Controversies in Trigeminal Neuralgia: A Review

Abstract

Trigeminal neuralgia (TN) is an area full of controversies. The anatomical distribution of various sensory fibers in the sensory root of the trigeminal nerve at the root entry zone (REZ), the classification of TN, clinical features to differentiate from other facial pain syndromes, pathogenesis of TN, the plethora of treatment modalities for the medically intractable TN with their relative merits and demerits, are an interesting area of study. Understanding these aspects will help us to find concrete answers to these various issues. Dandy's concept of accessory fascicles near the trigeminal REZ, which carry the touch and proprioceptive fibers, paved the way for partial sensory rhizotomy by posterior fossa approach. Similarly, Jannetta's concept of microvascular compression at the REZ paved the way for the popular microvascular decompression surgery. The search for less risky, less invasive procedures has paved the way for the various percutaneous procedures and radiosurgery for intractable TN. But all the procedures have their share of complications and recurrence rates. Still, despite several theories and concepts, the exact pathogenesis of TN remains unclear. More research is needed to find the exact pathogenesis of TN and also a minimally invasive procedure without any recurrence of pain for medically intractable TN.

Keywords

controversies in trigeminal neuralgia - pathogenesis of trigeminal neuralgia - treatment of trigeminal neuralgia - trigeminal neuralgia - trigeminal neuralgia classification

Introduction

Neurosurgery, like the other branches of medicine, is full of controversies, both in the concept of disease conditions and the management of these conditions. One such condition is trigeminal neuralgia (TN). There are controversies in the anatomical and topographic concepts, nomenclature, diagnostic criteria, pathogenesis, and management. This review is an attempt to discuss in detail these controversies and provide some clarity on their implications in clinical practice. The various concepts about the anatomy of the trigeminal nerve roots, the various classifications and nomenclature of TN, various concepts on the pathogenesis of TN, and the various treatment modalities for TN with their relative merits and demerits are discussed.

Anatomical Concepts

The sensory root of the trigeminal nerve starts at the gasserian ganglion and ends at the root entry zone (REZ) in the pons. In the middle cranial fossa, the mandibular division (V₃) is represented laterally, and the ophthalmic division (V₁) is represented medially, with the maxillary division (V₂) in between. As it nears the REZ in pons, there are two parts, namely the portio minor (motor root) and the portio major (sensory root). The representation in the portio major is more oblique—the V₁ fibers are superomedial, and the V₃ fibers are inferolateral ([Fig. 1]). According to Dandy and others, at the REZ, there is more of a functional representation in the portio major than anatomical representation. The pain fibers are said to be in the inferolateral part of the portio major, and the touch and proprioceptive fibers are said to be in the superomedial part and also in the accessory fascicles that are said to separate from the sensory root (portio major) and join the motor root (portio minor) a few millimeters from the REZ. This is the basis for Dandy's selective sensory rhizotomy by posterior fossa approach for TN.[1] There have been many, including Frazier, who contest this view and believe that there is only an anatomical representation of various divisions at the trigeminal REZ.[2]

Fig. 1 Schematic diagram showing the relative representation of various sensory divisions of the trigeminal nerve in the middle fossa and at the root entry zone (REZ).

Nomenclature and Classification

Originally, the TN was classified as typical trigeminal neuralgia (the episodic shock-like pain over the distribution of the trigeminal nerve) and atypical facial pain (the continuous low-grade pain with exacerbations of severe pain over the face). Burchiel (2003) classified and named it as Type 1 (typical TN) and Type 2 (atypical) neuralgia.[3] The International Headache Society (IHS) classification classifies TN into Classical trigeminal neuralgia (attributed to neurovascular conflict at the REZ), Secondary trigeminal neuralgia (secondary to multiple sclerosis or tumors, or mass lesions), and Idiopathic trigeminal neuralgia (where there is no demonstrable cause).[4] The American Association of Neurology (2016) classification classifies TN as Possible trigeminal neuralgia, Clinically established trigeminal neuralgia, and Etiologically established trigeminal neuralgia. Still, there is no universally accepted nomenclature or classification of TN, though the IHS classification seems to be finding favor of late. In addition, the Trigeminal autonomic cephalalgias, including cluster headache, Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua, also mimic the TN and complicate matters further.

