CASE REPORT CASE REPORT TOPIC Pathologically Confirmed Cryptic Vascular Malformation as a Cause of Convexity Subarachnoid Hemorrhage: Case Report Tatsushi Mutoh, MD, DVM, PhD* Shinya Kobayashi, MD* Tatsuya Ishikawa, MD* Junta Moroi, MD* Hajime Miyata, MD, PhD‡ Akifumi Suzuki, MD, FAHA* Nobuyuki Yasui, MD* *Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan; ‡Department of Pathology, Division of Stroke Service, Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan Correspondence: Tatsushi Mutoh, MD, DVM, PhD, Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA, 6-10 Senshu-Kubota-machi, Akita 010-0874, Japan. E-mail: tmutoh@tiara.ocn.ne.jp Received, January 7, 2011. Accepted, May 17, 2011. Published Online, July 19, 2011. Copyright ª 2011 by the Congress of Neurological Surgeons BACKGROUND AND IMPORTANCE: We report a rare case of pathologically confirmed cryptic vascular malformation as a cause of primary convexity subarachnoid hemorrhage (SAH) of unknown etiology. CLINICAL PRESENTATION: A 48-year-old woman presented with sudden severe headache. Localized right convexity SAH was observed on computed tomography (CT) scan, but the origin could not be detected despite extensive workup covering the entire head by using 3.0-Tesla magnetic resonance (MR) imaging with MR angiography and CT angiography combined with venous-phase imaging with a 320-detector row CT scanner. Subsequent digital subtraction angiography (DSA) performed 2.5 hours after admission failed to reveal any cause of SAH; however, a right frontoparietal avascular region was suspected to be due to a newly developed intracerebral hematoma. The lesion was simultaneously confirmed by angiographic cone-beam CT imaging. Because she remained neurologically intact, we decided to perform a follow-up study later with medical management. However, she developed left hemiparesis 3 hours after DSA. CT scan demonstrated progression of the hematoma, and her symptoms gradually worsened. Emergent surgical exploration along the SAH superficial to the postcentral sulcus and hematoma evacuation were performed, with favorable functional outcome. Pathological examination confirmed cryptic vascular malformation with several abnormally dilated arterioles within the subarachnoid space surrounded by a thick SAH clot. CONCLUSION: It is important to consider the possibility of ruptured cryptic vascular malformation as a cause of nontraumatic nonaneurysmal convexity SAH when recurrent hemorrhage occurs despite thorough diagnostic workup, because surgical resection may be the only curative treatment option to eliminate the risk of rebleeding and disabling symptoms. KEY WORDS: Convexity subarachnoid hemorrhage, Cryptic vascular malformation, Subarachnoid hemorrhage of unknown etiology Neurosurgery 70:E1322–E1328, 2012 DOI: 10.1227/NEU.0b013e31822e0f87 N ontraumatic subarachnoid hemorrhage (SAH) along the cortical convexity is rare and may often be nonaneurysmal in origin and not demonstrable angiographically. Diverse etiologies have been suggested for its occurrence, including reversible cerebral vasoconstriction syndrome, posterior reversible leukoencephalopathy syndrome, cerebral amyloid angiopathy, dural sinus/cortical vein thrombosis, ABBREVIATIONS: DSA, digital subtraction angiography; ICH, intracerebral hematoma; SAH, subarachnoid hemorrhage E1322 | VOLUME 70 | NUMBER 5 | MAY 2012 www.neurosurgery-online.com coagulopathy, cocaine use, lupus vasculitis, cavernoma, and brain abscess.1-4 We report another potential cause of primary isolated convexity SAH in an extremely rare case of ruptured cryptic vascular malformation in the subarachnoid space in which emergent surgical exploration and resection of its origin effectively eliminated the risk of rebleeding and life-threatening/disabling symptoms. CASE REPORT A 48-year-old previously healthy woman presented in a neurosurgical clinic with sudden severe headache www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. CRYPTIC VASCULAR MALFORMATION-EVOKED CONVEXITY SAH FIGURE 1. Diagnostic workup for convexity SAH. A, plain head CT on admission. B, T2*-weighted image obtained on 3.0-Tesla MRI revealing hemosiderin deposits along the right cortical convexity. C, D, CT angiography using a 320-detector row volume CT scanner revealing no obvious findings indicative of the origin of hemorrhage. Volume rendering images of CT angiography alone (C) and combined with venous-phase imaging (D) in AP (left) and lateral (right) views covering the entire head. SAH, subarachnoid hemorrhage; AP, anteroposterior. NEUROSURGERY VOLUME 70 | NUMBER 5 | MAY 2012 | E1323 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. MUTOH ET AL FIGURE 2. A, cerebral DSA of the right internal carotid artery in the lateral view performed 2.5 hours after admission shows an avascular region in the frontoparietal lobe without extravasation (middle photograph, early venous phase) suspected to be due to newly developed intracerebral hematoma. The lesion was simultaneously confirmed by digital flat-panel detector angiographic cone-beam CT imaging (A, inset). B, postoperative DSA