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Morphological changes after percutaneous transluminal angioplasty
Morphological Changes after Percutaneous Transluminal Angioplasty Alexander Y. Zubkov, M.D.,* Adam I. Lewis, M.D.,* David Scalzo, M.D.,† David H. Bernanke, Ph.D.,‡ and H. Louis Harkey, M.D.* *Departments of Neurosurgery, †Radiology, and ‡Anatomy, The University of Mississippi Medical Center, Jackson, Mississippi
Zubkov AY, Lewis AI, Scalzo D, Bernanke DH, Harkey HL. Morphological changes after percutaneous transluminal angioplasty. Surg Neurol 1999;51:399 – 403. BACKGROUND
Percutaneous transluminal angioplasty (PTA) dilates constricted arteries at the circle of Willis to reverse cerebral ischemia caused by cerebral vasospasm. Although 90% of the patients show angiographic improvement after PTA, only 70% show clinical improvement. Why some patients do not improve after PTA is unknown. We report on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture. Pathologic studies were performed to determine why PTA failed to reverse the symptoms of cerebral ischemia. METHODS
The arteries of the brain were studied by light microscopy using Gomori’s trichrome stain. The arteries were also studied by scanning and transmission electron microscopy. RESULTS
The arteries that were dilated with PTA showed compression of the connective tissue, stretching of the internal elastic lamina, and a combination of compression and stretching of the smooth muscle. The small arteries and arterioles that had been treated with an infusion of intraarterial papaverine were constricted with a thickened intimal layer. CONCLUSION
The persistence of cerebral vasospasm in small and perforating arteries may contribute to the failure of cerebral ischemia to reverse after PTA. © 1999 by Elsevier Science Inc. KEY WORDS
Morphology, percutaneous transluminal angioplasty, cerebral vasospasm, subarachnoid hemorrhage.
Address reprint requests to: Dr. Alexander Y. Zubkov, Department of Neurosurgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. Received May 27, 1998; accepted June 22, 1998. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
erebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is the leading cause of morbidity and mortality in patients who suffer ruptured aneurysms. Despite the variety of therapies, delayed ischemic deficits occur in 15% to 30% of patients with cerebral vasospasm [9]. Percutaneous transluminal angioplasty (PTA) was introduced in 1984 by Yuri Zubkov et al [17] to dilate constricted arteries at the circle of Willis. According to Yuri Zubkov, the goal of PTA was to “preserve flow through the short arteries to the brain stem and deep brain nuclei, which may be involved indirectly in the vasospastic process” [16]. Percutaneous transluminal angioplasty reverses delayed ischemic deficits in nearly 70% of patients who fail hypervolemic, hypertensive, hemodilution (Triple H) therapy [2,9]. To determine why the remaining patients do not improve after PTA, we performed pathological studies on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture 8 days later. We found that small arteries remained in vasospasm after PTA.
C
Case Report This 48-year-old woman was admitted to the University of Mississippi Medical Center in poor clinical condition (Hunt-Hess Grade V) and unresponsive to voice and noxious stimuli. She had nonreactive pupils with absent corneal and gag reflexes. Her family reported that the patient had suffered from headaches over the previous seven days. A computed tomographic (CT) scan of the brain showed diffuse SAH and hydrocephalus (Figure 1). After a ventriculostomy was placed, the patient began to open her eyes and follow simple commands. Cerebral angiography demonstrated aneurysms of 0090-3019/99/$–see front matter PII S0090-3019(98)00133-5
400 Surg Neurol 1999;51:399 –403
Zubkov et al
arteries, middle cerebral arteries, and the anterior cerebral arteries (Figure 1). The cerebral vasospasm was treated with PTA and an infusion of intra-arterial papaverine with good radiographic results (Figure 1). Transcranial Doppler (TCD) ultrasound showed normalization of blood flow velocities (Figure 2). However, the patient did not improve clinically and she died from rerupture of the left ophthalmic artery aneurysm.