Pathogenesis

This is the most controversial aspect in TN. There are various theories on the pathogenesis of TN—some theories advocating peripheral origin, some theories advocating problems in the trigeminal REZ, and some advocating central origin.

Theories on the Peripheral Origin

There are several theories supporting the peripheral and dental origin of TN.[5] Some of the theories postulate a narrow osseous canal transmitting the peripheral branches of the trigeminal nerve as the cause for TN. Some studies have demonstrated varying degrees of dystrophy of the peripheral branches in the specimen obtained during peripheral rhizotomy. Trauma, inflammation of the peripheral branches of the trigeminal nerve also have been implicated in the pathogenesis of TN. Most of this literature is from oral and maxillofacial surgery journals.

Theories on the Trigeminal Root Entry Zone Origin

Microvascular Compression

This has been the main area of research. Pioneers like Dandy, during the posterior fossa rhizotomy for TN, found that some patients had structural abnormalities like vascular compression, small mass lesions, vascular malformations, etc., in patients with TN.[6] It was Jannetta who expanded this observation into the concept of microvascular compression (MVC) as the cause of TN.[7] Jannetta postulated that with advancing age blood vessels elongate and the elongated loop of blood vessel compresses the REZ leading to pulsatile compression, which causes hyperactive dysfunction like TN.[8] This concept forms the basis for microvascular decompression (MVD) surgery for TN, which is the most popular surgical procedure among neurosurgeons.

Though the MVC theory is appealing and accepted widely among the neurosurgeons, there are quite a few who contest this theory. Adams has argued against the MVC theory on the following grounds: (1) A good number of patients with TN do not have a neurovascular relationship at the REZ. (2) A good percentage of normal population without TN have neurovascular relationships at the trigeminal REZ. (3) There are many cranial nerves in close relationship with blood vessels normally, but there is no dysfunction of these cranial nerves due to the vascular relationship. (4) The MVC theory does not explain the spontaneous remissions in patients with TN. (5) The veins do not pulsate and cannot cause pulsatile compression of the nerve. (6) There is no motor manifestation in muscles supplied by trigeminal motor root, even with vascular contact. (7) The pain relief due to MVD surgery is because of microtrauma to the nerve during surgical manipulation.[9]

Hardy and Rhoton have found that 60% of trigeminal REZ who did not have TN during life had a vascular relationship during cadaveric dissection.[10] Klun and Prestor found 42 out of 130 (32%) trigeminal REZ studied in cadavers who did not have TN during life had a neurovascular relationship.[11] Ramesh and Premkumar found that 39% of patients who did not have TN during life had a neurovascular relationship, including distortion and grooving in a cadaveric dissection study.[12] Tsutsumi et al have found that 20% of normal individuals had vascular contact in trigeminal REZ in a magnetic resonance imaging (MRI) study.[13] Though MVD has come to stay as the mainstay treatment for TN, the exact pathogenesis of TN and the mechanism of pain relief by MVD surgery still remains unclear and a matter of intense debate.

Demyelination

Love and Coakham showed that there was focal demyelination at the trigeminal REZ by electron microscopic studies in specimens obtained during surgery. They concluded that focal demyelination is the basic pathology in TN patients, both with neurovascular relationship and multiple sclerosis.[14] The loss of myelin, leading to electrical short-circuiting, causes activation of pain fibers, resulting in the symptoms of TN due to ephaptic transmission, as per this theory. Mousavi et al have proposed that TN is primarily a demyelinating disease and should be treated as such.[15]

Ignition Hypothesis

Devor et al proposed the “ignition hypothesis.” They proposed that the partial injury to the trigeminal afferents renders the neurons hyperexcitable. This results in the paroxysmal pain as a result of “synchronized after-discharge activity.”[16] The ignition hypothesis seems to account for the major symptoms of TN and is a more acceptable theory for the pathogenesis of TN.

