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Comparison of Percutaneous Retrogasserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis
Original Article
Comparison of Percutaneous Retrogasserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis Andres M. Alvarez-Pinzon1,2, Aizik L. Wolf1, Heather N. Swedberg3, Kory A. Barkley4, Juan Cucalon5, Luciana Curia5, Jose E. Valerio1
OBJECTIVE: We compared and evaluated percutaneous retrogasserian balloon compression (PBC) and Gamma Knife radiosurgery (GKRS) for treatment of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS).
-
METHODS: In this 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. Between February 2009 and December 2013, 78 PBC procedures and 124 firstdosage GKRS procedures were performed. PBC procedures were successfully completed in all cases. The 2 groups were compared with regard to initial effect, duration of effect, and complications including type and severity.
-
RESULTS: Immediate pain relief occurred in 87% of patients treated with PBC and in 23% of patients treated with GKRS. Kaplan-Meier plots for the 2 treatment modalities were similar. The 50% recurrence rate was at 12 months for the PBC group and 18 months for the GKRS group. Complication (excluding numbness) rates were 3% for GKRS and 21% for PBC. The difference was statistically significant (c2 test, P [ 0.03).
-
CONCLUSIONS: PBC and GKRS are effective techniques for treatment of TN in patients with MS. Fewer complications and superior long-term relief were associated with GKRS. We consider GKRS as the first option for the treatment of TN in patients with MS, reserving PBC for patients with acute, intractable pain.
-
INTRODUCTION
T
rigeminal neuralgia (TN), also called tic douloureux, is characterized by paroxysmal unilateral facial pain described as severe, sharp, and excruciating. TN can be provoked or exacerbated through facial movements or tactile stimulation of facial trigger points. It often occurs with activities of daily living, such as talking, chewing, washing one’s face, and brushing one’s teeth, consequently affecting the daily lives of affected individuals.1 TN occurs with a prevalence of 3e5 per 100,000 people in the general population. Approximately 3% of patients with multiple sclerosis (MS) have a diagnosis of concomitant TN.1,2 Most commonly, TN is caused by microvascular compression of the trigeminal root entry zone. However, in patients with MS, TN is frequently attributed to demyelinating lesions and/or plaque formation of the central trigeminal pathways or trigeminal root entry zone. Therefore, the management of TN in MS must be individualized to each patient. Surgeons must be conscientious of the medical, surgical, and radiation treatment modalities available when developing a treatment plan.3 The traditional treatment approach when TN is initially diagnosed involves medical management with antiepileptic medications, such as carbamazepine, gabapentin, baclofen, and lamotrigine. However, medical management is often unsatisfactory because of the severity of adverse effects and the poor tolerance associated with many of these pharmacologic therapies. Although recurrence of symptoms varies widely, the rate and frequency of recurrence of TN in patients with MS are higher than in the general population, requiring more repeated treatments. The identification of an effective treatment modality in this unique population would likely improve symptoms and reduce the rate and/or frequency of repeated treatments.1,4,5
Key words - Balloon compression - Gamma Knife - Multiple sclerosis - Trigeminal neuralgia
From the 1Department of Neurological Surgery, Miami Neuroscience Center at Larkin, South Miami, Florida, USA; 2Biotechnology-Oncology, Advanced Academic Programs, Johns Hopkins University, Baltimore, Maryland, USA; 3St. George’s University School of Medicine, Grenada, West Indies; 4American University of the Caribbean School of Medicine, Cupecoy, St. Maarten; and 5Department of Anesthesiology, Larkin Community Hospital, South Miami, Florida, USA
Abbreviations and Acronyms GKRS: Gamma Knife radiosurgery MS: Multiple sclerosis MVD: Microvascular decompression PBC: Percutaneous retrogasserian balloon compression TN: Trigeminal neuralgia
To whom correspondence should be addressed: Andres M. Alvarez-Pinzon, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2017) 97:590-594. http://dx.doi.org/10.1016/j.wneu.2016.10.028 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.10.028
ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
Surgical intervention can be significantly helpful in improving health in patients. The therapy of TN is unique because the available surgical treatments range widely from minimally invasive percutaneous techniques to major intracranial operations. The choice of technique—that is, if microvascular decompression (MVD) is not an option—is often difficult for both the physician and the patient.6,7 Hence, the need for a comparative analysis of each surgical technique is evident. Surgical therapies in TN caused by MS include noninvasive stereotactic radiosurgery, such as Gamma Knife radiosurgery (GKRS), and percutaneous procedures, such as retrogasserian balloon compression (PBC) and glycerol and radiofrequency rhizotomies.2,8 Severe adverse effects reported to be associated with most percutaneous ablative procedures include postoperative dysesthesia, corneal hypoesthesia, transient facial muscle weakness, and permanent facial motor weakness of the operative side.9,10 In 1971, Lars Leksell was the first to use GKRS as a treatment for TN, offering an efficacious therapeutic option associated with relatively fewer severe side effects.9-11 Because of its noninvasive nature, this therapy has been used with increasing frequency since 1993.4,7 The success of GKRS stems from ablation and induction of axonal degeneration of the trigeminal ganglion or nerve root, as documented by several studies that reported histopathologic changes, including visible axonal fibrosis and degeneration.10,12 The main objective of the present study is to evaluate the efficacy, adverse effects, and possible complications in patients with MS receiving GKRS versus PBC for treatment of TN. MATERIALS AND METHODS In a retrospective, single-center, comparative cohort study, 78 PBC procedures and 124 GKRS procedures were performed between February 2009 and December 2013 (a 4-year period). The medical records, intraoperative fluoroscopic images, and GKRS plan for patients with a diagnosis of MS and TN were reviewed retrospectively (78 in the PBC group and 124 in the GKRS group). The analysis was contingent on the assumption that each case represents a single surgical procedure. The minimum follow-up was 24 months. The demographic characteristics of the 2 groups are
Table 1. Demographic Characteristics of Study Groups Characteristic
PBC
GKRS
Number of cases
78
124
Mean age, years
53 11
51 15
21:57
39:85
10 7
11 8
First division
39
37
Second division
83
80
Third division
45
64
Male-to-female ratio (%) Mean number of years of TN Involvement of trigeminal divisions (% of cases)
PBC, percutaneous retrogasserian balloon compression; GKRS, Gamma Knife radiosurgery; TN, trigeminal neuralgia.
