J Neurosurg 76:600-606, 1992
Etiological evaluation of dural arteriovenous malformations of the lateral and sigmoid sinuses based on histopathological examinations MICHIHARU NISHIJIMA, M.D, AKIRA TAKAKU, M.D., SHUNRO ENDO, M.D., NAOYA KUWAYAMA, M.D., FUMITOMO KOIZUMI, M.D., HIDEJI SATO, M.D., AND KENJI OWADA, M.D.
Departments of Neurosurgery and Pathology, Toyama Medical and Pharmaceutical University,
Toyama; Kanazawa NeurologicalHospital, Kanazawa;and Department of Neurosurgery, Isawa Hospital Isawa, Japan v- Controversypersists concerningthe pathogenesisof dural arteriovenous malformations(AVM's)and whether they are congenital or acquired. Furthermore, it remains undetermined whether the lesion is located in the sinus itself or within the sinus wail. In order to elucidate the pathogenesisof dural ArM's of the lateral and sigmold sinuses, histopathological profiles of this disease were studied in serial sections of completely resected lesions from three patients. The essential lesion was histologically confirmed to be a dural arteriovenous fistula within the wall of the venous sinuses. The etiology process of this disease and its progression were evaluated. KEY WORDS
"
dural arteriovenous malformation
ARIOUShypotheses have been presented concerning the etiology of dural arteriovenous malformations (AVM s) of the posterior fossa, u ~ ~s.:3.30Recent reports5'7't~have suggested that this is an acquired lesion that develops in the process of reopening the venous sinuses after sinus thrombosis. However, whether this disease is a congenital anomaly of the dural vessels in a true sense or an acquired lesion remains undetermined. Furthermore, there is as yet no agreement whether the lesion is located in the sinus itself*~ or within the sinus wall. 4 This controversy may be ascribed partly to insufficient histopathological investigations. We confirmed the presence of arteriovenous fistulas in the dura near venous sinuses and in the sinus walls by serial histological sections obtained from three patients with dural AVM's of the lateral and sigmoid sinuses. The histological findings in these patients are discussed in detail, and the etiology and the mechanisms of the disease progression are evaluated.
V
Clinical Material and Methods We have collected 12 cases involving dural AVM's of the lateral and sigmoid sinuses, nine of them treated surgically, and evaluated the histological findings in three patients who underwent resection of the affected 600
9 arteriovenous fistula
9 pathogenesis
venous sinuses. The resected venous sinuses were cut into serial sections approximately 4 #m thick along the long axis of the sinus and were alternately stained using the hematoxylin and eosin or the elastica van Gieson method. The histological findings in these specimens were compared with those in specimens of the dura and sinuses from five normal adults aged 30 to 63 years (mean 55 years).
Histological Findings of Normal Lateral and Sigmoid Sinuses The interior surface of the normal sinuses was smooth and usually covered with a single layer of endothelial cells. Immediately below the endothelium were fascicles of connective tissue, demarcated by an elastic lamina. The elastic lamina showed uneven development and was not uniformly present around the entire circumference of the sinus. The fascicles of connective tissue ran in random directions at angles formed by a fusion of two dural leaves. Dural vessels were more numerous at these angles, which were rich in veins of varying sizes communicating with one another. The dural arteries near venous sinuses were bent or elongated and showed slight thickening of the intima (Fig. l a). Dural arteries were not observed inside the elastic lamina of the sinuses, but branches of veins occasionJ. Neurosurg. / Volume 76/April, 1992
Etiology of dural arteriovenous malformations
FIG. 1. Photomicrographs showing transverse sections of normal lateral sinus (S) from a 62-year-old man. Elastica van Gieson, x 7 (a) and x 17 (b). A = dural artery; V = dural vein. a: The interior surface of the sinus is smooth and consists of a layer of endothelial ceils and elastic lamina. The elastic lamina shows uneven development and is not uniformly present around the entire circumference of the sinus. Dural vessels are more numerous at angles formed by the fusion of two dural leaves, b: Dural arteries and veins are shown located close to one another. Arteries often compressed accompanying veins or projected into their lumens.
ally penetrated through the walls of the sinuses and acquired communication with their lumens. No arteriovenous anastomosis was observed among the dural vessels, but the dural arteries and veins were located close to one another. Arteries often compressed accompanying veins or projected into their lumens near the sinuses (Fig. lb).
with a diameter of about 200 ~m and dilated dural veins (Fig. 4). These arteriovenous fistulas were present in the dura near the venous sinuses but not in their intima. The lumens of the venous sinuses were narrowed by thickening of the intima and organized thrombi. Polyvinyl alcohol, used for artificial embolization, was seen in the lumens or under the intima of the dural veins and in the arteriovenous fistulas.
Illustrative Cases
Case I This 58-year-old woman developed a dural AVM of the lateral and sigmoid sinuses with occlusion of the sigmoid sinus following spontaneous healing of a dural AVM of the cavernous sinus. Stenosis had been noted in the lateral sinus prior to the recurrence of the dural AVM (Fig. 2).
Case 2 This 53-year-old woman experienced pulsating tinnitus at the onset of the disease and was admitted 2 years later with convulsions and a disturbance of con-
Operation. Embolization with polyvinyl alcohol and resection of the affected sinus were performed 4 months after the recurrence. No further recurrence has been noted during the 2 years since surgery. This patient was reported on in detail previously in a study of multiple dural AVM's.~4 Pathological Examination. Organized thrombi were observed in part of the lateral sinus but its overall patency had been restored (Fig. 3a). The intima of the sinuses was thickened; interruption and thickening were noted in the elastic laminae. The dural arteries were markedly twisted and elongated, and showed remarkable fibrous thickening in the intima and adventitia. Their lumens were severely stenosed and occluded (Fig. 3b). The intimal thickening of the affected sinuses was remarkable. Veins were markedly dilated and had communication with one another and with the lumens of the venous sinuses (Fig. 3c). No direct communication was observed between dural arteries and venous sinuses; in the serial sections, fistulas were seen between arteries .I. Neurosurg. / Volume 76/April, 1992
FIG. 2. Angiograms obtained in Case 1. a: An occlusive lesion of the lateral sinus (arrow) is revealed which preceded the development of the second dural arteriovenous malformation (AVM) in the lateral and sigmoid sinuses after spontaneous healing of the first dural AVM in the cavernous sinus. b: The second dural AVM is demonstrated, with occlusion of the ipsilateral sigmoid sinus.
