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Trigeminal Neuralgia Radiosurgery






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Trigeminal Neuralgia Radiosurgery Trigeminal Neuralgia Radiosurgery Document Transcript

  • Trigeminal Neuralgia RadiosurgeryDouglas Kondziolka, M.D., M.Sc., F.R.C.S.C., F.A.C.S.,1,2,3L. Dade Lunsford, M.D., F.A.C.S.,1,2,3 and John C. Flickinger, M.D., F.A.C.R.1,2,3ABSTRACT Although medical therapy is of benefit to many patients with trigeminal neuralgia, surgical management is often performed for patients with medically refractory pain. Gamma knife radiosurgery has been advocated as a minimally invasive alternative surgical approach to microvascular decompression or percutaneous surgeries. In this article, we review the safety and efficacy of this technique and discuss potential ways to improve on results. KEYWORDS: Trigeminal neuralgia, radiosurgery, tic douloureuxObjectives: Upon completion of this article, the reader should be able to: (1) summarize the management options for patients withtrigeminal neuralgia; (2) discuss the technical aspects of trigeminal neuralgia radiosurgery; and (3) summarize the treatmentexpectations that follow this procedure. M edical therapy is the initial approach for most TECHNIQUE OF RADIOSURGERYpatients with trigeminal neuralgia. However, many pa- We use the model U or C gamma knife units inter-tients fail or cannot tolerate medical therapy and even- changeably for radiosurgery at our center. Patientstually require surgical intervention. Although often undergo the entire procedure during a 23-hour hospital-associated with initial pain relief, all surgical procedures ization. First, the Leksell model G stereotactic frameare associated with variable but definite rates of recur- (Elekta Instruments, Atlanta, GA) is attached to therence and morbidity. Gamma knife radiosurgery has head under local anesthesia. Second, the patient under-been advocated as a minimally invasive alternative sur- goes stereotactic magnetic resonance (MR) imaging togical approach to microvascular decompression (MVD) identify the trigeminal nerve. Rarely, patients haveor percutaneous surgeries. Stereotactic irradiation of the computed tomography (CT) imaging for targeting iftrigeminal ganglion was first reported by Leksell.1 More they cannot undergo MR imaging. MR imaging isrecently, numerous authors have reported their initial performed using contrast-enhanced, short repetitionresults with radiosurgery using high-resolution image time (TR) sequences and axial volume acquisitions ofguidance.2–9 These data testified to the accuracy of 512 Â 216 matrices divided into 1-mm slices. When theradiosurgical targeting and the initial safety of the trigeminal nerve is difficult to identify on imagingtechnique and provided dose-response information. In (usually because of prior MVD), additional axial longthis article, we review clinical outcomes following radio- relaxation time MR images were used. A single 4-mmsurgery and discuss indications and technical issues of isocenter is used for targeting, although in the past somethe procedure. patients have been treated with two-isocenter plans.Pain Management for the Neurosurgeon: Part 2; Editor in Chief, Winfield S. Fisher III, M.D.; Guest Editor, Kim J. Burchiel, M.D., F.A.C.S.Seminars in Neurosurgery, volume 15, numbers 2/3, 2004. Address for correspondence and reprint requests: Douglas Kondziolka, M.D., Ste. B-400,UPMC Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213. E-mail: kondziolkads@msx.upmc.edu. Departments of 1Neurological Surgery, and2 Radiation Oncology, University of Pittsburgh, and 3the Center for Image-Guided Neurosurgery, Pittsburgh, Pennsylvania. Copyright # 2004 byThieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. 1526-8012,p;2004,15,02/03,135,141,ftx,en;sns00195x. 135
