INTRODUCTION
Trigeminal neuralgia (TN) is a chronic pain disorder characterized by sudden, intense, electric shock-like facial pain originating from the trigeminal nerve [1]. Although medical treatment with anticonvulsants remains the first-line approach, many patients become refractory due to inadequate pain relief or side effects. Surgical interventions, particularly microvascular decompression (MVD), are considered the definitive treatment for classic TN, as they directly address neurovascular conflicts [2]. Despite the effectiveness of MVD, approximately 10% of patients experience recurrent pain, presenting significant clinical challenges [3].
When surgical outcomes are unsatisfactory or pain recurs postoperatively, treatment alternatives become limited. Gamma Knife radiosurgery (GKS) has emerged as a minimally invasive, safe, and effective option for managing TN. However, concerns about potentially negative outcomes with GKS in postoperative patients remain.
This study aims to evaluate the effectiveness of GKS in patients experiencing recurrent or persistent TN following MVD. Additionally, we seek to identify clinical and imaging-based factors that may help optimize patient outcomes.
MATERIALS AND METHODS
Between May 2010 and May 2025, a prospective cohort of 17 patients diagnosed with medically refractory TN was enrolled at our center. All participants had previously undergone MVD but subsequently experienced recurrent or residual pain despite adequate pharmacological management and nerve block procedures. GKS was performed as a secondary treatment in these cases.
Demographic and clinical data collected included patient age, sex, and the time interval between MVD and subsequent GKS. The patient cohort consisted of 5 males and 12 females, with a mean age of 62.8 years (range, 39-88 years). The average interval between initial MVD and the subsequent GKS procedure was 48.1±74.1 months.
The patients underwent magnetic resonance imaging (MRI) without Leksell stereotactic instrument. Imaging for Gamma Knife treatment planning included T2-weighted, T1-weighted, contrast-enhanced T1-weighted, T2 VISTA (Volume ISotropic Turbo spin echo Acquisition; Philips Healthcare), and T2 proton density (PD) sequences. We used the Leksell GammaPlan system 10.1 (Elekta AB) until May 2024; thereafter, we used the Leksell GammaPlan system 11.1 (Elekta AB).
In GKS, the anterior segment of the trigeminal nerve (retrogasserian portion) was preferentially targeted to minimize radiation exposure to the brainstem. However, in cases where imaging demonstrated Teflon adhesions or adjacent vascular structures within the intended irradiation field, the treatment focus was adjusted to irradiate only the segment in which the trigeminal nerve was clearly delineated.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board (IRB) of Kyung Hee Medical Center (approval number KMC IRB 1511-14) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent for publication was obtained from each patient participated in the study.
RESULTS
The outcomes of GKS treatment following MVD for recurrent or residual TN are summarized in Table 1.
The mean duration between MVD and GKS was 48.1 months, ranging widely from 4 to 303 months. Follow-up periods after GKS averaged 24.4 months (range, 2-83 months). Pain outcomes were assessed using the Barrow Neurological Institute (BNI) pain scale. All patients presented with severe pain prior to GKS, corresponding to a BNI score of V (severe pain/no pain relief).
The final pain outcomes revealed varied results: four patients (23.5%) achieved a BNI score of II (occasional pain, not requiring medication), seven patients (41.2%) achieved IIIa (no pain with continued medication), four patients (23.5%) had IIIb (some pain controlled with medication), and two patients (11.8%) reported a score of IV (some pain, not adequately controlled). Good outcome (BNI I-IIIb) was 88.2%. Most patients experienced a latent period before perceiving significant pain relief. In the majority of cases, noticeable improvement in pain symptoms began approximately 6 months following GKS (Fig. 1).
Following GKS, potential adverse effects, including hypoesthesia, dysesthesia, allodynia, and diminished corneal reflex, were monitored through outpatient follow-up evaluations. In the present study, no GKS-related complications were observed, except for mild sensory deficits in two patients.
The maximal radiation dose administered ranged from 80 to 88 Gy, with an average maximal dose of approximately 85.9 Gy. Target selection for radiosurgical treatment was not based on predefined anatomical zones such as the anterior portion of the nerve or the root entry zone (REZ). Instead, treatment planning was individualized using each patient’s postoperative imaging. The final target was selected by evaluating the location of the Teflon implant and surrounding vasculature, prioritizing regions with the lowest risk of complications (Fig. 2).
DISCUSSION
Recurrent TN following MVD presents a considerable clinical challenge, often necessitating alternative treatment strategies. Various studies have attributed recurrence to factors such as incomplete decompression, migration or displacement of the interposing material (e.g., Teflon) at the neurovascular interface, and granulomatous tissue formation [4]. Sun et al. [5] and Chen et al. [6] both identified Teflon granulomas in over half of patients with recurrent TN post-MVD, often accompanied by arachnoid adhesions at the surgical site. These structural changes may hinder the effectiveness of subsequent radiosurgical intervention.
