Abstract Smoker’s disease is a rare occlusive cerebrovascular disease of unknown origin with a progressive course and a high rate of death and disability. In this paper, we review the revascularization procedures used to treat this disease, including intracranial and extracranial direct anastomosis bypass and indirect bypass, and evaluate their efficacy in terms of clinical, cerebral angiography and cerebral blood flow and metabolic parameters measured by PET.
Keywords Anomalous vascular network disease of the cerebral base, surgical treatment, revascularization surgery
Moyamoya disease (MMD), a rare cerebrovascular disease, has been reported worldwide including China since its discovery in Japan in 1957, but the incidence is still higher in Japanese. The diagnostic criteria of the Japanese MMD Research Committee are: cerebral angiography showing occlusion or stenosis of the ends of the internal carotid artery (ICA) and its main branches, the middle cerebral artery (MCA) and the anterior cerebral artery (ACA), with the formation of an abnormal vascular network at the base of the brain visible in the arterial phase; lack of a known cause. The basic pathological changes of MMD are hyperplasia and thickening of the intimal cells of the ICA and its branches, flexion, thickening, thinning and even rupture of the intravascular elastic plate, loose arrangement of the smooth muscle cells of the middle membrane, and severe narrowing or even occlusion of the arterial lumen, There is also collateral vessel formation from the ICA, posterior cerebral artery (PCA), ophthalmic artery, septal artery, and dural artery. Although the disease was previously thought to be limited to the ICA system, recent studies have shown very similar pathological changes in the PCA, superficial temporal artery (STA), middle meningeal artery (MMA), and even in the coronary artery, pulmonary artery, renal artery, and pancreatic artery. It is believed that MMD is a systemic disease and is associated with local factors (e.g., hemodynamics) in the cerebral base arterial ring. Immunohistochemical studies have revealed the presence of basic fibroblast growth factor (bFGF) and its receptors on STA or MMA vascular smooth muscle and endothelial cells in MMD patients. bFGF plays a key role in the regulation of endothelial cell, smooth muscle cell proliferation, migration and invasion through autocrine action.
Therefore, it is hypothesized that bFGF is related to the pathogenesis of MMD. However, the etiology of MMD has not yet been elucidated. Depending on the rate of development of stenosis and occlusion and the status of collateral circulation compensation, the natural clinical and angiographic course of MMD can be progressive, rapidly deteriorating, or stable. In a group of pediatric cases observed by Olds, 77% deteriorated or died within 2 years, while 23% were relatively stable. In the six cases of unilateral disease reported by Matsushima, two cases developed bilaterally during a mean follow-up of 4.7 years, and the radiographic manifestation on the side of the first disease worsened. Because of the predominance of progressive MMD and the lack of specific medical treatment, surgical treatment is of great interest. This article reviews some recent advances in revascularization surgery (Revascularzation) for MMD.
1.Pathophysiological basis of surgical treatment
The basic pathophysiological change of MMD is cerebral ischemia, which may manifest clinically as TIA, RIND and cerebral infarction; hyperventilation may induce clinical ischemic attack and EEG “Re-build up” phenomenon. Ogawa [9] showed that the CBF of the cerebral hemispheres in both MMD and normal subjects decreased with age, but the decrease was more pronounced in the MMD group; the frontal lobe of rCBF was predominant in normal subjects, while the occipital lobe was predominant in MMD, suggesting that the ICA system Ischemia was more pronounced. The hemispheric CBF of adolescent patients correlated with the degree of angiographic occlusion, with a decrease in CBF with increasing occlusion and a significant increase in rCBF with increasing occlusion in the occipital lobe. Thus, theoretically, any surgical approach that directly increases cortical CBF (especially anterior CBF) is an option, and direct anastomotic bypass surgery is based on this.
The spontaneous massive collateral angiogenesis in MMD is a compensatory change in cerebral ischemia. The main sources are: narrowed or occluded terminals of the ICA and PCA; anastomoses from the ophthalmic and septal arteries to extracranial vessels; and dural vessels. In the natural situation, the formation of collateral circulation between the extracranial and cortical vessels is limited. To create the conditions for such collateral anastomoses, indirect bypass surgery has long been used to treat MMD,’ and substantial progress has been made in recent years. In addition, collateral angiogenesis after indirect bypass surgery may also reduce intracranial hemorrhage caused by microaneurysm formation and rupture due to spontaneous collateral vascular overdistension.
