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

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OBJECTIVE

Gamma 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.

METHODS

Thirty-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.

RESULTS

Trigeminal 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.

CONCLUSIONS

The 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.

ABBREVIATIONS AD = axial diffusivity; BNI = Barrow Neurological Institute; DTI = diffusion tensor imaging; FA = fractional anisotropy; FSPGR = fast spoiled gradient–recalled echo; GKRS = Gamma Knife radiosurgery; MD = mean diffusivity; RD = radial diffusivity; ROI = region of interest; TN = trigeminal neuralgia.

Article Information

Correspondence Mojgan Hodaie: Toronto Western Hospital, Toronto, ON, Canada. mojgan.hodaie@uhn.ca.

INCLUDE WHEN CITING Published online August 17, 2018; DOI: 10.3171/2018.3.JNS172936.

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

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    A: Schematic representation of the experimental timeline. B: Flow diagram of the MRI processing steps: for all patients, diffusion tensor images (upper left) are derived from the diffusion-weighted images. The T1-weighted anatomical images (upper right) are linearly registered to posttreatment diffusion space (lower). All images show the trigeminal nerves in the axial view, emerging from the midpontine level of the brainstem. The DTI is shown in color-by-orientation view (red: left-right; green: anterior-posterior; blue: superior-inferior). C: Flow diagram of process used to define the ROI: for each patient, the radiosurgical target location is determined from the Gamma Knife planning software as a DICOM image, which is superimposed on DTI—an example of a patient with left-sided TN is shown (upper). Masks 4 voxels in size are manually placed at this target ROI in red and the control ROI is placed in the contralateral, unaffected nerve in yellow (lower). Figure is available in color online only.

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    Diffusivity metrics taken at 6 months post-GKRS. A–D: Bar graphs showing the average DTI-derived values ± SEM with overlaid individual patient data for the affected (red) and unaffected (blue) trigeminal nerve in long-term responders and nonresponders. Responders show characteristically lower FA (A), higher MD (B), higher RD (C), and no change in AD (D) in their affected nerve compared to their unaffected nerve. Compared to nonresponders, responders also show distinctively lower FA (red bars, panel A) and a trend toward higher RD (p = 0.057) (red bars, panel C) in their affected nerve. E–H: Bar graphs showing the DTI-derived values computed as a percentage change for each individual: %DDTI Metric = Target - Contra/Contra × 100 (± SEM) for long-term responders (blue) and nonresponders (red). FA differentiates responders from nonresponders (E), whereas MD, RD, and AD do not (F–H). Aff = affected nerve; Unaff = unaffected nerve. * p < 0.05, ** p < 0.01. Figure is available in color online only.

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    Bar graphs showing the average FA values ± SEM with overlaid individual patient data at pretreatment (purple) and 6 months posttreatment (green) in the affected and unaffected trigeminal nerve of long-term responders (A) and nonresponders (B). Long-term responders show a substantial decrease in posttreatment FA in their affected nerve. These changes are not observed in nonresponders. The unaffected nerve remains unchanged between pre- and posttreatment for responders and nonresponders. Tx = treatment. * p < 0.05, ** p < 0.01. Figure is available in color online only.

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    Visual representation of the affected trigeminal nerve using tractography. The reconstructed tracts are overlaid onto the axial DTI/T1-weighted anatomical images at the midpontine level of the brainstem. The colors of the tracts represent the spectrum values of FA (0 to 0.7), as shown by the legend at the top right corner. The white box denotes the target area of the nerve where the radiation was delivered. The top 2 images (A and B) correspond to a long-term responder (single subject). Distinct changes in FA are visible at the target area when compared from pretreatment (A) to 6 months posttreatment (B), as represented by a shift in color from the purple/blue spectrum to green/yellow. The bottom 2 images (C and D) correspond to a nonresponder. In this patient, no FA changes are observed at the target area between pretreatment (C) and 6 months posttreatment (D). Figure is available in color online only.

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    Schematic representation comparing the current postoperative assessment, which relies solely on ongoing clinical follow-up (upper), with the expected postoperative assessment proposed in our study (lower). Our prognostic approach incorporates early DTI assessment with clinical measures. Patients who experience long-lasting pain relief after GKRS show a significant decrease in target zone FA, whereas patients who do not experience adequate pain relief show marginal changes in FA. This suggests that DTI metrics may help in earlier clinical decision-making for those who do not show improvement in pain following GKRS treatment. m = months. Figure is available in color online only.

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