Materials and Methods
Cerebral angiography is the best imaging study to evaluate cerebral vasospasm. (A) CT scan showing severe subarachnoid hemorrhage in the basal cistern; (B) left carotid angiogram showing severe vasospasm (arrows) involving all arteries, and a left ophthalmic artery aneurysm (arrowhead); (C) right carotid angiogram showing severe vasospasm (arrows) involving all arteries; (D) right carotid angiogram demonstrating the effects of percutaneous transluminal angioplasty.
1
the right posterior communicating artery and left ophthalmic artery (Figure 1). In addition, there was severe cerebral vasospasm in both internal carotid
Transcranial Doppler ultrasonographic (TCD) measurements showed severe vasospasm in the right middle cerebral artery (MCA R) and moderate vasospasm in the left middle cerebral artery (MCA L). On the third day of measurements, PTA causes a dramatic decrease in the TCD velocities.
2
The autopsy showed fresh subarachnoid hemorrhage in all basal cisterns. The circle of Willis was removed during the autopsy and prepared for light microscopy and for electron microscopy. The arteries were fixed with 4% paraformaldehyde in 0.1M sodium phosphate buffer, pH 7.3 for 7 days. Samples for light microscopy were embedded in paraffin or epoxy resin, and sections were stained with Gomori’s trichrome stain or toluidine blue stain. Samples for scanning electron microscopy (EM) were postfixed with osmium tetroxide, dehydrated in a graded series of acetone, dried using PelDri IIt, mounted on aluminum studs, coated with 200Å gold, and examined with a JOEL T300 scanning electron microscope. Samples for transmission EM were postfixed with osmium tetroxide, dehydrated in a graded series of acetone, embedded in epon-araldite epoxy resin, sectioned at 60Å, and examined with a LEO 906 transmission electron microscope.
Morphological Changes After PTA
Surg Neurol 401 1999;51:399 –403
Results Under light microscopy, cerebral vasospasm was seen in the arteries that were not dilated by PTA. These changes included thickening of the subendothelial layer, increased corrugation of internal elastic lamina, and increased deposition of connective tissue in the tunica media. Percutaneous transluminal angioplasty caused stretching of the internal elastic lamina (IEL) and muscle layer. Proliferation of the connective tissue was identified with Gomori trichrome stain. The vessel wall was dilated and stretched from the PTA. The scanning EM showed that the subendothelial layer was thickened and the IEL had increased corrugation in the spastic arteries. Increased luminal diameter was seen in the arteries treated by PTA. Examination of small branches that were not accessible to PTA showed increased thickening of the endothelial layer and decreased lumen diameter. The transmission EM studies showed vasospastic arteries with signs of degeneration, vacuolization, and desquamation of endothelial cells (Figure 3). There was corrugation of the internal elastic lamina and necrosis of single smooth-muscle cells. Percutaneous transluminal angioplasty caused stretching and compression of the IEl and smooth-muscle cells. Degenerative changes in endothelial and smooth-muscle cells were the same in PTA treated and nontreated arteries (Figure 4).
Discussion Several pathological studies have been performed in human cerebral arteries in vasospasm. Smith et al studied the morphological changes and found mild intimal thickening, marked medial necrosis, and fibrosis of the tunica media in the early stage of cerebral vasospasm [13]. There was proliferation of connective tissue in the subendothelial layer and smooth-muscle layer leading to narrowing of the arterial lumen in the later stages. Using electron microscopy, they showed necrosis within the medial layer and denuded endothelial cells. The subendothelial zone contained large amounts of collagen-like material with granular and cellular infiltrates [13]. Vascular endothlial cells often appear degenerated and contain large vacuoles. Many of the cells are desquamated from the basal membrane and cellular emboli have formed in penetrating arteries [15]. The internal elastic lamina shows increased corrugation in narrow arteries. There is disruption and fragmentation of the IEL and accumulation of glucosaminoglycans [11,15]. The tunica media is
Cerebral vasospasm has characteristic morphological changes. (A) Light microscopy slide of the vasospastic artery shows increased corrugation of IEL, increased thickness of the intima (arrow), and increased connective tissue in the medial layer (opened arrow). (B) Scanning electron microscopy of the small branch of the right internal carotid artery showing increased thickness of the intima (double arrow); (C) transmission electron microscopy (TEM) sample showing vacuolization and edema of the endothelial cells (arrow), and increased thickness of the subintimal layer (double arrow).
