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Vestibular Schwannoma Gamma Knife radiosurgery complications

Vestibular Schwannoma Gamma Knife radiosurgery complications

Patients treated with Stereotactic radiosurgery for vestibular schwannoma can have a similar complication profile to those treated with intracranial surgery. Vestibular Schwannoma Meta-analysis from early experience showed that 44% with serviceable hearing prior to treatment retained their ability after SRS, a statistically equivalent rate to the surgical data. This evidence also suggest that 37.9% of patients have other complications 1).

In the mid-1970s, early facial weakness occurred in 38% and facial numbness in 33%. This has gradually decreased to less than 2% in the 1990s. Preservation of hearing (unchanged or almost unchanged) is currently achieved in 65 to 70%. Tinnitus is rarely changed by the treatment. The risks of intracranial bleeding, infection, and CSF leak are avoided because of the non-invasive nature of the treatment. Hydrocephalus directly induced by the tumor occurred in 9.2% of patients. On the other hand, a treatment%related peritumoral reaction sufficient to block the CSF circulation and require shunt insertion was seen in only 1.4%. Based on experiences worldwide, the incidence of secondary neoplasia seems to be 0.1%. The effectiveness of GKR together with its low complication rate makes it a suitable treatment for anyone, regardless of age and general health 2).

Malignant transformation is possible 3). , and long-term post-SRS surveillance MRI is important 4).

Patients receiving > 13 Gy were significantly more likely to develop trigeminal neuropathy than those receiving < 13 Gy (p < 0.001) 5).

Case reports

Pollack et al. described an acute facial and acoustic neuropathy following gamma knife surgery (GKS) for vestibular schwannoma (VS). This 39-year-old woman presenting with tinnitus underwent GKS for a small right-sided intracanalicular VS, receiving a maximal dose of 26 Gy and a tumor margin dose of 13 Gy to the 50% isodose line. Thirty-six hours following treatment she presented with nausea, vomiting, vertigo, diminished hearing, and a House-Brackmann Grade III facial palsy. She was started on intravenous glucocorticosteroid agents, and over the course of 2 weeks her facial function returned to House-Brackmann Grade I. Unfortunately, her hearing loss persisted. A magnetic resonance (MR) image obtained at the time of initial deterioration demonstrated a significant decrease in tumor enhancement but no change in tumor size or peritumoral edema. Subsequently, the patient experienced severe hemifacial spasms, which persisted for a period of 3 weeks and then progressed to a House-Brackmann Grade V facial palsy. During the next 3 months, the patient was treated with steroids and in time her facial function and hearing returned to baseline levels. Results of MR imaging revealed transient enlargement (3 mm) of the tumor, which subsequently returned to its baseline size. This change corresponded to the tumor volume increase from 270 to 336 mm3. The patient remains radiologically and neurologically stable at 10 months posttreatment. This is the first detailed report of acute facial and vestibulocochlear neurotoxicity following GKS for VS that improved with time. In addition, MR imaging findings were indicative of early neurotoxic changes. A review of possible risk factors and explanations of causative mechanisms is provided 6).

Pseudoprogression

see Vestibular Schwannoma pseudoprogression.

1)

Kaylie DM, Horgan MJ, Delashaw JB, McMenomey SO. A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope. 2000 Nov;110(11):1850-6. doi: 10.1097/00005537-200011000-00016. PMID: 11081598.
2)

Norén G. Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg. 1998 Oct;70 Suppl 1:65-73. doi: 10.1159/000056408. PMID: 9782237.
3)

Yanamadala V, Williamson RW, Fusco DJ, Eschbacher J, Weisskopf P, Porter RW. Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. World Neurosurg. 2013 Mar-Apr;79(3-4):593.e1-8. doi: 10.1016/j.wneu.2012.03.016. Epub 2012 Apr 2. PubMed PMID: 22480982.
4)

Kawashima M, Hasegawa H, Shin M, Shinya Y, Katano A, Saito N. Outcomes of stereotactic radiosurgery in young adults with vestibular schwannomas. J Neurooncol. 2021 Jul 9. doi: 10.1007/s11060-021-03803-w. Epub ahead of print. PMID: 34241770.
5)

Sughrue ME, Yang I, Han SJ, Aranda D, Kane AJ, Amoils M, Smith ZA, Parsa AT. Non-audiofacial morbidity after Gamma Knife surgery for vestibular schwannoma. J Neurosurg. 2013 Dec;119 Suppl:E4. Review. PubMed PMID: 25077327.
6)

Pollack AG, Marymont MH, Kalapurakal JA, Kepka A, Sathiaseelan V, Chandler JP. Acute neurological complications following gamma knife surgery for vestibular schwannoma. Case report. J Neurosurg. 2005 Sep;103(3):546-51. doi: 10.3171/jns.2005.103.3.0546. PMID: 16235688.

Gamma Knife radiosurgery for acromegaly

Gamma Knife radiosurgery for acromegaly

Numerous studies of radiosurgery for acromegaly have been carried out. These illustrate an overall remission rate of over 40%. Morbidity from radiosurgery is infrequent but can include cranial nerve palsies and hypopituitarism. Overall, stereotactic radiosurgery is a promising therapy for patients with acromegaly and deserves further study to refine its role in the treatment of affected patients 1).

