Naomi Fukai

A new surgical treatment of moyamoya disease in children: A preliminary report

A new operative method, encephalo-duro-arterio-synangiosis, for the surgical treatment of pediatric moyamoya disease has been developed. The rationale of the operation is to help promote the natural tendency of this disease to develop cerebrovascular collaterals. The method is to transplant a scalp artery with a strip of galea, leaving the distal as well as the proximal arteries intact, to a narrow linear dural opening made under an osteoplastic craniotomy. A representative case is described and the operative procedure is outlined. Our new method is compared with other surgical treatments of this disease.

Early Development of Intimal Thickening in Superficial Temporal Arteries in Patients With Moyamoya Disease

BACKGROUND AND PURPOSE Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs in children. The etiology is unknown. We examined the superficial temporal arteries from patients with moyamoya disease, particularly children, to determine whether the extracranial arteries as well as the intracranial arteries are involved in this disease. METHODS Small branches of the superficial temporal arteries were obtained from 22 patients with moyamoya disease during indirect arterial bypass surgery. Histological examinations were performed, and the findings were compared with those of arteries from 12 control patients. RESULTS Intimal thickening was observed in 9 of 17 patients with moyamoya disease younger than 20 years but in none of 7 control patients under the age of 20 years (P < .02, Fishers exact test). Intimal thickening appeared from age 20 years in control patients. The arteries of moyamoya patients showed fibrocellular intimal thickening with a paucity of lipid. The arteries from moyamoya patients contained strongly stained multilayered elastic fibers in the thickened intima, while those from control patients showed only weakly stained elastic fibers in the intima. CONCLUSIONS Our findings suggest that moyamoya disease is a systemic vascular disease. The results indicate systemic etiologic factors that may promote the early development of intimal thickening in moyamoya disease.

Increase in Elastin Gene Expression and Protein Synthesis in Arterial Smooth Muscle Cells Derived From Patients with Moyamoya Disease

BACKGROUND AND PURPOSE Moyamoya disease is a progressive cerebrovascular occlusive disease that is rare in all ages but frequently presents in children. The etiology of the disease is unknown. We examined elastin gene transcripts and elastin synthesis in cultured arterial smooth muscle cells (SMCs) derived from moyamoya patients and compared them with those in SMCs from age-matched control subjects. METHODS We used six cell strains from moyamoya patients and four from controls. The expression of elastin protein was observed by Western blot analysis and metabolic labeling with 3H-valine. Elastin gene transcripts were identified by Northern blot analysis. RESULTS Elastin mRNA and protein levels were elevated in all SMCs from moyamoya patients compared with control SMCs. Although transforming growth factor-beta 1 (TGF-beta 1), a potent enhancer of the expression of elastin in arterial SMCs, upregulated elastin mRNA and protein levels in SMCs from both moyamoya patients and control subjects, the maximum levels of elastin synthesis and elastin gene transcripts in response to exogenous TGF-beta 1 were significantly greater in moyamoya SMCs than control SMCs. In addition, quiescent moyamoya SMCs secreted significantly more TGF-beta 1 into the culture medium than quiescent control SMCs (P < .01). CONCLUSIONS Our findings suggest that moyamoya disease may result, at least in part, from an abnormal regulation of extracellular matrix metabolism that leads to increased steady state levels of elastin mRNA and elastin accumulation in the intimal thickening and that increased elastin accumulation is a stable marker of SMCs from patients with moyamoya disease.

Increase in Prostaglandin E2 Production by Interleukin-1β in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease

Abstract—Moyamoya disease is a progressive cerebrovascular occlusive disease that primarily affects children. The cause is unknown. We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and 8 control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated with interleukin-1β (IL-1β), prostaglandin E2 (PGE2) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, whereas the amounts of prostacyclin and thromboxane B2 did not differ. IL-1β–induced PGE2 production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1β significantly stimulated cell migration and DNA synthesis in control SMCs but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migratio...

Differences in Cellular Responses to Mitogens in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease

BACKGROUND AND PURPOSE Moyamoya disease is a progressive cerebrovascular occlusive disease affecting primarily children. The etiology remains unknown. We examined the chemotactic and proliferative activities of inflammatory cell products from arterial smooth muscle cells (SMCs) derived from moyamoya patients and compared them with those from control subjects. METHODS We used 12 SMC strains from moyamoya patients and eight from control subjects. SMC migration was examined in a micro chemotaxis chamber. DNA synthesis was measured by an immunoperoxidase technique. RESULTS Platelet-derived growth factor (PDGF)-BB markedly stimulated cell migration and DNA synthesis in control SMCs. PDGF-AA stimulated only DNA synthesis in control SMCs. In moyamoya SMCs, PDGF-AA and PDGF-BB stimulated cell migration but not DNA synthesis. Basic fibroblast growth factor had little migratory activity but stimulated DNA synthesis in moyamoya SMCs and control SMCs. Conversely, hepatocyte growth factor stimulated cell migration but not DNA synthesis in moyamoya SMCs and control SMCs. In contrast, interleukin-1 beta (IL-1 beta) significantly stimulated the migration and DNA synthesis of control SMCs, while it inhibited moyamoya SMC migration. The levels of IL-1 beta-induced nitric oxide production did not differ between moyamoya SMCs and control SMCs, suggesting that IL-1 beta inhibits the migration of moyamoya SMCs through a nitric oxide-independent pathway. CONCLUSIONS The differences in responses to PDGF and IL-1 in moyamoya SMCs are involved in the mechanism by which intimal thickening develops in moyamoya disease.

Development of intimal thickening in superficial temporal arteries in patients with Moyamoya disease

To investigate the possible mechanism of neointimal formation in Moyamoya disease, we histologically examined the superficial temporal arteries and also investigated cultured smooth muscle cells (SMCs) from the arteries. Intimal thickening of the scalp arteries developed significantly at an early age in Moyamoya patients compared with control subjects. The histopathological findings of the neointima in scalp arteries were almost similar to those in intracranial arteries in Moyamoya patients. SMCs cultured from Moyamoya arteries responded significantly less to serum mitogens, especially to platelet derived growth factor (PDGF), than those of control patients, the finding of which was explained by the reduced number of PDGF receptor on Moyamoya SMCs. Our findings indicate the presence of systemic factors that promote migration and proliferation of SMCs from the media to the intima in Moyamoya disease. Our results suggest that alteration in vascular cells may contribute to the development of intimal thickening in Moyamoya disease.

Human arterial smooth muscle cell strains derived from patients with moyamoya disease: changes in biological characteristics and proliferative response during cellular aging in vitro

Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs frequently in children. The etiology is unknown. We examined changes in biological characteristics and responsiveness to serum mitogens during the in vitro cellular aging of arterial smooth muscle cell strains derived from patients with moyamoya disease (HMSMC) and compared them with those of cells from age-matched control patients (HCSMC). HMSMC had a normal human diploid chromosome constitution. HMSMC and HCSMC had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the doubling time at the early passages was significantly longer in moyamoya SMC than control SMC, although there was no significant difference at the late passages. Furthermore, the poor responsiveness of moyamoya SMC to platelet-derived growth factor was retained throughout the life span in vitro. These results support the hypothesis that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.

Retroflexed Holoprosencephaly: X-ray CT findings and MRI findings

Holoprosencephaly is a developmental field defect of the embryonic prosencephalon, associated with malformation of the telencephalon and diencephalon. The condition can be graded according to the degree of severity as alobar, semilobar, and lobar holoprosencephaly. We report a case of lobar type holoprosencephaly with retroflexion and discuss the usefulness of X-ray CT and MRI in its diagnosis.