Case Kurume Report Antiphospholipid Syndrome in a Patient with MASAHIDE KAJI, YOSHIHIRO HISAMICHI AIZAWA*, Department of Neurology, Departments of Medicine* and Little (MG), although woman with Kurume and extremity 3 University Radiology**, were demonstrated a a new on prolonged improved mg/day) for 18 lesion in the fluid attenuated findings on antibodies stroke case. in similar right parietal and lobe. 2 She laboratory We believe recommend that for small (FLAIR) then •@for A was treated with oral no multiple to left (5.9 elevation of Neurological prednisolone (30 cerebrovascular infarcts are caused recurrent gravis, lower the infarcts an new prevent myasthenia experienced and observed. and in subcortical sec), were had the infarct Thrombocytopenia 50.2 therapy of old images. U/mL) 47-year-old She and (aPTT; gravis hemiparesis. cortical 55.7 patient's stroke, patients. right an abnormalities our myasthenia phlebothrombosis Multiple glucocorticoid ischemic of demonstrated time with MG onset treated ( /32-GPIaCL; of and of Medicine, patients (CT) thromboplastin weeks. antibodies, Strokes 839-0863 School many acute recovery resolution Kurume in in an was inversion over imaging. antiphospholipid and antibodies with occurrence tomography partial significantly months, antiphospholipid Key words previously Computed I anticardiolipin defects or had activated fit-IgG-glycoprotein events detectable MG previously. 2002 Japan are years and 830-0011, antibodies 10 lobe Center, University generalized thymectomy years Medical stroke of 49, 211-216, Gravis Kurume ischemic history lschemic Myasthenia about 20-year frontal •~ 10•¬4/ƒÊL), known antiphospholipid a undergone is Journal, SATO, HARUKO KUNOH, AYA WATANABE, KOTARO OIZUMI* AND TOSHI ABE** Kurume Summary: Multiple Medical of steroid therapy, phlebothrombosis by ischemic stroke of the left lower INTRODUCTION extremity Although antiphospholipid antibodies are not uncommonin patients with myasthenia gravis (MG) [1-4] and cerebral infarction frequently complicates anti-phospholipid syndrome (APS) [5,6], little is known about the occurrence of ischemic stroke in MG patients. We report an MG patient with an elevated serum antiphospholipid antibody titer who developedmultiple ischemicstrokes.Recurrencewas preventedby glucocorticoidadministration. A 47-year-old generalized right upper CASE REPORT woman with 3 thymectomy 10 history of MG suddenly developed weakness of the limb. She had been treated with warfarin previously, years Other prior treatment years before the pyridostigmine controlling initial included stroke myasthenia discontinued. and after bromide was some weakness of arms exertion. No history lesions, uveitis, and ongoing which was and legs of arthritis, events diagnosis of to until treatment fairly MG. 3 with effective in prednisolone live was independently, occurred and moderate occurred with prolonged spontaneous cardiac was undergone after able diplopia had prednisolone even She although cerebrovascular a 20-year years abortion, disease, or skin previous present. On examination, blood pressure was 120/80 mmHg; no carotid bruits or cardiac murmurs were audible. She was alert with normal memory; aphasia, apraxia and agnosia were not observed. No diplopia Received for publication August 27, 2002 Corresponding author: Dr. Masahide Kaji, Center for rheumatic diseases, Kurume University Medical Center, 155-1 Kokubu-machi, Kurume 839-0863, Japan. Tel: +81-942-22-6111 Fax: +81-942-22-6657 E-mail:mkaji@ktarn.or.jp KAJI ET AL. Fig. 1. Initial imaging studies. A. B. Computes] tomography scan 2 days after onset of right hemiparesis showed areas of decreased attenuation consistent with infarction in the left frontal and right parietal lobes. The attenuation decrease in was marked in the left frontal lobe and only slight in the right parietal lope. C, 1). Fluid attenuated inversion recovery (FLAIR) images 4 days alter stroke onset disclosed multiple small cortical and subcortical infarcts in addition to the two larger lesions. Kurume Medical Journal Vol. 49, No. 4, 2002 MULTIPLE 2. Follow-up onset Fig. showed further Fluid attenuated new lesions. Kurume Medical Journal Vol. 49, No. 4, 2002 imaging. decrease inversion STROKES A. B. Computed in attenuation recovery AND (FLAIR) MYASTHENIA tomography in the right parietal images 18 months 213 GRAVIS 18 months alter lobe. and no new after stroke clinical stroke lesions. C. D. onset revealed no KAJI ET AL. or ptosis was evident. In addition to a nasal voice and