GKS is an effective adjuvant treatment option for remnant tumors inside the cavernous sinus (CS) after transsphenoidal surgery (TSS). Maximal surgical resection leaving a minimal volume of remnants only inside the CS allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS 2).

Case series

Losa et al. performed a study to investigate, which would be the outcome of GKRS, independently on the response to somatostatin receptor ligand (SRL).

Design: Retrospective, observational study.

Patients: Ninety-six patients with active acromegaly were included.

Measurements: The cumulative probability of normalization of insulin-like growth factor 1 (IGF-1) levels after GKRS was assessed by the Kaplan-Meier method. The association of several clinical characteristics with GKRS outcomes was explored with the use of a Cox proportional-hazard model with the relative hazard ratio and 95% confidence interval (CI).

Results: Resistance to SRL occurred in 39 of the 96 patients (40.6%). After GKRS, patients resistant to SRL had a 5- and 10-year probability of remission of 40.7% (95% CI: 23.7%-57.7%) and 75.9% (95% CI: 57.9%-93.9%), respectively. Patients responding to SRL had a 5- and 10-year probability of remission of 46.8% (95% CI: 32.2%-61.4%) and 58.1% (95% CI: 41.5%-74.7%), respectively. The difference was not significant (p = .48 by the log-rank test). Multivariate Cox analysis confirmed that the only independent variables associated with GKRS outcome were basal growth hormone (GH; p = .001) and IGF-1 multiple of the upper limit of normal levels before GKRS (p = .013).

Conclusion: They demonstrate for the first time that the responsiveness to SRL has no effect on the probability to obtain remission of acromegaly after GKRS. The remission of disease occurred more frequently in patients who had lower GH and IGF-1 levels before GKRS 3).

Forty-two patients (minimum 6 months follow-up) were included. The mean marginal dose was 27.7 (median 28, 20-35), and the mean BED received by the tumor was 193.1 Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients into the high tumor BED group (H-BEDtm, 199.7-237.1 Gy2.47, n = 12) and low BED one (L- BEDtm, 64.1-199.7 Gy2.47 , n = 10). The two groups did not differ by pre-therapeutic IGF-1 levels (p = .1) or by the prescribed dose (p = .6).

Results: The mean follow-up period was 62.5 months (median 60.5, 9-127). The probability of IGF-1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogs. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during the follow-up course. In univariate analysis, the only statistically significant parameter was pre-therapeutic serum IGF-1 and IGF-1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with an actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05).

The study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pre therapeutic serum levels of IGF-1 were the only statistically significant parameters for endocrine remission 4).

A retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 to 2009. The mean age at treatment was 42.3 years (range 22-67 yy). 103 acromegalic patients participated in the study. The median follow-up was 71 months (IQ range 43-107). All patients were treated with GK for residual or recurrent GH-secreting adenoma. Results. Sixty-three patients (61.2%) reached the main outcome of the study. The rate of remission was 58.3% at 5 years (95% CI 47.6-69.0%). Other 15 patients (14.6%) were in remission after GK while on treatment with somatostatin analogs. No serious side effects occurred after GK. Eight patients (7.8%) experienced a new deficit of pituitary function. New cases of hypogonadism, hypothyroidism and hypoadrenalism occurred in 4 of 77 patients (5.2%), 3 of 95 patients (3.2%), and 6 of 100 patients at risk (6.0%), respectively. Conclusion. In a highly selected group of acromegalic patients, GK treatment had good efficacy and safety 5).

Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high-resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity 6).

149 patients with GH-secreting pituitary adenoma, 97 males and 52 females, aged 42.8 (12-72 years), with a course of 6-240 months (72.5 months) and with the mean volume of tumor of 2.36 cm(3) (0.11-12.7 cm(3)) were treated by GKS. The mean dose to tumor margin was 20.87 Gy (10-30 Gy). 124 of them were followed up for 30 months (6-72 months).

The serum GH returned normal in 74 patients (64.9%) and declined in comparison with the level before radiosurgery in 23 patients (18.5%). The tumor volume was reduced in 84 patients (67.7%) and remained unchanged in 124 patients (32.4%). Ambiopia appeared in one patient. No other complication was found during the follow-up.

GKS is safe and effective on the treatment of GH-secreting pituitary adenoma 7).

1)

Rolston JD, Blevins LS Jr. Gamma knife radiosurgery for acromegaly. Int J Endocrinol. 2012;2012:821579. doi: 10.1155/2012/821579. Epub 2012 Feb 13. PMID: 22518132; PMCID: PMC3296174.
2)

Kim EH, Oh MC, Chang JH, Moon JH, Ku CR, Chang WS, Lee EJ, Kim SH. Postoperative Gamma Knife radiosurgery for cavernous sinus-invading growth hormone-secreting pituitary adenomas. World Neurosurg. 2017 Nov 16. pii: S1878-8750(17)31966-6. doi: 10.1016/j.wneu.2017.11.043. [Epub ahead of print] PubMed PMID: 29155347.
3)

Losa M, Resmini E, Barzaghi LR, Albano L, Bailo M, Webb SM, Mortini P. Resistance to first-generation somatostatin receptor ligands does not impair the results of gamma knife radiosurgery in acromegaly. Clin Endocrinol (Oxf). 2021 Jul 4. doi: 10.1111/cen.14547. Epub ahead of print. PMID: 34219264.
4)