WORLD NEUROSURGERY 97: 590-594, JANUARY 2017
listed in Table 1. Our clinical research design strictly documents patients without prior surgical treatment or evidence of vascular compression on brain magnetic resonance imaging. Definitions The groups were compared with regard to preoperative visual analog scale, initial effects and duration of effects after treatment, and rate of adverse effects including type of complications and severity. An initial positive response was defined as 50% complete pain relief within 2 weeks after intervention. The duration of effect of the treatment was measured in months and calculated using the date of procedure to the point in time when pain recurred or the end of the study was reached (December 2013). The main clinical diagnosis was TN secondary to MS. Patients who had bilateral neuralgia without a definite diagnosis of MS were excluded. PBC Procedure The operation was performed under general anesthesia with a short-acting anesthetic agent. The patient was intubated and positioned supine on the operating table. The head was stabilized using a vacuum pillow. A C-arm fluoroscopic image intensifier was used to obtain lateral skull images and frontal fluoroscopy. The 3 landmarks of the Hartel route were addressed on the right or left hemiface. The first landmark corresponded to the location of the skin puncture: 2.5 cm lateral to the angle of the lip. The second landmark corresponded to the inferior edge of the zygomatic arch, 3 cm anterior to the external auditory canal. The third landmark was along the line joining the first point to the pupil on the inferior edge of the orbit. An incision was created with a sharp, large-bore needle. A Fogarty 4-F catheter was tested for integrity and prepared to remove air bubbles during inflation of the balloon with contrast material. A specially designed 14-gauge needle with a blunt obturator was advanced slowly toward the foramen ovale using external Hartel’s landmarks, along with the assistance of lateral fluoroscopic images. When the needle passed the foramen ovale and was not advanced further, the stylet was withdrawn, and the Fogarty catheter was inserted until it protruded 17 mm from the needle’s tip. The balloon was slightly inflated with contrast material, retracted into Meckel cave, reinflated, and inspected for shape and position. The balloon was inflated with approximately 0.7 mL of contrast material until it resembled a pear or dumbbell shape and remained inflated for 60 seconds (the institution standard for a first treatment). After compression, the balloon was deflated, and the needle and catheter were simultaneously removed. Firm pressure was applied to the cheek for a few minutes. Intraluminal pressure recordings were not used. The procedure usually required <25 minutes of operative time. Frontal fluoroscopy was not routinely used in this series of cases. GKRS Procedure The GKRS procedure was performed in conjunction with a radiation oncologist, physics specialist, and neurosurgeon specialist in radiosurgery. A dose of 37 Gy (50% isodose line) for the first treatment was administered. For each treatment session, the patient’s clinical history and any intraoperative findings or complications were recorded. Follow-up data were obtained through a combination of regular postoperative visits, e-mails, and phone calls at 4 weeks, 6 weeks, and 6 months after treatment. Follow-up
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ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
evaluations continued every 6 months until complete pain resolution was achieved or if additional treatment was necessary. The mean follow-up duration was 37.6 months. Statistical Analysis Student t test and c2 test were used for group comparisons. The outcome was analyzed using a c2 test for the initial response and complication rate variables. RESULTS Acute Pain Relief The rates of immediate pain relief were 87% for patients treated with PBC and 23% for patients treated with GKRS. With PBC, 50% of patients who experienced pain relief were pain-free immediately after the operation, whereas the other 50% responded after approximately 6 weeks. In the GKRS group, 23% of patients who experienced pain relief were pain-free within 30 days after the procedure, whereas the other 67% were pain-free within 2e6 months. No late responders were identified in the GKRS group. The medication for TN was gradually tapered with the goal of complete cessation by 3 months after the procedure. Recurrence-Free Interval The follow-up time for patients who did not experience recurrent pain was extended to 18 months in the PBC group and 24 months in the GKRS group. Kaplan-Meier plots were generated for both treatment modalities (Figure 1). According to the Kaplan-Meier plots, the 50% recurrence time (after an initially successful
Figure 1. Recurrence-free interval. GKRS, Gamma Knife radiosurgery; NS, numerical scale; PBC, percutaneous
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procedure) was 10 months for PBC and 18 months for GKRS. The actuarial chances for each group to obtain and maintain a painfree outcome at 2-year post-treatment follow-up are presented in Table 2. PBC was characterized by early recurrences more than not. These findings are evident in the large difference between the mean time of recurrence and the mean time of follow-up. Complication rates are reported in Table 3. Complications The complication rates (excluding numbness) were 10% for GKRS and 21% for PBC. This difference was statistically significant (c2 test, P ¼ 0.04). As shown in Table 3, dysesthesia was the most frequent type of complication with PBC. In the GKRS group, there was less diversity of complications, mainly including dysesthesia and cranial nerve dysfunction (masseter muscle weakness, diplopia, and hearing and olfactory disturbances). No cases of corneal anesthesia or anesthesia dolorosa were observed. Concerning postoperative hypoesthesia, the figures were considerably but not unexpectedly higher in the PBC group (81% vs. 28%; c2 test, P ¼ 0.02). The rate in the PBC group was still higher, even when the groups were compared for persistent hypoesthesia that lingered within the time boundaries of the study (10% vs. 26%; c2 test, P ¼ 0.02). Many surgeons consider sensory loss a positive indicator in patients who have undergone PBC but not necessarily in patients who have undergone GKRS.7 However, in our series, we found that patients with postoperative hypoesthesia fared better with both modalities, and this result was statistically significant (CoxMantel test, P ¼ 0.023 and P ¼ 0.02).
