Caucasian Familial Moyamoya Syndrome With Rare Multisystemic Malformations

Moyamoya disease is an idiopathic progressive steno-occlusive disorder of the intracranial arteries located at the base of the brain. It is associated with the development of compensatory extensive network of fine collaterals. Moyamoya disease is considered syndromic when certain genetic or acquired disorders such as polycystic kidney disease, neurofibromatosis, or meningitis are also present. Although the genetic contribution in moyamoya is indisputable, its cause and pathogenesis remain under discussion. Herein, we report a rare occurrence of moyamoya syndrome in two European Caucasian siblings in association with unusual multisystemic malformations (polycystic kidney disease in one, and intestinal duplication cyst in the other). The karyotype was normal. No mutation in the RFN213 gene was found, and none of the HLA types linked to moyamoya disease or described in similar familial cases were identified. By describing these multisystemic associations, polycystic kidney disease for the second time, and intestinal malformation for the first time in the literature, our report expands the phenotypic variability of moyamoya syndrome. The coexistence of disparate malformations among close relatives suggests an underlying common genetic background predisposing to structural or physiological abnormalities in different tissues and organs.     

Disappearance of aneurysms associated with moyamoya disease after STA-MCA anastomosis with encephaloduro myosynangiosis

Moyamoya disease is a rare cerebrovascular disease characterized by steno-occlusive vasculopathy affecting the terminal internal carotid arteries. Although the effect of direct arterial bypass on the prevention of recurrent haemorrhage or ischemic events in patients with hemorrhagic moyamoya disease has been demonstrated, disappearance of aneurysms associated with moyamoya disease has rarely been reported. In this study, we present two patients with aneurysms associated with moyamoya disease. After superficial temporal artery to middle cerebral artery anastomosis combined with encephaloduro myosynangiosis, the aneurysms on the moyamoya vessels disappeared, which was confirmed by follow-up angiography.     

Intracranial hemorrhage in patients with polycystic kidney disease

To emphasize the important association of polycystic kidney disease and hypertensive cerebral hemorrhage, a registry of 900 consecutive cases of hemorrhagic stroke was reviewed. Eleven patients (1.2%) had intracranial hemorrhage (eight had hypertensive cerebral hemorrhage and the other three had aneurysmal subarachnoid hemorrhage) found to be associated with polycystic kidney disease. These 11 patients also accounted for 11% of the 98 cases of polycystic kidney disease during the 28-month study period. As verified by computed tomography, parenchymal hemorrhage occurred mainly in the putamen and the thalamus, the usual sites for hypertensive cerebral hemorrhage. One patient with cerebral hemorrhage was autopsied and one was studied angiographically, but in neither patient was an intracranial aneurysm identified. In the patients with polycystic kidney disease and intracranial hemorrhage, hypertension had been inadequately treated or even undetected; therefore, I emphasize early detection and more effective control of hypertension in patients with polycystic kidney disease for prophylaxis against hemorrhagic cerebrovascular events.     

Linkage analysis of moyamoya disease on chromosome 6

Genetic factors have been suggested to contribute to the etiology of moyamoya disease. The authors have previously reported an association between moyamoya disease and several alleles for human leukocyte antigens (HLA). To further specify the genetic component of moyamoya disease, a linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, was performed. The 15 microsatellite markers of chromosome 6 were studied in 20 affected sibling pairs. From an identical-by-descent analysis of these markers, an allele with possible linkage to moyamoya disease was identified. Sharing of the allele among affected members in 19 families was investigated, considering the haplotype. The marker, D6S441, might be linked to moyamoya disease. Considering the haplotype, the allele was shared among the affected members in 16 (82%) of the 19 families, but not in two others. In one family, sharing of the allele could not be determined because of low heterozygosity. Further studies are necessary to clarify multiple genetic factors that are definitely linked with moyamoya disease.     

