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Merkezi Sinir Sistemi Tümörleri/Trigeminal Nevralji

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Trigeminal Neuralgia

Epidemiology

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  • 15,000 new cases in US per year; incidence 4/100,000 - 5/100,000
  • Majority of idiopathic TN after age 50


Definition

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  • International Headache Society
    • Classical TN (also called Idiopathic, or tic douloureux)
      • A) Paroxysmal attack lasting from fraction of a second to 2 minutes, affecting one or more of the trigeminal nerve divisions
      • B) One of the two following: 1) intense, sharp, superficial, stabbing or 2) precipitated from trigger areas or by a trigger factor
      • C) Stereotyped in the individual patient
      • D) No other neurological deficits
      • E) Not attributed to another disorder
    • Symptomatic TN (also called Secondary)
      • Symptoms indistinguishable from Classical TN but caused by a demonstrable structural lesion (e.g. neuroma, vascular compression)


Signs and symptoms

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  • Idiopathic has five classical features:
    • Paroxysmal
    • Provokable
    • Unilateral
    • Confined to the trigeminal nerve distribution
    • Unassociated with gross trigeminal motor or sensory loss.
  • Atypical TN is any pain that lacks the 5 classical features.
  • Multiple sclerosis-associated TN similar pain as idiopathic, but in the setting of MS


  • Typically does not wake patient up at night
  • Unilateral in most cases, if bilateral then not simultaneously
  • Trigger zones in distribution of CN V, include light touch, chewing, talking, brushing teeth, cold air, smiling/grimacing


Pain Scales

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Barrow Neurological Institute (BNI)

Grade I no pain, no medication
Grade II occasional pain, no medication
Grade IIIa no pain, medication
Grade IIIb pain, medication controlled
Grade IV pain, not well controlled
Grade V no pain relief


Marseille scale

Class I no pain, no medication
Class II no pain, medication
Grade III >90% pain frequency reduction
Grade IV >50% pain frequency reduction
Grade V no significant pain relief
Grade VI pain worsening

Etiology

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  • Idiopathic TN
    • Compression of trigeminal nerve by aberrant artery or vein suspected in 80-90% of cases
    • Resulting demyelination somehow triggers TN (possibly via ephaptic cross-talk between fibers mediating light touch and pain)
    • Also evidence for central pain mechanisms (refractory period after episode, trans of pain after single stimulus, latency from stimulus to onset)
  • Secondary TN
    • Caused by other structural compressions (e.g. vestibular schwannoma, meningioma, epidermoid cyst, aneurysm, AVM)


  • Oregon, 2004 PMID 15540931 -- "Pathophysiology of trigeminal neuralgia: new evidence from a trigeminal ganglion intraoperative microneurographic recording. Case report. (Burchiel KJ, J Neurosurg. 2004 Nov;101(5):872-3.)
    • Intraop recordings suggest TN pain generated by an abnormal discharge within peripheral NS, both in trigeminal ganglion neurons and/or the nerve itself


Anatomy

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  • Trigeminal nerve (CN V) supplies sensory to the face, and sensory and motor to muscles of mastication
    • V1 - Ophthalmic
    • V2 - Maxillary
    • V3 - Mandibular
  • Nerve exits at midlateral surface of the pons
  • Meckel's cave - gasserian ganglion (sensory ganglion), located 2 cm anterior to trigeminal root entry zone.


Imaging

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  • Thin slice (1mm) MRI/MRA to rule out structural lesions. Sensitivity and specificity for identifying vascular compression 89% and 50%


