Gamma Knife radiosurgery for trigeminal neuralgia

Gamma Knife radiosurgery for trigeminal neuralgia

Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN).

The first use of SRS by Leksell was for the treatment of trigeminal neuralgia. Initially, this was reserved for refractory cases following multiple operations 1).

The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radiosurgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness.

CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe,and cranial nerves VII and VIII) and in steeper dose fall off away from the target. The clinical significance of these effects is unknown 2).

Indications

Generally recommended for patients with co-morbidities, high-risk medical illness, pain refractory to prior surgical procedures, or those on anticoagulants (anticoagulation does not have to be reversed to have SRS).

Mechanism

The exact mechanism of pain relief after radiosurgery is not clearly understood. Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results.

There is evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed and need to be explored in future studies 3).

Existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique 4).

Treatment plan

4 -5 mm isocenter in the trigeminal nerve root entry zone identified on MRI. Use 70–80 Gy at the center, keeping the 80% isodose curve outside of the brainstem.

Results: Significant pain reduction after initial SRS: 80–96% 5) 6) 7) 8) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 9).

Recurrent pain occurs with in three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Outcome

Favorable prognosticators: higher radiation doses, previously unoperated patient, absence of atypical pain component, normal pre-treatment sensory function 10).

Side effects: Hypesthesia occurred in 20% after initial SRS, and in 32% of those requiring repeat treatment 11) (higher rates associated with higher radiation doses) 12).

Repeat Radiosurgery for Trigeminal Neuralgia

Case series

A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study.

The median latency period of Facial pain response (PR) after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute Pain Scale I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%).

In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control 13).

2016

One hundred seventeen patients with medically refractory TN treated by GKRS at the Department of Functional Neurosurgery and Gamma Knife Radiosurgery, and Department of Neurology, Ruber International Hospital, Madrid, Spain were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. They considered classes I and II as a complete response. For toxicity, they use the Barrow Neurological Institute Pain Scale. Mean duration of follow-up was 66 months (range: 24-171 months).

Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%.

GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. They consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients 14).


In a single-center, retrospective comparative study, 202 patients with MS and concomitant TN were evaluated. A minimum follow-up of 24 months was required. Patients with a history of microvascular decompression or previous intervention were excluded. There were 78 PBC procedures performed and 124 first-dosage GKRS procedures for a total of 202 patients between February 2009 and December 2013. The PBC procedures were successfully completed in all cases. The two groups were compared with regards to initial effect, duration of effect, and rate of complication(s), including the type and severity of the complication(s).

Immediate pain relief resulted in 87% of patients treated with PBC and in 23% of patients treated with GKRS. The Kaplan-Meier plots for the two treatment modalities were similar. The 50% recurrence rate was at 12 months for the PBC and 18 months for the GKRS. The rates of complication (excluding numbness) were 3% for GKRS and 21% for PBC. The difference was statistically significant (Chi-square test, p = 0.03).

PBC and GKRS are effective techniques for the treatment of TN in patients with MS, with GKRS presenting fewer complications and superior long-term relief. For these reasons, we consider GKRS as the first option for the treatment of TN in MS patients, reserving PBC for patients with acute, intractable pain 15).

References

1)

Lunsford LD. Comment on Taha J M and Tew J M: Comparison of Surgical Treatmen ts for Trigemin al Neuralgia: Reevaluation of Radiofrequency Rhizotomy. Neurosurgery. 1996; 38
2)

Descovich M, Sneed PK, Barbaro NM, McDermott MW, Chuang CF, Barani IJ, Nakamura JL, Lijun M. A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia. J Neurosurg. 2010 Dec;113 Suppl:199-206. PubMed PMID: 21222296.
3)

Al-Otaibi F, Alhindi H, Alhebshi A, Albloushi M, Baeesa S, Hodaie M. Histopathological effects of radiosurgery on a human trigeminal nerve. Surg Neurol Int. 2014 Jan 18;4(Suppl 6):S462-7. doi: 10.4103/2152-7806.125463. eCollection 2013. PubMed PMID: 24605252.
4)