Cystic neurohypophysial germinoma associated with moyamoya disease

Moyamoya disease associated with a germinoma has never yet been reported in the literature. This report describes a case of a cystic neurohypophysial germinoma associated with moyamoya disease. A 15-year-old girl with central diabetes insipidus was admitted to the hospital. Radiological examination revealed a suprasellar tumor and moyamoya disease. Surgery and pathological study confirmed pure germinoma. After the patient was treated with radiation and chemotherapy, the tumor was controlled without any effect on the moyamoya vessels. This report describes a rare incidental combination of moyamoya disease and a suprasellar germinoma. In the management of such cases, physicians should be aware of the symptoms, course, and natural history of both diseases and the effects and side effects of each type of therapy.     

Moyamoya disease in children

Moyamoya disease is an uncommon cerebrovascular disease characterized by progressive steno-occlusive changes in the terminal internal carotid arteries (ICA) and their main branches, associated with the development of moyamoya vessels. The incidence of the disease is high in east Asia, especially in Japan and Korea. The familial form accounts for 10-15%. Moyamoya disease has two age distribution peaks at around 5 and 40 years. Most pediatric patients exhibit transient ischemic attacks or infarction. Headache and involuntary movements are serious symptoms associated with pediatric moyamoya disease. MRI and MR angiography (MRA) are useful and non-invasive methods for diagnosing or monitoring moyamoya disease. Cerebral angiography is still the gold standard for a diagnosis, however, it is not mandatory when MRI and MRA show typical findings of moyamoya disease; steno-occlusive changes at the ends of ICA and an abnormal vascular network in the basal ganglia. Other MRI findings have been reported, including T2 shortening in the white matter, the ivy sign on fluid-attenuated inversion recovery (FLAIR) images, and medullary streaks on FLAIR or enhanced T1-weighted images.     

Moyamoya disease in childhood: a familial case report

Moyamoya 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. No 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 moyamoya with clinical onset of the neurological symptoms within the 3rd year of life; during the child's illness the maternal grandmother presented with moyamoya 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.     

Moyamoya disease

The authors reviewed the Japanese literature on moyamoya disease. In the article we discuss the history of such investigations in Japan, the signs and symptoms, the diagnosis (especially concerning diagnostic criteria and magnetic resonance imaging), the pathology in relation to its etiology, and the current methods of treatment. On the whole, the main aim of the paper was to introduce our concept of moyamoya disease that is now current in Japan.     

Moyamoya disease associated with hemoglobin Fairfax and beta-thalassemia

Moyamoya disease is a rare cerebrovascular condition characterized by steno-occlusive disease of the major intracranial arteries at the base of the brain, and the appearance of innumerable, tiny, arterial collaterals that resemble a "puff of smoke." Although it has been associated with hematologic diseases such as sickle-cell disease, the association with other hemoglobinopathies is less frequently observed. We describe the association of a unique hemoglobinopathy (hemoglobin Fairfax) with beta-thalassemia and moyamoya disease in a 9-year-old girl with a history of stroke. To our knowledge, this is the first report of this unstable hemoglobin with moyamoya disease, and it emphasizes the potential for cerebral infarction due to the severe anemia of hemolytic disease.     

Renal agenesis and external iliac artery stenosis in an infant with moyamoya disease

We describe a 14-month-old girl who presented with arterial ischemic stroke due to moyamoya disease, unilateral renal agenesis and external iliac artery stenosis. The association of moyamoya disease with renal agenesis and external iliac artery stenosis has not been described before. This report expands the spectrum of moyamoya disease and suggests that moyamoya disease may have an intrauterine onset.     

Familial hypertensive intracerebral hemorrhage and autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a generalized disease known to be associated with intracranial aneurysms. Non-aneurysmal intracerebral hemorrhage (ICH) has also been reported in ADPKD. We report a familial clustering of ICH and symptomatic ADPKD. This pedigree had at least six affected family members who suffered from ADPKD, hypertension and non-aneurysmal ICH. The proband demonstrated ADPKD, hypertension and cerebral hemorrhage. To our knowledge, this is the first report of familial ICH in ADPKD, which may have underlying genetic and environmental etiologies.     