retrogasserian balloon compression; VAS, visual analog scale.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.10.028
ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
Table 2. Actuarial Probability of Absolute Pain Relief 2 Years After Treatment Group or Subgroup
Probability (%)
PBC
40
GKRS
78
general anesthesia and may be risky for older and debilitated patients. The management of TN in patients with MS is a dilemma, as the pathophysiology is caused by inflammation and nonvascular compression.13,14 At the other end of the treatment spectrum are the percutaneous techniques, with percutaneous radiofrequency rhizotomy being the oldest and most appreciated and Gamma Knife irradiation of the trigeminal root considered by many to be the least invasive intervention.3,9
PBC, percutaneous retrogasserian balloon compression; GKRS, Gamma Knife radiosurgery.
DISCUSSION Therapeutic Spectrum for TN In 1971, Leksell was the first to use GKRS as a treatment for TN, offering an efficacious therapeutic option that was associated with relatively few major side effects.9 Since then, GKRS has become increasingly popular because of its benefit of being noninvasive as well as effective in the treatment of TN, and it has been used with increasing frequency since 1993.4-7 PBC is considered close to other intervention modalities and is a minimally invasive procedure but not the gold standard. The etiology of TN associated with MS is different compared with primary TN. Primary TN is due to a vessel compressing the nerve, whereas TN secondary to MS is related to an inflammatory process in the trigeminal nerve caused by an MS lesion. At the more invasive end of the treatment spectrum is the only procedure that addresses a presumptive pathophysiologic mechanism of TN, which is MVD of a vascular conflict at the dorsal root entry zone of the trigeminal nerve. Additionally, it is not a common case in MS that approximately 75% of cases had plaque in the trigeminal nerve distribution. Although MVD has proven to be very effective because it carries low risk in experienced hands, it is still a major intracranial operation that requires
Table 3. Complication Rates and Postoperative Hypoesthesia* Complications Complications other than hypoesthesia (%)
GKRS
PBC
10
21
Dysesthesia
2
10
Diplopia
0
0
Masseter weakness
0
10
Corneal anesthesia/keratitis
0
0
Herpes eruption
0
0
AV fistula
0
0
Hearing/olfactory
0
3
0
0
Hypoesthesia (%)
Anesthesia dolorosa
28
81
Persistent hypoesthesia (%)
10
26
GKRS, Gamma Knife radiosurgery; PBC, percutaneous retrogasserian balloon compression; AV, arteriovenous. *Values represent percentage of cases in which the given complication occurred.
WORLD NEUROSURGERY 97: 590-594, JANUARY 2017
Advantages and Disadvantages of PBC versus GKRS Although PBC has gained many advocates, it is purely mechanical. The experience of the surgeon can play an important role in the outcome, an observation that is reflected in the aforementioned diverse results reported in the literature.5,14,15 A study in 2015 measured the long-term outcome of balloon compression in the treatment of TN in patients with MS and patients without MS.4 There were 144 PBC procedures performed in 80 patients. The study concluded that PBC was effective in the treatment of TN in both patients with MS and patients without MS; however, the patients with MS experienced a higher symptom recurrence rate after the first operation (86% vs. 47%) than the patients without MS, necessitating multiple procedures.4 PBC is preferential in cases of medically intractable TN, as it allows for almost immediate postoperative pain relief, as opposed to treatment with GKRS, where 1 study reported a median of 4 weeks for pain improvement.16 Therefore, patients should be advised to continue taking their medication for pain management. However, GKRS is preferential in nonacute settings because it is noninvasive, does not require administration of a general anesthetic, does not require cessation of anticoagulants, and reduces the length of hospital stay. A study published in 2013 measuring the long-term outcome of GKRS in the treatment of TN revealed that of 216 patients treated, 185 patients (85.6%) reported a decrease in pain intensity after GKRS.17 Likewise, 89.5% of the patients reported at least 50% pain relief, and 71.4% were completely pain-free after GKRS treatment. Only 31 patients (14.3%) reported the recurrence of pain with a mean length of time until recurrence of 20.4 months 28.10,13,14 The success of GKRS stems from ablation and induction of axonal degeneration of the trigeminal ganglion and/ or nerve root, as documented by several studies that reported histopathologic changes, including visible axonal fibrosis and degeneration.10-12 Another study published in 2015 measuring clinical outcomes after GKRS for TN concluded that most of the patients treated responded to the GKRS treatment within 6 months with a median of 2 months, along with 64.9% experiencing complete pain relief at 6 months, 70.3% experiencing complete pain relief at 1 year, and 75.4% experiencing complete pain relief at 33 months postoperatively, with only 10.2% of patients developing new or increased facial pain and/or paresthesias.15 Multiple studies have shown that facial numbness and paresthesia were rarely seen as complications with GKRS compared with other invasive procedures, including PBC.1,5,9,14 Outcome and Complication Rates Effectiveness is the second component of cost-effectiveness, and this is what gives meaning to cost restriction. A therapeutic
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ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