Balossier A, Tuleasca C, Cortet-Rudelli C, Soto-Ares G, Levivier M, Assaker R, Reyns N. Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases. Clin Endocrinol (Oxf). 2021 Mar;94(3):424-433. doi: 10.1111/cen.14346. Epub 2020 Oct 10. PMID: 32984972.
5)

Franzin A, Spatola G, Losa M, Picozzi P, Mortini P. Results of gamma knife radiosurgery in acromegaly. Int J Endocrinol. 2012;2012:342034. doi: 10.1155/2012/342034. Epub 2012 Feb 19. PMID: 22518119; PMCID: PMC3296167.
6)

Attanasio R, Epaminonda P, Motti E, Giugni E, Ventrella L, Cozzi R, Farabola M, Loli P, Beck-Peccoz P, Arosio M. Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J Clin Endocrinol Metab. 2003 Jul;88(7):3105-12. doi: 10.1210/jc.2002-021663. PMID: 12843150.
7)

Wang MH, Liu P, Liu AL, Luo B, Sun SB. [Efficacy of gamma knife radiosurgery in treatment of growth hormone-secreting pituitary adenoma]. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2045-8. Chinese. PubMed PMID: 14703413.

Gamma Knife radiosurgery for cavernous malformation

Gamma Knife radiosurgery for cavernous malformation

Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients.

Gamma Knife radiosurgery (GKRS) has been used to treat cavernous malformations (CMs) located in basal ganglia and thalamus. However, previous reports are limited by small patient population.

Hu et al. retrospectively reviewed the clinical and radiological data of 53 patients with CMs of basal ganglia and thalamus who underwent GKRS at West China Medical Center between May 2009 and July 2018. All patients suffered at least once bleeding before GKRS. The mean volume of these lesions was 1.77 cm3, and the mean marginal dose was 13.2 Gy. After treatment, patients were followed to determine the change in symptom and hemorrhage event.

The mean follow-up period was 52.1 months (6.2-104.3 months). The calculated annual hemorrhage rate (AHR) was 48.5% prior to GKRS and 3.0% after treatment (p < 0.001). The Kaplan-Meier analysis revealed that 2-, 3-, and 5-year hemorrhage-free survival were 88, 80.9, and 80.9%, respectively. Preexisting symptoms were resolved in 11 patients, improved in 14, and stable in 5. Only 2 patients (3.8%) developed new neurological deficit.

This study suggests that AHR after GKRS was comparable to the recorded AHR of natural history (3.1-4.1%) in previous studies. GKRS is a safe and effective treatment modality for CMs of basal ganglia and thalamus. Considering the relative insufficient understanding of natural history of CMs, future study warrants longer follow-up 1)

Meta-analysis

Wen et al., from the West China Hospital performed a meta-analysis is to evaluate the clinical efficacy of gamma knife radiosurgery for treating cavernous malformation.

PUBMED, OVID EMBASE, and OVID MEDLINE electronic databases are searched. The primary outcome is hemorrhage rate and this meta-analysis is performed with REVMAN 5.3.

9 studies are included in this meta-analysis. The overall RR of hemorrhage rate of pre-GKRS and post-GKRS is 6.08(95% CI: 5.04-7.35). The overall RR is 3.03(95% CI: 2.65-4.11) between the hemorrhage rate of pre-GKRS and the first 2 years of post-radiosurgery, and the overall RR is 12.13 (95% CI: 1.73-85.07) comparing pre-GKRS with 2 years after GKRS. There is no significant difference of the hemorrhage rate between the first 2 years of post-radiosurgery and 2 years after GKRS (RR =2.81, 95% CI: 0.20-13.42). The neurological deficiency is the commonest radiosurgery related complications.

Patients with cerebral CMs, especially who were deep seated and surgically inaccessible, seems to benefit from GKRS due to a reduction of annual hemorrhage rate in the first 2 years, and after that time, despite of a number of cases that suffer from negative side effects of radiation 2).

Case series

Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities 3).

Shin et al. aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.

During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.

Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.

Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role 4).

From 1994 to 2001, 92 patients with 114 CMs were treated by GKS and then followed up for 2-8 years (mean 4.1+/-1.9). We analyzed the MRI features of CMs bleeding, efficacy of GKS, and the complications of treatment. Six pathological specimens after radiosurgery (1 from our group, 5 from other centers) were also assayed.

Among 43 patients who were treated by GKS to control their epilepsy, epileptic paroxysm was alleviated in 36 patients (83.7%), including 12 (27.9%) seizure-free. Rebleeding was confirmed in 9 patients (9.8%) by neuroimage, one of whom died. Transient symptomatic radiation edema occurred in 7 cases (7.6%) within 6-12 months after radiosurgery, and one patient underwent open surgery for cerebral decompression. The main pathological changes of cavernoma were coagulation necrosis and the vessels obliterated gradually after radiosurgery.

It is feasible to treat small and surgically high risk CMs by radiosurgery. The treatment has to be prudent in an acute bleeding and symptomatic progression. Optimal treatment timing and dose planning are prerequisites to reduce radiation-related complications. GKS is safe and effective to control the epilepsy caused by CMs, and also to bring down the rebleeding rate after a latency interval of several years 5).

Gamma knife radiosurgery for brainstem cavernous malformation

Gamma knife radiosurgery for brainstem cavernous malformation.

