Acta Neurochir (Wien) (1994) 131:157 159 :~___Actn . . Ndurochlrurglca 9 Springer-Verlag 1994 Printed in Austria Raymond's Syndrome Following Petrosal Sinus Sampling H. Seyer 1, J. Honegger 1, W. Schott 1, M. Kiichle 2, W. J. Huk 3, R. Fahlbusch 1, and H. Frisch 4 t Department ofNeurosurgery, 2 Department of Ophthalmology, 3Department of Neuroradiology, University of Erlangen-Niirnberg,Erlangen, Federal Republic of Germany, and 4 Department of Pediatrics, University of Vienna, Vienna, Austria Summary Inferior petrosal sinus sampling (IPSS) is used to evaluate the pituitary-dependency of Cushing's disease, and to predict the laterality of a microadenoma prior to transsphenoidal operation. A serious complication occured in a 14-year-old boy: he suffered brain stem ischaemia with abducens nerve palsy and hemiparesis (Raymond's syndrome). The case prompted us to reconsider the indication for this investigation. Keywords." Pituitary adenoma; Cushing's disease, inferior petrosal sinus sampling (IPSS); Raymond's syndrome. Introduction I n r e c e n t years, i n f e r i o r p e t r o s a l sinus s a m p l i n g (IPSS) has b e c o m e a m a i n s t a y i n the p r e o p e r a t i v e evalu a t i o n o f C u s h i n g ' s disease. I P S S is v a l u a b l e to a s s u r e the p i t u i t a r y - d e p e n d e n c y o f the disease, a n d m a y give a h i n t for the l a t e r a l i t y o f the m i c r o a d e n o m a 1' 3, 5, 7, H, b u t this is also still u n d e r d e b a t e 4. T h e p r o c e d u r e is g e n e r a l l y c o n s i d e r e d to i m p l y m i n i m a l m o r b i d i t y 6. H o w e v e r , in o u r series o f 79 I P S S (6 c h i l d r e n a n d 73 a d u l t s , 1987-1993), we e n c o u n t e r e d o n e serious c o m plication: an abducens nerve palsy and contralateral h e m i p a r e s i s d e v e l o p e d i m m e d i a t e l y after the p r o c e dure. This, as far as we k n o w , has n o t p r e v i o u s l y b e e n r e p o r t e d . W e p r e s e n t the case r e p o r t o f the afflicted p a t i e n t a n d discuss the p o s s i b l e m e c h a n i s m s . endocrinological re-assessment revealed unchanged activity of Cushing's disease. In January 1992, the patient was admitted to our department. At that time, MRI showed a suspicious but uncertain area on the left side of the sella turcica. Petrosal sinus sampling was considered appropriate to provide safer information about the side of the ACTH-source. Bilateral sampling of venous blood was performed simultaneously from the inferior petrosal sinuses. The left one was narrow, while the right one was wide, but both were easily catheterized. The tips of the catheters were flushed with heparine solution (5,000 IU/L) between the blood collections. The sampling including CRH stimulation lasted for about 30 minutes. Both catheters were withdrawn immediately thereafter. Sampling results revealed markedly higher ACTH values on the left side, suggesting a left-sided adenoma. Immediately after the procedure, the boy experienced double vision. A complete sixth nerve palsy of the left eye developed within the following hour (Fig. 1), together with a contralateral hemiparesis. For about two days, the patient had also the feeling of hyperacusis on the left side, and a discrete asymmetry of the corners of his mouth was suspected during that time. CT revealed no haemorrhage, thus Case Report A 14-year-old boy presented in January 1991 with obesity, moonface, striae, and hirsuties. Endocrinologic assessment revealed Cushing's disease. A hypo-intense area of 3 mm was detected on the right side of the pituitary gland by magnetic resonance imaging. The patient was operated on in another neurosurgical department by a transsphenoidal approach, and a right-sided microadenoma was removed, which was confirmed by histological examination. Postoperative