performed 1 week after surgery demonstrating the disappearance of this region. C, CT scans performed when focal neurological symptoms occurred 3 hours after DSA demonstrated the progression of intracerebral hematoma deep along the convexity SAH protruding into the right lateral ventricle. DSA, digital subtraction angiography; SAH, subarachnoid hemorrhage. E1324 | VOLUME 70 | NUMBER 5 | MAY 2012 www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. CRYPTIC VASCULAR MALFORMATION-EVOKED CONVEXITY SAH FIGURE 3. Intraoperative photograph. A, isolated SAH in the right convexity approached via a temporoparietal craniotomy. B, active bleeding from pseudoaneurysms along with an abnormal tangle of dilated subpial vessels superficial to the postcentral gyrus abutting the hematoma cavity. There are no obvious findings of nidus formation or venous drainage in the surgical field. SAH, subarachnoid hemorrhage. Siemens Medical Solutions, Erlangen, Germany) and CT angiography combined with venous-phase imaging with a 320-detector row volume CT scanner (Aquilion ONE, Toshiba Medical Systems, Tokyo, Japan) covering the entire head (Figure 1C and 1D), no abnormal findings indicative of the cause of hemorrhage were noted throughout the arterial and venous phases. Subsequent digital subtraction angiography (DSA) with a biplanar digital flat-panel detector angiography system (AXIOM Artis dBA, Siemens Medical Solutions, Erlangen, Germany) performed 2.5 hours after admission under mild sedation for further diagnostic yield failed to reveal any cause of SAH including tumor blush, multifocal vasospasm, or vascular malformation, although a right frontoparietal avascular region without extravasation (Figure 2A) was suspected to be due to a newly developed intracerebral hematoma (ICH). The lesion was simultaneously confirmed by flat-panel detector angiographic cone-beam CT scan imaging (Sygno Dyna-CT, Siemens Medical Solutions, Erlangen, Germany) (Figure 2A, inset). Because she remained neurologically intact, we decided to perform medical management (systolic blood pressure reduction ,140 mm Hg) to avoid hematoma expansion5 and to perform a follow-up study later after reduction of the mass effect. However, she developed left hemiparesis and numbness of the left hand accompanied by nausea and vomiting 3 hours after DSA. CT scan demonstrated progression of intracerebral hematoma deep along the convexity SAH protruding into the right lateral ventricle (Figure 2C). The symptoms progressively worsened, and left hemispatial neglect developed within the next hour. In view of the negative workup and accessible location with progressive focal neurological deficits, we elected to perform emergent surgical exploration of the convexity SAH with ICH via a temporoparietal craniotomy 2 hours after the initial deterioration (Figure 3A). Intraoperatively, active bleeding from an abnormal cluster of subpial vessels superficial to the postcentral sulcus abutting the hematoma cavity was seen (Figure 3B). No arterialized cortical veins, microaneurysm, cavernous angioma, or hemorrhagic tumor was observed. The lesion was resected en bloc following hematoma evacuation. Pathological examination confirmed cryptic vascular malformation with several abnormally dilated arterioles with a distended inner layer of the media and smooth muscle fibers within the subarachnoid space surrounded by a thick SAH clot (Figure 4). Postoperative CT revealed removal of intracerebral hematoma without evidence of rebleeding (Figure 5A). MRI revealed gross total resection with reduction of mass effect in the eloquent area (Figure 5B and 5C). The avascular region disappeared on postoperative DSA performed 1 week after resection (Figure 2B). Further recovery was uneventful, and at the time of discharge (approximately 3 months after surgery) no deficits were present other than mild numbness of the left hand. DISCUSSION preceded by transient numbness of the right hand. She was neurologically intact on examination, but localized right convexity SAH was observed on plain head computed tomography (CT) scan (Figure 1A). She was then referred to the stroke service of our center for further diagnosis and treatment. Despite extensive radiological workup covering the entire head using 3.0-Tesla brain magnetic resonance (MR) imaging (Figure 1B) with MR angiography (MAGNETOM Verio, NEUROSURGERY This is, to the authors’ knowledge, the first report of ruptured cryptic vascular malformation presenting with primary isolated convexity SAH of unknown etiology confirmed pathologically by examination of a surgical specimen resected directly from the bleeding point. One cohort2 and 2 case series 3,4 have been published on nontraumatic nonaneurysmal SAH in the cortical convexity in which 2 VOLUME 70 | NUMBER 5 | MAY 2012 | E1325 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. MUTOH ET AL FIGURE 4. Microsection of the specimen with cryptic vascular malformation. A, low-power cross-sectional view of resected abnormal vasculature surrounded by SAH clot. B, higher magnification of the boxed area in A (original magnification ·10) including the bleeding point of the pseudoaneurysm in Figure 3B. High-power views (original magnification ·40) revealing several abnormally dilated arterioles with distended inner layer of the media and smooth muscle fibers (*) located within subarachnoid space clearly separate from the brain parenchyma (**) via a lepotomeninges-like membrane (C). Note other vascular structures (same magnification as in C) are smaller and pathologically intact without any microscopic evidence of nidus formation, microaneurysm, or cavernoma (D). Elastica-Masson trichrome stain. SAH, subarachnoid hemorrhage. FIGURE 5. A, postoperative CT performed immediately after surgery revealing removal of intracerebral hematoma without evidence of rebleeding. Diffusion-weighted (B) and T2-weighted (C) axial MRI performed on postoperative day 3 showing gross total resection along the right postcentral sulcus. E1326 | VOLUME 70 | NUMBER 5 | MAY 2012 www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. CRYPTIC VASCULAR MALFORMATION-EVOKED CONVEXITY SAH common patterns of presentation were identified: younger patients #60 years with sudden onset of headache similar to aneurysm rupture are frequently diagnosed with a primary vasoconstriction syndrome following exclusion of vascular malformations on repeated DSA, and older patients who have temporary sensory or motor symptoms and typically exhibit amyloid angiopathy. These studies consistently indicate a benign clinical course and outcome for convexity SAH in younger patients, but note the possibility of small superficial arteriovenous malformations or microangiomas that may have escaped detection in radiological workup, but that can be lethal. The presence of acute ICH in a young and healthy adult in the absence of an obvious cause is strongly suggestive of an underlying pathological condition. It should be noted that convexity SAH carries significant risks of recurrent ICH and high mortality (50%) in the elderly, mostly in association with amyloid angiopathy.2 On the other hand, the natural history of vascular malformations that cause primary isolated convexity SAH and the actual risk of massive hemorrhage of them are unclear, because fewer than 5% of all ruptured arteriovenous malformations causes extravasation in the subarachnoid space without ICH.6 Given the pathophysiological similarity of amyloid angiopathy originating in the subarachnoid space, particularly the cerebral sulci, and causing multiple rupture of meningeal arteries,7,8 it may also be the case that isolated vascular malformations located primarily in the subarachnoid space of the convexity (Figure 4) are a source of ICH. Despite the lack of evidence for nidus formation or major draining veins, the presence of pseudoaneurysms, which increase the risk of hemorrhage,9 suggests the vulnerability of dilated vessels to hemodynamic stress, triggering vessel rupture. The term “cryptic” has been proposed by Crawford and Russell to describe small vascular malformations less than 2 to 3 cm in diameter that cause spontaneous cerebral hemorrhage.10 Currently, the combination of meeting the criterion for size (,1 cm in diameter and often a few millimeters in size)11 and being angiographically occult12,13 can be used to define lesions. Despite extensive workup using advanced modalities of high diagnostic yield (3.0-Tesla MRI/MRA, 3D-CT DSA with 320-detector row CT system, and flat-panel detector DSA with volumetric CT imaging system), the lesion in the present case was too small to specify its origin radiologically without evidence of newly developed ICH and/or neurological deterioration and to proceed with early surgical exploration.14 Of course, we still cannot rule out the possibility of negative catheter DSA findings in situations in which mass effect from the intraparenchymal hemorrhage can compress and stop flow into the microateriovenous malformation,9 preventing it from being visualized on the angiogram, and thus repeated DSA may have contributed to obtaining a useful diagnostic yield. In any event, it was fortunate in this case that intraoperatively we could obtain a specimen of vascular malformation from a few abnormally dilated small vessels that was successfully visualized NEUROSURGERY in the subarachnoid space by careful inspection of the hematoma cavity and SAH clots and examine it for abnormal vasculature. The management of angiographically and MRI-negative convexity SAH has not been clearly defined, because the risk of rebleeding is not clearly known. However, based on these findings and those already published in the literature regarding intraparenchymal hemorrhage,14 surgical exploration of patients strongly suspected to have an underlying origin, if there is no ICH and only convexity SAH, may be considered. In particular, the presence of symptomatic hemorrhage accompanied by progressive and/or recurrent focal signs (eg, transient sensory/ motor deficits, as observed in convexity SAH caused by amyloid angiopathy2) in an accessible and noneloquent area is another factor facilitating early/emergent surgical inspection. On the other hand, if the