Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? a prospective double-blind, randomized study

doi:10.1016/S0360-3016(01)01606-6

International Journal of Radiation OncologyBiologyPhysics

Volume 51, Issue 2, 1 October 2001, Pages 449-454

https://doi.org/10.1016/S0360-3016(01)01606-6 Get rights and content

Abstract

$Purpose:$ To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief.

$Methods and Materials:$ Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1–36).

$Results:$ Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% ± 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018).

$Conclusions:$ Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.

Introduction

Patients with trigeminal neuralgia (tic douloureux) have severe episodic facial pain. Trigeminal neuralgia most commonly is caused by vascular compression of the trigeminal nerve, but occasionally is associated with skull base tumors or multiple sclerosis 1, 2, 3, 4. The initial management of tic pain consists of medical therapy, such as carbamazepine, phenytoin, gabapentin, or baclofen (2). When medical therapy is ineffective or causes intolerable side effects, surgical intervention becomes necessary. Surgical options include decompression of the affected nerve (retromastoid craniectomy with microvascular decompression of the trigeminal nerve) and various percutaneous rhizotomies of the trigeminal nerve using heat, mechanical compression, radiation, or osmotic injury to interrupt the pain transmission 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23. Microvascular decompression entails higher operative risks, and trigeminal rhizotomy procedures are associated with deafferentation of the face (2). Although microvascular decompression is a potentially curative procedure for eligible healthy patients, many patients with tic douloureux are elderly or have medical contraindications to invasive surgery (2). Approximately 30% of patients who undergo initial microvascular decompression eventually have a relapse 1, 2. Retrogasserian radiosurgical rhizotomy is a relatively noninvasive and safe procedure that is suitable for patients with and without a history of prior surgery 3, 12, 15, 16, 17.

Radiosurgery to alleviate trigeminal neuralgia was first advocated in 1951 24, 25. Recent experience indicates that after retrogasserian radiosurgery (maximal dose 70–80 Gy with 4-mm diameter collimators), 58–70% of trigeminal neuralgia patients will eventually obtain complete relief from their pain 15, 17.

Studies of patients with trigeminal nerve injury after radiosurgery to adjacent tumor correlated the risk of radiation injury to the length of exposed cranial nerve 26, 27. A recent baboon study demonstrated that retrogasserian radiosurgery produces a rhizotomy effect with partial axonal degeneration of the trigeminal nerve. The present study tested the hypothesis that extending the radiosurgery treatment volume to include a longer segment of the retrogasserian trigeminal nerve would improve the relief from trigeminal neuralgia. We also considered that with the improved pain control, radiosurgery to a longer length of the affected trigeminal nerve might be accompanied by a modest increase in the risk of developing new or increased trigeminal dysfunction (numbness or paresthesias).

Section snippets

Study design and randomization

In designing this study, we hypothesized that including a longer length of the trigeminal nerve within the radiosurgery treatment volume would increase the proportion of trigeminal neuralgia patients with complete pain relief from approximately 61% with one isocenter to 86% with two isocenters. Power calculations indicated that a total of 90 trigeminal neuralgia patients should be randomized for an 80% chance (power = 0.80) of demonstrating this degree of improvement with a 95% significance

Pain relief

Complete pain relief was achieved in 57 patients (12 with low-dose and 45 without medication). The median time for complete pain relief was 3 months after radiosurgery (range 1 week to 17 months). Pain improved partially in 15 patients, and 15 other patients had no benefit. The actuarial rate of obtaining complete pain relief (with or without low-dose medication) was 67.7% ± 5.1%. As shown in Table 2, the proportions achieving different categories of pain relief were essentially identical for

Discussion

We designed this study to help define the optimum nerve length that should be enclosed within the radiosurgery treatment volume for trigeminal neuralgia. Previously published experience with trigeminal neuralgia radiosurgery, other than single-isocenter treatment with 4-mm diameter collimators, is limited and certainly inadequate to address this question 3, 12, 13, 15, 16, 17, 18, 19. Trigeminal neuralgia is categorized by periods of spontaneous partial or complete remission in some patients.

Acknowledgements

The following individuals also contributed to this study: Michael Habeck, P.A.-C., Ann Maitz, M.S., Deborah A. Gorman, R.N., Satoshi Maesawa, M.D., and Charlene Baker.

