Gamma Ray Radiosurgery for Trigeminal Neuralgia: Targeting Proximal or Distal to the Dorsal Root Entry Zone

Abstract

Introduction Stereotactic radiosurgery for trigeminal neuralgia (TN) has gained interest among patients who are not suitable for surgical procedures. Although two target zones are more recognized - dorsal root entry zone (DREZ) and retrogasserian zone (RGZ) - the optimal targeting technique remains controversial in terms of clinical outcomes and rates of complications. Therefore, various modifications to the radiosurgical technique for TN have been made. Objective This study aimed to determine the differences in shoot location (i.e., RGZ vs. DREZ) regarding effectiveness and adverse effects in patients with medically refractory TN. Additionally, we evaluated the effect of the integral dose (ID) on treatment outcomes and complications. Methods We present a retrospective cohort study of 49 patients with primary, drug-resistant TN treated with gamma knife radiosurgery targeting the distal and proximal parts of the nerve regarding the DREZ with a prescription dose of 90 Gy (80 to 96 Gy). A subset of these patients (n=38) where the ID could be measured to the nerve was correlated to treatment outcomes and complications. Results The median follow-up time was 36 months for RGZ and 51 months for DREZ targets. Neurovascular conflict was identified in 87.5% of the RGZ group and 88.2% of the DREZ group. Using the Barrow Neurological Institute (BNI) pain score, 26 (81.3%) RGZ and 12 (70.6%) DREZ patients were successfully treated (BNI I-IIIb; p=0.02). Seven (21.9%) RGZ and eight (47.1%) DREZ patients reported complete pain relief without medication (BNI I). Time response was 22.3 days for RGZ and 34.1 days for DREZ (p=0.277). There were 10 (31.3%) patients in the RGZ group with associated complications versus six (35.3%) patients in the DREZ group (χ²=0.0826, degree of freedom=1, p=0.773). Treatment outcomes using higher ID were better in the RGZ than DREZ (81.8% vs. 57.1, respectively), and a significant association was found between a higher ID delivered to the nerve and the development of complications (p=0.02). Conclusion Based on the obtained results, the RGZ was a more effective targeting area with better treatment outcomes without significant differences in complication rates than DREZ. A higher ID at the RGZ than DREZ had a greater therapeutical effect. Further investigation regarding the optimal target area along the ID delivered and clinical outcomes are required.

Keywords: gamma knife (gk) radiosurgery; intracranial radiosurgery; secondary trigeminal neuralgia; stereotactic and functional neurosurgery; trigeminal nerve.

Figure 1. Different shoot strategies

(A) Axial CISS sequence of the left trigeminal nerve, a small area of the brainstem has been drawn in yellow. The distance from the nerve entrance to the brainstem is 3.2 mm to the isocenter of the 4-mm collimator shoot. Green isodose line represents 50% of the prescription dose that transduce to 45 Gy. (B) Same sequence with a blue isodose line that represents 20 Gy for the DREZ shoot. (C) The same sequence with the isocenter of the 4-mm shoot has been moved forward 11.5 mm posterior to the gasserian portion of the nerve outlined in orange. (D) The same sequence with a blue isodose line that represents 20 Gy for the RGZ shoot. Abbreviations: CISS, constructive interference in steady state; DREZ, dorsal root entry zone; RGZ, retrogasserian zone.

Figure 2. Measurement of the integral dose

(A) T1 MPR gadolinium axial images of the entire right trigeminal nerve of a DREZ targeting, green circle corresponds to the 50% isodose line with a 90-Gy prescription dose. Inside the isodose line, the nerve has been drawn in orange to obtain the target volume of 31.7 mm³ multiplied by the mean dose of 66 Gy divided by 1,000, ID is equal to 2.09. (B) CISS axial images of the entire left trigeminal nerve of an RGZ targeting, the green circle corresponds to the 50% isodose line with a 90-Gy prescription dose, and the nerve inside it has been drawn in orange. By performing the same calculation, the ID for this patient is equal to 1 as the nerve volume is now 16.5 mm³ and the mean dose is 61.2 Gy. Abbreviations: CISS, constructive interference in steady-state; DREZ, dorsal root entry zone; ID, integral dose; MPR, multiplanar reconstruction; RGZ, retrogasserian zone.

Figure 3. Comparison between dose registered by millimeter from the DREZ

Target definition apart from anatomical identification was also determined by dose measurement at 1 mm, 2 mm, 3 mm, and 4 mm of the DREZ in each group. Dose variation delivered at each mm had significant association as shown in the box and whiskers plot (p=0.001); such findings reinforce target location and dose variation between the RGZ and DREZ and could be determined despite anatomical variations of the nerve. Abbreviations: DREZ, dorsal root entry zone; RGZ, retrogasserian zone.

Figure 4. Comparison of medication use between groups before and after radiosurgery

Medication use before and after radiosurgery was made between both groups of treatment. A significant association was found among RGZ and DREZ patients when comparing medication use before and after radiosurgery (p=0.004 for RGZ and p=0.002 for DREZ). Both groups showed an increase in patients not using any type of medication after radiosurgery and decreased medication use after the treatment. Abbreviations: DREZ, dorsal root entry zone; RGZ, retrogasserian zone.