Clinical Neurology and Neurosurgery 124 (2014) 192–193
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Letters to the Editor Mechanisms of cyst formation after radiosurgery for intracranial arteriovenous malformations Keywords: Cyst Intracranial arteriovenous malformation Radiosurgery Stroke
Dear Sir, I have read, with interest, a recently published article in Clinical Neurology and Neurosurgery by Matsuo et al. titled ‘Cyst formation after linac-based radiosurgery for arteriovenous malformation: examination of predictive factors using magnetic resonance imaging’ [1]. The authors analyzed the neuroimaging and clinical characteristics of five patients who developed cysts following radiosurgical treatment of intracranial arteriovenous malformations (AVM). The incidence of post-radiosurgery cyst formation in 109 AVMs treated at the authors’ institution was 5.5%. All five patients had complete AVM obliteration, and cyst formation occurred after AVM obliteration in three patients (60%). Longitudinal analysis showed the emergence of perinidal low magnetic resonance imaging (MRI) T2-weighted signal, suggestive of subclinical hemorrhage, prior to cyst formation. Shuto et al. reported cyst formation following AVM radiosurgery in 18 out of 775 patients (2.3%) [2]. Craniotomy for cyst excision was performed in 10 patients (56%). Based on the histopathology of the resected cysts, the authors hypothesized that the initial process underlying cyst formation is radiation-induced inflammation of the perinidal brain parenchyma. Subsequently, inflammation-induced breakdown of the blood–brain barrier results in fluid extravasation and formation of a perinidal cavity. Inflammation can, in some cases, promote neovascularization of the cyst wall. These fragile, de novo capillaries are prone to rupture, thereby increasing the cyst’s protein content and promoting osmotic cyst expansion. Hemorrhage of an angiomatous lesion, which is present in a fraction of cysts and is evident on MRI as an enhancing nodule in the cyst wall, into the adjacent parenchyma contributes to cyst development and progression whereas hemorrhage primarily within the angiomatous lesion results in formation of a chronic encapsulating hematoma (CHE; 28% of cysts in this series). Since the formation of both post-radiosurgery cysts and CHEs can originate from angiomatous lesions, these entities may be two ends of the same pathophysiological spectrum. Thus, in the same manner as postradiosurgery cysts, CHEs may be encouraged and maintained by radiation-induced inflammation. In a study of 444 patients with unruptured AVMs, we found cyst formation in 2.3% at a median interval of 80 months following radiosurgery [3]. Patients with radiation-induced changes (RIC), defined 0303-8467/© 2014 Elsevier B.V. All rights reserved.
as perinidal T2-weighted hyperintensities on magnetic resonance imaging, were more likely to develop radiosurgery-induced cysts (P = 0.032). The rate of cyst formation in 565 patients with ruptured AVMs was 1.1% [4]. The rate of cyst formation may be higher in unruptured AVMs due to the relatively increased susceptibility of the normal brain parenchyma surrounding unruptured AVMs to radiation-induced effects, such as inflammation, compared to the gliotic brain surrounding ruptured AVMs [5–7]. Similarly, Yen et al. found that patients with unruptured AVMs were more susceptible to developing RIC than patients with ruptured AVMs [8]. Due to the uncommon occurrence of cyst formation following AVM radiosurgery, the optimal management of these patients is unknown. Additionally, post-radiosurgery cysts are heterogeneous lesions with dynamic radiologic and clinical natural histories. Therefore, each case should be managed on an individual basis, whether it is conservatively or invasively with stereotactic drainage, Ommaya reservoir placement, cyst shunting, or craniotomy for cyst excision. In general, asymptomatic cysts may be managed conservatively while intervention should be undertaken for symptomatic cysts. In carefully selected cases, small symptomatic cysts may be managed with medical treatment of the clinical sequelae and serial neuroimaging. However, failure to respond to medical therapy or clinical deterioration should prompt intervention, even in the absence of cyst enlargement. Intervention may also be warranted for large asymptomatic cysts resulting in significant local mass effect or herniation. Stereotactic drainage without placement of an Ommaya reservoirs or shunt will likely only result in temporary cyst reduction. Patients with cysts associated with an angiomatous lesion or with CHEs should undergo craniotomy with opening of the cyst and resection of the angiomatous lesion or resection of the CHE, respectively [2].
