Moyamoya, Dystonia During Hyperventilation, and Antiphospholipid Antibodies Tarif Bakdash, MD*,‡, Alan R. Cohen, MD*,†, Joanne M. Hempel, MD*,‡, Jason Hoagland, MD*,‡, and Arthur J. Newman, MD*,§ A 5-year-old Asian male presented with episodes of dystonia involving the right upper extremity during vigorous crying. He was diagnosed with moyamoya disease. Initial laboratory evaluation revealed positive anticardiolipin and antinuclear antibodies. © 2002 by Elsevier Science Inc. All rights reserved. Bakdash T, Cohen AR, Hempel JM, Hoagland J, Newman AJ. Moyamoya, dystonia during hyperventilation, and antiphospholipid antibodies. Pediatr Neurol 2002;26: 157-160. Introduction Moyamoya disease is a progressive vascular stenosis and blockage involving mostly the supraclinoid segment of the internal carotid arteries and the first part of the middle or anterior cerebral arteries and, to a lesser extent, the posterior cerebral arteries. Extensive collateral circulation appears angiographically like a “puff of smoke,” which is the Japanese term for moyamoya disease. Most of the patients are under 10 years of age. Symptoms include seizures, stroke-like events, or transient ischemic attacks during hyperventilation. Moyamoya disease may cause From the *Department of Pediatrics; Division of Pediatric Neurology; University Hospitals Health System; Rainbow Babies & Children’s Hospital; Cleveland, Ohio; †Department of Neurological Surgery; Division of Pediatrics; ‡Department of Pediatrics; and the §Department of Pediatrics; Division of Pediatric Rheumatology; University Hospitals Health System; Case Western Reserve University; Cleveland, Ohio. © 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(01)00367-8 ● 0887-8994/02/$—see front matter mental retardation and epilepsy. Neurofibromatosis type I, sickle cell disease, homocystinuria, Down syndrome, meningitis, and radiation have been noted with moyamoya syndrome. A review of the literature from 1966 to 2000 does not reveal a previously described case of childhood moyamoya disease associated with dystonia during hyperventilation. Case Report A 5-year-old Asian male born to a 28-year-old gravida 1 para 1 at 36 weeks gestation after a normal pregnancy. He weighed 2330 gm after a normal vaginal delivery. The patient achieved all of his milestones at the appropriate times, and he was in kindergarten doing well. His immunizations were current. He had no cardiovascular, respiratory, gastrointestinal, genitourinary, or skin-related disorders. In February of 1999 the patient began having episodes while crying, during which his right hand became stiff. The fingers curled and he was unable to move them in any direction actively or passively. His right lower extremity was also stiff. These episodes would last for a few minutes, and they were noticed initially by his grandmother and then his parents. During these events the patient had no alteration of consciousness and no activities to indicate seizures, such as tonic-clonic, myoclonic, or atonic-related events. In between these episodes the patient seemed normal. He was evaluated in the pediatric neurology clinic at Rainbow Babies and Children’s Hospital. Physical examination disclosed three small café-au-lait spots. Family history was unremarkable for any neuromuscular-related disorders and no history of stroke, congenital heart disease, juvenile diabetes, short stature, deafness, or movement disorders. The patient was hospitalized to evaluate the possibility of decreased blood supply to the left hemisphere during hyperventilation that would explain the above-mentioned dystonia while crying. Cranial magnetic resonance imaging and magnetic resonance angiography of the head and neck were obtained. Magnetic resonance imaging revealed a deep left centrum semiovale infarct and magnetic resonance angiography revealed severe stenosis of the intracranial carotid arteries bilaterally (Fig 1). A cerebral angiogram confirmed the diagnosis of moyamoya disease (Figs 2 and 3). The electroencephalographic result without hyperventilation was normal. Laboratory evaluation revealed findings suggestive of connective tissue disease and the presence of antiphospholipid antibodies (Tables 1 and 2). The patient underwent bilateral cerebral revascularization procedures under general anesthetic. The right side was performed first. A frontotemporoparietal craniotomy was performed to permit a pial synangiosis. In