British Journal of Neurosurgery
ISSN: 0268-8697 (Print) 1360-046X (Online) Journal homepage: http://www.tandfonline.com/loi/ibjn20
First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis Victor M. Lu, Julia B. Duvall, Kevin Phan & Benjamin P. Jonker To cite this article: Victor M. Lu, Julia B. Duvall, Kevin Phan & Benjamin P. Jonker (2018): First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis, British Journal of Neurosurgery, DOI: 10.1080/02688697.2018.1472213 To link to this article: https://doi.org/10.1080/02688697.2018.1472213
Published online: 10 May 2018.
Submit your article to this journal
Article views: 18
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ibjn20
BRITISH JOURNAL OF NEUROSURGERY https://doi.org/10.1080/02688697.2018.1472213
REVIEW ARTICLE
First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis Victor M. Lua, Julia B. Duvallb, Kevin Phana and Benjamin P. Jonkerc a
Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; bDepartment of Neuroscience, Johns Hopkins, Baltimore, MD, USA; Department of Neurosurgery, RPA Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, The University of Sydney, Sydney, NSW, Australia
c
ABSTRACT
ARTICLE HISTORY
Purpose: Procedures to treat medically refractory trigeminal neuralgia (MRTN) include stereotactic radiosurgery (SRS) and microvascular decompression (MVD). The aim of this study was to compare outcomes of SRS versus MVD in the treatment of MRTN, with a subgroup focus on those being treated for the first time. Methods: Search strategy was performed using the PRISMA guidelines for article identification, screening, eligibility and inclusion. Relevant articles were identified from six electronic databases from their inception to June 2017. These articles were screened against established criteria for inclusion into this study. Metaanalysis was conducted by pooling results with odds ratios and subgroup analysis. Results: From 13 relevant studies identified, 683 patients treated by SRS were compared with 670 patients treated by MVD for MRTN. Overall, the significant findings were that compared to MVD, SRS was associated with lower rates of short-term (OR ¼ 0.16; 95%CI ¼ 0.11–0.22; p < .001) and long-term pain freedom (OR ¼ 0.31; 95%CI ¼ 0.22-0.44; p < .001), fewer postoperative complications (OR ¼ 0.06; 95%CI ¼ 0.02–0.16; p < .001), more facial numbness and dysesthesia (OR ¼ 1.64; 95%CI ¼ 1.08–2.49; p ¼ .02), and more pain recurrence (OR ¼ 2.28; 95%CI ¼ 1.32–3.93; p ¼ .003). These trends were all reflected in MRTN patients being treated for the first time. Conclusion: Both SRS and MVD alleviate pain in MRTN patients. MVD results in superior rates of shortand long-term pain relief, facial numbness and dysesthesia control, and less recurrence amongst those in whom pain freedom was achieved, at the cost of greater postoperative complications when compared to SRS. Although no significant difference was found in terms of the need for retreatment surgery, there was a trend towards less procedures favoring MVD. First treatment by either technique represents the overall trends reported.
Received 22 August 2017 Revised 9 January 2018 Accepted 30 April 2018
Introduction Trigeminal neuralgia (TN) is a severe facial pain syndrome characterized by paroxysmal and lancinating pain along unilateral divisions of the trigeminal nerve. Studies of general populations posit that the lifetime incidence of TN is as high as 0.3%, peaking in the sixth decade of life, and with a slight preference for females.1 While medical management remains the initial treatment modality for TN, estimates suggest that, after optimal dose-titration to avoid unwanted side effects, only 70% will respond completely, and this effect is typically expected to diminish over time.2,3 There are many treatment options are for TN patients that are unable to obtain sufficient relief with medication, or for whom the side effects cannot be tolerated. The most common non-ablative technique is microvascular decompression (MVD), which involves microsurgical exploration at the cerebellopontine angle by retrosigmoidal approach under general anesthesia. An alternative ablative technique is stereotactic radiosurgery (SRS), which involves the precise delivery of collimated high-dose single fraction radiation to the trigeminal nerve itself. It has been maintained for many years by many that MVD remains the gold standard initial surgical option for medically
refractive trigeminal neuralgia (MRTN).4 However, SRS is becoming an increasingly popular alternative due to its non-invasive nature, no need for general anesthesia, and same day discharge procedure. Nonetheless, recent case series continue to demonstrate MVD5–7 and SRS8–10 both produce satisfactory outcomes in managing pain in MRTN. In fact, in recent years alone, there has been a noticeable increase in comparative studies11–14 of first treatment MRTN cases. These complement the more established literature describing retreatment by either technique. The aim of this study was to incorporate these new findings into a systematic review with meta-analysis to provide an up-to-date comparison of MVD versus SRS in the treatment of MRTN, and infer if overall trends are reflected in patients being treated for the first time versus repeat surgery.
