Indian Journal of Pain

REVIEW ARTICLE
Year
: 2022  |  Volume : 36  |  Issue : 4  |  Page : 31--39

Percutaneous treatment of trigeminal neuralgia: A narrative review


Anurag Agarwal1, Shivani Rastogi1, Neha Singh1, Manish Kumar Singh2, Yasum Litin1, Sunny Bhasin3,  
1 Department of Anesthesiology, Dr. RMLIMS, Lucknow, India
2 Department of Neurosurgery, GSVM Medical College, Kanpur, Uttar Pradesh, India
3 Department of Anesthesiology, Aastha Pain Clinic, Jabalpur, Madhya Pradesh, India

Correspondence Address:
Dr. Anurag Agarwal
Department of Anesthesiology, Dr. RMLIMS, Lucknow, Uttar Pradesh
India

Abstract

Background: Minimally invasive and percutaneous treatments are effective treatment options for idiopathic trigeminal neuralgia (TN).Objectives: Multiple approaches have been described for the treatment of TN. This narrative review has been done to evaluate the current literature on different percutaneous treatment options for TN and to determine whether anyone treatment is better. Methods: The literature through a search of PubMed and Google Scholar was done and the review of the citations of relevant literature, and the authors knowledge of the literature and activity in the field. The literature was reviewed to find the preferred technique of preferred percutaneous treatment by different investigators and the difference in the outcome and/or complications and side effects. Results: Multiple techniques of such as percutaneous retrogasserian glycerol rhizolysis (PRGR), radiofrequency thermal coagulation (RFTC), and percutaneous balloon compression (PBC) for idiopathic TN have been used by different researchers. Effective pain relief and improved quality of life have been reported to be achieved by all the approaches. RFTC has been the most extensively used method, but PBC has been found to be more suitable for corneal preservation in cases of ophthalmic (V1) division pain. The most common imaging method used by large number of researchers is fluoroscope, though few authors have recommended computed tomography scan guidance for placement of cannula in foramen ovale and Meckle's cave, especially in cases with difficult anatomy. Limitations: This review has focused only on percutaneous techniques used by pain physicians. Other techniques such as radiosurgery and gamma knife used by radiologists and neurologists are not included. Conclusions: minimally invasive and percutaneous treatments such as PRGR, RFTC, and PBC are effective methods for the treatment of idiopathic TN. Selection of approach is largely dependent on the pain physician's choice, experience, and equipment available and can be used interchangeably; although for V1 neuralgia, PBC has superiority due to the preservation of corneal reflex.



How to cite this article:
Agarwal A, Rastogi S, Singh N, Singh MK, Litin Y, Bhasin S. Percutaneous treatment of trigeminal neuralgia: A narrative review.Indian J Pain 2022;36:31-39


How to cite this URL:
Agarwal A, Rastogi S, Singh N, Singh MK, Litin Y, Bhasin S. Percutaneous treatment of trigeminal neuralgia: A narrative review. Indian J Pain [serial online] 2022 [cited 2023 Feb 1 ];36:31-39
Available from: https://www.indianjpain.org/text.asp?2022/36/4/31/366474


Full Text



 Introduction



Trigeminal neuralgia (TN) is an extremely debilitating condition; the paroxysmal pain is so unbearable that it completely breaks down the mental strength of a person, sometimes to the point of driving him/her to even attempting suicide. Since prehistoric times, there are many descriptions of human afflictions from TN. Modern-day TN therapy is the result of concerted efforts invested in understanding the pathophysiology and treatment outcomes.

 Lterature Search



The literature search of PubMed and Google Scholar was done using MeSH words TNs, Tic dolourex, Fothergill Disease, radiofrequency thermocoagulation, percutaneous retrogasserian glycerol rhizolysis, and percutaneous balloon compression (PBC). The review of the citations of relevant literature and the author's knowledge of the literature and activity in the field was done. The literature was reviewed to find the preferred treatment of TN by different investigators and the difference in the outcome and/or complications and side effects.

