Case Report 29 Rare Intramedullary Hemorrhage of a Brainstem Hemangioblastoma Seltene intramedulläre Blutung eines Hirnstammhämangioblastoms Author Y.-M. Ryang1, M. F. Oertel1, A. Thron2, J. Gilsbach1, V. Rohde3 Affiliation 1 Department of Neurosurgery, RWTH Aachen University, Aachen, Germany Department of Neuroradiology, RWTH Aachen University, Aachen, Germany 3 Department of Neurosurgery, Georg-August-University, Goettingen, Germany Key words 䉴 brainstem hemorrhage 䊉 䉴 hemangioblastoma 䊉 䉴 von Hippel-Lindau disease 䊉 Schlüsselwörter 䉴 Hirnstammblutung 䊉 䉴 Hämangioblastom 䊉 䉴 von Hippel-Lindau Er䊉 krankung Bibiliography DOI 10.1055/s-2007-968167 Zentralbl Neurochir 2007; 68: 29–33 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0044-4251 Correspondence Y.-M. Ryang Department of Neurosurgery University Hospital (RWTH) Aachen (Aachen University) Pauwelsstr. 30 50274 Aachen Germany Tel.: +49/2 41/8 08 84 81 Fax: +49/2 41/8 08 24 20 ryang@gmx.de Abstract & Zusammenfassung & Object: Hemorrhages caused by hemangioblastomas are very rare and mostly located in the subarachnoid space. Intraparenchymal bleedings due to hemangioblastomas are even less frequent, and these hemorrhages are almost exclusively located in the supratentorial brain, cerebellum and spinal cord. We report the first case of a brainstem hemorrhage due to a hemangioblastoma of the medulla oblongata. Case Report: A 47-year-old woman presented with acute onset of headache, anarthria, inability to swallow, left-sided hemiparesis and hemidysesthesia with varying states of vigilance, finally developing acute respiratory failure. Cranial computed tomography (CT) scanning and magnetic resonance imaging (MRI) revealed a small hemangioblastoma of the posterior medulla oblongata causing intraparenchymal hemorrhage and acute occlusive hydrocephalus due to intraventricular hematoma extension. Result: After implantation of an external ventricular catheter to treat acute hydrocephalus, the hemangioblastoma as well as its associated hemorrhage could be removed in toto via a microsurgical posterior median suboccipital approach with minimal foramen magnum enlargement. During the follow-up period of six months postoperatively the patient showed good recovery with only slight residual neurological deficits. Conclusion: The most common causes of brainstem hemorrhages are arterial hypertension and cavernous hemangiomas. However, hemangioblastomas should not be ignored as a possible differential diagnosis for intraparenchymal brainstem hemorrhage. While the prognosis in hypertensive brainstem bleedings is mostly disastrous and surgery rarely indicated, an operative therapy should be considered in cases of hemorrhages caused by underlying tumors. Especially in the treatment of heman- Blutungen von Hämangioblastomen sind sehr selten und meist subarachnoidal lokalisiert. Die noch selteneren intraparenchymatösen Blutungen treten fast ausschließlich supratentoriell, zerebellär sowie im Rückenmark auf. Wir berichten über den ersten Fall einer Hirnstammblutung verursacht durch ein Hämangioblastom der Medulla oblongata. Fallbericht: Eine 47-jährige Patientin klagte über akut aufgetretene Kopfschmerzen, eine Anarthrie sowie Schluckstörungen und wies eine linksseitige Hemiparese und -dysästhesie auf. Sie bot wechselnde Vigilanzzustände und entwickelte letztendlich eine respiratorische Insuffizienz. Kranielle computer- und kernspitomographische Untersuchungen zeigten ein kleines Hämangioblastom in der dorsalen Medulla oblogata als Ursache der intraparenchymatösen Blutung mit begleitendem Ventrikeleinbruch und nachfolgendem akutem Hydrocephalus occlusus. Ergebnis: Der akute Hydrozephalus wurde mit einer externen Ventrikeldrainage behandelt. Die Blutung als auch das Hämangioblastom konnten in toto über eine posteriore mediane subokzipitale osteoklastische Erweiterung des Foramen magnum mikrochirurgisch entfernt werden. Im Verlauf von sechs Monaten postoperativ hatte sich die Patientin gut erholt und wies nur noch minimale residuelle neurologische Defizite auf. Schlussfolgerung: Zu den häufigsten Ursachen von Hirnstammblutungen gehören die arterielle Hypertonie und kavernöse Hämangiome. Dennoch sollten Hämangioblastome als eine weitere mögliche Differentialdiagnose nicht außer Acht gelassen werden. Während die Prognose hypertensiver Hirnstammblutungen meist ungünstig und eine Operation nicht sinnvoll ist, sollte eine mikrochirurgische Behandlung bei der Blutung zugrunde liegenden Tumoren in Betracht gezogen werden. Insbesondere bei Hämangioblastomen Ryang Y-M et al. Rare Intramedullary Hemorrhage… Zentralbl Neurochir 2007; 68: 29–33 Downloaded by: University of Pittsburgh. Copyrighted material. 