Predicting Outcomes in Patients with Trigeminal Neuralgia: Preoperative FIESTA MRI and Microvascular Decompression Kurt J Niesner, BSc1,2 Jon Forbes, MD2 Calvin Cooper, MD2 Peter Konrad, MD, PhD2 Joseph Neimat, MD, MS2 Vanderbilt University Medical Center 1Center for Health Services Research 2Department of Neurological Surgery April 2012

Background Microvascular compression (MC) and TN Intense lancinating pain in areas innervated by the trigeminal nerve Reports indicate that 80-90% of TN is caused by MC1,2 75% of these compressions caused by SCA,10% by vein2 Past uses of imaging in preoperative evaluation Assess for presence of tumors and alternative etiologies Technological advances in MRIs Higher Tesla MRI, MRA, and 3D sequences explored3,4 Novel sequences increase reliability and specificity3 As you well know, trigeminal neuralgia is described as an intense lancinating pain in areas innervated by the trigeminal nerve. Reports currently indicate that approximately 80 to 90% of cases are caused by microvascular compression. In these cases, it’s been argued that approximately 75% are caused by the SCA, with approximately 10% caused by a vein. In the past, imaging methods were common in preoperative evaluations, but were usually limited to evaluating pts for tumors or alternative etiologies to their trigeminal neuralgia. Technological advances in MRIs include higher Teslas, angiography, and 3D sequences. Studies now describe the reliability and specificity advantages of novel sequencing in 3D MRI 1Forbes et al. J. Vis. Exp. (53), e2590, DOI : 10.3791/2590 (2011). 2Barker FG et al. N Engl J Med 334:1077–1083. 3Leal PR et al. Acta Neurochir 2010; 152:817-825. 4 Patel et al. Br J Neurosurg. 2003 Feb;17(1):60-4.

Background Advances in imaging technology Various 3D MRI technologies1 3D hi resolution MRI with steady state acquisition (3D FIESTA) 3D fast spoiled gradient echo (3D-FSPGR) sequences Provide clarity and contrast to visualize nerve and vasculature Could improved imaging facilitate planning? More rigorous MRI techniques have been demonstrated to have high sensitivity and specificity for identifying vascular compression in several studies2,3,4 Fidelity to specific intraoperative findings questioned Preoperative 3D MRIs may predict surgical outcome Some common 3D advances include hi resolution with steady state acquisition and 3D fast spoiled gradient echo sequences. These sequences provide us with increased clarity and contrast to facilitate visualizing the nerve and surrounding vasculature. So, taking these imaging advances into consideration, could these novel sequences improve preoperative planning? Several studies point to the high sensitivity and specificity of identifying and locating vascular compression. However, whether or not these loci hold true intraoperatively remains a question: What about pts without visualization but with positive compression, or pts with a visualized compression in one locus and one found intraoperatively in another locus? Therefore, we wanted to examine if preoperative MRIs were predictive of surgical outcome rather than the presence or absence of intraoperative compression. 1Leal PR et al. Acta Neurochir 2010; 152:817-825. 2Patel NK et al. Brit J Neurosurg 2003; 17:60-64. 3Anderson VC et al. Neurosurgery. 2006 Apr;58(4):666-73; discussion 666-73. 4Leal PR et al. Neurosurgery.  2011 Jul;69(1):15-25; discussion 26.

Methods Collected preoperative 3D MRIs of MVD cases Large academic tertiary medical center in the Southeast Obtained data on all MVD cases done in the past 5 years Limited the data set to patients with 3D MRIs Only reviewed 3D MRIs with FIESTA or FSPGR technology After exclusions, 47 patients were identified and reviewed Analyzed each patient’s MRI Assessed each patient’s post-operative pain status at follow-up We gathered a sample of all of the MVD cases done within the last 5 years at a large academic, tertiary medical center in the southeast. We limited these cases to pts with preoperative 3D MRIs and further limited that subset to pts with FIESTA and/or FSPGR sequencing, leaving us with a sample of 47 pts. We then analyzed each pt’s MRI and assessed each pt’s pain status at their first follow-up visit.

Methods Blinded attending neurosurgeon reviewed MRIs Classified locus and degree of compression Locus of compression: Left versus Right side Compression of root entry zone (REZ) versus distal nerve Degree of compression: 0-No compression 1-Vascular contact without obvious compression 2-Obvious compression or deviation of nerve So how did we go about reviewing the MRIs? Dr. Neimat, an attending neurosurgeon, was blinded to all variables and was only given a deidentified MRI slice to: Classify the locus and degree of compression, locus meaning left versus right and compression of the REZ versus the distal nerve And two, the degree of compression, where 0 was no compression, 1 was vascular contact without obvious compression, and 2 being obvious compression or deviation of the nerve.