The annual incidence of TN is estimated between12.6 and 28.9 cases per 10 million people.[1]

According to the International Association for the Study of Pain classification, there are three subtypes of TN [Table 1].[2]{Table 1}

TN more frequently involves maxillary and mandibular divisions of the trigeminal nerve then the ophthalmic division.[3],[4],[5] There is a higher prevalence of pain on the right side which may probably due to the fact that the foramen rotundum and ovale are significantly narrower on the right side as compared to the left which predisposes it to compression.[6]

Pain in TN is attributed to dysfunctional hyperactivity of the trigeminal nerve. The most common cause is a vascular loop compressing the nerve root entry zone (REZ); other causes of compression may include tumors, vascular malformations, and cysts.[7],[8] The most common vessel involved is the superior cerebellar artery in 85% of cases followed by the anterior inferior cerebellar artery, posterior inferior cerebellar artery, and vertebral artery (VA).[9],[10]

Magnetic resonance imaging (MRI) based grading of neurovascular compression:[11]

[INLINE:1]

MRI is the mainstay of diagnosis as it reveals fine anatomic details and helps analysing the entire course of the trigeminal nerve.[12] Interventional treatment of patients (three-dimensional) is usually based on fluoroscopic images (two-dimensional).[13]

Medical drugs were the only acceptable mode of treatment of TN up until the nineteenth century. Compounds historically used included quinine, mercury, camphor, opium, arsenic, ether, and powder of gelsemium. Trichloroethylene and stilbamidine became popular in the early 20th century. The response to treatment with these drugs was poor, short-lived, and accompanied by serious side effects. Bergouignan was the first to describe the use of anti-epileptic medications for TN treatment with sodium diphenylhydantoin.[14] In a landmark paper published in 1962, Blom proposed the use of carbamazepine for treating TN. Since then, several antiepileptic drugs such as lamotrigine, clonazepam, valproateand gabapentin have been used. Carbamazepine and oxcarbazepine are the “Drug of choice” for TN, found to have robust efficacy in four randomized controlled trials (RCTs).[15],[16],[17],[18],[19]

 Percutaneous Procedures for Treatment of Trigeminal Neuralgia



A plethora of percutaneous procedures is available for the management of TN. Percutaneous procedures are useful in patients with drug-refractory cases, who either refuse surgery or in those with significant medical risks to undergo major invasive surgical procedures [Figure 1].{Figure 1}

 Ideal Candidates for Percutaneous Procedures of Trigeminal Neuralgia



 Microvascular Decompression



Percutaneous procedures are mostly suited for elderly patients and patients with multiple co-morbidities or even in younger patients who wish to minimize postoperative side effects. In addition to age, co-morbidities, other clinical radiological features, symptom duration, and fractional anisotropy value (obtained from diffusion tensor imaging) which shows directionality of the diffusion and provides information about white matter pathologies affecting water diffusion, might be of valuable information in interventional decision making.[20] However, age is not an absolute contraindication for Craniotomy because Microvascular Decompression has been well tolerated in patients older than 75 years.

Radiofrequency Thermo coagulation (RFTC) is not appropriate for patients who cannot tolerate awake procedures or who are unable to cooperate with localization.

PBC is associated with trigeminal depressor response, hypotension, and bradycardia making it less appropriate for patients with cardiovascular disease. Nucleus caudalis dorsal REZ lesioning has been shown to be effective means for treating Atypical TN.[21]

 Fluoroscopic Anatomy for Percutaneous Treatment of Trigeminal Neuralgia



The procedural interventions on a patient are carried out in three-dimensional way based on fluoroscopic images, which are two-dimensional. Different views available to the clinician by fluoroscopy are: (a) postero-anterior (PA) view, (b) submental/occipitomental view, (c) ipsilateral oblique view, and (d) lateral view.

Postero-anterior view

Intervention of Gasserian ganglion starts with PA view of the face. The patient is placed supine, with the neck slightly extended keeping the head in the neutral position. In this view, the orbital line and the petrous ridge should be visualized through the orbits.

Submental view and ipsilateral oblique view

A combination of submental and oblique views is the final view to visualize the foramen ovale (FO), over which the entry point for the cannula or needle in the fluoroscopic image lies. The head is kept extended (usually 45°) and the fluoroscope is tilted cranially by 20°–30°. To see the FO, the fluoroscope is tilted ipsilateral oblique by approximately20°, so that the foramen is visualized just medial to the anterior border of the ramus of the mandible, or between the anterior border of the ramus of the mandible and lateral wall of the maxillary sinus.