2.Surgical methods
The surgical methods of MMD are divided into two categories: direct anastomosis bypass and indirect bypass. Cervical sympathectomy is now rarely used due to poor results.
2.1 Direct anastomosis and bypass surgery
It is a direct anastomosis between the external cerebral vessels and the corticocerebral vessels, and the supplying artery is most often the STA, but the MMA and occipital artery (OA) are also used. The most common procedure is STA-MCA anastomosis. In patients with significant ischemic symptoms in the PCA, OA has been chosen as the donor artery for direct bypass. Yasargil pioneered the STA-MCA procedure in 1972 for the treatment of atherosclerotic cerebrovascular disease, and it became the traditional procedure for the treatment of MMD after Krayenbiihl used it in 1975. The advantage of this method is that it immediately improves the blood supply to the affected area, resulting in symptomatic relief. The disadvantages of this method are: surgical trauma; difficult to anastomose the thin branches of the MCA in children; disruption of the already formed dural-cerebral collateral circulation; narrowing or occlusion of the STA or the anastomosed MCA branches, which makes the long-term effect difficult to be sure; poor improvement of blood supply to the ACA and PCA distribution areas.
2.2 Indirect bypass surgery
EMS, EDAS, EDAMS, and EOS, which are supplied by the ECA system.
2.2.1 EMS
EMS has the effect of increasing the blood supply in the long term. Disadvantages of EMS: compression of brain tissue by the temporalis muscle; postoperative seizures; destruction of the established collateral circulation; slow improvement of blood supply after surgery; no direct relief of blood supply to the ACA and PCA distribution areas.
2.2.2 EDAS
The EDAS was developed by Matsushima Y in 1981. The method is to select a frontal or parietal branch of the STA according to the site of the ischemic cortex, form a tendon-arterial flap near it (without severing the distal end), and suture it to the incised dural edge through a slender bone window. The advantages of this procedure are its simplicity, short duration, minimal trauma, and the fact that it does not disrupt the existing collateral vessels, making it particularly suitable for pediatric cases. It is currently one of the most popular procedures.
2.2.3 EDAMS
This procedure was first reported by Kinagasa et al. in 1993. Based on EDAS, the temporalis muscle is fixed to the free dural edge parietal to the dural incision margin, in addition to suturing the STA parietal branch to the dural incision margin and cutting the dura along the MMA in a serrated fashion. The advantage of this method is that both the STA and MMA and the deep anterior middle and posterior temporal artery supplying the temporalis muscle are used as blood supply arteries, thus facilitating the formation of a more abundant lateral branch anastomosis.
2.2.4 EOS
EOS can be divided into two types: free patching (intracranial grafting of the greater omentum) and tipped greater omental patching (greater omental transfer). The greater omental graft was used by Karasawa in 1980 for the treatment of MMD, and later by Miyamato et al. for the treatment of posterior circulation-based MMD with success. In this procedure, the greater omentum is firstly removed from the abdominal cavity, then the superficial temporal artery/vein or occipital artery/vein is removed from the temporal or occipital region, and the greater omentum is successfully applied to the temporal parietal or occipital cortex by performing a terminal anastomosis with the gastroduodenal artery/vein that has been removed from the greater omentum. The greater omentum is transferred from the abdominal cavity through a subcutaneous tunnel to the head and applied to the cerebral cortex. Goldsmith [18] recommended this procedure for patients who failed STA-MCA or EDAS, especially those with ischemic symptoms in the PCA or ACA distribution.
3. Evaluation of surgical efficacy
3.1 Clinical evaluation
In the literature, STA-MCA was mostly used alone in the early stages, but later it tended to be used in combination with EMS. Karasawa (1992) summarized 104 pediatric cases with bilateral STA-MCA and/or EMS. After surgery, 47 cases showed immediate resolution of symptoms, 40 cases showed significant improvement, 12 cases showed mild improvement, 3 cases showed no change, and 2 cases showed deterioration. At a long-term follow-up of 9.6 years, the GOS prognosis was good in 79 cases, moderately disabled in 13 cases, severely disabled in 9 cases, and dead in 1 case. Intelligent prognosis was assessed by IQ: normal in 66 cases, critical in 19 cases, mildly decreasing in 9 cases, moderately decreasing in 4 cases, and seriously decreasing in 6 cases. It was also concluded that early clinical improvement after surgery was associated with long-term prognosis.