Theories on the Central Origin

Some authors proposed that TN originated in the brainstem. King proposed the brainstem origin for TN to account for its paroxysms, remissions, and response to antiepileptic medication.[17] There are also many reports which suggest that intrinsic pontine lesions, including infarction, can produce typical TN.[18] Imaging studies, including MRI, have shown changes in the brainstem, corpus callosum, cingulum, corona radiata, and superior longitudinal fasciculus, and also volumetric changes in the primary and secondary somatosensory areas of cerebral cortex in patients with TN. Different patterns of brain activation have been observed in functional MRI of TN patients.[19]

The exact pathogenesis of TN is yet to be fully understood, and the various theories are only conjectural. The role of various biomarkers in TN is being studied, which may throw further light on the pathogenesis and treatment of TN.[20] The advances in deep learning methods for neuroimaging, especially the convolutional neural networks, including U-Net architectures, are able to enable automatic segmentation of the trigeminal nerve and radiomic measurement of the degree of neurovascular compression. These may help to stratify surgery more objectively and also help to differentiate classical and idiopathic TN.[21]

Treatment of Trigeminal Neuralgia

Medical Treatment

Carbamazepine is a very effective first-line drug in the treatment of TN, and the majority of patients respond well to this drug. Oxcarbazepine is also equally effective. For patients who cannot tolerate carbamazepine due to drowsiness or skin reaction, other drugs like phenytoin, topiramate, lamotrigine, pregabalin, gabapentin, etc. Most patients respond well to medications initially. Some patients may require an increased dose of the drugs or the addition of more drugs. Some of them become refractory to medical treatment or develop intolerance to the medicines. These patients would require surgical and other options.

Surgical Treatment

“Whenever any clinical problem is treated with a wide variety of surgical alternatives, it is because one procedure does not provide a uniform benefit for all patients” (Kondziolka and Lunsford).[22] This statement is very apt for TN. Since the exact pathogenesis of TN is still unclear, no procedure can claim to address the root of the problem, and no procedure can claim to guarantee complete freedom from recurrence. Most of the patients respond to medical treatment initially, but many become refractory to medical treatment and seek surgical treatment, or some seek surgical treatment because of intolerance to drugs. Historically, various procedures have been tried for TN—Peripheral neurectomy, Alcohol, Phenol ablation of peripheral nerve/gasserian ganglion, Surgical rhizotomy by middle fossa approach, [Extradural (Frazier's modified Hartley–Krause procedure), Intradural (Horsley)], Posterior fossa rhizotomy (Dandy), Compression–decompression (Taarnhoj), Medullary trigeminal tractotomy (Sjoquist)—to name a few. Most of the above procedures have been given up, barring peripheral neurectomy, which is still practiced by some, and posterior fossa rhizotomy, which is done in cases where there is no neurovascular compression at the REZ.

The procedures used in the present day are listed below.

Open Surgery

• Microvascular decompression

• Endoscopic microvascular decompression

Percutaneous Procedures

• Radiofrequency thermocoagulation

• Percutaneous balloon compression

• Percutaneous retrogasserian glycerol rhizotomy

Radiosurgery

• Gamma knife

• X knife

• Cyberknife

All the procedures mentioned above have their own merits and demerits, which are discussed below.

