulcerations in plaques is essentialbecauseof embolic implications. There is stenosisof the external carotid artery (vertical arrow) an unusual site of involvement.
PBIhXAFiY
DISEASES
OF THE CEREBRAL
BLOOD
VESSELS
Fig. X-Collateral circulation. A. Absence of filling of the middle cerebral artery on the initial film of a serial left carotid angiogram. Note marked stenosis at the junction of the cavernous and supraclinoid segments of the internal carotid artery (arrow). B. Middle cerebral branches (horizontal arrows) are filled in retrograde fashion via pial collaterals (vertical arrows). Intermediate arterial phase.
38
GEORGE,
KISHORE
AND
CHASE
PFUMARYDISEASESOF'JXECEl3EBFiALBLOOD!'ESSELS
Fig. 5.-Occlusion of tbe left vertebral artery at origin. Filling of the distal intraos-
seous segment of the vertebral artery (arrows)via collateralsfrom branches(arrowhead) of thyrocervical and ascendingcervical trunks. Left retrograde brachial angiogram at 3 seconds. the collateral channels as well as such physiologic factors as cardiac output, systemic blood pressure, blood viscosity, and oxygenation. It is not uncommon to see patients with complete occlusion of three of the four major vessels who have no significant neurologic deficit because of good collateral circulation. Development of effective collaterals depends upon the status of the circle of Willis. The most frequent anastomotic pathways are the anterior and posterior communicating arteries. Pial collaterals occur most commonly between the anterior, middle, and posterior cerebral, and between the superior and inferior cerebellar arteries (Fig. 3). Collaterals are also seen between the internal and external carotid arteries via ophthalmic or meningeal branches in cases of internal carotid artery occlusion; between the external carotid and vertebral arteries in common carotid occlusion; and between cervical and vertebral arteries in occlusion of the origin of the vertebral artery (Figs. 4 and 5). Detailed discussion of collateral circulation is beyond the scope of this communication and the reader is referred to the excellent monograph by Fields et al.’ HYPERTENSIVECEREBROVASCXJLARDISEASE (WITH ORWITHOUTINTRACRANIALHEMORRHAGE) The association of arteriosclerotic cerebrovascular disease and hypertension is not uncommon, increasing the severity of cerebrovascular insufficiency. A necrotizing arteriopathy of diffuse or focal nature occurs in the brain in hypertension. The basic process is one of hyaline and fibrinous changes (rarely with evidence of inflammation) and frequent microaneurysm formation. The arterial lesion occurs in the brain stem and deep nuclei and not in the subarachnoid vessels. The common sites are the gangliothalamic areas, including the internal
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Fig. 6.-Arteritis in a 24 year old man with a history of tuberculous meningitis.
Left carotid angiogram shows irregularity of the internal carotid (horizontal arrows), proximal middle cerebral (vertical arrows). and anterior cerebral arteries (arrowhead). and external capsule and pons. When bleeding occurs, the angiographic findings are essentially those of intracerebral hemorrhage. ARTERITIS
Arteritis is a less common cause of cerebral vascular insufficiency. Inflammation of cerebral vesselscan be conveniently divided into infectious, collagen, and nonspecific forms. In the infectious group are included syphilis, tuberculosis, hemophilus influenza, and more rarely salmonella. Irregular narrowing of the lumen of the large vessels of the circle of Willis in a patient with a previous history of one of these diseasessuggests the diagnosis (Fig. 6). Infectious arteritis may be associated with mycotic aneurysm, or with epidural, subdural, or intracerebral abscess. Polyarteritis is by far the commonest collagen disease to affect cerebral blood vessels. Lupus erythematosus and rarely rheumatoid arteritis and scleroderma are also known to involve the intracranial vessels. Giant cell arteritis and Takayasu’s disease, the latter by involvement of the aortic arch and its major branches, may rarely produce cerebral ischemia. MISCELLANEOUS
CAUSES
Angiography should be avoided in cases of migraine for fear of increasing spasm. When performed, the angiograms may be completely normal or may show evidence of spasm or branch occlusion. An increased incidence of thromboembolic disorders leading to cerebral ischemia in women using oral contraceptives has been reported.?