  • Tufts
    • 2006 PMID 16436823 -- "Nerve atrophy in severe trigeminal neuralgia: noninvasive confirmation at MR imaging--initial experience." (Erbay SH, Radiology. 2006 Feb;238(2):689-92.)
      • 31 patient MRIs reviewed. Mean diameter on symptomatic side 2.11 mm vs. 2.62 mm (SS). Mean cross-başlıkal area 4.50 mm2 vs. 6.28 mm2 (SS)
    • 2005 PMID 15662790 -- "Targeting the cranial nerve: microradiosurgery for trigeminal neuralgia with CISS and 3D-flash MR imaging sequences." (Zerris VA, J Neurosurg. 2005 Jan;102 Suppl:107-10.)
      • Multiple imaging sequences evaluated. CISS/3D-Flash preferred method
  • MC Wisconsin PMID 16029818 -- "Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation." (Jursinic PA, Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1559-67.)
    • Conclusion: uncertainty of target by MRI >2x than by CT. 4&8 mm collimator higher isodose line than 4mm collimator
  • UCLA PMID 15730595 -- "Three-dimensional fast imaging employing steady-state acquisition magnetic resonance imaging for stereotactic radiosurgery of trigeminal neuralgia." (Chavez GD, Neurosurgery. 2005 Mar;56(3):E628; discussion E628.)
    • Evaluation of 3-D-FIESTA sequence in 15 patients. 3-D-FIESTA sequence successfully demonstrated the trigeminal complex (root entry zone, trigeminal ganglion, rootlets, and vasculature) in 14 patients (93.33%). The 3-D-FIESTA sequence also allowed visualization of the branches of the trigeminal nerve inside Meckel's cavity.
    • Conclusion: SRS targeting of specific trigeminal branches may be feasible
  • Rosewell Park PMID 11733329 -- "Focal enhancement of cranial nerve V after radiosurgery with the Leksell gamma knife: experience in 15 patients with medically refractory trigeminal neuralgia." (Alberico RA, AJNR Am J Neuroradiol. 2001 Nov-Dec;22(10):1944-8.)
    • Retrospective. 15 patient MRIs. RT dose 35-45 Gy at 50% isodose line. Mean time to follow-up imaging 61 days
    • Target enhancement in 10/15; remaining 5 had RT dose 35 Gy

Treatment

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Cost-Effectiveness

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  • Mayo
    • 1999-2001 PMID 15951649 -- "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
    • PMID 14677455 -- "CSNS Resident Award: the economics of trigeminal neuralgia surgery." (Ecker RD, Clin Neurosurg. 2003;50:387-95.)
      • No abstract

Radiation Oncology:TOC


Trigeminal Neuralgia Treatment


Treatment Overview

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  • 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

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  • 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

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  • Pittsburg
    • 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 questionnnaire
    • 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

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  • 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 başlık 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

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  • 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

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  • 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

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Please see the Literature Review


GKS Technique

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  • 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 lenght 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 singnificantly 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

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Linac Outcomes

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  • 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%. Lenght of pain relief, good&excellent response better in 90Gy
      • Side effects: 70-85Gy - 31% numbness, none bothersome. 90Gy - 32% numbness, none bothersome

Linac technique

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  • 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

değiştir
  • 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

değiştir
  • 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

değiştir
  • 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

değiştir
  • 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.)

Radiation Oncology:TOC


Trigeminal Neuralgia Retreatment


Gamma Knife Retreatment

değiştir
Re-treatments
Institution Patients F/U (mo) First GKS Dose Second GKS Dose Success Side Effect
SD Gamma Knife Center 26 ? 97 Gy 97 Gy 85% ?
Columbia 40 18 75 Gy 40 Gy 45% 7% moderate, 3% severe
Prague 19 ? 70-80 Gy 70-80 Gy 89% 32% hypesthesia
Mayo Clinic 19 24 87 Gy 76.1 Gy 61% 58% dysfunction, 16% bothersome
Maryland 28 14 75 Gy 70 Gy 82% 43% numbness, 14% bothersome
Kentucky 35 19 90 Gy 90 Gy 84% 33% dysfunction, 3% bothersome
Barrow Neurological Institute 19 14 78.2 Gy 46.6 Gy 73% 42% numbness, 0% bothersome
Pittsburgh 27 20 75.6 Gy 64.4 Gy 48% 13% dysfunction
Tianjin 12 18 75.6 Gy 74.2 Gy 92% 11% numbness
Northwest Hospital 51 ? 76-98 Gy ? 80% 16% numbness