References [1] Matsuo T, Kamada K, Izumo T, Hayashi N, Nagata I. Cyst formation after linac-based radiosurgery for arteriovenous malformation: examination of predictive factors using magnetic resonance imaging. Clin Neurol Neurosurg 2014;121:10–6. [2] Shuto T, Ohtake M, Matsunaga S. Proposed mechanism for cyst formation and enlargement following gamma knife surgery for arteriovenous malformations. J Neurosurg 2012;117(Suppl.):135–43. [3] Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP. Radiosurgery for patients with unruptured intracranial arteriovenous malformations. J Neurosurg 2013;118(5):958–66. [4] Ding D, Yen CP, Starke RM, Xu Z, Sheehan JP. Radiosurgery for ruptured intracranial arteriovenous malformations. J Neurosurg 2014, http://dx.doi.org/10.3171/2014.2.jns131605 [Epub date 2014 Mar 21]. [5] Ding D, Yen CP, Starke RM, Xu Z, Sun X, Sheehan JP. Radiosurgery for SpetzlerMartin Grade III arteriovenous malformations. J Neurosurg 2014;120(4):959–69. [6] Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP. Radiosurgery for lowgrade intracranial arteriovenous malformations. J Neurosurg 2014, http://dx.doi.org/10.3171/2014.1.jns131713 [Epub date 2014 Mar 7]. [7] Ding D, Yen CP, Starke RM, Xu Z, Sun X, Sheehan JP. Outcomes following singlesession radiosurgery for high-grade intracranial arteriovenous malformations.
Letters to the Editor / Clinical Neurology and Neurosurgery 124 (2014) 192–193 Br J Neurosurg 2013, http://dx.doi.org/10.3109/02688697.2013.872227 [Epub date 2013 Dec 27]. [8] Yen CP, Matsumoto JA, Wintermark M, Schwyzer L, Evans AJ, Jensen ME, et al. Radiation-induced imaging changes following gamma knife surgery for cerebral arteriovenous malformations. J Neurosurg 2013;118(1):63–73.
Dale Ding ∗ University of Virginia, Department of Neurosurgery, Charlottesville 22908, USA
193
is seen to be hyperintense in the T2 sequence of MRI. The ratio of reduction in size of the HNP is even higher in T2 hyperintense herniations [6]. The contrast enhancement in the neovascularization areas of HNP, presenting an enhancing rim, is thought to be a major determinant of spontaneous regression of the HNP [7]. However, the degree of neovascularization is varied. The thickness of rim enhancement is a more important factor to spontaneous regression than the extent of rim enhancement [7].
∗ Correspondence
to: University of Virginia, Department of Neurosurgery, P.O. Box 800212, Charlottesville 22908, USA. Tel.: +1 434 924 2203; fax: +1 434 982 5753. E-mail address: [email protected] 6 June 2014 Available online 17 July 2014 http://dx.doi.org/10.1016/j.clineuro.2014.06.042
The prediction of MRI for the possibility of regression of herniated nucleus pulposus Dear Sir, We are pleased to read the interesting article by Mohamed Macki and colleagues [1] in the May 2014 issue of Clinical Neurology and Neurosurgery. The authors reviewed the spontaneous regression of sequestrated intervertebral discs, which definitely would add to the current literature. We want to contribute to the evaluation of the herniated nucleus pulposus (HNP) for the possibility of regression in magnetic resonance imaging (MRI). In the literature, there is no clear information about the possibility of the regression of HNP and studies have reported different occurrence times and rates of regression [2,3]. Spontaneous regression of HNP is a rare condition. Unless the patient wants surgical treatment, if there are high risk factors for the surgical approach and there is no neurological deficit, the conservative treatment and the follow-up MRI study may be needed, even though the size of herniated disk is large. In such cases, the contrast-enhanced MRI can give us several predictions associated with the prognosis of HNP as follows: (1) The type of HNP is more related to the spontaneous regression than the size of HNP [4]. In case of extrusion or sequestration, an autoimmune response is promptly activated, which is a mechanism of the spontaneous regression [5]. The regression of HNP is seen frequently in the cases of migrating disk herniation [2]. It is presumed that the disk is much more interacted with the epidural vascular supply and this is another regression mechanism, which is about inflammation and neovascularization. (2) The neovascularization of the HNP is easily detected by MRI. The edema of the inflammation and neovascularization of HNP
