cyberknife treatment of trigeminal neuralgia

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A84 | VOLUME 64 | NUMBER 2 | FEBRUARY 2009 SUPPLEMENT www.neurosurgery-online.com

FUNCTIONAL RADIOSURGERY

John R. Adler, Jr., M.D.

Department of Neurosurgery,

Stanford University Medical Center,Stanford, California

Regina Bower, M.D.

Department of Neurological Surgery,

Mayo Clinic College of Medicine,Rochester, Minnesota

Gaurav Gupta, M.S.E.

Department of Neurosurgery,Stanford University Medical Center,

Stanford, California

Michael Lim, M.D.

Department of Neurosurgery,Johns Hopkins School of Medicine,

Baltimore, Maryland

Allen Efron, M.D.

Department of Neurosurgery,Stanford University Medical Center,

Stanford, California

Iris C. Gibbs, M.D.

Department of Radiation Oncology,

Stanford University Medical Center,Stanford, California

Steven D. Chang, M.D.

Department of Neurosurgery,Stanford University Medical Center,Stanford, California

Scott G. Soltys, M.D.

Department of Radiation Oncology,Stanford University Medical Center,Stanford, California

Reprint requests:

John R. Adler, Jr., M.D.,Department of Neurosurgery,

Stanford University Medical Center,300 Pasteur Drive,Stanford, CA 94305.

Email: [email protected]

Received,June 13, 2008.

Accepted, October 27, 2008.

Copyright 2009 by theCongress of Neurological Surgeons

The treatment of trigeminal neuralgia (TN)

by radiosurgical rhizotomy was con-ceived by Lars Leksell (9). Over the past

several decades, radiosurgical parameters fortreating this condition have been optimized,

NONISOCENTRIC RADIOSURGICAL RHIZOTOMYFOR TRIGEMINAL NEURALGIA

OBJECTIVE: Although stereotactic radiosurgery is an established procedure for treat-ing trigeminal neuralgia (TN), the likelihood of a prompt and durable complete responseis not assured. Moreover, the incidence of facial numbness remains a challenge. Toaddress these limitations, a new, more anatomic radiosurgical procedure was devel-oped that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongatedsegment of the retrogasserian cisternal portion of the trigeminal sensory root. Becausethe initial experience with this approach resulted in an unacceptably high incidence offacial numbness, a gradual dose and volume de-escalation was performed over sev-eral years. In this single-institution prospective study, we evaluated clinical outcomesin a group of TN patients who underwent lesioning with seemingly optimized non-isocentric radiosurgical parameters.

METHODS: Forty-six patients with intractable idiopathic TN were treated betweenJanuary 2005 and June 2007. Eligible patients were either poor surgical candidates or hadfailed previous microvascular decompression or destructive procedures. During a singleradiosurgical session, a 6-mm segment of the affected nerve was treated with a meanmarginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthlyneurosurgical follow-up was performed until the patient became pain-free. Longer-termfollow-up was performed both in the clinic and over the telephone. Outcomes weregraded as excellent (pain-free and off medication), good (90% improvement while stillon medication), fair (5090% improvement), or poor (no change or worse). Facial numb-ness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.

RESULTS: Symptoms disappeared completely in 39 patients (85%) after a mean latencyof 5.2 weeks. In most of these patients, pain relief began within the first week. TNrecurred in a single patient after a pain-free interval of 7 months; all symptoms abatedafter a second radiosurgical procedure. Four additional patients underwent a repeatrhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients(72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significantipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) wasreported in 7 patients (15%).

CONCLUSION: Optimized nonisocentric CyberKnife parameters for TN treatmentresulted in high rates of pain relief and a more acceptable incidence of facial numbnessthan reported previously. Longer follow-up periods will be required to establish whetheror not the durability of symptom relief after lesioning an elongated segment of thetrigeminal root is superior to isocentric radiosurgical rhizotomy.

