Child's Nerv Syst (1993) 9:215-219 l NS 9 Springer-Verlag 1993 Moyamoya disease in childhood: a familial case report S. Soriani 1, p. Scarpa 1, A. Voghenzi 1, L. De Carlo 1, R. Cilio 2 1 Istituto di Pediatria, Universifft di Ferrara, Via Savonarola, 9, 1-44100 Ferrara, Italy z Service de Neurologie Pediatrique, Universit6 Catholique de Louvain, Louvain, Belgium Received: 3 December 1991/Revised: 28 July 1992 Abstract. M o y a m o y a is an obstructive cerebrovascular disease characterized by a cerebral angiographic picture of stenosis or occlusion of main cerebral arteries with an abnormal vascular network at the base of the brain. N o definitive cause has been found for this disease and opinion is still divided between a congenital and an acquired etiology. Hemiplegia of sudden onset and epileptic seizures are the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. We report a new case of childhood m o y a m o y a with clinical onset of the neurological symptoms within the 3rd year o f life; during the child's illness the maternal grandmother presented with m o y a m o y a disease too. Antiaggregating and calcium-antagonist drugs seem effective in preventing further vascular accidents, while a surgical approach is not possible. Computed tomography, single positron emission computed tomography, and magnetic resonance imaging are very useful in the diagnosis of this rare disease. Key words: M o y a m o y a disease - Children - Cerebral angiography - M R I - Seizures Introduction M o y a m o y a disease is a rare cerebrovascular disorder of u n k n o w n etiology consisting of stenosis or occlusion of main cerebral arteries which causes an abnormal vascular network at the base of the brain. The Japanese term " m o y a m o y a " ("something hazy, like a puff of smoke drifting in the air") describes the angiographic appearances [13, 23]. The vascular abnormalities are bilateral in the disease, while a unilateral appearance (known as the m o y a m o y a phenomenon) can occur in other conditions such as neurofibromatosis, tuberous sclerosis, tuberculous meningitis, etc. [8]. The disease c o m m o n l y presents with strokes in childhood, while in adults subarachnoid Correspondence to: S. Soriani and intracranial hemorrhage is the prevailing presentation [8]. A b o u t 200 childhood cases have been reported (two-third in Japan) with a male-female ratio of 2:3 [2], in Italy there are less than ten. We discuss here the case of a child with clinical onset of the neurological symptoms in the 3rd year o f life. Case report The patient is a boy aged 3 years and 2 months. The family history revealed febrile convulsions in the mother and transient ischemic attacks in the maternal grandmother. The child's past history was unremarkable except for a febrile convulsion at 15 months. The child was admitted at the age of 26 months because of a sudden right hemiparesis; 3 days before hospitalization he had suffered vomiting and partial seizures. On admission, cranial computed tomography (CT) revealed two cortical-subcortical hypodense zones in the left temporoparietal-occipital and right parietal areas, both without contrast enhancement. Magnetic resonance imaging (MRI) of the brain (Fig. 1) showed cerebral infarction with cortical-subcortical atrophy in the right parietal area and cortical atrophy in the left parietal area. The striate and perforating arteries and the medullary vessels were markedly hypertrophic. EEG showed a slowwave pattern localized in the right occipital-temporal and left frontal regions. Blood biochemistry showed no abnormalities. Lumbar puncture yielded normal spinal fluid under normal pressure. Subsequently the patient's neurologic status improved. EEG and CT scan showed only abnormalities in the right area. Two weeks later pharyngitis with fever developed and the patient suffered from two clonic partial seizures affecting his left face, so he was treated with phenobarbital. EEG was unchanged. Fifteen days later he presented left-sided status epilepticus, followed by a residual left hemiparesis and disturbance of cranial nerve VII and aphasia. CT scanning showed the reappearance of cortical abnormalities in the left temporoparietal-occipital area and revealed recent corticosubcortical lesions in the right temporoparietal region, near to the territory of previous parietal posterior cerebral infarction. CT scanning also revealed dilatation of the supratentorial ventricles and enlarged frontal subarachnoid space. Single positron emission computed tomography (SPECT) with 99mTc HmPAO showed diffuse low perfusion in the bilateral frontoparietal, right temporoparietal and left parieto-occipital regions. EEG revealed a diffuse increase of slow frequencies and high voltage sharps in the right parietal rolandic area. Upon admission, the patient's hemiparesis began to 216 improve and reached an almost complete neurologic recovery except for persisting aphasia. Because clinical, neuroradiological, and EEG findings suggested the diagnosis of moyamoya disease, cerebral angiography was performed. Angiographic study (Fig. 2) showed stenosis of both carotid siphons distal to the origin of the ophthalmic arteries. Above the stenosis there was a marked collateral circulation