3
thickened because of accumulation of connective tissue as well as necrosis of smooth-muscle cells [5,11] Hughes et al observed “plump” cells in the
402 Surg Neurol 1999;51:399 –403
Zubkov et al
changes, the morphological changes found in animal SAH are variable [7]. For example, the primate SAH model shows corrugation and thickening of the media but there is no thickening of the subendothelial layer. In addition there is no correlation between the number of proliferating cells and the presence of cerebral vasospasm [12]. The most striking morphological feature after PTA is stretching of the arterial wall. Flattening of the endothelial layer, straightening and thinning of the IEL and smooth-muscle cells are found after PTA [1,4,10]. Balloon angioplasty stretches the normal architecture of the collagen lattice and deforms the organization of the fibers [14]. Our study showed that PTA caused flattening of all the arterial wall layers without significant alteration of the vessel structure. This has been reported in other studies performed in humans [16] and animals [1,6]. The failure of PTA to reverse cerebral ischemia in this case may be attributable to persistent cerebral vasospasm in small and penetrating arteries. The small and penetrating arteries have a reduced luminal diameter due to infiltration of protein and macrophages into the intima [5,15]. Small branches and penetrating arteries cannot be treated with PTA. Intra-arterial papaverine infusion may dilate these small arteries transiently in the acute phase of cerebral vasospasm. In cases of chronic cerebral vasospasm, arteries are refractory to intra-arterial papaverine infusion [3,8]. Percutaneous transluminal angioplasty and intra-arterial papaverine infusion must be performed early in the course of cerebral vasospasm to increase luminal diameter of the arteries and reverse cerebral ischemia.
Conclusion PTA dilates arteries without additional morphological damage to the arteries. (A) After PTA there is straightening of the IEL (arrow) and compression of the layers of the vessel wall; (B) high magnification shows increased thickness of the intima in the small vessel; (C) transmission EM shows straightening of IEL and smoothmuscle cells after PTA.
4
tunica media and immediately beneath the intima [5]. The tunica adventitia frequently shows increased deposition of connective tissue and accumulation of lymphocytes, macrophages, and plasma cells. Unlike human cerebral vasospasm where every layer of the vessel wall has distinct morphological
Percutaneous transluminal angioplasty is an effective method of treatment for cerebral vasospasm. It effectively dilatates the arterial lumen without additional destruction of the arterial wall. The failure of the patient to improve after PTA is likely due to persistent vasospasm of the small and perforating arteries which are altered by structural changes. Early aggressive therapy with PTA and infusion of intra-arterial papaverine is required to reverse cerebral ischemia because papaverine does not dilate affected arteries in the chronic phase of cerebral vasospasm. This work is dedicated to the memory of Prof. Yuri N. Zubkov, M.D.