1)

Hu YJ, Zhang LF, Ding C, Tian Y, Chen J. Gamma Knife Radiosurgery for Cavernous Malformations of Basal Ganglia and Thalamus: A Retrospective Study of 53 Patients. Stereotact Funct Neurosurg. 2021 Jun 9:1-8. doi: 10.1159/000510108. Epub ahead of print. PMID: 34107485.
2)

Wen R, Shi Y, Gao Y, Xu Y, Xiong B, Li D, Gong F, Wang W. The efficacy of gamma knife radiosurgery for cavernous malformation: a meta-analysis and review. World Neurosurg. 2018 Dec 21. pii: S1878-8750(18)32869-9. doi: 10.1016/j.wneu.2018.12.046. [Epub ahead of print] Review. PubMed PMID: 30583131.
3)

Lee CC, Wang WH, Yang HC, Lin CJ, Wu HM, Lin YY, Hu YS, Chen CJ, Chen YW, Chou CC, Liu YT, Chung WY, Shiau CY, Guo WY, Hung-Chi Pan D, Hsu SPC. Gamma Knife radiosurgery for cerebral cavernous malformation. Sci Rep. 2019 Dec 24;9(1):19743. doi: 10.1038/s41598-019-56119-1. PMID: 31874979; PMCID: PMC6930272.
4)

Shin SS, Murdoch G, Hamilton RL, Faraji AH, Kano H, Zwagerman NT, Gardner PA, Lunsford LD, Friedlander RM. Pathological response of cavernous malformations following radiosurgery. J Neurosurg. 2015 Oct;123(4):938-44. doi: 10.3171/2014.10.JNS14499. Epub 2015 Jun 19. PubMed PMID: 26090838.
5)

Liu AL, Wang CC, Dai K. [Gamma knife radiosurgery for cavernous malformations]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Feb;27(1):18-21. Chinese. PMID: 15782486.

Cavernous sinus hemangioma Gamma Knife surgery

Cavernous sinus hemangioma Gamma Knife surgery

A study aimed to evaluate the efficacy of Gamma Knife surgery (GKS) on cavernous sinus hemangioma and to analyze the temporal volume change.

Cho et al. retrospectively reviewed the clinical data of 26 cavernous sinus hemangioma patients who were treated with GKS between 2001 and 2017. Before GKS, 11 patients (42.3%) had cranial neuropathies and 5 patients (19.2%) complained of headache, whereas 10 patients (38.5%) were initially asymptomatic. The mean pre-GKS mass volume was 9.3 mL (range, 0.5-31.6 mL), and the margin dose ranged from 13 to 15 Gy according to the mass volume and the proximity to the optic pathway. All cranial neuropathy patients and half of headache patients showed clinical improvement. All 26 patients achieved mass control; remarkable responses (less than 1/3 of the initial mass volume) were shown in 19 patients (73.1%) and moderate responses (more than 1/3 and less than 2/3) in 7 patients (26.9%). The mean final mass volume after GKS was 1.8 mL (range, 0-12.6 mL). The mean mass volume at 6 months after GKS was 45% (range, 5-80%) compared to the mass volume before GKS and 21% (range, 0-70%) at 12 months. The higher radiation dose tended to induce more rapid and greater volume reduction. No treatment-related complication was observed during the follow-up period. GKS could be an effective and safe therapeutic strategy for CSCH. GKS induced very rapid volume reduction compared to other benign brain tumors 1).

An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12-19 Gy) at a median isodose of 55%. RESULTS Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up. CONCLUSIONS Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors’ experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed. 2).

Between August 2011 and April 2014, 7 patients with CSHs underwent GKS. GKS was performed as the sole treatment option in 5 patients, whilst partial resection had been performed previously in 1 patient and biopsy had been performed in 1 patient. The mean volume of the tumors at the time of GKS was 12.5±10.2 cm3 (range, 5.3-33.2 cm3), and the median prescription of peripheral dose was 14.0 Gy (range, 10.0-15.0 Gy). The mean follow-up period was 20 months (range, 6-40 months). At the last follow-up, the lesion volume had decreased in all patients, and all cranial neuropathies observed prior to GKS had improved. There were no radiation-induced neuropathies or complications during the follow-up period. GKS appears to be an effective and safe treatment modality for the management of CSHs 3).

A retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed.

Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow-up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery.

GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas 4).

References

1)

Cho JM, Sung KS, Jung IH, Chang WS, Jung HH, Chang JH. Temporal Volume Change of Cavernous Sinus Cavernous Hemangiomas after Gamma Knife Surgery. Yonsei Med J. 2020 Nov;61(11):976-980. doi: 10.3349/ymj.2020.61.11.976. PMID: 33107242.
2)

Lee CC, Sheehan JP, Kano H, Akpinar B, Martinez-Alvarez R, Martinez-Moreno N, Guo WY, Lunsford LD, Liu KD. Gamma Knife radiosurgery for hemangioma of the cavernous sinus. J Neurosurg. 2017 May;126(5):1498-1505. doi: 10.3171/2016.4.JNS152097. Epub 2016 Jun 24. PMID: 27341049.
3)

Xu Q, Shen J, Feng Y, Zhan R. Gamma Knife radiosurgery for the treatment of cavernous sinus hemangiomas. Oncol Lett. 2016 Feb;11(2):1545-1548. doi: 10.3892/ol.2015.4053. Epub 2015 Dec 23. PMID: 26893777; PMCID: PMC4734249.
4)

Chou CW, Wu HM, Huang CI, Chung WY, Guo WY, Shih YH, Lee LS, Pan DH. Gamma knife surgery for cavernous hemangiomas in the cavernous sinus. Neurosurgery. 2010 Sep;67(3):611-6; discussion 616. doi: 10.1227/01.NEU.0000378026.23116.E6. PMID: 20647963.

