Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma Knife radiosurgery for trigeminal neuralgia (GKRS) is a noninvasive surgical treatment option. The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear.

Studies focusing on the electrophysiology properties of partially demyelinated trigeminal nerves submitted to radiosurgery are vital to truly advance our current knowledge in the field 1).

To better understand this topic, Shih-Ping Hung et al., used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.

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.

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.

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 2).

Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results.

There is evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed and need to be explored in future studies 3).

Existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique 4).



Gorgulho A. Radiation mechanisms of pain control in classical trigeminal neuralgia. Surg Neurol Int. 2012;3(Suppl 1):S17-25. doi: 10.4103/2152-7806.91606. Epub 2012 Jan 14. PubMed PMID: 22826806; PubMed Central PMCID: PMC3400477.

Shih-Ping Hung P, Tohyama S, Zhang JY, Hodaie M. Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia. J Neurosurg. 2019 Jul 12:1-9. doi: 10.3171/2019.4.JNS19380. [Epub ahead of print] PubMed PMID: 31299654.

Al-Otaibi F, Alhindi H, Alhebshi A, Albloushi M, Baeesa S, Hodaie M. Histopathological effects of radiosurgery on a human trigeminal nerve. Surg Neurol Int. 2014 Jan 18;4(Suppl 6):S462-7. doi: 10.4103/2152-7806.125463. eCollection 2013. PubMed PMID: 24605252.

Varela-Lema L, Lopez-Garcia M, Maceira-Rozas M, Munoz-Garzon V. Linear Accelerator Stereotactic Radiosurgery for Trigeminal Neuralgia. Pain Physician. 2015 Jan-Feb;18(1):15-27. PubMed PMID: 25675056.

Handbook of Trigeminal Neuralgia

Handbook of Trigeminal Neuralgia

Girija Prasad Rath (Editor)

Price: $149.99


This book covers all aspects of trigeminal neuralgia (TGN) which is a common yet very painful condition of face and scalp. Chapters include historical perspective of the condition, clinical presentations, diagnosismanagement strategy, drug therapy, different interventional techniques utilized, and non-invasive modalities offered. The book has ample images to explain three main percutaneous procedures carried out for this condition such as radiofrequency thermocoagulation, glycerol rhizolysis and balloon microcompression in detail. It also covers open neurosurgical procedures including microvascular decompression and certain non-conventional and non-invasive methods.

This book provides assistance to pain physicians to have a comprehensive knowledge of trigeminal neuralgia. It is also relevant to neurosurgeons, neurologists, anesthesiologists, dental surgeons and resident doctors.

Trigeminal neuralgia pathogenesis

Trigeminal neuralgia pathogenesis

Neurovascular contact in trigeminal neuralgia

see Neurovascular contact in trigeminal neuralgia.

see Tumor associated trigeminal neuralgia.

Other anatomical abnormalities have been considered, including differences of trigeminal nerve (TN) volume.

No correlation between volumetry and clinical data was detected 1).

see Multiple sclerosis related trigeminal neuralgia.

The incidence rates of posterior fossa tumor-induced TN range from 2.1–11.6% percent; in the literature; these cases mainly comprise meningiomas (14–54% percnt;), epidermoid tumors (8–64% percent;), and vestibular schwannomas (7–31% percnt;) 2) 3) 4) 5).

It appears that aggressive bony edges may contribute-at least indirectly-to the neuralgia. This should be considered for surgical indication and conduct of surgery when patients undergo MVD 6).

Posterior fossa volume

Abarca et al. data support the theory that a small volume of the posterior fossa cisterns containing the trigeminal nerve may increase the incidence of ITN 7).

Horínek et al. did not find any association between the clinical neurovascular conflict (NVC) and the size of the posterior fossa and its substructures. MRI volumetry may show the atrophy of the affected trigeminal nerve in clinical neuromuscular conflict 8).

Park et al. did not find any volumetric differences (including the cisternal and parenchymal volumes) 9).