Methods Search strategy The strategy was designed around the PICO format - Do patients with medically refractory trigeminal neuralgia (Population) treated with stereotactic radiosurgery (Indicator) compared to
CONTACT Victor M. Lu
[email protected] Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Supplemental data for this article can be accessed here. ß 2018 The Neurosurgical Foundation
KEYWORDS Medically refractory; metaanalysis; microvascular decompression; pain; stereotactic radiosurgery; trigeminal neuralgia
2
V. M. LU ET AL.
those treated with microvascular decompression (Comparator) differ in proportion achieving pain freedom or complications (Outcome)? The present review was conducted according to PRISMA guidelines and recommendations.15,16 Electronic searches were performed using Ovid Embase, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), American College of Physicians (ACP) Journal Club and Database of Abstracts of Review of Effectiveness (DARE) from their dates of inception to June 2017. The literature involving all comparative studies were searched by using the MeSH term enquiry “trigeminal neuralgia AND (radiosurgery OR gamma OR knife) AND (microvascular OR decompression OR exploration)”. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. All identified articles were then systematically assessed against the inclusion and exclusion criteria. Selection criteria The inclusion criteria used to screen all identified articles were (1) confirmed clinical diagnosis of medically refractory trigeminal neuralgia (2) reported in a comparative study comparing radiosurgery and microvascular decompression (3) in patients over the age of 18 years and (4) with at least either short-term or longterm pain freedom reported. Pain freedom was inferred from either a BNI score of 1 (pain free without medication), 2 (occasional pain without medication), or after careful evaluation of the pain relief definition by each study. The definitions of short-term and long-term used in this study were within and after the first three months of treatment respectively. Studies that reported outcomes for first MRTN treatment outcomes only were classed as Group 1, and any studies that reported MRTN retreatment outcomes, were classed as Group 2, which may have included some first treatment outcomes as well if the outcomes were not separable. The exclusion criteria used applied all identified articles were (1) unclear outcome measures and (2) other surgical techniques were incorporated and not discernible (3) other significant neurological conditions such as multiple sclerosis. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, and when studies reported multiple time courses of the same treated cohort, only the most complete reports were included for quantitative assessment at each time interval. All publications were limited to those involving human subjects and in the English language. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded. Review articles were omitted because of potential publication bias and duplication of results.
independently appraised each article included in our analysis according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) criteria.17
Meta-analysis The odds ratio (OR) was used as the summary statistic for each outcome measure. Each outcome was presented as a forest plot; the weighted OR, the 95% Confidence Interval (CI) and the relative weightings were represented by the middle of the square, the horizontal line, and the relative size of the square respectively. In the present study, a random-effect model was tested to take into account the possible clinical diversity and methodological variation between studies. v2 tests were used to study heterogeneity between trials. I2 statistic was used to estimate the percentage of total variation across studies, owing to heterogeneity rather than chance, with values greater than 50% considered as substantial heterogeneity. I2 can be calculated as: I2 ¼ 100% (Q – df)/Q, with Q defined as Cochrane’s heterogeneity statistics and df defined as degree of freedom. Publication bias was assessed through the generation of funnel plots for all outcomes and assessed for asymmetry. If there was substantial heterogeneity, the possible clinical and methodological reasons for this were explored qualitatively, and quantitatively, any outlying study was removed and effect on overall trend direction and significance was reassessed for any significant change. All p values were 2sided and significance set as p < .05. All statistical analysis was conducted with Review Manager Version 5.3.3 (Cochrane Collaboration, Software Update, Oxford, United Kingdom).
Results Literature search The search strategy identified a total of 532 studies (Figure 1). After removal of 179 duplicate studies, inclusion and exclusion criteria were applied to titles and abstracts of the 353 articles. This yielded 39 studies that underwent full-text analysis. Thirteen comparative studies11–14,18–26 were included in this current review for quantitative analysis. All studies included were observational in nature, four of which were prospective11,19,21,24 and nine of which were retrospective.12–14,18,20,22,23,25,26 Eight studies11–14,18,19,21,26 reported groups undergoing first treatment only, and were classified into Group 1. The remaining five studies19,22–25 were classified into Group 2. Study characteristics and design are summarized in Tables 1 and 2 respectively.
