Case Report Stereotact Funct Neurosurg DOI: 10.1159/000504264 Received: June 23, 2019 Accepted after revision: October 19, 2019 Published online: November 26, 2019 Symptomatic Post-Radiosurgery Intratumoral Hemorrhage in a Case of Vestibular Schwannoma: A Case Report and Review of the Literature Bhushan Thombre Nishanth Sadashiva Jeeva Balu Krishnan Andiperumal Raj Prabhuraj Kannepalli Narasingha Rao Arivazhagan Arima Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, India Abstract Gamma knife radiosurgery (GKRS) is considered an established treatment for vestibular schwannoma (VS) in selected patients. Spontaneous intratumoral hemorrhage in VS after GKRS is very rare. In this report, we present a 63-year-old gentleman who had right-side severe sensorineural hearing loss on MRI showing a right cerebellopontine angle tumor (volume 4.96 cm3) with an internal acoustic meatus extension. He underwent GKRS with the prescription dose of 12 Gy to the 50% isodose line, covering 4.66 cm3 (i.e., 94%) of the tumor. Ten days later, he experienced a symptomatic intra­ lesional hemorrhage with a mass effect over the brainstem. When symptoms did not resolve after an initial conservative approach, he underwent surgical decompression of the lesion. Postoperatively, the patient had facial palsy but was free of disabling vertigo and ataxia. At the 6-month followup, he was doing well without any other complaints. Although rare, an intralesional bleed can occur after GKRS in VS and should be suspected when new severe symptoms develop immediately after therapy. © 2019 S. Karger AG, Basel © 2019 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/sfn Introduction Vestibular schwannoma (VS) represents 8% of all primary intracranial neoplasms and >80% of tumors involving the cerebellopontine angle and internal auditory canal [1]. There are various treatment options available for VS, ranging from watchful waiting to microsurgical tumor resection, stereotactic radiosurgery (SRS), or fractionated therapy. Often, patients end up having multiple treatments during their lifetime. GKRS is considered one of the established treatments for VS In selected patients [2]. Many patients opt for GKRS when both surgery and GKRS are available, because with GKRS there is no scarring, no postprocedural admission, and a low risk of developing complications. The standard dosage is considered to be ≤13 Gy, as established by Yang et al. [3]. Although rare, complications have been reported, like facial palsy, hearing loss, and vertigo, or sometimes facial numbness or brainstem edema. A post-GKRS intralesional bleed has been reported only in a few cases of VS. Here, we report a patient with VS who underwent GKRS, and had an intralesional bleed with worsening symptoms due to the mass effect on the brainstem for which surgery was done. Dr. Nishanth Sadashiva, MCh Department of Neurosurgery, 2nd Floor, Neurosciences Faculty Block National Institute of Mental Health and Neurosciences Bengaluru 560029 (India) E-Mail nishanth46 @ gmail.com, nishanth @ nimhans.ac.in Downloaded by: University of Western Ontario 129.100.58.76 - 12/10/2019 1:50:13 PM Keywords Gamma knife radiosurgery · Vestibular schwannoma · Radiosurgery · Intratumoral hemorrhage · Acoustic neuroma a1 b1 c1 d1 a2 b2 c2 d2 Fig. 1. Axial cuts of T2-weighted (a1) and post-contrast T1-weighted (a2) images of the patient done 2 weeks before gamma knife radiosurgery (GKRS). b1, b2 Corresponding images at GKRS. Axial cuts of T2-weighted image showing layering (c1) and post-contrast T1-weighted image done 12 days after gamma knife treatment (c2). d1 T1-weighted plain image showing layering and hyperintense blood layering. d2 Susceptibility-weighted images with hyperintense blood inside the lesion suggestive of a bleed. A 63-year-old gentleman presented to us with a history of right-side hearing loss and tinnitus for 2 and half years. On examination, he had severe sensorineural hearing loss on the right side with a sensory loss in touch and