technique, above all, must be effective. This study confirms the favorable results reported for PBC in previous studies and simultaneously questions the decision of many surgeons to abandon other percutaneous interventions. The use of PBC carries with it a relatively high frequency of marked hypoesthesia and infrequent side effects, such as masseter weakness and diplopia, which often regresses spontaneously within a few weeks. Choice of Therapy Our department’s policy is to offer the most minimal and effective procedure to patients with MS. GKRS is offered as a first option for elderly or weak patients; patients with MS (who often experience major side effects of pharmacotherapy even at modest doses); patients unwilling to undergo an intracranial operation; and patients with recurrent TN after MVD, especially patients with negative findings. PBC is usually offered as a second option for patients who experience a rapid recurrence of pain after a technically successful trigeminal block. GKRS is offered as a first option when clinical treatment has failed. The GKRS procedure has been used at our center primarily for these patients. A clear disadvantage of this method is that the median time to pain relief may be 4 weeks.16 Therefore, several patients scheduled for a Gamma Knife
REFERENCES 1. Brola W, Mitosek-Szewczyk K, Opara J. Symptomatology and pathogenesis of different types of pain in multiple sclerosis. Neurol Neurochir Pol. 2014;48:272-279. 2. Chen DQ, DeSouza DD, Hayes DJ, Davis KD, O’Connor P, Hodaie M. Diffusivity signatures characterize trigeminal neuralgia associated with multiple sclerosis. Mult Scler. 2016;22:51-63. 3. Lummel N, Mehrkens JH, Linn J, Buchholz G, Stahl R, Bochmann K, et al. Diffusion tensor imaging of the trigeminal nerve in patients with trigeminal neuralgia due to multiple sclerosis. Neuroradiology. 2015;57:259-267. 4. Martin S, Teo M, Suttner N. The effectiveness of percutaneous balloon compression in the treatment of trigeminal neuralgia in patients with multiple sclerosis. J Neurosurg. 2015;123:1507-1511. 5. Cheng JS, Sanchez-Mejia RO, Limbo M, Ward MM, Barbaro NM. Management of medically refractory trigeminal neuralgia in patients with multiple sclerosis. Neurosurg Focus. 2005;18: 1-5. 6. Zorro O, Lobato-Polo J, Kano H, Flickinger JC, Lunsford LD, Kondziolka D. Gamma knife radiosurgery for multiple sclerosis-related trigeminal neuralgia. Neurology. 2009;73:1149-1154. 7. Asplund P, Blomstedt P, Bergenheim AT. Percutaneous balloon compression vs percutaneous retrogasserian glycerol rhizotomy for the primary
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procedure have been treated with other procedures before GKRS because of the need for more immediate pain relief. Limitations Because our study was retrospective and not a prospective, randomized, controlled study, it does not represent a true, valid comparison with nonbiased or statistical criteria. However, we believe some useful conclusions can be extracted, especially in consideration of the absence of any other comparative studies between these 2 methods in the literature. CONCLUSIONS Investigations are ongoing to create a single technique that will be minimally invasive, cost-effective, and powerful in the long run. Overall, TN in patients with MS requires a multidisciplinary approach, and we are obliged to optimally use the existing techniques, each with its advantages and limitations. The effectiveness of PBC is confirmed in this study. Furthermore, it has been shown that GKRS, when applied correctly, shows great results with a lower complication rate. We believe that the minimal invasiveness and satisfying results of GKRS support its use as the first-line treatment of TN in patients with MS, followed by PBC when GKRS fails or no longer offers pain relief to the patient.
treatment of trigeminal neuralgia. Neurosurgery. 2016;78:421-428. 8. Ko AL, Lee A, Raslan AM, Ozpinar A, McCartney S, Burchiel KJ. Trigeminal neuralgia without neurovascular compression presents earlier than trigeminal neuralgia with neurovascular compression. J Neurosurg. 2015;123: 1519-1527. 9. Montano N, Papacci F, Cioni B, Di Bonaventura R, Meglio M. The role of percutaneous balloon compression in the treatment of trigeminal neuralgia recurring after other surgical procedures. Acta Neurol Belg. 2014;114:59-64. 10. Patwardhan RV, Minagar A, Kelley RE, Nanda A. Neurosurgical treatment of multiple sclerosis. Neurol Res. 2006;28:320-325. 11. Rogers CL, Shetter AG, Ponce FA, Fiedler JA, Smith KA, Speiser BL. Gamma Knife radiosurgery for trigeminal neuralgia associated with multiple sclerosis. J Neurosurg. 2002;97:529-532. 12. Kondziolka D, Zorro O, Lobato-Polo J, Kano H, Flannery TJ, Flickinger JC, et al. Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2010;112:758-765. 13. Tyurnikov VM, Peresedova AV, Gushcha AO, Koval’ KV. [Experience in the use of highfrequency selective percutaneous rhizotomy in trigeminal neuralgia associated with multiple sclerosis]. Zh Vopr Neirokhir Im N N Burdenko. 2015; 79:34-41 [discussion: 41-42] [in Russian].
14. Ali Eissa AA, Reyad RM, Saleh EG, El-Saman A. The efficacy and safety of combined pulsed and conventional radiofrequency treatment of refractory cases of idiopathic trigeminal neuralgia: a retrospective study. J Anesth. 2015;29:728-733. 15. Shimanskiĭ VN, Taniashin SV, Kolycheva MV, Karnaukhov VV, Odamanov DA. [Surgical treatment of trigeminal neuralgia in patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115:66-70 [in Russian]. 16. Park SH, Hwang SK. Outcomes of Gamma Knife radiosurgery for trigeminal neuralgia after a minimum 3-year follow-up. J Clin Neurosci. 2011;18: 645-648. 17. Young B, Shivazad A, Kryscio RJ, St Clair W, Bush HM. Long-term outcome of high-dose Gamma Knife surgery in treatment of trigeminal neuralgia. J Neurosurg. 2013;119:1166-1175.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 1 August 2016; accepted 4 October 2016 Citation: World Neurosurg. (2017) 97:590-594. http://dx.doi.org/10.1016/j.wneu.2016.10.028 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.10.028
Comparison of Percutaneous Retrogasserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis Andres M. Alvarez-Pinzon1,2, Aizik L. Wolf1, Heather N. Swedberg3, Kory A. Barkley4, Juan Cucalon5, Luciana Curia5, Jose E. Valerio1
OBJECTIVE: We compared and evaluated percutaneous retrogasserian balloon compression (PBC) and Gamma Knife radiosurgery (GKRS) for treatment of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS).
