Clinical features of familial moyamoya disease.

OBJECTS: This study aims to clarify the genetic background of moyamoya disease by comparing clinical features between familial and sporadic cases to reveal the responsible genes for familial moyamoya disease. METHODS: This study included 155 Japanese patients with moyamoya disease, which included 24 familial cases (10 family pedigrees) and 131 sporadic cases. Clinical features were compared between the familial and sporadic cases. RESULTS AND CONCLUSION: A female preponderance was significantly more prominent in the familial than in the sporadic group (P=0.0421). Mean age at onset was significantly lower in familial than in sporadic cases (P=0.004). In eight parent-offspring pairs, mean age at onset was significantly lower in the second than in the first generation (P<0.0001). These results suggest that familial moyamoya disease is associated with genetic anticipation and female predominance and that a genetic analysis study focused on expanded triplet repeats may clarify the pathogenesis of the disease.

Incidence and clinical features of disease progression in adult moyamoya disease.

BACKGROUND AND PURPOSE: The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. METHODS: For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography. RESULTS: Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97). CONCLUSIONS: The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

A novel coating biomaterial for intracranial aneurysms: effects and safety in extra- and intracranial carotid artery.

Methyl-2-cyanoacrylate, a widely used material for coating cerebral aneurysm, was recently withdrawn. The aim of the present study was to develop an alternative coating material for cerebral aneurysm, which is safe, effective and stable within the brain. In the first experiment, an aneurysm model of the common carotid artery was produced in a rabbit by the local application of elastase. The aneurysm produced was covered by no material (Group A), a cellulose cotton sheet and conventional methyl-2-cyanoacrylate (Group B), a newly produced polyglycolic acid felt and fibrin glue (Group C), or a cellulose cotton sheet and fibrin glue (Group D). Histological examination showed that the materials resulted in the formation of tight connective tissue around the artery, and that the material was completely replaced by the connective tissue after 12 weeks. This change was found exclusively in Group C, but not in Group A or the other materials, although a temporary thickening of the intima was also observed at the site of the elastase application in Group C. In Group D, a long-term, marked thickening of the intima was observed. In the second experiment, using an intracranial internal carotid artery from a beagle, the applied polyglycolic acid felt and fibrin glue to the intracranial artery induced the formation of connective tissue around the artery that was completely absorbed 16 weeks after surgery. There were no signs of intimal thickening or of adverse reactions in nervous tissue. The present results suggest that polyglycolic acid felt and fibrin glue is a possible candidate for a safe, effective biomaterial to wrap or coat cerebral aneurysm.

Sequence analysis and bioinformatics analysis of chromosome 17q25 in familial moyamoya disease.

OBJECTS: The pathogenesis of moyamoya disease is still unknown. The present study aimed to find out the responsible genes that are located in the 17q25 locus. METHODS: Considering the function, we selected nine genes as candidates from a total of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome 17q25, and performed sequence analysis on the DNA samples obtained from a pedigree of familial moyamoya disease, which showed a complete linkage to the region by a haplotype analysis. Also, we attempted to identify candidate genes that have not been known but might be functionally relevant to the disease among a total of 2,100 expressed sequence tag (EST) sequences using bioinformatics techniques. RESULTS AND CONCLUSION: The sequence analysis could detect no mutation in the nine genes. Nor could we identify a novel candidate gene by the EST analysis. Further studies using alternative approaches are warranted to clarify the pathogenesis of moyamoya disease.

Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in moyamoya disease.

BACKGROUND AND PURPOSE: The etiology of moyamoya disease still remains unknown. This study was aimed to explore the role of hepatocyte growth factor (HGF), a strong inducer of angiogenesis, in development of moyamoya disease. METHODS: We studied cerebrospinal fluid (CSF) from 39 patients with moyamoya disease (24 children and 15 adults), 6 control patients with cervical spondylosis, and 7 control patients with internal carotid artery occlusion. CSF level of HGF was determined by enzyme-linked immunosorbent assay technique. We also evaluated the distribution of HGF and its cellular receptor c-Met in the carotid fork obtained from 2 patients with moyamoya disease and 2 control patients. RESULTS: CSF level of HGF was 408.2+/-201.6 pg/mL and 443.2+/-193.5 pg/mL in patients with cervical spondylosis and internal carotid artery occlusion, respectively (mean+/-SD). On the other hand, CSF level of HGF was 820.3+/-319.0 pg/mL in patients with moyamoya disease, being significantly higher than those in 2 control groups (P<0.01). Both HGF and c-Met were widely distributed in the media and thickened intima of the carotid fork in patients with moyamoya disease but not in control patients. CONCLUSIONS: This study revealed that HGF is densely found in the carotid fork, and its CSF level is markedly elevated in moyamoya disease, suggesting that HGF may be a key protein for pathogenesis of moyamoya disease.