Data extraction and critical appraisal All data were extracted from article texts, tables and figures with any estimates made based on the presented data and figures. Two investigators (V.M.L. and J.B.D.) independently reviewed each included article with any discrepancy resolved by discussion to reach consensus. In addition to the incidence of at least either short- or long-term pain freedom for inclusion, additional outcome incidences extracted from the selected studies included postoperative complications, facial numbness and dysesthesia, pain recurrence, and subsequent procedures performed. All attempts were made to contact study authors for any clarification of data if needed. Because quality scoring is controversial in meta-analyses of observational studies, two reviewers
Demographics The included studies describe a total of 1353 patients with MRTN, with 683 (50.4%) and 670 (49.6%) treated with SRS and MVD, respectively. The median maximum dosage in the SRS group was 81.3 Gy. Collectively, there were 1111 (82%) patients treated for the first time (Group 1). Their demographic features are reported in Table 1. Mean age range was 54–74 years in the SRS group and 51–73 years in the MVD group. The range of male proportion was 33–55% in the SRS group and 26–67% in the MVD group.
BRITISH JOURNAL OF NEUROSURGERY
3
Figure 1. Flowchart showing the results of systematic review of the literature with methods of study identification and exclusion.
Pain freedom The definitions of pain freedom used for each study are described in Table 2. For short-term pain freedom, data were extracted from nine studies (average 1 month after treatment), seven of them being first treatment studies (Figure 2(A)). The incidences of short-term pain freedom after SRS and MVD were 380/574 (66.2%) and 570/625 (91.2%) respectively and were significantly different (OR ¼ 0.16; 95%CI ¼ 0.11–0.22; p < .001). This trend was significant in both Group 1 (OR ¼ 0.12; 95%CI ¼ 0.08–0.18; p < .001) and Group 2 (OR ¼ 0.41; 95%CI ¼ 0.18–0.95; p ¼ .42). Subgroup difference was significant (I2 ¼ 84.9%; p ¼ .01). For long-term pain freedom, data were extracted from thirteen studies (average 33 months after treatment), eight of them being first treatment studies (Figure 2(B)). The incidences of long-term pain freedom after SRS and MVD were 296/666 (44.4%) and 393/567 (69.3%) respectively and were significantly different (OR ¼ 0.31; 95%CI ¼ 0.22–0.44; p < .001). This trend was significant in both Group 1 (OR ¼ 0.29; 95%CI ¼ 0.19–0.46; p < .001) and Group 2 (OR ¼ 0.34; 95%CI ¼ 0.18–0.62; p < .001). Subgroup difference was not significant (I2 ¼ 0%; p ¼ .71). Postoperative complications No intraoperative complications were reported in the included studies. For postoperative complications, data were extracted
from eight studies, five of them being first treatment studies (Figure 3). The incidences of postoperative complications after SRS and MVD were 0/555 (0.0%) and 58/499 (11.6%) respectively and was significantly different (OR ¼ 0.06; 95%CI ¼ 0.02–0.16; p < .001). This trend was significant in both Group 1 (OR ¼ 0.05; 95%CI ¼ 0.01–0.18; p < .001) and Group 2 (OR ¼ 0.06; 95%CI ¼ 0.02–0.16; p ¼ .003). Subgroup difference was not significant (I2 ¼ 0%; p ¼ .69). Of the 58 reported complications, the most common complications were CSF leak (28%), hearing loss (19%) and wound infection (16%) (Table 2). The authors also note that one case of deep vein thrombosis (DVT) and one case of pneumonia have also been reported which are very serious complications in select demographics.19 Facial numbness and dysesthesia For facial numbness and dysesthesia, data were extracted from seven studies, four of them being first treatment studies (Figure 4). The incidences of facial numbness and dysesthesia after SRS and MVD were 69/349 (19.8%) and 65/432 (15.0%) respectively and was significantly different (OR ¼ 1.64; 95%CI ¼ 1.08–2.49; p ¼ .02). This trend was significant in Group 1 (OR ¼ 2.04; 95%CI ¼ 1.22–3.41; p ¼ .0070), but not in Group 2 (p ¼ .85). Subgroup difference was not significant (I2 ¼ 63.7%; p ¼ .10).