Chiari’s malformation and hydrocephalus are rare associates of TN. The pathophysiology of TN in these cases may be due to neurovascular conflict, related to raised intracranial pressure from the hydrocephalus and/or the small posterior fossa volume in these patients. Drainage of associated hydrocephalus may be an effective surgical treatment 10).

Pontomesencephalic cistern

High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN 11).

Park et al. confirmed that small pontomesencephalic cistern volumes were more frequent in patients with TN 12).

Uric acid in trigeminal neuralgia



Urgosik D, Keller J, Svehlik V, Pingle M, Horinek D. Trigeminal nerve asymmetry in classic trigeminal neuralgia – pretreatment volumetry and clinical evaluation in patients irradiated by Leksell Gamma Knife. Neuro Endocrinol Lett. 2014 Jul 20;35(4). [Epub ahead of print] PubMed PMID: 25038607.

Barker FG, 2nd, Jannetta PJ, Babu RP, Pomonis S, Bissonette DJ, Jho HD. Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors. J Neurosurg. 1996;84:818–825.

Jamjoom AB, Jamjoom ZA, al-Fehaily M, el-Watidy S, al-Moallem M, Nain Ur R. Trigeminal neuralgia related to cerebellopontine angle tumors. Neurosurg Rev. 1996;19:237–241.

Nomura T, Ikezaki K, Matsushima T, Fukui M. Trigeminal neuralgia: differentiation between intracranial mass lesions and ordinary vascular compression as causative lesions. Neurosurg Rev. 1994;17:51–57.

Shulev Y, Trashin A, Gordienko K. Secondary trigeminal neuralgia in cerebellopontine angle tumors. Skull Base. 2011;21:287–294

Brinzeu A, Dumot C, Sindou M. Role of the petrous ridge and angulation of the trigeminal nerve in the pathogenesis of trigeminal neuralgia, with implications for microvascular decompression. Acta Neurochir (Wien). 2018 Jan 20. doi: 10.1007/s00701-018-3468-1. [Epub ahead of print] PubMed PMID: 29353407.

Abarca-Olivas J, Feliu-Rey E, Sempere AP, Sanchez-Payá J, Baño-Ruiz E, Caminero-Canas MA, Nieto-Navarro J, Botella-Asunción C. [Volumetric measurement of the posterior fossa and its components using magnetic resonance imaging in idiopathic trigeminal neuralgia]. Rev Neurol. 2010 Nov 1;51(9):520-4. Spanish. PubMed PMID: 20979031.

Horínek D, Brezová V, Nimsky C, Belsan T, Martinkovic L, Masopust V, Vrána J, Kozler P, Plas J, Krýsl D, Varjassyová A, Ghaly Y, Benes V. The MRI volumetry of the posterior fossa and its substructures in trigeminal neuralgia: a validated study. Acta Neurochir (Wien). 2009 Jun;151(6):669-75. doi: 10.1007/s00701-009-0283-8. Epub 2009 Apr 7. PubMed PMID: 19350204.
9) , 12)

Park YS, Ha SM. Does a small posterior fossa increase nerve vascular conflict in trigeminal neuralgia? Acta Radiol. 2014 Dec 8. pii: 0284185114561914. [Epub ahead of print] PubMed PMID: 25487716.

Gnanalingham K, Joshi SM, Lopez B, Ellamushi H, Hamlyn P. Trigeminal neuralgia secondary to Chiari’s malformation–treatment with ventriculoperitoneal shunt. Surg Neurol. 2005 Jun;63(6):586-8; discussion 588-9. Review. PubMed PMID:

Rasche D, Kress B, Stippich C, Nennig E, Sartor K, Tronnier VM. Volumetric measurement of the pontomesencephalic cistern in patients with trigeminal neuralgia and healthy controls. Neurosurgery. 2006 Sep;59(3):614-20; discussion 614-20. PubMed PMID: 16955043.
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