Clinical Characteristics Of Hemorrhagic Moyamoya Disease And The Changes Of BFGF And VEGF In CSF In Patients With Moyamoya Disease

Moyamoya disease(moyamoya disease,MMD) is a kind of unexplained chronic progressive stenosis to occlusion at the apices of the intracranial internal carotid arteries,including the proximal anterior cerebral arteries and middle cerebral arteries,with associated development of a fragile network of basal collateral vessels, resulting in successive ischemic or hemorrhagic events.Children moyamoya patients usually present with TIAs or strokes.In contrast,adult often present with hemorrhage, the majority of which are intra-ventricular or the basal ganglia in location.Moyamoya disease was divided into 4 types:transient ischemic attack(TIA) type,infarction type, epilepsy type and hemorrhage type.There is an obvious regional and ethnic difference in the distribution of moyamoya disease.The clinical data of patients with moyamoya disease in our country is still imperfect at present.Part 1 Clinical features of hemorrhagic moyamoya diseaseIn order to explore the clinical features of hemorrhagic moyamoya disease,we analyzed 127 cases of patients,which were diagnosed with hemorrhagic moyamoya disease by DSA,TCCS and CT at neurosurgery department of Wuhan General Hospital of Guangzhou Command from January 2002 to December 2008.We analyzed the clinical data and obtained the following results:The gender distribution of cases in this group:65 cases were male,accounting for 51.2%;female,62 cases,accounting for 48.8%;male/female ratio was 1.05:1,age 7-73 years old.The age span of patients is 66 years,and the average age is 38.35±10.10 years.The coefficient of skewness is 0.199.The kurtosis coefficient is 1.696. The age span of male patients is 54 years.The average age is 37.14±9.80 years.The skewness coefficient is -0.526.The kurtosis coefficient is 1.569.The age span of female patients is 57 years.The average age is 39.63±10.32 years.The skewness coefficient is 0.827.The kurtosis coefficient is 1.431.The incidence of hemorrhagic moyamoya disease is relatively high among the patients between 30 to 49 years old, which is accounted for 75.6%of the total patients.127 cases of patients in this group are located in Hubei,Hunan,Henan,Anhui and Jiangxi Province,most of whom are located in the southeastern part of Hubei Province,such as Wuhan,Huangshi,Ezhou,Huanggang,and Xiaogan.The symptoms and signs of patients included headache and vomiting(127 cases), consciousness barrier(103 cases) and hemiplegia(38 cases).From CT image,we found that 51 cases were suffered with purely intraventricular hemorrhage(40.1%); 17 cases with subarachnoid hemorrhage(13.4%);the left basal ganglia hemorrhage in 21 cases(16.5%),16(76.2%) of which were broken into the ventricle;right basal ganglia cerebral hemorrhage in 17 cases(13.4%),11(64.7%) of which were broken into the ventricle;the left side lobar hemorrhage in 10 cases(7.9%),five cases of which were broken into the ventricle(50%);the right side lobar hemorrhage in 11 cases(8.7%),six cases of which were broken into the ventricle(54.5%).DSA is the gold standard in diagnosis of moyamoya disease.There were 104 cases(81.9%) with bilateral vascular stenosis/occlusion in 127 cases of moyamoya patients.Only 10 cases(7.9%) suffered from left side vascular stenosis/occlusion,and 13 cases(10.2%) showed a stenosis/occlusion at right side vascular(Table 1 -2).All patients had basal collateral vessels.Abnormal cortex collateral vessels could be found in 93 cases(73.2%).Abnormal branches of ophthalmic artery provided blood supply to ischemic area in 14 cases(11%).This abnormal vessels participate in blood supply were significantly enlarged.Cerebral blood circulation slowed in 103 cases (81.1%).In this group there were 7 cases with posterior circulation stenosis(5.5%).No matter where did the hemorrhage occur,most patients were of bilateral vascular stenosis/occlusion.The proportion of bilateral vascular stenosis/occlusion in patients with intra-ventricular hemorrhage is higher than that of other patients with other cerebral hemorrhage.There was a statistically significant difference(P=0.014). If the hemorrhage site was located at the left side of the brain,no right side vascular stenosis/occlusion was found in all patients.If the hemorrhage