Morphological Changes After PTA
Surg Neurol 403 1999;51:399 –403
REFERENCES 1. Chan PD, Findlay JM, Vollrath B, Cook DA, Grace M, Chen MH, Ashforth RA. Pharmacological and morphological effects of in vitro transluminal balloon angioplasty on normal and vasospastic canine basilar arteries. J Neurosurg 1995;83:522–30. 2. Eskridge JM, Newell DW, Winn HR. Endovascular treatment of vasospasm. Neurosurg Clin N Am 1994; 5:437– 47. 3. Fujiwara N, Honjo Y, Ohkawa M, Tanabe M, Irie K, Nagao S, Takashima H, Satoh K, Kojima K. Intraarterial infusion of papaverine in experimental cerebral vasospasm. AJNR 1997;18:255– 62. 4. Honma Y, Fujiwara T, Irie K, Ohkawa M, Nagao S. Morphological changes in human cerebral arteries after percutaneous transluminal angioplasty for vasospasm caused by subarachnoid hemorrhage. Neurosurgery 1995;36:1073– 80. 5. Hughes JT, Schianchi PM. Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 1978;48:515–25. 6. Kobayashi H, Ide H, Aradachi H, Arai Y, Handa Y, Kubota T. Histological studies of intracranial vessels in primates following transluminal angioplasty for vasospasm. J Neurosurg 1993;78:481– 6. 7. Liszczak TM, Black PM, Tzouras A, Foley L, Zervas NT. Morphological changes of the basilar artery, ventricles, and choroid plexus after experimental SAH. J Neurosurg 1984;61:486 –93. 8. Macdonald RL, Zhang J, Sima B, Johns L. Papaverinesensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs. Neurosurgery 1995;37:962–7. 9. Newell DW, Eskeridge J, Mayberg M, Grady MS, Lewis D, Winn HR. Endovascular treatment of intracranial aneurysms and cerebral vasospasm. Clin Neurosurg 1992;39:348 – 60. 10. Ohkawa M, Fujiwara N, Tanabe M, Takashima H, Satoh K, Kojima K, Irie K, Honjo Y, Nagao S. Cerebral vasospastic vessels: histologic changes after percutaneous transluminal angioplasty. Radiology 1996; 198:179 –184. 11. Peerless SJ, Kassell NF, Komatsu K, Hunter IG. Cerebral vasospasm: acute proliferative vasculopathy? II.
12. 13. 14. 15.
16. 17.
morphology. Proceedings of the Second International Workshop, Amsterdam, the Netherlands. Baltimore, Williams & Wilkins 1980:88 –96. Pluta RM, Zauner A, Morgan JK, Muraszko KM, Oldfield EH. Is vasospasm related to proliferative arteriopathy? J Neurosurg 1992;77:740 – 8. Smith RR, Clower BR, Grotendorst GM, Yabuno N, Cruse JM. Arterial wall changes in early human vasospasm. Neurosurgery 1985;16:171– 6. Yamamoto Y, Smith RR, Bernanke DH. Mechanism of action of balloon angioplasty in cerebral vasospasm. Neurosurgery 1992;30:1–5; discussion 5– 6. Zakarevicius Z. Constrictive-stenotic angiopathy in patients in hemorrhagic period of cerebral aneurysms. Polenov Neurosurgical Institute, St. Petersburg, Russia. Thesis 1995:85–129. Zubkov YN, Alexander LF, Smith RR, Benashvili GM, Semenyutin V, Bernanke DH. Angioplasty of vasospasm: is it reasonable? Neurol Res 1994;16:9 –11. Zubkov YN, Nikiforov BM, Shustin VA. Balloon catheter technique for dilatation of constricted cerebral arteries after aneurysmal SAH. Acta Neurochir (Wien) 1984;70:65–79.
COMMENTARY
Balloon angioplasty for cerebral vasospasm was pioneered by Yuri Zubkov, who published his series in 1984. With this case, Dr. Zubkov’s son clearly illustrates clearly why certain patients die in spite of balloon angioplasty. Although we concur with him that this is the best tool to reverse the catastrophic effects of vasospasm, we have been disappointed with the use of papaverine, which dilates the spastic vessels only transiently and often raises the intracranial pressure. Gerard Debrun, M.D. Departments of Neurosurgery and Radiology University of Illinois at Chicago Chicago, Illinois
Fly bit the bare head of a Bald Man who, endeavoring to destroy it, gave himself a heavy slap. Escaping, the Fly said mockingly, “You who have wished to revenge, even with death, the prick of a tiny insect, see what you have done to yourself to add insult to injury?” The Bald Man replied, “I can easily make peace with myself, because I know there was no intention to hurt. But you, an ill-favored and contemptible insect who delights in sucking human blood, I wish that I could have killed you even if I had incurred a heavier penalty.”
