J Neurosurg 48:292-296, 1978 The angiographically occult cerebrovascular malformation Report of three cases JAMES B. GOLDEN, M . D . , AND RICHARD A. KRAMER, M . D . Departments of Neurosurgery and Radiology, Palo Alto Medical Clinic, Palo Alto, California v" Three cases presenting with hemiparesis, headache, or seizures gave no history suggestive of subarachnoid or intracerebral hemorrhage. Carotid arteriograms were performed, and in each case failed to demonstrate a vascular malformation. In all three cases cerebral lesions were shown by either computerized tomographic (CT) scan, radionuclide scan, or both. Surgical exploration and biopsy revealed a vascular malformation in each case. The CT scans in two of the cases showed dense lesions that could suggest vascular malformation as a diagnostic possibility. KEY WORDS 9 cerebral arteriovenous malformation 9 radionuclide scan 9 computerized t o m o g r a p h y T HE typical cerebral arteriovenous malformation ( A V M ) presents clinically as the source of subarachnoid or intracerebral hemorrhage, as a seizure focus, or as the cause of slowly progressive, localized cerebral deficiency. In the absence of spontaneous hemorrhage, the s y m p t o m s and signs of increased intracranial pressure (ICP) are m o r e often absent, but m a y be present. However, headache m a y be a complaint with or without increased ICP. Calcification in the lesion is occasionally seen on radiographs of the skull, but usually not. An A V M larger than 2 to 3 cm will most often be demonstrated by radionuclide scan.' The exact diagnosis is usually obtained only by cerebral angiography. 4 One notable exception to angiographic d e m o n s t r a t i o n of these lesions has been in those cases of spontaneous intracerebral h e m a t o m a in which careful micro292 9 cerebral angiography scopic e x a m i n a t i o n of the excised clot has revealed the presence of A V M tissue. These lesions have been described by Margolis, et al. 3 In this report we present the clinical and radiographic features of three histologically proven cases of s y m p t o m a t i c cerebrovascular m a l f o r m a t i o n , none of which had shown evidence of bleeding or diagnostic angiographic features. The preoperative diagnosis in all three cases was probable glioma. C a s e Reports Case 1 This 36-year-old left-handed w o m a n complained of slowly progressive deterioration of handwriting of 6 years' duration. For 5 years she had been noted to drag the left leg slightly. She had not had tremor or speech J. Neurosurg. / Volume 48 / February, 1978 Angiographically occult cerebrovascular malformation disturbance. There had been no events to suggest spontaneous hemorrhage. Examination. Examination revealed decreased movement of the lower portion of the left side of the face, and impaired rapid movements in the left hand and foot. Tendon reflexes were increased in the left upper extremity, and plantar responses were flexor. Optic fundi appeared normal. There were no bruits. Electroenceph-alography ( E E G ) showed a slow-wave focus in the right frontal region. L u m b a r puncture revealed clear, colorless fluid and n o r m a l pressure. Radiographs of the skull and radionuclide brain scan showed no abnormalities. Serial internal carotid angiograms revealed no abnormalities (Fig. 1). A computerized tomography (CT) scan revealed a high-density lesion adjacent to the superior part of the anterior horn of the right lateral ventricle. The density of the lesion was clearly increased following infusion of contrast medium, but the size of the lesion remained unchanged (Fig. 2). Although the preoperative diagnosis was that of a slowly growing glioma, interpretation of the CT scan raised the possibility of vascular malformation. The patient was advised to have the lesion biopsied and then to have radiation treatment if the lesion proved to be a glioma. Operation. Through a small incision in the right middle frontal gyrus, firm tissue was encountered in the white matter. The lesion was firm and avascular. Some of the tissue was removed and a frozen section obtained. There was some uncertainty whether the lesion was a glioma or a vascular malformation. Additional biopsy specimens were removed for permanent section. N o bleeding occurred. Histological Findings. An unusual AVM was revealed on histological examination. It had extremely thick-walled vascular structures, some Qf which showed old thrombosis and recanalization. The thick outer walls of these vessels were acellular and positive to periodic acid-Schiff (PAS), whereas elastic tissue and amyloid stains were negative. Surrounding the large blood vessels was a stroma of benign glial cells with a glial matrix. There was no neoplastic glial tissue. The tissue was diagnosed as A V M (Fig. 3). Postoperative Course. The patient had a slight increase in awkwardness of the left hand, but soon returned to her usual activity. She has had no further symptoms for 1 year. J. Neurosurg. / Volume 48 / February, 1978 FIG. 1. Case 1. Lateral internal carotid arteriogram showing absence of demonstrable feeding arteries and no abnormal vessels. FIG. 2. Case 1. CT scans before (left) and after contrast infusion (right) show dense lesion adjacent to right lateral ventricle. Density of the lesion is increased following infusion. (Reproduced from Kramer RA, Wing SD: Computed tomography of angiographically occult cerebral vascular malformations. Radiology 123:649-652, 1977, by permission of the publisher.) FIG. 3. Case 1. Photomicrograph of operative specimen showing arteriovenous malformation. Vessel walls are thick and there is organization in the lumens of many vessels after thrombosis. Glial stroma is present. PAS, • 60. 