Treatment of trigeminal neuralgia in older adults: a narrative review based on literature published between 2005 and 2021

Introduction

The first edition of the International Orofacial Pain Classification was published in Cephalalgia in January 2020 as an international orofacial pain classification/diagnostic standard. Here, trigeminal neuralgia (TN), characterized by paroxysmal pain, was classified into three pathological conditions: classical, idiopathic, and secondary TN (1).

TN is a severe orofacial pain disorder that mostly occurs in older individuals. Specifically, severe paroxysmal pain manifests in the area innervated by the trigeminal nerve. This pain is repetitive and short-term, akin to being stabbed using a knife. A characteristic feature of TN is that innocuous stimuli “trigger” the pain. For example, mouth movements such as tooth brushing, mastication, and speech cause severe pain in the teeth and gingivae, which may prompt repeated dental visits. Undiagnosed patients may undergo irreversible and invasive treatments, including tooth extraction. Therefore, there is a need for collaboration among related specialties, including dentistry/oral surgery, pain clinics, and neurosurgery (2).

Pharmacotherapy comprises the first-line therapy for TN (3). Carbamazepine, an antiepileptic drug, is the drug of choice for TN treatment. Oxcarbazepine, baclofen, and lamotrigine are considered second- and third-line drugs (4). Other therapeutic methods are classified as surgical and non-surgical treatment. Based on international guidelines, surgical treatment is recommended when drug therapy is unavailable or insufficient (3).

Surgical treatments for TN include microvascular decompression (MVD); percutaneous surgery, i.e., radiofrequency thermocoagulation (RF); and low-level radiotherapy, i.e., gamma knife surgery. Surgery is an effective treatment option for TN not improved by carbamazepine (5).

TN treatment using RF involves blockade of pain signal conduction either by nerve destruction through high temperatures (up to 90 ℃) or modulation of the nociceptive function of the trigeminal nerve at temperatures not exceeding 42 ℃. Although TN disappears immediately after RF, this is accompanied by desensitization of the nerve area. Patients have reported a gradual decrease in hypoesthesia, which is simultaneously accompanied by the return of severe pain (3). The efficacy durations for infraorbital and mandibular nerve blocks are 1–1.5 and 2–3 years, respectively (6). Previous studies have provided detailed descriptions of the temperature conditions (7-9).

A high proportion of older individuals take anticoagulants and antiplatelet drugs (10). Shortening the surgery duration is necessary for the safe administration of trigeminal nerve block in patients taking anticoagulants and antiplatelet drugs. There has been a previous review on the effectiveness and safety of TN treatment through different RF approaches. However, few studies have investigated trigeminal nerve blocks in medically compromised patients or compared nerve blocks and MVD (7-9). Therefore, there is a need for studies comparing RF with other surgical procedures, investigating the RF effectiveness according to the temperature setting or pain control period, and assessing the feasibility of trigeminal nerve blocks in patients taking anticoagulants and antiplatelet drugs.

The research questions of the present narrative review were as follows. Does RF or PRF yield adequate nerve blockade in TN? How does nerve block compare to other surgical procedures? Is it safe to administer trigeminal nerve block to patients taking anticoagulants and antiplatelet drugs? How do the efficiency and safety differ across temperature settings for nerve blocks? We present the following article in accordance with the Narrative Review reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-22-2/rc).

Methods

Study selection

We performed a PubMed search of studies published from April 2005 to September 2021. We used the following search terms: (Trigeminal Neuralgia OR Orofacial Pain) and (Radiofrequency OR Pulsed Radiofrequency) and (Elderly Patients OR Medically Compromised Patients) and (2005/04/01:2021/9/01[Date-Entry]). Two hundred and four studies were found. Review articles, meta-analysis, original studies published in English were included but case reports, protocols, short communications, personal opinions, letters, conference abstracts or laboratory research were excluded. N Noma and K Takizawa screened full-text article independently and all disagreements were resolved through consensus with K Ozasa, R Tanaka, Z Yan and A Young (Table 1).

Results

The PubMed search yielded 204 potentially relevant studies. After reading the titles and abstracts of the articles, we included 24 articles. Among them, nine investigated RF combined with PRF or other treatments, eight investigated whether RF is a viable treatment option and temperature setting for TN, seven focused on MVDs with other surgical procedure.

Discussion

Comparison of RF thermocoagulation with pulsed radiofrequency (PRF) stimulation

None of the four included randomized controlled trials (RCTs) (9,11-13) compared RF with sham treatment or treatments other than nerve block. However, they compared the treatment site (trigeminal ganglion vs. peripheral branches of the trigeminal nerve) and RF combined with PRF and RF alone. Therefore, only the analgesic effect could be evaluated as the outcome.

Compared with PRF alone, RF compared with PRF showed higher safety and efficacy (7,9). Therefore, it is recommended that PRF is combined with RF as an analgesic method for TN (9,11-13).