effect, this is a nonanastomotic bypass in which a branch of the superficial temporal artery is swung in continuity onto the surface of the brain. Additionally, an occipital burr hole was placed and the dura opened to encourage extracranial to intracranial revascularization. The identical procedures were then performed on the left side. Communications should be addressed to: Dr. Bakdash; Division of Pediatric Neurology; University Hospitals Health System; 11100 Euclid Avenue, Mather Dorm 6090; Cleveland, OH 44106. Received October 10 2000; accepted August 10, 2001. Bakdash et al: Moyamoya Disease 157 Discussion Figure 1. Deep left centrum semiovale infarct. The patient awoke from surgery with a dense left hemiparesis. This improved rapidly and by 6 weeks his strength was normal except for mild weakness of left ankle dorsiflexion. Follow-up computed tomography and magnetic resonance imaging revealed bilateral frontal lobe encephalomalacia. There was a small left epidural hematoma without mass effect, and this resolved spontaneously. The patient was maintained on aspirin and phenytoin. Children with moyamoya disease can have marginal cerebral perfusion. It is recognized that they can present with seizures, transient ischemic attacks, or strokes. Activities associated with hyperventilation, such as crying, can precipitate symptoms. This patient is unique in that transient dystonia caused by hyperventilation has not previously been reported in moyamoya disease, although there has been a case report of recurrent torticollis in an 8-month-old female with the disease [1]. It is known that patients with this disease may have a “rebuild-up phenomenon” [slow activity] on recorded electroencephalograms several minutes after hyperventilation [2,3]. In an attempt to explain the above phenomenon, studies have been performed using near infrared spectroscopy. It was found that during hyperventilation there is a decrease in the concentration of oxyhemoglobin and total hemoglobin. Termination of hyperventilation was followed by partial recovery of these values, although they dropped subsequently. It was found that cytochrome oxidase was also reduced. The above disturbances were closely correlated to the rebuild-up phenomenon and with transient ischemic attacks [4]. The same results were reached by Lin et al. [5]. In another study 99mTc-HmPAO single-photon electron spectroscopy (SPECT) revealed a critical decrease of regional blood flow during the rebuild-up phenomenon in the parietal and occipital regions bilaterally. Acetazolamide testing indicated a severe deficit of perfusion reserve. This finding was also related to the rebuild-up phenomenon observed in the entire hemisphere 30 seconds later, includ- Figure 2. Left side of cerebral angiogram confirms the diagnosis of moyamoya disease. 158 PEDIATRIC NEUROLOGY Vol. 26 No. 2 Figure 3. Right side of cerebral angiogram also confirms the diagnosis of moyamoya disease. ing the areas where ischemic changes were not noted [6]. Fujiwara et al. [7] administered oxygen to children with moyamoya disease and found that it eliminated the rebuild-up phenomenon. In a study measuring intraoperative cortical blood flow and CO2 response during hyperventilation in children with moyamoya disease, it was demonstrated that basal moyamoya vessels were constricted by hyperventilation. This may explain the ischemic symptomatology observed during hyperventilation [8]. Togawa et al. concluded that in young children even a moderate decrease in blood flow could cause metabolic impairment. This impairment is caused by high cerebral metabolic demands, which may explain why we see transient ischemic attacks in children with moyamoya disease during hyperventilation [9]. From Table 1. the above literature, we can speculate on the mechanism of the above presentation of our patient with dystonia during hyperventilation. The weakness and numbness observed could be caused by decreased blood supply with decreased oxygen and vasoconstriction of the basal ganglia regions. An asymmetric blood supply may explain why he presented with unilateral transient dystonia during hyperventilation. The laboratory findings suggest that his presentation might be secondary to autoimmune phenomena. This presentation has been reported in pediatric patients with moyamoya disease who had antiphospholipid antibodies [10-12]. Elevation of antinuclear, anti-DNA, anti-SM, and anti SS-A