Spontaneous regression of the HNP in contrast-enhanced MRI usually correlates with clinical improvement. MRI is considered to be a useful tool to predict the spontaneous regressive potential of HNP. Although there is not much study stated in the literature, Splendiani et al. reported that contrast-enhanced MRI offers predictive information about evaluation of disk herniation. Studies included large number of patients are needed to support this conclusion but we also avoid using contrast agent which might have an adverse effect for renal function. This issue is important for elderly patients at high risk for surgery. Diffusion sequence of MRI without needs of contrast shows the cellular density changes in the neovascularization quantitatively. This would allow quantitative evaluation of the disk management and is easily repeated for follow up. Although we have not encountered studies in the literature, this point could be evaluated in future studies. References [1] Macki M, Hernandez-Hermann M, Bydon M, Gokaslan A, McGovern K, Bydon A. Spontaneous regression of sequestrated lumbar disc herniations: literature review. Clin Neurol Neurosurg 2014;120(May):136–41. [2] Komori H, Shinomiya K, Nakai O, Yamaura I, Takada S, Furuya K. The natural history of herniated nucleus pulposus with radiculopathy. Spine 1996;21:225–9. [3] Masui T, Yukawa Y, Nakamura S, Kajino G, Matsubara Y, Kato F, et al. Natural history of patients with lumbar disc herniation observed by magnetic resonance imaging for minimum 7 years. J Spinal Disord Tech 2005;18:121–6. [4] Ahn SH, Ahn MW, Byun WM. Effect of the transligamentous extension of lumbar disc herniations on their regression and the clinical outcome of sciatica. Spine (Phila Pa 1976) 2000;25(4):475–80. [5] Kim SG, Yang JC, Kim TW, Park KH. Spontaneous regression of extruded lumbar disc herniation: three cases report. Korean J Spine 2013;10(2):78–81. [6] Splendiani A, Puglielli E, De Amicis R, Barile A, Masciocchi C, Gallucci M. Spontaneous resolution of lumbar disk herniation: predictive signs for prognostic evaluation. Neuroradiology 2004;46:916–22. [7] Autio RA, Karppinen J, Niinimaki J, Ojala R, Kurunlahti M, Haapea M, et al. Determinants of spontaneous resorption of intervertebral disc herniations. Spine (Phila Pa 1976) 2006;31(11):1247–52.
Ferhat Cuce ∗ Ahmet Eroglu Van Military Hospital, Van, Turkey ∗ Tel.: +90 536 8515475; fax: +90 4324220244. E-mail address: [email protected] (F. Cuce)
9 June 2014 Available online 12 July 2014 http://dx.doi.org/10.1016/j.clineuro.2014.07.005
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Letters to the Editor Mechanisms of cyst formation after radiosurgery for intracranial arteriovenous malformations Keywords: Cyst Intracranial arteriovenous malformation Radiosurgery Stroke
Dear Sir, I have read, with interest, a recently published article in Clinical Neurology and Neurosurgery by Matsuo et al. titled ‘Cyst formation after linac-based radiosurgery for arteriovenous malformation: examination of predictive factors using magnetic resonance imaging’ [1]. The authors analyzed the neuroimaging and clinical characteristics of five patients who developed cysts following radiosurgical treatment of intracranial arteriovenous malformations (AVM). The incidence of post-radiosurgery cyst formation in 109 AVMs treated at the authors’ institution was 5.5%. All five patients had complete AVM obliteration, and cyst formation occurred after AVM obliteration in three patients (60%). Longitudinal analysis showed the emergence of perinidal low magnetic resonance imaging (MRI) T2-weighted signal, suggestive of subclinical hemorrhage, prior to cyst formation. Shuto et al. reported cyst formation following AVM radiosurgery in 18 out of 775 patients (2.3%) [2]. Craniotomy for cyst excision was performed in 10 patients (56%). Based on the histopathology of the resected cysts, the authors hypothesized that the initial process underlying cyst formation is radiation-induced inflammation of the perinidal brain parenchyma. Subsequently, inflammation-induced breakdown of the blood–brain barrier results in fluid extravasation and formation of a perinidal cavity. Inflammation can, in some cases, promote neovascularization of the cyst wall. These fragile, de novo capillaries are prone to rupture, thereby increasing the cyst’s protein content and promoting osmotic cyst expansion. Hemorrhage of an angiomatous lesion, which is present in a fraction of cysts and is evident on MRI as an enhancing nodule in the cyst wall, into the adjacent parenchyma contributes to cyst development and progression whereas hemorrhage primarily within the angiomatous lesion results in formation of a chronic encapsulating hematoma (CHE; 28% of cysts in this series). Since the formation of both post-radiosurgery cysts and CHEs can originate from angiomatous lesions, these entities may be two ends of the same pathophysiological spectrum. Thus, in the same manner as postradiosurgery cysts, CHEs may be encouraged and maintained by radiation-induced inflammation. In a study of 444 patients with unruptured AVMs, we found cyst formation in 2.3% at a median interval of 80 months following radiosurgery [3]. Patients with radiation-induced changes (RIC), defined 0303-8467/© 2014 Elsevier B.V. All rights reserved.