Microvascular Decompression

MVD is the most common surgical procedure performed by neurosurgeons for intractable TN. Barker et al have published one of the largest series of MVD for TN. This series had 1,185 patients with over 10 years' follow-up. Immediate pain relief was seen in 82% of the patients. About 2% did not have any pain relief. Most recurrences happened within the first 2 years after surgery; 30% of patients had recurrence of TN following MVD, and 11% needed a second surgery. Major complications included deaths (0.2%), brainstem infarct (0.1%), and ipsilateral hearing loss (1.3%).[23] A systematic review of 2,102 cases treated with MVD with up to 10 years' follow-up has shown that 82.9% of patients had immediate pain relief with recurrence of pain in 19.2% and the commonest complication was CSF leak (2.4%); death occurred in 0.1%; facial numbness (2.1%) and hearing impairment (1.1%) were the other major complications.[24] MVD is claimed to treat the exact cause of TN, “non-destructive” to the trigeminal nerve, and is claimed to have the best long-term pain relief. The arguments against MVD are: It is a major surgical procedure with the attendant surgical risk, morbidity, and mortality (which is not acceptable for a benign pain-relief procedure). It is also relatively very costly. There is a risk of other (VII, VIII) cranial nerve dysfunction. MVD also has a recurrence rate, which is marginally better than the other procedures. A good percentage of patients do not have neurovascular contact, and one has to perform a partial sensory rhizotomy in these patients. Though MVD gives good and long-term pain relief, the exact mechanism of pain relief is a matter of intense debate. There is a theory that MVD may give pain relief because of microtrauma to the nerve during surgical manipulation. The other questions asked about the MVD procedure are: How does the Teflon or the other material placed between the vessel and the nerve during surgery hold in position without displacement throughout life? How can the veins, which themselves are compressible, cause pulsatile compression on the nerve? It is also not clear how the normal and complete remyelination occurs at the area of neurovascular contact in the long-term to contribute to the resolution of the pathology. These are the questions to which there are still no convincing answers or explanations. But still, the MVC theory and MVD surgery are very popular and widely accepted among the neurosurgeons.

Endoscopic Microvascular Decompression

With the introduction of the endoscope in neurosurgery, endoscopic microvascular decompression (E-MVD) is becoming more popular. The advantages claimed for E-MVD are better visualization of the entire course of the nerve, better visualization of all the offending vessels, minimal cerebellar retraction, and reduced incidence of complications. A meta-analysis comparing E-MVD and MVD has shown that E-MVD is superior to MVD. There have been fewer perioperative complications, better short-term and long-term pain relief, and better discovery of the offending vessel.[25] Guan et al in a series of 95 cases treated by E-MVD showed that immediate pain relief was seen in 97.9% with recurrence in 3.2% during a follow-up period of 12 to 36 months, and the main complication of facial numbness was seen in 3.2% of patients.[26] The disadvantages of E-MVD are a steep learning curve and a need for an assistant to support the endoscope.

Percutaneous Radiofrequency Thermocoagulation

Radiofrequency thermocoagulation is the most preferred procedure for TN after MVD. Sweet and Wepsic reported one of the early large experiences with percutaneous radiofrequency thermocoagulation (RF lesion). They had 214 patients undergoing RF lesion for TN with a follow-up of up to 6 years. About 91% of the patients had early pain relief. Recurrence rate was 22%. Complications included sensory loss (proportionate to the lesion temperature). Twenty-eight patients had corneal anesthesia. There was no mortality.[27] Wang et al, in a meta-analysis of 54 studies involving 13,410 patients who underwent RF lesion for TN, found initial pain relief in 95% of patients. Recurrence of pain was seen in 15% to 75% of patients at 5 years, and the maximum incidence of recurrence was seen 1 to 2 years after the procedure. Major complications included facial hypoesthesia, dysesthesia, and corneal anesthesia, but these complications have been less frequent in the last decade.[28] The advantages of RF lesion are: It is a percutaneous daycare procedure, has good immediate pain relief, and the selectivity of the division of the sensory root to be lesioned is possible. The major disadvantages are: It requires costly equipment (RF lesion generator), which makes it a costly procedure. RF lesion produces more severe sensory impairment, including corneal anesthesia, which makes it unsuitable for TN involving the ophthalmic (V₁) division.

