Neurosurg Rev (2006) 29: 82–87 DOI 10.1007/s10143-005-0406-5 CASE REPORT Noboru Kusaka . Takashi Tamiya . Yoshiaki Adachi . Shinji Katayama . Shimpei Namba . Koji Tokunaga . Kenji Sugiu . Isao Date . Takashi Ohmoto Adult unilateral moyamoya disease with familial occurrence in two definite cases: a case report and review of the literature Received: 13 March 2005 / Revised: 30 April 2005 / Accepted: 26 May 2005 / Published online: 15 July 2005 # Springer-Verlag 2005 Abstract We documented an interesting case of adult “unilateral (probable)” moyamoya disease displaying familial occurrence in two “definite” cases. A 55-year-old female presented with motor aphasia, involuntary movement of the right hand and right homonymous hemianopia due to cerebral infarction. Cerebral angiography revealed typical angiographic findings on the left side and normal findings on the right side; consequently, the patient was diagnosed with probable moyamoya disease. Previously, her mother and nephew had been diagnosed with definite moyamoya disease with bilateral involvement. The patient continued to exhibit unilateral involvement on angiography for more than 4 years. Clinical features such as absence of familial occurrence suggest that most cases of probable moyamoya disease are distinct from definite cases, especially in adults. To the best of our knowledge, this report appears to be the first involving an adult probable case characterized by familial occurrence. The literature pertaining to adult probable moyamoya disease was reviewed and the etiology of this disease was discussed. Keywords Probable moyamoya disease . Unilateral moyamoya disease . Adult . Familial occurrence N. Kusaka (*) . Y. Adachi . S. Katayama . S. Namba . T. Ohmoto Department of Neurosurgery, Okayama Rosai Hospital, Okayama, Japan e-mail: kusaka@iwakuni-nh.go.jp Tel.: +81-86-2357335 Fax: +81-86-2270191 T. Tamiya Department of Neurological Surgery, Kagawa University, Kagawa, Japan K. Tokunaga . K. Sugiu . I. Date Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Introduction Moyamoya disease is a clinical entity of unknown etiology; moreover, this condition is characterized by progressive bilateral stenosis or occlusion of the ICA with the vascular network, the so-called moyamoya vessels, at the base of the brain. Moyamoya disease is generally defined as a bilateral lesion; however, unilateral abnormalities also occur. The official diagnostic criteria of the Research Committee on the Spontaneous Occlusion of the Circle of Willis of the Ministry of Health and Welfare, Japan (RCMJ) classify adult cases with bilateral occlusive lesions as “definite” moyamoya disease and those with unilateral involvement as “probable” moyamoya disease [10]. The etiology of moyamoya disease has not been clarified. Familial history of moyamoya disease was apparent in 10.0% of patients in Japan [45]. The predisposition of this disease among oriental populations and occasional familial occurrence strongly suggest a congenital link. However, following analysis of unilateral (probable) moyamoya cases, Houkin et al. observed no familial occurrence [19]. Therefore, they concluded that unilateral disease is quite different from typical bilateral disease. The relationship between probable moyamoya disease with unilateral involvement and typical bilateral moyamoya disease remains controversial. We documented an interesting case of adult probable moyamoya disease with familial occurrence in two definite cases. This very rare case is presented; furthermore, the literature pertaining to adult probable moyamoya disease is reviewed. Case report The family pedigree of our patient, a 55-year-old female, is illustrated in Fig. 1. Her mother presented with right hemiparesis at the age of 58 years in 1976. Computed tomography (CT) demonstrated a cerebral infarction, and conventional angiography disclosed typical type moyamoya disease with bilateral involvement at our institute. 