Novel epidemiological features of moyamoya disease.

BACKGROUND: Many clinical features that are specific to moyamoya disease have been reported and cited in textbooks based on previous data. The purpose of this study is to investigate the present epidemiological features of moyamoya disease based on recently obtained regional all-inclusive data. METHODS: The authors performed an all-inclusive survey of moyamoya disease in Hokkaido, one of the major islands in Japan that has a population of 5.63 million. The epidemiological features were analysed based on the data from 267 newly registered patients with moyamoya disease in Hokkaido from 2002 to 2006. These analysed data were adjusted to the whole Japanese population at 2005. RESULTS: The detection rate of the disease per year was 0.94 patients per 100,000 people, and prevalence was 10.5 patients per 100,000 people. The incidence of ischaemia concerned with the disease was 0.53 patients per 100,000 people-years and haemorrhage was 0.2 patients per 100,000 people-years. The ratio of female to male patients was 2.18. The ratio of patients aged 10 years and above to under 10 years of age at onset was 6.18. Two peaks for age of onset were seen: the highest was observed between 45 and 49 years, and the second between 5 and 9 years. Asymptomatic patients comprised 17.8% of the total number of patients. CONCLUSION: The epidemiological features of moyamoya disease determined by this survey varied considerably from previous data. The detection rate and prevalence of the disease were higher than those reported previously. The highest peak of onset age was older than those reported previously. In addition, it was revealed that asymptomatic moyamoya patients are not always rare in Japan.

Interstitial spinal-cord oedema in syringomyelia associated with Chiari type 1 malformations.

OBJECT: The pathophysiology of syringomyelia in Chiari type 1 malformations has not been clarified. Oedema-like spinal-cord swelling was recently reported in several pathological conditions, including Chiari type 1 malformations as a pre-syrinx state. However, the role of the pre-syrinx state in the development of syringomyelia is unknown. The purpose of this study is to investigate the parenchymal changes of the spinal cord in syringomyelia associated with Chiari type 1 malformations. METHODS: Pre- and postoperative MRI findings in 14 patients who underwent foramen magnum decompression in our institute were reviewed. The analysis was focused on differences in visualisation of the syrinx between T1- and T2-weighted images and abnormal parenchymal signal changes. There were 6 men and 8 women, aged from 6 to 79 years. No patients showed hydrocephalus. RESULTS: Twelve patients had large and expansive syrinx, whereas 2 patients showed small syrinx confined to the centre of the spinal cord. T2-weighted images displayed significantly larger intramedullary abnormal signal areas. Nine patients showed parenchymal hyperintensity areas around the enlarged central canal or base of the posterior white columns adjacent to the syringomyelic cavity. Such parenchymal hyperintensity areas markedly diminished with reduction of the syrinx after surgery and were considered to be interstitial oedema. CONCLUSIONS: From this study, the interstitial oedema of the spinal cord commonly accompanies syringomyelia with Chiari type 1 malformations. Accumulation of the extracellular fluid due to disturbed absorption mechanisms may play an important role in the pathophysiology of syringomyelia associated with Chiari type 1 malformations.

Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia.

Intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischaemia models. Placental growth factor (PlGF) is angiogenic to impaired non-neural tissue. To test the hypothesis that PlGF contributes to the therapeutic benefits of MSC delivery in cerebral ischaemia, we compared the efficacy of systemic delivery of human MSCs (hMSCs) and hMSCs transfected with a fibre-mutant F/RGD adenovirus vector with a PlGF gene (PlGF-hMSCs). A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. hMSCs and PlGF-hMSCs were intravenously injected into the rats 3 h after MCAO. Lesion size was assessed at 3 and 6 h, and 1, 3, 4 and 7 days using MR imaging and histology. Functional outcome was assessed using the limb placement test and the treadmill stress test. Both hMSCs and PlGF-hMSCs reduced lesion volume, induced angiogenesis and elicited functional improvement compared with the control sham group, but the effect was greater in the PlGF-hMSC group. Enzyme-linked immunosorbent assay of the infarcted hemisphere revealed an increase in PlGF in both hMSC groups, but a greater increase in the PlGF-hMSC group. These data support the hypothesis that PlGF contributes to neuroprotection and angiogenesis in cerebral ischaemia, and cellular delivery of PlGF to the brain can be achieved by intravenous delivery of hMSCs.

