Microvascular decompression versus stereotactic radiosurgery as primary treatment modality for trigeminal neuralgia: A systematic review and meta-analysis of prospective comparative trials
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.232342
Source of Support: None, Conflict of Interest: None
Keywords: Gamma knife therapy, meta-analysis, microvascular decompression, stereotactic radiosurgery, trigeminal neuralgia
Trigeminal neuralgia (TN) is one of the most common paroxysmal facial pain syndromes. It is not just a matter of physical pain but an emotional one that sometimes culminates into clinical depression and may even result in suicide.
There are several treatment modalities available for trigeminal neuralgia. Medical treatment is the first line treatment and surgical interventions are reserved for the refractory cases. The drugs used for the treatment of trigeminal neuralgia are carbamazepine, oxcarbazepine, baclofen, gabapentin, lamotrigine, and phenytoin. Out of these, carbamazepine is the preferred first line drug.
The surgical options include microvascular decompression (MVD), percutaneous destructive procedures, and stereotactic radiosurgery. Microvascular decompression surgically addresses the basic etiology of classical TN by relieving the arterial or venous compression over the trigeminal nerve. In the cases associated with other pathologies like multiple sclerosis (MS), percutaneous neurolysis or stereotactic radiosurgery (SRS) is considered as a better option due to the absence of vascular compression as an etiological factor. Percutaneous neurolysis can be done using a variety of chemical and physical agents like glycerol, radiofrequency impulse or balloon compression of the Gasserian ganglion More Details or the retrogasserian nerve root. Stereotactic radiosurgery (SRS) using gamma knife (GK) or linear accelerator (LINAC) is another method that has gained popularity due to the absence of surgical risk, and may be used in patients who are medically unfit or unwilling to undergo a surgical procedure.
Though the absence of the risks of surgery makes SRS an attractive alternative, there is need for systematic evaluation of the existing literature for assessing the long-term efficacy and complications of gamma knife therapy (GKT) with respect to the gold standard, MVD. This systematic review and meta-analysis is an attempt to summarise the findings of the existing literature comparing SRS and MVD and understand the larger picture. This would help in the decision making regarding the preferred treatment modality in medically refractory cases of TN.
Study eligibility criteria
The studies satisfying the following criteria were included:
Review articles and letter to editors were excluded. Studies from across the globe were selected matching the above criteria without any preference for a particular geographical region. Study eligibility was assessed by two independent observers (RS and VK) and any disagreements were resolved with the opinion of a third independent observer (MP).
Searching the relevant literature
The studies were searched on PubMed, Google Scholar, and Cochrane Library using key words “(microvascular decompression OR MVD) AND (stereotactic radiosurgery OR SRS OR gamma knife therapy OR GKT)” AND “(trigeminal neuralgia OR TN)” with all the possible combinations used. The titles of the studies were used to shortlist the relevant articles followed by their abstracts. The references of the relevant studies were also used to complement the initial search. The relevant articles at this stage were read in full and evaluated with respect to our inclusion criteria.
Data compilation process
The variables of interest for the review and meta-analysis were identified and data was extracted after reading of the full articles by one independent reviewer (VK). Data was then entered in Microsoft Excel by another reviewer (RS), which was then verified by the third reviewer (MP). In case of any disagreement, the opinion of the fourth reviewer (SB) was taken. The studies included were those that reported the percent pain-free rate at variable durations after surgery. Thus, for the purpose of meta-analysis, responses were studied immediately after treatment, 1 year after the procedure, as well as between 1 and 3 years, and between 3 and 5 years after the procedure. All the studies included, except that of Wang et al., did not have sufficient information to find out the exact number of patients in the follow up period at different times after the procedure, and only the percent pain-free rate was reported. Hence, the percent pain-free rate was used to calculate the number of patients who were pain free at the time, assuming that there was no loss to follow up. A similar procedure was used by Wang et al., as well because using the original numbers reported in the article would have resulted in giving less weightage to this study as compared to others.