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FIG. 3. Photomicrographs of histopathological sections from Case 1. a: Organized thrombi and recanalization are observed in part of the lateral sinus. The intima of the sinus is thickened, and the elastic lamina is interrupted and thickened. Elastica van Gieson, x 7. b: Transverse section of a dural artery (A) near the sinus (S) showing it to be markedly twisted and elongated, with marked fibrous thickening in the intima and adventitia, Multiple layers of elastic lamina are observed. The lumens show severe stenosis. Elastica van Gieson, • 35. c: Section showing marked thickening of the sinus intima and several dilated veins. The elastic lamina is obliterated (arrow9, and dilated veins are observed in the dura mater near the sinus and in the sinus inlima. Polyvinyl alcohol (PVA), used for artificial embolization, is seen in the lumens or under the intima of the dural veins. S = lateral sinus; V = dilated dural veins. Elastica van Gieson, • 3.5. sciousness. Cerebral angiographic studies disclosed a dural AVM of the latera/ and sigmoid sinuses with occlusion of the sigmoid sinus (Fig. 5). Venous reflux and an occipital intracerebral hematoma were noted.
Operation. The sinuses were resected and the hematoma was removed. No recurrence has been noted for 5 years after the operation.
Pathological Examination. Macroscopically, the lateral sinus tapered to occlusion toward the sigmoid sinus and showed a nodular protrusion of the sinus wall (Fig. 6a). No thrombi were present in the sinus lumina. In the serial sections, arteriovenous fistulas were observed in the dura near the venous sinuses (Fig. 6b), as in Case 1, In the markedly thickened intima of the lateral sinus, the veins developed thickened walls and
FIG. 4. Photomicrographs of 4-/~m serial sections of the lateral sinus (S) in Case 1. The artery shews fibrous thickening of the intima and irregular thickening and obliteration of the elastic lamina. This artery branched off the artery illustrated in Fig. 3b. The vein shows dilatation and thickened walls. An arteriovenous fistula (arrow, c) is clearly demonstrated between a dural artery (A} about 200 um in diameter and a dilated dural vein (V). Elastica van Gieson, x 16.
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Etiology of dural arteriovenous malformations
FIG. 5. Left external carotid angiogram in Case 2. showing dural arteriovenous malformmion of the lateral and sigmoid sinuses with occlusion of the sigmoid sinus and reverse flow to the cortical veins. The lateral sinus was filled in the arterial phase via middle meningeal branches, the superficial temporal artery., and the occipital ancr2,.
had communication with vessels on the dural side (Fig. 7a). Intimal thickening of dural arteries and veins was more notable than in Case 1. In the thickened intima of the sigmoid sinus, a large number of dural arteries, dural veins, and arteriovenous fistulas were observed (Fig. 7b). The network created by these vessels narrowed the sinus lumen.
Results In the three cases presented, the dural AVM's were fed by branches of the inlernal and external carotid arteries, with occlusion of the sigmoid sinus. In review-
ing the serial angiograms it was impossible to precisely determine if arteries were communicating directly with the sinus itself or if arteriovenous fistulas were located within the wall of affected sinuses (see Fig, 5). However, the fistulas were observed within the sinus wall on serial histological sections. Table 1 summarizes the histological findings in the three cases so examined. No signs of inflammation or tumors were noted in any case. Sinus thrombosis and recanalization of organized thrombi were observed in only one patient (Case 1). Although direct communication was not observed between dural arteries and the lumens of the venous sinuses, arteriovenous fistulas were noted in the dural vessels. Thickening of the intima of the venous sinuses, thickening and interruption of the elastic lamina of the sinuses, thickening of the intima of dilated dural veins, and changes in dural arteries were most notable in Cases 2 and 3, in which both patients were examined 2 and 4 years, respectively, after the onset of symptoms; Case 1 was examined only 4 months after onset. Arteriovenous fistulas were observed only in the dura near the sinuses in Case 1 (Fig. 4), but they were seen in the intima of the sinuses in Cases 2 and 3 (Figs. 6b and 7b).
Discussion Review of the Literature There have been few hislopathological studies of dural AVM's in serial sections. The histologtcal characteristics reported to date included the presence of an abnormal vascular network and various changes in the dural arteries and veins. LT.s.,~.,7.3oHowever, these observations were made during examination of only a single aspect of the lesion. This is not considered sufficient histological evidence for an etiological evaluation.
I'm. 6. t'holom~erographs of resected tissue in Case 2. Elastica van Gieson, x 17. a: Macroscopic appearance of the affected sinus showing the lateral sinus tapering to occlusion toward the sigmoid sinus and a nodular protrusion of the sinus wall (arroa9. No thrombi were observed in the lumens of the sinuses. Measure is in centimeters, b: An aneriovenous fistula in the dura immediately adjacent to the lumen of the sinus. The part of the fistula that is surrounded by elastic lamina (arrow) is the arterial component (A) and the part without elastic lamina is the venous component (V).
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FIG. 7. Photomicrographs of resected lateral (a) and sigmoid (b) sinus tissue in Case 2. Elastica van Gieson, x 7. a: Several thick-walled veins are demonstrated in the markedly thickened sinus wall and have communication with vessels on the dural side through the obliterated portion of the elastic lamina of the sinus (arrow). S = lateral sinus; V = vein in the sinus intima, b: A large number of dural arteries (A), dural veins (V), and arteriovenous fistulas (AVF) are observed in the markedly thickened sinus intima. The network created by these vessels narrowed the lumen of the sinus. SS = sigmoid sinus.
