Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia

2020 ◽  
Vol 133 (3) ◽  
pp. 727-735
Author(s):  
Peter Shih-Ping Hung ◽  
Sarasa Tohyama ◽  
Jia Y. Zhang ◽  
Mojgan Hodaie
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Pain Intensity ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Diffusion Tensor ◽  
Gamma Knife Radiosurgery ◽  
Time Points ◽  
Microstructural Effect

OBJECTIVEGamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.METHODSNinety-two sets of 3-T anatomical and diffusion-weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.RESULTSGKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.CONCLUSIONSUltimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN.

scholarly journals Early postsurgical diffusivity metrics for prognostication of long-term pain relief after Gamma Knife radiosurgery for trigeminal neuralgia

2019 ◽  
Vol 131 (2) ◽  
pp. 539-548 ◽  
Author(s):  
Sarasa Tohyama ◽  
Peter Shih-Ping Hung ◽  
Jidan Zhong ◽  
Mojgan Hodaie
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Fractional Anisotropy ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Gamma Knife Radiosurgery ◽  
Mean Diffusivity ◽  
Clinical Effectiveness ◽  
Radial Diffusivity

OBJECTIVEGamma Knife radiosurgery (GKRS) is an important treatment modality for trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies primarily on clinical diagnostic measures, which are highly limited in the prediction of long-term clinical benefit. An objective, noninvasive, predictive tool would be of great utility to advance the clinical management of patients. Using diffusion tensor imaging (DTI), the authors’ aim was to determine whether early (6 months post-GKRS) target diffusivity metrics can be used to prognosticate long-term pain relief in patients with TN.METHODSThirty-seven patients with TN treated with GKRS underwent 3T MRI scans at 6 months posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted bilaterally from the radiosurgical target of the affected trigeminal nerve and its contralateral, unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following GKRS.RESULTSTrigeminal nerve diffusivity at 6 months post-GKRS was predictive of long-term clinical effectiveness, where long-term responders (n = 19) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes after GKRS.CONCLUSIONSThe authors demonstrate that early postsurgical target diffusivity metrics have a translational, clinical value and permit prediction of long-term pain relief in patients with TN treated with GKRS. Importantly, an association was found between the footprint of radiation and clinical effectiveness, where a sufficient level of microstructural change at the radiosurgical target is necessary for long-lasting pain relief. DTI can provide prognostic information that supplements clinical measures, and thus may better guide the postoperative assessment and clinical decision-making for patients with TN.

Long-term outcome of high-dose Gamma Knife surgery in treatment of trigeminal neuralgia

2013 ◽  
Vol 119 (5) ◽  
pp. 1166-1175 ◽  
Author(s):  
Byron Young ◽  
Armin Shivazad ◽  
Richard J. Kryscio ◽  
William St. Clair ◽  
Heather M. Bush
Keyword(s):  
Quality Of Life ◽  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Pain Intensity ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Gamma Knife Surgery