network mainly composed of near perforating arteries and others arising from the posterior choroidal arteries. A right carotid angiogram did not visualize the origin of the anterior and middle cerebral arteries, while in the left carotid angiogram the same arteries were markedly stenosed and opacified only for the first 2 - 3 cm. There was a dilated external carotid network. Subsequently, the child presented with another right-sided status epilepticus, with a residual hemiparesis. In the mean-while a therapy was started with antiaggregating and calcium-antagonist drugs. Phenobarbital was stopped and carbamazepine was initiated. The patient began physical therapy. After a few days the right hemiparesis improved, while aphasia and left motor disturbance persisted. Today, after a 14-month follow-up, the left hemiparesis has improved, but the aphasia has persisted. The child's abilities are underdeveloped for his age; his IQ (Brunet-Lezine scale) is 62. He has no more seizures. EEG is normal. MRI shows cerebral infarction in fronto-temporoparietal-occipital cortical-subcortical areas of both the hemispheres, and dilatation of the lateral ventricles and subarachnoid space. Discussion Fig. 1 a, b. Magnetic resonance imaging shows cerebral infarction with cortical-subcortical atrophy in the right parietal area and cortical atrophy in the left parietal area R e p o r t s o f m o y a m o y a in i n f a n c y are rare: in I t a l y (Table 1) t h e y are v e r y few [4], w i t h a n o n s e t m o s t f r e q u e n t l y marked by convulsions and episodes of sudden hemiplegia in p a t i e n t s a g e d less t h a n 2 y e a r s (6 o u t o f 9 cases); the clinical c o u r s e s h o w s irreversible n e u r o l o g i c a l deficits a n d intellectual regression. T h e v a s c u l a r a b n o r m a l i t i e s are b i l a t e r a l in the disease, while a u n i l a t e r a l a p p e a r a n c e ( k n o w n as the m o y a m o y a p h e n o m e n o n ) c a n o c c u r in o t h e r c o n d i t i o n s , such as neur o f i b r o m a t o s i s , t u b e r o u s sclerosis, etc. O u r p a t i e n t suffers f r o m m o y a m o y a disease, n o t the m o y a m o y a p h e nomenon. It h a s been r e p o r t e d in u n c o n t r o l l e d studies [8] t h a t m o y a m o y a disease is o f t e n p r e c e d e d b y a p r o d r o m e such as a n u p p e r r e s p i r a t o r y t r a c t infection, o r a seizure o r a fever o f u n k n o w n etiology. O u r p a t i e n t suffered v o m i t ting a n d p a r t i a l seizures 3 d a y s b e f o r e the h o s p i t a l i z a t i o n . T h e o n s e t w i t h n e u r o l o g i c a l deficits d u e to c e r e b r a l i n f a r c t i o n , f o l l o w e d b y r e p e a t e d e p i s o d e s o f c e r e b r a l inf a r c t i o n , suggests t h e p a t t e r n o f stage V m o y a m o y a disease a c c o r d i n g to S u z u k i a n d T a k a k u [23]. This t y p e is u n u s u a l in c h i l d r e n a n d c o r r e s p o n d s to the s o - c a l l e d Table I. Symptoms and clinical data in Italian cases of childhood moyamoya disease Authors Year n Sex Age Symptoms Follow-up Galligioni et al. [7] 1971 1 F 4 years Convulsion, hemiparesis Mental and motor disturbance Motor disturbance Lanzi et al. [15] 1974 2 F 8 months Convulsion, hemiparesis Benedetti et al. [3] 1977 3 M 11 months Convulsion, hemiparesis Motor disturbance Not reported Carella et al. [4] 1977 4 M 8 years Convulsion, hemiparesis Piattella et al. [18] 1981 5 F 6 months Convulsion, hemiparesis Recurrent episodes of motor disturbance Piattella et al. [18] 1981 6 M 2 years Convulsion, hemiparesis Recurrent episodes of motor disturbance Di Rocco et al. [5] 1984 7 M 13 months Not reported Not reported Di Rocco et al. [5] 1984 8 M 18 months Not reported Not reported Battistella et al. [2] 1987 9 F 5 years Hemiparesis, headache Normal 217 Fig. 2 a - h . Bilateral carotid angiograms showed stenosis of both carotid siphons distal to the origin of the ophthalmic arteries. The right carotid angiogram (a-d) revealed no origin of the anterior and middle cerebral arteries; in the left carotid angiogram (e-f) the same arteries were markedly stenosed and opacified only for the first 2 - 3 cm 218 adult m o y a m o y a disease that is often observed in patients older than 20 years of age. In Suzuki and T a k a k u ' s series of 81 childhood patients there was only one with type V disease, and this presented in the patient when he was almost adult [23]. Onset under the age of 4 years, seizures, and cerebral infarctions are risk factors [8] suggesting irreversible neurological deficits and intellectual regression, as demonstrated in our patient after a 14-month follow-up. The medical treatment of m o y a m o y a disease with antibodies, low molecular-weight dextran and steroids is not very effective [8]. In our patient, pharmacological therapy with antiaggregating and calcium-antagonist drugs was carried out and seems to be effective in preventing further vascular accidents. Antiaggregating drugs seem useful because of the increased platelet aggregability in m o y a m o y a disease. As for calcium-antagonist drugs, there is a report of two children [5] with m o y a m o y a disesase treated with verapamil which