# Radiation Oncology/CNS/Trigeminal neuralgia/Treatment

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Trigeminal Neuralgia Treatment

## Treatment Overview

* Medical (carbamazepine, phenytoin, gabapentin, baclofen) first, until failure
* Surgical
** Destructive: radiofrequency rhizotomy, glycerol rhizotomy, balloon compression, peripheral neurectomy
** Non-destructive: microvascular decompression
* Radiosurgery
** Gamma Knife
** Linac-based

## Medical treatment

* Meta-analysis (1960-2005) PMID 17174762 -- "Drug treatment of trigeminal neuralgia: a systematic review of the literature." (Chole R, J Oral Maxillofac Surg. 2007 Jan;65(1):40-5.)
** 21 publications with high level of evidence (6 randomized, 15 controlled clinical trials), 348 patients
** Conclusion: Anticonvulsants effective, but difficult to compare/combine data in a scientifically meaningful manner

## Surgery

* Pittsburgh
** 1972-1991 -- "The Long-term Outcome of Microvascular Decompression for Trigeminal Neuralgia." (Barker et al. NEJM. 1996, 334:17, 1077-1083)
*** Retrospective study of 1185 patients who underwent microvascular decompression.
*** Immediate pain relief in 82%, partial 16%, and none in 2%. 75% had complete relief at 1 year, 9 % partial. 64% had complete relief at 10 years, 4 had partial (first surgery).
*** 11% had re-operation for recurrent or refractory symptoms-total 80% had complete relief at 1 year and 8% partial, 70% had complete relief at 10 years, 4 had partial.
Decision Analysis
* Queen Mary; 2007 PMID 17451880 -- "Decision analysis of medical and surgical treatments for trigeminal neuralgia: how patient evaluations of benefits and risks affect the utility of treatment decisions." (Spatz AL, Pain. 2007 Oct;131(3):302-10. Epub 2007 Apr 23.)
** 156 patients evaluated with time-trade-off utility measurement questionnaire
** Outcome: MVD highest maximum expected utility (16.08), followed by balloon compression (15.97), glycerol rhizolysis (15.61), and RFA (14.93). Meds alone worst at 14.61. Difference between highest and lowest treatments 7%, and sensitive to utility values
** Conclusion: Patients should consider surgery over meds, but treatment utility differences minimal

