Neurol Med Chir (Tokyo) 44, 479¿483, 2004 Cerebral Infarction Following Pituitary Apoplexy —Case Report— Hiroyoshi AKUTSU, Shozo NOGUCHI, Takashi TSUNODA, Mamoru SASAKI, and Akira MATSUMURA* Department of Neurosurgery, Ibaraki Prefectural Central Hospital, Ibaraki; *Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki Abstract A 29-year-old man presented with lethargy, headache, high fever, and visual disturbance. Neurological examination showed mydriatic pupil, ptosis, diminished light reflex, and ophthalmoplegia on the left. Magnetic resonance (MR) imaging showed the typical findings of pituitary apoplexy, and cerebral angiography disclosed mild narrowing of the A1 segment of the left anterior cerebral artery (ACA). Transsphenoidal tumor resection was performed. Transient severe right hemiparesis occurred directly after the operation. Computed tomography demonstrated cerebral infarction in the territory of the left Heubner's and medial lenticulostriate arteries. Pituitary apoplexy followed by cerebral infarction is very rare. Vasospasm of the perforating arteries of the ACA probably caused the cerebral infarction. Subarachnoid blood or vasoactive agents released from the tumor were the most likely cause of the vasospasm. MR imaging findings of contrast enhancement around the vessels may indicate reactive processes around the vessels. Key words: pituitary apoplexy, cerebral infarction, Introduction vasospasm diminished light reflex, and ophthalmoplegia on the left. His left eye could discern only light. His body temperature was 399C and his neck was stiff. Blood tests showed the white cell count was 9400 mm3, C-reactive protein level was 24.66 mg/dl, and sodium level was 126 mmol/l. The thyroid hormone and prolactin levels were slightly decreased but other hormone levels were normal. Cerebrospinal fluid was not examined. Computed tomography (CT) showed a large pituitary tumor with suprasellar and lateral extension into the left cavernous sinus. No subarachnoid hemorrhage (SAH) was detected (Fig. 1). Magnetic resonance (MR) imaging indicated that the tumor was partially hyperintense on T1-weighted images, suggesting hematoma, with enhancement of the peritumoral brain surface (including the hypothalamus), and around the walls of the A1 segment of the left anterior cerebral artery (ACA) and the M1 segment of the left middle cerebral artery (MCA) Pituitary apoplexy is a well-known clinical syndrome manifesting as headache, meningeal irritation, visual loss, ophthalmoplegia, and changes in consciousness. Cerebral infarction associated with pituitary apoplexy is rare. Here we describe a case of pituitary apoplexy complicated by cerebral infarction. Case Report A 29-year-old man developed high fever and diarrhea, and several hours later suffered sudden onset of headache and visual disturbance. He was lethargic and unable to walk the next day. On admission 2 days later, the patient was drowsy but welloriented, and could obey verbal commands. Neurological examination revealed hypalgesia in the left forehead, anisocoria (left À right), ptosis, Received August 29, 2003; Accepted April 14, 2004 Author's present address: H. Akutsu, M.D., Department of Neurosurgery, Tsukuba Medical Center, Tsukuba, Ibaraki, Japan. 479 H. Akutsu et al. 480 (Fig. 2A, B). T2-weighted MR imaging revealed hyperintense areas in the bilateral frontal lobes and hypothalamus suggesting edema (Fig. 2C). Cerebral angiography on the day of admission disclosed mild narrowing of the A1 segment of the left ACA. The patient was treated with antibiotics and C, but the steroids. His temperature decreased to 379 consciousness disturbance progressed slightly, his left eye became blind and fixed in the mid-position, and light reflex was lost on the left. Transsphenoidal excision of the tumor was per- formed on the day after admission. The sphenoid sinus was filled with hematoma. The tumor was hemorrhagic and necrotic, and was subtotally removed except for a small portion invading the left cavernous sinus. Histological examination of the specimen revealed diffuse necrosis and hemorrhage in the pituitary adenoma, compatible with pituitary apoplexy. The left pupil became reactive to light but he remained drowsy with severe right hemiparesis directly after the operation. CT immediately after Fig. 3 Fig. 1 Computed tomography scan showing a heterogeneous mass of slightly high density in the suprasellar cistern. Fig. 2 Computed tomography scan taken immediately after the operation showing hypodense areas in the territory of the left Heubner's and medial lenticulostriate arteries. Coronal T1-weighted magnetic resonance (MR) images (A) and with gadolinium (B) showing the intra- and suprasellar mass and enhancement of the peritumoral brain surface, and the walls of the A1 segment of the left anterior cerebral artery and the M1 segment of