Percutaneous Balloon Compression

Percutaneous balloon compression (PBC) has been used for TN since 1983 by Mullan. It is also being increasingly used in the present day. Lichtor and Mullan reported their experience with PBC in 100 patients. Immediate success was seen in 97%. Recurrence of pain was seen in 20% at 5 years and 30% at 10 years.[29] Burchiel and Moore in their review reported immediate pain relief in 90% to 100% patients and recurrence varying from 30% to 77%.[30] Du et al, in a series of 68 patients who underwent PBC, showed immediate pain relief in 97% of patients.[31] The advantage of PBC is that since the procedure is done under general anesthesia, patient cooperation is not required. The disadvantages: It requires hospitalization and general anesthesia. Cannulating a 14G needle through the foramen ovale may be difficult, but this has been overcome by modern imaging methods. Masseter weakness is more common with PBC. However, PBC has the highest recurrence rate.

Percutaneous Retrogasserian Glycerol Rhizotomy

Hakanson made the famous serendipitous discovery of the efficacy of glycerol in the treatment of TN during the radiosurgery procedure for TN. Since then, the percutaneous retrogasserian glycerol rhizotomy (PRGR) has come to stay as one of the major options for the treatment of TN.[32] Kondziolka and Lunsford have reported one of the largest experience with PRGR. They reviewed 1,174 patients treated with PRGR and found long-lasting pain relief in 77% of patients, with 55% being pain-free without medications and 22% requiring some medication.[22] Kodeeswaran et al reported 93 patients treated with PRGR and observed that there was immediate pain relief in 96.8% of patients, long-term pain relief in 89.4%, and recurrence of pain in 10.4% of patients.[33] PRGR is a technically simple, cost-effective daycare procedure, without need for any costly equipment and with good long-term pain relief. There is no need for sensory testing during the procedure, and a very small chance of facial sensory loss. It can also be safely repeated in cases of recurrent TN, either after PRGR or other procedures, including MVD. The disadvantages of this procedure are the difficulty in procuring anhydrous glycerol, which is absolutely needed for the best results, and transient dysesthesia over the face. PRGR is being increasingly favored percutaneous procedure for TN.

Radiosurgery

Stereotactic radiosurgery for TN is increasingly being used of late. Leksell introduced the stereotactic radiosurgery for TN in the 1950s.[34] Later, with the advent of Gamma knife, Linear accelerator (LINAC/X knife), and Cyberknife, radiosurgery has become more precise. The principle of radiosurgery is to give a high dose (60–90 Gy) of radiation to the trigeminal sensory root in the anterior cisternal segment or at the REZ. Tuleasca et al have, in a systematic review, analyzed the results of various radiosurgery procedures for TN. This review included 65 studies covering 6,461 patients treated by radiosurgery. This included 5,687 patients treated with gamma knife, 511 treated with LINAC, and 263 treated with Cyberknife. Initial good pain relief was seen in 53% of patients treated by gamma knife, 49% of patients treated by LINAC, and 56% of patients treated by Cyberknife. Recurrence was seen in 24% of patients treated by gamma knife, 32% of patients treated by LINAC, and 26% of patients treated by Cyberknife. Time to pain relief was between 10 and 90 days with the gamma knife and 8.5 to 60 days with LINAC. There is no information on this with Cyberknife. Common complications noted were facial hypoesthesia and dysesthesia.[35] There is no consensus regarding the site of lesion (anterior cisternal segment or REZ) or the dosage of radiation. But most of the studies recommend against a dosage of more than 90 Gy. The advantages of radiosurgery are: It is relatively less invasive and has fewer side effects. The disadvantages are: It takes a long time (from a few days to a few months) for the onset of pain relief, and it is costlier compared with the other procedures. Radiosurgery is available in relatively fewer centers.