83 Sex Age of onset (years) Type of moyamoya disease F F M 58 55 3 definite probable definite 1 1 2 3 2 3 Fig. 1 Family pedigree of the patient. The arrow indicates the proband patient and the closed circles indicate individuals displaying definite or probable moyamoya disease Fig. 2 Angiogram obtained in May 2000. Upper row: left carotid angiograms demonstrated occlusion of the internal carotid artery (ICA) with moyamoya vessels. Middle row: right carotid angiograms revealed no abnormalities in the right ICA and its branches. The left anterior and middle cerebral arteries were filled from the unaffected right ICA via the anterior communicating artery. Lower row: left vertebral angiograms revealed an abnormal vascular network in the left thalamic region She was treated conservatively; however, she presented with a new cerebral infarction and died of the sequelae in 1994. Her nephew also presented with transient right hemiparesis at 3 years of age in 1982. CT revealed a small cerebral infarction and conventional angiography disclosed definite moyamoya disease. Left encephalo-duro-arteriosynangiosis (EDAS) was performed at another hospital and post-operative course was uneventful. However, 3 years later, he presented with transient left hemiparesis. Right EDAS was conducted in 1985; currently, he is doing well with mild intellectual deterioration. The proband patient presented with sudden onset of motor aphasia, involuntary movement of the right hand and 84 Fig. 3 Follow-up angiograms 2 years later. Upper row: left carotid angiograms demonstrated good collateral flow through the bypass. The basal moyamoya vessels were sparse in comparison with initial angiograms. Lower row: right internal carotid angiograms showed neither a steno-occlusive lesion nor abnormal vasculature right homonymous hemianopia in May 2000. Magnetic resonance imaging (MRI) and CT demonstrated an infarction in the left temporo-occipital area. Left carotid angiography revealed an occlusion of the internal carotid artery (ICA) immediately distal to the origin of the ophthalmic artery with basal moyamoya vessels (Fig. 2, upper row). Right carotid angiography revealed no stenotic lesion on the right side (Fig. 2, middle row). Left anterior cerebral (ACA) and middle cerebral (MCA) arteries were filled from the unaffected right ICA via the anterior communicating artery. Left vertebral angiography showed an abnormal vascular network from the left posterior cerebral artery in the left thalamic region (Fig. 2, lower row). Single photon emission computed tomography (SPECT) exhib- ited a low level of perfusion in the left cerebral hemisphere. No obvious basic disorder related to cerebrovascular occlusion or stenosis was detected. Therefore, the diagnosis in this case was probable moyamoya disease in accordance with the guidelines of the RCMJ. The patient underwent superficial temporal artery (STA)-MCA anastomosis on the left side in July 2000. Post-operative course was uneventful and neurological recovery, with the exception of homonymous hemianopia, was satisfactory. Follow-up angiography was conducted 2 years later. No definite angiographical change was apparent on the unaffected side (Fig. 3, lower row). Right carotid angiography demonstrated neither stenosis of the ICA nor abnormal vessels. Left carotid angiography revealed abundant collateral circulation to the MCA territory through the bypass (Fig. 3, upper row). The basal moyamoya vessels were sparse in comparison with initial angiograms. Magnetic resonance angiography (MRA) obtained in May 2004 also showed unilateral involvement (Fig. 4). Additional symptoms of cerebral hemorrhage or ischemia were not detected during the observation period. Discussion Fig. 4 Magnetic resonance angiography (MRA) 4 years later revealed unilateral involvement Moyamoya disease is a rare cerebrovascular disorder characterized by progressive arterial stenosis of the circle of Willis with abnormal vascular networks at the base of the brain. The etiology of this disease has not been clarified. 