65 (65–73) (41–75) (21–72) (58–85) 10, 7, 9, 10, 4,
– 57.6
58 54 56 37, 41% 14, 39% 17, 52%
41.0%
80 77.8 – 75 77
81.3
68 (65–85) (40–88) (44–86) (55–91)
68.3
670
45% 26% 45% 42% 67%
85 80 83.5 67 74 68
22 27 20 24 6
80 85 80 – 84.4 72 (35–99) 63 (26–89) 60 (37–71) 63 –
Retreatment surgery For retreatment surgery, data were extracted from eight studies, five of them being first treatment studies (Figure 6). The incidences of retreatment surgery after SRS and MVD were 71/418 (17.0%) and 48/465 (10.3%) respectively and was not significantly different (OR, 1.76; 95%CI, 0.93–3.35; p ¼ .08). This trend was reflected in Group 1 (p ¼ .50), but not in Group 2 where it was significant (OR ¼ 1.76, 95%CI ¼ 0.93–3.35; p ¼ .007). Subgroup difference was not significant (I2 ¼ 57.4%; p ¼ .60).
43.4% 683 92% 588, 41% 1353 33
46% 33% 40% 43% 35% 11, 6, 8, 26, 7,
Overall Sum/Weighted Average
may include some first treatment R, OS, 1 institution, 1 surgeon R, OS, 1 institution R, OS, 2 institutions P, OS, 1 institution, 1 surgeon R, OS, 1 institution Group 2: Retreatment, which Pollock19, 2010b, US Oh22, 2008. Korea Tarricone23, 2008. Italy Brisman24, 2007, US Sanchez-Meija25, 2005, US
1999–2008 1995–2005 2004–2005 2003–2006 1997–2004
35 35 6 14 23
46% 29% 48% 42% 42%
0% 89% 65% 74% 0% 21, 13, 17, 36, 11, 46 45 40 85 26
24 18 20 61 20
27, 55% 19, 43% 32, 46% 49 44 69 64, 46% 33, 41% 49, 48% 140 80 102 38 41 21 2001–2007 1999–2003 1999–2001 P, OS, 1 institution, 1 surgeon P, OS, 1 institution, 1 surgeon R, OS, 1 institution, 1 surgeon Pollock20, 2010a, US Linskey21, 2008, US Pollock26, 2005, US
1 1 1 1 1 OS, OS, OS, OS, OS, Group 1: First treatment only
100% 100% 100%
131, 39% 90, 45% 10, 40% 23, 33% – 332 202 25 69 161 institution, 2 surgeons institution institution institution institution P, R, R, R, R, Wang11, 2017, US Dai12, 2016, China DeSouza14, 2015, Canada Nanda13, 2015, US Han18, 2010, Korea
1997–2014 2013–2014 – – 1992–2007
58 24 6 63 56
Mean Study Period FU (mo)
100% 100% 100% 100% 100%
First Male (n, %) treatment n
n
168 115 15 49 31
65, 39% 55, 35% 6, 40% – –
Male (n, %)
Study bias assessment
Study Design First Author, Year, Country
For pain recurrence, data were extracted from five studies, four of them being first treatment studies, and were compared to the cohorts reported to have had short-term pain freedom (Figure 5). The incidences of pain recurrence after SRS and MVD were 55/ 186 (29.5%) and 26/183 (14.2%) respectively and was significantly different (OR ¼ 2.28; 95%CI ¼ 1.32–3.93; p ¼ .003). This trend was significant in Group 1 (OR ¼ 2.32; 95%CI ¼ 1.25–4.29; p ¼ .008), but not in Group 2 (p ¼ 0.58). Subgroup difference was not significant (I2 ¼ 0%; p ¼ .71).
71 74 69 69
Median 100% Dose (Gy)
91 36 33
68 62 54 73
63 (18–87) 58 (36–77) 54 (36–68) 61 – 66, 40% 35, 44% 4, 40% – – 164 87 10 20 130
Mean age (yrs) Male (n, %)
Pain recurrence
Mean age (yrs)
n
MVD SRS Total
Table 1. Study design and features of included studies. SRS, stereotactic radiosurgery; MVD, microvascular decompression; P, prospective; R, retrospective; OS, observational study; FU, follow-up.
No previous MVD – – Young, healthy –