High short-term and long-term pain relief rates were reported for percutaneous RF rhizotomy of the trigeminal ganglion and RF of the peripheral branches of the trigeminal nerve, respectively (7,14). RF combined with PRF is a relatively new treatment method for TN, especially in the V1 branch. This procedure (RF at 62–75 ℃ combined with PRF at 42 ℃) has improved long-term efficacy (85–92% and 70–92% 1- and 2-year efficacy rate, respectively) and a reduced incidence of adverse effects (8,9,15); however, this approach remains controversial (16). Further clinical trials are warranted to evaluate the effectiveness of RF combined with PRF for TN treatment (Figure 1).

Figure 1 Comparison of radiofrequency thermocoagulation with the pulsed high-frequency method (7-9,11-16). RFT, radiofrequency thermocoagulation; PRF, pulsed radiofrequency; NL, not listed; RF, radiofrequency; TN, trigeminal neuralgia; CRF, continuous radiofrequency thermocoagulation; CCPRF, combined continuous and pulsed radiofrequency; VAS, visual analogue scale; MVD, microvascular decompression; HRQoL, health-related quality of life; SCRF indicates 75 ℃ CRF for 120 to 180 s; LCRF indicates 75 ℃ CRF for 240 to 300 s; PCRF indicates 42 ℃ PRF for 60 s.

Comparison of RF thermocoagulation with other surgical procedures

The analgesic effects of MVD, RF, and radiosurgery were compared. The proportion of patients requiring postoperative medication was similar between MVD and RF, while MVD was superior to radiosurgery (17). Compared with radiosurgery, MVD yielded a higher pain relief rate after 5 years (18).

Sanchez-Mejia et al. reported that compared with MVD or RF, radiosurgery involved lower retreatment rates (19). Radiosurgery was more likely to be the final treatment for recurrent TN, irrespective of the initial treatment.

Compared with radiosurgery, MVD involved a higher improvement rate in the quality of life (QOL) (20). The postoperative pain recurrence rates of MVD and radiosurgery were 11% and 25%, respectively, with no between-method difference in the time to recurrence (20). For RF, the pain recurrence rate was 80%, 75%, and 73% after 1 year, 3, and 5 years, respectively (21). Among the three treatment methods, MVD showed the lowest rate of recurrence that required a repeat procedure. Although RF yielded immediate relief, it was associated with high rates of facial numbness and recurrence. Compared with MVD, RF was used more commonly in patients requiring secondary treatment (retreatment) for postoperative pain recurrence (22).

Koopman et al. reported that compared with percutaneous RF, MVD and partial sensory rhizotomy were associated with a lower risk of undergoing a repeat procedure; however, they were more prone to complications requiring rehospitalization (23). Hitchon et al. conducted a 15-year retrospective review of the treatment experience of 195 TN cases (24). They found that RF showed the highest recurrence rate of TN (64%) (Figure 2).

Figure 2 Comparison of radiofrequency thermocoagulation with the pulsed high-frequency method (17-20,22-24). MVD, microvascular decompression; GKT, gamma knife therapy; SRS, stereotactic radiosurgery; TN, trigeminal neuralgia; RF, radiofrequency thermocoagulation/rhizotomy; RS, radiosurgery; NL, not listed; PRT, percutaneous radiofrequency thermocoagulation; PSR, partial sensory rhizotomy; RR, relative risk.

Trigeminal nerve block in patients taking anticoagulants and antiplatelet drugs

Many older individuals with TN are usually undergoing anticoagulants or antiplatelet therapy, which increases the risk of bleeding during invasive microsurgical or percutaneous procedures (25). Additionally, numerous patients with TN have other comorbidities. There have been no RCTs on whether trigeminal ganglion block is safe for patients taking anticoagulants or antiplatelet drugs and whether their risk of bleeding is comparable to patients not taking these medications. There have been no case reports of hemorrhagic complications resulting from the trigeminal ganglion block (26).

Currently, international guidelines do not mention trigeminal ganglion block (26). Deep nerve blocks are classified as medium-risk procedures based on anatomical characteristics that impede compression hemostasis or high-risk factors for bleeding (advanced age, history of bleeding disorders, and anticoagulant use). Accordingly, trigeminal ganglion block is considered a high-risk procedure in patients taking other drugs/anticoagulants and in patients with liver cirrhosis or advanced renal disease (27).

Therefore, caution is necessary when administering the trigeminal ganglion nerve block to prevent bleeding events; however, there have been no reports of bleeding complications. Several international guidelines indicate that peripheral nerve blockade can be performed without stopping non-steroidal anti-inflammatory drugs, including aspirin. However, the trigeminal ganglion block is a deep nerve block involving a risk of persistent bleeding (26). Therefore, trigeminal ganglion block should be ideally performed with an appropriate drug holiday for all antiplatelets and anticoagulants.

The strengths of gamma knife surgery include the immediate analgesic effect and the low recurrence rate. Gamma knife surgery may be the ideal option for recurrent medically refractory TN in patients with advanced age or medical comorbidities, especially patients on a long-term regimen of anticoagulants or antiplatelet therapy (Figure 3).