The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride inhibits acute platelet aggregation in injured endothelium.

In this study, the effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2A receptor antagonist, on platelet aggregation at the site of injured carotid artery endothelium was examined. The rat common carotid artery was clamped for 30 min to induce endothelial injury. Sarpogrelate hydrochloride was administered before and after the injury, and the effects were compared with those in rats receiving sham operation only and those receiving clipping injury but no sarpogrelate hydrochloride. The animals were killed 24 h after the procedure. The common carotid artery was examined by scanning electron microscopy and stained immunochemically for factor VIII. Sarpogrelate hydrochloride treatment was associated with reduced aggregation of platelets on electron microscopy and lower expression of factor VIII at the injured intima. Sarpogrelate hydrochloride has an inhibitory effect on platelet aggregation at the intima in the acute stage after injury, suggesting that this drug may be used to prevent early ischaemic complications after surgical or endovascular arterial intervention.

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Long-term prognosis of medically treated patients with internal carotid or middle cerebral artery occlusion: can acetazolamide test predict it?

BACKGROUND AND PURPOSE: The importance of hemodynamic parameters for predicting outcome in patients with occlusive carotid disease remains controversial. The present study was aimed at testing the hypothesis that regional cerebrovascular reactivity (rCVR) to acetazolamide can be a reliable predictor of subsequent ischemic stroke in medically treated patients with internal carotid artery or middle cerebral artery occlusion. METHODS: Seventy-seven symptomatic patients were enrolled in this prospective, longitudinal cohort study. All patients met inclusion criteria of cerebral angiography, no or localized cerebral infarction on MRI or CT, and no or minimal neurological deficit. Regional cerebral blood flow (rCBF) and rCVR to acetazolamide were quantitatively determined by (133)Xe SEPCT. All patients were categorized into 4 types on the basis of SPECT studies. RESULTS: During an average follow-up period of 42.7 months, 16 total and 7 ipsilateral ischemic strokes occurred. The annual risks of total and ipsilateral stroke in patients with decreased rCBF and rCVR were 35.6% and 23.7%, respectively, risks that are higher than those in other types of patients. When strokes were categorized into patients with and without decreased rCBF and rCVR, Kaplan-Meier analysis revealed that the risks of total and ipsilateral stroke in patients with decreased rCBF and rCVR were significantly higher than in those without (P<0.0001 and P=0.0001, respectively, log-rank test). Relative risk conferred by decreased rCBF and rCVR was 8.0 (95% CI, 1.9 to 34.4) for ipsilateral stroke and 3.6 (95% CI, 1.4 to 9.3) for total stroke. CONCLUSIONS: Decreased rCBF and rCVR to acetazolamide may identify a subgroup of patients who have a higher risk of subsequent ischemic stroke when treated medically.

Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation.

The origins of reflected light changes associated with neuronal activity (optical signals) were investigated in rat somatosensory cortex with optical imaging, microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local hemoglobin concentration and oxygenation were focused on. Functional activation was carried out by 2-second, 5-Hz electrical stimulation of the hind limb under chloralose anesthesia. These measurements were performed at the contralateral parietal cortex through a thinned skull. Regional cortical blood flow (rCBF) started to rise 1.5 seconds after the stimulus onset, peaked at 3.5 seconds (26.7% +/- 9.7% increase over baseline), and returned to near baseline by 10 seconds. Optical signal responses at 577, 586, and 805 nm showed a monophasic increase in absorbance coincident with the increase in rCBF; however, the signal responses at 605 and 760 nm were biphasic (an early increase and late decrease in absorbance) and microanatomically heterogeneous. The spectral changes of absorbance indicated that the concentrations of both total hemoglobin and oxyhemoglobin increased together with rCBF; deoxyhemoglobin, increased slightly but distinctly (P = 0.016 at 1.0 seconds, P = 0.00038 at 1.5 seconds) just before rCBF increases, then decreased. The authors conclude that activity-related optical signals are greatly associated with a moment-to-moment adjustment of rCBF and metabolism to neuronal activity.