85 Table 1 Summary of the reported cases with adult probable (unilateral) moyamoya disease Authors Year Case Age Sex Familial occurrence Hirotsune [15] 1997 Case 13 Case 14 Case 15 Case 16 Case 17 17 20 21 44 45 58 48 34 25 33 32 54 28 56 33 53 33 37 30 29 27 30 55 53 57 20 37 M F F F F M F M F M M M F F F M M M F F F F F F F F M None None None None None None None None None None None None None None None None None None None None None None None None None No mention No mention No details Fujiwara [8] Borota [4, 5] 1997 1997 Tsuda [43] Houkin [19] 1997 1996 Miyazaki [28] Hardy [13] Aoki [2] Kasamo [23] Fukawa [9] Tanaka [40] Hong [17] Tomida [41] Ikezaki [21] Graham [12] Battistella [3] Wanifuchi [46] Kawano [24] Shin [37] Kurose [26] Tomura [42] 1992 1991 1989 1984 1982 1978 2002 2000 1997 1997 1997 1996 1994 1991 1991 1989 Wanifuchi [47] Chen [6] Sawamura [36] 1988 1988 1987 Gomez [11] Honda [16] Nijdam [33] Nagamine [31] Murphy [30] Tanaka [40] 1987 1987 1986 1981 1980 1978 Case 4 Case 18 Case 20 Case 24 Case 30 Case 31 Case 16 Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 3 112 cases 4 cases 1 case Case 2 15 cases 17 Case 2 Case 3 Case 8 Case 9 17 cases Case 11 Case 1 Case 2 Case 3 Case 4 Case 2 No mention No mention 38 M 16 48 44 60 55 F F M F M M 31 19 42 43 47 31 33 34 36 29 40 M F M F F F F F M F M No details No mention No details No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention No mention Table 1 (continued) Authors Year Case Age Sex Familial occurrence Vignaendra [44] 1977 Yasargil [48] 1976 Case 5 Case 7 Case 1 Case 2 33 16 38 38 F M M F No mention No mention No mention No mention Histopathological studies have revealed stenosis and occlusion of the main arterial trunk, usually due to fibrocellular thickening of the intima [18]. Moyamoya disease was first described in 1957 by Japanese investigators; subsequently, this disease has been examined primarily by Japanese researchers [39]. However, research presented at the International Symposium on Moyamoya Disease in Fukuoka, Japan in 1996 stimulated international interest in this disease. Moyamoya disease exists in all races; however, a high incidence of this disease is apparent in Japanese and other oriental populations [3, 4, 7, 12, 20, 34, 49]. Among Japanese, the annual incidence rate is 0.35 per 100,000 populations; moreover, estimation of the frequency of familial occurrence is 10.0% [45]. High prevalence among oriental populations, occasional familial occurrence and several genetic factors suggest an inherited tendency for this disease [22]. Moyamoya disease is generally defined as bilateral stenosis or occlusion of the ICA; however, unilateral abnormalities also occur. Several reports have suggested that bilateral progression could arise from unilateral moyamoya disease; furthermore, most young children tend to develop bilateral lesions within 1–2 years, whereas adults tend to display a unilateral lesion [15, 19, 24, 27]. In instances of juvenile unilateral disease, it appears quite reasonable that some cases involve an early form of typical moyamoya disease. Therefore, juvenile cases characterized by typical angiographic findings on one side and significant stenosis of the terminal portion of the ICA on the opposite side have been classified as “definite” in accordance with the revised diagnostic criteria established by the RCMJ since 1988 [10]. On the other hand, most adult unilateral cases are believed to involve an unusual form of unilateral stenoocclusive process of the ICA or MCA with no genetic factor involvement [1, 14, 19, 35]. The diagnostic criteria classify those adult cases displaying bilateral occlusive lesions as “definite” moyamoya disease and those exhibiting unilateral involvement as “probable” moyamoya disease [10]. Kitamura also classified cases of probable moyamoya disease into three types according to the findings on the side opposite the occlusive changes: (1) very minimal stenosis, (2) atypical findings, and (3) no abnormalities [25]. Numerous English and Japanese reports regarding adult unilateral (probable) moyamoya disease were obtained following an exhaustive literature search (Table 1). Confusion remains as to whether the term “probable” or “unilateral” should be used in earlier publications, despite the RCMJ proposal that the term “probable” is most 86 appropriate for diagnoses [32]. Patients presenting with “probable moyamoya disease”, “unilateral moyamoya disease”, “moyamoya syndrome”, “moyamoya phenomenon”, “quasi-moyamoya disease” and “akin-moyamoya disease” were included in the present investigation. Probable moyamoya disease was diagnosed in the presence of typical angiographic findings of moyamoya disease on one side concomitant with normal angiographic