improved their acute neurological deficits [16]. Subsequently other authors have stressed the efficacy of flunarizine in the treatment of ischemic attacks in m o y a m o y a disease [17]. M a n y reports have described the promising effects of revascularization procedures for the prevention o f ischemic cerebral attacks in m o y a m o y a disease [21]. However, it is still a matter of debate whether such procedures prevent progression o f the disease or only stabilize it temporarily. Anyway, we ruled out the possibilty o f a surgical approach for our patient because o f the severity o f the case: our patient's condition fits the criteria of stage V m o y a m o y a disease according to the angiographic classification described by Suzuki and Takaku [23]. N o definite cause has been found for m o y a m o y a disease; opinion is still divided between a congenital and an acquired etiology, in particular infection [8]. A primary m a l f o r m a t i o n of blood vessels has been suggested by Galligioni et al. [7]. The association with a history o f trauma, infection, brain tumor, or radiation suggests there m a y also be an acquired form. Recurrence of m o y a m o y a within the same family seems a point in favor of congenital malformation. K i t a h a r a et al. [12] stressed the hereditary c o m p o n e n t in the pathogenesis of the disease as a cause o f the relatively high familial incidence (7 %) found in his totally Japanese series. Case reports found in the literature that deal with familial cases are summarized in Table 2. In the present case the family history is very interesting: during the child's illness, the maternal grandmother, living together with the patient, experienced some transient ischemic attacks in the same time period. She underwent cerebral angiography that showed the occlusion at the origin of the right internal carotid artery, a high grade of stenosis o f the left internal carotid artery, and moya m o y a collateral circulation. Our data support a familial congenital disease of possible hereditary origin, but an infectious cause can not be ruled out, because of the presence of the illness in the child and in his g r a n d m o t h e r at the same time. In conclusion, the reported case confirms that the prognosis is p o o r if the patient is under 4 years of age at onset and seizures and cerebral infarctions appear. We Table 2. Familial cases of moyamoya disease (from the literature) Authors Year Reported cases Austin and Stears [1] Praud et al. [19] Sogaard and Jorgensen [22] Kudo [14] 1971 1972 1975 1975 Richman et al. [20] 1977 Fijiwara et al. [6] 1977 Kitahara et al. [12] Yamada et al. [27] Vinals et al. [25] Kawamura et al. [11] Ikeda et al. [9] 1979 1980 1986 1987 1990 Usuki et al. [24] Iwamoto et al. [10] 1991 1991 Two (or three) brothers Two brothers Three patients in a family Seven instances of familial occurrence Two adults (a man and his niece) Two cases (a mother and her child) Three familial cases Two identical twin girls A familial presentation Two twin girls Two cases (a mother and her daughter) One familial case Three patients in a family stress the importance of the genetic factor in the pathogenesis o f the disease and the effectiveness o f p h a r m a c o logical therapy in our patient. Finally, our data underline that CT, S P E C T and especially M R I [26], are very useful to reach a suspected diagnosis o f m o y a m o y a disease, which must be confirmed by cerebral angiography. References 1. Austin JH, Stears JC (1971) Familial hypoplasia of both internal carotid arteries. Arch Neurol 24:1-10 2. Battistella PA, Pardatscher K, Laverda AM, Casara GL, Matin G (1987) La sindrome di moyamoya: progressivit~ del quadro angiografico e prospettive terapeutiche. Pediatr Med Chir 9:41-46 3. Benedetti P, Curatolo P, Porro G (1977) Un cast di moya moya nel primo anno di vita. Neuropsichiatr Infant 188:190-193 4. Carella A, Lamberti P, Perniola T, Livrea P, Federico F, Lochi L, Della Rosa A, Fiore T, Liquori R (1977) Contributo clinico ed angiografico alia sindrome di moya-moya. Acta Neurol 5:658-673 5. Di Rocco C, Velardi F, Moschini M, Rinaldi A (1984) Surgical treatment of moya-moya disease in infancy. Neuropediatrics 15:243 6. Fijiwara K, Takada I, Suematsu K (1977) Moyamoya syndrome in a mother and child (in Japanese). Brain Dev 9:233236 7. Galligioni F, Andrioli GC, Marin G, Briani S, Iraci G (1971) Hypoplasia of the internal carotid artery associated with cerebral pseudoangiomatosis. Am J Roentgenol 112:251-262 8. Gordon N, Islet W (1989) Childhood moyamoya disease. Dev Med 31:98-107 9. Ikeda A, Iguchi I, Hara M, Yamamoto I, Sato O (1990) Familial occurrence of moyamoya disease with intracranial hemorrhage. Report of two cases. Neurol Med Chir (Tokyo) 30:4346 10. Iwamoto T, Nishizaki T, Tsuha M, Wakuta Y, Nagamitsu T, Adachi N, Yamashita K (1991) One pedigree of "moyamoya" disease (in Japanese). No Shinkei Geka 19:781-787 11. Kawamura S, Hadeishi H, Suzuki A, Yasui N (1987) Moyamoya disease in twins (in Japanese). No To Shinkei 39:119-125 12. Kitahara T, Ariga N, Yamaura A, Makino H, Maki Y (1979) Familial occurrence of moya-moya disease: report of three Japanese families. 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