Treatment outcome of single or hypofractionated single-isocentric stereotactic irradiation (STI) using a linear accelerator for intracranial arteriovenous malformation.

BACKGROUND AND PURPOSE: We investigated the use of hypofractionated stereotactic radiotherapy (HFSR) to reduce adverse radiation effects in comparison to single-fraction stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs). MATERIALS AND METHODS: This study includes 53 intracranial AVMs treated between 1991-1998. HFSR was selected for 26 AVMs with a maximum diameter > or 2.5 cm or at eloquent area. Twenty-seven patients were treated with SRS (18 AVMs < 2.5 cm at non-eloquent area, nine patients who were unfit for prolonged ring-wearing). The most frequent minimum dose (Dmin) was 20 Gy for SRS and 28 Gy for HFSR in four fractions. The mean follow-up duration was 34.6 months for SRS and 35.4 months for HFSR. RESULTS: As a whole, the 3 and 5-year actuarial obliteration rates were 64 and 92%. Age <20 years old (P=0.02) and a maximum diameter <2 cm were favorable factors (P=0.05). A difference in the distribution of patients was observed in size (> or =2.5 cm or not) (P<0.001) and location (eloquent or not) (P<0.001) between SRS and HFSR due to the treatment selection. However, no significant differences were observed in the actuarial rates of obliteration and transient increased signals with T2-weighted MR images between SRS and HFSR. Radiation necrosis occurred in two patients treated with SRS and in none with HFSR. Intracranial hemorrhage after treatment happened in two treated with SRS and three with HFSR. CONCLUSIONS: HFSR appears to be at least as effective as SRS in achieving complete obliteration of intracranial AVM, although its definitive role remains to be investigated.

Enhanced late components of AEFs associated with the temporal lobe lesions.

We recorded auditory evoked magnetic fields (AEFs) by presenting pure tone bursts once every 4000 ms in 11 patients with a brain lesion in or in the vicinity of the auditory cortex. AEFs on the damaged side revealed several enhanced deflections in late-latency AEFs (slow AEFs), peaking at approximately 320 (DI), 1030 (D2) and 1600 (D3) ms post-stimulus in eight patients. All the dipoles of slow AEFs were concentrated in the superior temporal regions which were not involved by brain lesions. D1, D2 and D3 dipoles were uniformly upward, downward and upward, respectively. The dipole moment varied from 12 to 122 nAm and had no consistent relationship with latency. This is the first report describing slow AEFs in cases with temporal lobe lesions.

The cerebrospinal fluid in patients with moyamoya disease (spontaneous occlusion of the circle of Willis) contains high level of basic fibroblast growth factor.

The level of basic fibroblast growth factor (bFGF) in cerebrospinal fluid (CF) was measured by an EIA in 15 patients with moyamoya disease, in 11 patients with atherosclerotic occlusive disease, and in 8 patients with spinal disc disease. In the moyamoya patients, bFGF was found in 13 out of 15 CF samples with a mean value of 101 pg/ml. However, bFGF was detected in only 4 out of 11 patients with atherosclerotic disease with a mean of 8 pg/ml. In all the patients with disc disease, bFGF was not detected. The elevated level of bFGF may play a crucial role in the pathogenesis of moyamoya disease.

Multiple varices in the unilateral cerebral venous system.

A case of multiple cerebral varices located in the superficial cerebral veins and ipsilateral internal jugular vein is reported.

Identification of central sulcus by using somatosensory evoked magnetic fields and brain surface MR images: three dimensional projection analysis.

We present a novel non-invasive technique for identification of the central sulcus on the brain surface by using three-dimensional magnetic resonance imaging (3D-MRI) in combination with somatosensory evoked magnetic fields (SEFs). The central sulcus was supposed anatomically on the brain surface by using 3D-MRI. On the other hand, the primary somatosensory area is determined by using SEF data with median nerve stimulation. Superimposition of the SEFs of the 25 ms response onto the brain surface MR images clearly demonstrated the dipole source located in the gyral fold just behind the supposed central sulcus in all subjects analyzed. Three-dimensional reconstruction of the brain surface image data facilitated visualizing the precise anatomical localization of the magnetic field activities from any angle and measuring the distance from the source to any point of interest. The potential clinical application of this technique is discussed.