  • 136 SEMINARS IN NEUROSURGERY/VOLUME 15, NUMBERS 2/3 2004 Figure 1 Magnetic resonance images at gamma knife radiosurgery for an 80-year-old woman with right trigeminal neuralgia. A maximum dose of 75 Gy was delivered to the nerve using a single 4-mm isocenter. Coronal and sagittal views are shown on the right. With a single isocenter, the target is 2 to 4 mm anterior of pain relief being studied (complete or > 50%) was from the junction of the trigeminal nerve and pons achieved. To identify any correlation of outcomes (time (Fig. 1). The isocenter is usually located so that brain- to initial response, duration of benefit, and complica- stem surface is irradiated at the 30% isodose line. Past tions) with treatment parameters that include sex, age, patients received maximum doses of 60, 70, 80, 85, or duration of symptoms, presence or absence of preopera- 90 Gy, although 80 Gy is our usual dose (Fig. 2). tive paresthesia or additional atypical features, number of prior surgeries, maximum dose, and number of iso- centers, stepwise (forward conditional) multivariate METHOD OF PATIENT EVALUATION analyses using the Cox proportional hazards model are Following radiosurgery, we evaluate patients for the performed. degree of pain relief, latency interval to pain relief, need for further surgical procedures, use of medication, and complications. In addition, up-to-date clinical in- UNIVERSITY OF PITTSBURGH formation is obtained by telephone interview at periodic EXPERIENCE intervals.10 To evaluate effectiveness over time (besides Our current experience included 513 patients. There the typical measure of the proportion of patients with were 305 (60%) women and 208 men. The mean age pain relief at initial or last follow-up), we calculate the was 68 years (range, 16–92). The mean duration of time to initial response from radiosurgery and the dura- symptoms was 8 years. tion of pain relief using the product limit method of Our last detailed review studied patients managed Kaplan and Meier.11 The time to onset of complications between December 1992 and December 1998 (n ¼ 264 after radiosurgery (new or increased sensory disturbance) consecutive radiosurgery procedures for trigeminal neu- is also calculated using the same methods. Pain relief ralgia).10 Of these 264 procedures, 25 were performed for duration is calculated from the time when the level nonidiopathic trigeminal neuralgia (19 were associated
  • TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL 137Figure 2 Magnetic resonance images at gamma knife radiosurgery for a 78-year-old woman with right trigeminal neuralgia. Note theprominent arteries surrounding the nerve. A maximum dose of 80 Gy was delivered using a single 4-mm isocenter. She had relief of painand tapered her medications.with multiple sclerosis, three were secondary to tumors, trigeminal nerve (29.5%), followed by V2 alone (22.3%)and three were secondary to other pathological condi- and V3 alone (13.2%). Patients with first-divisiontions such as a herpetic infection, Lyme disease, or pain often had radiosurgery as an alternative to otherWallenberg’s syndrome). These 25 procedures were procedures. Although all patients complained of theexcluded from this study. Of the 239 procedures per- typical trigeminal neuralgia features of a sharp, lancinat-formed for idiopathic trigeminal neuralgia, 19 were ing, or shooting electric shock type of pain triggered by aa repeated radiosurgery after an initially successful variety of events, 16 (7.3%) complained of additionalprocedure. For these 19 patients, the outcome after features such as a more constant dull, aching, or burninginitial radiosurgery was included in this study as a poor pain. Eighty patients (36.4%) had some sensory disturb-result (subsequent outcomes of the repeated procedure ance (usually paresthesias) preoperatively, and threewere excluded). Thus, 220 procedures in 220 patients patients (1.4%) had partial deafferentation pain causedwere available for analysis. All 220 patients had trigem- by prior ablative procedures.inal neuralgia that was idiopathic, long standing, and Prior surgery was performed in 135 patientsrefractory to medication therapy such as carbamazepine, (61.4%), including MVD, glycerol rhizotomy, radio-phenytoin, baclofen, or gabapentin as well as a variety of frequency rhizotomy, balloon microcompression, pe-analgesic medications. ripheral neurectomy, or ethanol injections. Of these Of these 220 patients, 94 were male and 126 were 135 patients, 86 (39.1%) had one, 39 (17.7%) had two,female. The median age of the patients was 70 years and 10 (4.5%) had three or more procedures prior to(range 26–92). Most of the patients had long history of radiosurgery. Thus, the majority of patients representedmedical treatment with a median symptom duration of both medical and surgical failures. In the remaining96 months (range 3–564 months). Pain was predomi- 85 patients (38.6%), radiosurgery was the first surgicalnantly distributed in the V2 and V3 distributions of the procedure performed.
