592 Nagahiro et al. Multiple Cerebral Arterial Occlusions in a Young Patient with Sjogren's Syndrome: Case Report fixation method, was 1:45 (normal Rf titer, <25). Antinuclear antibody, de. Shinji Nagahiro, M.D., Akio Mantani, M.D., Kazumichi Yamada, M.D., Yukitaka Ushio, M.D. Department of Neurosurgery, Kumamoto University Medical School, Kumamoto, Japan W E DESCRIBE A case of a young patient with multiple occlusions of major cerebral arteries and Sjogren's syndrome. This 17-year-old female patient experienced repeated transient ischemic attacks of right hemiparesis, speech disturbance, and unconsciousness. Angiography revealed progressive occlu­ sion of the bilateral carotid and vertebral arteries. Examinations, including a serological test, a rose bengal test, Ga scintigraphy, and a biopsy of the parotid gland, indicated Sjogren's syndrome. The patient was successfully managed with bypass surgery. Patients with Sjogren's syndrome may expe­ rience progressive occlusion of the major cerebral arteries resembling that of moyamoya disease. (Neurosurgery 38:592-595, 1996) Key words: Cerebral arterial occlusion, Moyamoya disease, Multiple infarction, Sjogren's syn­ drome, Vasculitis ecurrent ischemic attacks caused by progressive multiple occlusion of the main intracranial arteries in children or young patients may occur in moy­ amoya disease or in association with diseases such as neurofibromatosis (7), sickle cell anemia (11), Down's syn­ drome (10), inflammation, and collagen disease (13). Moyamoya disease pro­ duces spontaneous occlusion of the in­ tracranial terminal portions of the bilat­ eral internal carotid arteries associated with the collateral vascular network in the base of the brain or the transdural collateral supplies (12, 13). The patho­ genesis of moyamoya disease is un­ known. Suzuki and Takaku (12) suspect an autoimmune mechanism. However, there have been few case reports in which moyamoya disease was associ­ ated with autoimmune disease (6). We describe a patient with subclinical Sjogren's syndrome who experienced cerebral ischemic attacks and a brain stem stroke caused by progressive oc­ clusion of the bilateral internal carotid R and vertebral arteries. We also discuss the cerebral arterial occlusions seen in this patient in relation to moyamoya disease and Sjogren's syndrome. CASE REPORT This 17-year-old female patient had an 8-year history of occasional transient attacks of unconsciousness that espe­ cially occurred when she hyperventi­ lated while playing a melodica or exer­ cising. Recently, she developed several transient ischemic attacks with speech disturbance and right hemiparesis and fell into a depressive state 3 months be­ fore admission. At admission, she had a low-grade fever and was depressed; she rarely laughed or spoke. Neurological exam i­ nation revealed slurred speech and mild weakness of the right hand. Serological examinations were posi­ tive for rheumatoid factor (RF), antinuclear antibody, and anti-Ro/SS-A anti­ body. The RF titer, assayed bv the latex Neurosurgery, Vol. 38, No. 3, March 1996 tected by the immunofluorescent tech­ nique was 1:160 (normal antinudear an­ tibody, <20). Anti-Ro/SS-A antibodv determined by the Ouchterlony doubh diffusion technique, was 1:4 (normal anti-Ro/SS-A antibody, undetectable). Decreased lacrimation was suspected, because the results of the rose bengal and fluorescent tests were positive; the results of the Schirmer test were nega­ tive. Decreased salivary secretion was detected by a gum test; only 3.6 ml of saliva was obtained (normal salivary se­ cretion, > 1 0 ml). Whole-body Ga scin­ tigraphy showed high uptake in both the parotid and submandibular glands, A biopsy of the parotid gland demon­ strated almost complete loss of the gland structure with fatty degeneration and mild infiltration of inflammatory cells. These data indicated a diagnosis of Sjogren's syndrome, although the pa­ tient had exhibited no clinical manifes­ tation of the svndrome, such as drveve, ^ J J dry mouth, or connective tissue disease. Magnetic resonance imaging revealed multiple lacunal infarctions in both the basal ganglia and the paraventricular regions (Fig. 1). Carotid angiograms demonstrated occlusion of the bilateral internal carotid arteries at the C3 level just distal to the ophthalmic artery, pro­ viding collaterals to form a fine vascular network in the base of the brain (Fig.