Percutaneous retrogasserian glycerol rhizolysis

PRGR was one of the most popular methods of treatment for TN in earlier days. It is carried out by injecting anhydrous glycerol into the Meckel's cave.[22],[23],[24],[25] The major advantages of PRGR are: (1) Long-term pain relief following single injection, (2) significant reduction in postoperative facial deafferentation compared to thermal rhizotomy, and (3) simple to perform with an image intensifier. Precise anatomic placement of anhydrous glycerol is achieved with the help of intra-operative trigeminal water-soluble contrast.[26],[27],[28],[29]

 Various Studies and Their Results Showing Efficacy and Side-effects of Percutaneous Retrogasserian Glycerol Rhizolysis [Table 2]



The discovery of the beneficial effects of glycerol in patients with TN was purely accidental. In an attempt of lesioning the Gasserian ganglion using the Leksell gamma knife in Stockholm in 1970s, patients were injected with tantalum powder, a radiopaque substance intended to be used as a marker, and glycerol as the vehicle. It was found that the injection alone produced pain relief, and in 1981 Håkanson[22] developed the technique of percutaneous glycerol rhizolysis for TN and published the first series of 75 patients. It was found that Glycerol injection induces changes in osmolarity and subsequent demyelination and axonal damage.{Table 2}

Several large series of patients with TN treated with PRGR have been reported representing variations in the technique and length of follow-up. Very high rates of initial pain relief were noticed after the injection, ranging from 73% to 99.6%.[30],[31],[32] The duration of follow-up varies widely among the studies, ranging from 6 months to 6 years. Given the wide variability of follow-up times, recurrence rates are difficult to estimate. The average risk of early recurrence, within the first 2 years after treatment ranges from 2% to 45% with an average of 20% and the risk of late recurrence (>2 years after treatment) ranges from 10% to 72% with an average of approximately 50%.

PRGR is an overall safe procedure with a low risk of significant morbidity and mortality. The most common postprocedure finding is a disturbance of facial sensation that may last for a few hours to 1 or 2 weeks. Complications include facial hypesthesia lasting longer than 2 weeks and the rates range from 0% to 30%. The wide variability is a result of the different techniques used among the different studies. The incidence of painful facial dysesthesia and allodynia ranges between 0% and 4% with few studies rates as high as 11% and 26%. Infectious complications are rare after PRGR. Reactivation of latent herpes simplex virus has been described at a rate ranging from 3% to 77% and cases of aseptic meningitis have a frequency of 0%–7% but the rate has been decreased due to the current use of Iohexol. Similarly, the rates of other cranial neuropathies and bacterial meningitis are low and both range between 0% and 2% with inadvertent and unrecognized entry into the oral cavity being the most common etiology for bacterial meningitis after PRGR.

There have been few studies trying to identify predictive factors for pain relief after a procedure. A prospective analysis of factors related to pain relief after PRGR was published in 2005 by Bruce Pollock[33] and reports that predictive factors for success included patients without any constant facial pain, patients with immediate facial pain during glycerol injection, and patients with new trigeminal deficits after PRGR. Repeat PRGR remains safe and effective. Bender et al.[34] and Harries and Mitchell[35] in 2011 described their experience with around 500 patients with repeat PRGR and reported similar rates of initial and long-term pain relief compared to the initial PRGR.

Thus, PRGR is the initial minimally invasive treatment for elderly patients due to the ease and safety of the procedure. However, in less experienced hands risks are considerably higher, though most side effects can be prevented by proper identification of anatomical structure under continuous fluoroscopic guidance.

Percutaneous radiofrequency thermocoagulation

RFTC was first popularised by Sweet and Wepsic in 1974.[36] It offers a number of benefits over other percutaneous procedures. It is precise and gives the highest initial success rate with a low incidence of recurrence. It avoids damage to the unaffected division(s) of the trigeminal nerve, and the affected branch can be localized by the application of sensory and motor stimulation. It uses low energy, high frequency alternating electric field (oscillating frequency of about 500,000 Hz). When radiofrequency current is delivered to the target tissue, oscillation of the molecules within the tissue leads to the production of heat, thus a lesion is formed if the temperature exceeds 40°C.[37]

There are two types of radiofrequency application modes; conventional and pulsed radiofrequency (PRF).