Houser, et al., ~o observed what appeared to be multiple dysplastic vessels with a multilayered elastic tissue component immediately adjacent to the sinus wall in specimens of resected sinuses from 13 patients with lateral and sigmoid dural AVM's. Thrombotic material was seen in two of these specimens. Based on these histological findings and on a detailed investigation of sequential changes in angiographic findings, they proposed that dural sinus occlusion might precede the development of a dural AVM and that the pathogenesis might be partial recanalization of a thrombus. Their hypothesis has been widely accepted; S7'29 however, it appears that the morphology of arteriovenous fistulas was not addressed in detail. In the present study, the essential lesion of this disease was histologically confirmed as dural arteriovenous fis-
tulas within the wall of the venous sinuses. Arteriovenous fistulas were observed not only on the outside of the elastic lamina of the dural sinus in Case 1, but also in the thickened intima of the dural sinus in Cases 2 and 3. We speculate that these varying histological profiles reflect differences in the duration and progression of the disease. Lesion Location
Previous reports appear to classify these lesions into two types. 4'~~ One type has direct artery-to-sinus communication in the thrombosed sinus itself, t~ and the other exhibits arteriovenous fistulas within the wall of the sinus. 4 However, it appears that neither type has been addressed in detail histologically. Barnwell, et al.,4 reported seven cases with a unique type of dural arte-
TABLE 1 Summary of histopathologicalfindings in three cases of dural arteriovenous malformation" Normal Sinus
Case 1
Case 2
Case 3
d u r a t i o n o f illness sinus t h r o m b o s i s
-
4 mos + (focal)
2 yrs -
4 yrs -
inflammation intima of sinus
.
.
arteriovenous fistulas thickening vessels obliteration o f elastic l a m i n a o f sinus near the sinus arteritwenous fistulas dural artery i n t i m a l thickening elongation dural vein intimal thickening dilatation
_ _.+
+ + (vein alone) +
+ ++ + + (vein, artery) ++
+ ++ + + (vein, artery) ++
-
+
+
+
_+ _+
+ +
++ ++
++ ++
-
+
+ +
+ +
Factor
.
.
* Abbreviations: + = factor present; - = factor not present; _+ = factor presence equivocal.
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Etiology of dural arteriovenous malformations riovenous fistula in which only cortical venous drainage occurred, despite clearly involved sinuses; the fistula was located within the wall of the sinus, but outflow was not into the involved sinus. They evaluated these cases as a variant of arteriovenous fistula. Our study suggests that, in three patients with dural AVM's and occlusion of sigmoid sinus, the fistulas between dural arteries and dural veins were observed within the wall of the affected dural sinuses. It is not certain whether these forms of arteriovenous fistula are common to all dural AVM's. Histological profiles probably differ according to the duration and progression of the disease. However, it is possible that these aneriovenous fistulas develop in the early stage of the disease.
Pathogenesis Based on angiographic findings, various hypotheses have been proposed concerning the etiology of dural AVM's. j'~~176 According to reviews relative to congenital factors, particular emphasis is placed on the occurrence of this disease in infants and on cases of dural AVM complicated by an AVM of the cerebral parenchyma/2't8 Based on reports by Padget 2' and Streeter, 27 it is speculated that this disease is established with the enlargement of intradural arteriovenous shunts. These may arise during embryonic development, .2.~gor from abnormal growth of the vasa vasorum of the lateral sinusY On the other hand, those who regard this disease as an acquired condition s'7'~~ emphasize its occurrence after trauma, craniotomy, and sinus thrombosis. They attach particular importance to the rich communications in dural vessels, the physiological arteriovenous fistulas, ~t'25 and the presence of spongy structures on the walls of venous sinuses. ~'22 These have been confirmed by postmortem injection studies. Based on these findings, they consider that dural AVM's are caused by abnormal postnatal development of physiological arteriovenous fistulas. Based on their own cases and review of the literature, Awad, et al.,2 dassified the progression of dural AVM's into three stages. They speculated that sinus thrombosis and the opening of embryonic arteriovenous communication played an important role in the onset of this disease. In this study, we concur with the opinion that arteriovenous fistulas may be an acquired condition. Because arteries and veins are very close to one another in the normal dural sinuses24 (Fig. l b), mild trauma and/or pathological changes in dural vessels may readily induce their fistulation. Although mild arteriosclerotic changes related to the formation of arteriovenous fistulas were noted in the dural arteries in Case 1, these vessels showed no morphological difference when compared with the dural arteries observed near normal venous sinuses. The morphology of the fistulas was simple, and was not considered to have resulted from the development of latent arteriovenous fistulas (Fig. 4). In addition, physiological arteriovenous fistulas and spongy portions of the venous sinus walls are reported to be present primarily near the superior sagittal sinus ~'-~5
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but are infrequent in the lateral and sigmoid sinuses, where dural AVM's more frequently occur.
Significance of Sinus Thrombosis Sinus thrombosis has been regarded as an etiological factor since Houser, eta/., ~~reported dural AVM cases in which recanalized clots were observed histologically. However, it is also evaluated as a factor in the spontaneous resolution of dural AVM's. ~5~'2~ In addition to these conflicting interpretations, it has not been satisfactorily explained why sinus thrombosis occurs in this disease. We speculate that sinus thrombosis is a phenomenon thai may occur at any time arteriovenous fistulas are present within the wall of the sinuses. We base this hypothesis on the fact that, histologically, sinus thrombosis was noted in only one (Case 1) of our three cases. Stenosis of the sinus lumina occurred mainly due to the marked thickening of their intima and the development of abnormal vascular networks within their walls. Angiographically, the occlusion or stenosis of venous sinuses is not demonstrated in all patients, being noted in only seven of the 12 patients we encountered. The development of occlusive lesions of the venous sinuses has been reported elsewhere.~3 Occlusive lesions occurred prior to dural AVM's in some patients (Cases 1 and 3). In others, however, the lateral sinus became occluded without clinical symptoms after ligation of feeding arteries, j~ or the narrowed site was occluded causing symptomatic deterioration (Case 3). In another case, a dural AVM was accompanied by occlusion of the sigmoid sinus, but healed spontaneously with no angiographic opacification of the lateral sinus?