  • San Diego Gamma Knife Center 2006 NSA Abstract -- "Dose response of Gamma Knife surgery for trigeminal neuralgia and high-dose salvage of failed Gamma Knife surgery" (Ott K, Neurosurgical Society of America Abstract, 2006)
    • Retrospective. 263 patients treated, 26 retreated. RT dose range 26-140 Gy. Average f/u 32 months
    • Pain control: Typical TN 85% excellent/good, Atypical TN 46% excellent/good. Dose response present, now use 97 Gy for both treatment and retreatment.
    • Side effects: >50% facial numbness, usually transient. Better pain control results
    • Retreatment: Same benefit. Comparable facial numbness, better response. Some with fair/poor/no response initially had excellent response on retreatment
  • 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
    • 2003 PMID 14742963 1998-2003 -- "Repeat gamma knife radiosurgery for trigeminal neuralgia." (Brisman R, Stereotact Funct Neurosurg. 2003;81(1-4):43-9.)
      • Retrospective. 335 patients treated to 75 Gy, 45 patients retreated with 40 Gy. Mean 15 months f/u
      • Final pain relief: >50% in 62%. If no prior neurosurgical procedure, more likely to have better pain relief
      • Side effects: significant dysesthesias (>5/10) in 2 patients (4%)
  • Prague (Czech)
    • 2005 PMID 15662776 -- "Treatment of essential trigeminal neuralgia with gamma knife surgery." (Urgosik D, J Neurosurg. 2005 Jan;102 Suppl:29-33.)
      • Retrospective. 107 patients, retreat in 19 patients, same dose. RT 70-80 Gy.
      • Pain relief: Initial 96% (complete 80%). Median time to improvement 3 months (1 day, 13 months). Recurrence 25%, median interval 36 months (6, 94).
      • Retreatment: 19 patients (17%), initial pain relief 89% (complete 58%). Relapse 1 patient thus far
      • Side effects: Hypesthesia 20% after first GK, 32% after second GK. Median interval 35 months (3, 94) after first GK, 21 months (1, 72) after second
  • Mayo
    • 2005 PMID 15629611 1997-2002 -- "Repeat radiosurgery for idiopathic trigeminal neuralgia." (Pollock BE, Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):192-5.)
      • Retrospective. 19 patients retreated. Median interval 16 months. Median dose 76.1 Gy (median additive dose 163.1 Gy). Median f/u 24 months
      • Pain relief: 74% excellent, 95% >50% pain reduction. 61% excellent outcome at 2 years. 2 patients recurred at 7, 22 months.
      • Side effects: 58% facial parathesia, numbness or dyesthesia, 16% bothersome. 2 patients (11%) corneal numbness. Recommend reducing dose
    • 2000 PMID 11143237 1997-1999 -- "Results of repeated gamma knife radiosurgery for medically unresponsive trigeminal neuralgia." (Pollock BE, J Neurosurg. 2000 Dec;93 Suppl 3:162-4.)
      • Retrospective. 10 patients retreated. Median interval 13 months. All initially significant reduction, none with facial numbness
      • Pain relief: 80% excellent outcome at 1 year. All developed minor dysfunction
  • Maryland
    • 2005 ASTRO Abstract 1996-2004 -- "Comparison of Repeat GK-SRS for Refractory or Recurrent Trigeminal Neuralgia: Does Dose Matter" (Dutta PR, Abstract 2118)
      • Retrospective. 63/69 patients (Maryland 28, Kentucky 35).
      • Maryland:
        • First GKS RT median 75 Gy (70-80 Gy), second GKS 70 Gy (45-75 Gy). Median retreatment in 13 months. Median f/u 14 months
        • Pain control: Initially 43% excellent, 43% good. Retreatment 39% excellent, 43% good. All 3 with initially poor response did not respond to retreatment
        • Side effects: 25% new after 2nd GKS, total 43% numbness; 14% bothersome but had complete relief
      • Kentucky
        • First GKS median 90 Gy (80-90 Gy), second GKS 90 Gy (70-90 Gy). Median f/u 19 months