2 gioblastoma, the surgical management strategy is crucial for a successful result. Therefore, the authors recommend including the search for hemangioblastomas into the diagnostic workup in patients with brainstem hemorrhages. ist die richtige operative Strategie entscheidend für den Therapieerfolg. Daher empfehlen die Autoren, die Suche nach Hämangioblastomen in die diagnostische Abklärung von Patienten mit Hirnstammblutungen mit einzubeziehen. Introduction & Hemorrhage into a tumor-associated pseudocyst could not be verified. Furthermore, MRI revealed multiple strongly gadolinium-enhancing cerebellar lesions bilaterally of up to 8 mm in diameter compatible with multiple hemangioblastomas as in von Hippel-Lindau disease. Family history, ultrasonography of the abdomen and ophthalmological examination were negative for VHL disease. The presence of multiple hemangioblastomas is nearly always evidential for VHL disease and sufficient to determine the diagnosis of VHL [15, 24, 28]. VHL gene mutation analysis has therefore not been performed yet. Due to the small tumor size angiography to reveal the blood supply of the tumor was considered negligible. The patient remained analgosedated, intubated and mechanically ventilated and was taken to the operating room the following day. Microsurgery was carried out in a sitting position with the head fixed slightly anteflexed in a Mayfield clamp in an anterior-posterior position. Access was obtained through a minimal osteoclastic median foramen magnum enlargement. A straight Hemangioblastomas account for 3 % of all central nervous system (CNS) tumors. They occur sporadically in the majority of cases. About 20–30 % are associated with autosomal, dominantly inherited, von Hippel-Lindau (VHL) disease with frequent retinal and renal tumor manifestations [8, 28]. Up to 90 % of hemangioblastomas are located in the cerebellum, 3–13 % in the spinal cord and an average of 13 % (4–26 %) in the brainstem [2, 4–6, 10, 14, 17, 18, 22, 25, 26, 29–31, 33, 34]. According to the WHO (World Health Organization) classification they are considered tumors of uncertain histogenesis [12]. Despite their high vascularization, spontaneous hemorrhages are rare. Most reported cases include spinal subarachnoid hemorrhages [1, 3, 9, 16]. Only a few cases of intraparenchymal bleeding into the supratentorial brain, cerebellum and, even less frequently, the spinal cord have been reported [11, 27, 32]. A hemangioblastoma-associated bleeding into the brainstem has not been reported so far. Therefore, the authors feel encouraged to present the first case of a brainstem hemorrhage caused by a hemangioblastoma of the medulla oblongata and to discuss the potential differential diagnoses. Clinical Presentation & A 47-year-old female patient was admitted with headache of acute onset, severe dysarthria, difficulties in swallowing, leftsided hemiparesis and hemihypesthesia of her body and face which lasted for several hours prior to admission. She presented with alternating states of vigilance ranging from somnolence to distinct agitation. Gag reflexes were absent bilaterally with inability to swallow. In addition, she suffered from anarthria and inability to move her tongue caused by a bilateral plegia of the glossopharyngeal, vagal and hypoglossal nerves. Pupils were equally round and reactive to light. She showed a hemihypesthesia and a moderate hemiparesis including the face on the left side. Deep tendon reflexes were present bilaterally. Pyramidal tract signs were absent. A cranial computed tomography (CT) scan revealed an intramedullary hemorrhage located in the dorsomedian caudal medulla oblongata (MO), extending into the fourth and, to a lesser extent, the third ventricle causing acute occlusive hydrocephalus. After immediate transfer to the Neurosurgical Intensive Care Unit, she deteriorated rapidly and developed respiratory failure necessitating intubation. Acute hydrocephalus was treated by implantation of an external ventricular catheter. Magnetic resonance imaging (MRI) performed the following day showed a strongly gadolinium-enhancing lesion of 4 mm