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Several reports have described fibromuscular hyperplasia of the internal carotid artery, especially in women, based on the corrugated appearance at angiography. However, the close resemblance to stationary waves, a flow phenomenon, makes this diagnosis questionable unless proved by biopsy. Fibromuscular hyperplasia can be suspected, however, if the possibility of spasm due to needle trauma and stationary waves is ruled out and if the carotid bifurcation is spared.“’ A syndrome consisting of multiple progressive intracranial arterial occlusions in children, originally thought to occur only in Japanese ( Moya Maya’s disease) has recently been reported in this country.“’ This disease is characterized by rapidly progressive stenosing lesions of the major arterial channels along the circle of Willis leading to total occlusion of these vessels. Peculiarly, the process stops once total occlusion has taken place, so that if collaterial circulation is adequate most patients are able to lead a fairly normal life. Characteristically, the branches of the anterior, middle, and posterior cerebral arteries are not involved. The pathogenesis of this syndrome is unknown.““ INTRACRANIAL
ANEURYSM
Intracranial aneurysm is usually congenital or developmental ( berry), arteriosclerotic, or mycotic. Traumatic, luetic, and venous aneurysms are comparatively iare. Berry aneurysms are by far the commonest and their incidence in the general population has been variously estimated from 0.5 per cent to as high as 5.0 per cent. The age incidence varies from 20 to 70 years; it is rare below the age of 10.” Approximately 80 per cent of berry aneurysms occur on the carotid circulation, the remaining 20 per cent occurring on the vertebrobasilar circulation. About 15 to 20 per cent are multiple. An analysis of over 6000 aneurysms showed the following distribution: anterior communicating artery, 30 per cent; internal carotid artery at the origin of the posterior communicating, 24 per cent; and bifurcation of the middle cerebral artery, 13 per cent; only 5.5 per cent of single bleeding aneurysms occurred in the vertebrobasilar system.” Aneurysms account for 50 to 80 per cent of nontraumatized patients with blood in the cerebrospinal fluid. Occasionally, a large aneurysm may present as an intracranial mass. This is more frequent around the base of the brain where a large aneurysm of the internal carotid artery or basilar artery manifests as a para- or suprasellar mass. It is this feature that necessitates angiography to avoid a possible catastrophe when surgery is planned for a suprasellar mass. Angiography Although the diagnosis of bleeding aneurysm can be made clinically with some degree of accuracy, angiography is the only method for accurately localizing and evaluating the aneurysm. The purpose of angiography is to demonstrate the presence and location of the aneurysm, to localize a hematoma that may warrant immediate surgical intervention, and to rule out other causes of intracranial hemorrhage. A follow-up angiographic study in postoperative patients may be a useful prognostic tool.
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Fig. 7.-Severe spasm of proximal middle cerebral (vertical arrows), anterior cerebral (arrowheads), and internal carotid (horizontal arrow) arteries in a patient
with ruptured internal carotid aneurysm at bifurcation. Note normal size of distal middle cerebral and anterior cerebral branches. Identification of bleeding aneurysm can be difficult. A vascular loop may mimic an aneurysm and sometimes requires examination in multiple projections. Usually it is relatively denser than an aneurysm of the same diameter. The so-called junctional dilatation seen frequently at the origin of the posterior communicating artery and less commonly at the origin of the anterior choroidal artery should not be mistaken for aneurysm. It can be distinguished by its triangular shape, with the branch vessel arising from the apex of the triangle rather than adjacent to it as in aneurysm. Usually it measures less than 3 mm. at the base. It is essential to opacify the entire intracranial circulation in subarachnoid hemorrhage, in view of the significant incidence of multiple aneurysms. With multiple aneurysms, it may be possible to identify