Brain ischemia by arterial occlusion has been a focus of attention for decades, and cerebral venous disorders have been an underestimated condition of potentially good outcome if diagnosed and treated promptly. Recently, there has been considerable interest in cerebral injury following cerebral venous circulation disorders because diagnosis has improved as our understanding of the diseases and modern imaging technologies have advanced.
Ryunosuke Uranishi, Hiroyuki Nakase, and Toshisuke Sakaki
Object. Although various mechanisms of the development of dural arteriovenous fistula (AVF) have been described, the exact course of its pathogenesis, including molecular processes mediating its genesis, is still unknown. Recently, the importance of sinus thrombosis and venous hypertension has been reported in experimental and clinical studies. Additionally, a role of angiogenic growth factors in the pathogenesis of vascular malformations of the central nervous system has been reported. In this study, the authors investigated the existence of sinus thrombosis in dural AVF and the expression of angiogenic growth factors (basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF]) in nine patients with dural AVFs that were surgically resected.
Methods. The authors examined histological features of dural AVFs that involved the transverse/sigmoid sinus in seven patients and the superior sagittal sinus in two. Sinus thrombosis was verified angiographically in seven cases and histologically in all cases. In surgically resected specimens the angiogenic growth factors bFGF and VEGF were examined immunohistochemically in nine patients with dural AVFs, with five dural sinuses from cadavers with unrelated central nervous system diseases serving as a normal control group. The media and perivascular connective tissues of the arteries in the wall of the normal dural sinuses stained faintly for bFGF; on the other hand, the expression of VEGF was not detected. In all patients with dural AVFs, the thick wall of the dural sinus stained strongly for bFGF, mainly in the subendothelial layer and media of the strongly proliferative vessels in the sinus wall, in addition to the perivascular connective tissues. In all nine cases VEGF was expressed in the endothelium of the sinus and perivascular connective tissues. In two cases, VEGF was expressed in many capillaries proliferating in the granulation-like tissues in sinuses that were obliterated by organized thrombi.
Conclusions. It is concluded that the pathogenesis of dural AVF is still unknown, but that angiogenic growth factors, which might be produced by the healing process due to sinus thrombosis, may participate in the genesis of dural AVF. Understanding the mechanism of molecular pathogenesis in the development of dural AVF might aid in the establishment of a new therapeutic strategy for this dynamic vascular disease.
Takanobu Kaido, Hiroyuki Nakase, Ryunosuke Uranishi, and Toshisuke Sakaki
Report of two cases
Hiroyuki Nakase, Manabu Hisanaga, Shigeo Hashimoto, Masami Imanishi, and Shozaburo Utsumi
✓ Two patients with intraventricular arachnoid cysts are reported and a brief review of the relevant literature is presented. Arachnoid cysts are usually extracerebral or extraventricular. Intraventricular arachnoid cysts are rare: including the two cases reported here, only five cases have been described. The following characteristics were noted in these five patients: all were young; headache was the initial symptom in four; the cyst was in the trigone of a lateral ventricle in four; and there was dilatation of the inferior horn in three.
Toshisuke Sakaki, Tetsuya Morimoto, Hiroyuki Nakase, Toshio Kakizaki, and Kiyoshi Nagata
✓ In this article, the authors present five cases of dural arteriovenous fistula (AVF) that developed in the transverse—sigmoid sinus 2 to 6 years after sacrifice of the sigmoid sinus because of tumor involvement. The original tumor was meningioma in two patients and neurinoma, glomus jugulare tumor, and ameloblastoma in one patient each. The involved sigmoid sinus was resected along with the tumor and ligated at the normal edge; all that remained of the sigmoid sinus was a small stump on the retrosigmoid portion. Serial angiography performed before and after tumor surgery revealed no abnormal arteriovenous communications or dural AVF in any of the cases.
Although many reports have suggested that sinus thrombosis is a precipitating factor in the pathogenesis of dural AVFs, this has been difficult to verify because of the small number of cases in which serial angiography was performed before the development of a dural AVF. In all of the cases presented in this article, surgical resection of a dural AVF and histological examination were performed. Subintimal fibrous thickening was marked, and the sinus wall was found to contain many dural vessels. Organized thrombosis with neovascularization was seen in only two patients. These cases demonstrate that subintimal fibrous thickening and a hypertrophied sinus wall secondary to increased intrasinus pressure or sinus thrombosis occurring after sinus occlusion can provoke the development of a dural AVF within the course of a lifetime. Maintenance of intrasinus blood flow may be very important to prevent this late postoperative complication.
Hiroyuki Nakase, Kiyoshi Nagata, Hiroyuki Otsuka, Toshisuke Sakaki, and Oliver Kempski
Object. Maintenance of cerebral blood flow (CBF) autoregulation in the brain is of major importance for patient outcome in various clinical conditions. The authors assessed local autoregulation after “asymptomatic” cortical vein occlusion.
Methods. In Wistar rats, a single cortical vein was occluded photochemically by using rose bengal and fiberoptic illumination. In rats with bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension. Local CBF at each pressure level was assessed by performing laser Doppler (LD) scanning at 25 (5 × 5) locations within bilateral cranial windows. In this manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm Hg in both right and left hemispheres in Group A (five rats), in which the animals received illumination without rose bengal and had no venous occlusion. Of the 11 rats that underwent vein occlusion, three developed severe reductions in local CBF and/or a growing venous thrombus and were distinguished as Group C (symptomatic; three rats); from previous work we know that those animals are bound to experience venous infarction. The remaining rats formed Group B (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the left hemisphere without occlusion, whereas, in the right cortex with the occluded vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly ischemic range than that in the opposite normal hemisphere.
