CyberKnife radiosurgery for trigeminal neuralgia: a retrospective review of 168 cases

Albert GuillemetteCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM);

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Sami HeymannCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM);
Service of Neurosurgery, Centre Hospitalier de l’Université de Montréal (CHUM); and

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David RobergeCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM);
Department of Radiation Oncology, Centre Hospitalier de l’Université de Montréal (CHUM);

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Cynthia MénardCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM);
Department of Radiation Oncology, Centre Hospitalier de l’Université de Montréal (CHUM);

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Marie-Pierre Fournier-GosselinCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM);
Service of Neurosurgery, Centre Hospitalier de l’Université de Montréal (CHUM); and
Department of Surgery, Université de Montréal (UdeM), Montréal, Québec, Canada

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OBJECTIVE

Gamma Knife radiosurgery is recognized as an efficient intervention for the treatment of refractory trigeminal neuralgia (TN). The CyberKnife, a more recent frameless and nonisocentric radiosurgery alternative, has not been studied as extensively for this condition. This study aims to evaluate the clinical outcomes of a first CyberKnife radiosurgery (CKRS) treatment in patients with medically refractory TN.

METHODS

A retrospective cohort study of 166 patients (168 procedures) with refractory TN treated from 2009 to 2021 at the Centre Hospitalier de l’Université de Montréal was conducted. The treatment was performed using a CyberKnife (model G4, VSI, or M6). The treatment median maximum dose was 80 (range 70.0–88.9) Gy.

RESULTS

Adequate pain relief, evaluated using Barrow Neurological Institute pain scale scores (I–IIIb), was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 (range 0–202) days. The median duration of pain relief for cases with a recurrence of pain was 8.3 (range 0.6–85.0) months. The actuarial rates of maintaining adequate pain relief at 12, 36, and 60 months from the treatment date were 77.0%, 62.5%, and 50.2%, respectively. There was new onset or aggravation of facial numbness in 44 cases (26.2%). This facial numbness was predictive of better maintenance of pain relief (p < 0.001). The maintenance of adequate pain relief was sustained longer in idiopathic cases compared with cases associated with multiple sclerosis (MS; p < 0.001).

CONCLUSIONS

In the authors’ experience, CKRS for refractory TN is efficient and safe. The onset or aggravation of facial hypoesthesia after treatment was predictive of a more sustained pain relief, and idiopathic cases had more sustained pain relief in comparison with MS-related cases.

ABBREVIATIONS

BNI = Barrow Neurological Institute; CHUM = Centre Hospitalier de l’Université de Montréal; CKRS = CyberKnife radiosurgery; GKRS = Gamma Knife radiosurgery; MPRAGE = magnetization-prepared rapid gradient echo; MS = multiple sclerosis; MVD = microvascular decompression; PR = percutaneous rhizotomy; SRS = stereotactic radiosurgery; TMJ = temporomandibular joint; TN = trigeminal neuralgia; TN1 = TN type 1; TN2 = TN type 2.

OBJECTIVE

Gamma Knife radiosurgery is recognized as an efficient intervention for the treatment of refractory trigeminal neuralgia (TN). The CyberKnife, a more recent frameless and nonisocentric radiosurgery alternative, has not been studied as extensively for this condition. This study aims to evaluate the clinical outcomes of a first CyberKnife radiosurgery (CKRS) treatment in patients with medically refractory TN.

METHODS

A retrospective cohort study of 166 patients (168 procedures) with refractory TN treated from 2009 to 2021 at the Centre Hospitalier de l’Université de Montréal was conducted. The treatment was performed using a CyberKnife (model G4, VSI, or M6). The treatment median maximum dose was 80 (range 70.0–88.9) Gy.

RESULTS

Adequate pain relief, evaluated using Barrow Neurological Institute pain scale scores (I–IIIb), was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 (range 0–202) days. The median duration of pain relief for cases with a recurrence of pain was 8.3 (range 0.6–85.0) months. The actuarial rates of maintaining adequate pain relief at 12, 36, and 60 months from the treatment date were 77.0%, 62.5%, and 50.2%, respectively. There was new onset or aggravation of facial numbness in 44 cases (26.2%). This facial numbness was predictive of better maintenance of pain relief (p < 0.001). The maintenance of adequate pain relief was sustained longer in idiopathic cases compared with cases associated with multiple sclerosis (MS; p < 0.001).

CONCLUSIONS

In the authors’ experience, CKRS for refractory TN is efficient and safe. The onset or aggravation of facial hypoesthesia after treatment was predictive of a more sustained pain relief, and idiopathic cases had more sustained pain relief in comparison with MS-related cases.