Proposed Pathogenesis We speculate that the mechanisms of the progression of dural AVM's are as follows: First, for some reason, a single arteriovenous fistula forms in the dura near a venous sinus. The blood flow increases to some extent at the fistula because of a marked reduction in the peripheral vascular resistance. 28 Once the fistula has formed, arterial blood gathers around the fistula via the well-developed vascular system? When this state is sustained, dural arteries become twisted and intimal thickening develops. Dural veins dilate and become thickened due to increases in internal pressure caused by the influx of arterial blood. The fistula itself then becomes dilated and its wall thickens. The influx of arterial blood via dural veins induces thrombogenesis and injury to the intima due to turbulent flow near the vein's orifice into the sinus? These thrombi attach to part of the sinus wall and obstruct the orifice of the vein. This causes further dilatation and thickening of the intima of the vein directly involved in the fistula formation. Arterial blood begins to flow into the sinus via other communicating dural veins, leading to reformation of thrombosis. Regional thrombus formation progresses in the lumen of the venous sinus by repetition of the above process. Pressure in the venous sinus increases, and this 605
M. Nishijima, et al. increase in internal pressure along with the organization of thrombi causes marked fibrous thickening of the sinus intima and interruption or proliferation of the elastic lamina of the sinus. Even more remarkable changes take place in the dural veins, arteries, and the arteriovenous fistulas themselves. In this vicious circle, new arteriovenous fistulas develop between adjacent dural arteries and veins. Vein-like thinning of the dural arterial wall or artery-like thickening of the dural venous wail occurs. Arteriovenous fistulas, thickened dural arteries, and dilated dural veins form an abnormal vascular network. This gradually infiltrates the connective tissue of the dura and proceeds into the wall of the venous sinus through areas where the elastic lamina of the sinus is interrupted or poorly developed. This results in stenosis or occlusion of the sinus lumen.
Acknowledgment We are grateful for the technical assistance of Miss Ryoko Kato with the histopathologieal study.
References 1. Aminoff MJ: Vascular anomalies in the intracranial dura mater. Brain 96:601--612, 1973 2. Awad IA, Little JR, Akrawi WP, et al: Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course. J Neur~surg 72:839-850, 1990 3. Balo J: Dural venous sinuses. Anat Res 106:319-325, 1950 4. Barnwell SL, Halbach VV, Dnwd CF, et al: A variant of arteriovenous fistulas within the wall of dural sinuses. Results of combined surgical and endovascular therapy. J Nenrosurg 74:199-204, 1991 5. Chaudhary MY, Sachdev VP, Cho SH, et al: Dural arteriovenous malformation of the major venous sinuses: an acquired lesion. AJNR 3:13-19, 1982 6. Endo S, Koshu K, Suzuki J: Spontaneous regression of posterior fossa dural arteriovenous malformation. J Neurostlrg 51:715-717, 1979 7. Graeb DA, Dolman CL: Radiological and pathological aspects of dural arteriovenous fistulas. Case report. J Neurosurg 64:962-967, 1986 8. Handa J, Yoneda S, Handa H: Venous sinus occlusion with a dural arteriovenous malformation of the posterior fossa. Surg Neorol 4:433-437, 1975 9. Holman E: Reflections on arteriovenous fistulas. Ann Thorac Surg 11:176-186, 1971 10. Houser OW, Campbell JK, Campbell RJ, et al: Arteriovenous malformation affecting the transverse dural venous sinus - - an acquired lesion. Mayo Clio Proc 54: 651-66 l, 1979 I 1. Kerber CW, Newton TH: The macro and microvasculature of the dora mater. Neuroradiology 6:175-179, 1973 12. Kunc Z, Brat J: Congenital arterio-sinusal fistulae. Acta Neurochir 20:85-103, 1969
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13. Kuwayama N, Nishijima M, Endo S, et al: [Dural arteriovenous malformations and ecclusive sinus lesions. Report of two cases.] Surg Cereb Stroke 18:98-102, 1990 (Jpn) 14. Kuwayama N, Takaku A, Nishijima M, et al: Multiple dural arteriovenous malformations. Report of two cases. J Neurosurg 71:932-934, 1989 15. Magidson MA, Weinberg PE: Spontaneous closure of a dural arteriovenous malformation. Surg Neurol 6:107-110, 1976 16. Malik GM, Pearce JE, Ausman JI, et al: Dural arterioveonus malformations and intracranial hemorrhage. Neurosurgery 15:332-339, 1984 17. McCormick WF, Boulter TR: Vascular malformations ~"angiomas") of the dura mater. Report of two cases. J Neurosurg 25:309-311, 1966 18. Newton TH, Cronqvist S: Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 93:1071-1078, 1969 19. Ohm T, Kajikawa H: [Dural arteriovenous malformation.] Neuroi Meal Chir 18:439-472, 1978 (Jpn) 20. Olutola IS, Eliam M, Molot M, et al: Spontaneous regression of a dural arteriovenous malformation. Neurasurgery 12:687-690, 1983 21. Padget DH: The development of the cranial venous system in man, from the viewpoint of comparative anatomy. Contrib Embryol 36:79-140, 1957 22. Piton J, Guilleux MH, Guibert-Trainer F, et al: Fistulae of the lateral sinus. J Neuroradiol 11:143-159, 1984 23. Robinson JL, Sedzimir CB: External carotid-transverse sinus fistula. Case report. J Neurosurg 33:718-720, 1970 24. Roland J, Bernad C, Bracard S, et al: Microvascularization of the intracranial dora mater. Surg Radiol Anat 9: 43-49, 1987 25. Rowbotham GF, Little E: Circulations of the cerebral hemispheres. Br J Surg 52:8-21, 1965 26. Seeger JF, Gabrielson TO, Giannotta SL: Carotid-cavernous sinus fistulas and venous thrombosis. AJNR 1: 141-148, 1980 27. Streeter GL: The developmental alterations in the vascular system of the brain of the human embryo. Contrib Embryol 8:5-38, 1918 28. Stucker FJ: Extracranial arteriovenous fistulas. Laryngoscope 84:970-975, i974 29. Sundt TM Jr, Piepgras DG: The surgical approach to arteriovenous malformations of the lateral and sigraoid dural sinuses. J Neurosurg 59:32-39, 1983 30. Takaku A, Sato T, Sakamoto T, et al: [Dural artefiovenous malformation - - with special consideration to its nature and treatment.] Neurol Med Chir 18:67-74, 1978 (Jpn)
Manuscript received February 4, 1991. Accepted in final form September 9, 1991. Address reprint requests to." Michiharu Nishijima, M.D., Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama City 930-01, Japan.