The issues in the present-day treatment are: (1) There is no consensus or clear guidelines on the choice of the procedure. (2) None of these procedures can claim complete freedom from recurrence. The research on the choice of the procedure is further impeded by the following factors: (1) Since randomized control studies are not available, there is no level I evidence for the choice of the procedures. (2) No clear-cut diagnostic criteria and baseline assessment are available. (3) Outcome measures are not clearly defined. (4) All complications are not completely reported. (5) There is no independent evaluation of outcomes. “The best treatment option is yet to be defined, and this is related to the lack of definition in the treatment outcomes and outcome measures.”[36] A comparison of the various procedures available based on the systematic reviews and large reported series is given in [Table 1]. The immediate pain relief, recurrence, and complications of the individual procedures are stated. Most of the procedures, except radiosurgery, seem to have good immediate pain relief. Recurrence rate seems to be highly variable—3.2% on 36 months' follow-up for E-MVD, 19.2% on 10 years' follow-up for MVD, 19% for PBC on 40 months' follow-up, 15% to 75% for RF lesion in various series with 5 years' follow-up, 23% for PRGR on 11 years' follow-up, and 24% recurrence for radiosurgery with unspecified duration of follow-up. The common complication of facial numbness seems to be the highest for RF lesion (7–100% in various series) and PBC (97%), moderate for PRGR (10–20%) and radiosurgery (0–17%), and the least for MVD (2%) and E-MVD (3%). All these procedures are found to be highly safe—mortality of 0.1% reported for MVD and none for the other procedures. It is evident that the sample sizes, outcome measures, the technique adopted by various authors for the same procedure, and duration of follow-up are variable, and hence it is difficult to compare the procedures meaningfully. The lack of randomized control trials involving all these procedures reduces the strength of evidence.

Table 1 Comparison of various procedures for trigeminal neuralgia

Name of the procedure	Type of the report	Author & year	No. of cases	Follow-up	Immediate pain relief	Recurrence	Complications
Microvascular decompression (MVD)	Systematic Review	Di Carlo et al. 2023	2102	10 years	82.9%	19.2%	CSF leak 2.4%, Facial numbness 2.1%, Hearing impairment 1.1%, Death 0.1%
Endoscopic MVD	Single large series	Guan et al.2023	95	12-36 months	97.9%	3.2%	Facial numbness 3.2%
Radiofrequency thermocoagulation (RF lesion)	Systematic review	Wang et al. 2022	13410	5 years	95.3%	15 to 75%	Facial hypesthesia (7.1 to 100%), Dysesthesia (0 to 36%), Anesthesia dolorosa (0 to 9.6%)
Percutaneous balloon compression (PBC)	Single large series	Du et al. 2015	68	40 months	97%	19%	Facial numbness (97.1%), masseter weakness (27.9%), paresthesia (10.3%), abducens palsy (1.5%)
Percutaneous retrogasserian glycerol rhizotomy (PRGR)	Single large series	Kondziolka et al. 2005	1174	11 years	90%	23% at 11 years	Mild facial numbness/paresthesia (10 to 20%), Herpes simplex perioralis (12%)
Radiosurgery	Systematic review	Tuleasca et al. 2019	6461	Not specified	Nil (Time to pain relief 10 to 90 days)	24%	Facial hypesthesia and dysesthesia (0 to 17.3%)

Suggestions for Future Research

Since the randomized controlled trial for the treatment of TN is very difficult, a multicenter cooperative study can be undertaken. There must be a strict criterion for quantifying pain using a uniform pain scale. The same technique should be adopted for each of the procedures of TN. The number of cases should be similar for all the procedures. There should be a fixed duration of follow-up. The outcome measures should be standardized. Such a study may throw better light on the relative merits and effectiveness of various procedures for medically intractable TN.