## SRS vs. Surgery

* Columbia; 2007 PMID 17167238 -- "Microvascular decompression vs. gamma knife radiosurgery for typical trigeminal neuralgia: preliminary findings." (Brisman R, Stereotact Funct Neurosurg. 2007;85(2-3):94-8.)
** Prospective protocol. 85 patients (GKS 61, MVD 24). GKS 75 Gy max.
** Outcome: CR (no pain, no meds): 1 year GKS 58% vs. MVD 68%; 2 years 24% vs. 68% (p=0.09)
** Toxicity: no permanent complications
** Conclusion: MVD more likely than GKS to result in complete pain relief
* UCSF
** 2005 PMID 16419978 -- "Management of medically refractory trigeminal neuralgia in patients with multiple sclerosis." (Cheng JS, Neurosurg Focus. 2005 May 15;18(5):e13.)
*** Retrospective. 11 patients with TN-MS. Mean f/u 40 months
*** Conclusion: Complete pain relief in TN-MS significantly more difficult than other TN, including highly refractory TN. SRS effective procedure, resulting in fewer retreatments, longer pain-free intervals compared with MVD or RF ablation
** 2005 PMID 16419977 1997-2004 -- "Recurrent or refractory trigeminal neuralgia after microvascular decompression, radiofrequency ablation, or radiosurgery." (Sanchez-Mejia RO, Neurosurg Focus. 2005 May 15;18(5):e12.)
*** Retrospective. 32/209 patients treated with SRS, MVD or RFA required retreatment.
*** Outcome: 19/93 MVD retreated (20%). 5/12 RFA retreated (42%), 8/108 (7.7%) SRS retreated, 2 with SRS.
*** Conclusion: lowest re-treatment rates with SRS. SRS also more likely to be final treatment for recurrence, regardless of initial treatment
* Cooper University; 2005 1994-2002 PMID 16111575 -- "Glycerol rhizotomy versus gamma knife radiosurgery for the treatment of trigeminal neuralgia: an analysis of patients treated at one institution." (Henson CF, Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):82-90.)
** Retrospective. 36/79 patients (GR) and 63/109 (GK) evaluated. RT 70-90 Gy to 100% isodose.
** Initial success: (Barrow I-III) 86% GR vs. 92% GK. Median time to relief <24hr GR vs. 3 weeks GK.
** Failure or pain recurrence: 53% GR vs. 42% GK (NS). Median time to failure 5mo GR vs. 8 mo GK (NS). End of treatment 39% GR vs. 24% GK failed
** Side effects: facial numbness 54% GR vs. 30% GK, bothersome 33% GR vs. 11% GK. GK lower pain score (OR 4.3)
** Conclusion: GR for acute pain relief, GK otherwise
* Mayo
** 2005 PMID 15951649 1999-2001 -- "A prospective cost-effectiveness study of trigeminal neuralgia surgery." (Pollock BE, Clin J Pain. 2005 Jul-Aug;21(4):317-22.)
*** Prospective, nonrandomized. 126 patients (MVD 33, GR 51, SRS 69)
*** Outcomes (6 months, 24 months): MVD (85%, 78%) vs. GR (61%, 55%) vs. SRS (60%, 52%). MVD > GR = SRS
*** Cost per quality adjusted pain-free year: MVD $8174 vs. GR $6342 vs. SRS $8269
** 2005 PMID 15913282 1999-2004 -- "Comparison of posterior fossa exploration and stereotactic radiosurgery in patients with previously nonsurgically treated idiopathic trigeminal neuralgia." (Pollock BE, Neurosurg Focus. 2005 May 15;18(5):E6.)
*** Retrospective. 55 patients PFE (MVD 89%, partial nerve section 11%), 28 patients SRS as initial treatment. RT mean dose 89.1 Gy. Mean f/u 25.5 months
*** Outcome: Pain free at 1 year: 75% vs. 59% (SS). Additional surgery in 18% after PFE vs. 29% after SRS (NS)
*** Side effects: facial numbness/dysesthesias: PFE 15% vs. SRS 43%
*** Conclusion: PFE more effective as primary therapy

## Gamma Knife

* There is only one prospective trial published, from Marseille. At 1 year, 83% were pain free, with 58% off medications as well
* There are a number of retrospective, single institution studies published
* Target: ipsilateral trigeminal nerve adjacent to the pons with single shot 4mm collimator
* Dose: Typically 70-90 Gy

### Prospective

* Marseille, 2006 (France) PMID 16776335 -- "Prospective controlled trial of gamma knife surgery for essential trigeminal neuralgia." (Regis J, J Neurosurg. 2006 Jun;104(6):913-24.)
** Phase I. 100 patients, 42 prior surgical treatment. RT: median dose 85 Gy (70 - 90 Gy). Minimum F/U 12 months, median ?
** Pain relief: 83/100 patients pain free at 12 months, 58/100 patients pain free and off meds. 17 patients underwent additional procedures
** Probability of worse outcome (SS and trend): <60 year old, isocenter-nerve emergence distance >8mm, large cistern surface, lower minimal nerve dose, prior procedure
** Side effects: Mild facial paresthesia 6%, hypesthesia 4%