J. Neurosurg. / Volume 76 / April, 1992
Etiological evaluation of dural arteriovenous malformations of the lateral and sigmoid sinuses based on histopathological examinations MICHIHARU NISHIJIMA, M.D, AKIRA TAKAKU, M.D., SHUNRO ENDO, M.D., NAOYA KUWAYAMA, M.D., FUMITOMO KOIZUMI, M.D., HIDEJI SATO, M.D., AND KENJI OWADA, M.D.
Departments of Neurosurgery and Pathology, Toyama Medical and Pharmaceutical University,
Toyama; Kanazawa NeurologicalHospital, Kanazawa;and Department of Neurosurgery, Isawa Hospital Isawa, Japan v- Controversypersists concerningthe pathogenesisof dural arteriovenous malformations(AVM's)and whether they are congenital or acquired. Furthermore, it remains undetermined whether the lesion is located in the sinus itself or within the sinus wail. In order to elucidate the pathogenesisof dural ArM's of the lateral and sigmold sinuses, histopathological profiles of this disease were studied in serial sections of completely resected lesions from three patients. The essential lesion was histologically confirmed to be a dural arteriovenous fistula within the wall of the venous sinuses. The etiology process of this disease and its progression were evaluated. KEY WORDS
"
dural arteriovenous malformation
ARIOUShypotheses have been presented concerning the etiology of dural arteriovenous malformations (AVM s) of the posterior fossa, u ~ ~s.:3.30Recent reports5'7't~have suggested that this is an acquired lesion that develops in the process of reopening the venous sinuses after sinus thrombosis. However, whether this disease is a congenital anomaly of the dural vessels in a true sense or an acquired lesion remains undetermined. Furthermore, there is as yet no agreement whether the lesion is located in the sinus itself*~ or within the sinus wall. 4 This controversy may be ascribed partly to insufficient histopathological investigations. We confirmed the presence of arteriovenous fistulas in the dura near venous sinuses and in the sinus walls by serial histological sections obtained from three patients with dural AVM's of the lateral and sigmoid sinuses. The histological findings in these patients are discussed in detail, and the etiology and the mechanisms of the disease progression are evaluated.
V
Clinical Material and Methods We have collected 12 cases involving dural AVM's of the lateral and sigmoid sinuses, nine of them treated surgically, and evaluated the histological findings in three patients who underwent resection of the affected 600
9 arteriovenous fistula
9 pathogenesis
venous sinuses. The resected venous sinuses were cut into serial sections approximately 4 #m thick along the long axis of the sinus and were alternately stained using the hematoxylin and eosin or the elastica van Gieson method. The histological findings in these specimens were compared with those in specimens of the dura and sinuses from five normal adults aged 30 to 63 years (mean 55 years).
Histological Findings of Normal Lateral and Sigmoid Sinuses The interior surface of the normal sinuses was smooth and usually covered with a single layer of endothelial cells. Immediately below the endothelium were fascicles of connective tissue, demarcated by an elastic lamina. The elastic lamina showed uneven development and was not uniformly present around the entire circumference of the sinus. The fascicles of connective tissue ran in random directions at angles formed by a fusion of two dural leaves. Dural vessels were more numerous at these angles, which were rich in veins of varying sizes communicating with one another. The dural arteries near venous sinuses were bent or elongated and showed slight thickening of the intima (Fig. l a). Dural arteries were not observed inside the elastic lamina of the sinuses, but branches of veins occasionJ. Neurosurg. / Volume 76/April, 1992
Etiology of dural arteriovenous malformations
FIG. 1. Photomicrographs showing transverse sections of normal lateral sinus (S) from a 62-year-old man. Elastica van Gieson, x 7 (a) and x 17 (b). A = dural artery; V = dural vein. a: The interior surface of the sinus is smooth and consists of a layer of endothelial ceils and elastic lamina. The elastic lamina shows uneven development and is not uniformly present around the entire circumference of the sinus. Dural vessels are more numerous at angles formed by the fusion of two dural leaves, b: Dural arteries and veins are shown located close to one another. Arteries often compressed accompanying veins or projected into their lumens.
ally penetrated through the walls of the sinuses and acquired communication with their lumens. No arteriovenous anastomosis was observed among the dural vessels, but the dural arteries and veins were located close to one another. Arteries often compressed accompanying veins or projected into their lumens near the sinuses (Fig. lb).
with a diameter of about 200 ~m and dilated dural veins (Fig. 4). These arteriovenous fistulas were present in the dura near the venous sinuses but not in their intima. The lumens of the venous sinuses were narrowed by thickening of the intima and organized thrombi. Polyvinyl alcohol, used for artificial embolization, was seen in the lumens or under the intima of the dural veins and in the arteriovenous fistulas.
Illustrative Cases
Case I This 58-year-old woman developed a dural AVM of the lateral and sigmoid sinuses with occlusion of the sigmoid sinus following spontaneous healing of a dural AVM of the cavernous sinus. Stenosis had been noted in the lateral sinus prior to the recurrence of the dural AVM (Fig. 2).
Case 2 This 53-year-old woman experienced pulsating tinnitus at the onset of the disease and was admitted 2 years later with convulsions and a disturbance of con-
Operation. Embolization with polyvinyl alcohol and resection of the affected sinus were performed 4 months after the recurrence. No further recurrence has been noted during the 2 years since surgery. This patient was reported on in detail previously in a study of multiple dural AVM's.~4 Pathological Examination. Organized thrombi were observed in part of the lateral sinus but its overall patency had been restored (Fig. 3a). The intima of the sinuses was thickened; interruption and thickening were noted in the elastic laminae. The dural arteries were markedly twisted and elongated, and showed remarkable fibrous thickening in the intima and adventitia. Their lumens were severely stenosed and occluded (Fig. 3b). The intimal thickening of the affected sinuses was remarkable. Veins were markedly dilated and had communication with one another and with the lumens of the venous sinuses (Fig. 3c). No direct communication was observed between dural arteries and venous sinuses; in the serial sections, fistulas were seen between arteries .I. Neurosurg. / Volume 76/April, 1992
FIG. 2. Angiograms obtained in Case 1. a: An occlusive lesion of the lateral sinus (arrow) is revealed which preceded the development of the second dural arteriovenous malformation (AVM) in the lateral and sigmoid sinuses after spontaneous healing of the first dural AVM in the cavernous sinus. b: The second dural AVM is demonstrated, with occlusion of the ipsilateral sigmoid sinus.