Effects of surgical revascularization on peripheral artery aneurysms in moyamoya disease: report of three cases.

OBJECTIVE AND IMPORTANCE: The beneficial effects of surgical revascularization on rebleeding in moyamoya disease remain unclear. This report is intended to clarify the effects of surgical revascularization on peripheral artery aneurysms, which represent one of the causes of intracranial bleeding in moyamoya disease. CLINICAL PRESENTATION: Findings for three female patients who experienced intracranial bleeding are presented. Cerebral angiography revealed that intracranial bleeding resulted from the rupture of peripheral artery aneurysms arising from dilated collateral vessels such as the lenticulostriate artery. INTERVENTION: The patients successfully underwent superficial temporal artery-middle cerebral artery anastomosis combined with encephaloduromyoarteriosynangiosis. Angiography demonstrated obliteration of the peripheral artery aneurysms, together with the disappearance or decrease in caliber of the parent collateral arteries, after surgery. None of the patients experienced rebleeding during the follow-up period (up to 52 mo). CONCLUSION: The results strongly suggest that surgical revascularization potentially improves cerebral circulation and decreases hemodynamic stress on collateral vessels, obliterating peripheral artery aneurysms.

Pathological consideration of a "blister-like" aneurysm at the superior wall of the internal carotid artery: case report.

OBJECTIVE AND IMPORTANCE: Although the incidence is low, a very small aneurysm with a thin wall and no neck arises at the superior wall of the supraclinoid portion of the internal carotid artery and is called a "blister-like" aneurysm. However, the pathogenesis of such a vascular lesion remains uncertain. CLINICAL PRESENTATION: A 57-year-old man developed a fatal subarachnoid hemorrhage caused by the rupture of a blister-like aneurysm at the superior wall of the internal carotid artery. An autopsy was performed, and the lesion was pathologically examined. RESULTS: The internal elastic lamina and media had disappeared at the border between the eccentrically sclerotic and normal carotid wall. The gap in the internal elastica was covered with normal adventitia and fibrinous tissue. This portion was not composed of collagenous tissue as ordinarily seen in an aneurysmal wall. Neither infiltration of inflammatory cells nor dissection of the artery were observed. CONCLUSION: The blister-like aneurysm appeared to be a laceration of the carotid wall based on degeneration of the internal elastic lamina.

Ruptured dissecting vertebral artery aneurysm detected by repeated angiography: case report.

A case of a ruptured dissecting aneurysm of the vertebral artery, which was detected by repeated angiography (third time), is reported. A 59-year-old woman, whose preoperative angiogram showed no abnormality, underwent a bifrontal craniotomy and the total removal of the right frontal glioma. However, a subarachnoid hemorrhage was detected by computed tomography the day after the surgery. Conventional angiography performed on the same day revealed no definite abnormality. Nevertheless, 9 days after surgery, a second subarachnoid hemorrhage occurred. The dissecting aneurysm of the vertebral artery was revealed by angiography. It is important to suspect this type of aneurysm as a differential diagnosis when the cause of the subarachnoid hemorrhage is not clarified in the first angiogram.

Vascular reconstruction using interposed small vessels.

OBJECTIVE: This study presents the relationship between the patency of short-vessel graft bypasses and their diameter/length. METHODS: The authors performed interposed graft bypass operations using small vessels for four patients with moyamoya disease, six patients with cerebral thrombosis, and one patient with aortitis syndrome. The donor artery was the superficial temporal artery (10 patients) or the occipital artery (1 patient), and the recipient artery was the cortical branch of the middle cerebral artery (8 patients) or the cortical branch of the anterior cerebral artery (3 patients). The interposed graft used between these donor and recipient vessels was the superficial temporal vein (seven patients), the superficial temporal artery (three patients), or the epigastric artery (one patient). RESULTS: Good patency of the graft was confirmed for 7 of these 11 patients. Regarding the relationship between the diameter/length and the patency, we found that long-term patency could not be expected when the discriminant function of y = (15.39 x diameter) - (0.35 x length) - 14.37 was below zero. CONCLUSION: Short-vessel graft bypass is a practical option for cerebral revascularization surgery when short large vessels are used.