The following variables were collected from individual full articles and entered into the Microsoft Excel spread sheet: year and name of first author, duration of the study, the number of patients, the male–female distribution, the right–left distribution, the nerve division involved, the mean duration of symptoms, the mean age at treatment, the mean duration of follow-up, the long-term treatment success at different follow-up durations and the complications encountered in both the groups, i.e., MVD and SRS (GKT).
Comparisons of the proportions of pain-free rates between the two groups immediately after the procedure and during long term follow up were taken as the primary effect estimates in this study. To accommodate the differential reporting of response among the studies, for the purpose of meta-analysis, 'pain freedom' was defined as 100% pain relief or an excellent response or a BNI (Barrow Neurological Institute) score of 1. After identifying the eligible studies that met all the inclusion criteria, their quality was assessed using the Newcastle Ottawa Scale (NOS) for non-randomized interventional trials. A funnel plot was made to assess the publication bias. The estimates of total proportions of treatment successes at various durations of follow up and complications were compared using OpenMetaAnalyst software version 5.26.14, designed by the Center for Evidence Based Medicine, Brown School of Public Health. Data that was not available was reconstructed by two reviewers independently (VK and RS).
The heterogeneity between studies was calculated using the Q measure for statistical significance and the I 2 measure of the amount of heterogeneity, with P < 0.05 being statistically significant. Random effects model was used to analyze the data as the studies varied in terms of patient selection, treatment allocation, baseline patient parameters, and follow up time at which pain-free rate was measured. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were followed throughout to report the results of this analysis.
The initial literature search done using the keywords “(microvascular decompression OR MVD) AND (stereotactic radiosurgery OR SRS OR gamma knife therapy OR GKT)” AND “(trigeminal neuralgia OR TN)” yielded 160 articles. On screening these articles, 60 relevant abstracts were retrieved, out of which only 5 full articles ,,,, met the eligibility criteria representing a comparison between microvascular decompression and gamma knife therapy for TN in terms of efficacy and complications to be included in the final analysis, as shown in the PRISMA flow diagram [Figure 1].
The general characteristics and results of various studies comparing MVD and GKT for the treatment of TN have been summarized in [Table 1]. All the studies were assessed for quality using the Newcastle Ottawa scale (NOS) and had a score greater than or equal to 6. All the studies included lacked random allocation of treatment, with GKT being prescribed preferentially to the older patients. Also, there were more female subjects in the MVD group in the pooled data, while the sex distribution was more or less equal in the GKT group; however, this difference was not found to be significant. The mean duration of symptoms was significantly different between the two groups in two of the five studies., The mean age of the patients was found to be significantly different in all the studies with the GKT arm having a higher mean age than the MVD group. The pooled analysis of these characteristics could not be performed due to lack of required information in the articles.
The treatment was considered successful if the patient was pain free, an excellent response was documented, or the patient had attained a post-procedural score on BNI of 1. The initial success rate with MVD was 96% (95% C.I. 93.3%–98.6%) as compared to GKT, where the success rate was 71.8% (95% C.I. 64.9%–78.7%). The initial success rate was significantly higher in patients who had undergone a MVD versus GKT with a ratio of 1.309 (95% C.I. 1.217–1.409; P= <0.001) as shown in [Figure 2]a. The effect sizes of the ratios of immediate efficacy of the studies when plotted in the funnel plot [Figure 3] revealed an asymmetric distribution. With the increasing duration of follow up, there were an increasing number of patients who experienced recurrence in both the groups; however, the superiority of MVD over GKT was sustained at 1 year, 1–3 years, and 3–5 years, as shown in [Figure 2]b, [Figure 2]c, [Figure 2]d and [Table 2]. However, on conducting a separate meta-analysis for the two studies, which have reported the 5 year follow up, it was determined that although MVD was found to be better than GKT with the ratio of pain free rate of 1.693, it fell slightly short of statistical significance (95% C.I. 0.944-3.037; P= 0.077).