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FIG. 3. Photomicrographs of histopathological sections from Case 1. a: Organized thrombi and recanalization are observed in part of the lateral sinus. The intima of the sinus is thickened, and the elastic lamina is interrupted and thickened. Elastica van Gieson, x 7. b: Transverse section of a dural artery (A) near the sinus (S) showing it to be markedly twisted and elongated, with marked fibrous thickening in the intima and adventitia, Multiple layers of elastic lamina are observed. The lumens show severe stenosis. Elastica van Gieson, • 35. c: Section showing marked thickening of the sinus intima and several dilated veins. The elastic lamina is obliterated (arrow9, and dilated veins are observed in the dura mater near the sinus and in the sinus inlima. Polyvinyl alcohol (PVA), used for artificial embolization, is seen in the lumens or under the intima of the dural veins. S = lateral sinus; V = dilated dural veins. Elastica van Gieson, • 3.5. sciousness. Cerebral angiographic studies disclosed a dural AVM of the latera/ and sigmoid sinuses with occlusion of the sigmoid sinus (Fig. 5). Venous reflux and an occipital intracerebral hematoma were noted.
Operation. The sinuses were resected and the hematoma was removed. No recurrence has been noted for 5 years after the operation.
Pathological Examination. Macroscopically, the lateral sinus tapered to occlusion toward the sigmoid sinus and showed a nodular protrusion of the sinus wall (Fig. 6a). No thrombi were present in the sinus lumina. In the serial sections, arteriovenous fistulas were observed in the dura near the venous sinuses (Fig. 6b), as in Case 1, In the markedly thickened intima of the lateral sinus, the veins developed thickened walls and
FIG. 4. Photomicrographs of 4-/~m serial sections of the lateral sinus (S) in Case 1. The artery shews fibrous thickening of the intima and irregular thickening and obliteration of the elastic lamina. This artery branched off the artery illustrated in Fig. 3b. The vein shows dilatation and thickened walls. An arteriovenous fistula (arrow, c) is clearly demonstrated between a dural artery (A} about 200 um in diameter and a dilated dural vein (V). Elastica van Gieson, x 16.
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Etiology of dural arteriovenous malformations
FIG. 5. Left external carotid angiogram in Case 2. showing dural arteriovenous malformmion of the lateral and sigmoid sinuses with occlusion of the sigmoid sinus and reverse flow to the cortical veins. The lateral sinus was filled in the arterial phase via middle meningeal branches, the superficial temporal artery., and the occipital ancr2,.
had communication with vessels on the dural side (Fig. 7a). Intimal thickening of dural arteries and veins was more notable than in Case 1. In the thickened intima of the sigmoid sinus, a large number of dural arteries, dural veins, and arteriovenous fistulas were observed (Fig. 7b). The network created by these vessels narrowed the sinus lumen.
Results In the three cases presented, the dural AVM's were fed by branches of the inlernal and external carotid arteries, with occlusion of the sigmoid sinus. In review-
ing the serial angiograms it was impossible to precisely determine if arteries were communicating directly with the sinus itself or if arteriovenous fistulas were located within the wall of affected sinuses (see Fig, 5). However, the fistulas were observed within the sinus wall on serial histological sections. Table 1 summarizes the histological findings in the three cases so examined. No signs of inflammation or tumors were noted in any case. Sinus thrombosis and recanalization of organized thrombi were observed in only one patient (Case 1). Although direct communication was not observed between dural arteries and the lumens of the venous sinuses, arteriovenous fistulas were noted in the dural vessels. Thickening of the intima of the venous sinuses, thickening and interruption of the elastic lamina of the sinuses, thickening of the intima of dilated dural veins, and changes in dural arteries were most notable in Cases 2 and 3, in which both patients were examined 2 and 4 years, respectively, after the onset of symptoms; Case 1 was examined only 4 months after onset. Arteriovenous fistulas were observed only in the dura near the sinuses in Case 1 (Fig. 4), but they were seen in the intima of the sinuses in Cases 2 and 3 (Figs. 6b and 7b).
Discussion Review of the Literature There have been few hislopathological studies of dural AVM's in serial sections. The histologtcal characteristics reported to date included the presence of an abnormal vascular network and various changes in the dural arteries and veins. LT.s.,~.,7.3oHowever, these observations were made during examination of only a single aspect of the lesion. This is not considered sufficient histological evidence for an etiological evaluation.
I'm. 6. t'holom~erographs of resected tissue in Case 2. Elastica van Gieson, x 17. a: Macroscopic appearance of the affected sinus showing the lateral sinus tapering to occlusion toward the sigmoid sinus and a nodular protrusion of the sinus wall (arroa9. No thrombi were observed in the lumens of the sinuses. Measure is in centimeters, b: An aneriovenous fistula in the dura immediately adjacent to the lumen of the sinus. The part of the fistula that is surrounded by elastic lamina (arrow) is the arterial component (A) and the part without elastic lamina is the venous component (V).
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FIG. 7. Photomicrographs of resected lateral (a) and sigmoid (b) sinus tissue in Case 2. Elastica van Gieson, x 7. a: Several thick-walled veins are demonstrated in the markedly thickened sinus wall and have communication with vessels on the dural side through the obliterated portion of the elastic lamina of the sinus (arrow). S = lateral sinus; V = vein in the sinus intima, b: A large number of dural arteries (A), dural veins (V), and arteriovenous fistulas (AVF) are observed in the markedly thickened sinus intima. The network created by these vessels narrowed the lumen of the sinus. SS = sigmoid sinus.