findings or minimal equivocal signs of stenosis on the contralateral side. Cases associated with apparent basic diseases or conditions such as autoimmune disease, Down’s syndrome, von Recklinghausen’s disease, head trauma, etc., were excluded from this study. As a result, 20 papers were collected: moreover, adult probable moyamoya patients described in these papers totaled 173. We described long-term follow-up of unilateral disease in an earlier publication [15]. Between 1963 and 1996, 17 unilateral cases were diagnosed at Okayama University Hospital and its affiliates. The previous study did not present data corresponding to familial occurrence in 12 pediatric and five adult cases. Pediatric cases exhibited a congenital tendency consequent to familial occurrence in four instances. In contrast, familial occurrence was not observed in adult cases. In ten patients characterized by unilateral disease, Houkin et al. analyzed basic fibroblast growth factor (bFGF) concentration in the cerebrospinal fluid (CSF), which reaches very high levels in individuals with typical moyamoya disease, and familial occurrence [19]. Familial occurrence was not detected; consequently, they concluded that lack of familial occurrence and low levels of bFGF in the CSF of these patients strongly suggested that most unilateral cases, especially in adults, are distinct from typical bilateral moyamoya disease. Borota et al. also documented 31 moyamoya cases in Yugoslavia, which included six cases of adult unilateral disease; moreover, no familial occurrence or territorial clustering was evident in these patients [4, 5]. Other authors have described clinical features of adult unilateral disease in detail, including familial occurrence; however, familial occurrence has not been observed [2, 8, 9, 13, 23, 28, 40, 43]. Ikezaki et al. [21] conducted an investigation involving a large number of patients registered by the RCMJ in which 180 probable cases, 112 of which were adults (62%), were analyzed. They reported that the familial occurrence rate was 6.7%; furthermore, the difference between probable and definite cases was not statistically significant. However, familial occurrence with respect to age distribution was not examined; additionally, these cases included Suzuki’s stages 2 and 6 as well as stages 0 and 1 on the opposite side. According to Suzuki’s classification on the basis of angiographical findings, stage 2 displays initiation of basal moyamoya with stenosis or occlusion of ICA, whereas stage 6 exhibits disappearance of moyamoya vessels and absence of all main cerebral arteries [38]. Cases characterized by these angiographic findings on the opposite side may be categorized as an early or terminal form of typical bilateral moyamoya disease. Kawano et al. [24] documented 32 probable cases registered by the RCMJ (including 15 adults). Family history was evident in only three pa- tients; however, whether these individuals were adults or children is not known. As shown in Table 1, many authors described adult unilateral cases previously; however, familial occurrence was not observed. To the best of our knowledge, this report appears to be the first involving an adult probable case displaying familial occurrence. Bilateral progression in unilateral disease typically occurs within 1–2 years. Angiography confirmed unilateral involvement exclusively for more than 4 years in the current case; however, careful attention is essential in order to detect future bilateral progression. Previous reports indicated that genetic background factors may be involved in definite moyamoya disease [22]. On the other hand, adult unilateral moyamoya cases were thought to be most likely a different entity from definite ones. But our report shows a unilateral case and familial occurrence of definite cases. We suspect the possibility that genetic factors may play a role in the incidence of this adult probable case; moreover, “definite unilateral” and not “probable” moyamoya disease may exist. Although a high frequency of familial occurrence has been noted in typical moyamoya disease, few investigations related to familial occurrence in unilateral cases have been conducted [19, 21]. 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