Conclusions. The results of the present study suggest that cerebral venous circulation disorders are manifested via additional pathways, that is, from a partially impaired local autoregulation in the vicinity of the occluded vein, even under conditions in which the vein occlusion itself does not cause brain damage. Care should be taken in the control of blood pressure in patients with this pathological condition.
Hiroyuki Otsuka, Hiroyuki Nakase, Kiyoshi Nagata, Katsuhiro Ueda, Oliver Kempski, and Toshisuke Sakaki
Object. Mild cerebral venous circulation disturbances (CVCDs) in aged patients are frequently known to cause unexpectedly severe postoperative complications in neurosurgical practice. The object of the present study was to determine whether there are age-related differences involved in vulnerability to CVCDs.
Methods. Thirty-eight male Wistar rats were used. A single cortical vein with a 100-µm diameter was occluded photochemically by using rose bengal dye and fiberoptic illumination in young (Group Y, 19 animals aged 10–14 weeks) and aged (Group A, seven animals aged 80–100 weeks) rats. Five young and seven aged animals served as sham-operated controls. Regional cerebral blood flow (rCBF) was determined from local CBF, which was measured at 25 (5 × 5) identical locations, with the occluded vein located central to the scanning field, by using a laser Doppler scanning technique every 15 minutes for 90 minutes after venous occlusion. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after occlusion. Histological specimens were examined 24 hours after occlusion. In Group Y, rCBF did not change significantly after venous occlusion. However, in Group A, rCBF decreased rapidly beginning 15 minutes after occlusion. Significant intergroup differences were observed 30, 60, and 90 minutes after occlusion. Venous flow arrest, which resulted in venous infarct, was observed on angiography 90 minutes after occlusion in two (10.5%) of 19 young and six (85.7%) of seven aged rats. The venous thrombus in Group A rats was significantly larger than that in Group Y rats 90 minutes after occlusion. Venous infarction was seen in all aged rats (100%) and in six young rats (31.6%); the infarct size, expressed as a percentage of the size of the ipsilateral hemisphere, was significantly larger in aged rats than in young rats.
Conclusions. This study demonstrated an age-related increase in the rate and size of venous infarct following vein occlusion, suggesting that the greater vulnerability to CVCDs in the aged brain might be attributed to early and extensive hypoperfusion of circumscribed brain areas drained by the occluded vein. The larger thrombus formation in aged animals indicates that a shift in the thrombogenetic/thrombolytic equilibrium is responsible for the observed effect.
Tadashi Sugimoto, Young-Su Park, Ichiro Nakagawa, Fumihiko Nishimura, Yasushi Motoyama, and Hiroyuki Nakase
Intracranial pial arteriovenous fistulas (AVFs) are rare cerebrovascular lesions. The authors report a rare case of pediatric pial AVF treated by direct disconnection with the aid of indocyanine green (ICG) videoangiography. A 3-year-old girl presented with developmental problems. Magnetic resonance imaging revealed brain atrophy and an anomalous left temporal vascular mass. Angiography showed a high-flow pial AVF in the early arterial phase fed by the M1 portion of the left middle cerebral artery and draining into the superficial sylvian vein and the vein of Trolard with a large varix. Given that her fistula was located in a superficial region that was easily accessible by craniotomy, the authors successfully disconnected her pial AVF by direct surgery aided by ICG videoangiography, which clearly confirmed the shunting point. In this report, the authors discuss the existing literature and compare the relative merits of endovascular versus surgical options for the treatment of pial AVF.
Hiroyuki Nakase, Oliver S. Kempski, Axel Heimann, Toshikazu Takeshima, and Jaroslav Tintera
✓ Research on cerebral venous circulation disturbances (CVCDs) has been limited partly by the paucity of animal models that produce consistent venous infarction. Occlusion of two adjacent cortical veins in rats by means of a photochemical thrombotic technique provides a minimally invasive, clinically relevant, and reproducible model suited to study the pathophysiology of CVCDs. In this study, the effects of venous occlusion on regional cortical blood flow and the brain damage that ensues were evaluated.
Cortical vein occlusion was induced by photoactivation of rose bengal via 100-µm fiberoptic illumination. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after venous occlusion, and regional cerebral blood flow (rCBF) was determined at 48 locations by using laser Doppler scanning. Histological damage was assessed 48 hours after vein occlusion. Occlusion of two cortical veins (Group T; seven animals) was compared with single-vein occlusion and its ensuing brain damage (Group S; five animals) and with sham-operated control (five animals). An rCBF reduction occurred 30 minutes after occlusion in Group T and was more extensive than the decrease in Group S after 60 minutes. Observation frequency histograms based on local CBF data obtained in Group T demonstrated that local CBF at some sites decreased to a level below the ischemic threshold within 90 minutes. Six of the seven rats in Group T had a growing venous thrombus with extravasation of fluorescein. The resulting infarction was significantly larger in Group T (9.8 ± 4.5% of the hemispheric area) than in Group S (only 3 ± 1.5% of the hemispheric area).
In conclusion, microcirculation perturbations occur early after venous occlusion and result in the formation of a venous thrombus accompanied by local ischemia and severe venous infarction. The extent of vein occlusion determines the resulting brain damage. Based on the results of this study, the authors conclude that CVCDs may be attenuated by prevention of venous thrombus progression together with the use of protective measures against the consequences of ischemia.