in diameter on T1 -weighted images (䊉䉴 Figs. 2, 4 and 5). It was located on the surface of the right posterior medulla oblongata and accompanied by an intramedullary hematoma extending ventrally into the medial MO as visible on the T2 -weighted MRI scans (䊉䉴 Figs. 1 and 3). There was no clinical or anamnestic evidence for any neurological deficits caused by a symptomatic tumor-associated pseudocyst. On MRI the tumor appeared as a solid nodule. Fig. 1 Axial T2 -weighted MRI scan demonstrating the acute brainstem hemorrhage in the dorsomedian medulla oblongata. Fig. 2 Axial T1 -weighted gadolinium-enhanced MRI scan showing the strongly contrast-enhancing hemangioblastoma in the right posterior medulla oblongata causing the acute brainstem hemorrhage. Ryang Y-M et al. Rare Intramedullary Hemorrhage… Zentralbl Neurochir 2007; 68: 29–33 Downloaded by: University of Pittsburgh. Copyrighted material. 30 Case Report Fig. 3 Coronary T2 -weighted MRI scan demonstrating the intramedullary hemorrhage in the dorsomedian medulla oblongata. Fig. 5 Sagittal T1 -weighted gadolinium-enhanced MRI scan showing the strongly contrast-enhancing intramedullary hemangioblastoma in the dorsal medulla oblongata. Fig. 4 Coronary T1 -weighted gadolinium-enhanced MRI scan showing the strongly contrast-enhancing hemangioblastoma nodule in the posterior medulla oblongata. median dural incision was performed. The hemangioblastoma was identified immediately beneath the pia mater on the right surface of the posterior medulla oblongata between the posterior medullary velum and the obex. Small feeding vessels arising from the PICA were coagulated, the pia above the tumor nodule was incised and the hematoma opened. After complete hematoma evacuation the hemangioblastoma could be visualized more clearly. Intraoperatively, there also was no evidence of hemorrhage extension into a pre-existing pseudocyst. The hemangioblastoma was shrunken by bipolar coagulation which allowed development of a cleavage plane between tumor and brainstem tissue, and, finally, resection of the hemangioblastoma was carried out in toto. Postoperative cranial CT scans showed normal postoperative findings without signs of rebleeding. Histopathological investigation confirmed the diagnosis of a hemangioblastoma. Controlled extubation was attempted eight days after the hemorrhage but failed after several hours due to persisting difficulties in swallowing and in breathing caused by a compromized upper airway. She was reintubated and a percutaneous dilatational tracheotomy performed three days later. The patient could be successfully weaned from the ventilator and was breathing spontaneously after another week. Two weeks after the hemorrhage she was awake, fully orientated, communicating by writing on a cardboard, with improvement of her neurological deficits, and nutrition was supplied by a percutaneous endoscopic gastrostomy (PEG). Six months later, after the tracheotomy was removed, the patient had improved significantly with only slight neurological deficits. She was able to breathe and speak with a slightly guttural voice. Her swallowing disorders were confined to very solid food. Despite minor residual hemiparesis and hemidysesthesia she was able to ambulate without a walking aid. She is back home with her family and able to carry out most of the daily household chores without assistance. Discussion & Spontaneous hemorrhages caused by hemangioblastomas are rare. Recently, Gläsker and van Velthoven evaluated the risk of hemorrhage in hemangioblastomas of the CNS in a large retrospective clinical series of 204 patients with a follow-up time of between 1 and 33 years (mean, 14.2 years). In their series, seven Ryang Y-M et al. Rare Intramedullary Hemorrhage… Zentralbl Neurochir 2007; 68: 29–33 Downloaded by: University of Pittsburgh. Copyrighted material. Case Report 31 32 Case Report Conclusion & Spontaneous intraparenchymal hemorrhages, especially in small hemangioblastomas are extremely rare. A brainstem hemorrhage of a hemangioblastoma is an exceptional finding and, to the best of our knowledge, has not yet been reported so far. The surgical therapy of hemangioblastomas differs substantially from that of other pathologies. Therefore these tumor entities should not be forgotten as a possible cause of a brainstem hemorrhage and need to be properly diagnosed. References 1 Berlis A, Schumacher M, Spreer J, Neumann