-
METHODS: In this 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. Between February 2009 and December 2013, 78 PBC procedures and 124 firstdosage GKRS procedures were performed. PBC procedures were successfully completed in all cases. The 2 groups were compared with regard to initial effect, duration of effect, and complications including type and severity.
-
RESULTS: Immediate pain relief occurred in 87% of patients treated with PBC and in 23% of patients treated with GKRS. Kaplan-Meier plots for the 2 treatment modalities were similar. The 50% recurrence rate was at 12 months for the PBC group and 18 months for the GKRS group. Complication (excluding numbness) rates were 3% for GKRS and 21% for PBC. The difference was statistically significant (c2 test, P [ 0.03).
-
CONCLUSIONS: PBC and GKRS are effective techniques for treatment of TN in patients with MS. Fewer complications and superior long-term relief were associated with GKRS. We consider GKRS as the first option for the treatment of TN in patients with MS, reserving PBC for patients with acute, intractable pain.
-
INTRODUCTION
T
rigeminal neuralgia (TN), also called tic douloureux, is characterized by paroxysmal unilateral facial pain described as severe, sharp, and excruciating. TN can be provoked or exacerbated through facial movements or tactile stimulation of facial trigger points. It often occurs with activities of daily living, such as talking, chewing, washing one’s face, and brushing one’s teeth, consequently affecting the daily lives of affected individuals.1 TN occurs with a prevalence of 3e5 per 100,000 people in the general population. Approximately 3% of patients with multiple sclerosis (MS) have a diagnosis of concomitant TN.1,2 Most commonly, TN is caused by microvascular compression of the trigeminal root entry zone. However, in patients with MS, TN is frequently attributed to demyelinating lesions and/or plaque formation of the central trigeminal pathways or trigeminal root entry zone. Therefore, the management of TN in MS must be individualized to each patient. Surgeons must be conscientious of the medical, surgical, and radiation treatment modalities available when developing a treatment plan.3 The traditional treatment approach when TN is initially diagnosed involves medical management with antiepileptic medications, such as carbamazepine, gabapentin, baclofen, and lamotrigine. However, medical management is often unsatisfactory because of the severity of adverse effects and the poor tolerance associated with many of these pharmacologic therapies. Although recurrence of symptoms varies widely, the rate and frequency of recurrence of TN in patients with MS are higher than in the general population, requiring more repeated treatments. The identification of an effective treatment modality in this unique population would likely improve symptoms and reduce the rate and/or frequency of repeated treatments.1,4,5
Key words - Balloon compression - Gamma Knife - Multiple sclerosis - Trigeminal neuralgia
From the 1Department of Neurological Surgery, Miami Neuroscience Center at Larkin, South Miami, Florida, USA; 2Biotechnology-Oncology, Advanced Academic Programs, Johns Hopkins University, Baltimore, Maryland, USA; 3St. George’s University School of Medicine, Grenada, West Indies; 4American University of the Caribbean School of Medicine, Cupecoy, St. Maarten; and 5Department of Anesthesiology, Larkin Community Hospital, South Miami, Florida, USA
Abbreviations and Acronyms GKRS: Gamma Knife radiosurgery MS: Multiple sclerosis MVD: Microvascular decompression PBC: Percutaneous retrogasserian balloon compression TN: Trigeminal neuralgia
To whom correspondence should be addressed: Andres M. Alvarez-Pinzon, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2017) 97:590-594. http://dx.doi.org/10.1016/j.wneu.2016.10.028 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.10.028
ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
Surgical intervention can be significantly helpful in improving health in patients. The therapy of TN is unique because the available surgical treatments range widely from minimally invasive percutaneous techniques to major intracranial operations. The choice of technique—that is, if microvascular decompression (MVD) is not an option—is often difficult for both the physician and the patient.6,7 Hence, the need for a comparative analysis of each surgical technique is evident. Surgical therapies in TN caused by MS include noninvasive stereotactic radiosurgery, such as Gamma Knife radiosurgery (GKRS), and percutaneous procedures, such as retrogasserian balloon compression (PBC) and glycerol and radiofrequency rhizotomies.2,8 Severe adverse effects reported to be associated with most percutaneous ablative procedures include postoperative dysesthesia, corneal hypoesthesia, transient facial muscle weakness, and permanent facial motor weakness of the operative side.9,10 In 1971, Lars Leksell was the first to use GKRS as a treatment for TN, offering an efficacious therapeutic option associated with relatively fewer severe side effects.9-11 Because of its noninvasive nature, this therapy has been used with increasing frequency since 1993.4,7 The success of GKRS stems from ablation and induction of axonal degeneration of the trigeminal ganglion or nerve root, as documented by several studies that reported histopathologic changes, including visible axonal fibrosis and degeneration.10,12 The main objective of the present study is to evaluate the efficacy, adverse effects, and possible complications in patients with MS receiving GKRS versus PBC for treatment of TN. MATERIALS AND METHODS In a retrospective, single-center, comparative cohort study, 78 PBC procedures and 124 GKRS procedures were performed between February 2009 and December 2013 (a 4-year period). The medical records, intraoperative fluoroscopic images, and GKRS plan for patients with a diagnosis of MS and TN were reviewed retrospectively (78 in the PBC group and 124 in the GKRS group). The analysis was contingent on the assumption that each case represents a single surgical procedure. The minimum follow-up was 24 months. The demographic characteristics of the 2 groups are
Table 1. Demographic Characteristics of Study Groups Characteristic
PBC
GKRS
Number of cases
78
124
Mean age, years
53 11
51 15
21:57
39:85
10 7
11 8
First division
39
37
Second division
83
80
Third division
45
64
Male-to-female ratio (%) Mean number of years of TN Involvement of trigeminal divisions (% of cases)
PBC, percutaneous retrogasserian balloon compression; GKRS, Gamma Knife radiosurgery; TN, trigeminal neuralgia.