-)■ Meningeal arteries arising from the oph­ thalmic arteries or external carotid arter­ ies also contributed to the trans­ dural an asto m o sis over the convexityCerebral blood flow images, studied by single photon emission computed tom og rap h y (SPECT) using QwTchexam ethylpropyleneam ine oxime, re­ vealed a low perfusion area in the left frontoparietal region. Because the patient twice d e v e lo p e d transient ischemic attacks with right hemiparesis after admission and a SPECT study revealed h y p o p e r f u s i o n ot the left hemisphere, a parietal b r a n c h d the superficial temporal artery was anastomosed to a cortical brand11 the middle cerebral artery (MCA) “fid*1 Arterial Occlusion with Sjogren's Syndrome 593 4 FIGURE 3. Left extern al (A) and inter­ nal (B) ca ro tid angiography in the lat­ 1I eral p ro jectio n 3 m onths after surgery 1 FIGURE 1. The T 2-w eigh ted m a g n e tic e resonance images (repetition tim e, 2300 ms; echo time, 9 0 ms) reveal muls tiple areas of increased signal intensity 5 in both basal ganglia ( A , arrows) and 1 the paraventricular white m a tte r ( B , A d e m o n s tr a te s the p a te n cy of the STA (A, arrow) to MCA an astom osis with filling of the tem p o ral and parietal b r a n c h e s (arrowheads). The internal c a r o tid a rte ry w as o c c lu d e d at the C 3 portion (B, arrow). ^ arrow). a frontal branch of the STA was placed on "ty the frontal cortical surface (encephaloarteriosynangiosis) on the left side. An•ub giography performed 3 months after anc surgery demonstrated patent bypass lol grafts that provided blood flow to the leg MCA branches in the frontal and pariifla etal cortices (Fig. 3). The left vertebral die artery was occluded at the foramen jgf magnum, and its meningeal branches cal formed collaterals to the basilar and fiai posterior inferior cerebellar arteries (Fig. J 4A). The right vertebral artery was jng patent. Leptomeningeal anastomosis •■ il FIGURE 2. Left (A, B) and right (C, D ) ( °mmon carotid angiography. Lateral O and frontal (B, D) views d e m o n ­ strate occlusion of the internal ca ro tid artery (arrowheads) at the C 3 portion iUsf distal to the origin of the ophthalmK artery (short arrows ), providing a bansdural anastom otic n etw o rk (long arrows) by way of its meningeal ranches. A transdural an asto m o sis |rom the d'stal portion of the right STA ( arrow) is faintly seen o v e r the ri ’bt hemisphere. was observed at the base of the brain; it originated from the bilateral posterior cerebral arteries (Fig. 4B). There were no postoperative ischemic attacks involv­ ing the left hemisphere. One year after surgery, ischemic at­ tacks recurred with left arm weakness. The patient exhibited typical psychiatric symptoms of manic-depressive disor­ der. A SPECT study revealed a decrease in the cerebral blood flow to the right hemisphere, and a second bypass oper­ ation was performed. This time, encephaloduroarteriosynangiosis (8) was performed using the frontal and parietal branches of the right STA because a transdural anastomosis from the distal portion of the STA branches was faintly observed over the right hemisphere. The postoperative course of the patient was uneventful, and she was discharged 2 weeks after surgery. However, 1 month later, she suddenly developed dysarthria and weakness of the left hand and was readmitted. T2-weighted magnetic resonance imaging performed 2 weeks after this event revealed a highintensity area in the right pons (Fig. 4C). Vertebral angiograms demonstrated abrupt occlusion of the right vertebral artery (Fig. 4D), which had been patent on the angiogram obtained 1 year ear­ lier (Fig. 4B). The intracranial blood flow was maintained with a transdural anas­ tomosis via both internal and external carotid arteries, including the STA by­ pass grafts, and via meningeal arteries originating from both extracranial ver­ tebral arteries. The collaterals from the right STA used for encephaloduroarteriosynangiosis were seen over the right N eurosurg ery, Vol. 38, No. 3, Marc h 1996 FIGURE 4 . A , lateral view of a left v e r ­ tebral an giogram show ing the abrup t term in ation of flow (long, thin arrow) in the left vertebral arte ry at the f o r a ­ m en m agn u m . The basilar