Houser, et al., ~o observed what appeared to be multiple dysplastic vessels with a multilayered elastic tissue component immediately adjacent to the sinus wall in specimens of resected sinuses from 13 patients with lateral and sigmoid dural AVM's. Thrombotic material was seen in two of these specimens. Based on these histological findings and on a detailed investigation of sequential changes in angiographic findings, they proposed that dural sinus occlusion might precede the development of a dural AVM and that the pathogenesis might be partial recanalization of a thrombus. Their hypothesis has been widely accepted; S7'29 however, it appears that the morphology of arteriovenous fistulas was not addressed in detail. In the present study, the essential lesion of this disease was histologically confirmed as dural arteriovenous fis-
tulas within the wall of the venous sinuses. Arteriovenous fistulas were observed not only on the outside of the elastic lamina of the dural sinus in Case 1, but also in the thickened intima of the dural sinus in Cases 2 and 3. We speculate that these varying histological profiles reflect differences in the duration and progression of the disease. Lesion Location
Previous reports appear to classify these lesions into two types. 4'~~ One type has direct artery-to-sinus communication in the thrombosed sinus itself, t~ and the other exhibits arteriovenous fistulas within the wall of the sinus. 4 However, it appears that neither type has been addressed in detail histologically. Barnwell, et al.,4 reported seven cases with a unique type of dural arte-
TABLE 1 Summary of histopathologicalfindings in three cases of dural arteriovenous malformation" Normal Sinus
Case 1
Case 2
Case 3
d u r a t i o n o f illness sinus t h r o m b o s i s
-
4 mos + (focal)
2 yrs -
4 yrs -
inflammation intima of sinus
.
.
arteriovenous fistulas thickening vessels obliteration o f elastic l a m i n a o f sinus near the sinus arteritwenous fistulas dural artery i n t i m a l thickening elongation dural vein intimal thickening dilatation
_ _.+
+ + (vein alone) +
+ ++ + + (vein, artery) ++
+ ++ + + (vein, artery) ++
-
+
+
+
_+ _+
+ +
++ ++
++ ++
-
+
+ +
+ +
Factor
.
.
* Abbreviations: + = factor present; - = factor not present; _+ = factor presence equivocal.
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Etiology of dural arteriovenous malformations riovenous fistula in which only cortical venous drainage occurred, despite clearly involved sinuses; the fistula was located within the wall of the sinus, but outflow was not into the involved sinus. They evaluated these cases as a variant of arteriovenous fistula. Our study suggests that, in three patients with dural AVM's and occlusion of sigmoid sinus, the fistulas between dural arteries and dural veins were observed within the wall of the affected dural sinuses. It is not certain whether these forms of arteriovenous fistula are common to all dural AVM's. Histological profiles probably differ according to the duration and progression of the disease. However, it is possible that these aneriovenous fistulas develop in the early stage of the disease.
Pathogenesis Based on angiographic findings, various hypotheses have been proposed concerning the etiology of dural AVM's. j'~~176 According to reviews relative to congenital factors, particular emphasis is placed on the occurrence of this disease in infants and on cases of dural AVM complicated by an AVM of the cerebral parenchyma/2't8 Based on reports by Padget 2' and Streeter, 27 it is speculated that this disease is established with the enlargement of intradural arteriovenous shunts. These may arise during embryonic development, .2.~gor from abnormal growth of the vasa vasorum of the lateral sinusY On the other hand, those who regard this disease as an acquired condition s'7'~~ emphasize its occurrence after trauma, craniotomy, and sinus thrombosis. They attach particular importance to the rich communications in dural vessels, the physiological arteriovenous fistulas, ~t'25 and the presence of spongy structures on the walls of venous sinuses. ~'22 These have been confirmed by postmortem injection studies. Based on these findings, they consider that dural AVM's are caused by abnormal postnatal development of physiological arteriovenous fistulas. Based on their own cases and review of the literature, Awad, et al.,2 dassified the progression of dural AVM's into three stages. They speculated that sinus thrombosis and the opening of embryonic arteriovenous communication played an important role in the onset of this disease. In this study, we concur with the opinion that arteriovenous fistulas may be an acquired condition. Because arteries and veins are very close to one another in the normal dural sinuses24 (Fig. l b), mild trauma and/or pathological changes in dural vessels may readily induce their fistulation. Although mild arteriosclerotic changes related to the formation of arteriovenous fistulas were noted in the dural arteries in Case 1, these vessels showed no morphological difference when compared with the dural arteries observed near normal venous sinuses. The morphology of the fistulas was simple, and was not considered to have resulted from the development of latent arteriovenous fistulas (Fig. 4). In addition, physiological arteriovenous fistulas and spongy portions of the venous sinus walls are reported to be present primarily near the superior sagittal sinus ~'-~5
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but are infrequent in the lateral and sigmoid sinuses, where dural AVM's more frequently occur.
Significance of Sinus Thrombosis Sinus thrombosis has been regarded as an etiological factor since Houser, eta/., ~~reported dural AVM cases in which recanalized clots were observed histologically. However, it is also evaluated as a factor in the spontaneous resolution of dural AVM's. ~5~'2~ In addition to these conflicting interpretations, it has not been satisfactorily explained why sinus thrombosis occurs in this disease. We speculate that sinus thrombosis is a phenomenon thai may occur at any time arteriovenous fistulas are present within the wall of the sinuses. We base this hypothesis on the fact that, histologically, sinus thrombosis was noted in only one (Case 1) of our three cases. Stenosis of the sinus lumina occurred mainly due to the marked thickening of their intima and the development of abnormal vascular networks within their walls. Angiographically, the occlusion or stenosis of venous sinuses is not demonstrated in all patients, being noted in only seven of the 12 patients we encountered. The development of occlusive lesions of the venous sinuses has been reported elsewhere.~3 Occlusive lesions occurred prior to dural AVM's in some patients (Cases 1 and 3). In others, however, the lateral sinus became occluded without clinical symptoms after ligation of feeding arteries, j~ or the narrowed site was occluded causing symptomatic deterioration (Case 3). In another case, a dural AVM was accompanied by occlusion of the sigmoid sinus, but healed spontaneously with no angiographic opacification of the lateral sinus?