Trigeminal neuralgia (TN), originally referred to as "tic douloureux," is a highly debilitating facial pain that has a considerable negative impact on patient quality of life. TN is the most common type of neuralgia, with an incidence between 12.6 and 28.9 per 100,000 people.1 There are multiple possible etiologies for TN, such as high-grade neurovascular compression at the root entry zone, tumor compression, trauma, lacunar infarctions, and pontine demyelination in multiple sclerosis (MS), but in most cases the cause is idiopathic.2 There are two main clinical presentations of idiopathic TN. TN type 1 (TN1) is the most common form and is described as paroxysmal, intense, unilateral, electric-like facial pain. The pain occurs in one or more of the three branches of cranial nerve V. The electric shock can be triggered by eating or talking, and by innocuous stimuli such as shaving, tooth brushing, and receiving a light touch in a trigger zone innervated by the trigeminal nerve. The second type of presentation, TN type 2 (TN2), is described as a constant, aching, throbbing, and burning facial pain.3 TN is a condition that has a huge negative impact on the quality of life of patients, and in severe refractory cases, can lead to undernourishment, severe dehydration, and psychiatric disorders such as depression and anxiety.46 Patients experiencing TN require medical attention and specialized care.

The first therapeutic line of treatment is pharmacological, using antiepileptic drugs such as carbamazepine. In patients for whom the pharmacological approach is not effective or those with too many side effects from the medication, invasive approaches may be indicated. These approaches include percutaneous rhizotomy (PR; balloon compression, radiofrequency thermocoagulation, and glycerol lesioning), microvascular decompression (MVD), and stereotactic radiosurgery (SRS).7

Among the nonpharmaceutical approaches, SRS is frequently offered to elderly patients with medical comorbidities because it is the least invasive compared with the other approaches. It is also indicated for patients with MS or when another surgical treatment has failed.8 SRS can be delivered by various modalities: using a device delivering a spherical (or near-spherical) "shot" (devices with multiple cobalt sources [Gamma Knife, Elekta] or isocentric linear accelerators), or with a nonisocentric linear accelerator delivering a customized nonspherical dose distribution (CyberKnife, Accuray Inc.).9 The majority of clinical experience regarding SRS for TN treatment is based on Gamma Knife radiosurgery (GKRS).10 The principal aim of this study is to evaluate nonisocentric SRS using the CyberKnife radiosurgery (CKRS) system as a first radiosurgical treatment for patients with TN at our institution (Centre Hospitalier de l’Université de Montréal [CHUM]).

Several large GKRS studies for the treatment of TN have been published and they support the efficacy and safety of GKRS at different postintervention periods.1113 The most common complication after the intervention is the onset of facial hypoesthesia. There are positive predictors for the initial freedom from pain response and for pain relief maintenance, such as an onset of new facial numbness, no past surgery, higher age at first radiosurgery, and typical pain presentation. Negative predictors also exist, such as an MS etiology, prior surgery, atypical pain components, and diabetes mellitus.10 Evidence supporting the use of CKRS for TN is limited in comparison to the available evidence for GKRS. Table 1 summarizes the clinical outcomes of selected GKRS and CKRS studies of interest.

TABLE 1.

Clinical outcomes of interest in select GKRS and CKRS studies

Authors & YearNo. of PtsPain ReliefHypoesthesiaPredictive Factors
Better OutcomeWorse Outcome
GKRS
 Kondziolka et al., 20101250380%, 71%, & 46%*10.5%Atypical symptoms, no new sensory disturbance, ≥3 prior surgeries, age <65 yrs
 Régis et al., 20161149792.1%, 84.2%, & 79.7%*14.5%Onset of post-GKRS hypoesthesia≥3 prior surgeries
 Verheul et al., 201017450Idiopathic: 75%, 60%, & 58%; MS: 56%, 30%, & 20%*35.5%Idiopathic etiologyMS etiology
 Marshall et al., 20121344840% had a relapse at a median of 4.2 yrs27%Onset of post-GKRS hypoesthesiaLonger cisternal nerve length, prior RFA, diabetes mellitus
CKRS
 Romanelli et al., 20191549692% at 12 mos & 76% at 36 mos20.1%
 Conti et al., 20201626290.9%, 81.4%, & 71.2%*18%Nerve vol ≥30 mm3MS etiology, low integral dose, higher mean dose

Pts = patients; RFA = radiofrequency ablation.

Actuarial rates of adequate pain relief at 12, 36, and 60 months.

The aims of this present retrospective study are to 1) evaluate the efficacy of CKRS on pain relief, 2) evaluate the safety of CKRS, 3) identify potential predictive factors for the efficacy of CKRS, and 4) compare the efficacy of CKRS between idiopathic and MS-related cases.