In conventional radiofrequency aka radiofrequency thermocoagulation (RFTC), an alternate current is applied continuously to a target nerve; the aim is to produce a thermal lesion thereby causing interruption of afferent pathways for pain. Alignment of the active tip is usually desired alongside of the nerve targeted, and not perpendicular to it as energy is produced transversely along the active tip of the electrode.[38]

In PRF, an alternate current is applied to the target nerve without generating significant heat. Typically, high-frequency current of 50 kHz is delivered over 20 ms pulses at a frequency of 2 Hz, for a duration of 120 s or more. The long pause between pulses results in heat dissipation, thereby keeping tissue temperature below the neurodestructive threshold of 45°C. Pulsing the current also allows the generator power output to be substantially increased. Recently, some investigators have suggested the use of high fixed voltage and longer duration of PRF treatment to increase its efficacy.[39],[40]

 Various Studies and their Results Showing Efficacy and Side-effects of RFTC [Table 3]



A large number of series about RFTC have been published covering around 5000 patients with follow-up ranging from 1 to 14 years. The rates of initial pain relief have been reported as high as 97% to 100%. Rate of long-term pain relief range from 25% to 95%, but defining long-term recurrence rates becomes difficult because of the variable durations of follow-up for each study. Kanpolat et al.[41] in 2001 conducted a study with 1600 patients and described 52.3% of pain relief at 10-year follow-up and 41% pain relief at 20-year follow-up. In the same study, pain relief rates were better for patients having undergone multiple procedures and 94.2% and 100% of patients reported pain relief at 10 years and 20 years, respectively. Taha et al.[42] in 1995 described a 25% recurrence rate after 14 years in a group of 154 patients and the rate of recurrence correlated with the degree of sensory deficits elicited during the procedure. The milder the hypoalgesia noted, the higher the recurrence rate. In the same study, 15% of patients recurred within 5 years, 7% within 5–10 years, and 3% within 10–15 years. They concluded their result as high success rate but with high recurrence rate. Complications include persistent sensory deficit and paresthesias as a result of the lesioning and the rates range from 0.9% to 9% among the large patient series. Tew et al.[43] in 2012 reported on their experience with 1200 patients that Initial pain relief was observed in 99.4% of patients, total % recurrence is 20%, and noted a decrease in their rate of postoperative dysesthesias from 27% to 11% for minors and 5% to 2% for major symptoms, with the use of a curved electrode. Similarly, the rates of anesthesia Dolorosa decreased from 1.6% to 0.2%. Other strategies to decrease the risks of postoperative dysesthesias involved frequent sensory testing during treatment and an awake and actively participating patient. Corneal anesthesia has been reported ranging from 0% to 17%. Reactivation of herpes simplex virus has been reported in 3% of patients and the rate of cranial nerve palsies has ranged between 0% and 1%. In an attempt to decrease the rate of complications associated with percutaneous RFTC, there have been efforts to improve targeting accuracy through the use of intra-operative computed tomography and frameless stereotactic cannulation of the FO with good success. In a study conducted by Taha et al.[42] in 1995; they concluded that patients treated with RFTC has high long-term success rate but with high recurrence rate; analgesia was observed in 46% patients, decreased corneal reflexes in 13.63%, absent corneal reflexes in 5.19%, keratitis in 1.94%, masseteric weakness in 14.28%. In another study published by Tang et al.[44] in 2016 concluded that the optimal temperature for RFTC is 75°C. He further summarized that this is the optimal radiofrequency temperature to maximize pain relief and minimize facial numbness and dysesthesia. Agarwal et al.[45] in 2021, compared the RFTC with fixed high voltage and long duration PRF for idiopathic trigeminal neuralgia (ITN) in an RCT and found that RFTC is better than PRF for ITN. They also found that even increasing the duration of PRF to 10 min from 2 min and using high fixed voltage (50 V), does not improve the efficiency of PRF in the treatment of ITN.{Table 3}

Percutaneous balloon compression

PBC is considered as safe and effective modality for the treatment of TN. Large myelinated fibers are damaged with compression leaving the unmyelinated fibers intact and thus, the corneal reflex is preserved. It is a day-care procedure performed under general anesthesia.

A 14 gauge cannula with a blunt trocar is used to enter the FO to reach the Meckel's cave where the gasserian ganglion is situated. As entry was confirmed in Meckel's cave, the lateral view was obtained wherein 4-fr Fogarty catheter was gently threaded into Meckel's cave up to the clivus. After confirmation of the correct position, the balloon was inflated with 0.8–1 ml of water-soluble dye for 1.5–3 min. After that Fogarty balloon was deflated and removed along with cannula and manual digital pressure was applied for five minutes against the maxilla to stop any bleeding and cerebrospinal fluid drainage. A small dressing was applied on the skin puncture site.

