Case Report Moyamoya Disease Presenting as Thalamic Hemorrhage €gren’s Syndrome in A Patient With Neuromyelitis Optica and Sjo Yasumasa Asai, MD,* Hiroyuki Nakayasu, MD,* Emi Fusayasu, MD,* and Kenji Nakashima, MD† A 52-year-old woman was admitted to the hospital with right thalamic hemorrhage. A carotid angiogram revealed occlusion of the terminal portions of the bilateral internal carotid arteries with basal moyamoya vessels, which was diagnosed as moyamoya disease (MMD). At 31 years of age, she was diagnosed with multiple sclerosis because of optic neuritis and myelitis. Paraplegia appeared 14 days after admission. T2-weighted thoracic magnetic resonance imaging revealed a high intensity lesion extending from T4 to T6. Her left upper limb was partially paralytic and her lower limbs exhibited paraplegia and dysesthesia. Anti–aquaporin 4 and anti–Sj€ ogren’s syndrome-A and -B antibodies were positive. The pathogenesis of neuromyelitis optica may be associated with such immunologic factors, but there are no reports of simultaneous presentations of neuromyelitis optica and MMD. Autoimmunity may be associated with the etiology of MMD. Key Words: Aquaporin— moyamoya disease—multiple sclerosis—neuromyelitis optica—Sj€ ogren’s syndrome. Ó 2012 by National Stroke Association Moyamoya disease (MMD) is characterized by stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries and an abnormal vascular network referred to as moyamoya vessels. The pathogenesis of MMD remains uncertain; however, it has been reported that MMD may be associated with immunologic disorders such as Sj€ ogren’s syndrome (SS).1-6 Neuromyelitis optica (NMO) is characterized by optic neuritis and acute myelitis of unknown etiology. NMO has distinct features, such as a marked female preponderance, later age of onset, higher cell count in the cerebrospinal fluid, and lesions extending over several vertebral segments.7,8 NMO immunoglobulin G (IgG) can be detected in the serum of NMO patients. NMO IgG binds to aquaporin 4, which is the main channel that regulates water homoeostasis in the central nervous system.9 In NMO patients, antibodies, such as anti–SS-A and -B antibodies, and anti–double stranded DNA (dsDNA) antibodies, are frequently positive.7 We report the presence of MMD in a patient with NMO and SS, suggesting that autoimmunity may be associated with the etiology of MMD. Case Report From the *Department of Neurology at Tottori Prefectural Central Hospital; and †Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Tottori, Japan. Received December 7, 2010; revision received January 5, 2011; accepted January 8, 2011. Address correspondence to Yasumasa Asai, MD, Department of Neurology, Tottori Prefectural Central Hospital, 730 Ezu, Tottori 680-0901, Japan. E-mail: yasuyasu_005@mail.goo.ne.jp. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.01.003 Twenty-one years before admission, the patient, a 52year-old Japanese woman, developed right-sided blindness. In the ensuing year, the patient also became partially blind in her left eye and she was diagnosed with multiple sclerosis. At 18 and 15 years before admission, paraplegia, sensory disturbance bilaterally in the lower limbs, and urinary retention developed but gradually improved. Five years before admission, the patient developed left upper arm weakness. She never received interferon or Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 7 (October), 2012: pp 619.e7-619.e9 619.e7 619.e8 oral steroid therapy for prevention, magnetic resonance imaging (MRI) scans of her brain had not shown flow voids through the basal ganglia from the moyamoyaassociated collateral vessels, and magnetic resonance angiography (MRA) had not been performed. She was admitted to our hospital complaining of rightsided headache and left hemiparesis and hypesthesia. Her blood pressure was 137/81 mm Hg. There was no history of hypertension. A computed tomographic scan of her brain revealed a hemorrhage in the right thalamus (Fig 1). A MRI scan of her brain showed high signal intensity in the cerebral white matter on fluid attenuated imaging and no flow voids through the basal ganglia. A MRA scan of her brain revealed bilateral distal occlusion of the internal carotid arteries. A carotid angiogram revealed occlusion of the anterior and middle cerebral arteries bilaterally (Fig 1). Moyamoya vessels were shown in a bilateral carotid angiogram. She was diagnosed with MMD. Fourteen days later, she complained of hypesthesia of the lower (below T6) trunk and limbs, paraplegia, and urinary incontinence. On neurologic examination, the patient’s left upper limb was partially paralyzed and she had lower limb paraplegia. Superficial and deep sensations were almost completely absent below T6. Deep tendon reflexes were increased in all limbs and there was a positive Babinski sign. On immunologic examination, the patient tested positive for antinuclear antibody (1:80, speckled type), anti–SS-A, anti–SS-B, and anti–aquaporin 4 antibodies. Anti-dsDNA, -MPO-ANCA, -PR3-ANCA, -U1-RNP, and cardiolipin antibodies were all negative. Her white blood cell count was 10,940/mL and C-reactive protein was negative. Her erythrocyte sedimentation rate was 63. A cerebrospinal fluid examination showed 5 cells/mm3 (polymorphonuclear:mononuclear, 