Object Despite the widespread use of Gamma Knife surgery (GKS) for trigeminal neuralgia (TN), controversy remains regarding the optimal treatment dose and target site. Among the published studies, only a few have focused on long-term outcomes (beyond 2 years) using 90 Gy, which is in the higher range of treatment doses used (70–90 Gy). Methods The authors followed up on 315 consecutive patients treated with the Leksell Gamma Knife unit using a 4-mm isocenter without blocks. The isocenter was placed on the trigeminal nerve with the 20% isodose line tangential to the pontine surface (18 Gy). At follow-up, 33 patients were deceased; 282 were mailed an extensive questionnaire regarding their outcomes, but 32 could not be reached. The authors report their analysis of the remaining 250 cases. The patients' mean age at the time of survey response and the mean duration of follow-up were 70.8 ± 13.1 years and 68.9 ± 41.8 months, respectively. Results One hundred eighty-five patients (85.6%) had decreased pain intensity after GKS. Modified Marseille Scale (MMS) pain classifications after GKS at follow-up were: Class I (pain free without medication[s]) in 104 (43.7%), Class II (pain free with medication[s]) in 66 (27.7%), Class III (> 90% decrease in pain intensity) in 23 (9.7%), Class IV (50%–90% decrease in pain intensity) in 20 (8.4%), Class V (< 50% decrease in pain intensity) in 11 (4.6%), and Class VI (pain becoming worse) in 14 (5.9%). Therefore, 170 patients (71.4%) were pain free (Classes I and II) and 213 (89.5%) had at least 50% pain relief. All patients had pain that was refractory to medical management prior to GKS, but only 111 (44.4%) were being treated with medication at follow-up (p < 0.0001). Eighty patients (32.9%) developed numbness after GKS, and 74.5% of patients with numbness had complete pain relief. Quality of life and patient satisfaction on a 10-point scale were reported at mean values (± SD) of 7.8 ± 3.1 and 7.7 ± 3.4, respectively. Most of the patients (87.7%) would recommend GKS to another patient. Patients with prior surgical treatments had increased latency to pain relief and were more likely to continue medicines (p < 0.05). Moreover, presence of altered facial sensations prior to radiosurgery was associated with higher pain intensity, longer pain episodes, more frequent pain attacks, worse MMS pain classification, and more medication use after GKS (p < 0.05). Conversely, increase in numbness intensity after GKS was associated with a decrease in pain intensity and pain length (p < 0.05). Conclusions Gamma Knife surgery using a maximum dose of 90 Gy to the trigeminal nerve provides satisfactory long-term pain control, reduces the use of medication, and improves quality of life. Physicians must be aware that higher doses may be associated with an increase in bothersome sensory complications. The benefits and risks of higher dose selection must be carefully discussed with patients, since facial numbness, even if bothersome, may be an acceptable trade-off for patients with severe pain.

Outcome Predictors After Gamma Knife Radiosurgery for Recurrent Trigeminal Neuralgia

Neurosurgery ◽  
2010 ◽  
Vol 67 (6) ◽  
pp. 1637-1645 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
Huai-Che Yang ◽  
Oscar Zorro ◽  
Javier Lobato-Polo ◽  
...  
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Pain Control ◽  
Surgical Procedure ◽  
Gamma Knife Radiosurgery ◽  
Sensory Loss ◽  
Failed Surgery ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract BACKGROUND: Trigeminal neuralgia (TN) that recurs after surgery can be difficult to manage. OBJECTIVE: To define management outcomes in patients who underwent gamma knife stereotactic radiosurgery (GKSR) after failing 1 or more previous surgical procedures. METHODS: We retrospectively reviewed outcomes after GKSR in 193 patients with TN after failed surgery. The median patient age was 70 years (range, 26-93 years). Seventy-five patients had a single operation (microvascular decompression, n = 40; glycerol rhizotomy, n = 24; radiofrequency rhizotomy, n = 11). One hundred eighteen patients underwent multiple operations before GKSR. Patients were evaluated up to 14 years after GKSR. RESULTS: After GKSR, 85% of patients achieved pain relief or improvement (Barrow Neurological Institute grade I-IIIb). Pain recurrence was observed in 73 of 168 patients 6 to 144 months after GKSR (median, 6 years). Factors associated with better long-term pain relief included no relief from the surgical procedure preceding GKSR, pain in a single branch, typical TN, and a single previous failed surgical procedure. Eighteen patients (9.3%) developed new or increased trigeminal sensory dysfunction, and 1 developed deafferentation pain. Patients who developed sensory loss after GKSR had better long-term pain control (Barrow Neurological Institute grade I-IIIb: 86% at 5 years). CONCLUSION: GKSR proved to be safe and moderately effective in the management of TN that recurs after surgery. Development of sensory loss may predict better long-term pain control. The best candidates for GKSR were patients with recurrence after a single failed previous operation and those with typical TN in a single trigeminal nerve distribution.