  • 138 SEMINARS IN NEUROSURGERY/VOLUME 15, NUMBERS 2/3 2004 Pain Relief However, about 15% of patients had no improvement in The outcome of the intervention was graded in four their pain even after 12 months. Because no patient categories: excellent, good, fair, and poor. Complete pain achieved complete or even more than 50% pain relief relief without the use of any medication was defined as after 12 months follow-up, we believe that patients with an excellent outcome. We recommended that all patients unchanged pain at 1 year cannot expect any improve- with complete pain relief taper off their medications, and ment afterward. In reality, this is an uncommon situation some patients were in the process of tapering at the time because most patients would not wait so long to attain of evaluation (or refused to taper because of fear of a pain relief. Patients who have continued disabling recurrence). The patients with complete pain relief who pain after radiosurgery are managed with other surgical were still using some medication were considered as procedures. We advocate repeated radiosurgery only if having good outcomes. Patients with partial pain relief complete pain relief had been achieved with subsequent (more than 50% pain relief) were considered to have a recurrence. fair outcome.2 No pain relief or less than 50% pain relief Complete pain relief was achieved at a median was considered as poor. Placement within a category was time of 2 months, with most patients achieving this level decided by the patient rather than by the physician. of relief within 6 months. Interestingly, a further 10% of Criteria for improvement included a reduction in both patients achieved complete pain relief 6 to 33 months the frequency and severity of pain attacks. Of the 220 after radiosurgery. All of these patients obtained partial patients, 47 (25.1%) required further additional surgical pain relief within 6 months and then had complete re- procedures because of poor pain control. These patients solution of pain afterward. Thus, it appears that patients were considered as treatment failures (poor outcome), with partial pain relief may go on to complete relief over and the results after the additional procedure were time. This finding provides some ideas regarding the excluded from this analysis. mechanism of response to radiosurgery. Because most Most of the patients responded to radiosurgery patients responded in the initial months, electrophysio- within 6 months of the procedure (median 2 months). logic blocking of ephaptic transmission after nerve The first evaluation was performed for all patients within irradiation, which has been discussed as a possible 6 months after radiosurgery. At the initial follow-up mechanism by some authors,4,9 is possible. On the other assessment, excellent results were obtained in 105 pa- hand, because some patients responded or improved in a tients (47.7%), and excellent plus good results were later phase (more than 6 months after radiosurgery), a found in 139 patients (63.2%). More than 50% pain later radiation effect with axonal degeneration may be relief (excellent, good, or fair) was noted in 181 patients present. (82.3%). At the last follow-up evaluation, 88 patients (40%) had excellent outcomes, 121 patients (55.9%) had excellent plus good outcomes, and 152 were fair or better Maintenance of Pain Relief (69.1%). Thirty patients (13.6%) had recurrence of pain The duration of pain relief after the initial response in after the initial achievement of pain relief (25 patients all patients was also analyzed. Patients who never re- after complete relief, 5 patients after more than 50% sponded to radiosurgery were recorded as having a relief relief) between 2 and 58 months after radiosurgery. duration of zero months. More than 50% pain relief Recurrences occurred at a mean of 15.4 months from (excellent, good, or fair) was achieved and maintained in irradiation. 75.8 Æ 2.9% of patients at 1 year, 71.3 Æ 3.3% of patients at 2 years, 67.2 Æ 3.9% of patients at 3 years, 65.1 Æ 4.3% of patients at 3.5 years, and 55.8 Æ 9.3% of patients at Time to the Initial Response 5 years. Complete pain relief (excellent or good) was The time to response after radiosurgery was analyzed achieved and maintained in 63.6 Æ 3.3% of patients using the product limit method of Kaplan and Meier. at 1 year, 59.2 Æ 3.5% of patients at 2 years, and The median time to achieving more than 50% pain relief 56.6 Æ 3.8% of patients at 3 years. A history of no prior (excellent, good, or fair) was 2 months (2.0 Æ 0.05), and surgery was the only factor significantly associated median time to achieving complete pain relief (good or (p ¼ .01) with achieving and maintaining complete excellent) was also 2 months (2.0 Æ 5.1). At 6 months pain relief. after treatment, 81.4 Æ 2.6% of patients had achieved more than 50% pain relief, and by 12 months, 85.6 Æ 2.47% of patients had (actuarial statistics). Complete Side Effects of Radiosurgery pain relief (good or excellent) was achieved in 64.9 Æ No patient sustained an early complication after any 3.2% of the patients at 6 months, 70.3 Æ 3.16% by 1 year, radiosurgery procedure. Seventeen patients (7.7%) de- and 75.4 Æ 3.49% of patients by 33 months. veloped increased facial paresthesia and/or facial numb- Prior authors including our group noted a latency ness that lasted more than 6 months. The median interval to pain relief of approximately 1 to 2 months.2,4,9 time to developing paresthesia was 8 months (range
  • TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL 1391–19 months). After 19 months, no patient developed The low incidence of complications is the greatestany new sensory symptoms. No patient developed a advantage of stereotactic radiosurgery compared with allmastication deficit after radiosurgery or noted problems other surgeries. Paresthesia or numbness of varyingin facial motor function. One patient (0.4%) developed magnitude is observed in 20 to 70% of patients afterdeafferentation pain after radiosurgery. This patient had percutaneous thermorhizotomy, glycerol rhizotomy,recurrent trigeminal neuralgia previously treated by or balloon nerve compression.12,14–21 In this study, 17MVD. Following her MVD she had some decrease in patients (10.2 Æ 2.35% at 2 years) developed increasedfacial sensation, and her recurrent pain had some addi- facial paresthesia and/or facial numbness. The majoritytional atypical features such as constant burning. Eight of our patients described their numbness or paresthesiayears after initial surgery, radiosurgery was performed to as minor and not bothersome. Some authors advocateda maximum dose of 75 Gy using two isocenters. Eight percutaneous balloon nerve compression as advanta-months later, she developed increased constant burning geous for management of first-division trigeminal neu-pain with numbness consistent with deafferentation ralgia because of the lower risk for postoperative cornealpain. analgesia. In the present radiosurgery study, no patient developed this complication. The reduced rate of facial sensory deficits or symptoms indicates that the effectsComparing Radiosurgery with on nerve tissue may be less than after other ablativeOther Procedures surgeries. Thus, the mechanistic effect of radiosurgery isThe results of radiosurgery do not appear to be as good as probably a combination of both histologic and electro-those observed after a first MVD but appear to be as physiologic responses.good or better as a second procedure. Barker et al, in Radiosurgery can be repeated if pain returns afterreporting on Jannetta’s series of 1185 patients, found initial relief. We advocate a maximum dose of 50 tothat complete pain relief was maintained in 70% of 60 Gy at a second procedure and usually target a morepatients at 10 years.12,13 Thus, we continue to advocate anterior section of the nerve. Doing so has led to a painMVD for appropriate younger patients with trigeminal response similar to that after primary radiosurgery inneuralgia because of the potential for longer duration properly selected patients.22pain relief. Nevertheless, the possible risks of MVDmake it unsuitable for some patients. In addition, thebenefit of MVD is less when performed a second time or Effect of Radiation on Nerves:for recurrent trigeminal neuralgia. We consider radio- A Primate Model of Radiosurgerysurgery a good choice for patients with recurrent pain Peripheral nerves are considered highly radioresistant. Aafter MVD or percutaneous surgery has failed, even dose that produces delayed radiation necrosis of spinalthough prior surgical failure reduces the radiosurgical cord may have no effect on peripheral nerves. To studysuccess rate. the effects of radiosurgery on trigeminal nerve fibers, Other investigators have reported long-term re- we used a baboon radiosurgery model and deliveredsults following different percutaneous techniques for either 80 or 100 Gy to the nerve using a single 4-mmtrigeminal neuralgia. Percutaneous retrogasserian ther- isocenter.23 Trigeminal nerves that received 80 Gymal rhizotomy, first described in 1974 by Sweet and radiosurgery had no inflammation. Focal myelin pallorWepsic, has been widely performed.14 In Broggi and and vacuolation without fibrosis was noted with MassonFlanzini’s series of 1000 patients with 9.3 years of mean trichrome in the preganglionic nerve segments.follow-up, they found an initial pain relief rate of 95%, Immunoreactivity for neurofilament revealed sub-with recurrence in 18.1%.15 Scrivani et al reported their stantial axonal loss, fragmentation, and some swellings.series of 215 patients and found that 83% maintained Plastic sections and ultrastructural studies revealed apain relief at a mean interval of 32 months.16 Percuta- focal region near the center of the nerve exhibitingneous retrogasserian glycerol rhizotomy, first reported by acutely degenerating axons with preservation of someHakanson, is also widely used.17 Jho and Lunsford ˚ identifiable myelinated axons admixed with small foci ofreported that 90% of 523 patients achieved complete tissue necrosis (Fig. 3). Schwann cell nuclei were alsopain relief initially and that 77% maintained longer term necrotic. The surrounding region contained only rarepain control, sometimes requiring multiple procedures.18 degenerating axons in which the trigeminal gangliaThe pain recurrence rate was estimated to be between 30 appeared normal, as did the distal nerve beyond theand 50% over 2 to 10 years. Others reported a longer radiosurgery target.term pain control rate of 50 to 90%.14,19,20 Results Trigeminal nerves that received 100 Gy exhibitedfollowing percutaneous trigeminal nerve balloon com- axonal degeneration with myelin vacuolation and expan-pression indicated a high rate of initial pain relief, sion of the endoneurial intercellular matrix consistentbut that pain recurred in 26% (50 patients with average with edema. In one specimen, nearly the entire nerve3-year follow-up).21 width was necrotic. The ganglion remained normal.