### Retrospective

Please see the Literature Review

### GKS Technique

* Brussels (Belgium)
** 2007 PMID 17689881 -- "Clinical Evaluation of Targeting Accuracy of Gamma Knife Radiosurgery in Trigeminal Neuralgia." (Massager N, Int J Radiat Oncol Biol Phys. 2007 Aug 7; [Epub ahead of print])
*** Retrospective. 78 patients treated with 90 Gy. 68 (83%) had follow-up MRI with focal nerve enhancement. F/U MRI fused with treatment MRI and correlated
*** Outcome: Median deviation between pre and post MRI 0.91 mm. RT dose within contrast enhancement on post MRI median 77 Gy, range 49-85 Gy
*** Conclusion: Median deviation low
** 2007 PMID 17415205 -- "Influence of nerve radiation dose in the incidence of trigeminal dysfunction after trigeminal neuralgia radiosurgery" (Massager N, Neurosurgery. 2007 Apr;60(4):681-7; discussion 687-8.)
*** Comparative. 358 patients (109 Brussels, 259 Marseilles). Three dosimetry groups: Group I <90 Gy no blocking, Group II 90 Gy no blocking, Group III 90 Gy blocking
*** Toxicity: mild Group I 15% vs. Group II 21% vs. Group III 49%; bothersome 1.4% vs. 2.4% vs. 10%
*** Pain control: excellent 66% vs. 77% vs. 84%; good 81% vs. 85% vs. 90%
*** Conclusion: Incidence of TN dysfunction and pain relief vary according to energy deposited to retrogasserian nerve root. Effect may be related to energy to nerve root rather than maximal dose delivered
** 2006 PMID 16682146 -- "Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia." (Massager N, Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1200-5.)
*** Retrospective. 109 patients, 49 had channel blocking to brainstem. RT 90 Gy
*** Blocking increased length of trigeminal nerve exposure, and thus mean dose.
*** Outcome: better pain outcome (84% vs. 62% nonblocked), but worse trigeminal dysfunction (47% vs. 32%)
** 2004 PMID 15070111 -- "Gamma knife surgery for idiopathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation." (Massager N, J Neurosurg. 2004 Apr;100(4):597-605.)
*** Retrospective. 47 patients. Mean f/u 16 months
*** Pain relief: 68% excellent, 89% fair (>50%). Prognostic factors: higher dose, shorter distance to brainstem, development of facial sensory disturbance
*** Side effects: Mild facial numbness 38%, bothersome 4%
*** Conclusion: target nerve 5-8 mm from brainstem
* Wake Forest; 2006 PMID 17121135 -- "Does dose rate affect efficacy? The outcomes of 256 gamma knife surgery procedures for trigeminal neuralgia and other types of facial pain as they relate to the half-life of cobalt." (Balamucki CJ, J Neurosurg. 2006 Nov;105(5):730-5.)
** Retrospective. 239/326 patients. 80% experienced >50% pain relief, 56% complete relief
** Neither dose rate nor treatment time were significantly associated with control rate or degree of pain relief
** Conclusion: Consistent treatment any time during first half-life of Co source
* Columbia