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listed in Table 1. Our clinical research design strictly documents patients without prior surgical treatment or evidence of vascular compression on brain magnetic resonance imaging. Definitions The groups were compared with regard to preoperative visual analog scale, initial effects and duration of effects after treatment, and rate of adverse effects including type of complications and severity. An initial positive response was defined as 50% complete pain relief within 2 weeks after intervention. The duration of effect of the treatment was measured in months and calculated using the date of procedure to the point in time when pain recurred or the end of the study was reached (December 2013). The main clinical diagnosis was TN secondary to MS. Patients who had bilateral neuralgia without a definite diagnosis of MS were excluded. PBC Procedure The operation was performed under general anesthesia with a short-acting anesthetic agent. The patient was intubated and positioned supine on the operating table. The head was stabilized using a vacuum pillow. A C-arm fluoroscopic image intensifier was used to obtain lateral skull images and frontal fluoroscopy. The 3 landmarks of the Hartel route were addressed on the right or left hemiface. The first landmark corresponded to the location of the skin puncture: 2.5 cm lateral to the angle of the lip. The second landmark corresponded to the inferior edge of the zygomatic arch, 3 cm anterior to the external auditory canal. The third landmark was along the line joining the first point to the pupil on the inferior edge of the orbit. An incision was created with a sharp, large-bore needle. A Fogarty 4-F catheter was tested for integrity and prepared to remove air bubbles during inflation of the balloon with contrast material. A specially designed 14-gauge needle with a blunt obturator was advanced slowly toward the foramen ovale using external Hartel’s landmarks, along with the assistance of lateral fluoroscopic images. When the needle passed the foramen ovale and was not advanced further, the stylet was withdrawn, and the Fogarty catheter was inserted until it protruded 17 mm from the needle’s tip. The balloon was slightly inflated with contrast material, retracted into Meckel cave, reinflated, and inspected for shape and position. The balloon was inflated with approximately 0.7 mL of contrast material until it resembled a pear or dumbbell shape and remained inflated for 60 seconds (the institution standard for a first treatment). After compression, the balloon was deflated, and the needle and catheter were simultaneously removed. Firm pressure was applied to the cheek for a few minutes. Intraluminal pressure recordings were not used. The procedure usually required <25 minutes of operative time. Frontal fluoroscopy was not routinely used in this series of cases. GKRS Procedure The GKRS procedure was performed in conjunction with a radiation oncologist, physics specialist, and neurosurgeon specialist in radiosurgery. A dose of 37 Gy (50% isodose line) for the first treatment was administered. For each treatment session, the patient’s clinical history and any intraoperative findings or complications were recorded. Follow-up data were obtained through a combination of regular postoperative visits, e-mails, and phone calls at 4 weeks, 6 weeks, and 6 months after treatment. Follow-up
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evaluations continued every 6 months until complete pain resolution was achieved or if additional treatment was necessary. The mean follow-up duration was 37.6 months. Statistical Analysis Student t test and c2 test were used for group comparisons. The outcome was analyzed using a c2 test for the initial response and complication rate variables. RESULTS Acute Pain Relief The rates of immediate pain relief were 87% for patients treated with PBC and 23% for patients treated with GKRS. With PBC, 50% of patients who experienced pain relief were pain-free immediately after the operation, whereas the other 50% responded after approximately 6 weeks. In the GKRS group, 23% of patients who experienced pain relief were pain-free within 30 days after the procedure, whereas the other 67% were pain-free within 2e6 months. No late responders were identified in the GKRS group. The medication for TN was gradually tapered with the goal of complete cessation by 3 months after the procedure. Recurrence-Free Interval The follow-up time for patients who did not experience recurrent pain was extended to 18 months in the PBC group and 24 months in the GKRS group. Kaplan-Meier plots were generated for both treatment modalities (Figure 1). According to the Kaplan-Meier plots, the 50% recurrence time (after an initially successful
Figure 1. Recurrence-free interval. GKRS, Gamma Knife radiosurgery; NS, numerical scale; PBC, percutaneous
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procedure) was 10 months for PBC and 18 months for GKRS. The actuarial chances for each group to obtain and maintain a painfree outcome at 2-year post-treatment follow-up are presented in Table 2. PBC was characterized by early recurrences more than not. These findings are evident in the large difference between the mean time of recurrence and the mean time of follow-up. Complication rates are reported in Table 3. Complications The complication rates (excluding numbness) were 10% for GKRS and 21% for PBC. This difference was statistically significant (c2 test, P ¼ 0.04). As shown in Table 3, dysesthesia was the most frequent type of complication with PBC. In the GKRS group, there was less diversity of complications, mainly including dysesthesia and cranial nerve dysfunction (masseter muscle weakness, diplopia, and hearing and olfactory disturbances). No cases of corneal anesthesia or anesthesia dolorosa were observed. Concerning postoperative hypoesthesia, the figures were considerably but not unexpectedly higher in the PBC group (81% vs. 28%; c2 test, P ¼ 0.02). The rate in the PBC group was still higher, even when the groups were compared for persistent hypoesthesia that lingered within the time boundaries of the study (10% vs. 26%; c2 test, P ¼ 0.02). Many surgeons consider sensory loss a positive indicator in patients who have undergone PBC but not necessarily in patients who have undergone GKRS.7 However, in our series, we found that patients with postoperative hypoesthesia fared better with both modalities, and this result was statistically significant (CoxMantel test, P ¼ 0.023 and P ¼ 0.02).