KEY WORDS: CyberKnife, Nonisocentric, Radiosurgery, Rhizotomy, Trigeminal neuralgia

Neurosurgery 64:A84A90, 2009 DOI: 10.1227/01.NEU.0000341631.49154.62 www.neurosurgery-online.com

ABBREVIATIONS: BNI, Barrow NeurologicalInstitute; CT, computed tomographic; Dmax,maximal dose; MRI, magnetic resonance imag-ing; TN, trigeminal neuralgia


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ously (11). Both the CyberKnife Model G3 (400 monitor units/min) andthe CyberKnife Model G4 (600 monitor units/min) were used over thecourse of this study. To summarize, a customized Aquaplast mask(WFR/Aquaplast Corp., Wyckoff, NJ) was fashioned for each patient.While immobilized in the mask, the entire head was imaged with thin-section (1.25-mm slice thickness) contrast computed tomographic (CT)scanning; the first 15 cases in this series received a lumbar intrathecalinjection of iodinated contrast medium (8 mL of iohexol) before CTscanning. Patients were then imaged with fast imaging employingsteady-state acquisition sequence magnetic resonance imaging (MRI)using 3-dimensional volumetric acquisition and 1-mm slice thickness.These CT and MRI techniques reliably demonstrated the trigeminalnerve in negative relief as it transited the prepontine cistern (4). Midwaythrough the current series, we documented the reliability and spatialfidelity of radiosurgical targeting performed with only T2-weightedMRI scanning (4). Once we were confident in the accuracy of MRI-based targeting, the use of CT cisternography for this purpose waslargely abandoned.

On the CyberKnife treatment planning workstation, the MRI andCT scans were fused. Standard segmentation tools were used on thefused data sets to delineate a 6-mm length of the retrogasserian

trigeminal sensory root, as defined in the reconstructed sagittal planeof the nerve. This target volume deliberately spared the proximal 2 to3 mm of trigeminal dorsal root at the brainstem. Dose to the brain-stem and semilunar ganglia was restricted to the maximal extent pos-sible. Four of 5 repeat rhizotomies were performed with the sametreatment parameters as the original procedure; the first re-treatedpatient received a lower dose (Dmax was only 60 Gy). The earlierpatients in the current investigation were treated with a decreased 65-cm source-to-axis distance trigeminal node set, which provides aneffective smaller collimator diameter of approximately 6 mm at theisocenter; the 7.5-mm collimator of the CyberKnife is defined byconvention at a nominal source-to-axis distance of 80 cm. After thehigher-output CyberKnife G4 model was installed at Stanford,patients were treated using a 5-mm collimator and an 80-cm source-to-axis distance.

With increasing experience, treatment planning techniques haveevolved that enable ever better dosimetry for CyberKnife trigeminalrhizotomy. Some of the methods used in the current series include: 1)add a tuning structure to protect brainstem and ipsilateral temporallobe; 2) angle tuning structures to spill dose into the ambient cisternas much as possible; 3) to maximize the resolution of dose calculation,use the smallest calculation grid which covers the proximal brainstem,semilunar ganglion, and 7th and 8th cranial nerves; 4) slightly expandthe targeted nerve segment to improve dosimetric coverage; and 5)constrain the number of monitor units per beam to increase the totalnumber of treatment beams.

A mean marginal prescription dose of 58.3 Gy (range, 5662 Gy) andDmax of 73.5 Gy (range, 71.486.2 Gy) were used over the course of thisseries. The average prescription isodose line was 79%, whereas the doseat the edge of the brainstem was kept to less than 50% of the Dmax.Figure 1 depicts a representative radiosurgical plan for trigeminal neu-ralgia. In Figure 2, note the relatively homogeneous dose within the tar-get volume that is achievable with a nonisocentric technique.

Radiosurgery was performed as an outpatient procedure. Treatmentsessions lasted approximately 1 hour. At the end of the procedure,patients were given 4 mg of dexamethasone.