HP, van Velthoven V: Subarachnoid hemorrhage due to cervical spinal cord hemangioblastomas in a patient with von Hippel-Lindau disease. Acta Neurochir (Wien) 2003; 145: 1009–1013 2 Brown TR, Adams RD, Roberson GH: Hemangioblastoma of the spinal cord. Review and report of five cases. Arch Neurol 1976; 33: 435–441 3 Cervoni L, Franco C, Celli P, Fortuna A: Spinal tumor and subarachnoid hemorrhage: pathogenetic and diagnostic aspects in 5 cases. Neurosurg Rev 1995; 18: 159–162 4 Conway J, Chon D, Clatterbuck RE, Brem H, Long DM, Rigamonti D: Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001; 48: 55–63 5 de la Monte SM, Horowitz SA: Hemangioblastomas: clinical and histopathological factors correlated with recurrence. Neurosurgery 1989; 25: 695–698 6 Fukushima T, Sakamoto S, Iwaasa M, Hayashi S, Yamamoto M, Utsunomiya H, Tomonaga M: Intramedullary hemangioblastoma of the medulla oblongata – two case reports and review of the literature. Neurol Med Chir (Tokyo) 1998; 38: 489–498 7 Filling-Katz MR, Choyke PL, Oldfield E, Charnas L, Patronas NJ, Glenn GM, Gorin MB, Morgan JK, Lineham WM, Seizinger BR, Zbar B: Central nervous system involvement in von Hippel-Lindau disease. Neurology 1991; 41: 41–46 8 Gläsker S, van Velthoven V: Risk of hemorrhage in hemangioblastoma of the central nervous system. Neurosurgery 2005; 57: 71–76 9 Irie K, Kuyama H, Nagao S: Spinal cord hemangioblastoma presenting with subarchanoid hemorrhage. Neurol Med Chir (Tokyo) 1998; 38: 355–358 10 Jelsma RK, Jelsma LF, Johnson GS: Surgical removal of brainstem astrocytomas and hemangioblastomas: report of three cases and review. Surg Neurol 1993; 39: 494–510 11 Kikuchi K, Kowada M, Sasaki J, Yanagida N: Cerebellar hemangioblastoma associated with fatal intratumoral hemorrhage: report of an autopsied case [in Japanese]. No Shinkei Geka 1994; 22: 593–597 12 Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberge G, Burger PC, Cavenee WK: The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002; 61: 215–225 13 Konovalov AN, Spallone A, Makhmudov UB, Kukhlajeva JA, Ozerova VI: Surgical management of hematomas of the brain stem. J Neurosurg 1990; 73: 181–186 14 Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH: Posterior fossa hemangioblastomas: MR imaging. Radiology 1989; 171: 463–468 15 Maher ER, Iselius L, Yates JR, Littler M, Benjamin C, Harris R, Sampson J, Williams A, Ferguson-Smith MA, Morton N: Von Hippel- Lindau disease: a genetic study. J Med Genet 1991; 28: 443–447 16 Minami M, Hanakita J, Suwa H, Suzui H, Fujita K, Nakamura T: Cervical hemangioblastoma with a past history of subarachnoid hemorrhage. Surg Neurol 1998; 49: 278–281 17 Neumann HP, Eggert HR, Weigel K, Friedburg H, Wiestler OD, Schollmeyer P: Hemangioblastomas of the central nervous system: a 10year study with special reference to von Hippel-Lindau syndrome. J Neurosurg 1989; 70: 24–30 18 Okawara SH: Solid cerebellar hemangioblastoma. J Neurosurg 1973; 39: 514–518 19 Posadas G, Vaquero J, Herrero J, Bravo G: Brainstem haematomas: early and late prognosis. Acta Neurochir (Wien) 1994; 131: 189–195 20 Resche F, Moisan JP, Mantoura J, de Kersaint-Gilly A, André MJ, PerrinResche I, Menegalli- Boggelli D, Lajat Y, Richard S: Haemangioblastoma, haemangioblastomatosis, and von Hippel-Lindau disease. Adv Tech Stand Neurosurg 1993; 20: 197–304 21 Richard S, Campello C, Taillandier L, Parker F, Resche F: Haemangioblastoma of the central nervous system in von Hippel-Lindau disease. French VHL study Group. J Intern Med 1998; 243: 547–553 22 Rohde V, Voigt K, Grote EH: Intra-extradural hemangioblastoma of the cauda equina. Zentralbl Neurochir 1995; 56: 78–82 23 Rohde V, Ryang Y, Gilsbach JM: Management of brain stem hematomas. Monduzzi Editore, Bologna 2003; 141–144 24 Slater A, Moore NR, Huson SM: The natural history of cerebellar hemangioblastomas in von Hippel-Lindau disease. AJNR Am J Neuroradiol 2003; 24: 1570–1574 25 Spetzger U, Bertalanffy H, Huffmann B, Mayfrank L, Reul J, Gilsbach JM: Hemangioblastomas of the spinal cord and the brainstem: diagnostic and therapeutic features. Neurosurg Rev 1996; 19: 147–151 26 Standard SC, Ahuja A, Livingston K, Guterman LR, Hopkins LN: Endovascular embolization and surgical excision for the treatment of cerebel- Ryang Y-M et al. Rare Intramedullary Hemorrhage… Zentralbl Neurochir 2007; 68: 29–33 Downloaded by: University of Pittsburgh. Copyrighted material. symptomatic