Mild facial numbness and dysesthetic facial pain were the common complications after both the procedures. The rate of both these complications was significantly higher after GKT than following MVD, as elaborated in [Table 3] and [Figure 4]. There were no other complications reported after GKT; however, a small number of patients undergoing MVD suffered from serious complications like cerebrospinal fluid (CSF) leak (3.3%; 95% C.I.: 0.7%–5.9%), wound infection (1.3%; C.I: 0%–3.1%) and cranial venous sinus thrombosis (1.3%; C.I: 0%–3.1%). Only one study reported that 2 of the included patients suffered from hearing loss and one patient had pneumonia after an MVD procedure, out of the 91 patients who underwent MVD.
It was in 1934 that Dandy  postulated the role of vascular compression in the pathogenesis of trigeminal neuralgia. This was followed by attempts at surgical vascular decompression by Gardner  and later introduction of microscopic surgery for the same by Jannetta  and Barker. Since then, MVD has become the gold standard for the treatment of TN.
However, like any other medical fact, exceptions are always round the corner. It is being realised now that vascular compression may not be the only pathogenetic factor involved. It is not always vascular contact that plays a major role, as even those patients not suffering from TN may have such findings; displacement or atrophy of the trigeminal nerve, however, shows better correlation with symptoms. Some authors are of the opinion that it is inflammatory and demyelinating changes in the trigeminal nerve that may play a role not only in the obvious demyelinating disorders like multiple sclerosis (MS) but also in a few cases of typical TN., As a result of consideration of this alternate hypothesis, other treatment modalities which include the destructive procedures like percutaneous balloon compression (PBC), percutaneous retrogasserian glycerol rhizotomy (PRGR), radiofrequency lesioning (RFL), and GKT have garnered attention. There is a prevailing consensus to prefer GKT for older patients and those with a brainstem lesion, an extrinsic compression or with no demonstrable vascular compression on radiological imaging, while for all other patients, MVD is the preferred first line treatment.,,,,
We found that MVD provides a much better initial success rate of around 96% (95% C.I. 93.3%–98.6%) as compared to the success rate of 71.8% (95% C.I. 64.9%–78.7%) for SRS/GKT. The success rate after 1 year also shows a significant difference between the two modalities with MVD emerging as the clear winner. The results of the long-term follow up studies have been summarised in [Table 2]. From these findings, it is clear that MVD has a significantly greater efficacy in terms of not only the initial pain relief but also of sustained pain free rate.
There are several factors that have been evaluated in different studies that may predict the outcome in both the modalities of treatment. The presence of a typical trigeminal pain, a demonstrable vascular compression, and a shorter duration of preoperative symptoms suggest a greater chance of pain relief from MVD. As far as GKT is concerned, it has been found that the success of the procedure is closely linked to one of the side effects, i.e., facial numbness.,
However, another factor to be accommodated in the choice of preferred treatment is the association of complications with the two procedures. MVD being an invasive procedure has greater surgical risks that include cerebrospoinal fluid leak, wound infection, cranial venous sinus thrombosis, hearing loss, pneumonia, facial paresis, stroke, and even death has been rarely reported. On the other hand, GKT has only limited complications of facial numbness and dysesthetic pain, which occur as an extension of its therapeutic mechanism. It is also noted in our meta-analysis that these occur significantly more frequently with GKT as compared to MVD. Based on the earlier observations of higher complication rates of MVD in the elderly population, GKT is preferred as first line therapy for them. However, a few authors are of the opinion that without medical comorbidities hampering the fitness for surgery, age does not per se affect the success rate or the complication rate of MVD., Still, most neurosurgeons prefer GKT in their elderly patients, considering a moderate rather than a complete pain relief a good trade-off for the morbidity associated with a major surgical procedure. Owing to the attractiveness of the noninvasiveness of GKT and its fair success rate, it might seem plausible to use GKT as the first-line modality in this subgroup of patents and move on to MVD only after its failure. However, there are two reasons against this line of thought. First, there is evidence supporting the inverse relationship between the pre-treatment symptom duration and the treatment success. Prolonging the course of the trigeminal neuralgia by initially trying out GKT as the primary modality of treatment may render MVD ineffective after 8 years, as elaborated by Barker et al., with the hazard ratio of recurrence being 1.3 (C.I. 1-1.5; P= 0.03). It has also been observed that MVD fairs much better as the first line of treatment than when it is used after failure of some other form of therapy. It is usually seen that in the absence of demonstrable vascular compression, the efficacy of MVD is lower;,, however, Barker et al., found the opposite findings.
