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

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OBJECTIVE

Gamma 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.

METHODS

Ninety-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.

RESULTS

GKRS 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.

CONCLUSIONS

Ultimately, 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.

ABBREVIATIONS CBZ = carbamazepine; DTI = diffusion tensor imaging; FA = fractional anisotropy; GKRS = Gamma Knife radiosurgery; NRS = numerical rating scale; TN = trigeminal neuralgia.

Article Information

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

INCLUDE WHEN CITING Published online July 12, 2019; DOI: 10.3171/2019.4.JNS19380.

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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    Temporal profiles of TN pain intensities after GKRS. Responders to GKRS had significantly reduced numerical rating of pain intensity (NRS) at all posttreatment time points compared to pretreatment levels (A–C, Wilcoxon signed-rank tests). Nonresponders to GKRS had significantly reduced NRS at 6- and 12-month time points (D and E). Pain intensity for nonresponders to GKRS at the 24-month posttreatment time point was statistically indistinguishable from pretreatment levels (F). Black whiskers indicate standard errors of the mean, gray dots indicate individual pain intensity ratings. Blue lines depict individual posttreatment decreases in NRS. ** p < 0.01, *** p < 0.001 (false discovery rate corrected). Figure is available in color online only.

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    Posttreatment patterns of target microstructural diffusivities in responders. Microstructural diffusivities were contrasted between treatment target and contralateral controls within 6- (A–D), 12- (E–H), and 24-month posttreatment (I–L) time points. Successful TN pain relief was associated with significantly reduced treatment target FA at 12- (E) and 24-month (I) posttreatment time points compared to contralateral, untreated trigeminal nerve controls (Wilcoxon signed-rank tests). Black whiskers indicate 1.5 interquartile range, gray dots are individual diffusivity measurements. Blue lines depict individual decreases in diffusivity measurements in the treatment target compared to contralateral control. Red lines depict individual increases in diffusivity measurements in the treatment target compared to contralateral control. * p < 0.05 (false discovery rate corrected). 1e-3 = 1 × 10−3. Figure is available in color online only.

  • View in gallery

    Posttreatment patterns of target microstructural diffusivities in nonresponders. Microstructural diffusivities were contrasted between treatment target and contralateral controls within 6- (A–D), 12- (E–H), and 24-month posttreatment (I–L) time points. Bilateral diffusivities remained statistically indistinguishable between treated and contralateral control nerves across all posttreatment time points (Wilcoxon signed-rank tests). Black whiskers indicate 1.5 interquartile range, gray dots are individual diffusivity measurements. Blue lines depict individual decreases in diffusivity measurements in the treatment target compared to contralateral control. Red lines depict individual increases in diffusivity measurements in the treatment target compared to contralateral control. Figure is available in color online only.

  • View in gallery

    A biomarker of successful pain relief after GKRS. Microstructural diffusivity analyses revealed that delayed reductions in FA may uniquely indicate treatment success as it coincides with successful pain relief (defined as 75% or greater reduction in pain intensity after radiosurgery) at 12- and 24-month posttreatment time points. Furthermore, given that FA is a measure of myelination, this suggests that a unique association exists between altered myelination and successful pain relief. Figure is available in color online only.

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