The prognosis was poor for both neurological function and intelligence in patients under 6 years of age at the time of surgery, especially those under 3 years of age, and in those with multiple cerebral infarcts suggested by preoperative CT. Matsushima Y (1986) [19] reported that after EDAS in 38 cases of 70-sided MMD, 100% of them showed varying degrees of clinical improvement. Matsushima T (1990) [13] reported that in 16 patients with MMD, TIA, RIND or involuntary movements disappeared (31%) or partially disappeared (44%) after bilateral EDAS in 75% of the cases. The majority of children with onset of EDAS before the age of 9 years had a good intellectual prognosis. Kinugasa (1993) performed EDAMS on 17 patients with MMD, and after surgery (mean follow-up 3 years and 2 months), the clinical outcome was excellent in 13 cases (80%), effective in 16 cases (94%), and ineffective in only one case.
3.2 Evaluation of cerebral angiography
A comparative study of ECA angiography before and after the 196-sided STA-MCA and/or EMS procedures showed that 124 of them had excellent lateral branch anastomosis (majority filling of the MCA through the STA and deep temporal artery), and 72 had good lateral anastomosis (filling of one or several MCAs). However, Asfora’s dynamic study of STA-MCA plus EMS postoperative angiography found that both the anterior branch of the STA with direct anastomosis and the posterior branch of the STA with apposition were thickened in the early postoperative period, and then the anterior branch gradually became thinner, while the posterior branch continued to thicken. This suggests that direct anastomosis is beneficial for increasing cerebral blood supply in the early postoperative period, while EMS is beneficial for maintaining long-term blood supply. 72-90% of the lateral branches in the operated area have excellent vascularity after EDAS or EDAMS. Matsushima Y (1992)[7] analyzed the angiographic results of 27 cases before and after EDAS surgery and found that the formation of collateral vessels in the MCA distribution area was excellent in 16, good in 25, and poor in 13 of 54 sides. The more severe the stenosis, the better the collateral vessel formation. However, in those with complete occlusion (including ICA, MCA and ACA trunk), the collateral vessel formation was reduced, which was accompanied by clinical and CT manifestations of cerebral infarction, indicating the importance of early surgery. The source of collateral vessels was mainly STA and MMA, and the degree of postoperative STA and MMA expansion was correlated with the number of collateral vessels. In addition, a reduction in the anomalous vascular network from ICA was seen in 13 of the 54 sides and a reduction in the anomalous vessels from PCA was seen in 12 of the 54 sides after EDAS. This reduction of abnormal vessels is beneficial for the prevention of intracranial hemorrhage due to its overdistension, and also indicates the effectiveness of revascularization.
3.3 Positron emission computed tomography (PET) evaluation
PET measurements of preoperative rCBF, local cerebral blood volume (rCBV) and local oxygen uptake fraction (rOEF) in children with MMD showed that CBF was decreased in the cerebral cortex and striatum, while rCBV and rOEF were increased compensatorily. rCBV was especially increased in the striatum to maintain local cerebral perfusion and cerebral metabolism,, EMS, STA-MCA or a combination of STA-MCA and indirect After bypass surgery (mean 8.6 months), rCBF increased significantly in the frontotemporal and parietal frontal cortex, but not in the striatum; rOEF decreased significantly in the frontoparietal and temporal lobes; rCBV decreased significantly in the striatum and tended to decrease in the frontotemporoparietal lobe. This indicates that the circulatory parameters of the brain improved significantly after direct, indirect, or combined bypass surgery. It was also found that clinical symptoms and PET parameters improved in the same direction after surgery. It was further suggested that clinical symptoms and CT without cerebral infarction, frequent TIA and RIND, and decreased PET parameters rCBF and increased rOEF and rCBV are indications for bypass surgery.
4. Postoperative complications
Complications after MMD bypass surgery include: new ischemic symptoms or aggravation of existing symptoms, intracranial hemorrhage, epileptic seizures, wound and/or intracranial infection. The frequency of TIA or RIND episodes increased more frequently after surgery, but most of them decreased gradually in a short period of time. In 22 cases of EDAS, Matsushima T (1990) found one case of cerebral infarction and one case of seizure. In contrast, Matsushima Y (1991) [22] found 6 cases of cerebral infarction after 161 EDAS, and suggested that this was related to postoperative crying of the child, which led to hyperventilation and a further decrease in cerebral blood supply due to cerebral vasoconstriction, which was already at a critical state. Prevention should be done by avoiding stimulation of the child, and sedation should be given if necessary.