[Joint therapy of a dural arteriovenous fistula in the transverse-sigmoid sinus using surgical excision and direct sinus packing: a case report].

Combined therapy of direct sinus packing and surgical excision for intracranial dural arteriovenous fistula (dAVF) has not been reported in the literature. A 53-year-old male was admitted to our hospital due to sudden onset of seizure and consciousness disturbance. Plain CT scan showed subcortical hematoma in the right temporal lobe. Cerebral angiography revealed dAVF involved in the right transverse and sigmoid sinuses. The lesion was associated with retrograde venous drainage into the right cerebellum, temporal, and occipital lobes. Positron emission tomography (PET) showed typical findings of venous hypertension in the involved areas. MRI also demonstrated a high intensity lesion in the medulla oblongata, suggesting critical venous congestion. First, we aimed to pack the involved sinus through a minor craniotomy, but cannulation into the sinus was impossible probably because of a marked fibrosis in the involved sinus. Then, we completely exposed the involved sinus through craniotomy. Through a microcatheter inserted into the sinus, the lower part of the sigmoid sinus was directly packed, and the remaining lesion was excised. Postoperative course was uneventful. Disappearance of dAVF resolved the findings on PET and MRI. Combined therapy would be a safe, non-invasive, and useful option for patients with a complex intracranial dAVF.

[Clinical manifestations of infantile moyamoya disease].

PURPOSE: The present study aimed to clarify clinical manifestations of infantile moyamoya disease by comparing them with those of schoolchild moyamoya disease. SUBJECTS AND METHODS: This study included a total of 55 patients who were diagnosed as moyamoya disease on cerebral angiography. Their medical records were precisely evaluated. CT or MRI was performed to examine the location of cerebral infarction in all subjects. Cerebral blood flow was measured in 33 patients before surgery, using the 133-xenon inhalation method and single photon emission computed tomography (SPECT). Postoperative full-scale IQ (FSIQ) was also examined. RESULTS: Of 55 patients, onset age was < 6 yr in 32 (infantile group) and > or = 6 yr in 23 (schoolchild group). Completed stroke was significantly more frequent in the infantile group than in schoolchild group (p = 0.0014). Incidence of cerebral infarct was also higher in the infantile group than in the schoolchild group (p = 0.0023). PCA stenosis/occlusion was observed in 14 of 32 infantile patients, but only in 4 of 23 schoolchild patients (p = 0.0474). Mean cerebral blood flow value was significantly lower than control value in the infantile group, but not in the schoolchild group. The effect of bypass surgery on cerebral ischemic attack was satisfactory in both groups. However, the postoperative FSIQ value was significantly lower in the infantile group than in the schoolchild group (p = 0.0452). CONCLUSIONS: The present study showed that infantile moyamoya disease involves a higher risk for cerebral infarct and completed stroke due to its more advanced stage, and that earlier diagnosis and treatment should be performed to improve the mental prognosis of patients.

[Clinical features and outcomes of 10 asymptomatic adult patients with moyamoya disease].

Recent development of non-invasive diagnostic technology, such as magnetic resonance imaging (MRI) and angiography (MRA), is believed to have made possible on increase in the diagnoses of asymptomatic moyamoya disease. However, no criteria have been established for the management of such cases. The present study aimed to clarify the natural history of asymptomatic moyamoya disease retrospectively. Ten patients were included in this study. None of them had experienced any episode due to moyamoya disease and were only incidentally diagnosed as having moyamoya disease. There were 4 males and 6 females. Their ages ranged from 30 to 67 years, with the mean age of 46.2. Cerebral angiography showed there was the tendency of disease progression in elder patients. MRI detected cerebral infarction in 3 of 10 patients (30%). Hemodynamic ischemia, such as impaired reactivity to acetazolamide and/or elevated oxygen extraction fraction, was observed in 4 of 10 patients. Only one patient underwent surgical revascularization. Antiplatelet or anticonvulsant medication was administered in 5 of 10 patients. The mean follow-up period was 4.1 years, ranging from 0.5 to 13 years. During follow-up periods, the moyamoya lesion markedly progressed and caused cerebral infarction in one patient. However, neither ischemic nor hemorrhagic stroke occurred in the other 9 patients. Multi-center nation-wide study should be planned to clarify the natural course of asymptomatic moyamoya disease and establish the management guidelines for patients with asymptomatic moyamoya disease.