Figure 3 Flowchart with TN patients with anticoagulants and antiplatelet drugs. TN, trigeminal neuralgia; PT-INR, prothrombin time-international normalized ratio.

RF thermocoagulation: temperature settings

There remain no specific standard temperature settings for RF, which vary widely across studies (60–95 ℃) (28-30). High-temperature RF often causes serious complications, including severe facial numbness, ptosis, diplopia, keratitis, corneal ulcers, abducens nerve damage, transient vision loss and blindness, mandibular deviation, hearing loss, masticatory muscle weakness, cerebrospinal fluid leakage, and death. Tang et al. examined the optimal temperature for computed tomography (CT)-guided RF for TN treatment (28). They observed no significant differences in the rate of excellent pain relief across the various RF temperature setting used in 1,161 procedures. However, most patients experienced no facial numbness (which gradually resolved if it occurred); additionally, patients treated at 75 ℃ exhibited a lower rate of grade IV facial numbness/dysesthesia than those treated at other temperatures. In a prospective study with a 15-year follow-up, Taha et al. reported that 99% of patients with TN (n=154) achieved initial pain relief after one session of percutaneous stereotactic rhizotomy (29). Moreover, dysesthesia, mild initial hypalgesia, dense hypalgesia, and analgesia were observed in 23%, 7%, 15%, and 36% of the patients, respectively (29).

The recurrence rate is used as an indicator of the efficacy of high-temperature RF for TN, which ranges from 7.8% to 42.7%, with a follow-up period of 11.6 to 15 years (31,32). However, the included studies had several limitations. First, they did not determine whether patients used pain medication after the procedures. Second, they included patients with secondary TN caused by other diseases, including brain tumors, who had unsuccessfully undergone other invasive interventions. Nonetheless, there was no significant difference between the long-term pain relief rates of high- and low-temperature RF.

The short-term mild facial numbness after RF treatment is associated with the temperature used for RF. Zhao et al. examined the complications of combining RF and PRF for TN treatment (8). Patients either received RF at 70 or 75 ℃; further, each group was classified into two subgroups receiving percutaneous RF (240 s) with or without PRF (42 ℃, 2 Hz, 240 s) (8), with patients who received combined RF and PRF treatment showing a more rapid recovery of facial numbness and masticatory muscle weakness. Further, Yao et al. assessed postoperative complications and long-term health-related QoL (HRQoL) (15). They observed that the temperature was positively correlated with the incidence rate of facial numbness, masticatory atonia, and corneal hypoesthesia. Further, the highest HRQoL scores were observed in the group treated at 68 ℃, followed by the groups treated at 65 and 62 ℃, which suggests that 68 ℃ is a good choice for RF of V2/V3 for TN treatment (Figure 4).

Figure 4 Radiofrequency thermocoagulation: temperature setting (8,15,28-32). RFT, radiofrequency thermocoagulation; PRF, pulsed radiofrequency; NL, not listed; CRF, continuous radiofrequency thermocoagulation; PRT, percutaneous radiofrequency thermocoagulation; TN, trigeminal neuralgia; RF-TR, percutaneous, controlled radiofrequency trigeminal rhizotomy.

This review has several limitations. First, since we only used the PubMed database, we did not include all target data. Second, we included a broad range of study designs, with weaker study designs increasing the risk of bias. Third, the sample sizes were not balanced between MVD and nerve block. Regarding the effectiveness of nerve block, the number of patients with and without guidance such as three-dimensional CT varied, which impeded proper evaluation. Finally, the long-term follow-up data regarding the treatment effect were inconsistent across studies. Future high-quality cross-sectional surveys using standard sampling methods and surgical treatment are warranted to elucidate the efficacy of RF, PRF, and other surgical procedures in TN treatment.

Conclusions

This review demonstrated the clinical utility of PRF combined with RF for TN treatment, which is a relatively new approach. This approach can increase the long-term efficacy and minimize the incidence of adverse effects. Compared with RF alone, combined RF and PRF treatment allowed more rapid recovery of postoperative complications, including facial numbness and masticatory muscle weakness. However, gamma knife surgery appears to be more suitable than nerve blockade for patients taking anticoagulants and antiplatelet drugs. We recommend combining PRF with RF when drug therapy is unavailable or insufficient. This review will guide clinicians in making informed decisions. Future studies are warranted to validate these results.

Acknowledgments

Funding: This work was supported in part by research grants from the Sato and Uemura funds, the Dental Research Center of Nihon University School of Dentistry, and KAKENHI {Grant-in-Aid for Scientific Research [C] [20K10171]}.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Mythili Kalladka) for the series “Orofacial Pain: Diagnostic and Therapeutic Topicals, Nerve Blocks and Trigger Point Injection” published in Journal of Oral and Maxillofacial Anesthesia. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://joma.amegroups.com/article/view/10.21037/joma-22-2/rc

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-22-2/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-22-2/coif). The series “Orofacial Pain: Diagnostic and Therapeutic Topicals, Nerve Blocks and Trigger Point Injection” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work by ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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