Gamma Knife radiosurgery for trigeminal neuralgia

Gamma Knife radiosurgery for trigeminal neuralgia

Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN).

The first use of SRS by Lars Leksell was for the treatment of trigeminal neuralgia. Initially, this was reserved for refractory cases following multiple operations 1).

The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radiosurgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness.

CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe,and cranial nerves VII and VIII) and in steeper dose fall off away from the target. The clinical significance of these effects is unknown 2).

Indications

Generally recommended for patients with co-morbidities, high-risk medical illness, pain refractory to prior surgical procedures, or those on anticoagulants (anticoagulation does not have to be reversed to have SRS).

Mechanism

see Gamma Knife radiosurgery for trigeminal neuralgia mechanism

Treatment plan

4 -5 mm isocenter in the trigeminal nerve root entry zone identified on MRI. Use 70–80 Gy at the center, keeping the 80% isodose curve outside of the brainstem.

Results: Significant pain reduction after initial SRS: 80–96% 3) 4) 5) 6) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 7).

Recurrent pain occurs with in three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Outcome

see Gamma Knife Radiosurgery for trigeminal neuralgia outcome.

Repeat Radiosurgery for Trigeminal Neuralgia

see Repeat Radiosurgery for Trigeminal Neuralgia.

Case series

A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study.

The median latency period of Facial pain response (PR) after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute Pain Scale I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%).

In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control 8).

2016

One hundred seventeen patients with medically refractory TN treated by GKRS at the Department of Functional Neurosurgery and Gamma Knife Radiosurgery, and Department of Neurology, Ruber International Hospital, Madrid, Spain were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. They considered classes I and II as a complete response. For toxicity, they use the Barrow Neurological Institute Pain Scale. Mean duration of follow-up was 66 months (range: 24-171 months).

Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%.

GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. They consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients 9).

In a single-center, retrospective comparative study, 202 patients with MS and concomitant TN were evaluated. A minimum follow-up of 24 months was required. Patients with a history of microvascular decompression or previous intervention were excluded. There were 78 PBC procedures performed and 124 first-dosage GKRS procedures for a total of 202 patients between February 2009 and December 2013. The PBC procedures were successfully completed in all cases. The two groups were compared with regards to initial effect, duration of effect, and rate of complication(s), including the type and severity of the complication(s).

Immediate pain relief resulted in 87% of patients treated with PBC and in 23% of patients treated with GKRS. The Kaplan-Meier plots for the two treatment modalities were similar. The 50% recurrence rate was at 12 months for the PBC and 18 months for the GKRS. The rates of complication (excluding numbness) were 3% for GKRS and 21% for PBC. The difference was statistically significant (Chi-square test, p = 0.03).

PBC and GKRS are effective techniques for the treatment of TN in patients with MS, with GKRS presenting fewer complications and superior long-term relief. For these reasons, we consider GKRS as the first option for the treatment of TN in MS patients, reserving PBC for patients with acute, intractable pain 10).

Case reports

A 72-year-old -female presented with trigeminal neuralgia (TN) and radiological evidence of neurovascular compression on the affected side. She had complete resolution of her pain for 7 years after treatment with GKRS. The patient experienced recurrence and underwent repeat GKRS, this time resulting in another 3 years of pain relief. After the second recurrence, repeat intracranial imaging demonstrated resolution of neurovascular compression.

GKRS is an important treatment option for TN, although the mechanisms behind pain relief from this procedure still remain unclear. While prior histological and radiological studies point to ablative mechanisms for pain relief, this case report suggests that GKRS may result in a decompressive effect in TN due to changes in neurovascular architecture. Despite this finding, TN is known to occur and recur in the absence of neurovascular compression; thus, further work is necessary to understand the etiology of TN and its treatments.

In this case, Moosa et al. demonstrated that vessel-nerve relationships may change over time in TN patients treated with GKRS, which raises the possibility that GKRS could release a neurovascular compression 11).

References

1)

Lunsford LD. Comment on Taha J M and Tew J M: Comparison of Surgical Treatmen ts for Trigemin al Neuralgia: Reevaluation of Radiofrequency Rhizotomy. Neurosurgery. 1996; 38
2)

Descovich M, Sneed PK, Barbaro NM, McDermott MW, Chuang CF, Barani IJ, Nakamura JL, Lijun M. A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia. J Neurosurg. 2010 Dec;113 Suppl:199-206. PubMed PMID: 21222296.
3)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
4)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gorman DA. High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
5)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotact ic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
6)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotch i J, Levivier M. Gamma kn ife surgery for idiopathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vladyka V. Treatment of essential trigeminal neuralgia with gamma knife surgery. J Neurosurg. 2005; 102 Suppl:29–33
8)