** 2005 PMID 15850900 -- "Where to locate the isocenter? The treatment strategy for repeat trigeminal neuralgia radiosurgery." (Zhang P, Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):38-43.)
*** Retrospective. 40 patients with repeat GK. RT max 75 Gy initially, 40 Gy retreatment. Median f/u 28 months
*** Pain relief: complete 27%, nearly complete 18%, partial 20%, minimal/none 35%
*** Isocenter distance: mean 2.86 mm (complete/nearly complete relief) vs. 1.93 (partial/none relief). Farther distance with trend to better pain relief
*** Side effects: 7% moderate dysesthesia (4/10), 3% severe dysesthesia (7/10) after retreatment. Not related to isocenter distance
** 2002 PMID 12015844 -- "Trigeminal Nerve-Blood Vessel Relationship as Revealed by High-resolution Magnetic Resonance Imaging and Its Effect on Pain Relief after Gamma Knife Radiosurgery for Trigeminal Neuralgia." (Brisman R, Neurosurgery. 2002 Jun;50(6):1261-6, discussion 1266-7.)
*** Blood vessel - CNV contact evaluated. Group I (none) 24%, Group II (close) 17%, Group III (contact) 59%. Contact more often in men (SS), more often with unilateral TN.
*** If no prior surgery, BV-CNV contact may be prognostic factor
** 2000 PMID 11143235 -- "Gamma knife radiosurgery for trigeminal neuralgia: dose-volume histograms of the brainstem and trigeminal nerve." (Brisman R, J Neurosurg. 2000 Dec;93 Suppl 3:155-8.)
*** Volume of brainstem that receives >20% of Dmax (VB20), and volume of trigeminal nerve that receives >50% of Dmax (VT50) assessed
*** VB20 excellent pain control: 6 months <20mm3 32% vs. >20mm3 56% (SS), 12 months <20mm3 27% vs. >20mm3 50% (SS)
*** VB20 is lower in TN-MS. VB20 is inversely related to VT50
*** Conclusion: isocenter proximity to brainstem (reflected by higher VB20) is better
* Upstate 2005 1998-2003 PMID 15662807 -- "Gamma knife surgery for trigeminal neuralgia: improved initial response with two isocenters and increasing dose." (Alpert TE, J Neurosurg. 2005 Jan;102 Suppl:185-8.)
** Retrospective. 63 patients, 1 shot in 27 vs 2 shots in 36 patients. Dose 20 patients <=80 Gy, 21 patients 85 Gy, 22 patients >=90 Gy. Pain evaluated using BNI scale
** Pain relief: Initial 90%, overall 27%. Facial numbness 8%
** Number of shots: "2" 2.83 BNI improvement vs. "1" 1.72 BNI improvement (SS)
** Dose: SS improvement with each higher dose group
* Maryland
** 2005 ASTRO Abstract 2336 -- "Evaluating the Influence of Dose-Rate on Outcome with Gamma-Knife Stereotactic Radiosurgery in the Treatment of Trigeminal Neuralgia" (Patel S)
*** Retrospective. 61 patients. 31 prior to source change, 30 after source change. RT dose 75 Gy (70-80 Gy). Median f/u 30 months
*** Dose rate: 161.6 cGy/min (151-179) vs. 342.9 cGy/min (321-366)
*** Pain control: 61% vs. 83% (SS). Recommend dose escalation below dose rate 179.4 cGy/min
*** Side effects: 16% vs. 10% (NS)
** 2004 PMID 15380590 1996-2001 -- "Gamma knife surgery for trigeminal neuralgia: outcome, imaging, and brainstem correlates." (Cheuk AV, Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):537-41.)
*** Retrospective. 96/112 patients. RT 75 Gy (60-80Gy)
*** Imaging: 58% good, 31% fair, 10% poor. No correlation to outcome
*** Dose to brain stem: 44% received 10% of Dmax, 56% received 20% of Dmax. No correlation to outcome
*** Nerve compression: 11% by MRI. No correlation to outcome
** 2004 PMID 15379025 -- "Selective source blocking for Gamma Knife radiosurgery of trigeminal neuralgia based on analytical dose modelling." (Li K, Phys Med Biol. 2004 Aug 7;49(15):3455-63.)