 Various Studies and their results Showing Efficacy and Side-effects of Percutaneous Balloon Compression [Table 4]



There are several literatures available regarding efficacy and side effects of PBC. Rates of initial pain relief are high ranging from 91% to 100%, however, long-term pain relief rates range from 68% to 91%, with an average follow-up of 1 to 10.7 years. Recurrence rates range from 10% to 14% at 2 years, 15% to 19%at 3 years, and 19.2% to 32.5% at 5 years.Complications of the procedure include development of significant dysesthesias in a trigeminal distribution and rates vary from 0% to 15%. Disruption of the corneal reflex and subsequent corneal analgesia is rare and was not observed in all studies, except one or two where the rate was around 3%. Trigeminal motor weakness typically involves the masseter and has been reported at rates of 0% to 33%, but typically resolves within 12 months. Cranial nerve palsies are less common and have been reported at rates of 0% to 1.9%. Last, postoperative morbidity including infection and meningitis can occur at a rate of 0% to 5%in few cases. There are very few comparisons of the efficacy and complications of the different percutaneous techniques in the literature and the results are varied at times conflicting. No randomized comparisons exist and most studies are retrospective reviews.{Table 4}

 Treatment Efficacy and Comparitive Analysis [Table 5]



After analysing different studies of percutaneous treatment options for TN individually, we have tried to incorporate few more studies which had compared the outcomes for PBC, RFTC and PRGR. Lopez and colleagues[59] in 2004 in a review of the different procedures described higher rates of pain relief, but also higher rates of complications with RFTC compared with PBC. Kouzounias and colleagues[60] in 2010 compared PBC with PRGR and reported similar efficacy between the 2 procedures, but lower rates of complications with PRGR. In our institution, PBC is used mostly for elderly patients who are not a candidate for MVD or those patients with multiple sclerosis-related TN.{Table 5}

Fraioli and colleagues[61] compared outcomes for all three percutaneous procedures and they recommended PBC as a first line choice for percutaneous treatment due to its high efficacy and low complication rate. Udupi and colleagues[62] compared outcomes in patient undergoing PRGR and RFTC and found that initial pain relief was 84.6% in RFTC compared to 58.9% in PRGR but this difference was not statistically significant. Asplund and colleagues[63] compared PBC with PRGR recommended PBC as the First line given its lower complication rates. Similarly, Kouzounias[60] and colleagues also examined outcomes in patients undergoing PBC and PRGR and recommended that though initial pain relief rate and times to recurrence are comparable but overall complication rates in PBC is 23% and PRGR is 11%. masseteric weakness, diplopia and olfactory disturbances are more seen in PBC Thus they suggested PRGR should be the first choice however Patients who had undergone PBC had previously experienced surgical intervention compared to those who had undergone PRGR which may result in higher complication rates.

There has been no study to demonstrate completely the superiority of one procedure over the other. The selection of procedure depends on technical advantages and disadvantages. Some say that PBC is done under general anaesthesia thus there is no discomfort to the patient but again general anaesthesia has its own risk and may not be ideal for all patients.[64],[65] The main disadvantages of the procedure is significant bradycardia and hypotension that occurs due to engagement of foramen ovale and upon compression. While RFTC is division selective however there is challenge of performing the procedure in awake patient thus it is painful procedure and patient need to participate in localization and tolerate pain. Outcomes of PRGR and RFTC procedure is highly operator dependent compared to PBC.

Percutaneous procedures in all its forms offer immediate pain relief and tolerable side effect. However treatment selection remains controversial topic in absence of high quality of outcomes data.

The treatment of TN is a challenge for the pain physicians. Lack of a full comprehension of the complex pathogenesis is the key factor that produces unsatisfactory results to medical therapy. In the recent years a lot of progress has been made both in understanding the disease pathogenesis as well as minimally invasive percutaneous options along with improved neuroradiological interventions for successful treatment of TN.

 Conclusion



Percutaneous treatment of TN is associated with excellent pain relief rates with low morbidity and mortality. These three percutaneous interventions are safe and effective and can be easily repeated in case of recurrence. Due to varied nature of published literature, it is difficult to prove superiority of any one treatment over the others, yet, as PBC has the lowest incidence of corneal affliction, it can be considered as preferable technique for ophthalmic nerve TN. Finally the choice of percutaneous treatment depends of available resources, technical expertise and operator preference.

Limitations

Till date, no randomized trial exists that compare the three minimally invasive percutaneous approaches, therefore current knowledge is majorly based on retrospective comparative studies only. Different parameters in these studies like duration of compression in PBC, temperature during RFTC , amount of glycerol used in PRGR, follow up duration; are not uniform and poses a difficulty in analysis. Similarly, Patients experiencing immediate pain relief were on or off medication is not included in majority of studies, so further randomized trial are anticipated to validate the conclusion of following study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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