site was located at the right side of the brain,nor was the left side vascular stenosis/occlusion.In the 51 patients with intra-ventricular hemorrhage,4 cases(7.8%) suffered from intracranial aneurysm associated with blood flow;In the 17 cases with subarachnoid hemorrhage,11 cases(64.7%) had intracranial aneurysm associated with blood flow.No intracranial aneurysms were found in the remaining patients. Only one patient suffered from cerebral arteriovenous malformation.If the CT image of patients with moyamoya disease showed subarachnoid hemorrhage,we should highly suspect the possibility of intracranial aneurysm associated with blood flow combined.(P=0.000).In the 15 cases of combined aneurysms,there were 2 cases with anterior communicating artery aneurysm,1 case with middle cerebral artery bifurcation aneurysm,4 cases with Posterior communicating artery aneurysm,1 case with anterior cerebral artery A1 aneurysm,1 case with anterior cerebral artery A2 aneurysm,2 cases with posterior cerebral artery P1 aneurysm,1 case with basilar artery aneurysm,1 case with choroidal artery aneurysm,1 case with arteria lenticulostriate aneurysm,1 case with bilateral posterior cerebral artery aneurysm and vertebral artery dissecting aneurysm.All the aneurysms were saccular aneurysm except basilar artery aneurysm which is fusiform aneurysm.Of all the 127 cases,119 cases were diagnosed with moyamoya disease by transcranial color-coded sonography(TCCS),and 2 cases wre diagnosed with cerebral vasospasm.It was difficult to make a judgement in other 6 cases because we could not get intracranial blood flow information through bilateral temporal acoustic window.After excluding the 6 cases,the diagnose accordance rate of moyamoya disease by TCCS reached 98.35%compared with DSA.Between the two there was no significant statistical difference(P＞0.05).The diagnosis accordance rate is associated with the experience of the examiner and individual differences in patients. There will be a missed diagnosis in some patients due to skull thickness which may cause no acoustic window.By means of TCCS,101 cases were found with bilateral vascular stenosis/occlusion,and 18 cases suffered from unilateral vascular stenosis/occlusion.The performance of TCCS is different because of the different stages of the disease.TCCS can be used as the first choice of moyamoya disease screening and follow-up study.The goal of the treatment for patients with this chronic occlusive cerebrovascular disorder is to increase the cerebral blood supply,reduce the chance of cerebral hemorrhage,and prevent further attacks.When patients are in the acute stage of cerebral hemorrhage,the conservative treatment should be given.If the hematoma volume is too big,a surgical operation should be given to remove the hematoma.The natural pathway of collateral circulation should be protected.Do not attempt to "remove" the "smoke" vessels while in the progress of surgical operation,for this is the collateral circulation pathways,and such damage of the collateral circulation may lead to cerebral ischemia.Many different operative techniques have been described, all with the main goal of preventing further ischemic injury by increasing collateral blood flow to hypoperfused areas of cortex,using the external carotid circulation as a donor supply.Various bypass procedures have been performed in the treatment of moyamoya disease,which can generally be divided into direct,indirect and combined types.In the 127 patients of moyamoya disease,63 cases(49.6%) underwent conservative treatment(when patients were in stable condition,STA-MCA bypass +EMS surgery was given to five patients.EMS was given to 5 patients,and EDAS was given to 6 patients).40 cases(31.5%) were given ventricular drainage,13 cases (10.2%) underwent hematoma removal+EMS+decompressive craniectomy surgery.2 cases(1.6%) underwent wrapping of aneurysm + EMS surgery.6 cases(4.7%) underwent aneurysm clip +EMS surgery.Endovascular embolization was given to 3 patients(2.4%) with aneurysm.4 cases(3.1%) with intracranial aneurysms were given no surgical treatment.Review after revascularization,collateral circulation could be seen in the surgical area.External carotid artery could supply a significant amount of additional collateral blood supply to the brain.But the further assessment of surgery still