*** Algorithm to selectively block sources to minimize dose to brainstem.
*** Moderate number of plugs (30-50) significantly lowers (40%) dose to brainstem. No mention of dose to trigeminal nerve in abstract
** 2003 PMID 12870587 -- "A technique to sharpen the beam penumbra for Gamma Knife radiosurgery." (Guerrero M, Phys Med Biol. 2003 Jun 21;48(12):1843-53.)
*** Physical penumbra (defined as distance 90% to 50% isodose) typically 1-2 mm. Technique to insert a conic filter into individual plug collimator to flatten beam profile
*** Able to reduce single penumbra width by 30-60%, at cost of reduced beam intensity by 20-50%
* 2005 Northwest Hospital (Seattle) ASTRO Abstract -- "Dose-Response and Dose-Complication Relationships in Stereotactic Radiosurgery for Trigeminal Neuralgia" (Meier R, Abstract 2353)
** Retrospective. 252 patients, typical or atypical TN. RT to 76 Gy (58 patients), 87 Gy (101 patients), or 98 Gy (93 patients) using 0.87 output factor. Mean f/u 3.9 years, 2.0 years, 1.7 years
** Pain control: favorable 74%, 75%, 76% (NS)
** Side effects: sensory deficit 9%, 22%, 39% (SS)
** Conclusion: dose escalation doesn't improve pain control, but has more complications
* Cleveland Clinic 2004 PMID 15007220 -- "Gamma knife radiosurgery for trigeminal neuralgia: comparing the use of a 4-mm versus concentric 4- and 8-mm collimators." (Kanner AA, Stereotact Funct Neurosurg. 2004;82(1):49-57.)
** 101 patient evaluated, 54 treated with 4-mm helmet, and 47 with 4/8-mm helmet. RT 75 Gy to 100% isodose line
** No difference in outcome
* Royal Hallamshire 2002 (UK) PMID 12507100 -- "The clinical application of plugging patterns for the Leksell gamma knife." (Vaughan P, J Neurosurg. 2002 Dec;97(5 Suppl):579-81.)
** Plugging significantly improved conformity and reduced brain stem exposure, without altering length of TN treated
* Mayo 2001 PMID 11440460 1997-1999 -- "High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction." (Pollock BE, Neurosurgery. 2001 Jul;49(1):58-62; discussion 62-4.)
** Retrospective. 68 patients. 40% 70 Gy, 60% 90 Gy. Mean f/u 14.4 months
** Pain control: 70 Gy 41% pain free vs. 90 Gy 61% (NS)
** Side effects: 70 Gy 15% TN dysfunction vs. 90 Gy 54% (SS). Bothersome in 4% vs. 32%. Corneal numbness in 3/41 (8%). Pain control better in those with TN dysfunction
** Conclusion: recommend dose <90 Gy
** Comment in PMID 12051192 "High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction." (Regis J, Neurosurgery. 2002 Jun;50(6):1401-2; author reply 1402-3.)
* Pittsburgh 2001 PMID 11567820 -- "Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind, randomized study." (Flickinger JC, Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):449-54.)
** Randomized. 87 patients. RT 75 Gy to 1 or 2 isocenters. Median f/u 26 months
** Pain relief: excellent 52%, good (low dose meds) 14%, partial 17%, failed 17%. Identical for 1 or 2 isocenters. Relapse in 42% of responding patients
** Side effects: 14% of 2 isocenters vs. 7% of 1 isocenter (NS). Complications correlated (SS) to nerve length irradiated