Follow-up

Patients were followed at 1-month intervals until they were pain-free, at which point anticonvulsants were tapered. Subsequent

follow-up occurred at monthly intervals to ensure a stable clinicalstatus. Any relapse of pain or the development of facial numbnesswas clinically re-evaluated in person. At each point of contact,patients were grouped into 1 of 4 categories: excellent (pain-freeand off medication), good (90% improvement while still on med-ication), fair (5090% improvement), or poor (no change or worsen-ing pain). The presence and timing of facial numbness were alsorecorded and classified according to the BNI Facial Numbness Scalescore (Table 2) (19). Five patients (11%) underwent repeat CyberKniferhizotomy more than 6 months after the initial procedure. In 4 ofthese cases, there was inadequate clinical response to the first radio-surgical procedure, whereas in 1 patient there was a relapse in TNsymptoms 5 months after the initial operation. Longer-term follow-up was done by mail and telephone. Follow-up data were main-tained in a prospective database approved by the Stanford Institu-tional Review Board.

RESULTS

Thirty-nine patients (85%) in this study had complete disap-

pearance of their TN and were off medications at some pointover the course of follow-up. At a mean follow-up duration of14.7 months (range, 629 months; median, 10.5 months), 34patients (72%) graded their pain relief as excellent, and 11 (24%)described it as good. Consequently, 96% of patients obtainedmeaningful relief of TN symptoms after CyberKnife rhizotomy.Within this group were 4 patients whose TN did not improveand 1 patient who, at 7 months, experienced recurrent pain. Allof these patients were re-treated, and the eventual outcome forthese 5 salvage cases was generally excellent (2 patients) orgood (2 patients). However, 1 of the 5 re-treated patients had apoor outcome. Although, across the entire series, an improve-ment in symptoms was typically experienced within a few daysor weeks of radiosurgery, the full benefits were obtained aftera mean latency of 5.2 weeks (ranging from immediately to 6months after the procedure).

TN recurred in only a single patient, 7 months after radio-surgery; 9 months after the first procedure, repeat CyberKniferadiosurgical rhizotomy rendered this patient pain-free. At thetime of the last follow-up evaluation, 11 patients (24%) reporteda significant improvement (3 patients) or even complete abate-ment (8 patients) in TN symptoms but required, or elected tocontinue, anticonvulsants for controlling their pain; 3 patientsrefused to give up their medication only because of concernthat their pain might return. Meanwhile, after rhizotomy, TNsymptoms were deemed to be worse in only 1 case.

Among the 41 patients who had only a single radiosurgi-

cal rhizotomy, significant new ipsilateral facial numbnesswas reported in 7 cases (17%). New-onset sensory loss typi-cally involved the hemicranium and occurred an average of7 months after the procedure. Interestingly, only 1 of 5patients who underwent repeat radiosurgery (after a previ-ous gamma knife or CyberKnife rhizotomy) developed sig-nificant subsequent facial numbness. At the time of the mostrecent follow-up evaluation, facial sensation and dysesthesiawere categorized in all patients according to BNI Scale scoreas follows: BNI I, 28 patients; BNI II, 11 patients; and BNI III,


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7 patients (Table 2). Three of the 7 patients who reportedsomewhat bothersome facial numbness treated these symp-toms with either neurontin (2 patients) or amitriptyline. It isimportant to note that 11 patients had some measure ofnumbness before CyberKnife rhizotomy, and at the time of

the last follow-up evaluation, there were no cases of anesthe-sia dolorosa.

Twenty-eight patients (61%) reported the optimal result ofbeing pain-free and off anticonvulsants, while retaining pre-treatment facial sensation. Six additional patients were pain-free but either elected to remain on reduced doses of anticonvul-

sants or were unable to taper off such drugs completely withoutexperiencing some recurrent symptoms. Consequently, Cyber-Knife rhizotomy resulted in 74% of all patients experiencinggood to excellent pain relief without significant facial numbness.If one includes 9 additional patients who developed significantfacial numbness, 96% of all patients experienced complete ornear-complete relief of trigeminal neuralgia. It is especially note-worthy that among the 31 TN patients who had never under-gone any previous surgical procedure, 100% had either a goodor excellent response to CyberKnife rhizotomy.

FIGURE 1. Screen shot taken from the CyberKnife (Accuray, Inc., Sunnyvale,CA) treatment planning workstation depicting a representative radiosurgical

plan for trigeminal neuralgia and illustrating the relatively homogeneous dosewithin the target volume that is achievable with a nonisocentric technique.