GKS has emerged as a valuable salvage treatment for recurrent TN after MVD. Despite concerns that prior surgical intervention might reduce the efficacy of GKS, several studies demonstrate that outcomes in recurrent cases can approach those of primary (de novo) TN. For example, Huang et al. [7] reported a long-term pain control rate of approximately 65% with a median follow-up of 5 years, finding no significant difference in outcomes between patients who underwent primary versus salvage GKS. Similarly, Kano et al. [8] observed initial pain relief in approximately 85% of post-MVD patients treated with GKS, with durable pain control maintained in 54-66% of cases at 3 to 5 years. These rates closely parallel outcomes reported in patients without prior surgical treatment.
However, nuanced differences have been observed. Tuleasca et al. [9] and Wang et al. [10] reported that patients with a history of MVD had significantly lower rates of complete initial pain relief following GKS compared to those with no surgical history. This discrepancy may be due to anatomical and structural changes from the previous surgery, such as adhesions or granulomas, which could impact the radiation dose distribution or target accuracy.
Despite these considerations, the safety profile of GKS in patients with prior MVD remains favorable. The incidence of new trigeminal sensory disturbances, such as mild facial numbness, ranges from 5% to 15%, which is comparable to that seen in primary GKS treatments [9,10]. Notably, such sensory changes have been associated with better pain control outcomes, a phenomenon well-documented in TN radiosurgery literature [8]. Importantly, prior MVD does not appear to significantly increase the risk of serious adverse effects from GKS.
Target selection and imaging are critical components in the successful application of GKS for TN, particularly in patients who have previously undergone MVD. In these cases, anatomical distortion from prior surgery—such as scar tissue formation, adhesions, displacement of the nerve, and the presence of Teflon implants—can present significant challenges in identifying and accurately targeting the trigeminal nerve during radiosurgical planning.
Following MVD, structural changes are commonly observed. Reoperation studies have consistently reported the presence of dense arachnoid adhesions, Teflon granulomas, and fibrosis at the surgical site [5,6]. These post-surgical changes can distort the typical curvature and position of the trigeminal nerve, alter cerebrospinal fluid (CSF) separation from surrounding tissue, and obscure the REZ, which is typically the preferred target for radiosurgery. In some instances, a “piston effect” has been described, in which pulsations from surrounding arteries are transmitted directly to the nerve due to scar tethering, leading to dynamic nerve deformation that further complicates targeting [11]. Additionally, implanted foreign material and scar tissue can introduce signal artifacts on MRI, making visualization even more difficult.
In this context, conventional MRI sequences such as standard T1- or T2-weighted images may not provide adequate resolution to differentiate the nerve from surrounding postoperative changes. Therefore, advanced imaging techniques have become increasingly essential for precise GKS planning in the post-MVD setting. High-resolution three-dimensional (3D) T2-weighted sequences, such as FIESTA (Fast Imaging Employing Steady-state Acquisition; GE Healthcare) or CISS (Constructive Interference in Steady State; Siemens Healthineers), allow for fine anatomical delineation of the cisternal portion of the trigeminal nerve [12,13]. These sequences improve contrast between the nerve and CSF or scar tissue, which is particularly valuable when normal anatomical landmarks are disrupted.
PD-weighted MRI has also shown exceptional utility in cranial nerve imaging. PD sequences suppress CSF signal more effectively than T2-weighted sequences, thereby enhancing visualization of neural structures against the background of CSF [14]. This is particularly advantageous in post-MVD cases where the nerve may be compressed, atrophic, or surrounded by fibrosis. In such scenarios, PD imaging can help identify remaining nerve segments or subtle gaps between adhesions suitable for radiosurgical targeting.
Furthermore, multiplanar image reconstruction and fusion of high-resolution MRI with planning computed tomography are essential to refine the isocenter placement and avoid mistargeting, such as irradiation of the brainstem or surrounding non-target tissues. In some cases, shifting the target zone slightly distal to the typical REZ may be warranted due to anatomical displacement.
Kondziolka et al. [15] emphasized the necessity of accurate dose delivery and meticulous target localization in optimizing GKS outcomes. Because the therapeutic mechanism of radiosurgery involves focal demyelination of the nerve, precise identification and targeting of the lesion site are essential to achieve effective pain relief while minimizing complications.
Beyond structural MRI, emerging functional imaging techniques such as diffusion tensor imaging and fiber tractography offer the potential to quantify trigeminal nerve integrity and microstructural damage [16]. preliminary studies have shown that changes in fractional anisotropy and mean diffusivity measured a few months after GKS correlate with pain outcomes. These tools may eventually contribute not only to improved targeting but also to prognostication and personalized treatment planning.
CONCLUSION
GKS is a safe and effective salvage treatment for patients with recurrent or residual TN following MVD. In our cohort, 88.2% of patients experienced favorable outcomes (BNI grade I-IIIb), demonstrating the therapeutic value of GKS even in the setting of prior surgery.
Although anatomical changes such as adhesions and nerve displacement may complicate targeting, these challenges can be addressed with high-resolution imaging techniques, including 3D T2-weighted and PD-weighted MRI. With meticulous planning and individualized imaging guidance, GKS remains a highly viable and minimally invasive option in the management of refractory TN.
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