clinical course, however, showed further weight gain, and Fig. 1. Left abducens nerve palsy, documented the day after brain stem ischaemia. Extraocular eye movements in nine fields of gaze. In the middle, primary position. Upper line shows upward gaze, lower line shows downward gaze. Conjugate eye palsy is not evident 158 H. Seyer et al.: Raymond's Syndrome Following Petrosal Sinus Sampling Fig. 3. Coronal view of the T l-weighted MRI shows a well demarcated lesion close to the midline of the brain stem (arrow), at the level of the fourth ventricle and the cerebellar peduncles, but evidently not involving the abducens nucleus Fig. 2. T 1-weighted MRI showing zone of infarction in the brain stem (sagittal view), in between the lower rear part of the pons and the medulla oblongata (arrow), supposed to involve the intrapontine abducens fascicle anticoagulation with heparine could be commenced. While hemiparesis improved partly during the following months, abducens paralysis persisted. Therefore, transsphenoidal re-explorationwas postponed. T 1-weighted MRI showed a left-sided hypo-intense area in the brain stem at the level of the lower pons, which subsequently developed into a well demarcated infarction zone (Fig. 2). Four months after the event, a left-sided adenoma was removed, and replacement therapy with hydrocortisone was required for postoperative hypocortisolism. Pituitary function was otherwise normal. One year after the operation, hemiparesis has partly regressed, but the abducens nerve palsy shows no improvement. Therefore, extraocular muscle surgery is planned. Discussion F r o m the clinical p o i n t o f view, a b d u c e n s nerve palsy a n d c o n t r a l a t e r a l hemiparesis c o r r e s p o n d e d to the s y n d r o m e described by R a y m o n d a n d Cestan in 19039 . D o u b l e vision a n d isolated progressive a b d u c e n s nerve p a l s y c o u l d have been caused by t h r o m b o s i s o f the inferior p e t r o s a l sinus which is a d j a c e n t to the nerve a n d m i g h t have effected it by p e r i p h e r a l c o m p r e s s i o n . T h r o m b o s i s o f the c a v e r n o u s sinus was also imaginable. But as no a d d i t i o n a l o c u l o r - m o t o r or trigeminal nerve palsy occured, b o t h m e c h a n i s m s were less likely. H e m i p a r e s i s s u p p o s e d a b r a i n stem lesion near the c o r t i c o s p i n a l tract. As hemiparesis p r o v e d to be regressive, the c o r t i c o s p i n a l tract c o u l d n o t have been Fig. 4. Axial view of T 2-weighted MRI shows an area of ischaemic lesion in the more ventral medulla oblongata, involving the corticospinal tract (arrow) c o m p l e t e l y involved by infarction. The lesion also did n o t directly i m p a i r the a b d u c e n s nucleus, because ipsilateral c o n j u g a t e gaze p a l s y was n o t evident. The ipsilateral facial nerve m i g h t have been involved intermittently, p o s s i b l y by o e d e m a , as m a y be indicated by brief hyperacusis (stapedius muscle weakness). Thus, the lesion was s u p p o s e d to involve the adducens nerve fascicle, a n d p a r t l y include the corticospinal tract. T h e often a s y m m e t r i c a l inferior petrosal sinuses H. Seyer etal.: Raymond's Syndrome Following Petrosal Sinus Sampling c o m m u n i c a t e amongst others with the basilar venous plexus10, 12, which p r o b a b l y drains the blood supply 159 References Acknowledgement 1. Boolell M, McNeil P, Gilford E, Cummins J, Arnott R, Alford F (1990) An overview of bilateral synchronous inferior petrosal sinus sampling (BSIPSS) in the pre-operative assessment of Cushing's disease. Aust NZ J Med 20:765-770 2. Findling JW, Kehoe ME, Shaker JL, Raft H (1991) Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome. J Clin Endocrinol Metab 73:408-413 