the left middle cerebral artery. T2-weighted MR image showing edema on the surface of the bilateral frontal lobes and hypothalamus (C). Neurol Med Chir (Tokyo) 44, September, 2004 Pituitary Apoplexy and Cerebral Infarction Fig. 4 481 Magnetic resonance images taken 1 month after the operation. Fluid-attenuated inversion recovery image showing high intensity areas in the territory of the left Heubner's and medial lenticulostriate arteries (A), and T1-weighted images showing contrast enhancement in the territory of the left Heubner's and medial lenticulostriate arteries, and small residual tumor (B), and contrast enhancement on the surface of the bilateral frontal lobes and hypothalamus (C). the operation demonstrated hypodense areas in the territory of the left Heubner's and medial lenticulostriate arteries (Fig. 3). The right hemiparesis disappeared 3 hours after onset and his level of consciousness gradually improved. He became alert 2 weeks after the operation. His visual acuity recovered completely, but right homonymous hemianopsia persisted. The third, fourth, and sixth cranial nerve pareses resolved. Endocrinologic testing revealed hypoadrenalism, and cortisone replacement therapy was started. MR imaging 1 month after the operation revealed cerebral infarction in the territory of the left Heubner's and medial lenticulostriate arteries, and contrast enhancement in the bilateral frontal lobes, hypothalamus, and areas of cerebral infarction, and a small residual tumor (Fig. 4). Discussion Cerebral ischemia associated with pituitary apoplexy is very rare, with only nine reported cases as summarized in Table 1.3–5,7,8,11,12) The ischemic events were attributed to cerebral vasospasm in six cases and to mechanical compression by the tumor in three cases. The cerebral infarction was located at the ACA territory in four cases, the MCA territory in two cases, and diffusely in one case. Angiographical stenosis was detected in the internal carotid artery in six cases, in the MCA in two cases, in the ACA in three cases, and in the basilar artery in one case. SAH appeared in only one case. The tumor size was large in all eight described cases and suprasellar Neurol Med Chir (Tokyo) 44, September, 2004 extension was present in all cases. The ischemic event occurred at the day of onset in five cases, 1 day after onset in one case, 5 days after onset in one case, 14 days after onset in one case, and 21 days (postoperatively) after onset in one case. The etiology of cerebral infarction was difficult to determine in our case because angiography did not show apparent vasospasm, and was performed only at admission, and not when the ischemic event occurred. One possible cause of the cerebral infarction was vasospasm due to subarachnoid blood released from the pituitary apoplexy or intraoperative vessel injury, other chemical substances, or mechanical compression during the operation. However, we thought that mechanical compression during operation was not associated with the ischemia because CT immediately after operation had already detected hypodense areas, which indicated that irreversible ischemic change had occurred between the admission and the beginning of the operation (the operative time was within 3 hours). Other possible causes of cerebral infarction include mechanical compression of the arterial vessels due to the mass effect of the tumor or intraoperative manipulation, and dehydration due to hyperthermia, cerebral salt wasting syndrome, or some other factor. Some cases of pituitary apoplexy were associated with cerebral infarction due to mechanical compression of the arterial vessels caused by the tumor mass effect.4,8,12) However, in our case, cerebral angiography showed no apparent mechanical compression of intracranial arteries. The pathophysiology of vasospasm following H. Akutsu et al. 482 Table 1 Reported cases of cerebral ischemia following pituitary apoplexy Author (Year) Age/ Sex Vascular territory of infarction Rosenbaum et al. (1977)12) Cardoso and Peterson (1983)3) 77/M rt MCA 34/F diffuse 38/M - 43/M D'Haens et al. (1983)5) Pozzati et al. (1987)11) Clark et al. (1987)4) Itoyama et al. (1990)7) Lath and Rajshekhar (2001)8) Present case Angiographical findings SAH in CT Symptom Tumor size Days after onset Mechanism rt ICA occlusion, lt ICA stenosis bil ICA, MCA, and ACA stenoses n.e. lt hemiparesis large 0 compression n.e. altered consciousness large 21 (postop.) vasospasm n.e. - n.d. 0 vasospasm bil ACAs bil ICA and BA stenoses lt ICA stenosis - large 0 vasospasm 15/M rt MCA bil ICA stenoses - large 0 vasospasm 40/M lt ACA - large 0 compression 45/M - + large 14 vasospasm 40/M rt ACA rt ICA stenosis, lt ICA occlusion lt ACA and MCA stenoses - aphasia, rt hemiparesis drowsiness, rt facial palsy rt hemiplegia, rt facial palsy rt hemiparesis - lt hemiplegia large 1 compression 