TABLE 2. Barrow Neurological Institute Facial Numbness Scalescore and outcomes

No. ofGrade Description

patients

I No facial numbness 28

II Mild facial numbness, not bothersome 11

III Facial numbness, somewhat bothersome 7

IV Facial numbness, very bothersome 0


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the outcome with nonisocentric radiosurgical rhizotomy is at leastcompetitive in terms of overall rate of response. Ideally, the currentexperience could provide a reasonable substrate for a randomizedtrial that compares the 2 procedures.

The rate of numbness observed in the present series appearsto be greater than first reported by several groups using an

isocentric gamma knife technique (12, 17, 19). However, higherrates of facial numbness after gamma knife rhizotomy havealso been reported, especially with larger and more effectivedosing regimens (14, 16). Consequently, the overall incidenceand characteristics of sensory loss experienced by some of thepatients in the current CyberKnife study seem comparable towhat has been reported previously with more conventionalisocentric procedures.

Although there are important technical differences, the rel-atively unremarkable incidence of facial sensory changes thatwe observed in the present series may challenge one of the keyfindings reported by Flickinger et al. (6). This randomizedtrial, which examined the usefulness of 2 adjacent 4-mm

gamma knife shots when lesioning the trigeminal nerve,needed to be terminated prematurely when patients in theexperimental arm developed severe dysesthesias. The investi-gators concluded that a longer radiosurgical lesion merelyincreased the likelihood of complications without alteringthe pain response. What remains unclear is why Flickingeret al. did not encounter an increased rate of response amongpatients treated with a longer lesion of the trigeminal sensoryroot. The failure to find such a response would appear to runcounter to the experience described by our group (10, 23) and,perhaps, the reports of other gamma knife series that found adirect correlation between integral dose to the trigeminal nerveand the likelihood of pain relief (16). Moreover, the findings ofFlickinger et al. (6) would seem to be at odds with the widelyobserved dose-volume-response phenomenon seen through-out most of radiosurgery. Of note, the Flickinger et al. studycompared the standard 1-isocenter treatment with a solitaryexperimental group in which the longer rhizotomy consistedof 2 adjacent isocenters. By comparison, our group requiredseveral years to slowly titrate a radiosurgical dose and volumefor lesioning the trigeminal nerve, which is proving, in ourexperience, to be more optimal in terms of pain relief andavoidance of facial numbness. Perhaps a wider investigation ofvolumes and doses delivered with a 2-isocenter gamma knifetechnique might reveal a combination that improves pain reliefwithout further risk of unpleasant facial numbness. Only fur-ther study, and most probably a randomized trial, can deter-

mine whether or not a longer trigeminal rhizotomy ultimatelyhas any clinical advantages.

One of the primary rationales for modifying the standardradiosurgical rhizotomy technique was to increase the durabil-ity of pain relief. Because only 1 of 39 patients experienced arelapse in their TN (7 months after stereotactic radiosurgery),the current experience is encouraging. Nevertheless, muchlonger follow-up periods will be required to prove that lesion-ing a longer segment of nerve can significantly increase thedurability of the radiosurgical rhizotomy.

DISCUSSION

The benefits of radiosurgical rhizotomy for TN using the stan-dard isocentric technique are, for many patients, insufficient.Because of the latency of pain relief, overall rate of response,and recurrence of TN symptoms, radiosurgical rhizotomy haslimited appeal in the eyes of some neurosurgeons. In an attemptto address the shortcomings of the standard isocentric technique,our group has sought, over several years, to refine a procedurethat uses nonisocentric radiosurgery to lesion an elongated seg-ment of the retrogasserian portion of the trigeminal sensory root.Over time, treatment parameters have been optimized toenhance the pain response and reduce facial numbness. The pri-mary objective of the current prospective single-institution studywas to characterize short-term outcomes with this technique.

The overall response rate observed in the current CyberKnifeseries appears satisfactory. In fact, 100% of the patients who hadnot previously undergone a surgical procedure reported theiroutcome as either good (13%) or excellent (87%); 1 of thesepatients needed to be treated twice to achieve this outcome. It isreasonable to propose that this high rate of response is attribut-able, at least in part, to the longer length of trigeminal nervelesioned with the CyberKnife.