A
“Revenge will hurt the avenger.” —Æsop’s Fables
Zubkov AY, Lewis AI, Scalzo D, Bernanke DH, Harkey HL. Morphological changes after percutaneous transluminal angioplasty. Surg Neurol 1999;51:399 – 403. BACKGROUND
Percutaneous transluminal angioplasty (PTA) dilates constricted arteries at the circle of Willis to reverse cerebral ischemia caused by cerebral vasospasm. Although 90% of the patients show angiographic improvement after PTA, only 70% show clinical improvement. Why some patients do not improve after PTA is unknown. We report on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture. Pathologic studies were performed to determine why PTA failed to reverse the symptoms of cerebral ischemia. METHODS
The arteries of the brain were studied by light microscopy using Gomori’s trichrome stain. The arteries were also studied by scanning and transmission electron microscopy. RESULTS
The arteries that were dilated with PTA showed compression of the connective tissue, stretching of the internal elastic lamina, and a combination of compression and stretching of the smooth muscle. The small arteries and arterioles that had been treated with an infusion of intraarterial papaverine were constricted with a thickened intimal layer. CONCLUSION
The persistence of cerebral vasospasm in small and perforating arteries may contribute to the failure of cerebral ischemia to reverse after PTA. © 1999 by Elsevier Science Inc. KEY WORDS
Morphology, percutaneous transluminal angioplasty, cerebral vasospasm, subarachnoid hemorrhage.
Address reprint requests to: Dr. Alexander Y. Zubkov, Department of Neurosurgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. Received May 27, 1998; accepted June 22, 1998. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
erebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is the leading cause of morbidity and mortality in patients who suffer ruptured aneurysms. Despite the variety of therapies, delayed ischemic deficits occur in 15% to 30% of patients with cerebral vasospasm [9]. Percutaneous transluminal angioplasty (PTA) was introduced in 1984 by Yuri Zubkov et al [17] to dilate constricted arteries at the circle of Willis. According to Yuri Zubkov, the goal of PTA was to “preserve flow through the short arteries to the brain stem and deep brain nuclei, which may be involved indirectly in the vasospastic process” [16]. Percutaneous transluminal angioplasty reverses delayed ischemic deficits in nearly 70% of patients who fail hypervolemic, hypertensive, hemodilution (Triple H) therapy [2,9]. To determine why the remaining patients do not improve after PTA, we performed pathological studies on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture 8 days later. We found that small arteries remained in vasospasm after PTA.
C
Case Report This 48-year-old woman was admitted to the University of Mississippi Medical Center in poor clinical condition (Hunt-Hess Grade V) and unresponsive to voice and noxious stimuli. She had nonreactive pupils with absent corneal and gag reflexes. Her family reported that the patient had suffered from headaches over the previous seven days. A computed tomographic (CT) scan of the brain showed diffuse SAH and hydrocephalus (Figure 1). After a ventriculostomy was placed, the patient began to open her eyes and follow simple commands. Cerebral angiography demonstrated aneurysms of 0090-3019/99/$–see front matter PII S0090-3019(98)00133-5
400 Surg Neurol 1999;51:399 –403
Zubkov et al
arteries, middle cerebral arteries, and the anterior cerebral arteries (Figure 1). The cerebral vasospasm was treated with PTA and an infusion of intra-arterial papaverine with good radiographic results (Figure 1). Transcranial Doppler (TCD) ultrasound showed normalization of blood flow velocities (Figure 2). However, the patient did not improve clinically and she died from rerupture of the left ophthalmic artery aneurysm.