a rte ry (arrowheads) and the posterior inferior ce re b e lla r arte ry (thick arrow) a r e seen by w ay of the m eningeal b ra n ch e s. B , right vertebral an giogram reveals p aten t right vertebral a rte ry , basilar arte ry , and posterior ce re b ra l arteries provid­ ing a fine vascular n etw ork in the base of the brain (arrow). A m eningeal branch (arrowheads) originating from the vertebral arte ry m akes a transdural anastom osis. C, T 2-w eigh ted m a g n e tic re s o n a n c e image obtained 2 weeks after the se co n d o p eratio n d e m o n ­ strates pontine infarction on the right side (arrow). D, right vertebral a n g io ­ gram obtained 3 m onths after the s e c ­ ond o p eratio n reveals abrup t t e r m in a ­ tion of flow in the right vertebral arte ry at the foram en m agn u m (arrow) just distal to the meningeal b ran ch (arrow­ heads) providing collaterals to the c e r e ­ bellum. hemisphere, although these were less developed than the collaterals from the left STA-MCA bypass graft. The dysar­ thria and the clumsy hand syndrome gradually improved, and the patient was discharged in good condition ex­ cept for mild dysarthria. In the past 4 years, the patient has had no more isch­ emic attacks and her manic-depressive disorder is well controlled by medica­ tion. Follow-up serological examina- 594 Nagahiro et al. tions were positive for the RF, the antinuclear antibody, and the anti Ro/SS-A antibody. DISCUSSION Progressive cerebral artery occlusion including the bilateral internal carotid and vertebral arteries was noted in this young woman with subclinical Sjogren's syn­ drome. Sjogren's syndrome is an autoim­ mune connective tissue disorder primar­ ily characterized by xerophthalmia and xerostomia in association with chronic in­ flammation of the lacrimal and salivary glands. Diagnosis of Sjogren's syndrome has been made with the use of the follow­ ing criteria: 1) objective evidence of di­ minished lacrimation (rose bengal or flu­ orescent test); 2) objective evidence of diminished salivation (gum test); 3) posi­ tive minor salivary gland biopsy; and 4) evidence of a systemic autoimmune pro­ cess, as manifested by the presence of au­ toantibodies, such as RF or antinuclear antibody (3). The patient described was regarded to have subclinical Sjogren's syndrome, because she met all four crite­ ria and she exhibited no clinical manifes­ tation of Sjogren's syndrome. Angiographic findings resembled those seen in moyamoya disease; how­ ever, they were different from those of typical moyamoya disease in which oc­ clusion is usually seen at the terminal internal carotid arteries (at the C l level). The moyamoya vessels originating from the internal carotid arteries form fine vascular networks in the basal ganglia (basal moyamoya), and involvement of the vertebral arteries is rare (5, 12, 13). However, occlusion of the internal ca­ rotid artery can progress to a more prox­ imal portion in the late stage of moy­ amoya disease, and the moyamoya vessels in the basal ganglia may disap­ pear (12). Therefore, we cannot exclude the possibility that our patient was in the late stage of moyamoya disease co­ incidentally accompanied by subclinical Sjogren's syndrome. The occurrence of central nervous system disorders in association with Sjogren's syndrome is considered to be rare (2). Alexander et al. (2) reported the association of major central nervous sys­ tem disorders in eight patients with pri­ mary Sjogren's syndrome. Of the eight patients, five presented with hemiparesis or aphasia, which were regarded as ischemic symptoms and three of five showed abnormalities on computed to­ mographic scans. Angiographic study in one patient revealed an isolated pro­ gressive stenotic lesion at the distal right internal carotid artery. Giordano et al. (4) reported a patient with Sjogren's cerebritis complicated by subarachnoid hemorrhage and bilateral superior cere­ bellar artery occlusion. These reports suggest that cerebral vasculitis resem­ bling moyamoya disease can occur in patients with Sjogren's syndrome. Alex­ ander et al. (1, 2) suggested a possible relationship between positive anti-Ro/ SS-A antibody and vasculitis. Provost et al. (9) also reported a patient with pos­ itive anti-Ro/SS-A and anti-La/SS-B antibodies and cerebral vasculopathy associated with