Obvious Compression To give you a better picture, here we have an obvious compression at the right REZ.

Vascular Contact Here we have vascular contact at the right REZ.

No Compression And here we have no compression with a pt presenting with a right sided cluster symptoms thought to be secondary to trigeminal neuralgia.

Methods Compared to postoperative follow-up results Classified on a scale of 0 to 3 0-No improvement in pain 1-Slight improvement 2-Significant improvement. 3-Complete pain resolution. Statistical Analysis Cohorts compared using Fisher’s exact test Analyzes contingency tables in small sample sizes (N=47) We compared each pt’s MRI, again degree of compression and locus of compression, to the pt’s pain status at the first postoperative folow-up visit. Pain status was classified on a scale of 0 to 3, where 0 was no improvement in pain, 1 was slight improvement in pain, 2 was significant improvement, and 3 was complete pain resolution. We decided to use the Fisher’s Exact Test to analyze our data since it’s commonly used to analyze contingency tables in small sizes.

Results 47 patients received 3D preoperative MRIs Patients were evaluated as described: Females highly represented in the sample Age typical of TGN population Gender (Male/Female) 9/38 Average Age (years ± SD) 55 ±14 Average Time to Follow-Up (days ± SD) 36 ±17 Again, we analyzed 47 pts, 9 of which were male, 38 of which were female. The average age was 55 years old with a standard deviation of 14. The average time to folow-up across the sample was 36 days with a standarf deviation of 17. Obviously, females were highly represented in the sample. The age was right on target and representative of the typical trigeminal neuralgia population.

Response to MVD surgery (short term) Vascular contact (even at REZ) did not correlate with outcome. Obvious compression showed trend toward predicting outcome: 15/17 patients (88%) reported complete or significant pain relief (Outcome 2 or 3), 19/30 patients (63%) without compression pain free. Fisher's Exact Test p=0.09 Obvious compression at REZ was significantly predictive of pain relief: 14/15 patients with REZ compression(93%) reported complete or significant pain relief, 20/32 patients (62%) without compression pain free. Fisher's Exact Test p=0.037 At face value, vascular contact, even at the REZ, did not correlate with outcome. However, as noted in our abstract, an obvious compression correlated with outcome. Here we saw that 15 of 17 patients with an obvious compression reported complete or significant pain relief versus 19 pain free patients of 30 without compression. This represents a trend of 88% versus 63% of patients with a Fisher’s Exact Test p-value of 0.09. In reassessing our data, we found a very interesting trend when adding locus in our comparison. Here we found that 14 of 15 patients with REZ compression reported complete or significant pain relief compared to 20 patients of 32 without compression, for a comparative value of 93% versus 62%. Here we have a significant comparision, with a Fisher’s exact p value of 0.037! ----------- Abstract if had 2 anywhere on nerve it had .09. increase specific compare pts who have a compression at the drez compared to any other compression yields significant data. We looked at this a couple different ways, 2 different logical comparisons. Will become clearer when we have a larger sample. Did contact anywhere at the REZ whether or not is. Must have highly compressed and located and REZ to get significant. REZ COMP No REZ COMP Significant or complete Relief 14 20 Little or No Relief 1 12

Response to MVD surgery (short term) In order to visualize the significance of this latter comparison, I inserted this bar graph to show just how drastic this effect really is. The blue bar represents percent of patients that are pain free or with significant pain relief versus the red bar which represents the percent of patients without significant pain relief as a function of REZ compression Fisher's Exact Test p=0.037

Conclusion Preliminary data suggest predictability of MRI Preoperative MRIs showing REZ compression predicted surgical relief in 93% vs 62% of patients. FIESTA MRI may be useful in guiding decision to operate May also be useful in counseling patients Future study currently underway Larger sample of 100+ cases of MVD and RFL/Balloon Rhizotomy Examining outcome via long-term follow up Quality of life several years post-surgery Administering Brief Pain Inventory—Facial1 to assess pain These preliminary data suggest that preoperative 3D MRIs with FSPGR or FIESTA sequencing may predict surgical relief in this population of patients suffering from trigeminal neuralgia deemed secondary to microvascular compression. Thus, these sequences may be useful in guiding the decision to operate and in providing patients with concrete numbers in helping them decide whether or not to pursue surgical intervention. We’re currently conducting Study II wherein we plan to evaluate a larger sample size of pts undergoing MVD and RFL or Balloon Rhizotomy. We’ve begun examining long-term outcome in this population, too, by assessing their quality of life via the facial Brief Pain Inventory developed by Lee an colleagues. This will also provide us with an assessment of how these pts are doing several years out of surgery. We think these results will shed even more light on both the efficacy of preoperative MRIs and MVD itself. 1Lee JY, Chen HI, Urban C, et al. J Neurosurg. 2010 113(3): 516-523.