Although the methods used to score the response of TN totrigeminal rhizotomy are relatively consistent among most clinicalseries, patient inclusion criteria, length of follow-up, and measuresof facial numbness and/or dysesthesia vary widely. Consequently,it is difficult to directly compare those outcomes with those in thecurrent study, and as a result, it cannot be determined at presentwhether or not irradiating a longer nerve segment is clinically

beneficial. Nevertheless, crude comparisons with published radio-surgical rhizotomy series that have used isocentric gamma knife(16, 18) and linear accelerator-based (21) procedures suggest that

FIGURE 2. Sagittal magnetic resonance imaging reconstruction demon-strating relative dose homogeneity.


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There are significant differences between the treatment plan-ning parameters used throughout the current series and thosethat have been reported in previous descriptions of CyberKnifenonisocentric rhizotomy (23). In the study by Villavicencio et al.(23), the length of lesioned nerve ranged from 3 to 12 mm,whereas the marginal prescription ranged from 40 to 70 Gy

and the Dmax ranged from 50 to 86.4 Gy. Moreover, the dose atthe edge of the brainstem was as high as 50% in that study.These values contrast markedly with the more uniform 6-mmlength of lesioned nerve used throughout the current investiga-tion. Meanwhile, the mean marginal prescription dose that wenow report ranged only between 56 and 62 Gy, and the Dmaxranged between 71.4 and 86 Gy. Of note, there was only a sin-gle patient who received a dose of 86 Gy, and the next highestDmax was 77 Gy. Finally, in the present series, we kept thedose at the edge of the brainstem to less than 30% of Dmax.These sizeable differences in treatment planning parametersrelative to the series reported by Villavicencio et al. (23) wouldseem to be responsible for the seemingly better outcome we

now report.Unlike the more defined and reproducible isocentric lesionmade with the gamma knife, treatment planning for CyberKnifetrigeminal rhizotomy introduces a number of novel yet highlycritical treatment planning variables. As a consequence, treat-ment planning techniques have evolved with ever greater expe-rience, and as a result, the procedure (and dosimetry) used inthe current investigation represents an improvement over whatwas described in the study by Villavicencio et al. (23). Some ofthe specific treatment planning tactics used in the current seriesare described previously in Methods. In addition to designing

better treatment plans, surgical experience has also been impor-tant in better defining the targeted nerve segment. With imag-ing, the relevant anatomy can be ambiguous in some TNpatients, especially after a failed microvascular decompression.Given all of the above factors, improved surgical technique mayhave been yet another factor in the somewhat different outcome

being reported here relative to that of Villavicencio et al. (23).The incidence and intensity of delayed numbness observed in

the current series represents a substantial improvement overwhat was previously reported for CyberKnife rhizotomy (11, 23).For example, the 17% rate of bothersome facial numbness (BNIIII) that we describe in the current report is a significantly lowerrate than the 28% observed by Villavicencio et al. (23), which alsoincluded BNI scores of III (16%) and IV (12%). In addition, noneof the patients in the current series developed other, even moreserious complications such as anesthesia dolorosa, trismus, mas-

ticator weakness, diplopia, decreased hearing, dry eye syndrome,or paresis, all of which were described by Villavicencio et al. Asa consequence, it appears that the dose-volume parameters beingused with the present nonisocentric technique make for a betterclinical outcome. Given the reported latency between radio-surgery and the onset of facial numbness, it is quite possible that,with further follow-up, additional patients will develop sensorysymptoms. However, because the mean overall follow-up dura-tion is 14.7 months in the present study, whereas the mean timeto occurrence of numbness is 7 months, it seems unlikely that loss

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of facial sensation will occur in enough additional patients toalter this primary finding. Ultimately, it seems clear that numb-ness is significantly less likely using the optimized treatmentparameters of the present study than it was during the develop-mental stages of CyberKnife rhizotomy for TN.