Varela-Lema L, Lopez-Garcia M, Maceira-Rozas M, Munoz-Garzon V. Linear Accelerator Stereotactic Radiosurgery for Trigeminal Neuralgia. Pain Physician. 2015 Jan-Feb;18(1):15-27. PubMed PMID: 25675056.
5)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
6)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gorman DA. High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
7) , 12)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotact ic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
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Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotch i J, Levivier M. Gamma kn ife surgery for idiopathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
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Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vladyka V. Treatment of essential trigeminal neuralgia with gamma knife surgery. J Neurosurg. 2005; 102 Suppl:29–33
10)

Maesawa S, Salame C, Flickinger JC, Pirris S, Kondziolka D, Lunsford LD. Clinical outcomes after stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2001; 94:14–20
13)

Xu Z, Mathieu D, Heroux F, Abbassy M, Barnett G, Mohammadi AM, Kano H, Caruso J, Shih HH, Grills IS, Lee K, Krishnan S, Kaufmann AM, Lee JYK, Alonso-Basanta M, Kerr M, Pierce J, Kondziolka D, Hess JA, Gerrard J, Chiang V, Lunsford LD, Sheehan JP. Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study. Neurosurgery. 2019 Feb 1;84(2):499-505. doi: 10.1093/neuros/nyy142. PubMed PMID: 29688562.
14)

Martínez Moreno NE, Gutiérrez-Sárraga J, Rey-Portolés G, Jiménez-Huete A, Martínez Álvarez R. Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery: A Retrospective Study in Patients With Minimum 2-Year Follow-up. Neurosurgery. 2016 Dec;79(6):879-888. PubMed PMID: 27560193.
15)

Alvarez-Pinzon AM, Wolf AL, Swedberg HN, Barkley KA, Cucalon J, Curia L, Valerio JE. Comparison of Percutaneous Retrograsserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis: A Clinical Research Study Article. World Neurosurg. 2016 Oct 15. pii: S1878-8750(16)31016-6. doi: 10.1016/j.wneu.2016.10.028. PubMed PMID: 27756676.

International Gamma Knife Research Foundation

Upcoming Meetings

ASSFN 2016

IGKRF Biennial Scientific Session
University of Pennsylvania
Philadelphia, Pa.
June 23, 2017
Meeting Brochure
http://www.igkrf.org/
The International Gamma Knife Research Foundation consists of academic and clinical centers of excellence where brain Stereotactic Radiosurgery is performed using the Leksell Gamma Knife. All participating centers have a track record of outcomes research and participation in clinical trials.
The primary goal of the IGKRF is to facilitate retrospective and prospective clinical trials and outcomes analysis that evaluate the role of Gamma Knife radiosurgery in a wide spectrum of clinical indications.
Because individual centers may evaluate only a small number of patients with rare conditions, pooling of information is critical to evaluate and to improve outcomes. Each center has a professional team consisting of one or more neurological surgeons, radiation oncologists, and medical physicists. Participation is by invitation of the Board of Directors. ​ The IGKRF is a non-profit scientific, educational, and research entity incorporated in the state of Pennyslvania.​

Case series

2017

Ding et al. evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes.
The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms ( P = .001), and higher margin dose ( P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001).
Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs 1).

2016

Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed.
The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.
GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery 2). ​
1)

Ding D, Starke RM, Kano H, Lee JYK, Mathieu D, Pierce J, Huang P, Missios S, Feliciano C, Rodriguez-Mercado R, Almodovar L, Grills IS, Silva D, Abbassy M, Kondziolka D, Barnett GH, Lunsford LD, Sheehan JP. Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study. Neurosurgery. 2017 Jun 1;80(6):888-898. doi: 10.1093/neuros/nyx181. PubMed PMID: 28431024.
2)

Starke RM, Kano H, Ding D, Lee JY, Mathieu D, Whitesell J, Pierce JT, Huang PP, Kondziolka D, Yen CP, Feliciano C, Rodgriguez-Mercado R, Almodovar L, Pieper DR, Grills IS, Silva D, Abbassy M, Missios S, Barnett GH, Lunsford LD, Sheehan JP. Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort. J Neurosurg. 2016 Mar 4:1-9. [Epub ahead of print] PubMed PMID: 26943847.
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