needs a long-term,large sample and multi-center retrospective analysis to be carried out.For the MMD patients with aneurysms,we can use direct vascular surgery or endovascular embolization to treat the aneurysms.Endovascular embolization is a better way to solve peripheral artery aneurysms.Rebleeding is an important factors leading to poor prognosis.The mortality rate is significantly higher.The condition of 116 cases in this group(91.4%) improved,six cases(4.7%) died,and 5 cases(3.9%) whose condition had deteriorated gave up the treatment.Rebleeding occurred in six cases(4.7%),and two cases(33.3%) died.One patient after EDAS surgery one-year later showed that external carotid artery supply a significant amount of additional collateral blood supply to the brain.Part 2 Changes of bFGF and VEGF level in CSF in patients with moyamoya diseaseMoyamoya disease is characterized by chronic progressive stenosis to occlusion at the apices of the intracranial internal carotid arteries,including the proximal anterior cerebral arteries and middle cerebral arteries,with associated development of a fragile network of basal collateral vessels,resulting in successive ischemic or hemorrhagic events.The goal of the treatment for patients with MMD is to increase the cerebral blood supply.Angiogenisis needs a variety of cytokines.Whether angiogenesis happens or not depends on the balance between angiogenesis stimulating factor and inhibitory factor.Angiogenesis-stimulating factor is a protein molecules or compounds which can stimulate blood vessel growth.The most representative angiogenesis-stimulating factors are basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF).In the second part of this study,we analyzed the CSF bFGF and VEGF level in patients with moyamoya disease before and after surgery to discover the mechanism of the vascular changes in moyamoya disease.We selected 16 patients suffering from moyamoya disease at neurosurgery department of Wuhan General Hospital of Guangzhou Command from January 2007 to December 2008.7 cases were male and 9 female.All the patients were diagnosed with moyamoya disease by DSA examination.All the patients were underwent extracranial-intracranial revascularization in their stable condition 3 months after stroke,5 of whom got STA-MCA + EMS surgery,6 got EDAS surgery,and 5 got EMS surgery.2ml CSF was taken from the subarachnoid space during the bypass surgery,bFGF and VEGF were measured with an enzyme-linked immunosorbent assay kit according to the manufacturer's instructions.The results showed that the average bFGF level in CSF pre-operation was 71.46±29.36 pg·ml^-1,bFGF level post-operation was 96.38±35.55 pg·ml^-1,and the bFGF level in control group was 13.46±1.91pg·ml^-1.There is a significant difference among the three groups(P=0.000),which note that bFGF in patients with moyamoya disease were significantly higher than that in control group,and bFGF level increased after operation.The average VEGF level in CSF pre-operative was 17.23±4.53 pg·ml^-1,VEGF level post-operative was 22.98±4.33 pg·ml^-1,and the VEGF level in control group is 11.62±1.98 pg·ml^-1.There is a significant difference among the three groups (P=0.000),which note that VEGF in patients with moyamoya disease were significantly higher than that in control group,and VEGF level increased post operation.From further analysis of bFGF and VEGF level we find that there is no significant difference between different genders(P＞0.05).The patients were devided into 3 groups based on Suzuki's grade.The bFGF and VEGF level of CSF in each group showed no significant difference(P＞0.05).The patients were devided into 3 groups based on different surgery.The bFGF and VEGF level of CSF in each group showed no significant difference(P＞0.05).bFGF and VEGF can not only promote angiogenesis,increase cerebral blood flow and microvascular permeability,but also has a direct neuroprotective effect.The experiment results show that bFGF and VEGF is not only involved in the pathophysiology of moyamoya disease,but also have some neuroprotective effect. bFGF and VEGF expression changes after the surgery,on the one hand,can promote the formation of new blood vessels to increase blood supply of the ischemic brain,on the other hand,they can also promote the healing of surgical wounds through various ways.