Methods

Patient Selection

The approval of our institutional (CR-CHUM) ethics review committee for the study was obtained prior to the beginning of this retrospective investigation. The inclusion criteria were a diagnosis of medically refractory TN and adequate patient demographics, treatment parameters, and clinical follow-up data. Patients who were previously treated with SRS on the same side as their first treatment at our institution were excluded. Additionally, repeat CKRS treatments were not analyzed in this study. In total, 198 patient charts were reviewed, but only 166 patients met the inclusion criteria.

Patients were treated with CKRS as a frameless alternative to GKRS at CHUM from 2009 to 2021. Because some patients were treated bilaterally, 168 total cases met the inclusion criteria and were treated at our institution during these 12 years.

Case Characteristics

Table 2 presents case characteristics. Of the 168 cases, 60 (35.7%) were male and 108 (64.3%) were female. The median age at first CKRS was 68.5 (range 23–90) years. The pain was on the right side in 94 cases (56.0%), on the left side in 64 cases (38.1%), and bilateral in 10 cases (5.9%). Pain was predominantly distributed in the V2 + V3 territory of the trigeminal nerve (40.5%), followed by V3 (27.4%), V1 + V2 (11.3%), V1 + V2 + V3 (10.1%), V2 (5.4%), and V1 (4.8%) territories. The cases had a predominantly idiopathic etiology (67.3%), followed by an MS etiology (26.2%), and finally, other etiologies (tumor, aneurysm, infarct, neuropathic, and postherpetic) accounting for 6.6% of all cases. The Burchiel classification was used to determine the type of facial pain.3 Among the idiopathic cases, typical shocklike pain presentation/TN1 was observed in 54.8% of cases and constant burning pain/TN2 was observed in 13.7% of cases.

TABLE 2.

Clinical and demographic data

CharacteristicValue
Total no. of cases168
Sex, n (%)
 Male60 (35.7)
 Female108 (64.3)
Median age at first CKRS (range), yrs 68.5 (23–90)
Median duration of symptoms before first CKRS (range), mos73.0 (2–606)
Side of pain, n (%)
 Rt94 (56.0)
 Lt64 (38.1)
 Bilat10 (5.9)
Pain distribution over the 3 branches of cranial nerve V, n (%)
 V18 (4.8)
 V29 (5.4)
 V346 (27.4)
 V1 + V219 (11.3)
 V1 + V30 (0.0)
 V2 + V368 (40.5)
 V1 + V2 + V317 (10.1)
Burchiel classification for pain, n (%)
 TN192 (54.8)
 TN223 (13.7)
 Symptomatic*50 (29.8)
 Neuropathic2 (1.2)
 Postherpetic1 (0.6)
Etiology, n (%)
 Idiopathic113 (67.3)
 MS44 (26.2)
 Other11 (6.6)
Vascular compression72 (42.9)
Prior surgery22 (13.1)
 PR11 (6.6)
 MVD10 (6.0)
 PR + MVD1 (0.6)
Pre-CKRS hypoesthesia, n (%)
 I152 (90.5)
 II14 (8.3)
 III0 (0.0)
 IV1 (0.6)§
Median max CKRS dose (range), Gy80 (70.0–88.9)

Includes MS, tumor, infarct, and aneurysm cases.

Includes tumor, aneurysm, infarct, neuropathic, and postherpetic cases.

BNI facial hypoesthesia scale.

Tumor case.

Preintervention MRI showed that 72 cases (42.9%) had an identifiable vascular compression. Twenty-two cases (13.1%) had prior nonradiosurgical interventions, with PR being the most frequent (6.6%), followed closely by MVD (6.0%), and finally, the combination of MVD and PR (0.6%). Pretreatment facial numbness was evaluated by the Barrow Neurological Institute (BNI) scale for facial hypoesthesia: 90.5% of patients had no facial numbness (score of I), 8.3% had mild facial numbness that was not bothersome (score of II), no patients had somewhat bothersome facial numbness (score of III), and 0.6% had very bothersome facial numbness (score of IV).14

CKRS

Treatment was performed using CyberKnife G4 (2009–2012), VSI (2012–2017), and M6 (2017–2021) systems (Accuray Inc.). Before treatment, planning each intervention included a high-resolution (1-mm slice thickness) CT scan and 3D magnetization-prepared rapid gradient echo (MPRAGE) T2-weighted MRI. For patients in whom MRI was not possible, a CT myelogram was performed for planning. The treatment was then planned on MultiPlan or Precision software (Accuray Inc.) with both CT and 3D MPRAGE MRI. CKRS dose planning was conducted by a radiation oncologist, a neurosurgeon, and a medical physicist. The targeting location along the cisternal portion of the trigeminal nerve varied based on the anatomy. The median maximal dose was 80 (range 70.0–88.9) Gy.