pain sensations across the right side of his face. Audiological evaluation revealed right-side profound hearing loss with pure tone audiometry showing >90 dB hearing loss, with no definable peak at even 90 dB in a brainstem auditory-evoked response (BAER) test. Magnetic resonance imaging (MRI) showed a right cerebellopontine angle tumor measuring 4.96 cm3 with extension into the internal acoustic meatus (Fig. 1). Vitals and other routine investigations done during evaluation showed normal for bleeding and clotting abnormalities. He was then given various available treatment options and finally planned for gamma knife irradiation. The Gamma Knife Clinic treatment protocol was followed at our institute with a model 4C gamma knife (Elekta Instruments, Atlanta, GA, USA) using Cobolt 60 as the source of the gamma rays. The patient was treated with the prescription dose of 12 Gy to the 50% isodose line, covering 4.66 cm3 (94%) of the tumor volume (Fig. 2). Planning was done on stereotactic con- 2 Stereotact Funct Neurosurg DOI: 10.1159/000504264 trast-enhanced T1 and T2 MRI sequences using a 1-mm-slice thickness. The treatment beam on-time was 57.4 min at a dose delivery rate of 2.199 Gy/min. The patient withstood the treatment well and was discharged the next day without any problems. Oral steroids were prescribed for 3 days after GKRS as an institute protocol. Ten days later, he visited the Outpatients Department with the complaints: severe vertigo, an increase in ataxia, and a mild facial deviation to the left side. These symptoms occurred over 2 days. He underwent an urgent MRI which showed an increase in lesion size and the blood level within. Susceptibility-weighted imaging (SWI) showed the presence of blooming, suggestive of intralesional hemorrhage (Fig. 1, C1–D2). There was an increase in mass effect over the brainstem. The condition of the patient was explained to him and he was given an option of surgical decompression of the lesion. He first wanted to see if the symptoms resolved over time, so he chose to wait and decide later. The symptoms did not resolve over a couple of weeks, so he decided to have surgery for decompression of the lesion. Postoperatively, he had facial palsy but was free of the disabling vertigo and ataxia. At the 6-month follow-up, the patient was doing well; he had facial palsy but no other complaints. Thombre/Sadashiva/Krishnan/Prabhuraj/ Rao/Arima Downloaded by: University of Western Ontario 129.100.58.76 - 12/10/2019 1:50:13 PM Case Report Color version available online Fig. 2. Gamma knife planning: tumor demarcation (red line), 50% isodose line receiving 12-Gy radiation (yellow Symptomatic intratumoral hemorrhage in vestibular schwannoma (VS) is a rare phenomenon [4], and in some cases it can be fatal [5]. It has been reported that varying levels of microhemorrhage occur in nearly all cases of VS, with approximately 4% exhibiting diffuse microhemorrhage spanning >50% of the tumor volume [6]. Several potential triggers have been reported including hypertension, pregnancy, excessive straining, minor head trauma, and antiplatelet or anticoagulant therapy [4]. None of these predisposing factors was present in this reported case. Hemorrhage in VS after GKRS has been reported rarely (Table 1). Post-GKRS hemorrhage has been reported in arteriovenous malformations [7], intracranial metastasis [8], meningiomas [9], and cavernomas [10]. There have also been reports of likely de novo aneurysm formation in patients with VS treated with SRS [11]. Several groups have reported that radiation therapy itself increases the risk of delayed hemorrhage in VS [12]. Niknafs et al. [13], in their review of the literature in 2014, found 7 of 39 pa- tients (20%) in whom hemorrhagic VS developed following SRS. There was only 1 report with 4 cases [14] and the rest were single-case reports [12, 15, 16]. In our experience of > 850 patients, this is the only patient who had a hemorrhagic complication early after GKRS. A thinwalled tumor-associated