Gamma Knife radiosurgery for trigeminal neuralgia: the impact of magnetic resonance imaging–detected vascular impingement of the affected nerve

2010 ◽  
Vol 113 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Jason P. Sheehan ◽  
Dibyendu Kumar Ray ◽  
Stephen Monteith ◽  
Chun Po Yen ◽  
James Lesnick ◽  
...  
Keyword(s):  
Pain Relief ◽  
Mr Imaging ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Gamma Knife Radiosurgery ◽  
Vascular Compression ◽  
Pain Intensity Score ◽  
The Impact

Object Trigeminal neuralgia is believed to be related to vascular compression of the affected nerve. Radiosurgery has been shown to be reasonably effective for treatment of medically refractory trigeminal neuralgia. This study explores the rate of occurrence of MR imaging–demonstrated vascular impingement of the affected nerve and the extent to which vascular impingement affects pain relief in a population of trigeminal neuralgia patients undergoing Gamma Knife radiosurgery (GKRS). Methods The authors performed a retrospective analysis of 106 cases involving patients treated for typical trigeminal neuralgia using GKRS. Patients with or without single-vessel impingement on CISS MR imaging sequences and with no previous surgery were included in the study. Pain relief was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at the last follow-up. Degree of impingement, nerve diameter preand post-impingement, isocenter placement, and dose to the point of maximum impingement were evaluated in relation to the improvement of BNI score. Results The overall median follow-up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of patients at last follow-up. Vessel impingement was seen in 63 patients (59%). There was no significant difference in pain relief between those with and without vascular impingement following GKRS (p > 0.05). In those with vascular impingement on MR imaging, the median fraction of vessel impingement was 0.3 (range 0.04–0.59). The median dose to the site of maximum impingement was 42 Gy (range 2.9–79 Gy). Increased dose (p = 0.019) and closer proximity of the isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a statistically significant fashion with improved BNI scores in those demonstrating vascular impingement on the GKRS planning MR imaging Conclusions Vascular impingement of the affected nerve was seen in the majority of patients with trigeminal neuralgia. Overall pain relief following GKRS was comparable in those with and without evidence of vascular compression on MR imaging. In subgroup analysis of those with MR imaging evidence of vessel impingement of the affected trigeminal nerve, pain relief correlated with a higher dose to the point of contact between the impinging vessel and the trigeminal nerve. Such a finding may point to vascular changes affording at least some degree of relief following GKRS for trigeminal neuralgia.

Trigeminal Nerve-Blood Vessel Relationship as Revealed by High-resolution Magnetic Resonance Imaging and Its Effect on Pain Relief after Gamma Knife Radiosurgery for Trigeminal Neuralgia

Neurosurgery ◽  
2002 ◽  
Vol 50 (6) ◽  
pp. 1261-1267 ◽  
Author(s):  
Ronald Brisman ◽  
Alexander G. Khandji ◽  
Robertus B.M. Mooij
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
High Resolution ◽  
Pain Relief ◽  
Blood Vessel ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Gamma Knife Radiosurgery ◽  
Resonance Imaging

Abstract OBJECTIVE Blood vessel (BV) compression of the trigeminal nerve (Cranial Nerve [CN] V) is a common cause of trigeminal neuralgia (TN). High-resolution magnetic resonance imaging scans obtained during gamma knife radiosurgery (GKRS) in patients with TN may be used to analyze the BV-CN V relationship. Follow-up data from a large series of patients treated with GKRS for TN were used to provide information regarding the BV-CN V relationship and pain relief. METHODS T1-weighted, axial 1-mm-thick volume acquisition magnetic resonance imaging scans were obtained through the area of CN V at its exit from the brainstem after injection of 15 ml of gadolinium. The BV-CN V relationship on the symptomatic side that was treated with GKRS was categorized into the following groups: Group 1 (no close relationship), Group 2 (BV close to CN V but not touching it), and Groups 3 and higher (BV-CN V contact). RESULTS A total of 181 symptomatic nerves were studied in 179 patients with TN who were treated with GKRS. In BV-CN V Groups 1, 2, and 3 and higher, respectively, were 43 sides (24%), 31 sides (17%), and 107 sides (59%). In 100 sides where there was no surgical procedure before GKRS, 50% or greater pain relief was more likely in those with BV-CN V contact (51 [88%] of 58 sides) than in those without BV-CN V (29 [69%] of 42 sides) (P = 0.024). BV-CN V contact was observed more often in men (55 [69%] of 80 sides) than in women (52 [52%] of 101 sides) (P = 0.023) and more often in patients who had unilateral TN (104 [62%] of 169 patients) rather than bilateral TN (2 [20%] of 10 patients) (P = 0.016). CONCLUSION In patients who have not undergone previous surgery for TN, BV-CN V contact revealed by high-resolution magnetic resonance imaging may indicate a particularly favorable response to GKRS.