Outcome Measures

Facial pain was evaluated using the BNI scale for pain (score I–V): I, no trigeminal pain, no medications; II, occasional facial pain, not requiring medication; IIIa, no pain, continued medication; IIIb, persistent pain, controlled with medications; IV, some pain, not adequately controlled with medication; and V, severe pain/no pain relief.14 BNI scores I–IIIb were classified as adequate pain relief, whereas BNI scores IV and V were considered treatment failure.

Statistical Analysis

Overall, maintenance of adequate pain relief after CKRS was examined using the Kaplan-Meier method. Patients were censored if they remained pain-free at their last follow-up. Group comparisons were performed using the log-rank test. Pain relief intervals for 12, 36, and 60 months were calculated with their respective standard errors. To find potential risk factors associated with a better or worse outcome, uni- and multivariate Cox regression analyses were performed. The potential risk factors were chosen based on findings in previous publications.10 All statistical analyses were conducted using Jamovi open-source software (The Jamovi Project 2021, version 1.6; retrieved from https://www.jamovi.org). The results were considered significant when p values were < 0.05.

Results

Follow-Up and Rate of Adequate Pain Relief

Table 3 reports that the median follow-up period was 36.7 (range 0.8–192.2) months. One hundred forty-six TN cases (86.9%) responded well to the CKRS and experienced initial adequate pain relief. Among these cases, 101 were idiopathic and 36 were MS-related. The median latency period before the onset of the pain relief was 35 (range 0–202) days. For the idiopathic cases, the median latency period was 46 (range 0–202) days, whereas for the MS-related cases it was 14 (range 0–96) days.

TABLE 3.

Clinical outcomes following CKRS

OutcomeValue
Median follow-up (range), mos36.7 (0.8–192.2)
Initial adequate pain relief,* n (%)146 (86.9)
 Idiopathic101 (89.4)
 MS36 (81.8)
 Other9 (81.8)
Median days from CKRS to onset of adequate relief (range)35 (0–202)
 Idiopathic46 (0–202)
 MS14 (0–96)
 Other47 (2–177)
Failure of CKRS after an adequate initial pain relief was obtained, n (%)53 (31.5)
 Idiopathic27 (23.9)
 MS24 (54.5)
 Other2 (18.2)
Median mos from adequate initial pain relief to failure of CKRS (range)8.3 (0.6–85.0)
 Idiopathic6.6 (0.6–85.0)
 MS8.7 (0.7–48.1)
 Other28.8 (18.4–38.0)
Additional treatments after CKRS, n (%)60 (35.7)
 CKRS15 (8.9)
 PR31 (18.5)
 MVD3 (1.8)
 PR + MVD1 (0.6)
 CKRS + other10 (6.0)

Adequate initial pain relief = BNI score I–IIIb response on the BNI pain intensity scale.

Failure of CKRS = BNI score IV–V.

Recurrence of TN and Additional Treatments

Table 3 reports that 53 TN cases (31.5%) had treatment failures (BNI score IV–V) after a median of 8.3 (range 0.6–85.0) months from the initial adequate pain relief response. Among these 53 cases, 27 were idiopathic and 24 were MS-related. For the idiopathic cases, the median time between the initial adequate pain relief response and the CKRS failure was 6.6 (range 0.6–85.0) months. The median time was 8.7 (range 0.7–48.1) months for the MS-related cases. Sixty TN cases (35.7%) underwent additional treatments after their first CKRS. Of those 60 cases, 31 underwent PR and 15 had a second CKRS treatment.

Maintenance of Adequate Pain Relief After CKRS

Figure 1 is the Kaplan-Meier survival curve of all the cases, for the maintenance of pain relief after CKRS, with a median duration of 86 months. The actuarial probabilities of maintaining adequate pain relief at 1, 3, and 5 years were 77%, 63%, and 50%, respectively (Table 4). Figure 2 shows the Kaplan-Meier curves of patients with idiopathic TN, MS-related TN, and cases with other TN etiologies. The median actuarial failure-free interval for the MS-related cases was 17 months, and 100 months for the idiopathic cases. For the idiopathic cases, the actuarial probabilities of maintaining adequate pain relief at 1, 3, and 5 years were 85%, 73%, and 60%, respectively. For the MS-related cases, these values were 52%, 32%, and 22%, respectively. For the TN cases with other etiologies, these rates were 100%, 88%, and 73%, respectively (Table 4).

FIG. 1.
FIG. 1.

Graph of actuarial Kaplan-Meier curve showing the proportion of TN cases maintaining adequate pain relief (BNI scale score I–IIIb) over time from CKRS.

TABLE 4.

Maintenance of pain relief following CKRS at 1, 3, and 5 years for idiopathic, MS, and other cases

Time After CKRSSurvival (%)Standard Error
At 1 yr77.03.7
 MS51.78.7
 Idiopathic84.63.8
 Other100.00.0
At 3 yrs62.54.6
 MS32.38.3
 Idiopathic72.55.4
 Other87.511.7
At 5 yrs50.25.9
 MS22.28.3
 Idiopathic60.27.9
 Other72.916.5
FIG. 2.
FIG. 2.