the bleeding aneurysm on the basis of the neurologic deficit. However, certain angiographic findings, such as a clot in the aneurysm, arterial spasm, intracerebral or subdural hematoma, or extravasation are helpful in pinpointing the bleeding site. In the absence of any of these signs, it is more likely that the largest aneurysm bled.” The phenomenon of spasm may represent a defensive mechanism to prevent further bleeding. Spasm is usually seen between 2 and 14 days after the onset of subarachnoid hemorrhage and may last for several weeks. A high percentage of patients with ruptured aneurysm have spasm, and this may lead to cerebral infarction. Spasm is diagnosed by a smooth narrowing of the vessel adjacent to the ruptured aneurysm, Arteriosclerotic narrowing is usually more irregular and involves vessels in many areas. One should not mistake a hypoplastic origin of the anterior cerebral artery for spasm. Narrowing of the proximal part
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of the pericallosal or callosal marginal arteries with normal caliber distally is essential for a diagnosis of spasm (Fig. 7). The extent of spasm is variable and may occasionally involve the entire hemisphere and rarely even the contralateral side. It is extremely unusual, however, to see the spasm extend extradurally. Rarely, spasm may prevent the filling of the aneurysm. A repeat examination is required, preferably after a delay of a week or tw0.l’ A space occupying lesion is not infrequent with aneurysmal rupture and is helpful in identifying the site of bleeding (Fig. 8). It may be due to diffuse cerebral edema associated with spasm or to localized intracerebral or subdural clot. Intracerebral hematoma indicates a grave prognosis and may warrant immediate surgical intervention. Hematoma from aneurysm rupture is usually cortical in location, in contrast to the deep capsular lesion seen in hypertensive cerebral hemorrhage. Occasionally, intraventricular clots are visible after subarachnoid hemorrhage. Extravasation of contrast material in the proximity of an aneurysm is rare and also implies grave prognosis. Irregularity secondary to clot formation is often seen in the bleeding aneurysm (Fig. 8). Occasionally, an intraluminal clot may be seen as a filling defect surrounded by contrast material. A tentlikc projection in the dome of the aneurysm is presumptive of the actual bleeding site.
Fig. 8.-Temporal hematoma from ruptured aneurysm. The
large middle cerebral aneurysm has irregular margins due to clot (arrows). Note the elevation and medial displacement of the middle cerebral artery (arrowheads).
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GEORGE,KISHOREANDCHASE
As with any other large intracranial mass, transtentorial herniation may result from subarachnoid hemorrhage. Hydrocephalus is a frequent complication of subarachnoid hemorrhage and is usually seen about two weeks after the hemorrhage. This delayed ventricular enlargement is apparently due to incisural block secondary to arachnoidal adhesions, in contrast to the hydrocephalus occurring within hours of the bleeding, which is due to obstruction of the ventricular system by an intraventricular clot or posterior fossa hemorrhage. Failure to demonstrate the aneurysm in subarachnoid hemorrhage after adequate examination (including multiple projections and films of good technical quality) is rare. The prognosis of such patients on conservative management is considered to be much better than those with demonstrable lesions.” As mentioned earlier, angiographic evaluation of an aneurysm is not considered complete unless the neck of the aneurysm is demonstrated. Multiple projections are often necessary for this purpose. Finally, the patency of the anastomotic channels around the circle of Willis, particularly the anterior communicating artery, should be evaluated by compressing the carotid artery on the side of lesion with contralateral injection when carotid artery ligation is contemplated. Cross-filling of the involved side by such a maneuver suggests that the patient can tolerate carotid ligation. Aneurysm of the vein of Galen is exceedingly rare and presents as a posterior third ventricular mass on pneumoencephalography. It has a characteristic calcification and angiographic features.* VASCULARMALFORMATIONS