The specific treatment parameters used in the current series

to achieve a lower complication rate thus far do not appear tohave compromised the short-term efficacy of radiosurgical rhi-zotomy when a comparison is made to the Villavicencio et al.series (23). The 72% rate of being pain-free and off medicationthat is observed in the current investigation compares favor-ably with the 67% rate of excellent outcome described in theearlier study. Although the longer-term likelihood of TN recur-rence when both the length of nerve and dose have been opti-mized remains unknown, the preliminary 2% rate of relapse weobserve in the current study seems competitive with the 37%rate of recurrent TN noted by Villavicencio et al., albeit thefollow-up period for their study is longer, at 2 years. Clearly,additional follow-up is needed to compare the ultimate dura-

bility of these 2 procedures.It is worth pointing out that TN is somewhat unique amongpain syndromes in that pain is usually either present or absent.As a consequence, the large majority of patients with completerelief were easy to categorize as such. In contrast, the nature ofsymptoms and outcome among patients with only partial painrelief was more complex and less conducive to the relativelysimplistic measuring tools used in this investigation. Moreover,several of the patients in this series had coexisting facial painsyndromes that were not TN-like and were precipitated in part

by previous failed ablative procedures or microvasculardecompression. Because some of these same patients also even-tually developed post-rhizotomy delayed facial numbness, itwas often difficult to distinguish new sensory symptoms fromtheir preexisting pain condition. Therefore, one of the limita-tions of the current investigation is that, unlike the recent study

by Rgis et al. (18), there is not a more detailed analysis of ourpatients ultimate facial sensation. Despite this shortcoming,the current investigation should provide a useful starting pointfor future investigation.

The biological mechanism underlying the cessation of TNsymptoms after radiosurgical rhizotomy remains poorlydefined. Some investigators have concluded that the likelihoodof a clinical response to radiosurgery correlates with the devel-opment of facial numbness (16, 19). This suggests that a com-mon mechanism underlies these 2 phenomena. However, theirvery different time course implies that distinct mechanisms

underlie pain relief and facial numbness; TN pain abates rela-tively rapidly after a radiosurgical rhizotomy, whereas facialnumbness is clearly a delayed event (69 months or more afterradiosurgery). Meanwhile, both the latency of sensory changesand the appearance of enhancement on contrast MRI at theroot entry zone, the latter being consistent with breakdown inthe blood-brain barrier, strongly suggest that facial numbnessstems from injury to the microvasculature of the trigeminalnerve and adjacent brainstem (7). If so, such a phenomenonraises some intriguing possibilities for intervention. In particu-


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improve trigeminal neuralgia radiosurgery? A prospective double-blind, ran-

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of trigeminal neuralgia. Surg Neurol 66:350356, 2006.8. Kondziolka D, Lunsford LD, Flickinger JC, Young RF, Vermeulen S, Duma

CM, Jacques DB, Rand RW, Regis J, Peragut JC, Manera L, Epstein MH,Lindquist C: Stereotactic radiosurgery for trigeminal neuralgia: A multiinsti-tutional study using the gamma unit.J Neurosurg 84:940945, 1996.

9. Leksell L: Stereotaxic radiosurgery in trigeminal neuralgia. Acta Chir Scand137:311314, 1971.

10. Lim M, Cotrutz C, Romanelli P, Schaal D, Gibbs I, Chang SD, Adler JR:Stereotactic radiosurgery using CT cisternography and non-isocentric planningfor the treatment of trigeminal neuralgia. Comput Aided Surg 11:1120, 2006.

11. Lim M, Villavicencio AT, Burneikiene S, Chang SD, Romanelli P, McNeely L,McIntyre M, Thramann JJ, Adler JR: CyberKnife radiosurgery for idiopathictrigeminal neuralgia. Neurosurg Focus 18:E9, 2005.

12. Maesawa S, Salame C, Flickinger JC, Pirris S, Kondziolka D, Lunsford LD:Clinical outcomes after stereotactic radiosurgery for idiopathic trigeminalneuralgia.J Neurosurg 94:1420, 2001.

13. Massager N, Lorenzoni J, Devriendt D, Levivier M: Radiosurgery for trigem-inal neuralgia. Prog Neurol Surg 20:235243, 2007.