Xu Z, Mathieu D, Heroux F, Abbassy M, Barnett G, Mohammadi AM, Kano H, Caruso J, Shih HH, Grills IS, Lee K, Krishnan S, Kaufmann AM, Lee JYK, Alonso-Basanta M, Kerr M, Pierce J, Kondziolka D, Hess JA, Gerrard J, Chiang V, Lunsford LD, Sheehan JP. Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study. Neurosurgery. 2019 Feb 1;84(2):499-505. doi: 10.1093/neuros/nyy142. PubMed PMID: 29688562.
9)

Martínez Moreno NE, Gutiérrez-Sárraga J, Rey-Portolés G, Jiménez-Huete A, Martínez Álvarez R. Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery: A Retrospective Study in Patients With Minimum 2-Year Follow-up. Neurosurgery. 2016 Dec;79(6):879-888. PubMed PMID: 27560193.
10)

Alvarez-Pinzon AM, Wolf AL, Swedberg HN, Barkley KA, Cucalon J, Curia L, Valerio JE. Comparison of Percutaneous Retrograsserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis: A Clinical Research Study Article. World Neurosurg. 2016 Oct 15. pii: S1878-8750(16)31016-6. doi: 10.1016/j.wneu.2016.10.028. PubMed PMID: 27756676.
11)

Moosa S, Wang TR, Mastorakos P, Sheehan JP, Elias WJ. Gamma Knife Radiosurgery for Trigeminal Neuralgia Reduces Neurovascular Compression: A Case Report after 11 Years. Stereotact Funct Neurosurg. 2019 Sep 5:1-5. doi: 10.1159/000501624. [Epub ahead of print] PubMed PMID: 31487732.

Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma Knife radiosurgery for trigeminal neuralgia (GKRS) is a noninvasive surgical treatment option. The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear.

Studies focusing on the electrophysiology properties of partially demyelinated trigeminal nerves submitted to radiosurgery are vital to truly advance our current knowledge in the field 1).

To better understand this topic, Shih-Ping Hung et al., used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.

Ninety-two sets of 3-T anatomical and diffusion weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.

GKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.

Ultimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN 2).

Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results.

There is evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed and need to be explored in future studies 3).

Existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique 4).

References

1)

Gorgulho A. Radiation mechanisms of pain control in classical trigeminal neuralgia. Surg Neurol Int. 2012;3(Suppl 1):S17-25. doi: 10.4103/2152-7806.91606. Epub 2012 Jan 14. PubMed PMID: 22826806; PubMed Central PMCID: PMC3400477.
2)

Shih-Ping Hung P, Tohyama S, Zhang JY, Hodaie M. Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia. J Neurosurg. 2019 Jul 12:1-9. doi: 10.3171/2019.4.JNS19380. [Epub ahead of print] PubMed PMID: 31299654.
3)

Al-Otaibi F, Alhindi H, Alhebshi A, Albloushi M, Baeesa S, Hodaie M. Histopathological effects of radiosurgery on a human trigeminal nerve. Surg Neurol Int. 2014 Jan 18;4(Suppl 6):S462-7. doi: 10.4103/2152-7806.125463. eCollection 2013. PubMed PMID: 24605252.
4)

Varela-Lema L, Lopez-Garcia M, Maceira-Rozas M, Munoz-Garzon V. Linear Accelerator Stereotactic Radiosurgery for Trigeminal Neuralgia. Pain Physician. 2015 Jan-Feb;18(1):15-27. PubMed PMID: 25675056.

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Significant pain reduction after initial SRS: 80–96% 1) 2) 3) 4) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 5).

Recurrent pain occurs within three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Favorable prognosticators: higher radiation doses, previously unoperated patient, absence of atypical pain component, normal pre-treatment sensory function 6).

Side effects: Hypesthesia occurred in 20% after initial SRS, and in 32% of those requiring repeat treatment 7) (higher rates associated with higher radiation doses) 8).

Outcome prediction of this modality is very important for proper case selection. The aim of a study was to create artificial neural networks (ANN) to predict the clinical outcomes after gamma knife radiosurgery (GKRS) in patients with TN, based on preoperative clinical factors.

They used the clinical findings of 155 patients who were underwent GKRS (from March 2000 to march 2015) at Iran Gamma Knife center, Tehran, Iran. Univariate analysis was performed for a long list of risk factors, and those with P-Value < 0.2 were used to create back-propagation ANN models to predict pain reduction and hypoesthesia after GKRS. Pain reduction was defined as BNI score 3a or lower and hypoesthesia was defined as BNI score 3 or 4.

Typical trigeminal neuralgia (TTN) (P-Value = 0.018) and age>65 (P-Value = 0.040) were significantly associated with successful pain reduction and three other variables including radiation dosage >85 (P-Value = 0.098), negative history of diabetes mellitus (P-Value = 0.133) and depression (P-Value = 0.190). On the other hand, radio dosage > 85 (P-Value = 0.008) was significantly associated with hypoesthesia, other related risk factors (with p-Value < 0.2), were history of multiple sclerosis (P-Value = 0.106), pain duration more than 10 years before GKRS (P-Value = 0.115), history of depression (P-Value = 0.139), history of percutaneous ablative procedures (P-Value = 0.148) and history of diabetes mellitus (P-Value = 0.169).ANN models could predict pain reduction and hypoesthesia with the accuracy of 84.5% and 91.5% respectively. By mutual elimination of each factor in this model we could also evaluate the contribution of each factor in the predictive performance of ANN.