mild generalized limbs weakness, moderate right hemiparesis without sensory impairment was present, mainly in the upper limb. A Chaddock sign was present on the right. Noncontrast computed tomography (CT) disclosed two areas (left frontal and right parietal) with decreased attenuation suggesting infarction. Decrease the attenuation was marked in the left frontal lobe but very slight in the right parietal lobe (Figs 1A and B). Four days after onset, only the lesion in the right parietal lobe was enhanced on CT with contrast. Magnetic resonance imaging (MRI) revealed left frontal and right parietal lesions, as seen on CT. Fluid attenuated inversion recovery (FLAIR) images disclosed multiple small cortical and subcortical infarcts in addition to the other two lesions (Figs 1C and D). Small lesions in the left frontal cortex were felt to be responsible for her right pure motor hemiparesis. MR angiography (MRA) showed no narrowing or occlusion. mine bromide, oral anticoagulation were administered 214 Negative laboratory white blood cell bin A1C total studies count, C-reactive factor, DNA trophil cytoplasmic syphilis, and national normalized ratio laboratory results included 10•¬4/ƒÊL), prolonged a test (aPTT; serologic tests An was Abnormal sec: 1.11. 24 to 43) I anticardiolipin 55.7 (ƒÀ2-GPIaCL; itive at antinuclear 1:160 with single-stranded was 100 receptor <2). revealed 3 cells/mm3; and C3, IgM, gram 0.1 was pos- speckled pattern, and the anti- no heart diomyopathy, septal defect. sinus antibody anti-acetylcholine A Repeated was fluid 22 0.2 61 mg/dL; of analysis glucose, IgG,1 56 mg/dL; echocardioatrial intracardiac heart nmol/L (CSF) mg/dL; two-dimensional evidence <3.5 concentration Serum C4, disease, valvular regular IgG mg/dL; showed ischemic titer protein; mg/dL. antibody (ANF) Cerebrospinal <1 ele- factor concentration (normal, an normal, (normal,<10). antibody and U/mL; DNA U/L mg/dL; a (5.9 •~ thromboplastin concentration An for inter- thrombocytopenia normal, disease, One month that to farmn was ulcer occurred. from 5.9 •~ nmol/L. 10•¬4 to trations of ƒÀ2-GPIaCL were and aPTT was 0.98. platelet was and no further by (Figs 2A-D). mainly in Mild weakness She upper longer prolonged in had remained proconcenreceptor nmol/L, normal respec- (14.5•~10•¬4/ƒÊL) (41.1 sec). of the right CT, and no new lesion CT and MRI over 18 a very limb, other gastric serum 16 was follow-up the and slight and limbs parietal right a slightly had war- increased anti-acetylcholine count on from months, U/mL U/mL and count aPTT 18 Attenuation decreased detected After the 22.3 1.66, platelet 10.8•~10•¬4/ƒÊL, month, antibody was bleeding the 24.7 to receptor since sec). 1 initiation, fell INR and mg/day) thrombosis steroid The Although (53.3 The and systemic anti-acetylcholine 42 longed tively. after discontinued antibody or of ƒÀ2-GPIaCL of decreased 1 months stroke concentration and 18 mg/day) INR lesion was months hemiparesis nasal voice. disappeared. DISCUSSION complexes. partial new (30 warfarin, antineu- immune (INR) serum for No preparation, antibody, for respectively. occurred. prednisolone (potassium time, antibody, vated ƒÀ2-IgG-glycoprotein U/mL). hemoglo- LE IgG activated 50.2 normal prothrombin rheumatoid anti-double-stranded a protein, cholesterol, antithrombin III, time included oral fibrillation, thrombi, or electrocardiograms car- ventricular showed rhythm. Four days after stroke onset, thrombolytic therapy (urokinase, 480000 units i.v./day) and anticoagulation (heparin, 10000 units i.v./day) were initiated and continued for 2 weeks, during which hemiparesis improved markedly. Then, in addition to pyridostigKurume Medical Journal An ischemic stroke complicated a long course of generalized MG in the present patient. Serum concentrations of antiphospholipid antibody were elevated; other cerebrovascular risk factors were absent. She had an old lesion in the left frontal lobe and a recent lesion in the right parietal lobe, with intact higher cortical functions. No abnormalities of cerebral arteries were evident on MRA. Multiple small cortical and subcortical lesions were demonstrated in FLAIR images. Over half of patients with APSrelated ischemic stroke reportedly have at least one recurrent ischemic stroke, with IgG anticardiolipin concentrations over 100 U/mL associated with the shortest times to a subsequent thrombo-occlusive event [5]. APS has involved atherosclerotic largevessel disease in one-third of cases, small-vessel disease in another third, and