Conclusion

It is seen from the foregoing that there are many controversial aspects in TN. The anatomical arrangements of various sensory nerve fibers close to the trigeminal REZ are not conclusively settled yet. There is no consensus regarding the use of nomenclature, though the IHS classification is currently preferred. The other facial pain syndromes, like SUNCT, SUNA, hemicrania, etc., add to the confusion in the diagnosis of TN. The pathogenesis of TN is yet to be settled. The choice of treatment modality for medically intractable TN is highly controversial. Though the majority of neurosurgeons favor MVD, the percutaneous procedures and radiosurgery are also finding increasing use because of their less invasive nature without major morbidity and mortality. All these procedures involve manipulation/production of lesions at different places along the course of the trigeminal sensory root. Ultimately, it is the patient's own informed choice that shall determine the treatment modality. Though the MVC theory is fascinating, there is a need to look beyond MVC for the pathogenesis of TN. Further research using deep learning methods in neuroimaging and the biomarkers in TN may help to find the exact pathogenesis, and this will provide the key to better treatment for this condition. A multicenter cooperative study with well-defined fixed quantification of pain, a similar number of cases, with fixed duration of follow-up, and standardized outcome measures, may give some clarity on the choice of treatment.

Conflict of Interest

None declared.

• References

• 1 Rand RW. Functional and anatomical localization in the trigeminal root: In support of Dandy. In: Morley TP. ed. Current Controversies in Neurosurgery. WB Saunders; 1976. :pp. 533-538
• 2 Poulos DA. Functional and anatomical localization in the trigeminal root: In support of Frazier. In: Morley TP. ed. Current Controversies in Neurosurgery. WB Saunders; 1976. :pp. 539-545
• 3 Burchiel KJ. A new classification for facial pain. Neurosurgery 2003; 53 (05) 1164-1166
• 4 International Headache Society. Headache Classification Subcommittee of The International Headache Society. The International Classification of Headache Disorders. 3rd edition. Cephalalgia 2018; 38: 1-211
• 5 Dandy WE. Concerning the cause of trigeminal neuralgia. Am J Surg 1934; 24 (02) 447-455
• 6 Sabalys G, Juodzbalys G, Wang HL. Aetiology and pathogenesis of trigeminal neuralgia: A comprehensive review. J Oral Maxillofac Res 2013; 3 (04) e2
• 7 Jannetta PJ. Arterial compression of the trigeminal nerve at the pons in patients with trigeminal neuralgia. J Neurosurg 1967; 26 (01) 159-162
• 8 Jannetta PJ. Neurovascular compression in cranial nerve and systemic disease. Ann Surg 1980; 192 (04) 518-525
• 9 Adams CBT. Microvascular compression: An alternative view and hypothesis. J Neurosurg 1989; 70 (01) 1-12
• 10 Hardy DG, Rhoton Jr AL. Microsurgical relationships of the superior cerebellar artery and the trigeminal nerve. J Neurosurg 1978; 49 (05) 669-678
• 11 Klun B, Prestor B. Microvascular relations of the trigeminal nerve: An anatomical study. Neurosurgery 1986; 19 (04) 535-539
• 12 Ramesh VG, Premkumar G. An anatomical study of the neurovascular relationships at the trigeminal root entry zone. J Clin Neurosci 2009; 16 (07) 934-936
• 13 Tsutsumi S, Ono H, Yasumoto Y, Ishii H. The trigeminal root: An anatomical study using magnetic resonance imaging. Surg Radiol Anat 2018; 40 (12) 1397-1403
• 14 Love S, Coakham HB. Trigeminal neuralgia: Pathology and pathogenesis. Brain 2001; 124 (Pt 12): 2347-2360