Childhood moyamoya disease and moyamoya syndrome: a pictorial review

Moyamoya disease is an uncommon chronic cerebrovasculopathy, characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches, in association with the development of compensatory collateral vessels at the base of the brain. The etiology is unknown, and was originally considered exclusive to East Asia, with particular prevalence in Japan. Moyamoya disease is increasingly diagnosed throughout the world, and represents an important cause of childhood stroke in Western countries. In some cases, similar angiographic features are evident in children with other medical conditions, such as sickle cell disease and Down syndrome. In these instances, the term "moyamoya syndrome" is used. Diagnosing the vasculopathy, excluding possible associated conditions, and planning treatment and follow-up imaging comprise important aspects of clinical management. We review the key imaging features of childhood moyamoya disease and syndrome, present examples of its associations, and discuss new neuroradiologic methods that may be useful in management.     

Moyamoya disease associated with Behcet's disease.

A 32-year-old woman with Behcet's disease suffered repeated transient ischemic attacks (TIA) consisting of left hemiparesis. Cerebral angiography revealed the typical findings of moyamoya disease, with occlusion of the supraclinoid portion of both internal carotid arteries, coupled with abnormal collateral vessels. She underwent right superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalomyosynangiosis, due to decreased reserve capacity demonstrated on acetazolamide single positron emission computed tomography (SPECT). Postoperatively, the TIA symptoms subsided. This is the first report of moyamoya disease associated with Behcet's disease, and moyamoya disease should be considered in the differential diagnosis of cerebrovascular events in patients with Behcet's disease. Revascularization surgery is recommended for the prevention of ischemic insults resulting in permanent deficits.     

Pathological study of Willis's circle in autopsy cases of polycystic kidney disease

Two autopsy cases of polycystic kidney disease with intracranial aneurysms were reported. We made a pathological study of their vascular system with special reference to Willis's circle in order to prove the inherent abnormality of vascular system in patients with polycystic kidney disease. A 57-year-old man was revealed to have polycystic kidney disease with left middle cerebral artery aneurysm and aortic stenosis. The other 58-year-old man was revealed to have polycystic kidney disease with cerebral aneurysms both in anterior communicating artery and basilar artery, aortic dissecting aneurysm, cerebral infarction and myocardial infarction. Histologically, both abrupt interruption and partial disappearance of internal elastic lamina are found frequently in the wall of Willis's circle. This abnormality of internal elastic lamina may be attributable to congenital factors and rise the frequency of occurrence of intracranial aneurysms in polycystic kidney disease.     

De novo appearance of cerebellar cavernous malformation in a patient with moyamoya disease: case report and review of the literature

The authors report a case of cerebellar cavernous malformation associated with moyamoya disease. An adolescent male with moyamoya disease had undergone bilateral direct and indirect extracranial-intracranial anastomosis at 11 years of age, and the course had been uneventful until MRI detected the appearance of a cavernous malformation in the cerebellum 3 years later. The lesion had grown, bled, and caused headache and disturbance of consciousness 2 years after the initial detection. The cavernous malformation was removed surgically and pathologically verified. The patient has recovered without any neurological deficits. This is a quite rare case with cavernous malformation which appeared in a moyamoya disease patient. The association of the two different vascular disorders in a young patient may suggest the existence of some interaction in the pathogenesis of these diseases. Since cavernous malformations with a de novo appearance may grow and become clinically significant, careful observation is necessary.     

Pediatric moyamoya disease presenting with intracerebral hemorrhage--report of three cases and review of the literature

Intracerebral hemorrhage in patients with moyamoya disease is rare in children. We report three unique cases of pediatric moyamoya disease with hemorrhagic onset. Two 7-year-old girls and a 9-year-old girl were admitted to our hospital because of intracerebral hemorrhage associated with angiographically verified moyamoya disease. Two of them did not demonstrate either an ischemic episode or cerebral infarct on the magnetic resonance images. A decreased regional cerebral blood flow was revealed on single photon emission computed tomography in two patients, who developed cerebral infarction in the acute stage following hemorrhage. They underwent superficial temporal artery-middle cerebral artery anastomoses combined with encephalo-myo-synangiosis, and have not experienced any further ischemic episodes thereafter. Hemodynamic insufficiency associated with moyamoya disease could cause intracerebral hemorrhage even in children. Adequate management in the acute stage of hemorrhage and revascularization surgery are recommended to prevent cerebral infarction, which may easily occur in pediatric patients with moyamoya disease.     