cardioembolic disease in one-fifths [6]. Stenosis and occlusion in medium-size arteries have been described angiographically [1], and platelet-fibrin thrombi filling small vessels without signs of vasculitis have been demonstrated histologically in some cases of APS. Multiple subcortical lesions on MRI regarded as infarcts also have been reported in APS [7]. The small, multiple cortical and subcortical infarctions that we demonstrated by FLAIR are consistent with findings in APS [7,8]. Cardioembolic Vol. 49, No. 4, 2002 MULTIPLE STROKES AND thrombi can occur in APS [6,8] without evidence of a cardiac abnormality, as well as atherosclerotic large vessel disease; subsequently recanalized, APS-related thrombi may have resulted in our patient's old frontal and recent parietal infarcts. Infarction with a history of phlebothrombosis, elevated anticardiolipin anti body, and thrombocytopenia fulfilled the diagnostic criteria for APS proposed by Hughes et al. Systemic lupus erythematosus (SLE) can cause occlusion of both large and small cerebral vessels, and often is complicated by APS. As the present case did not ful fill the diagnostic criteria proposed by American Rheumatic Association for SLE despite the positive serum ANF, SLE was excluded as a cause of stroke. Four reports serum [1-4]. present at patients; One low [1], body in 94) 25% In >2 SD studies of first antiphospholipid [2]. In IgG 71) [4] two and to the no first a difference report, were very SD); in the second low and 90 U/mL. the concentrations controls. Even pholipid antibodies did show with a MG spontaneous MRA-confirmed sion 12 MG incidence of the the titer patient including criteria. Like MG was relatively high, clinical of with possibly because ventional risk diabetes mellitus, or patients whose IgG were very utive patients of low titers. factors for stroke CB, antibodies in neurological with anti-single stranded Ohishi no common IgG tions [5]. and of Two MG had MG this patients and been for 6 with 3. Rombos reported. months, 5. Levine have throm 6. titers of embolism bocytopenia, U/mL and and had small spontaneous a ƒÀ2-GPIaCL of pul multiple infarcts on MRI. platelet count and asymptomatic Prednisolone aPTT throm concentration [9]. of 125 subcortical normalized A 32-year-old Kurume M, S. Anti-cardicross-reaction activity. Nagasato Clin Exp K, Ichinose K, antibodies Acta the woman Medical Journal 1990; and Med in patients Nagasaki 1994; E, Leventakou Bernard 1994; Brey in the 38:119-124. IgG and in neurological diseases. D. Studies of IgG-class in myasthenia gravis. 18:57-63. RL, Sawaya J et al. Recurrent 1995; A, N et al. Serum 81:243-245. antibodies KL, stroke antiphospholipid Salowich-Palm L, and thrombo-occlusive syndrome. Ann Neurol The Antiphospholipid Antibodies in Stroke Study (APASS) Group. Antccardiolipin antibodies are an inde pendent risk factor for first ischemic stroke. Neurology 1993; 43:2069-2073. 7. Digre KB, Durcan MW et antiphospholipid 40-year-old abortion, M, antibodies Scand events FJ, al. Branch Amaurosis antibodies. WD, Jacobson fugax associated Ann Neurol DM, with 1989; 25:228- Focal cerebral 232. 8. Fulham monary Lockhart DNA K, Triantafyllou SR, Varner manifesta a history antiphospho and platelet disorders; Evangelopoulou-Katsiri anticardiolipin consec as A with and gravis. anticardiolipin 4. Sanmarco particularly clinical A, Kokkinos posi high myasthenia Acta Neurol in highly were GK, I, Motomura Autoimmunity to such aPTT antibodies APS with In antibod stroke. K et al. Antiphospholipid with con lowest of high 68:313-319. Voumvourakis [1-4], of found with 39:41-44. APS series abnormalities prolonged anticardiolipin woman [5]. APS-related and a Scadding 1987; 2. Kinoshita hypertension, ischemia rela U/mL). anticardiolipin olipin patients was APS, ischemic No a (55.7 develop 1. Colaco concentrations in cerebral antibodies group, as fibrillation U/mL with bocytopenia such diagnostic showed prednisolone was useful in decreasing lipid antibodies, normalizing aPTT count, and preventing recurrent stroke. U found frequency anticardiolipin high •¬100 antiphospholipid tive atrial The SLE patient IgG anticar [10]. concentration may occlu IgG Serum antiphospholipid antibody concentration should be measured if a patient with generalized MG develops venous or arterial thrombosis, spontaneous abortions, or thrombocytopenia. Since our patient was not receiving oral anticoagulation, the INR after 18 months was 0.98. 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