Materials and Methods
Cerebral angiography is the best imaging study to evaluate cerebral vasospasm. (A) CT scan showing severe subarachnoid hemorrhage in the basal cistern; (B) left carotid angiogram showing severe vasospasm (arrows) involving all arteries, and a left ophthalmic artery aneurysm (arrowhead); (C) right carotid angiogram showing severe vasospasm (arrows) involving all arteries; (D) right carotid angiogram demonstrating the effects of percutaneous transluminal angioplasty.
1
the right posterior communicating artery and left ophthalmic artery (Figure 1). In addition, there was severe cerebral vasospasm in both internal carotid
Transcranial Doppler ultrasonographic (TCD) measurements showed severe vasospasm in the right middle cerebral artery (MCA R) and moderate vasospasm in the left middle cerebral artery (MCA L). On the third day of measurements, PTA causes a dramatic decrease in the TCD velocities.
2
The autopsy showed fresh subarachnoid hemorrhage in all basal cisterns. The circle of Willis was removed during the autopsy and prepared for light microscopy and for electron microscopy. The arteries were fixed with 4% paraformaldehyde in 0.1M sodium phosphate buffer, pH 7.3 for 7 days. Samples for light microscopy were embedded in paraffin or epoxy resin, and sections were stained with Gomori’s trichrome stain or toluidine blue stain. Samples for scanning electron microscopy (EM) were postfixed with osmium tetroxide, dehydrated in a graded series of acetone, dried using PelDri IIt, mounted on aluminum studs, coated with 200Å gold, and examined with a JOEL T300 scanning electron microscope. Samples for transmission EM were postfixed with osmium tetroxide, dehydrated in a graded series of acetone, embedded in epon-araldite epoxy resin, sectioned at 60Å, and examined with a LEO 906 transmission electron microscope.
Morphological Changes After PTA
Surg Neurol 401 1999;51:399 –403
Results Under light microscopy, cerebral vasospasm was seen in the arteries that were not dilated by PTA. These changes included thickening of the subendothelial layer, increased corrugation of internal elastic lamina, and increased deposition of connective tissue in the tunica media. Percutaneous transluminal angioplasty caused stretching of the internal elastic lamina (IEL) and muscle layer. Proliferation of the connective tissue was identified with Gomori trichrome stain. The vessel wall was dilated and stretched from the PTA. The scanning EM showed that the subendothelial layer was thickened and the IEL had increased corrugation in the spastic arteries. Increased luminal diameter was seen in the arteries treated by PTA. Examination of small branches that were not accessible to PTA showed increased thickening of the endothelial layer and decreased lumen diameter. The transmission EM studies showed vasospastic arteries with signs of degeneration, vacuolization, and desquamation of endothelial cells (Figure 3). There was corrugation of the internal elastic lamina and necrosis of single smooth-muscle cells. Percutaneous transluminal angioplasty caused stretching and compression of the IEl and smooth-muscle cells. Degenerative changes in endothelial and smooth-muscle cells were the same in PTA treated and nontreated arteries (Figure 4).
Discussion Several pathological studies have been performed in human cerebral arteries in vasospasm. Smith et al studied the morphological changes and found mild intimal thickening, marked medial necrosis, and fibrosis of the tunica media in the early stage of cerebral vasospasm [13]. There was proliferation of connective tissue in the subendothelial layer and smooth-muscle layer leading to narrowing of the arterial lumen in the later stages. Using electron microscopy, they showed necrosis within the medial layer and denuded endothelial cells. The subendothelial zone contained large amounts of collagen-like material with granular and cellular infiltrates [13]. Vascular endothlial cells often appear degenerated and contain large vacuoles. Many of the cells are desquamated from the basal membrane and cellular emboli have formed in penetrating arteries [15]. The internal elastic lamina shows increased corrugation in narrow arteries. There is disruption and fragmentation of the IEL and accumulation of glucosaminoglycans [11,15]. The tunica media is
Cerebral vasospasm has characteristic morphological changes. (A) Light microscopy slide of the vasospastic artery shows increased corrugation of IEL, increased thickness of the intima (arrow), and increased connective tissue in the medial layer (opened arrow). (B) Scanning electron microscopy of the small branch of the right internal carotid artery showing increased thickness of the intima (double arrow); (C) transmission electron microscopy (TEM) sample showing vacuolization and edema of the endothelial cells (arrow), and increased thickness of the subintimal layer (double arrow).