Adult polycystic kidney disease and arachnoid cyst formation: Case report.

A 34 year old man is reported with adult polycystic kidney disease with an associated extensive arachnoid cyst occupyingmost of his left hemicranium. The aetiology of arachnoid cyst formation is discussed.     

Moyamoya disease: current concepts and future perspectives

Moyamoya disease is an uncommon cerebrovascular disease that is characterised by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. The disease is associated with the development of dilated, fragile collateral vessels at the base of the brain, which are termed moyamoya vessels. The incidence of moyamoya disease is high in east Asia, and familial forms account for about 15% of patients with this disease. Moyamoya disease has several unique clinical features, which include two peaks of age distribution at 5 years and at about 40 years. Most paediatric patients have ischaemic attacks, whereas adult patients can have ischaemic attacks, intracranial bleeding, or both. Extracranial-intracranial arterial bypass, including anastomosis of the superficial temporal artery to the middle cerebral artery and indirect bypass, can help prevent further ischaemic attacks, although the beneficial effect on haemorrhagic stroke is still not clear. In this Review, we summarise the epidemiology, aetiology, clinical features, diagnosis, surgical treatment, and outcomes of moyamoya disease. Recent updates and future perspectives for moyamoya disease will also be discussed.     

Intraaneurysmal embolization of an unruptured basilar tip aneurysm associated with moyamoya disease.

We describe a patient with moyamoya disease associated with an unruptured basilar tip aneurysm which was treated by endovascular embolization using Guglielmi detachable coils (GDCs). A 53-year-old man presented with left hemiparesis persisting for 3 mon ths before admission. Cerebral angiography revealed occlusion of the bilateral middle cerebral arteries and the left anterior cerebral artery, stenosis of the right anterior cerebral artery, and basal moyamoya vessels. In addition, a saccular small aneurysm was seen at the top of the basilar artery. The aneurysm was completely embolized by intraaneurysmal GDCs. Direct surgical clipping is often selected for the treatment of posterior fossa aneurysms in moyamoya disease. However, complete clipping is usually difficult due to the difficulties in operative technique associated with moyamoya disease. We suggest that the endovascular treatment using GDCs is comparatively safe and effective for the treatment of surgically difficult aneurysms in patients with moyamoya disease.     

Plasma fibronectin level in patients with moyamoya disease

Moyamoya disease is generally considered as a slowly progressive occlusive disease of the circle of Willis. Pathological investigation has revealed that the occlusion develops due to fibrocellular thickening of the intima. In spite of various studies, however, the etiology of this disease and the mechanism of the intimal thickening remain unknown. Fibronectin (FN) is a high molecular weight glycoprotein which is found in an insoluble form in many tissues and in a soluble form in plasma and other body fluids. FNs have many biological activities and play an important role in the formation of connective tissue under physiological and pathological conditions. In the present study we have determined the plasma FN levels in order to investigate the relationship between FN and moyamoya disease. The subjects were 39 patients with moyamoya disease who were in the chronic stage after reconstructive surgery, 39 age- and sex-matched normal healthy controls, and 39 patients with atherosclerotic cerebrovascular disease in the chronic stage. The plasma FN levels were measured by the single radial immunodiffusion method using venous blood samples. The plasma FN level in healthy subjects was 33.9 +/- 6.3 mg/dl (mean +/- standard deviation) which almost agreed with the level, 30-35 mg/dl, reported by some investigators. In the patients with moyamoya disease the level was 42.5 +/- 7.9 mg/dl, showing a significant increase (p less than 0.001) compared with the healthy subjects. Then the subjects were classified into a child group (15 years or younger) and an adult group (16 years or older) and their levels were examined.(ABSTRACT TRUNCATED AT 250 WORDS)