14. Massager N, Murata N, Tamura M, Devriendt D, Levivier M, Rgis J:Influence of nerve radiation dose in the incidence of trigeminal dysfunctionafter trigeminal neuralgia radiosurgery. Neurosurgery 60:681688, 2007.

15. Nicol B, Regine WF, Courtney C, Meigooni A, Sanders M, Young B: Gammaknife radiosurgery using 90 Gy for trigeminal neuralgia. J Neurosurg 93[Suppl 3]:152154, 2000.

16. Pollock BE, Phuong LK, Foote RL, Stafford SL, Gorman DA: High-dosetrigeminal neuralgia radiosurgery associated with increased risk of trigemi-nal nerve dysfunction. Neurosurgery 49:5864, 2001.

17. Rgis J, Metellus P, Dufour H, Roche PH, Muracciole X, Pellet W, Grisoli F,Peragut JC: Long-term outcome after gamma knife surgery for secondarytrigeminal neuralgia.J Neurosurg 95:199205, 2001.

18. Rgis J, Metellus P, Hayashi M, Roussel P, Donnet A, Bille-Turc F: Prospectivecontrolled trial of gamma knife surgery for essential trigeminal neuralgia.

J Neurosurg 104:913924, 2006.19. Rogers CL, Shetter AG, Fiedler JA, Smith KA, Han PP, Speiser BL: Gamma

knife radiosurgery for trigeminal neuralgia: The initial experience of The BarrowNeurological Institute. Int J Radiat Oncol Biol Phys 47:10131019, 2000.

20. Shetter AG, Rogers CL, Ponce F, Fiedler JA, Smith K, Speiser BL: Gammaknife radiosurgery for recurrent trigeminal neuralgia.J Neurosurg 97 [Suppl

5]:536538, 2002.21. Smith ZA, De Salles AA, Frighetto L, Goss B, Lee SP, Selch M, Wallace RE,

Cabatan-Awang C, Solberg T: Dedicated linear accelerator radiosurgery forthe treatment of trigeminal neuralgia.J Neurosurg 99:511516, 2003.

22. Taha JM, Tew JM Jr, Buncher CR: A prospective 15-year follow up of 154 con-secutive patients with trigeminal neuralgia treated by percutaneous stereotac-tic radiofrequency thermal rhizotomy.J Neurosurg 83:989993, 1995.

23. Villavicencio AT, Lim M, Burneikiene S, Romanelli P, Adler JR, McNeely L,Chang SD, Fariselli L, McIntyre M, Bower R, Broggi G, Thramann JJ:CyberKnife radiosurgery for trigeminal neuralgia treatment: A preliminarymulticenter experience. Neurosurgery 62:647655, 2008.

AcknowledgmentWe acknowledge the helpful suggestions and diligent edits made by David

Schaal, Ph.D., during the preparation of this manuscript.

lar, the use of an intravascular free radical scavenger, like ami-fostine (Ethyol; Medimmune, Gaithersburg, MD), at the time ofradiosurgery might provide relative radioprotection to theendothelium and limit the incidence of delayed microvascularinjury. Theoretically, such an agent would not alter the biolog-ical mechanism underlying the therapeutic benefits of radio-

surgery. A randomized trial is being planned to investigatesuch a possibility.

CONCLUSION

Compared with previous reports that describe the clinicaloutcome after nonisocentric radiosurgical rhizotomy in patientswith TN, the present investigation demonstrates both highrates of pain relief and an acceptable incidence of facial numb-ness. We are not able to determine whether or not this tech-nique can ultimately improve on either the rate of response orthe durability of symptom relief that can be achieved with thestandard isocentric radiosurgical rhizotomy. Further study is

warranted, and, ideally, a randomized trial comparing isocen-tric and nonisocentric techniques should be conducted.

DisclosureFunding for this investigation came from the Victoria and Gary Reed Fund for

Radiosurgical Research. John R. Adler, Jr., M.D., is a shareholder and a member

of the board of directors of Accuray, Inc., the manufacturer of the CyberKnife

radiosurgical system. The other authors have no personal financial or institu-

tional interest in any of the drugs, materials, or devices described in this article.

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