Graph of actuarial Kaplan-Meier curves showing the proportion of TN cases maintaining adequate pain relief (BNI scale score I–IIIb) according to the TN etiology.

Predictive Factors of Treatment Outcomes

Predictive factors are presented in Table 5. In the univariate Cox survival analysis, predictors for a better outcome were an older age (p < 0.001), a shorter duration of symptoms before CKRS (p = 0.006), the presence of hypoesthesia before CKRS (p = 0.010), an aggravation or onset of hypoesthesia after CKRS (p < 0.001), and an idiopathic etiology (p = 0.004). Underlying MS predicted worse outcomes (p < 0.001). In the multivariate Cox survival analysis, the only predictor for a better outcome was the aggravation/onset of hypoesthesia after CKRS (p < 0.001). The log-rank comparison for maintaining adequate pain relief between MS and idiopathic cases was significant (p < 0.001).

TABLE 5.

Univariate Cox survival analysis and multivariate Cox regression of factors affecting the pain outcome

Predictive FactorUnivariateMultivariate
HR95% CIp ValueHR95% CIp Value
Age, yrs0.970.95–0.98<0.0010.990.97–1.010.245
Symptom duration, mos1.000.99–1.000.0061.000.99–1.000.075
Sex, male vs female1.470.86–2.520.158
Side, left vs right1.100.68–1.760.702
Trigeminal nerve division, simple vs multiple0.180.73–1.900.494
Etiology
 Idiopathic0.500.31–0.800.0041.740.61–4.950.302
 MS2.491.54–4.03<0.0012.710.93–7.860.067
 Other0.660.24–1.830.427
Presence of hypoesthesia before2.351.23–4.480.0101.230.59–2.570.588
Presence of prior surgery0.810.37–1.770.593
Maximum Gy dose, <80 vs ≥800.720.38–1.380.322
Presence of vascular compression0.740.46–1.200.224
New or worsening hypoesthesia after CKRS0.200.09–0.42<0.0010.220.11–0.48<0.001

HR = hazard ratio.

Boldface type indicates statistical significance.

Clinical Complications After CKRS

Forty-four TN cases (26.2%) had a new onset of numbness or aggravation of their preexisting numbness (Table 6). Of those 44 TN cases, 21 had a BNI numbness scale score of II, 13 had a BNI numbness scale score of III, and 10 had a BNI numbness scale score of IV/anesthesia dolorosa. Other notable complications were the onset of a transient facial spasm (n = 4), diminution of the corneal reflex (n = 12), keratitis/dry eye syndrome (n = 4), tinnitus (n = 2), and facial motor deficit/temporomandibular joint (TMJ) dysfunction (n = 3).

TABLE 6.

Clinical complications after CKRS

ComplicationNo. (%)
Hypoesthesia onset/aggravation after CKRS*44 (26.2)
 II21 (12.5)
 III13 (7.7)
 IV/anesthesia dolorosa10 (6.0)
Facial spasm 4 (2.4)
Diminution of corneal reflex12 (7.1)
Keratitis/dry eye4 (2.4)
Tinnitus2 (1.2)
Facial motor deficit & TMJ dysfunction3 (1.8)
Other3 (1.8)

BNI numbness scale.

Discussion

The present results were compared with the two largest previously published studies on CKRS and with the results of a systematic review by Tuleasca et al.10,15,16 In the systematic review, the median follow-up period for CKRS studies ranged from 22 to 23 months.6 In the Romanelli et al. and Conti et al. studies, the follow-up periods were at least 3 years (36 months) and 38 months, respectively.11,12 In this study, the median follow-up was 36.7 months.

In the systematic review, the post-CKRS median latency period before the onset of adequate pain relief was not reported for any of the CKRS studies,6 nor was it directly reported in any of the two largest series.11,12 However, Romanelli et al. reported that at a median of 3 weeks, 67% of their patients had significant pain relief (i.e., a decrease of more than 5 on the visual analog scale).15 In this study, the median latency period was 35 (range 0–202) days.

In terms of initial adequate pain relief rates after CKRS, Conti et al. reported that pain control was acquired in 88.2% of their cases.11 Romanelli et al. reported that only 8% of their patients did not have pain relief.15 In their systematic review, Tuleasca et al. reported a 79% median initial pain relief rate of the included CKRS studies.6 In this study, the initial adequate pain relief rate was 86.9%. This rate is similar to the rate found in the two largest studies and slightly higher than the rate in the systematic review.