retrogasserian balloon compression; VAS, visual analog scale.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.10.028
ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
Table 2. Actuarial Probability of Absolute Pain Relief 2 Years After Treatment Group or Subgroup
Probability (%)
PBC
40
GKRS
78
general anesthesia and may be risky for older and debilitated patients. The management of TN in patients with MS is a dilemma, as the pathophysiology is caused by inflammation and nonvascular compression.13,14 At the other end of the treatment spectrum are the percutaneous techniques, with percutaneous radiofrequency rhizotomy being the oldest and most appreciated and Gamma Knife irradiation of the trigeminal root considered by many to be the least invasive intervention.3,9
PBC, percutaneous retrogasserian balloon compression; GKRS, Gamma Knife radiosurgery.
DISCUSSION Therapeutic Spectrum for TN In 1971, Leksell was the first to use GKRS as a treatment for TN, offering an efficacious therapeutic option that was associated with relatively few major side effects.9 Since then, GKRS has become increasingly popular because of its benefit of being noninvasive as well as effective in the treatment of TN, and it has been used with increasing frequency since 1993.4-7 PBC is considered close to other intervention modalities and is a minimally invasive procedure but not the gold standard. The etiology of TN associated with MS is different compared with primary TN. Primary TN is due to a vessel compressing the nerve, whereas TN secondary to MS is related to an inflammatory process in the trigeminal nerve caused by an MS lesion. At the more invasive end of the treatment spectrum is the only procedure that addresses a presumptive pathophysiologic mechanism of TN, which is MVD of a vascular conflict at the dorsal root entry zone of the trigeminal nerve. Additionally, it is not a common case in MS that approximately 75% of cases had plaque in the trigeminal nerve distribution. Although MVD has proven to be very effective because it carries low risk in experienced hands, it is still a major intracranial operation that requires
Table 3. Complication Rates and Postoperative Hypoesthesia* Complications Complications other than hypoesthesia (%)
GKRS
PBC
10
21
Dysesthesia
2
10
Diplopia
0
0
Masseter weakness
0
10
Corneal anesthesia/keratitis
0
0
Herpes eruption
0
0
AV fistula
0
0
Hearing/olfactory
0
3
0
0
Hypoesthesia (%)
Anesthesia dolorosa
28
81
Persistent hypoesthesia (%)
10
26
GKRS, Gamma Knife radiosurgery; PBC, percutaneous retrogasserian balloon compression; AV, arteriovenous. *Values represent percentage of cases in which the given complication occurred.
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Advantages and Disadvantages of PBC versus GKRS Although PBC has gained many advocates, it is purely mechanical. The experience of the surgeon can play an important role in the outcome, an observation that is reflected in the aforementioned diverse results reported in the literature.5,14,15 A study in 2015 measured the long-term outcome of balloon compression in the treatment of TN in patients with MS and patients without MS.4 There were 144 PBC procedures performed in 80 patients. The study concluded that PBC was effective in the treatment of TN in both patients with MS and patients without MS; however, the patients with MS experienced a higher symptom recurrence rate after the first operation (86% vs. 47%) than the patients without MS, necessitating multiple procedures.4 PBC is preferential in cases of medically intractable TN, as it allows for almost immediate postoperative pain relief, as opposed to treatment with GKRS, where 1 study reported a median of 4 weeks for pain improvement.16 Therefore, patients should be advised to continue taking their medication for pain management. However, GKRS is preferential in nonacute settings because it is noninvasive, does not require administration of a general anesthetic, does not require cessation of anticoagulants, and reduces the length of hospital stay. A study published in 2013 measuring the long-term outcome of GKRS in the treatment of TN revealed that of 216 patients treated, 185 patients (85.6%) reported a decrease in pain intensity after GKRS.17 Likewise, 89.5% of the patients reported at least 50% pain relief, and 71.4% were completely pain-free after GKRS treatment. Only 31 patients (14.3%) reported the recurrence of pain with a mean length of time until recurrence of 20.4 months 28.10,13,14 The success of GKRS stems from ablation and induction of axonal degeneration of the trigeminal ganglion and/ or nerve root, as documented by several studies that reported histopathologic changes, including visible axonal fibrosis and degeneration.10-12 Another study published in 2015 measuring clinical outcomes after GKRS for TN concluded that most of the patients treated responded to the GKRS treatment within 6 months with a median of 2 months, along with 64.9% experiencing complete pain relief at 6 months, 70.3% experiencing complete pain relief at 1 year, and 75.4% experiencing complete pain relief at 33 months postoperatively, with only 10.2% of patients developing new or increased facial pain and/or paresthesias.15 Multiple studies have shown that facial numbness and paresthesia were rarely seen as complications with GKRS compared with other invasive procedures, including PBC.1,5,9,14 Outcome and Complication Rates Effectiveness is the second component of cost-effectiveness, and this is what gives meaning to cost restriction. A therapeutic
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ORIGINAL ARTICLE ANDRES M. ALVAREZ-PINZON ET AL.