collateralization resem­ bling the moyamoya phenomenon, al­ though there was no other laboratory and clinical evidence of Sjogren's syn­ drome or systemic lupus erythemato­ sus. This is interesting, inasmuch as Su ­ zuki and Takaku (12) have suggested that the cause of moyamoya disease is related to an autoimmune mechanism because tonsillitis and infections around the neck were frequently present in the history of patients with moyamoya dis­ ease and because the disease resembled Takayasu's arteritis or Kawasaki dis­ ease. In our patient, the progressive multiple occlusions of the major intra­ cranial arteries may have resulted from vasculitis caused by the autoimmune mechanism involved in Sjogren's syn­ drome. The effective treatment of occlusive cerebrovascular disorders associated with Sjogren's syndrome is not estab­ lished, because the association of both disorders is considered to be rare and the details of treatment results were lacking in most of these reports (1, 2, 4, 9). Corticosteroids might be effective (2), although no corticosteroids were used in our patient because she exhibited no clinical manifestation of Sjogren's syn­ drome. We regarded central nervous system involvement in our patient as a moyamoya-like disorder, because an­ giographic findings in our patient re­ sembled those seen in patients with moyamoya disease. Because surgical Neurosurgery, Vol. 38 , No. 3, March 1998 therapy to augment the collateral circu lation is considered to be promising as treatment to prevent the recurrence ot ischemia in moyamoya disease (13), W e performed direct and indirect bypass operations using superficial temper; arteries on both sides in our patient. Th, second operation, an encephaloduroarteriosynangiosis procedure on the right hemisphere, was delayed until the pa­ tient became symptomatic and SPECT demonstrated a decrease in the cerebral blood flow to the right hemisphere, be­ cause the clinical course of such a pa­ tient with a rare association of multi­ ple cerebral arterial occlusions and Sjogren's syndrome was unknown. Ex­ cept for a brain stem stroke that oc­ curred shortly after the second opera­ tion, our patient has had no further ischemic attacks in the 3 years since her bilateral bypass operation. Her manicdepressive disorder is effectively con­ trolled by medication. Bypass surgery might be an effective treatment to pre vent the recurrence of ischemia in pa­ tients with multipole occlusion of major cerebral arteries and Sjogren's syn­ drome. ACKNOW LEDGM ENTS We thank Dr. E. Uyama, D e p a rtm e n t of Medicine, Kumamoto University Medical School, for contribution to ex­ aminations of the patient and helpful suggestions. R e c e i v e d , Ju n e 1 2 , 1 9 9 5 . A c c e p t e d , Sep te m b e r 2 5 , 1 9 9 5 . R e p r i n t r e q u e s t s : Shinji Nagahiro, MD, partm ent of N eurosurgery, Kumamoto U 1 versity M edical School, 1 - 1 - 1 H o n jo , Kum­ am o to 860, Japan. REFERENCES 1. Alexander EL, Craft C, Dorsch C, Moster K Provost TT, Alexander GE: Necrotizing arte* and spinal subarachnoid hemorrhage in ‘'>1L syndrome. Ann Neurol 1 1 :632- 635, 1^~ 2. Alexander GE, Provost TT, Stevens MB. ^ ander EL: Sjogren syndrome: Central neIT , -51 i'W l-13'* system manifestations. Neurology k 1 9 8 1 ‘ 3. Fox RL Robinson CA, Curd JG, Kozin F, Hi’ FV: Sjogren's syndrome proposed criteria t°r*• situation Arthritis Rheum 29:577 - 585, 1 ^ Arterial Occlusion with Sjogren's Syndrome 4. Giordano MJ, Commins D, Silbergeld DL: Sjogren's cerebritis complicated by subarach­ noid hemorrhage and bilateral superior cerebel­ lar artery occlusion: Case report. Surg Neurol 43:48-51, 1995. 5. Handa J, Handa H: Progressive cerebral arterial occlusive disease: Analysis of 27 cases. Neuro­ radiology 3:119-133, 1972. 6. Hattori T, Niikawa S, Ohkuma A, Takenaka K, Deguchi K: Moyamoya disease associated with progressive systemic sclerosis: A case report, jpn J Stroke 12:436-442, 1990. 7. Lamas E, Lobato RD, Cabello A, Abad JM: Mul­ tiple intracranial arterial occlusions (moyamoya disease) in patients with neurofibromatosis. Acta Neurochir (Wien) 45:133-145, 1978. 8. Matsushima Y, Fukai N, Tanaka K, Tsuruoka S, Inaba Y, Aoyagi M, Ohno K: A new surgical treatment of moyamoya disease in children: A preliminary report. Surg Neurol 15:313-320, 1980. 