spontaneous hemorrhages in five patients were found. Six hemorrhages were located in the subarachnoid space, whereas only one hemorrhage occurred intraparenchymally in the thoracic spinal cord. A very low risk of spontaneous hemorrhage of 0.24 % per person per year was calculated. The authors clearly associated the risk of bleeding with large tumor size. According to Gläsker and van Velthoven, tumors below 1.5 cm in diameter have virtually no risk of bleeding. However, in the present case the intraparenchymal brainstem hemorrhage was caused by a small hemangioblastoma with a diameter of only 4 mm [8]. Arterial hypertension is the most common cause of intraparenchymal hemorrhage into the brainstem in adults. The majority of hypertensive brainstem hemorrhages lead to immediate coma and have a devastating, mostly fatal prognosis. In these cases, surgery is usually not a therapeutic option [35]. Another common source of brainstem bleeding are underlying cavernous hemangiomas, which tend to have a better prognosis and usually cause only focal neurological deficits but no coma [23]. In cases of close proximity of the cavernoma to the brainstem surface, surgery is generally indicated to avoid rebleeding. Whether hematoma and cavernoma should be removed immediately or with some delay remains a topic of discussion [13, 19]. Since different causes of brainstem hemorrhages require different management strategies, proper preoperative workup to exclude or confirm the diagnosis of a possible underlying lesion are of immense importance. As we report here the first case of a brainstem hemorrhage caused by a hemangioblastoma, we recommend adding contrast-enhanced MRI, either primarily or after absorption of the hematoma as the method of choice for early diagnosis of CNS hemangioblastomas into the diagnostic workup in all cases of a suspected underlying tumorous lesion and to include hemangioblastoma into the differential diagnosis of a hemorrhage-causing tumor [7, 20, 21]. There is general agreement that symptomatic hemangioblastomas should be treated surgically; the operative strategy consists of coagulation of the feeding arteries and tumor shrinkage to develop a cleavage plane between tumor and brain tissue, which is of utmost importance in highly eloquent areas such as the brainstem and the spinal cord. Opening the tumor has to be avoided by all means to prevent brisk bleeding. Furthermore, bleeding obscures the cleavage plane, making tumor removal more hazardous. Therefore, the authors believe that the correct diagnosis prior to surgery is crucial in hemangioblastomas of the brainstem to avoid severe surgical complications. In the present case the intraparenchymal hematoma largely facilitated tumor removal because the existing bleeding had already created a cleavage plane between the ventral tumor surface and brainstem tissue. Case Report 33 32 Yu JS, Short MP, Schumacher J, Chapman PH, Harsh 4th GR: Intramedullary hemorrhage in spinal cord hemangioblastoma. Report of two cases. J Neurosurg 1994; 81: 937–940 33 Zhou LF, Du G, Mao Y, Zhang R: Diagnosis and treatment of brainstem hemangioblastomas. Surg Neurol 2005; 63: 307–315 34 Zimmermann M, Seifert V, Schreyer T, Stolke D, Dietz H: Hemangioblastomas: description of a disease picture and report of 41 cases. Zentralbl Neurochir 1997; 58: 1–6 35 Zuccarello M, Iavicoli R, Pardatscher K, Scanarini M, Fiore D, Andrioli GC: Primary brain stem haematomas. Diagnosis and treatment. Acta Neurochir (Wien) 1980; 54: 45–52 Downloaded by: University of Pittsburgh. Copyrighted material. lar and brain stem hemangioblastomas. Surg Neurol 1994; 41: 405–410 27 Wakai S, Inoh S, Ueda Y, Nagai M: Hemangioblastoma presenting with intraparenchymatous hemorrhage. J Neurosurg 1984; 61: 956–960 28 Wanebo JE, Lonser RR, Glenn GM, Oldfield EH: The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg 2003; 98: 82–94 29 Wang C, Zhang J, Liu A, Sun B: Surgical management of medullary hemangioblastoma. Report of 47 cases. Surg Neurol 2001; 56: 218–226 30 Weil RJ, Lonser RR, DeVroom HL, Wanebo JE, Oldfield EH: Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg 2003; 98: 95–105 31 Young S, Richardson AE: Solid haemangioblastomas of the posterior fossa: radiological features and results of surgery. J Neurol Neurosurg Psychiatry 1987; 50: 155–158 Ryang Y-M et al. Rare Intramedullary Hemorrhage… Zentralbl Neurochir 2007; 68: 29–33