293 j. B. G o l d e n FIG. 4. Case 2. Lateral internal carotid arteriogram film shows no abnormal vessels. Case 2 This 32-year-old woman had complained for many years of intermittent headache, thought to be psychogenic. Following a recent minor closed-head injury, the headaches became more debilitating. The problem was clouded by litigation regarding the injury. Examination. Neurological examination revealed no abnormalities. An EEG was read as normal, and radiographs of the skull showed no abnormalities. A radionuclide brain scan showed a 2- to 3-cm area of increased uptake in the superior aspect of the FIG. 5. Case 2. CT scans before (left) and after contrast infusion (right). The dense lesion in the left frontal region increases in density after infusion. 294 and R. A. K r a m e r left frontal pole. Serial internal carotid angiography showed no abnormalities (Fig. 4). A C T scan showed a 2-cm zone of increased density in the left frontal region. Following infusion of contrast medium, the density of the lesion increased, but the size did not (Fig. 5). There was question whether the abnormality seen on the CT scan was a resolving area of contusion, a small glioma, or some other lesion. Repeat CT scans were obtained at 1 and 2 months following the initial scan and showed that the lesion persisted unchanged in appearance. Her symptoms remained unchanged and therefore craniotomy for the purpose of biopsy was advised. Operation. At surgery a superficial, purplish vascular lesion 2 cm in diameter was found. The lesion had the appearance of a collection of small tortuous veins (Fig. 6). Surrounding the lesion there was a yellowstained cleavage plane, and it was possible to remove the lesion completely with very little bleeding. Histological Findings. A vascular malformation with both thin- and thick-walled vascular channels was seen. There was fresh and old hemorrhage and a moderate amount of surrounding gliosis (Fig. 7). The tissue was diagnosed as AVM. Postoperative Course. A wound infection in the early postoperative course was treated with antibiotics and disappeared without further complications. The patient still has headaches, but they are diminished. For 2 years she has had no neurological sequelae and no signs or symptoms of intracranial bleeding. Case 3 Over a period of 9 months this 20-year-old woman had three focal motor seizures starting in the left upper extremity. Examination. Neurological examination revealed no a b n o r m a l i t i e s except for decreased fine motor skills and increased tendon reflexes in the left upper extremity. An EEG showed no abnormalities. Lumbar puncture revealed clear, colorless fluid with one white blood cell and 22 mg% of protein. Skull films were negative. A radionuclide brain scan revealed a sharply circumscribed lesion in the right frontoparietal area (Fig. 8). Serial films of the right internal carotid injection showed a large parietal mass lesion with stretched vessels and slight contrast stain, but J. Neurosurg. / Volume 48 / February, 1978 Angiographically occult cerebrovascular malformation FIG. 6. Case 2. Operative photograph showing vascular malformation on surface of left frontal cortex. FIG. 7. Case 2. Photomicrograph of operative specimen showing vascular malformation composed of closely packed thick-walled vessels some of which are filled with organized thrombus and surrounding glial stroma. PAS, • 16. no vascular malformation could be identified. There was a shift of the pericallosal artery toward the left, and the internal cerebral vein was displaced 5 m m to the left of the midline. This case was encountered in 1968, before CT scanning. The preoperative diagnosis was glioma and the patient was advised that a limited r e m o v a l should be attempted, followed by radiation treatment. Operation. The surface of the brain did not appear abnormal. In the posterior frontal region a ventricular needle was inserted and encountered a very firm mass at 2 cm depth. The lesion was exposed and appeared very unusual. There were several shiny, brownishgray nodules averaging 0.5 cm in diameter. Some of these apparently hemorrhagic cystic structures were removed. The surrounding tissue was yellowish and very firm, and this tissue was removed for biopsy. There was little or no bleeding from this lesion. Histological-Findings. All fragments of tissue e x a m i n e d included areas where relatively normal brain lay adjacent to a densely coUagenous mass of abnormal blood channels of varying size, showing only rare elastic