The findings show that artificial neural networks can predict post operative outcomes in patients who underwent GKRS with a high level of accuracy. Also the contribution of each factor in the prediction of outcomes can be determined using the trained network 9).

Case series

The long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up.

The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia.

The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN 10).

Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications.

The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery.

The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options 11).

From 1994 to 2009, 40 consecutive patients with typical, intractable TN received GKRS. Among these, 22 patients were followed for >60 months. The mean maximum radiation dose was 77.1 Gy (65.2-83.6 Gy), and the 4 mm collimator was used to target the radiation to the root entry zone.

The mean age was 61.5 years (25-84 years). The mean follow-up period was 92.2 months (60-144 months). According to the pain intensity scale in the last follow-up, 6 cases were grades I-II (pain-free with or without medication; 27.3%) and 7 cases were grade IV-V (<50% pain relief with medication or no pain relief; 31.8%). There was 1 case (facial dysesthesia) with post-operative complications (4.54%).

The long-term results of GKRS for TN are not as satisfactory as those of microvascular decompression and other conventional modalities, but GKRS is a safe, effective and minimally invasive technique which might be considered a first-line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable 12).

Kondziolka et al., evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery.

All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients.

After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity.

Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted 13).

References

1)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
2) , 8)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gor- man DA. High-dose trigeminal neuralgia radiosur- gery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
3)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
4)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotchi J, Levivier M. Gamma knife surgery for idi- opathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
5) , 7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vlady- 1982 ka V. Treatment of essential trigeminal neuralgia with gamma knife surgery.JNeurosurg.2005; 102 Suppl:29–33
6)

Maesawa S, Salame C, Flickinger JC, Pirris S, Kond- ziolka D, Lunsford LD. Clinical outcomes after ster- eotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2001; 94:14–20
9)

Ertiaei A, Ataeinezhad Z, Bitaraf M, Sheikhrezaei A, Saberi H. Application of an artificial neural network model for early outcome prediction of gamma knife radiosurgery in patients with trigeminal neuralgia and determining the relative importance of risk factors. Clin Neurol Neurosurg. 2019 Feb 12;179:47-52. doi: 10.1016/j.clineuro.2018.11.007. [Epub ahead of print] PubMed PMID: 30825722.
10)

Régis J, Tuleasca C, Resseguier N, Carron R, Donnet A, Yomo S, Gaudart J, Levivier M. The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia. Stereotact Funct Neurosurg. 2016;94(1):24-32. doi: 10.1159/000443529. Epub 2016 Feb 17. PubMed PMID: 26882097.
11)

Karam SD, Tai A, Wooster M, Rashid A, Chen R, Baig N, Jay A, Harter KW, Randolph-Jackson P, Omogbehin A, Aulisi EF, Jacobson J. Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up. J Radiat Oncol. 2014;3:125-130. Epub 2013 Nov 20. PubMed PMID: 24955219; PubMed Central PMCID: PMC4052001.
12)

Lee JK, Choi HJ, Ko HC, Choi SK, Lim YJ. Long term outcomes of gamma knife radiosurgery for typical trigeminal neuralgia-minimum 5-year follow-up. J Korean Neurosurg Soc. 2012 May;51(5):276-80. doi: 10.3340/jkns.2012.51.5.276. Epub 2012 May 31. PubMed PMID: 22792424; PubMed Central PMCID: PMC3393862.
13)

Kondziolka D, Perez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998 Dec;55(12):1524-9. PubMed PMID: 9865796.

International Gamma Knife Research Foundation

Upcoming Meetings

ASSFN 2016

​IGKRF Biennial Scientific Session
University of Pennsylvania
Philadelphia, Pa.
June 23, 2017
Meeting Brochure
http://www.igkrf.org/
The International Gamma Knife Research Foundation consists of academic and clinical centers of excellence where brain Stereotactic Radiosurgery is performed using the Leksell Gamma Knife. All participating centers have a track record of outcomes research and participation in clinical trials.
The primary goal of the IGKRF is to facilitate retrospective and prospective clinical trials and outcomes analysis that evaluate the role of Gamma Knife radiosurgery in a wide spectrum of clinical indications.
Because individual centers may evaluate only a small number of patients with rare conditions, pooling of information is critical to evaluate and to improve outcomes. Each center has a professional team consisting of one or more neurological surgeons, radiation oncologists, and medical physicists. Participation is by invitation of the Board of Directors. ​ The IGKRF is a non-profit scientific, educational, and research entity incorporated in the state of Pennyslvania.​

Case series

2017

Ding et al. evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes.
The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms ( P = .001), and higher margin dose ( P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001).
Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs 1).

2016

Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed.
The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.
GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery 2). ​
1)

Ding D, Starke RM, Kano H, Lee JYK, Mathieu D, Pierce J, Huang P, Missios S, Feliciano C, Rodriguez-Mercado R, Almodovar L, Grills IS, Silva D, Abbassy M, Kondziolka D, Barnett GH, Lunsford LD, Sheehan JP. Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study. Neurosurgery. 2017 Jun 1;80(6):888-898. doi: 10.1093/neuros/nyx181. PubMed PMID: 28431024.
2)

Starke RM, Kano H, Ding D, Lee JY, Mathieu D, Whitesell J, Pierce JT, Huang PP, Kondziolka D, Yen CP, Feliciano C, Rodgriguez-Mercado R, Almodovar L, Pieper DR, Grills IS, Silva D, Abbassy M, Missios S, Barnett GH, Lunsford LD, Sheehan JP. Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort. J Neurosurg. 2016 Mar 4:1-9. [Epub ahead of print] PubMed PMID: 26943847.