Proposed Pathogenesis We speculate that the mechanisms of the progression of dural AVM's are as follows: First, for some reason, a single arteriovenous fistula forms in the dura near a venous sinus. The blood flow increases to some extent at the fistula because of a marked reduction in the peripheral vascular resistance. 28 Once the fistula has formed, arterial blood gathers around the fistula via the well-developed vascular system? When this state is sustained, dural arteries become twisted and intimal thickening develops. Dural veins dilate and become thickened due to increases in internal pressure caused by the influx of arterial blood. The fistula itself then becomes dilated and its wall thickens. The influx of arterial blood via dural veins induces thrombogenesis and injury to the intima due to turbulent flow near the vein's orifice into the sinus? These thrombi attach to part of the sinus wall and obstruct the orifice of the vein. This causes further dilatation and thickening of the intima of the vein directly involved in the fistula formation. Arterial blood begins to flow into the sinus via other communicating dural veins, leading to reformation of thrombosis. Regional thrombus formation progresses in the lumen of the venous sinus by repetition of the above process. Pressure in the venous sinus increases, and this 605
M. Nishijima, et al. increase in internal pressure along with the organization of thrombi causes marked fibrous thickening of the sinus intima and interruption or proliferation of the elastic lamina of the sinus. Even more remarkable changes take place in the dural veins, arteries, and the arteriovenous fistulas themselves. In this vicious circle, new arteriovenous fistulas develop between adjacent dural arteries and veins. Vein-like thinning of the dural arterial wall or artery-like thickening of the dural venous wail occurs. Arteriovenous fistulas, thickened dural arteries, and dilated dural veins form an abnormal vascular network. This gradually infiltrates the connective tissue of the dura and proceeds into the wall of the venous sinus through areas where the elastic lamina of the sinus is interrupted or poorly developed. This results in stenosis or occlusion of the sinus lumen.
Acknowledgment We are grateful for the technical assistance of Miss Ryoko Kato with the histopathologieal study.
References 1. Aminoff MJ: Vascular anomalies in the intracranial dura mater. Brain 96:601--612, 1973 2. Awad IA, Little JR, Akrawi WP, et al: Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course. J Neur~surg 72:839-850, 1990 3. Balo J: Dural venous sinuses. Anat Res 106:319-325, 1950 4. Barnwell SL, Halbach VV, Dnwd CF, et al: A variant of arteriovenous fistulas within the wall of dural sinuses. Results of combined surgical and endovascular therapy. J Nenrosurg 74:199-204, 1991 5. Chaudhary MY, Sachdev VP, Cho SH, et al: Dural arteriovenous malformation of the major venous sinuses: an acquired lesion. AJNR 3:13-19, 1982 6. Endo S, Koshu K, Suzuki J: Spontaneous regression of posterior fossa dural arteriovenous malformation. J Neurostlrg 51:715-717, 1979 7. Graeb DA, Dolman CL: Radiological and pathological aspects of dural arteriovenous fistulas. Case report. J Neurosurg 64:962-967, 1986 8. Handa J, Yoneda S, Handa H: Venous sinus occlusion with a dural arteriovenous malformation of the posterior fossa. Surg Neorol 4:433-437, 1975 9. Holman E: Reflections on arteriovenous fistulas. Ann Thorac Surg 11:176-186, 1971 10. Houser OW, Campbell JK, Campbell RJ, et al: Arteriovenous malformation affecting the transverse dural venous sinus - - an acquired lesion. Mayo Clio Proc 54: 651-66 l, 1979 I 1. Kerber CW, Newton TH: The macro and microvasculature of the dora mater. Neuroradiology 6:175-179, 1973 12. Kunc Z, Brat J: Congenital arterio-sinusal fistulae. Acta Neurochir 20:85-103, 1969
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13. Kuwayama N, Nishijima M, Endo S, et al: [Dural arteriovenous malformations and ecclusive sinus lesions. Report of two cases.] Surg Cereb Stroke 18:98-102, 1990 (Jpn) 14. Kuwayama N, Takaku A, Nishijima M, et al: Multiple dural arteriovenous malformations. Report of two cases. J Neurosurg 71:932-934, 1989 15. Magidson MA, Weinberg PE: Spontaneous closure of a dural arteriovenous malformation. Surg Neurol 6:107-110, 1976 16. Malik GM, Pearce JE, Ausman JI, et al: Dural arterioveonus malformations and intracranial hemorrhage. Neurosurgery 15:332-339, 1984 17. McCormick WF, Boulter TR: Vascular malformations ~"angiomas") of the dura mater. Report of two cases. J Neurosurg 25:309-311, 1966 18. Newton TH, Cronqvist S: Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 93:1071-1078, 1969 19. Ohm T, Kajikawa H: [Dural arteriovenous malformation.] Neuroi Meal Chir 18:439-472, 1978 (Jpn) 20. Olutola IS, Eliam M, Molot M, et al: Spontaneous regression of a dural arteriovenous malformation. Neurasurgery 12:687-690, 1983 21. Padget DH: The development of the cranial venous system in man, from the viewpoint of comparative anatomy. Contrib Embryol 36:79-140, 1957 22. Piton J, Guilleux MH, Guibert-Trainer F, et al: Fistulae of the lateral sinus. J Neuroradiol 11:143-159, 1984 23. Robinson JL, Sedzimir CB: External carotid-transverse sinus fistula. Case report. J Neurosurg 33:718-720, 1970 24. Roland J, Bernad C, Bracard S, et al: Microvascularization of the intracranial dora mater. Surg Radiol Anat 9: 43-49, 1987 25. Rowbotham GF, Little E: Circulations of the cerebral hemispheres. Br J Surg 52:8-21, 1965 26. Seeger JF, Gabrielson TO, Giannotta SL: Carotid-cavernous sinus fistulas and venous thrombosis. AJNR 1: 141-148, 1980 27. Streeter GL: The developmental alterations in the vascular system of the brain of the human embryo. Contrib Embryol 8:5-38, 1918 28. Stucker FJ: Extracranial arteriovenous fistulas. Laryngoscope 84:970-975, i974 29. Sundt TM Jr, Piepgras DG: The surgical approach to arteriovenous malformations of the lateral and sigraoid dural sinuses. J Neurosurg 59:32-39, 1983 30. Takaku A, Sato T, Sakamoto T, et al: [Dural artefiovenous malformation - - with special consideration to its nature and treatment.] Neurol Med Chir 18:67-74, 1978 (Jpn)
Manuscript received February 4, 1991. Accepted in final form September 9, 1991. Address reprint requests to." Michiharu Nishijima, M.D., Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama City 930-01, Japan.
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