• 15 Mousavi SH, Lindsey JW, Westlund KN, Alles SRA. Trigeminal neuralgia as a primary demyelinating disease: Potential multimodal evidence and remaining controversies. J Pain 2024; 25 (02) 302-311
• 16 Devor M, Amir R, Rappaport ZH. Pathophysiology of trigeminal neuralgia: the ignition hypothesis. Clin J Pain 2002; 18 (01) 4-13
• 17 King RB. Evidence for a central etiology of tic douloureux. J Neurosurg 1967; 26 (01) 175-180
• 18 Peker S, Akansel G, Sun I, Pamir NM. Trigeminal neuralgia due to pontine infarction. Headache 2004; 44 (10) 1043-1045
• 19 Gambeta E, Chichorro JG, Zamponi GW. Trigeminal neuralgia: An overview from pathophysiology to pharmacological treatments. Mol Pain 2020; 16: 1744806920901890
• 20 Doshi TL, Nixdorf DR, Campbell CM, Raja SN. Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain. Can J Pain 2020; 4 (01) 1-18
• 21 Abikenari M, Jain B, Xu R. et al. Bridging imaging and molecular biomarkers in trigeminal neuralgia: Toward precision diagnosis and prognostication in neuropathic pain. Med Res Arch 2025; 13 (05) 1-11
• 22 Kondziolka D, Lunsford LD. Percutaneous retrogasserian glycerol rhizotomy for trigeminal neuralgia: Technique and expectations. Neurosurg Focus 2005; 18 (05) E7
• 23 Barker II FG, Jannetta PJ, Bissonette DJ, Larkins MV, Jho HD. The long-term outcome of microvascular decompression for trigeminal neuralgia. N Engl J Med 1996; 334 (17) 1077-1083
• 24 Di Carlo DT, Benedetto N, Perrini P. Clinical outcome after microvascular decompression for trigeminal neuralgia: A systematic review and meta-analysis. Neurosurg Rev 2022; 46 (01) 8
• 25 Zagzoog N, Attar A, Takroni R, Alotaibi MB, Reddy K. Endoscopic versus open microvascular decompression for trigeminal neuralgia: A systematic review and comparative meta-analysis. J Neurosurg 2018; 131 (05) 1532-1540
• 26 Guan H, Li S, Wang X. Fully endoscopic microvascular decompression for trigeminal neuralgia: Technical note and early outcomes. Neurosurg Rev 2023; 46 (01) 292
• 27 Sweet WH, Wepsic JG. Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers. 1. Trigeminal neuralgia. J Neurosurg 1974; 40 (02) 143-156
• 28 Wang Z, Wang Z, Li K, Su X, Du C, Tian Y. Radiofrequency thermocoagulation for the treatment of trigeminal neuralgia. Exp Ther Med 2022; 23 (01) 17
• 29 Lichtor T, Mullan JF. A 10-year follow-up review of percutaneous microcompression of the trigeminal ganglion. J Neurosurg 1990; 72 (01) 49-54
• 30 Burchiel KJ, Moore KL. Neurosurgical treatment of pain: Trigeminal neuralgia. In: Swash M. ed. Outcomes in Neurological and Neurosurgical Disorders. Cambridge University Press; 1998. :pp. 507-532
• 31 Du YF, Gu Q, Yang DB. et al. Percutaneous balloon compression for primary trigeminal neuralgia in patients older than 80 years. Chin Neurosurg J 2015; 1: 8
• 32 Håkanson S. Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 1981; 9 (06) 638-646
• 33 Kodeeswaran M, Ramesh VG, Saravanan N, Udesh R. Percutaneous retrogasserian glycerol rhizotomy for trigeminal neuralgia: A simple, safe, cost-effective procedure. Neurol India 2015; 63 (06) 889-894
• 34 Tuleasca C, Régis J, Sahgal A. et al. Stereotactic radiosurgery for trigeminal neuralgia: a systematic review. J Neurosurg 2019; 130 (03) 733-757
• 35 Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951; 102 (04) 316-319
• 36 Nova CV, Zakrzewska JM, Baker SR, Riordain RN. Treatment outcomes in trigeminal neuralgia-a systematic review of domains, dimensions and measures. World Neurosurg X 2020; 6: 100070

Publikationsverlauf

Artikel online veröffentlicht:
05. Januar 2026