In terms of maintenance of pain relief, the results of this study are inferior to the results of previous studies on CKRS.15,16 Romanelli et al. reported an actuarial pain control rate at 12 and 36 months of 87% and 76%, respectively.15 Conti et al. reported actuarial pain control rates at 12, 36, and 60 months of 90.9%, 81.4%, and 71.2%, respectively.16 In the present study, the actuarial pain relief rates at 12, 36, and 60 months were 77%, 63%, and 50%, respectively. Our results need to be interpreted in the context of having a larger proportion of MS-related cases.

Assessing this difference between the etiologies, a GKRS study by Verheul et al. revealed significatively worse maintenance of adequate pain relief for their MS patients in comparison with their idiopathic patients (p < 0.001).17 In the present study, a significantly worse outcome was also reported for the MS cases in comparison with the idiopathic cases (p < 0.001).

When we look specifically at the adequate pain relief for our 44 MS-related cases, results tend to be lower compared with previous GKRS studies.18,19 Xu et al. conducted the largest multicenter study, with 263 MS-related patients treated with GKRS; their actuarial adequate pain control maintenance rates at 12, 24, and 48 months were 54%, 35%, and 24%, respectively.18 Furthermore, in their 35-patient cohort, Weller et al. reported that the actuarial adequate pain control rates at 12, 36, and 60 months were 57%, 57%, and 53%.19 In this study, the actuarial probabilities of maintaining adequate pain relief at 1, 3, and 5 years were 52%, 33%, and 22%.

When we compare our CKRS results for idiopathic TN to the results of two large GKRS studies, the rates of maintaining adequate pain relief were similar.12,20 In fact, in their cohort of 503 patients, Kondziolka et al. reported that the actuarial pain control rates at 12, 36, and 60 months were 80%, 71%, and 46%, respectively.12 In their 446-patient cohort, Lucas et al. reported that at 12, 36, and 60 months, their adequate pain relief rates were 84.5%, 70.4%, and 46.9%.20 In this study, the actuarial pain control rates for the idiopathic cases at 12, 36, and 60 months were 84.6%, 72.5%, and 60.2%. Thus, the rates for idiopathic TN in this study are similar at 12 and 36 months, but tend to be higher at 60 months.

Regarding predictors of outcomes, Tuleasca et al. reported that the factors associated with better pain relief maintenance were new facial numbness and no past surgery in their systematic review of 65 eligible studies.10 In this study, only one predictor for a better outcome was significant after the multivariate analysis, that is, aggravation/onset of numbness after CKRS (p < 0.001). Currently, the mechanism of action of radiosurgery for TN remains uncertain. However, it is postulated that radiosurgery iatrogenically causes axonal degeneration of the sensory part of the trigeminal nerve that contains nociceptive and sensory fibers.21 This axonal degeneration could explain why the radiosurgically induced facial sensory dysfunction is associated with a better outcome, because if the sensitive fibers are injured, the nociceptive fibers could also be injured.22

Regarding complications and safety, Tuleasca et al. reported that there was a mean hypoesthesia onset after CKRS of 29.1%. In the present study, the hypoesthesia onset/aggravation rate was slightly lower at 26.2%. Tuleasca et al. also reported that a mean of 9% of the cases developed a bothersome or very bothersome numbness (BNI numbness scale score of III or IV).10 In the current study, 13.7% of the cases had a BNI numbness scale score of III or IV. The rate of new hypoesthesia is slightly lower in the present study compared with the rate in the study of Tuleasca et al., but a higher rate of more severe hypoesthesia is noticeable among its cases.

Limitations of the Study

This study contains some intrinsic limitations because of its design. First, because this is a retrospective study, recall bias is to be expected. Second, some radiosurgical data were not analyzed in detail, such as heterogeneous target delineation, target location, dose at the brainstem, and nerve volume irradiated. Those parameters may influence the outcomes of our treatment. And third, even though our follow-up period is reasonably long, a longer follow-up is always desirable.

Future Studies

Our brief review of available data about CKRS in MS-related TN has revealed that, so far, very limited analysis has been dedicated to this population. It would be interesting to further evaluate the characteristics of MS patients undergoing CKRS for TN. In addition, a more thorough investigation of the complications associated with CKRS could be conducted. In comparison to the studies assessing the complications after SRS in the systematic review of Tuleasca et al., our patients tend to have more severe hypoesthesia.10 The characteristics of the hypoesthesia could be better defined and evaluated. Also, for a more global perspective, it would be interesting to use more precise and standardized patient-reported outcomes questionnaires. Finally, because CKRS is a nonisocentric SRS modality, radiosurgical data could be analyzed regarding the dosimetric parameters and physiological radiation dose delivered at the cisternal portion of the trigeminal nerve.

Conclusions

This current study is consistent with prior experience of CKRS for TN. The results suggested that CKRS is a favorable treatment for patients with medically refractory TN with a low risk of incapacitating complications. Patients who experienced an onset or aggravation of hypoesthesia after their treatment were more likely to achieve longer adequate pain control. Patients with MS had significantly worse outcomes than patients with an idiopathic etiology.