as perinidal T2-weighted hyperintensities on magnetic resonance imaging, were more likely to develop radiosurgery-induced cysts (P = 0.032). The rate of cyst formation in 565 patients with ruptured AVMs was 1.1% [4]. The rate of cyst formation may be higher in unruptured AVMs due to the relatively increased susceptibility of the normal brain parenchyma surrounding unruptured AVMs to radiation-induced effects, such as inflammation, compared to the gliotic brain surrounding ruptured AVMs [5–7]. Similarly, Yen et al. found that patients with unruptured AVMs were more susceptible to developing RIC than patients with ruptured AVMs [8]. Due to the uncommon occurrence of cyst formation following AVM radiosurgery, the optimal management of these patients is unknown. Additionally, post-radiosurgery cysts are heterogeneous lesions with dynamic radiologic and clinical natural histories. Therefore, each case should be managed on an individual basis, whether it is conservatively or invasively with stereotactic drainage, Ommaya reservoir placement, cyst shunting, or craniotomy for cyst excision. In general, asymptomatic cysts may be managed conservatively while intervention should be undertaken for symptomatic cysts. In carefully selected cases, small symptomatic cysts may be managed with medical treatment of the clinical sequelae and serial neuroimaging. However, failure to respond to medical therapy or clinical deterioration should prompt intervention, even in the absence of cyst enlargement. Intervention may also be warranted for large asymptomatic cysts resulting in significant local mass effect or herniation. Stereotactic drainage without placement of an Ommaya reservoirs or shunt will likely only result in temporary cyst reduction. Patients with cysts associated with an angiomatous lesion or with CHEs should undergo craniotomy with opening of the cyst and resection of the angiomatous lesion or resection of the CHE, respectively [2].
References [1] Matsuo T, Kamada K, Izumo T, Hayashi N, Nagata I. Cyst formation after linac-based radiosurgery for arteriovenous malformation: examination of predictive factors using magnetic resonance imaging. Clin Neurol Neurosurg 2014;121:10–6. [2] Shuto T, Ohtake M, Matsunaga S. Proposed mechanism for cyst formation and enlargement following gamma knife surgery for arteriovenous malformations. J Neurosurg 2012;117(Suppl.):135–43. [3] Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP. Radiosurgery for patients with unruptured intracranial arteriovenous malformations. J Neurosurg 2013;118(5):958–66. [4] Ding D, Yen CP, Starke RM, Xu Z, Sheehan JP. Radiosurgery for ruptured intracranial arteriovenous malformations. J Neurosurg 2014, http://dx.doi.org/10.3171/2014.2.jns131605 [Epub date 2014 Mar 21]. [5] Ding D, Yen CP, Starke RM, Xu Z, Sun X, Sheehan JP. Radiosurgery for SpetzlerMartin Grade III arteriovenous malformations. J Neurosurg 2014;120(4):959–69. [6] Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP. Radiosurgery for lowgrade intracranial arteriovenous malformations. J Neurosurg 2014, http://dx.doi.org/10.3171/2014.1.jns131713 [Epub date 2014 Mar 7]. [7] Ding D, Yen CP, Starke RM, Xu Z, Sun X, Sheehan JP. Outcomes following singlesession radiosurgery for high-grade intracranial arteriovenous malformations.
Letters to the Editor / Clinical Neurology and Neurosurgery 124 (2014) 192–193 Br J Neurosurg 2013, http://dx.doi.org/10.3109/02688697.2013.872227 [Epub date 2013 Dec 27]. [8] Yen CP, Matsumoto JA, Wintermark M, Schwyzer L, Evans AJ, Jensen ME, et al. Radiation-induced imaging changes following gamma knife surgery for cerebral arteriovenous malformations. J Neurosurg 2013;118(1):63–73.
Dale Ding ∗ University of Virginia, Department of Neurosurgery, Charlottesville 22908, USA
193
is seen to be hyperintense in the T2 sequence of MRI. The ratio of reduction in size of the HNP is even higher in T2 hyperintense herniations [6]. The contrast enhancement in the neovascularization areas of HNP, presenting an enhancing rim, is thought to be a major determinant of spontaneous regression of the HNP [7]. However, the degree of neovascularization is varied. The thickness of rim enhancement is a more important factor to spontaneous regression than the extent of rim enhancement [7].