3. Liidecke DK (1989) Intraoperative measurement of adreno-corticotropin hormone in peripituitary blood in Cushing's disease. Neurosurgery 24:201-205 4. McCane DR, Mdrath E, McNeill A, Gordon DS, Hadden DR, Kennedy L, Sheridan B, Atkinson B (1989) Bilateral inferior petrosal sinus sampling as a routine procedure in ACTH-dependent Cushing's syndrome, Clin Endocrinol 30:157-166 5. Miiier DL, Doppman JL, Nieman LK, Cutler GB, Chrousos G, Loriaux DL, Oldfidd ED (1990) Petrosal sinus sampling: discordant lateralization of ACTH-secreting pituitary microadenomas before and after stimulation with corticotropin-releasing hormone. Radiology 176:429-431 6. Miller DL, Doppman JL (1991) Petrosal sinus sampling: technique and rationale. Radiology 178:37-47 7. Oldfield EH, Chrousos GP, Schulte HM, Schaaf M, KcKeever PE, Krudy AG, Cutler CB, Loriaux DL, Doppman JL (1985) Preoperative Iateralization of ACTH-secreting pituitary microadenomas by bilateral arid simultaneous inferior petrosal venous sinus sampling. N Engl J Med 312:100-103 8. Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB, Loriaux L (1991) Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. N Engl J Med 325:897-905 9. Raymond A, Cestan B (1903) Gaz Hopit Paris 76:829 10. Shiu PC, Hanafee WN, Wilson GH, Rand RW (1968) Cavernous sinus venography. Am J Roentgenol 104:57-62 11. Tabarin A, Greselle JF, San-Galli F, Lepart F, Caille JM, Latapie JL, Guerin J, Roger P (1991) Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease. J Clin Endocrinol Metab 73:53-59 12. Zovickian J, Oldfield EH, Doppman JL, Cutler GB, Loriaux DL (1988) Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease. J Neurosurg 68:205-210 The authors thank Prof. Dr. P. Thierauf, Department of Neuropathology, University of Erlangen-Niirnberg, for reviewing the literature about venous drainage of the brain stem. Correspondence: Hendrikus Seyer, M.D., Department of Neurosurgery, University of Erlangen-Nfirnberg, Schwabachanlage 6, D-91054 Erlangen, Federal RepubIic of Germany. f r o m the lower pons. We suppose that thrombosis o f this basilar venous plexus was the m o s t likely cause o f the syndrome. As hemiparesis was regressive, thrombosis might have been only partial, or regressive, too. The anatomical site o f the lesion could be evaluated by M R I (Figs. 2-4). Inferior petrosal sinus sampling (IPSS) in patients with Cushing's disease has become a well-established tool in the preoperative evaluation o f the presence and laterality o f A C T H - p r o d u c i n g microadenomas. Findling and Oldfield 2' 8 perform IPSS in all patients with A C T H - d e p e n d e n t Cushing's syndrome on a routine basis for accurate differential diagnosis. With respect to this serious complications o f brain stem insult, we advocate that in patients with Cushing's disease, IPSS should only be used if M R I shows no adenoma, or if the pituitary dependency o f Cushing's s y n d r o m e is unsolved. The investigation improves the chance o f a surgical cure, if no a d e n o m a is f o u n d during systematic exploration o f the pituitary, and h e m i h y p o p h y s e c t o m y on the side o f p r e d o m i n a n t A C T H - s e c r e t i o n will be required 7. It has been p r o p o s e d that prediction o f the correct side by IPSS reduces dissection o f the gland 1. In our opinion, this benefit o f IPSS is less significant. But in cases where no m i c r o a d e n o m a can be found by systematic exploration, h e m i h y p o p h y s e c t o m y on the side o f elevated ACTH-levels provides a chance for surgical cure. However, h e m i h y p o p h y s e c t o m y has been performed in only 5% o f our patients. Therefore, whether IPSS is justified at all should be discussed, unless pituitary dependency o f Cushing's s y n d r o m e is unclear from conventional endocrine evaluation.