lesion is surgically inaccessible or asymptomatic, waiting and conservative management are possible with follow-up imaging studies for the resolution of SAH clots without recurrence at least during the time of hospital stay (approximately 16.5 days)3 for most patients presenting with a benign clinical course. In conclusion, it is important to consider the possibility of ruptured cryptic vascular malformation as a cause of nontraumatic nonaneurysmal convexity SAH when recurrent hemorrhage is observed despite rigorous diagnostic workup, because surgical resection may be the only curative treatment option and eliminate the risk of rebleeding and disabling symptoms. Disclosure The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Patel KC, Finelli PF. Nonaneurysmal convexity subarachnoid hemorrhage. Neurocrit Care. 2006;4(3):229-233. 2. Kumar S, Goddeau RP Jr, Selim MH, et al. Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology. 2010;74(11):893-899. 3. Refai D, Botros JA, Strom RG, Derdeyn CP, Sharma A, Zipfel GJ. Spontaneous isolated convexity subarachnoid hemorrhage: presentation, radiological findings, differential diagnosis, and clinical course. J Neurosurg. 2008;109(6):1034-1041. 4. Spitzer C, Mull M, Rohde V, Kosinski CM. Non-traumatic cortical subarachnoid haemorrhage: diagnostic work-up and aetiological background. Neuroradiology. 2005;47(7):525-531. 5. Arima H, Anderson CS, Wang JG, et al. Lower treatment blood pressure is associated with greatest reduction in hematoma growth after acute intracerebral hemorrhage. Hypertension. 2010;56(5):852-858. 6. Aoki N. Do intracranial arteriovenous malformations cause subarachnoid haemorrhage? Review of computed tomography features of ruptured arteriovenous malformations in the acute stage. Acta Neurochir (Wien). 1991;112(3-4): 92-95. 7. Katoh M, Yoshino M, Asaoka K, et al. A restricted subarachnoid hemorrhage in the cortical sulcus in cerebral amyloid angiopathy: could it be a warning sign? Surg Neurol. 2007;68(4):457-460. 8. Takeda S, Yamazaki K, Miyakawa T, et al. Subcortical hematoma caused by cerebral amyloid angiopathy: does the first evidence of hemorrhage occur in the subarachnoid space? Neuropathology. 2003;23(4):254-261. VOLUME 70 | NUMBER 5 | MAY 2012 | E1327 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. MUTOH ET AL 9. Dillon WP. Cryptic vascular malformations: controversies in terminology, diagnosis, pathophysiology, and treatment. AJNR Am J Neuroradiol. 1997;18 (10):1839-1846. 10. Crawford JV, Russell DS. Cryptic arteriovenous and venous hamartomas of the brain. J Neurol Neurosurg Psychiatry. 1956;19(1):1-11. 11. Rajshekhar V, Chandy MJ. What is a "cryptic" arteriovenous malformation? J Neurol Neurosurg Psychiatry. 1988;51(11):1459. 12. Robinson JR Jr, Awad IA, Masaryk TJ, Estes ML. Pathological heterogeneity of angiographically occult vascular malformations of the brain. Neurosurgery. 1993;33 (4):547-554; discussion 554-555. 13. Ogilvy CS, Heros RC, Ojemann RG, New PF. Angiographically occult arteriovenous malformations. J Neurosurg. 1988;69(3):350-355. 14. Elhammady MS, Baskaya MK, Heros RC. Early elective surgical exploration of spontaneous intracerebral hematomas of unknown origin. J Neurosurg. 2008;109 (6):1005-1011. Acknowledgments We thank Kaoru Sato, Keita Narita, CE, Kimio Yoshioka, CE, and Hideto Toyoshima BSc, for their invaluable support in the acquisition of radiological and intraoperative data. COMMENT I n this case report, the authors describe a patient with a cryptic arteriovenous malformation (AVM) presenting with isolated subarachnoid E1328 | VOLUME 70 | NUMBER 5 | MAY 2012 hemorrhage (SAH) initially on computed tomography (CT) scan that was angiographically normal, followed by a rebleed, resulting in a symptomatic intraparenchymal hematoma requiring surgical evacuation. During evacuation, the contents of the hematoma were found to contain a small bundle of abnormally dilated vessels consistent with an AVM, later confirmed histologically. The authors are correct in stating that there were no previous reports of a cryptic AVM initially presenting with only SAH. Others have described cryptic lesions identified at the time of surgical exploration for intraparenchymal hemorrhages, and these references are cited and briefly discussed by the authors. Surgical exploration in patients with angiographically and magnetic resonance imaging-negative, convexity SAH without IPH (intraparenchymal hemorrhage), is not a reasonable option for patients. However, cryptic AVMs should be in the differential diagnosis in such cases, particularly because the AVM may be not be visualized radiographically as a result of thrombosis or from compression by the mass effect of IPH. In short, it still appears that surgical exploration in such a case should be reserved only for those who also have a symptomatic IPH with mass effect, while those with angiographic- and magnetic resonance imaging-negative convexity SAH alone, should be followed carefully with follow-up imaging studies. Eric M. Deshaies Syracuse, New York www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.