fibers and lined by thin, fiat, singlelayered endothelium. The majority of these channels were thrombosed and undergoing various stages o f organization. The vascular channel walls were closely contiguous, and contained hemosiderin deposits and scattered foci of amorphous calcification. At the edges of the lesion the hemosiderin deposition was dense, and there was intense gliosis of the surrounding brain tissue. Several groups of dilated capillaries a n d / o r veins, and some groups of normal, medium-sized arteries were seen in the adjacent brain. There was intervascular glial tissue. The lesion was diagnosed as venous angioma. Postoperative Course. Eight years after the operation, the patient is leading a normal life. She takes anticonvulsant medication and has had no seizures. There has been nothing suggestive o f intracranial bleeding. T h e radionuclide scan was repeated 2 years postoperatively, and showed no abnormality. J. Neurosurg. / Volume 48 / February, 1978 FIG. 8. Case 3. Radionuclide static scan showing circumscribed abnormality in right frontoparietal region. 295 J. B. Golden and R. A. Kramer Discussion The three cases of histologically verified cerebral vascular malformation encountered in this small series presented with mild hemiparesis, possible headaches, and focal seizures, respectively. In none of the three had there been clinical evidence of hemorrhage. In two cases, however, there was microscopic evidence o f extravascular hemosiderin deposits in small amounts. Paradoxically, the angiograms in all three cases showed no evidence of pathological vessels; however, the lesion in one case was d e m o n s t r a t e d angiographically as a mass with slight stain. The lesions in this series were 2- to 4-cm in size. Preoperatively all were thought to be gliomas. Radionuclide scans were positive in two of the three cases. Kramer and Wing s have reported the CT scan characteristics in a group of similar lesions, and in their group of 10 cases, the radionuclide scan was positive in four of the seven cases where this study was done. Morphologically, the lesions described in this series, while they were clearly vascular malformations, were different from the more frequently encountered malformations with large feeding arteries, rapid flow rate, and huge dilated draining veins. All three lesions reported here lacked any major feeding vessels. T h e y were, therefore, low-flow m a l f o r m a t i o n s , and the vessels showed widespread intravascular clot formation. Microscopic sections showed the simultaneous development of clot organization and attempts at recanalization. The endothelial wall layer was thin and elastic fibers were absent. Between the vascular channels lay abnormal glial tissue. These pathological features correlated well with the images that were obtained on CT scanning before and after contrast infusion. The density of the lesion on a noninfused C T scan was relatively high, reading" 20 to 35 on the EMI scale, consistent with the partially thrombosed vascular channels demonstrated histologically. Increase in density following intravenous contrast infusion probably resulted from a combination of extravascular extravasation due to the altered blood-brain barrier, and opacification of vascular channels. These channels, 296 although not apparent angiographically, may be shown on C T scanning due to the greater contrast resolution of the latter technique. We believe that a carefully conducted CT scan can raise a high index of suspicion in the preoperative recognition of cerebral vascular malformations even though they may be angiographically occult. Summary Three cases of vascular malformation without abnormal vessels on serial angiograms have been biopsied. Preoperatively all three were thought to be gliomas. There had been no clinical evidence of hemorrhage in any of the three. Radionuclide scan was positive in two and negative in one. The CT scans in two of the patients showed high-density lesions that increased in density following contrast infusion. Acknowledgment We would like to thank Lucien J. Rubinstein, M.D., Department of Pathology, Stanford University, for preparation and review of the tissue specimens. References 1. Kelly DL Jr, Alexander E Jr, Davis CH Jr, et al: Intracranial arteriovenous malformations: clinical review and evaluation of brain scans. J Neurosurg 31:422-428, 1969 2. Kramer RA, Wing SD: Computed tomography of angiographically occult cerebral vascular malformations. Radiology 123:649-652, 1977 3. Margolis G, Odom GL, Woodhall B, et al: The role of small angiomatous malformations in the production of intracerebral hematomas. J Neurosurg 8:564-575, 1951 4. Newton TH, Troost BT: Arteriovenous malformations and fistulae, in Newton TH, Potts DG (eds): Radiology of the Skull and Brain, Vol. 2, Book 4. St. Louis: CV Mosby, 1974, pp 2490-2565 This paper was presented at the OdomWoodhall Legion Meeting, Durham, North Carolina, October 22, 1976. Address reprint requests to: James B. Golden, M.D., Palo Alto Medical Clinic, 300 Homer Avenue, Palo Alto, California 94301. J. Neurosurg. / Volume 48 / February, 1978