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La radiochirurgie pour le traitement de la névralgie du trijumeau délivre une très forte dose en une seule séance, sur quelques millimètres, au niveau d’un isocentre unique placé le long du nerf. Nous présentons ici les différentes étapes qui ont été réalisées pour valider des petits faisceaux par collimateurs coniques, et rapportons les résultats cliniques des premiers patients pris en charge sur Novalis Tx® sans cadre invasif.
Nous avons d’abord été évalué l’exactitude géométrique des collimateurs coniques de 4 et 6 mm à l’aide de tests de Winston-Lutz ; puis l’acquisition des données dosimétriques a été réalisée grâce à des détecteurs de haute résolution spatiale (microdiamant PTW 60019 et une diode E PTW 60017). Les facteurs correctifs du rapport TRS n^o 483 ont été appliqués pour le calcul des facteurs d’ouverture du collimateur. Ces données dosimétriques ont ensuite été comparées avec les données implémentées dans le système de planification de traitement iPlan®. Puis des tests end-to-end ont permis de contrôler l’ensemble du processus de traitement à l’aide d’un fantôme anthropomorphique stereotactic end-to-end verification. Entre 2020 et 2022, 18 patients ont été traités pour névralgie trigéminale réfractaire sur Novalis Tx® sans cadre invasif avec repositionnement par Exactrac®. Dix-sept patients ont été évalués (un a été perdu de vue) à l’aide du score du Barrow Neurological Institute pour l’évaluation de la douleur, et par IRM avec un suivi médian de 12 mois.
Les critères de qualité d’exactitude géométrique et dosimétriques ont été atteints pour le cône de 6 mm mais pas pour le cône de 4 mm. Tous les patients ont été traités avec un cône de 6 mm avec une dose de 90 Gy prescrite à l’isocentre ciblée au niveau de la root entry zone. Le contrôle initial de la douleur a été obtenu chez 70,5 % de nos patients, et 53 % ont conservé ce contrôle avec un suivi médian de 12 mois. Toutes les récidives sont survenues dans un délai de 3 à 6 mois après la radiochirurgie. Aucune toxicité n’a été observée sur le tronc cérébral. Trois patients ont eu une hypoesthésie faciale non invalidante.
Le traitement des névralgies trigéminales sur accélérateur linéaire dédié est un traitement de haute technicité dont l’exactitude et la sécurité est primordiale. Les mesures physiques ont permis la mise en service de la technique avec un cône de 6 mm. Nos premiers résultats cliniques sont conformes aux données de la littérature.
Radiosurgery for the treatment of trigeminal neuralgia delivers a very high dose in a single fraction, over a few millimeters, at a single isocenter placed along the nerve. We present here the different steps that have been performed to validate small beams by conical collimators, and report the clinical results of the first patients treated on Novalis Tx®, frameless.
First, the geometric accuracy of 4 and 6 mm conical collimators was evaluated using Winston-Lutz tests; then dosimetric data acquisition was performed using high spatial resolution detectors (PTW 60019 microdiamond and a PTW 60017 E-diode). The corrective factors of the TRS 483 report were applied to calculate the collimator aperture factors. These dosimetric data were then compared with the data implemented in the iPlan® treatment planning system. Then end-to-end tests were performed to control the entire treatment process using an anthropomorphic phantom “STEEV”. Between 2020 and 2022, 18 patients were treated for refractory trigeminal neuralgia on Novalis Tx®, frameless, with Exactrac® repositioning. A total of 17 patients were evaluated (one was lost to follow-up) using the BNI score for pain assessment and MRI with a median follow-up of 12 months.
The quality criteria of geometric and dosimetric accuracy were met for the 6-mm cone but not for the 4-mm cone. All patients were treated with a 6-mm cone with a dose of 90 Gy prescribed at the isocenter at the root entry zone. Initial pain control was obtained in 70.5% of our patients, and 53% maintained pain control with a median follow-up of 12 months. All recurrences occurred within 3 to 6 months after radiosurgery. No brainstem toxicity was observed. Six patients had non-disabling facial hypoesthesia, half of whom already had pretreatment hypoesthesia.
The treatment of trigeminal neuralgia on a dedicated linear accelerator is a highly technical treatment whose accuracy and safety are paramount. The physical measurements allowed the commissioning of the technique with a 6 mm cone. Our first clinical results are in accordance with the literature.
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Spontaneous Trigeminal Neuralgia is a painful condition of the face which may require interventional treatment if medicines fail to control the pain. These include microvascular decompression (MVD) and GKNS. The former is moderately more effective but GKNS has become accepted both as an alternative to MVD or as an adjunct. Like all treatments of the condition, it is successful in a majority of patients but by no means all. Repeat treatments are possible.
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Citation Excerpt :
However, Weller et al.8 and Helis et al.11 found that the 39% and the 26% of patients included in their studies, respectively, experienced post-GKRS facial sensory disturbances, including 3 cases of bothersome numbness and 3 cases of ipsilateral corneal anesthesia. This high rate of facial numbness was related to the use of greater doses and from targeting the root entry zone early in the series, which is a known factor for increasing sensory disturbances based on studies of GKRS for idiopathic TN.26,27 In a similar way, Huang et al.22 found that by targeting the root entry zone with high doses, 4 of 7 patients with MS developed facial numbness.
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Clinical investigation: benign diseaseDoes increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? a prospective double-blind, randomized study

Abstract

Introduction

Section snippets

Study design and randomization

Pain relief

Discussion

Acknowledgements

Neurosurg Clin North Am

Radiother Oncol

The long-term outcome of microvascular decompression for trigeminal neuralgia

N Engl J Med

Choice of surgical therapeutic modalities for treatment of trigeminal neuralgiaMicrovascular decompression, percutaneous retrogasserian thermal, or glycerol rhizotomy

Clin Neurosurg

Gamma knife radiosurgery for treatment of trigeminal neuralgiaIdiopathic and tumor related

Neurology

Stereotactic radiosurgery for tumor related trigeminal pain

Neurosurgery

Long-term results of percutaneous retrogasserian thermorhizotomy for “essential” trigeminal neuralgiaConsiderations in 1000 consecutive patients

Neurosurgery

Percutaneous trigeminal nerve compression for treatment of trigeminal neuralgiaResults in 50 patients

Neurosurgery

Treatment of trigeminal neuralgia by thermocoagulation, glycerorhization, and percutaneous compression of the gasserian ganglion and/or retrogasserian rootletsLong-term results and therapeutic protocol

Neurosurgery

Percutaneous retrogasserian glycerol injection in the management of trigeminal neuralgiaLong-term follow-up results

J Neurosurg

Trigeminal neuralgia treated by injection of glycerol into trigeminal cistern

Neurosurgery

Functional radiosurgery

Neurosurgery

Stereotactic radiosurgery for trigeminal neuralgiaA multiinstitutional study using gamma knife unit

J Neurosurg

Gamma knife radiosurgery as the first surgery for trigeminal neuralgia

Stereotact Funct Neurosurg

Histological effects of trigeminal nerve radiosurgery in a primate modelImplications for trigeminal neuralgia radiosurgery

Neurosurgery

Clinical investigation: benign disease
Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? a prospective double-blind, randomized study