Gamma knife radiosurgery for trigeminal neuralgia: dose—volume histograms of the brainstem and trigeminal nerve

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 155-158 ◽  
Author(s):  
Ronald Brisman ◽  
R. Mooij
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Maximum Dose ◽  
Gamma Knife Radiosurgery ◽  
Content Type ◽  
Dose Volume Histograms ◽  
Dose Volume ◽  
Fine Print

Object. The purpose of this study was to assess the relationship between the volume of brainstem that receives 20% or more of the maximum dose (VB20) and the volume of the trigeminal nerve that receives 50% or more of the maximum dose (VT50) on clinical outcome following gamma knife radiosurgery (GKS) for trigeminal neuralgia (TN). Methods. Patients with TN were treated with a single 4-mm isocenter with a maximum dose of 75 Gy directed at the trigeminal nerve close to where it leaves the brainstem. The VB20 and VT50, as determined on dose—volume histograms, were correlated with clinical outcomes at 6 and 12 months, laterality, presence of multiple sclerosis (MS), and each other. At 6 months excellent pain relief (no pain or required medicine) was achieved in 27 of 48 patients (p = 0.009) when VB20 was greater than or equal to 20 mm3 and in 25 of 78 when VB20 was less than 20 mm3, when all patients are considered. At 12 months excellent pain relief was achieved in 16 of 32 patients (p = 0.038) when VB20 was greater than or equal to 20 mm3 and in 14 of 52 when VB20 less than 20 mm3, when all patients are considered. When VB20 was less than 20 mm3 in MS patients, five of 21 had an excellent result at 6 months and two of 13 at 12 months. The VB20 was 20 mm3 or more in 38 of 64 on the right side and in eight of 41 on the left side (p < 0.001) in patients with TN and without MS. There is a difference between left and right dose—volume histograms even when the same isodose is placed on the surface of the brainstem. The VB20 was 20 mm3 or more in 45 of 105 patients with TN and without MS but in only three of 21 patients with TN and MS (p = 0.014). There was an inverse relationship between VB20 and VT50 (p = 0.01). Conclusions. Isocenter proximity to the brainstem, as reflected in a higher VB20, is associated with a greater chance of excellent outcome at 6 and 12 months. Worse results in patients with TN and MS may be partly explained by a lower VB20.

Repeat Gamma Knife surgery for trigeminal neuralgia: long-term results

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 178-183 ◽  
Author(s):  
Brent Y. Kimball ◽  
Jeffrey M. Sorenson ◽  
David Cunningham
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Treatment Plan ◽  
Gamma Knife Surgery ◽  
Long Term Results ◽  
Long Term Outcome ◽  
Facial Numbness