Transverse cervical artery bypass pedicle for treatment of common carotid artery occlusion: new adjunct for revascularization of the internal carotid artery domain.

OBJECTIVE: We present two cases of common carotid artery occlusion that were treated by vascular reconstruction using the transverse cervical artery. METHODS: Two patients with common carotid artery occlusion presented with transient ischemic attacks resulting from decreased cerebral blood flow on the affected side. Both patients underwent vascular reconstruction using the transverse cervical artery. The transverse cervical artery was anastomosed to the ipsilateral external carotid artery at its origin, as a pedicle graft. A superficial temporal artery-middle cerebral artery anastomosis was then performed. RESULTS: The postoperative courses were uneventful. The transverse cervical artery bypass grafts were patent, and cerebral blood flow increased to normal levels. CONCLUSION: Transverse cervical artery grafting provides a less tedious alternative to saphenous vein interposition grafting for revascularization of the internal carotid artery domain.

Visualization of the ostium of an arteriotomy in bypass surgery.

Visualization of the ostium of an arteriotomy by staining it blue with methylrosaniline chloride (pyoctaninum blue) in anastomotic bypass surgery for children with moyamoya disease is described. This technique enables surgeons to create an anastomosis more precisely and quickly. No adverse effects were observed.

Induction of macrophage migration inhibitory factor messenger ribonucleic acid in rat forebrain by reperfusion.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a cytokine that has the potential to immobilize and activate monocytes/macrophages. To examine whether MIF may potentially be involved in the pathogenesis of reperfusion injury of the brain, we investigated the expression of MIF in a rat model of reperfusion. METHODS: A four-vessel occlusion procedure was performed for 30 minutes using male Wistar rats to obtain a moderate reperfusion in the forebrains. Semiquantitatively calibrated reverse-transcription polymerase chain reaction analysis was conducted to examine temporal profiles of messenger ribonucleic acid (mRNA) expression for MIF and macrophage chemoattractant protein 1. MIF protein assays expression was assessed with specific Western blot analysis. For anatomic mapping of MIF, an immunohistochemical study was performed. RESULTS: Reverse-transcription polymerase chain reaction demonstrated that the mRNA level of MIF increased depending on the duration of reperfusion (< or = 24 h) subsequent to global ischemia. The macrophage chemoattractant protein 1 mRNA was also observed to increase after reperfusional stress, but its maximum expression was reached earlier (1 h after the stress) than was MIF mRNA. Increase of MIF protein was also shown by Western blot. MIF-positive staining was observed in the neuronal processes (neuropil) in the cortex and basal growth ganglia of a rat forebrain. CONCLUSION: This protein is up-regulated and may modulate immunological reaction in secondary brain damage after ischemia and reperfusion stress.

Intracranial aneurysms associated with aortitis syndrome: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Aortitis syndrome is a systemic vasculitis of unknown etiology, affecting mainly the major branches of the aorta and leading to stenosis or occlusion. Intracranial aneurysms are rarely associated with this syndrome. Only 15 cases have been previously reported. CLINICAL PRESENTATION: A 54-year-old woman with a 10-year history of aortitis syndrome demonstrated nonruptured cerebral aneurysms in the left internal carotid and anterior communicating arteries, with decreased flow in the right internal carotid artery and ipsilateral A1 segment. INTERVENTION: The patient underwent clipping of the aneurysms through a left pterional craniotomy and transsylvian approach. CONCLUSION: In our review of 16 reported cases, including the present case (13 with ruptured aneurysms and 3 with nonruptured aneurysms), there were 25 saccular aneurysms, and we noted the following clinical characteristics: 1) patient age was 26 to 64 years, with an average of 50.2 years; 2) aneurysms arose predominantly along the course of collateral flow, especially in the vertebrobasilar system (13 of 25 aneurysms, 52.0%); 3) there was a high incidence of multiplicity (7 of 16 cases, 43.8%). These characteristics suggest that increased hemodynamic stress, produced by stenosis or occlusion of the major branches of the aorta and systemic hypertension, plays an important role in the development of cerebral aneurysms in patients with this syndrome.