29/M lt Heubner's and medial lenticulostriate arteries - drowsiness, lt hemiplegia (transient) large 5 vasospasm lt ACA mild stenosis ACA: anterior cerebral artery, BA: basilar artery, CT: computed tomography, ICA: internal carotid artery, MCA: middle cerebral artery, n.d.: not described, n.e.: not examined, postop.: postoperative, SAH: subarachnoid hemorrhage. pituitary apoplexy is still unclear, although several hypotheses have been advanced, such as the presence of subarachnoid blood, vasoactive chemical substances released from the tumor or the hypothalamohypophyseal area, hypothalamic damage and dysfunction, and intraoperative manipulation.3–5,7,8,11–13) These factors are also possible causes of vasospasm following surgery for pituitary adenoma and other parasellar tumors.1,2,6,10) Subarachnoid blood is well known as a possible primary cause of vasospasm after aneurysmal SAH. In our case, SAH may have been involved in the vasospasm although CT did not show SAH, possibly because 3 days had passed since the onset. The other likely cause of vasospasm is vasoactive agent released from the tumor or the hypothalamohypophyseal area. Extracts obtained from the hypothalamus and pituitary stalk induce vasospasm,13) so vasospasm following pituitary apoplexy may be caused by the release of vasoactive agents from the tumor or the hypothalamohypophyseal area.9,11) In the present case, MR imaging before and after the operation demonstrated contrast enhancement of the parasellar brain surface and the walls of the left ACA and MCA. Similar MR imaging findings have been described in a case of vasospasm caused by chemical meningitis after the spontaneous rupture of a craniopharyngioma cyst.14) Therefore, the same etiological factor may be involved in the present case. Future findings of this type should be carefully noted in cases of pituitary apoplexy. Cerebral infarction following pituitary apoplexy is rare, but clinicians should be aware of the possibility as treatment as early as possible is necessary to obtain favorable therapeutic results. Cerebral angiography should be performed in patients who develop neurological deterioration to determine the cause as vasospasm or other factors. MR imaging detection of contrast enhancement around the vessels may be a helpful clue in the diagnosis of reactive processes of the vessels, as in our patient. Early treatment may be also possible if such findings are recognized on the initial MR imaging. References 1) Aoki N, Origitano TC, Al-Mefty O: Vasospasm after resection of skull base tumors. Acta Neurochir (Wien) 132: 53–58, 1995 2) Camp PE, Paxton HD, Buchan GC, Gahbauer H: Vasospasm after trans-sphenoidal hypophysectomy. Neurosurgery 7: 382–386, 1980 3) Cardoso ER, Peterson EW: Pituitary apoplexy and vasospasm. Surg Neurol 20: 391–393, 1983 4) Clark JDA, Freer CEL, Wheatley T: Case report: pituitary apoplexy: an unusual cause of stroke. Clin Radiol 38: 75–77, 1987 Neurol Med Chir (Tokyo) 44, September, 2004 Pituitary Apoplexy and Cerebral Infarction 5) 6) 7) 8) 9) 10) D'Haens J, Baleriaux D, Mockel J, Flament-Durand J, Brotchi J: Apoplexie hypophysaire isch áemique et accident vasculaire c áer áebral. Neurochirurgie 29: 401–405, 1983 (Fre, with Eng abstract) Hyde-Rowan MD, Roessmann U, Brodkey JS: Vasospasm following transsphenoidal tumor removal associated with arterial change of oral contraception. Surg Neurol 20: 120–124, 1983 Itoyama Y, Goto S, Miura M, Kuratsu J, Ushio Y, Matsumoto T: Intracranial arterial vasospasm associated with pituitary apoplexy after head trauma — case report. Neurol Med Chir (Tokyo) 30: 350–353, 1990 Lath R, Rajshekhar V: Massive cerebral infarction as a feature of pituitary apoplexy. Neurol India 49: 191–193, 2001 Mawk JR, Ausman JI, Erickson DL, Maxwell RE: Vasospasm following transcranial removal of large pituitary adenomas. Report of three cases. J Neurosurg 50: 229–232, 1979 Nishioka H, Ito H, Haraoka J: Cerebral vasospasm following transsphenoidal removal of pituitary Neurol Med Chir (Tokyo) 44, September, 2004 483 adenoma. Br J Neurosurg 15: 44–47, 2001 Pozzati E, Frank G, Nasi MT, Giuliani G: Pituitary apoplexy, bilateral carotid vasospasm, and cerebral infarction in a 15-year-old boy. Neurosurgery 20: 56–59, 1987 12) Rosenbaum TJ, Houser OW, Laws ER: Pituitary apoplexy producing internal carotid artery occlusion. J Neurosurg 47: 599–604, 1977 13) Rovit RL, Fein JM: Pituitary apoplexy: a review and reappraisal. J Neurosurg 37: 280–288, 1972 14) Shida N, Nakasato N, Mizoi K, Kanai M, Yoshimoto T: Symptomatic vessel narrowing caused by spontaneous rupture of craniopharyngioma cyst — case report. Neurol Med Chir (Tokyo) 38: 666–668, 1998 11) Address reprint requests to: H. Akutsu, M.D., Department of Neurosurgery, Tsukuba Medical Center, 1–3–1 Amakubo, Tsukuba, Ibaraki 305–8558, Japan. e-mail: akutsuh@zf6.so-net.ne.jp