In one of the studies included, rhizotomy was done in addition to MVD in patients without demonstrable vascular compression; however, it was not found to have a statistically significant difference on the outcomes. The authors of this study also found MVD to be as effective in these patients without a vascular loop, as in those who had a vascular compression, with the additional rhizotomy being associated with higher long-term recurrence rates. Whether this is attributable to the lack of vascular compression or the rhizotomy per se is an unanswered question. There is still no study that has compared the efficacy of MVD and GKT/SRS, exclusively in those patients without radiographic evidence of vascular compression. Although, according to the existing evidence it seems more likely that MVD would fare better than GKT even in this subgroup, well designed randomized studies are required to validate the hypothesis and also to understand the biological mechanisms that may be responsible for the effectiveness of MVD without the presence of a vascular loop.
Berger et al., conducted a decision tree analysis with the purpose of comparing GKT and MVD, in terms of the postoperative quality of life. However, they have included all the studies, irrespective of the study type and the intervention evaluated, to make the decision tree, which may have resulted in a selection bias.
This is the first meta-analysis of all the prospective cohort studies comparing the efficacy of the two procedures till date, to the best of our knowledge. The current opinion among neurosurgeons regarding the selection between the two procedures is not based on clear evidence. The paucity of any large randomised controlled trial perpetuates the problem. With this meta-analysis, we have tried to summarise the results of all the major interventional cohort studies undertaken to address this question.
We had to club the follow-up pain-free rates across the studies into the 1 to 3, and the 3 to 5 year categories for the purpose of the meta-analysis due to lack of uniformity regarding the duration of sustained pain relief following the procedure undertaken among the studies. Also, the procedure we have used to extrapolate data regarding the percent pain free rate has two implicit assumptions that may deviate from reality. One, it assumes that the attrition of patients is completely independent of their responsiveness to the therapy. Two, it assumes that the attrition rate of all the studies included in this metanalysis was comparable. In case the actual reality is grossly different from these assumptions, the results of this meta-analysis may not truly represent the summary statistic of the studies included, due to the resultant erroneous weight allotment during the statistical calculation.
The studies have used different scales to assess the pain response rate, although most commonly, the Barrow Neurological Institute (BNI) scale was used. However, the effect of this heterogeneity is minimised as we have meta analysed only 100% pain-free rate, which is exactly similar to the category of BNI I and the corresponding level of pain freedom of the other scales. The asymmetric funnel plot is also suggestive of a publication bias. The studies reporting a weaker advantage or no advantage of MVD over GKT seem to have been a victim of 'file drawer effect' (a tendency to publish positive results but not to publish negative or nonconfirmatory results). Further studies with random intervention allocation and larger sample size must be conducted to help in making evidence-based decisions between the two procedures for treatment of this troubling disease.
In spite of multiple studies evaluating the treatment of trigeminal neuralgia, there is still much to be agreed upon regarding the management plan of this disease. From the bulk of existing literature, it seems safe to conclude that MVD is a better option than GKT as a first-line treatment for trigeminal neuralgia. In spite of clear superiority in terms of efficacy, the dilemma still remains for special subgroups of patients, like the elderly ones, due to the seemingly higher risk of side effects; and, in those without any evidence of vascular compression.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]