These relatively rare lesions may be divided into arteriovenous malformation ( the most common), capillary telangiectasia, and cavernous vascular malformation on the basis of the angiographic appearance. Vascular malformations constitute 4 per cent of brain lesions initially diagnosed as tumor” and 6 per cent of the lesions causing subarachnoid hemorrhage.‘” In the second decade of life, vascular malformations and intracranial aneurysms are equally probable as the cause of subarachnoid hem0rrhage.l’ By shunting blood away from normal tissues, vascular malformations may be the cause of epileptic seizures, mental deterioration, underdevelopment and weakness of one or more extremity, and an audible bruit. Hemorrhage occurs in 40 to 60 per cent.l’ They may occasionally produce hydrocephalus by obstructing the ventricular system. Arteriovenous
Malformation
Pathophysiologically, arteriovenous malformation represents the persistence of embryonic arteriovenous shunts. It may be composed in varied proportion of dilated, tortuous, venous and arterial structures and shunts. Krayenbiihl’s review of 800 cases shows the distribution of lesions to be extracranial in 3.1 per cent, supratentorial in 85.7 per cent, and infratentorial in 6.2 per cent.” The site of greatest predilection is the region of the sylvian fissure (36.1 per cent) where it obtains its main blood supply from the middle cerebral artery. The arteriovenous malformation is usually localized in the pial region in the shape
PRIMARY
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Fig. 9.-Arteriovenous malformation. A. Fine curvilinear calcihca-
tion on the right. The patient had subarachnoid hemorrhage and history of previous seizures. B. Right carotid angiogram of same patient showsa large A-V malformation in the right cerebral hemisphere. C. Different patient. Enlarged corkscrew middle meningeal groove (arrows), indicating external carotid artery supply to the arteriovenous malformation. of a broad-based cone whose apex is directed toward the deep structures of the brain. Radiologic findings include fine curvilinear calcifications, seen in about 25 per cent of the patients (Fig. 9A), and dilated vascular channels, evident in the skull when meningeal vessels are involved (Fig. SC). Angiography (Fig. 9B) usually reveals more than one major vessel supplying the arteriovenous malformation. Not uncommonly, the full extent of the malformation is not demonstrated until all of the intracranial vesselsare studied. Occasionally, blood is supplied from the external carotid artery. The caliber of the feeding vessels increases as the malformation is approached. Large draining veins are evident usually on the first or second film of serial angiography. This
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finding and the lack of mass effect (unless associated with hemorrhage) help in distinguishing an arteriovenous malformation from a highly vascular neoplastic lesion. Neurosurgical excision, when feasible, offers the best results. In selected patients, embolization with small plastic fragments via the carotid artery may prove beneficial. Ligation of feeding vessels may result in temporary decrease in the size of the anomaly but will frequently be followed by enlargement of other feeding arteries. In terms of prognosis, the arteriovenous malformation has no neoplastic potential but may expand in response to the increased blood ilow over a span of many years. Capillary
Telangiectasia
This is a local collection of vessels histologically similar to dilated capillaries, separated by normal brain parenchyma. These lesions are extremely rare, are usually located in the brain stem, and are seldom demonstrable on routine angiography. Sturge-Weber
Disease (Capillary-Venous
Calcifying
Angioma)
This condition can be classified either as a variant of arteriovenous malformation or of capillary telangiectasia. Cutaneous nevi along the course of the first branch of the trigeminal nerve are almost invariably associated with this condition. Plain films reveal characteristic “railroad track” calcifications in the cerebral cortical layers (not in blood vessels, as is sometimes thought). These parallel lines are usually limited to the occipitoparietal area. At angiography, a diffuse increase in density of the involved area may be seen as well as small arterial thrombosis. Cavernous