Acknowledgments

We wish to thank Dr. Frédéric Racicot and Dr. Sami Obaïd for their help and support. A PREMIER-CRCHUM research scholarship was awarded to Albert Guillemette.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Fournier-Gosselin, Guillemette, Roberge. Acquisition of data: Fournier-Gosselin, Guillemette, Roberge. Analysis and interpretation of data: Fournier-Gosselin, Guillemette. Drafting the article: Fournier-Gosselin, Guillemette. Critically revising the article: Fournier-Gosselin, Heymann, Roberge. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Fournier-Gosselin. Statistical analysis: Fournier-Gosselin, Guillemette. Administrative/technical/material support: Fournier-Gosselin, Roberge. Study supervision: Fournier-Gosselin, Roberge.

Supplemental Information

Previous Presentations

The abstract was presented at the Canadian Neurological Science Federation Congress in Montréal on June 26, 2022, in the form of a poster presentation.

References

  • 1

    van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654662.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Silva M, Ouanounou A. Trigeminal neuralgia: etiology, diagnosis, and treatment. SN Compr Clin Med. 2020;2(9):15851592.

  • 3

    Eller JL, Raslan AM, Burchiel KJ. Trigeminal neuralgia: definition and classification. Neurosurg Focus. 2005;18(5):E3.

  • 4

    Knafo H, Kenny B, Mathieu D. Trigeminal neuralgia: outcomes after gamma knife radiosurgery. Can J Neurol Sci. 2009;36(1):7882.

  • 5

    Zakrzewska JM, Linskey ME. Trigeminal neuralgia. BMJ. 2014;348:g474.

    • Crossref
    • Export Citation
  • 6

    Wu TH, Hu LY, Lu T, et al. Risk of psychiatric disorders following trigeminal neuralgia: a nationwide population-based retrospective cohort study. J Headache Pain. 2015;16:64.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Bendtsen L, Zakrzewska JM, Abbott J, et al. European Academy of Neurology guideline on trigeminal neuralgia. Eur J Neurol. 2019;26(6):831849.

  • 8

    Kondziolka D, Pérez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998;55(12):15241529.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Adler JR Jr, Bower R, Gupta G, et al. Nonisocentric radiosurgical rhizotomy for trigeminal neuralgia. Neurosurgery. 2009;64(2 Suppl):A84A90.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Tuleasca C, Régis J, Sahgal A, et al. Stereotactic radiosurgery for trigeminal neuralgia: a systematic review. J Neurosurg. 2018;130(3):733757.

  • 11

    Régis J, Tuleasca C, Resseguier N, et al. Long-term safety and efficacy of Gamma Knife surgery in classical trigeminal neuralgia: a 497-patient historical cohort study. J Neurosurg. 2016;124(4):10791087.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Kondziolka D, Zorro O, Lobato-Polo J, et al. Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2010;112(4):758765.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Marshall K, Chan MD, McCoy TP, et al. Predictive variables for the successful treatment of trigeminal neuralgia with Gamma Knife radiosurgery. Neurosurgery. 2012;70(3):566573.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Rogers CL, Shetter AG, Fiedler JA, Smith KA, Han PP, Speiser BL. Gamma knife radiosurgery for trigeminal neuralgia: the initial experience of The Barrow Neurological Institute. Int J Radiat Oncol Biol Phys. 2000;47(4):10131019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Romanelli P, Conti A, Redaelli I, et al. CyberKnife radiosurgery for trigeminal neuralgia. Cureus. 2019;11(10):e6014.

  • 16

    Conti A, Acker G, Pontoriero A, et al. Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study. Radiat Oncol. 2020;15(1):115.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Verheul JB, Hanssens PEJ, Lie ST, Leenstra S, Piersma H, Beute GN. Gamma Knife surgery for trigeminal neuralgia: a review of 450 consecutive cases. J Neurosurg. 2010;113 Suppl:160-167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Xu Z, Mathieu D, Heroux F, et al. Stereotactic radiosurgery for trigeminal neuralgia in patients with multiple sclerosis: a multicenter study. Neurosurgery. 2019;84(2):499505.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Weller M, Marshall K, Lovato JF, et al. Single-institution retrospective series of gamma knife radiosurgery in the treatment of multiple sclerosis-related trigeminal neuralgia: factors that predict efficacy. Stereotact Funct Neurosurg. 2014;92(1):5358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Lucas JT Jr, Nida AM, Isom S, et al. Predictive nomogram for the durability of pain relief from Gamma Knife radiation surgery in the treatment of trigeminal neuralgia. Int J Radiat Oncol Biol Phys. 2014;89(1):120126.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Gorgulho A. Radiation mechanisms of pain control in classical trigeminal neuralgia. Surg Neurol Int. 2012;3(Suppl 1):S17S25.