∗ Correspondence
to: University of Virginia, Department of Neurosurgery, P.O. Box 800212, Charlottesville 22908, USA. Tel.: +1 434 924 2203; fax: +1 434 982 5753. E-mail address: [email protected] 6 June 2014 Available online 17 July 2014 http://dx.doi.org/10.1016/j.clineuro.2014.06.042
The prediction of MRI for the possibility of regression of herniated nucleus pulposus Dear Sir, We are pleased to read the interesting article by Mohamed Macki and colleagues [1] in the May 2014 issue of Clinical Neurology and Neurosurgery. The authors reviewed the spontaneous regression of sequestrated intervertebral discs, which definitely would add to the current literature. We want to contribute to the evaluation of the herniated nucleus pulposus (HNP) for the possibility of regression in magnetic resonance imaging (MRI). In the literature, there is no clear information about the possibility of the regression of HNP and studies have reported different occurrence times and rates of regression [2,3]. Spontaneous regression of HNP is a rare condition. Unless the patient wants surgical treatment, if there are high risk factors for the surgical approach and there is no neurological deficit, the conservative treatment and the follow-up MRI study may be needed, even though the size of herniated disk is large. In such cases, the contrast-enhanced MRI can give us several predictions associated with the prognosis of HNP as follows: (1) The type of HNP is more related to the spontaneous regression than the size of HNP [4]. In case of extrusion or sequestration, an autoimmune response is promptly activated, which is a mechanism of the spontaneous regression [5]. The regression of HNP is seen frequently in the cases of migrating disk herniation [2]. It is presumed that the disk is much more interacted with the epidural vascular supply and this is another regression mechanism, which is about inflammation and neovascularization. (2) The neovascularization of the HNP is easily detected by MRI. The edema of the inflammation and neovascularization of HNP
Spontaneous regression of the HNP in contrast-enhanced MRI usually correlates with clinical improvement. MRI is considered to be a useful tool to predict the spontaneous regressive potential of HNP. Although there is not much study stated in the literature, Splendiani et al. reported that contrast-enhanced MRI offers predictive information about evaluation of disk herniation. Studies included large number of patients are needed to support this conclusion but we also avoid using contrast agent which might have an adverse effect for renal function. This issue is important for elderly patients at high risk for surgery. Diffusion sequence of MRI without needs of contrast shows the cellular density changes in the neovascularization quantitatively. This would allow quantitative evaluation of the disk management and is easily repeated for follow up. Although we have not encountered studies in the literature, this point could be evaluated in future studies. References [1] Macki M, Hernandez-Hermann M, Bydon M, Gokaslan A, McGovern K, Bydon A. Spontaneous regression of sequestrated lumbar disc herniations: literature review. Clin Neurol Neurosurg 2014;120(May):136–41. [2] Komori H, Shinomiya K, Nakai O, Yamaura I, Takada S, Furuya K. The natural history of herniated nucleus pulposus with radiculopathy. Spine 1996;21:225–9. [3] Masui T, Yukawa Y, Nakamura S, Kajino G, Matsubara Y, Kato F, et al. Natural history of patients with lumbar disc herniation observed by magnetic resonance imaging for minimum 7 years. J Spinal Disord Tech 2005;18:121–6. [4] Ahn SH, Ahn MW, Byun WM. Effect of the transligamentous extension of lumbar disc herniations on their regression and the clinical outcome of sciatica. Spine (Phila Pa 1976) 2000;25(4):475–80. [5] Kim SG, Yang JC, Kim TW, Park KH. Spontaneous regression of extruded lumbar disc herniation: three cases report. Korean J Spine 2013;10(2):78–81. [6] Splendiani A, Puglielli E, De Amicis R, Barile A, Masciocchi C, Gallucci M. Spontaneous resolution of lumbar disk herniation: predictive signs for prognostic evaluation. Neuroradiology 2004;46:916–22. [7] Autio RA, Karppinen J, Niinimaki J, Ojala R, Kurunlahti M, Haapea M, et al. Determinants of spontaneous resorption of intervertebral disc herniations. Spine (Phila Pa 1976) 2006;31(11):1247–52.
Ferhat Cuce ∗ Ahmet Eroglu Van Military Hospital, Van, Turkey ∗ Tel.: +90 536 8515475; fax: +90 4324220244. E-mail address: [email protected] (F. Cuce)
9 June 2014 Available online 12 July 2014 http://dx.doi.org/10.1016/j.clineuro.2014.07.005