TREATMENT OF TRIGEMINAL NEURALGIA IN MULTIPLE SCLEROSIS
technique, above all, must be effective. This study confirms the favorable results reported for PBC in previous studies and simultaneously questions the decision of many surgeons to abandon other percutaneous interventions. The use of PBC carries with it a relatively high frequency of marked hypoesthesia and infrequent side effects, such as masseter weakness and diplopia, which often regresses spontaneously within a few weeks. Choice of Therapy Our department’s policy is to offer the most minimal and effective procedure to patients with MS. GKRS is offered as a first option for elderly or weak patients; patients with MS (who often experience major side effects of pharmacotherapy even at modest doses); patients unwilling to undergo an intracranial operation; and patients with recurrent TN after MVD, especially patients with negative findings. PBC is usually offered as a second option for patients who experience a rapid recurrence of pain after a technically successful trigeminal block. GKRS is offered as a first option when clinical treatment has failed. The GKRS procedure has been used at our center primarily for these patients. A clear disadvantage of this method is that the median time to pain relief may be 4 weeks.16 Therefore, several patients scheduled for a Gamma Knife
REFERENCES 1. Brola W, Mitosek-Szewczyk K, Opara J. Symptomatology and pathogenesis of different types of pain in multiple sclerosis. Neurol Neurochir Pol. 2014;48:272-279. 2. Chen DQ, DeSouza DD, Hayes DJ, Davis KD, O’Connor P, Hodaie M. Diffusivity signatures characterize trigeminal neuralgia associated with multiple sclerosis. Mult Scler. 2016;22:51-63. 3. Lummel N, Mehrkens JH, Linn J, Buchholz G, Stahl R, Bochmann K, et al. Diffusion tensor imaging of the trigeminal nerve in patients with trigeminal neuralgia due to multiple sclerosis. Neuroradiology. 2015;57:259-267. 4. Martin S, Teo M, Suttner N. The effectiveness of percutaneous balloon compression in the treatment of trigeminal neuralgia in patients with multiple sclerosis. J Neurosurg. 2015;123:1507-1511. 5. Cheng JS, Sanchez-Mejia RO, Limbo M, Ward MM, Barbaro NM. Management of medically refractory trigeminal neuralgia in patients with multiple sclerosis. Neurosurg Focus. 2005;18: 1-5. 6. Zorro O, Lobato-Polo J, Kano H, Flickinger JC, Lunsford LD, Kondziolka D. Gamma knife radiosurgery for multiple sclerosis-related trigeminal neuralgia. Neurology. 2009;73:1149-1154. 7. Asplund P, Blomstedt P, Bergenheim AT. Percutaneous balloon compression vs percutaneous retrogasserian glycerol rhizotomy for the primary
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procedure have been treated with other procedures before GKRS because of the need for more immediate pain relief. Limitations Because our study was retrospective and not a prospective, randomized, controlled study, it does not represent a true, valid comparison with nonbiased or statistical criteria. However, we believe some useful conclusions can be extracted, especially in consideration of the absence of any other comparative studies between these 2 methods in the literature. CONCLUSIONS Investigations are ongoing to create a single technique that will be minimally invasive, cost-effective, and powerful in the long run. Overall, TN in patients with MS requires a multidisciplinary approach, and we are obliged to optimally use the existing techniques, each with its advantages and limitations. The effectiveness of PBC is confirmed in this study. Furthermore, it has been shown that GKRS, when applied correctly, shows great results with a lower complication rate. We believe that the minimal invasiveness and satisfying results of GKRS support its use as the first-line treatment of TN in patients with MS, followed by PBC when GKRS fails or no longer offers pain relief to the patient.
treatment of trigeminal neuralgia. Neurosurgery. 2016;78:421-428. 8. Ko AL, Lee A, Raslan AM, Ozpinar A, McCartney S, Burchiel KJ. Trigeminal neuralgia without neurovascular compression presents earlier than trigeminal neuralgia with neurovascular compression. J Neurosurg. 2015;123: 1519-1527. 9. Montano N, Papacci F, Cioni B, Di Bonaventura R, Meglio M. The role of percutaneous balloon compression in the treatment of trigeminal neuralgia recurring after other surgical procedures. Acta Neurol Belg. 2014;114:59-64. 10. Patwardhan RV, Minagar A, Kelley RE, Nanda A. Neurosurgical treatment of multiple sclerosis. Neurol Res. 2006;28:320-325. 11. Rogers CL, Shetter AG, Ponce FA, Fiedler JA, Smith KA, Speiser BL. Gamma Knife radiosurgery for trigeminal neuralgia associated with multiple sclerosis. J Neurosurg. 2002;97:529-532. 12. Kondziolka D, Zorro O, Lobato-Polo J, Kano H, Flannery TJ, Flickinger JC, et al. Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2010;112:758-765. 13. Tyurnikov VM, Peresedova AV, Gushcha AO, Koval’ KV. [Experience in the use of highfrequency selective percutaneous rhizotomy in trigeminal neuralgia associated with multiple sclerosis]. Zh Vopr Neirokhir Im N N Burdenko. 2015; 79:34-41 [discussion: 41-42] [in Russian].
14. Ali Eissa AA, Reyad RM, Saleh EG, El-Saman A. The efficacy and safety of combined pulsed and conventional radiofrequency treatment of refractory cases of idiopathic trigeminal neuralgia: a retrospective study. J Anesth. 2015;29:728-733. 15. Shimanskiĭ VN, Taniashin SV, Kolycheva MV, Karnaukhov VV, Odamanov DA. [Surgical treatment of trigeminal neuralgia in patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115:66-70 [in Russian]. 16. Park SH, Hwang SK. Outcomes of Gamma Knife radiosurgery for trigeminal neuralgia after a minimum 3-year follow-up. J Clin Neurosci. 2011;18: 645-648. 17. Young B, Shivazad A, Kryscio RJ, St Clair W, Bush HM. Long-term outcome of high-dose Gamma Knife surgery in treatment of trigeminal neuralgia. J Neurosurg. 2013;119:1166-1175.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 1 August 2016; accepted 4 October 2016 Citation: World Neurosurg. (2017) 97:590-594. http://dx.doi.org/10.1016/j.wneu.2016.10.028 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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