antibodies are observed in children with systemic lupus erythematous but may be temporarily Laboratory results Von Willebrand’s factor C3 complement C4 complement CH 50-complement total C-reactive protein Westergren erythrocyte sedimentation rate Immunoglobulin M Immunoglobulin A Immunoglobulin G Activated partial thromboplastin time Platelets Epstein-Barr virus viral capsid antigen IgG Epstein-Barr virus early antigen IgG Epstein-Barr virus nuclear antigen IgG Patient’s Values Normal Range 159 254 60 20 3.38 76 279 271 1157 36 503 2.5 ⬎5 ⬎5 50-150% 77-168 mg/dL 13-36 mg/dL 100-300 CH50 units 0-1 mg/dL 0-13 mm/h 25-136 mg/dL 23-116 mg/dL 429-1131 mg/dL 25-33 sec 150-400 ⫻ 109/L ⬍1-Negative ⬍1-Negative ⬍1-Negative Bakdash et al: Moyamoya Disease 159 Table 2. Laboratory results Laboratory Tests Abnormal Values Normal Values/ Reference Antinuclear antibody screen Antinuclear antibody titer Anti-Sm Anti-SS-A (Anti-Ro) Anti-DNA Positive 1:80 1.9 2.1 35 Negative ⬍1:80 ⬍1-Negative ⬍1-Negative ⬍25 Negative IU/mL 25–30 Borderline positive 30–60 Low positive 60–200 Positive ⬎200 Strong positive ⬍1-Negative Negative 0-12 GPL units Equivocal 13-18 Positive ⬎18 Negative 0-10 APL units Equivocal 11-15 Positive ⬎15 Negative Anti-Scl-70 Anticardiolipin IgG immunoglobulin G 1.1 75 Anticardiolipin IGA immunoglobulin A 85 Antinuclear antibody screen increased after infection with the Epstein-Barr virus, although active lupus usually results in decreased levels of complement C3 and C4. In this patient, they are increased, although the functional level of CH50 is decreased. This decrease may occur if the functional assay is not performed promptly after phlebotomy or if another constituent of the compliment cascade is decreased or absent. Prolongation of the activated partial thromboplastin time may be due to the presence of a lupus anticoagulant or deficiency of other clotting factors. The elevated anticardiolipin antibody does not cause prolongation of the activated partial thromboplastin time. The high sedimentation rate C-reactive protein platelet count and Von Willebrand factor could be observed in patients with vasculitis. Could moyamoya disease be the cerebral equivalent of Takayasu disease? Further studies are required. References [1] Yasutomo K, Hashimoto T, Miyazaki M, et al. Recurrent torticollis as a presentation of moyamoya disease. J Child Neurol 1993;8:187-8. [2] Sunder TR, Erwin CW, Dubois PJ. Hyperventilation induced abnormalities in the electroencephalogram of children with moyamoya disease. Electroencephalogr Clin Neurophysiol 1980;49:414-20. [3] Kodama N, Aoki Y, Hiraga H, Wada T, Suzuki J. Electroencephalographic findings in children with moyamoya disease. Arch Neurol 1979;36:16-9. 160 PEDIATRIC NEUROLOGY Vol. 26 No. 2 Positive [4] Kuroda S, Houkin K, Hoshi Y, Tamura M, Kazumata K, Abe H. Cerebral hypoxia after hyperventilation causes “re-build-up” phenomenon and TIA in childhood moyamoya disease. A near-infrared spectroscopy study. Childs Nerv Syst 1996;12:448-53. [5] Lin Y, Yoshiko K, Negoro T, Watanabe K, Negoro M. Cerebral oxygenation state in childhood moyamoya disease: A near-infrared spectroscopy study. Pediatr Neurol 2000;22:365-9. [6] Kazumata K, Kuroda S, Houkin K, Abe H, Mitumori K. Regional cerebral hemodynamics during re-build-up phenomenon in childhood moyamoya disease. An analysis using 99mTc-HMPAO SPECT. Child Nerv Syst 1996;12:161-5. [7] Fujiwara J, Nakahara S, Enomoto T, Nakata Y, Takita H. The effectiveness of O2 administration for transient ischemic attacks in moyamoya disease in children. Child Nerv Syst 1996;12:69-75. [8] Nakao K, Yamada K, Hayakawa T, Tagawa T, Yoshimine T, Ushio Y, Mogami H. Intraoperative measurement of cortical blood flow and its CO2 response in childhood moyamoya disease. Neurosurgery 1987;21:509-14. [9] Tagawa T, Naritomi H, Mimaki T, Yabuuchi H, Sawada T. Regional cerebral blood flow, clinical manifestations, and age in children with moyamoya disease. Stroke 1987;18:906-10. [10] Booth F, Yanofsky R, Ross IB, Lawrence P, Oen K. Primary antiphospholipid syndrome with moyamoya-like vascular changes. Pediatr Neurosurg 1999;31:45-8. [11] Schoning M, Klein R, Krageloh-Mann I, et al. Antiphospholipid antibodies in cerebrovascular ischemia and stroke in childhood. Neuropediatrics 1994;25:8-14. [12] Takanashi J, Sugita K, Miyazato S, et al. Antiphospholipid antibody syndrome in childhood strokes. Pediatr Neurol 1995;13:323-6.