  • 22.

    Pollock BE. Radiosurgery for trigeminal neuralgia: is sensory disturbance required for pain relief?. J Neurosurg. 2006;105 Suppl:103-106.

  • Collapse
  • Expand
  • View in gallery
    FIG. 1.

    Graph of actuarial Kaplan-Meier curve showing the proportion of TN cases maintaining adequate pain relief (BNI scale score I–IIIb) over time from CKRS.

  • View in gallery
    FIG. 2.

    Graph of actuarial Kaplan-Meier curves showing the proportion of TN cases maintaining adequate pain relief (BNI scale score I–IIIb) according to the TN etiology.

  • 1

    van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654662.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Silva M, Ouanounou A. Trigeminal neuralgia: etiology, diagnosis, and treatment. SN Compr Clin Med. 2020;2(9):15851592.

  • 3

    Eller JL, Raslan AM, Burchiel KJ. Trigeminal neuralgia: definition and classification. Neurosurg Focus. 2005;18(5):E3.

  • 4

    Knafo H, Kenny B, Mathieu D. Trigeminal neuralgia: outcomes after gamma knife radiosurgery. Can J Neurol Sci. 2009;36(1):7882.

  • 5

    Zakrzewska JM, Linskey ME. Trigeminal neuralgia. BMJ. 2014;348:g474.

    • Crossref
    • Export Citation
  • 6

    Wu TH, Hu LY, Lu T, et al. Risk of psychiatric disorders following trigeminal neuralgia: a nationwide population-based retrospective cohort study. J Headache Pain. 2015;16:64.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Bendtsen L, Zakrzewska JM, Abbott J, et al. European Academy of Neurology guideline on trigeminal neuralgia. Eur J Neurol. 2019;26(6):831849.

  • 8

    Kondziolka D, Pérez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998;55(12):15241529.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Adler JR Jr, Bower R, Gupta G, et al. Nonisocentric radiosurgical rhizotomy for trigeminal neuralgia. Neurosurgery. 2009;64(2 Suppl):A84A90.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Tuleasca C, Régis J, Sahgal A, et al. Stereotactic radiosurgery for trigeminal neuralgia: a systematic review. J Neurosurg. 2018;130(3):733757.

  • 11

    Régis J, Tuleasca C, Resseguier N, et al. Long-term safety and efficacy of Gamma Knife surgery in classical trigeminal neuralgia: a 497-patient historical cohort study. J Neurosurg. 2016;124(4):10791087.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Kondziolka D, Zorro O, Lobato-Polo J, et al. Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2010;112(4):758765.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Marshall K, Chan MD, McCoy TP, et al. Predictive variables for the successful treatment of trigeminal neuralgia with Gamma Knife radiosurgery. Neurosurgery. 2012;70(3):566573.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Rogers CL, Shetter AG, Fiedler JA, Smith KA, Han PP, Speiser BL. Gamma knife radiosurgery for trigeminal neuralgia: the initial experience of The Barrow Neurological Institute. Int J Radiat Oncol Biol Phys. 2000;47(4):10131019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Romanelli P, Conti A, Redaelli I, et al. CyberKnife radiosurgery for trigeminal neuralgia. Cureus. 2019;11(10):e6014.

  • 16

    Conti A, Acker G, Pontoriero A, et al. Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study. Radiat Oncol. 2020;15(1):115.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Verheul JB, Hanssens PEJ, Lie ST, Leenstra S, Piersma H, Beute GN. Gamma Knife surgery for trigeminal neuralgia: a review of 450 consecutive cases. J Neurosurg. 2010;113 Suppl:160-167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Xu Z, Mathieu D, Heroux F, et al. Stereotactic radiosurgery for trigeminal neuralgia in patients with multiple sclerosis: a multicenter study. Neurosurgery. 2019;84(2):499505.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Weller M, Marshall K, Lovato JF, et al. Single-institution retrospective series of gamma knife radiosurgery in the treatment of multiple sclerosis-related trigeminal neuralgia: factors that predict efficacy. Stereotact Funct Neurosurg. 2014;92(1):5358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Lucas JT Jr, Nida AM, Isom S, et al. Predictive nomogram for the durability of pain relief from Gamma Knife radiation surgery in the treatment of trigeminal neuralgia. Int J Radiat Oncol Biol Phys. 2014;89(1):120126.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Gorgulho A. Radiation mechanisms of pain control in classical trigeminal neuralgia. Surg Neurol Int. 2012;3(Suppl 1):S17S25.

  • 22.

    Pollock BE. Radiosurgery for trigeminal neuralgia: is sensory disturbance required for pain relief?. J Neurosurg. 2006;105 Suppl:103-106.

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