  • 140 SEMINARS IN NEUROSURGERY/VOLUME 15, NUMBERS 2/3 2004 Figure 3 Electron micrograph of a baboon trigem- inal nerve 6 months following 80 Gy radiosurgery (top). Note the partial nerve degeneration. Distal to the target, the nerve appeared normal (bottom). On plastic sections, axonal degeneration was noted out- substantiated by the findings of our experiments. We side the necrotic zone, but the histology normalized could not detect a substantial difference in axonal injury toward the ganglion (Fig. 3). Ultrastructural studies among small myelinated, large myelinated, and unmye- revealed that the axonal degeneration around the irra- linated fibers. Through partial (focal) axonal degenera- diated targets affected large and small myelinated axons tion, radiosurgery probably relieves trigeminal neuralgia similarly at both radiosurgery doses. Only rare primary pain by affecting an axon population large enough demyelination (vesicular demyelination) was noted out- to result in pain relief. On the other hand, the low side the necrotic zones. Only rare intact unmyelinated incidence of lost facial sensation indicates that the axons were identified within and surrounding the major remaining intact axonal population is enough to main- foci of nerve injury in both the 80 and 100 Gy groups.23 tain neurologic function in the majority of patients. This We know from rat brain parenchymal experi- balance between pain relief and preservation of sensation ments that doses of 100 Gy or more will lead to tissue is dose related. necrosis after a 3-month time interval.24 In an attempt to avoid nerve necrosis and maintain facial sensation, we have chosen doses below 100 Gy in patients. As this Improving Radiosurgery Technique study showed, the histologic effect was dose related. We compared radiosurgery using two 4-mm isocenters Radiosurgery at 100 Gy was followed by nerve necrosis with that using one isocenter with a maximum dose of in each animal and with a more pronounced axonal effect 75 Gy. Our hypothesis was that irradiation of a longer than radiosurgery at 80 Gy. The hypothesis that radio- nerve segment may have led to an improved rate of pain surgery might affect different fiber types selectively (i.e., relief. This randomized, blinded trial found no pain those conducting pain rather than light touch) was not benefit to two-isocenter radiosurgery but a higher rate
  • TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL 141of facial sensory loss.25 Regis et al advocate a maximum 14. Sweet WH, Wepsic JG. Controlled thermocoagulation ofdose of 90 Gy and a more anterior radiosurgery target.26 trigeminal ganglion and rootlets for differential destruction ofWith this approach, they have reported a low rate of pain fibers. J Neurosurg 1974;40:143–156 15. Broggi G, Flanzini A. Long-term results of percutaneousfacial sensory loss despite using a higher dose. Reports retrogasserian thermorhizotomy for ‘‘essential’’ trigeminalfrom Pollock et al found a higher rate of sensory loss at neuralgia: considerations in 1000 consecutive patients.90 Gy, although they used the more traditional posterior Neurosurgery 1990;26:783–787nerve target.27,28 These questions, dose and target, are 16. Scrivani JS, Keith DA, Mathews ES. Percutaneous stereo-appropriate considerations for randomized clinical trials. tactic differential radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia. J Oral Maxillofac Surg 1999;57:104–111 17. Hakanson S. Trigeminal neuralgia treated by injection ofREFERENCES glycerol into trigeminal cistern. Neurosurgery 1981;9:638– 646 1. Leksell L. Stereotaxic radiosurgery in trigeminal neuralgia. 18. Jho HD, Lunsford LD. Percutaneous retrogasserian glycerol Acta Chir Scand 1971;137:311–314 rhizotomy. Current techniques and results. Neurosurg Clin N 2. Kondziolka D, Lunsford L, Flickinger JC, et al. Stereotactic Am 1997;8:63–74 radiosurgery for trigeminal neuralgia. A multiinstitutional 19. Fraioli B, Esposito V, Guidetti B, et al. Treatment of study using gamma knife unit. J Neurosurg 1996;84:940–945 trigeminal neuralgia by thermocoagulation, glycerolization, 3. Kondziolka D, Lunsford L, Flickinger JC. 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