## Linac
### Linac Outcomes

* Wisconsin 2005 PMID 16331167 -- "Linear accelerator radiosurgery for trigeminal neuralgia." (Richards GM, Neurosurgery. 2005 Dec;57(6):1193-200; discussion 1193-200.)
** Retrospective. 28 patients. RT 80 Gy with 4-mm collimator and 7-arc technique. Median f/u 12 months
** Outcome: 57% complete pain relief, 75% 3 point pain reduction (10 point scale). Median time to pain relief 1 month. Mean time to pain recurrence 14 months. Women longer mean time to pain recurrence (16 vs. 7 months)
** Side effects: 3 patients mild facial numbness; 1 neurotrophic keratopathy
* Stanford
** 2005 PMID 15913285 2002-2004 -- "CyberKnife radiosurgery for idiopathic trigeminal neuralgia." (Lim M, Neurosurg Focus. 2005 May 15;18(5):E9.)
*** Retrospective. 41 patients with typical TN. Mean follow-up 11 months
*** Pain control: Initial 93% at median 7 days. Pain control 88% excellent, 5% moderate, 7% no change. Recurrence 16%, median time to recurrence 6 months. Long term response (@ 11 months) 78%
*** Higher prescribed doses not associated with pain relief or recurrence rate. Hypesthsia rate related to length of trigeminal nerve treated
** 2003 PMID 14742972 -- "Cyberknife radiosurgery for trigeminal neuralgia." (Romanelli P, Stereotact Funct Neurosurg. 2003;81(1-4):105-9.)
*** Preliminary report. CT cisternography for localization. 10 patients, 7 achieved pain relief.
* Minnesota 2004 PMID 15637446 -- "Long-term follow-up of trigeminal neuralgia treatment using a linear accelerator." (Kubicek GJ, Stereotact Funct Neurosurg. 2004;82(5-6):244-9.)
** Retrospective. 20 patients. RT 82.3 - 100 Gy. Median f/u 56.5 months
** Pain control: 35% complete, 78% >50% improvement. Recurrence 63%, mean interval 21.5 months
* Kaiser Permanente 2004 2002-2003 PMID 15537188 -- "Treatment of trigeminal neuralgia with linear accelerator radiosurgery: initial results." (Chen JC, J Neurosurg. 2004 Nov;101 Suppl 3:346-50.)
** Retrospective. Novalis. 32 patients treated. RT 85-90 Gy in 5- or 7- noncoplanar arcs with 4-mm collimator. For GKS retreatment, 60 Gy dose
** Pain relief: BNI I-III in 78% patients, median time to relief 6 weeks.
* UCLA
** 2004 PMID 14981193 -- "Noninvasive linear accelerator radiosurgery as the primary treatment for trigeminal neuralgia." (Frighetto L, Neurology. 2004 Feb 24;62(4):660-2.)
*** Retrospective. 22 patients treated on dedicated Linac
*** Pain control: 95.5% significant pain relief
** 2003 PMID 14519214 1999-2001 -- "Linear accelerator radiosurgery using 90 gray for essential trigeminal neuralgia: results and dose volume histogram analysis." (Goss BW, Neurosurgery. 2003 Oct;53(4):823-8; discussion 828-30.)
*** Retrospective. 25 patients. RT 90 Gy with 5-mm collimator. Median f/u 18 months
*** Pain relief: 76% excellent, 100% >50% relief
*** Side effects: 32% facial numbness, none painful. No correlation with brainstem volume
** 2003 PMID 12959439 1995-2001 -- "Dedicated linear accelerator radiosurgery for the treatment of trigeminal neuralgia." (Smith ZA, J Neurosurg. 2003 Sep;99(3):511-6.)
*** Retrospective. 60 patients, 68% essential TN, 20% secondary, 11% atypical. RT mean 83 Gy (70-90 Gy). 5-mm collimator in 75% patients, 7.5-mm collimator in 25% patients. Mean f/u 23 months
*** Pain relief: essential TN 56% excellent, 88% good+excellent; secondary pain 58% significant; atypical pain "worse results". Relief experienced at mean 2.7 months
*** Side effects: 25% new numbness
** 2002 ASTRO Abstract 1995-2001 -- "Linear Accelerator Radiosurgery Comparing 90Gy and Less Than 90 Gy for Essential Trigeminal Neuralgia" (Goss B, Abstract 247, 2002)
*** Retrospective. 41 patients treated. RT dose 70-85 Gy (16 patients), 90 Gy (25 patients). Median f/u 13 months
*** Pain control: 70-85Gy - 37% excellent, 31% good. Relapse 50%. 90Gy - 76% excellent, 24% good. Relapse 32%. Length of pain relief, good&excellent response better in 90Gy
*** Side effects: 70-85Gy - 31% numbness, none bothersome. 90Gy - 32% numbness, none bothersome