Gamma Knife Radiosurgery of Brainstem Cavernous Malformations

Gamma knife radiosurgery for brainstem cavernous malformation

Case series

2016

All patients who underwent GKS for the treatment of a hemorrhagic brainstem CM(s) in the Department of Neurosurgery, Lille University Hospital, CHU Lille, Université de Lille, Lille, France. between January 2007 and December 2012. The GKS was privileged when the surgical procedure was evaluated as very risky. The mean dose of radiation was 14.8 Gy, and the mean target volume was 0.282 cm3. All patients participated in a scheduled clinical follow-up. The posttreatment MRI was performed after 6 months and after 1 year, and then all patients had an annual MRI follow-up.
There were 19 patients with a mean age of 36.7 years. The mean follow-up period was 51.2 months. The annual hemorrhage rate (AHR) was 27.31% before GKS, 2.46% during the first 2 years following the GKS, and 2.46% after the first 2 years following the GKS. The decrease in AHR after GKS was significant (p < 0.001).
GKS should be suggested when the surgical procedure harbors a high risk of neurological morbidity in patients with brainstem CM. Compared to prior literature results, a lower dose than applied in this study could be discussed 1).

Between January of 2009 and December of 2014, 43 patients (20 males and 23 females) with brainstem cavernous malformations were treated at the West China Hospital, Sichuan University, Gamma Knife Center. The mean age of these patients was 41.7 years. All of the patients experienced 1 or more episodes of symptomatic bleeding (range 1-4) before undergoing GKS. The mean volume of the malformations at the time of GKS was 442.1mm3, and the mean prescribed marginal radiation dose was 11.9Gy. The mean follow-up period after radiosurgery was 36 months (range 12-120 months).
Before GKS, 50 hemorrhages (1.2 per patient) were observed (25.0% annual hemorrhage rate). Three hemorrhages following GKS were observed within the first 2 years (3.92% annual hemorrhage rate), and 1 hemorrhage was observed in the period after the first 2 years (1.85% annual hemorrhage rate). In this study of 43 patients, new neurological deficits developed in only 1 patient (2.32%; permanent paresthesia on the left side of the face and the right lower limb of the patient). There were no deaths in this study.
GKS is a favorable alternative treatment for brainstem CMs. Using a low marginal dose treatment might reduce the rate of hemorrhage and radiation-induced complications2).

2014

From 1992 to 2011, 49 patients with brainstem CMs were treated with Gamma Knife radiosurgery (GKS). Lee et al., classified patients into two groups: Group A (n = 31), patients who underwent GKS for a CM following a single symptomatic bleed, and group B (n = 18), patients who underwent GKS for a CM following two or more symptomatic bleeds. The mean marginal dose of radiation was 13.1 Gy (range 9.0-16.8 Gy): 12.8 Gy in group A and 13.7 Gy in group B. The mean follow-up period was 64.0 months (range 1-171 months).
In group A, the annual hemorrhage rate (AHR) following GKS was 7.06 % within the first 2 years and 2.03 % after 2 years. In group B, four patients (22.2 %) developed new or worsening neurologic deterioration as a result of repeat hemorrhages. In group B, the AHR was 38.36 % prior to GKS, 9.84 % within the first two years, and 1.50 % after two years. There was no statistically significant difference in the AHRs at each follow-up period after GKS between the two groups. Adverse radiation effects (AREs) developed in a total of four patients (8.2 %); among them, one patient (2.0 %) developed a permanent case of diplopia. No mortality occurred in this series.
In this study, GKS was demonstrated to be a safe and effective alternative treatment for brain stem CMs that resulted in a reduction in the AHR. Consequently, we suggest that even CM patients who have suffered only a single bleed should not be contraindicated for SRS 3).

39 patients (16 males, 23 females) were treated with GKS for BSCA from January 1997 to September 2012. Clinical data were analyzed retrospectively. The mean age was 41.5 years. All patients had a history of symptomatic bleeding once or more before performing GKS. Mean volume of BSCA was 1095.3mm(3) and median prescribed marginal dose was 13 Gy.
Mean follow-up period since diagnosis was 4.1 years. The number of hemorrhagic events between initial diagnosis and GKS was 5 over a total of 14.9 patients-years with annual hemorrhagic rate of 33.6%. Following GKS, there were five hemorrhagic events within the first 2 years (8.1%/year) and two after the first 2 years (2.4%/year). The difference was not statistically significant. Neurologic status improved in 24 patients (61.5%), and stationary in eleven (28.2%). 4 patients (10.3%) experienced the exacerbation of symptoms at the last follow-up and none of them were related to the radiation injury. Significant volume reduction after GKS was observed in 24 patients (61.5%). Surgical excision was performed in one patient due to swelling and rebleeding after GKS. Age at presentation, sex, mass size of BSCA, and location, GKS dose did not affect post-GKS hemorrhage.
GKS for BSCA using relatively low marginal dose is safe and effective. Long-term prospective study is needed to confirm the optimal dose for BSCA 4).

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