3
thickened because of accumulation of connective tissue as well as necrosis of smooth-muscle cells [5,11] Hughes et al observed “plump” cells in the
402 Surg Neurol 1999;51:399 –403
Zubkov et al
changes, the morphological changes found in animal SAH are variable [7]. For example, the primate SAH model shows corrugation and thickening of the media but there is no thickening of the subendothelial layer. In addition there is no correlation between the number of proliferating cells and the presence of cerebral vasospasm [12]. The most striking morphological feature after PTA is stretching of the arterial wall. Flattening of the endothelial layer, straightening and thinning of the IEL and smooth-muscle cells are found after PTA [1,4,10]. Balloon angioplasty stretches the normal architecture of the collagen lattice and deforms the organization of the fibers [14]. Our study showed that PTA caused flattening of all the arterial wall layers without significant alteration of the vessel structure. This has been reported in other studies performed in humans [16] and animals [1,6]. The failure of PTA to reverse cerebral ischemia in this case may be attributable to persistent cerebral vasospasm in small and penetrating arteries. The small and penetrating arteries have a reduced luminal diameter due to infiltration of protein and macrophages into the intima [5,15]. Small branches and penetrating arteries cannot be treated with PTA. Intra-arterial papaverine infusion may dilate these small arteries transiently in the acute phase of cerebral vasospasm. In cases of chronic cerebral vasospasm, arteries are refractory to intra-arterial papaverine infusion [3,8]. Percutaneous transluminal angioplasty and intra-arterial papaverine infusion must be performed early in the course of cerebral vasospasm to increase luminal diameter of the arteries and reverse cerebral ischemia.
Conclusion PTA dilates arteries without additional morphological damage to the arteries. (A) After PTA there is straightening of the IEL (arrow) and compression of the layers of the vessel wall; (B) high magnification shows increased thickness of the intima in the small vessel; (C) transmission EM shows straightening of IEL and smoothmuscle cells after PTA.
4
tunica media and immediately beneath the intima [5]. The tunica adventitia frequently shows increased deposition of connective tissue and accumulation of lymphocytes, macrophages, and plasma cells. Unlike human cerebral vasospasm where every layer of the vessel wall has distinct morphological
Percutaneous transluminal angioplasty is an effective method of treatment for cerebral vasospasm. It effectively dilatates the arterial lumen without additional destruction of the arterial wall. The failure of the patient to improve after PTA is likely due to persistent vasospasm of the small and perforating arteries which are altered by structural changes. Early aggressive therapy with PTA and infusion of intra-arterial papaverine is required to reverse cerebral ischemia because papaverine does not dilate affected arteries in the chronic phase of cerebral vasospasm. This work is dedicated to the memory of Prof. Yuri N. Zubkov, M.D.