        • Pain control: initially 33% excellent, 22% good. Retreatment 64% excellent, 20% good. Of 8 with poor response, 50% excellent result after retreatment
        • Side effects: 25% new after 2nd GKS, total 33% numbness or dysesthesia. 3% bothersome
      • Conclusion: Cumulative dose 150 Gy vs. 180 Gy. Similar pain control, but 180 Gy more likely to have excellent outcome. Minimal bothersome effects.
    • 2004 1996-2001 PMID 15093906 -- "Repeat gamma knife radiosurgery for refractory or recurrent trigeminal neuralgia: treatment outcomes and quality-of-life assessment." (Herman JM, Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):112-6.)
      • Retrospective. 112 treated, 18 underwent repeat GKS. Median 8 months (3-42 months). Median RT 75 Gy first GKS, 70 Gy second GKS. Median f/u 37 months after first GKS, 24 months after second GKS
      • Pain control: Excellent 50%, good 28%, fair 6%, poor 16%. None of initial failures responded to repeat GKS
      • Side effects: 2 patients (11%) facial numbness, 1 bothersome
    • 2003 ASTRO Abstract -- "Repeat Gamma Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia" (Petit H, Abstract 22, 2003). Full paper Herman 2004 above
  • Barrow Neurological Institute; 2002 1997-2002 PMID 12507092 -- "Gamma knife radiosurgery for recurrent trigeminal neuralgia." (Shetter AG, J Neurosurg. 2002 Dec;97(5 Suppl):536-8.)
    • Retrospective. 19/29 patients. Questionnaires. Initial RT dose mean 78.2 Gy (70-90). RT retreatment mean dose 46.6 Gy (35-80). Mean f/u 13.5 months
    • Pain control: 53% excellent, 21% pain free but on reduced meds
    • Side effects: Facial numbness 42%, none bothersome. Those with facial numbness greater likelihood of being pain free
  • Pittsburgh 2002 PMID 11841716 -- "Repeat radiosurgery for refractory trigeminal neuralgia." (Hasegawa T, Neurosurgery. 2002 Mar;50(3):494-500; discussion 500-2.)
    • Retrospective. 27/31 patients assessed. Median dose 75.6 Gy (60-80 Gy), retreatment 64 Gy (50-80 Gy). Median f/u 43 months after 1st GKS, 20 months after 2nd GKS.
    • Pain control: 18% excellent, 30% good, 37% fair, 15% poor. Overall 48% complete pain relief (with or without meds)
    • Dose-response: low dose (120-135 Gy) vs. high dose (140-160 Gy): NS, although slightly fewer excellent and slightly more good outcomes with low dose. Now deliver 50-60 Gy)
    • Side effects: 13% dysfunction
  • Tianjin 2001 (China) 1996-1999 PMID 12007276 -- "Stereotactic radiosurgery for primary trigeminal neuralgia using the Leksell Gamma unit." (Zheng LG, Stereotact Funct Neurosurg. 2001;76(1):29-35.)
    • Retrospective. 80 patients. RT dose mean 75.6 Gy (70-90 Gy). Follow-up 24 months
    • Pain control: excellent 52%, good 31%, fair 10%, fail 6%. Mean time to improvement 22 days (1-120 days). Recurrence 10% in 5-26 months later
    • Retreatment: 12 patients (7 recurrent, 5 failures). RT dose mean 74.2 Gy (70-80 Gy). Mean f/u 18 months, 9/12 excellent result, 2/12 good result, 1 failed. Mean time to improvement 15 days (1-120)
    • Side effects: 11% facial numbness
  • Norhtwest Hospital 2000 Abstract 1991-1999 -- "Gamma Knife radiosurgery for treatment of trigeminal neuralgia: long term results" (Young RF, 3rd TN Conference, 2000)
    • Retrospective. 435 patients. RT 76-98 Gy. Median f/u 51 months. 51 patients retreated. Joint with Good Samaritan data??
    • Pain control: 6 months - 60% excellent, 30% good (some meds). Last f/u - 78% excellent/good. Including retreatment, 65% excellent, 20% good
    • Retreatment: success 80%
    • Side effect: 16% facial numbness
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