0:5), a protein level of 69 mg/dL, an IgG index of 0.79, and myelin basic protein .2000 pg/mL (control, ,102). Studies for oligoclonal bands were negative. The Shirmer test was 5 mm/2 mm, and a lip biopsy specimen revealed inflammation of the minor salivary glands. Based on these results, she was diagnosed with SS. In addition, a T2-weighted sagittal spinal magnetic resonance image in the absence of gadolinium enhancement showed a high signal intensity extending from T4 to T6 level (Fig 1). The patient was diagnosed with NMO, and steroid pulse therapy (methylprednisolone 1000 mg 3 3 days) was initiated. The patient’s sensory disturbance improved mildly, but she could not move her lower limbs. On day 120, she was transferred to another hospital for rehabilitation. Discussion Because of the presence of anti–aquaporin 4 antibody associated with the disease, NMO is considered an immunologic disease. The pathogenesis of NMO is often associated with such immunologic factors as the presence of anti–SS-A, -B, and ds-DNA antibodies.7 Pittock et al10 Y. ASAI ET AL. Figure 1. A computed tomographic scan of the brain reveals a hemorrhage in the right thalamus (A). Cerebral angiograms reveal occlusions of the bilateral distal portions of the internal carotid arteries and the bilateral anterior and middle cerebral arteries. (B) Left carotid artery angiogram in frontal projection. (C) Right carotid artery angiogram in frontal projection. (D) Left carotid artery angiogram in lateral projection. (E) Right carotid artery angiogram in lateral projection. Moyamoya vessels (arrows) are seen in both carotid artery angiograms. No stenosis is seen in either the left vertebral artery or the basilar artery in the left vertebral arteriogram in frontal projection (F) or in the lateral projection (G). T2-weighted sagittal spinal magnetic resonance imaging shows a high signal intensity (arrows) extending from T4 to T6 level (H). T2-weighted axial image of the T6 level shows centrally located high signal intensities (arrows) within the spinal cord (I). analyzed a set of patients with NMO and showed that NMO IgG was present in 66.7% of patients, antinuclear antibodies in 43.8%, and anti–SS-A antibodies in 15.7%. MOYAMOYA DISEASE, NEUROMYELITIS OPTICA, AND SS Moreover, there is a higher frequency of autoantibodies in NMO patients who are NMO IgG seropositive than in those who are NMO IgG seronegative, which may reflect a more intense autoimmune response in the former group.10 In a previous report, an anti–SS-A and -B antibody-positive patient presented with a cerebral vasculopathy resembling MMD.1 A patient with multiple occlusions of the major cerebral arteries and SS has also been described.2 In other reports, patients with systemic lupus erythematosus, Behçet disease, and myeloperoxidaseantineutrophil cytoplasmic antibody positivity have demonstrated MMD.3-6 These reports imply that MMD is sometimes associated with vasculitis from collagen disease or infection. There is no previous report, however, of anti–aquaporin 4 antibody being associated with MMD. Anti–aquaporin 4 antibody, which is one of the water channels, usually induces myelitis. In this case, anti–SS-A and -B antibody rather than anti– aquaporin 4 antibody might induce vasculitis. To our knowledge, there have been no previous reports of simultaneous presentation of NMO and MMD. It is possible that the coexistence of NMO and MMD is associated with the presence of immunologic antibodies, such as the anti–SS-A antibody. SS complicated with NMO might be associated with MMD. Similar cases will need to be examined to clarify if MMD is related to an autoimmune response such as vasculitis. Acknowledgment: We thank Dr. Toshiyuki Takahashi in the Department of Neurology at Tohoku University for measuring anti–aquaporin 4 antibody. 619.e9 References 1. Provist T, Moses H, Morris E, et al. Cerebral vasculopathy associated with collateralization resembling Moyamoya phenomenon and with anti–Ro/SS-A and anti-L1/SS-B antibodies. Arthritis Rheum 1991;34: 1052-1055. 2. Nagahiro S, Mantani A, Yamada K, et al. Multiple cerebral arterial occlusions in a young patient with Sj€ ogren’s syndrome: Case report. Neurosurgery 1996; 38:592-595. 3. Ramahi KM, Rayes HM. Systemic lupus erythematosus associated with moyamoya syndrome. Lupus 2000; 9:632-636. 4. Matsuki Y, Kawakami M, Ishizuka T, et al. SLE and Sj€ ogren’s syndrome associated with unilateral moyamoya vessels in cerebral arteries. Scand J Rheumatol 1997;26:392-396. 5. Joo SP, Kim TS, Lee JH, et al. Moyamoya disease associated with Behçet’s disease. J Clin Neurosci 2006; 13:364-367. 6. Yanagawa Y, Sugiura T, Suzuki K, et al. Moyamoya disease associated with positive findings for rheumatoid factor and myeloperoxidase-anti-neutrophil cytoplasmic antibody. West Indian Med J 2007;56:282-284. 7. Wingerchuk DM, Hogancamp WF, O’Brien PC, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999;53:1107-1114. 8. Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485-1489. 9. Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG maker of optic-spinal multiple sclerosis binds to the aquaporin 4 water channel. J Exp Med 2005;202:473-477. 10. Pittock S, Lennon V, Seze J, et al. Neuromyelitis optica and non–organ-specific autoimmunity. Arch Neurol 2008;65:78-83.