Object The purpose of this study was to assess the long-term outcome achieved after repeat Gamma Knife surgery (GKS) for trigeminal neuralgia (TN) using a uniform treatment plan. Methods Between 1985 and 2010, 53 patients underwent repeat GKS for refractory TN. In the initial GKS, which involved targeting the root entry zone of the trigeminal nerve, a maximal dose of 80 Gy was used with a 4-mm collimator so that the 50% isodose line abutted the pons. In the second GKS, the treatment plan consisted of a 70-Gy dose directed at a target 4–5 mm distal to the first target on the trigeminal nerve. The mean follow-up duration in these patients was 42 months. Outcomes were defined using the Marseille scale: excellent (Class I or II, no pain with or without medications), good (Class III or IV, ≥ 50% relief), and poor (Class V, < 50% relief). Results Trigeminal neuralgia pain was controlled (≥ 50% improvement with or without medications) after repeat GKS in 70% of patients at 1 year, 50% at 3 years, 50% at 5 years, and 50% at 10 years, as defined by a Kaplan-Meier analysis. A correlation was found between facial numbness and pain relief (p = 0.047). No difference was found between patients with Type 1 TN and those with Type 2 TN, and there was no correlation between the best relief obtained and long-term durability of relief from pain. Twenty-two patients (47.8%) described their trigeminal dysfunction in the following manner: numbness (45.6%), dry eye (10.9%), taste change (8.7%), or jaw weakness (2.2%). In only 8.7% of cases did the patient experience facial numbness that was regarded as bothersome. Conclusions Repeat GKS for TN at the doses used provides substantial long-term relief. Treatment failure occurred up to 28 months after the second GKS. Facial numbness correlated with more durable pain relief after repeat GKS in this series.

Long-term outcomes of Gamma Knife radiosurgery for classic trigeminal neuralgia: implications of treatment and critical review of the literature

2009 ◽  
Vol 111 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Anil A. Dhople ◽  
Jared R. Adams ◽  
William W. Maggio ◽  
Shahid A. Naqvi ◽  
William F. Regine ◽  
...  
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Response Duration ◽  
Invasive Treatment ◽  
Median Response ◽  
Late Failure

Object Few long-term studies of Gamma Knife surgery (GKS) for trigeminal neuralgia (TN) exist. The authors report their long-term experience with the use of GKS in a previously reported cohort of patients with TN that has now been followed since 1996. Methods One hundred twelve patients with TN were treated with GKS at the University of Maryland between June 1996 and July 2001. Of these, 67% had no invasive operations for TN prior to GKS, 13% had 1, 4% had 2, and 16% had ≥ 3. The right side was affected in 56% of cases, predominantly involving V2 (26%), V3 (24%), or a combination of both (18%) branches. The median age at diagnosis was 56 years, and median age at GKS was 64 years. The median prescription dose of 75 Gy (range 70–80 Gy) was delivered to the involved trigeminal nerve root entry zone. The authors assessed the degree of pain before and after GKS by using the Barrow Neurological Institute (BNI) pain scale. Results In total, 102 patients took the survey at least once, for a response rate of 91%. Although not found to alter the conclusions of this study, 7 cases of atypical TN were found and these patients were removed, for a total of 95 cases herein analyzed. The median follow-up was 5.6 years (range 13–115 months). Before GKS, 88% of patients categorized their pain as BNI IV or V (inadequate control or severe pain on medication), whereas the remainder described their pain as BNI III (some pain, but controlled on medication). After GKS, 64% reported a BNI score of I (no pain, no medications), 5% had BNI II (no pain, still on medication), 12% had BNI III, and 19% reported a BNI score of IV or V. The median time to response was 2 weeks (range 0–12 weeks) and the median response duration was 32 months (range 0–112 months). Eighty-one percent reported initial pain relief, and actuarial rates of freedom from treatment failure at 1, 3, 5, and 7 years were 60, 41, 34, and 22%, respectively. Response duration was significantly better for those who had no prior invasive treatment versus those in whom a previous surgical intervention had failed (32 vs 21 months, p < 0.02). New bothersome facial numbness was reported in 6% of cases. Conclusions This study represents one of the longest reported median follow-up periods and actuarial results for a cohort of patients with classic TN treated with GKS. Although GKS achieves excellent rates of initial pain relief, these results suggest a steady rate of late failure, particularly among patients who had undergone prior invasive surgical treatment. Despite a higher than expected recurrence rate, GKS remains a viable treatment option, particularly for patients who have had no prior invasive procedures. Patients with recurrences can still be offered salvage therapy with either repeat GKS, microvascular decompression, or rhizotomy.

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