Vascular Malformation
Since this is not a neoplasm, the term cauernous angioma should be avoided. The malformation is extremely rare and consists of closely packed sinusoidal vascular channels resembling large hollow spaces (cavernous), not arteries or veins, and has no interposed cerebral tissue.” It may occasionally calcify. Cerebral circulation time in these patients is only slightly altered, if at all. REFERENCES 1. Bauer, R. B., Meyer, J. S., Fields, W. S., Remington, R., Mcdonald, M. C., and Callen, P.: Joint study of extracranial arterial occlusion: III. Progress report of controlled study of long-term survival in patients with and without operation. JAMA 208:509, 1969. 2. Chase, N. E.: Radiology of cerebrovascular disease. Bull. N.Y. Acad. Med. 39:790, 1963. 3. Ehrenfeld, W. K., Hoyt, W. F., and Wylie, E. J.: Embolization and transient
blindness from carotid atheroma: surgical considerations. Arch. Surg. 93:787, 1966. 4. Fields, W. S., Bruetman, M. E., and Weibel, J.: Collateral Circulation of the Brain. Baltimore, Williams & Wilkins Co., 1965. 5. Fisher, C. M.: Observations of the fundus oculi in transient monocular blindness. Neurology 9:333, 1959. 6. Gunning, A. J., Pickering, G. W., RobbSmith, A. H. I., and Russell, R. R.: Mural
muhmw
DI~EASESOFTHECEREBRAL
BLOODVESSELS
thrombosis of the internal carotid artery and subsequent embolization. Quart. J. Med. 33: 155, 1964. 7. Inman, W. H. W., and Vessey, M. P.: Investigation of deaths from pulmonary coronary, and cerebral thrombosis and embolism in women of child-bearing age. Brit. Med. J. 2:193. 1968. 8. Julian, 0. C., Dye, W. S., Javid, H., and Hunter. J, A.: Ulcerative lesions of the carotid artery bifurcation. Arch. Surg. 86:803, 1963. 9. Kishore, P. R. S., Chase, N. E., and Kricheff, I. I.: Carotid stenosis and intracranial emboli. Unpublished. 10. Kishore, P. II. S., Lin, J. P., and Krichcff, I. I.: Fibromuscular hyperplasia of internal carotid artery and stationary waves. Acta Radiol. ( Diag. ) ( in press). 11. Krayenbiihl, II. A., and Yasargil, hl. Angiography. Philadelphia, C.: Cerebral Lippincott, 1968. 12. Kricheff, I. I., Chase, N. E., and Ransohoff, J. R.: The angiographic investigation of ruptured intracranial aneurysms. Radiology 83:1016, 1964. 13. Kudo, T.: Spontaneous occlusion of the circle of Willis: a disease apparently confined to Japanese. Neurology 18:485, 1968. 14. Lhermitte, F., Gautier, J, C., and Derouesne, C.: Nature of occlusions of the middle cerebral artery. Neurology 20: 82, 1970. 15. Locksley, H. B.: Report on the cooperative study of intracranial aneurysms and subarnchnoid hemorrhage. Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations: based on 6368 cases in the cooperative study. J. Neurosurg. 253219, 1966.
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16. Millikan, C. H.: The pathogenesis of transient focal cerebral ischemia. Circulation 32:438, 1965. 17. hloore, W. S., and Hall, A. D.: Ulcerated atheroma of the carotid artery: a cause of transient cerebral ischemia. Amer. J. Surg. 116:237,1968. 18. hloosy, J.: Morphology, Sites and Epidemiology of Cerebral Atherosclerosis in Cerebrovascular Disease. Association for Research in Nervous and Mental Disease. Baltimore, Williams & Wilkins, 1966. 19. Pool, J. L., and Potts, D. G.: Aneurysms and Arteriovenous Anomalies of the Brain. New York, Hoeber Med. Division, Harper and Row, 1965. 20. Taveras, J. XI.: Multiple progressive intracranial arterial occlusions: a syndrome of children and young adults. Amer. J. Roentgen. 106:235, 1969. 21. Taveras, J. M., and Wood, E. H.: Diagnostic Neuroradiology. Baltimore, Wdliams & Wilkins Co., 1964. 22. Walsh, L. S.: Results of treatment of spontaneous subarachnoid hemorrhage. In Williams, D. (Ed.): Modern Trends in Neurology. London, Butterworth, 1957, pp. 119-129. 23. Wilson, C. B.. and Roy, M.: Calcification within congenital aneurysms of vein of Galen. Amer. J. Roentgen. 91:1319, 1969. 24. Wood, E. H.: Angiographic identification of the ruptured lesion in patients with multiple cerebral aneurysms. J. Neurosurg. 21:182,1964. 25. Yates, P. O., and Hutchinson, E. C.: Cerebral infarction: the role of stenosis of the extracranial cerebral arteries. hledicnl Research Council Special Report Series No. 300. London, Her Majesty’s Stationery Office, 1961.