Morphological Changes After PTA
Surg Neurol 403 1999;51:399 –403
REFERENCES 1. Chan PD, Findlay JM, Vollrath B, Cook DA, Grace M, Chen MH, Ashforth RA. Pharmacological and morphological effects of in vitro transluminal balloon angioplasty on normal and vasospastic canine basilar arteries. J Neurosurg 1995;83:522–30. 2. Eskridge JM, Newell DW, Winn HR. Endovascular treatment of vasospasm. Neurosurg Clin N Am 1994; 5:437– 47. 3. Fujiwara N, Honjo Y, Ohkawa M, Tanabe M, Irie K, Nagao S, Takashima H, Satoh K, Kojima K. Intraarterial infusion of papaverine in experimental cerebral vasospasm. AJNR 1997;18:255– 62. 4. Honma Y, Fujiwara T, Irie K, Ohkawa M, Nagao S. Morphological changes in human cerebral arteries after percutaneous transluminal angioplasty for vasospasm caused by subarachnoid hemorrhage. Neurosurgery 1995;36:1073– 80. 5. Hughes JT, Schianchi PM. Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 1978;48:515–25. 6. Kobayashi H, Ide H, Aradachi H, Arai Y, Handa Y, Kubota T. Histological studies of intracranial vessels in primates following transluminal angioplasty for vasospasm. J Neurosurg 1993;78:481– 6. 7. Liszczak TM, Black PM, Tzouras A, Foley L, Zervas NT. Morphological changes of the basilar artery, ventricles, and choroid plexus after experimental SAH. J Neurosurg 1984;61:486 –93. 8. Macdonald RL, Zhang J, Sima B, Johns L. Papaverinesensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs. Neurosurgery 1995;37:962–7. 9. Newell DW, Eskeridge J, Mayberg M, Grady MS, Lewis D, Winn HR. Endovascular treatment of intracranial aneurysms and cerebral vasospasm. Clin Neurosurg 1992;39:348 – 60. 10. Ohkawa M, Fujiwara N, Tanabe M, Takashima H, Satoh K, Kojima K, Irie K, Honjo Y, Nagao S. Cerebral vasospastic vessels: histologic changes after percutaneous transluminal angioplasty. Radiology 1996; 198:179 –184. 11. Peerless SJ, Kassell NF, Komatsu K, Hunter IG. Cerebral vasospasm: acute proliferative vasculopathy? II.
12. 13. 14. 15.
16. 17.
morphology. Proceedings of the Second International Workshop, Amsterdam, the Netherlands. Baltimore, Williams & Wilkins 1980:88 –96. Pluta RM, Zauner A, Morgan JK, Muraszko KM, Oldfield EH. Is vasospasm related to proliferative arteriopathy? J Neurosurg 1992;77:740 – 8. Smith RR, Clower BR, Grotendorst GM, Yabuno N, Cruse JM. Arterial wall changes in early human vasospasm. Neurosurgery 1985;16:171– 6. Yamamoto Y, Smith RR, Bernanke DH. Mechanism of action of balloon angioplasty in cerebral vasospasm. Neurosurgery 1992;30:1–5; discussion 5– 6. Zakarevicius Z. Constrictive-stenotic angiopathy in patients in hemorrhagic period of cerebral aneurysms. Polenov Neurosurgical Institute, St. Petersburg, Russia. Thesis 1995:85–129. Zubkov YN, Alexander LF, Smith RR, Benashvili GM, Semenyutin V, Bernanke DH. Angioplasty of vasospasm: is it reasonable? Neurol Res 1994;16:9 –11. Zubkov YN, Nikiforov BM, Shustin VA. Balloon catheter technique for dilatation of constricted cerebral arteries after aneurysmal SAH. Acta Neurochir (Wien) 1984;70:65–79.
COMMENTARY
Balloon angioplasty for cerebral vasospasm was pioneered by Yuri Zubkov, who published his series in 1984. With this case, Dr. Zubkov’s son clearly illustrates clearly why certain patients die in spite of balloon angioplasty. Although we concur with him that this is the best tool to reverse the catastrophic effects of vasospasm, we have been disappointed with the use of papaverine, which dilates the spastic vessels only transiently and often raises the intracranial pressure. Gerard Debrun, M.D. Departments of Neurosurgery and Radiology University of Illinois at Chicago Chicago, Illinois
Fly bit the bare head of a Bald Man who, endeavoring to destroy it, gave himself a heavy slap. Escaping, the Fly said mockingly, “You who have wished to revenge, even with death, the prick of a tiny insect, see what you have done to yourself to add insult to injury?” The Bald Man replied, “I can easily make peace with myself, because I know there was no intention to hurt. But you, an ill-favored and contemptible insect who delights in sucking human blood, I wish that I could have killed you even if I had incurred a heavier penalty.”
A
“Revenge will hurt the avenger.” —Æsop’s Fables