### Linac technique

* Maryland PMID 16264249 -- "Comparative analyses of linac and Gamma Knife radiosurgery for trigeminal neuralgia treatments." (Ma L, Phys Med Biol. 2005 Nov 21;50(22):5217-27.)
** Dose fall-off and set-up error tolerance of linac vs. Gamma Knife
** Equivalent dose fall-off with high number of arcs. However, increased treatment time and icocenter accuracies a concern
* Minnesota PMID 15753942 -- "Linac-based stereotactic radiosurgery for treatment of trigeminal neuralgia." (Gerbi BJ, J Appl Clin Med Phys. 2004 Summer;5(3):80-92.)
** Accuracy comparable to Gamma Knife, dose distributions equivalent. Disadvantage time involved.

## Outcome Evaluation

* ESI-55 PMID 1556879 -- "A health-related quality of life instrument for patients evaluated for epilepsy surgery." (Vickerey BG, Med Care. 1992 Apr;30(4):299-319.)
** 55 item scale to measure health-related quality of life in epilepsy patients
** Reliable, valid, sensitive to differences in seizure status
** Used by Marseille group in the prospective TN trial to evaluate QOL

## Serious SRS side effects

* Semmelweist; 2007 (Hungary) PMID 17317993 -- "Pathological findings following trigeminal neuralgia radiosurgery." (Szeifert GT, Prog Neurol Surg. 2007;20:244-8.)
** Case report. Retreatment, initial dose 90 Gy distally, followed by 70 Gy proximally. Hemorrhagic stroke 26 days after 2nd treatment
** Autopsy: neurovascular conflict close to 2nd shot, with acute and chronic radiation-induced lesions in trigeminal nerve
* Amakusa; 2005 (Japan) PMID 16167795 -- "[A case of delayed facial palsy following gamma knife radiosurgery for intractable trigeminal neuralgia]" [Article in Japanese] (Itai K, Masui. 2005 Sep;54(9):1018-20.)
** Case report. 77 y/o F. SRS RT 77 Gy.
** After 20 months developed left facial palsy with hydropsia, left xerophthalmia, left facial hypesthesia. Resolved over several months on oral prednisolone
* Mayo
** 2004 PMID 15317722 -- "Vision loss as a complication of gamma knife radiosurgery for trigeminal neuralgia." (Naseri A, Br J Ophthalmol. 2004 Sep;88(9):1225-6.)
*** Case report. RT 40 Gy to the 50% isodose line. Presented 15 months later
*** Initial exam showed vision 20/25, fine punctate epitheliopathy, no corneal sensation. 10 weeks later vision 20/200, severe epithelial keratopathy. Punctal plug placed, artificial tears, vision returned to 20/60 over 6 weeks
** 2000 PMID 11077103 -- "Radiation induced vascular injury after stereotactic radiosurgery for trigeminal neuralgia: case report." (Maher CO, Surg Neurol. 2000 Aug;54(2):189-93.)
*** Case report. SRS failed, patient underwent MVD. At operation, two adjacent veins and the superior cerebellar artery noted to have focal changes consistent with atheromatous disease.
* Chiba; 2002 (Japan) PMID 12507089 -- "Gamma knife radiosurgery for trigeminal neuralgia: the dry-eye complication." (Matsuda S, J Neurosurg. 2002 Dec;97(5 Suppl):525-8.)
** Retrospective. 33/41 patients treated with GKS to 80 Gy, 4-mm collimator, single isocenter. Mean f/u 13 months
** 3 patients reported "dry eye", with diminution/absence of corneal reflex. No other abnormalities. Hypesthesia of V1 developed prior to "dry eye". Brain stem irradiated volume significantly correlated with complication
* UCLA; 1997 PMID 9018707 -- "Leksell Gamma Knife treatment of tic douloureux." (Rand RW, Neurosurg Clin N Am. 1997 Jan;8(1):75-8.)
** Retrospective. 12 patients. F/u 3-4 years. Pain control: 8/12 improvement or complete relief.
** Side effects: 1 radionecrosis in medial temporal lobe

## Radiobiology

* Maryland PMID 11674826 -- "An investigation of eye lens dose for gamma knife treatments of trigeminal neuralgia." (Ma L, J Appl Clin Med Phys. 2000 Autumn;1(4):116-9.)
** Phantom studies and in vivo dosimetry for 6 patients. Average dose to ipsilateral lens 7.7 cGy (+/- 0.6 cGy). Calculated cataract probability 0.1%
* Pittsburgh PMID 10764273 -- "Histological effects of trigeminal nerve radiosurgery in a primate model: implications for trigeminal neuralgia radiosurgery." (Kondziolka D, Neurosurgery. 2000 Apr;46(4):971-6; discussion 976-7.)
** 2 adult baboons SRS to 80 and 100 Gy (4 nerves total). Target proximal trigeminal nerve just anterior to pons. Nonirradiated baboon brains as controls. 6 months after MRI and pathology
** MRI: 4 mm area of contrast enhancement
** Pathology: axonal degeneration, mild edema, with remnants of myelinated axons. Large and small myelinated and unmyelinated fibers affected. No inflammation. Nerve necrosis at 100 Gy treatment. Trigeminal ganglion normal.
* NCI PMID 7607923 -- "Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model." (Johnstone PA, Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1031-4.)
** 40 animals, laparotomy with IORT 0-75 Gy to lumbosacral plexus. Then periodically sacrificed to monitor peripheral nerve. F/u 5 years
** Dose >= 25 Gy resulted in ipsilateral neuropathy. Inverse relationship between dose and time-to-neuropathy, ED50 for paralysis 17.2 Gy. One animal treated with 15 Gy IORT developed paralysis after much longer latency. Consider 15 Gy threshold for paralysis.

## Historical Note

* PMID 9309292 -- First use of RT for trigeminal neuralgia in 1897
* PMID 15397004 -- "Roentgenotherapy in trigeminal neuralgia." (Trostler IS, Miss Valley Med J. 1949 Nov;71(6):204.)