9. Provost TT, Moses H, Morris EL, Altman J, Harley JB, Alexander E, Reichlin M: Cerebral vasculopathy associated with collateralization resembling moyamoya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies. Ar­ thritis Rheum 34:1052-1055, 1991. 10. Schrager GO, Cohen SJ, Vigman MP: Acute hemiplegia and cortical blindness due to moya­ moya disease: Report of a case in a child with Down's syndrome. Pediatrics 60:33-37, 1977. 11. Seeler RA, Royal JE, Powe L, Goldbarg HR: Moy­ amoya in children with sickle cell anemia and cerebrovascular occlusion. J Pediatr 93:808-810, 1978. 12. Suzuki J, Takaku A: Cerebrovascular 'moy­ amoya' disease. Arch Neurol 20:288-299, 1969. 13. Yonekawa Y, Goto Y, Ogata N: Moyamoya dis­ ease: Diagnosis, treatment, and recent achieve­ ment, in Barnett HJM, Mohr JP, Stein BM, Yatsu FM (eds): Stroke: Pathophysiology, Diagnosis, and Management. New York, Churchill Livingstone, 1992, ed 2, pp 721-747. M jl- i COMMENTS These authors present an interesting case of a patient with multiple cerebral artery occlusion and Sjogren's syn­ drome. This patient ultimately required bilateral revascularization, one side with superficial temporal artery-middle cerebral artery (STA-MCA) bypass and the other with an encephaloduroarteriosynangiosis (EDAS) procedure. The out­ come seems to have been satisfactory. Although I have no experience with arterial occlusion in Sjogren's syndrome patients, my group has been called upon to treat a fair number of patients with moyamoya disease because the number of neurosurgeons in our area who are comfortable with revascularization pro­ cedures has decreased. I have some mis­ givings about the future of revascular­ ization, because our residents do not have nearly the amount of experience with and the exposure to these proce­ dures that previous residents had. I do not doubt that revascularization by ei­ ther STA-MCA or EDAS procedures is appropriate for patients with moy­ amoya disease and abnormalities such as that reported here, and I worry that a useful skill is being lost to the general neurosurgical community. Regarding this case, if faced with a patient with moyamoya disease and a unilateral symptomatic lesion but bilat­ eral angiographic findings, I most likely would have proposed revascularization of the contralateral asymptomatic side on a prophylactic basis some 2 to 3 months after treatment of the symptom­ atic side. These authors elected to wait because of the unusual nature of the case and, as has ultimately been demon­ strated, revascularization of the con­ tralateral side was required. It is unclear to me which is the procedure of choice in adult patients. Certainly, the EDAS is a simpler and quicker operation, but the morbidity of a STA-MCA bypass should also be quite low. In our most recent case of a Vietnamese national with bilat­ Neurosurgery, Vol. 38, No. 3, March 1996 595 eral moyamoya disease, the sym ptom ­ atic side was revascularized first with an EDAS procedure and the patient re­ turned 3 weeks later with a stroke on the contralateral side, which had previ­ ously been asymptomatic. After waiting a month for the patient to recover, we then performed a STA-MCA bypass in the hemisphere that had experienced the most recent stroke. The message here is that cerebral revas­ cularization of some kind clearly remains an appropriate treatment for patients with moyamoya disease or (as reported here) moyamoya-like disease states. We need to make an effort to continue training neu­ rosurgeons in these procedures, probably in certain specialized cerebrovascular cen­ ters where sufficient clinical material will still be available. For neurosurgeons un­ comfortable with STA-MCA bypass now, substitution of an EDAS procedure may allow them an acceptable alternative in the treatment of these patients. Christopher M. Loftus Iowa City, Iowa Nagahiro et al. report the association of bilateral internal carotid arteries with Sjogren's syndrome in a 17-year-old fe­ male patient. Although the single asso­ ciation of these rare diseases may not indicate a pattern, the discussion by the authors regarding the autoimmune hy­ pothesis for multiple cerebral artery oc­ clusions is of some interest. The role of revascularization procedures in patients with progressive arterial occlusions of this sort is unproven. Ralph G. Dacey, Jr. St. Louis, Missouri