vasculature and increased intratumoral vascularity are traits that appear to be common to all cases of hemorrhagic VS. Venous congestion resulting from SRS has been implicated in the occurrence of a spontaneous tumor bleed [17]. Liu et al. [18] performed a thorough histological analysis on patients who were operated on after previous GKRS therapy. They noted that, post-GKRS, the reason for surgical intervention was mostly the worsening of tumor-related signs and symptoms. Of 41 tumors, 13 developed some form of hemorrhage but 10 of them were cases pituitary adenoma. In the VS cases, the histopathological findings were suggestive of multiple microhemorrhages. They noticed that 2–3 months after GKRS therapy, the initial changes were tumor vascular degeneration and fibrinoid necrosis followed by hyaline degeneration. After this, there was cytoplasmic vacuole degeneration, thrombosis, Post-Gamma Knife-Bleed in Vestibular Schwannoma Stereotact Funct Neurosurg DOI: 10.1159/000504264 Discussion 3 Downloaded by: University of Western Ontario 129.100.58.76 - 12/10/2019 1:50:13 PM line), and demarcation of the brainstem (green line). Table 1. Review of the literature with bleed in vestibular schwannoma after gamma knife radiosurgery Study First author [ref.], year Cases, n Age, years Sex Dose during GKRS Time of bleed after GKRS Treatment 1 Iwai [16], 2003 2 n.a. n.a. n.a. n.a. <12 Gy <12 Gy 60 months 80 months surgery conservative 2 Karampelas [12], 2007 1 53 male 13 Gy to 46% isodose 27 months conservative 3 Dehdashti [15], 2009 1 47 female n.a. 18 months surgery 4 Murakami [14], 2011 4 39 37 33 25 female male female female 11.3 Gy 12 Gy 12 Gy 12 Gy 167 months 10 months 24 months 7 months surgery surgery surgery surgery 5 Our study 1 63 male 12 Gy to 50% isodose 10 days surgery GKRS, gamma knife radiosurgery; n.a., not available. and then lumen stenosis of the vessels after several years. Microbleeding and hemosiderin deposition were found in more than half of the VS cases [18]. In agreement with Carlson et al. [4], we speculate that microhemorrhage provides the inciting spark followed by secondary factor that promotes further bleeding. In our case, it was radiosurgery which led to the hemorrhage and acute symptomatic presentation. The mechanism underlying acute cranial neuropathy and neurologic decline presumably relates to rapid tumor expansion and the consequent compression or traction of coursing cranial nerves as well as brainstem compression. Tumor pseudoprogression is a known complication of GKRS [19]. We should keep in mind that tumor expansion with neurological deterioration can occur with hemorrhaging inside the lesion after GKRS. Prompt surgical decompression may be required to alleviate compressive symptoms. It should also be kept in mind that the rate of morbidity and mortality of after VS surgery is higher after hemorrhage than in tumors without hemorrhage. Caution should therefore be exercised during tumor management. Conclusion Although rare, an intralesional bleed can occur after gamma knife irradiation in VS, and it should be suspected immediately after therapy if a patient develops new or worsening symptoms. Statement of Ethics This work complies with standards set forth in the Declaration of Helsinki. Patients gave their informed consent to have their cases published. This work is IRB exempt. Disclosure Statement The authors have no conflicts of interest to declare. References 4 3 Yang I, Sughrue ME, Han SJ, Aranda D, Pitts LH, Cheung SW, et al. A comprehensive analysis of hearing preservation after radiosurgery for vestibular schwannoma. J Neurosurg. 2010 Apr;112(4):851–9. 4 Carlson ML, Tombers NM, Driscoll CL, Van Gompel JJ, Lane JI, Raghunathan A, et al. Clinically significant intratumoral hem- Stereotact Funct Neurosurg DOI: 10.1159/000504264 orrhage in patients with vestibular schwannoma. Laryngoscope. 2017 Jun; 127(6): 1420–6. 5 Yates CW, Weinberg M, Packer MJ, Jacob A. 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