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

References

1)

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.
2)

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.
3)

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.
4)

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.
5)

Shulev Y, Trashin A, Gordienko K. Secondary trigeminal neuralgia in cerebellopontine angle tumors. Skull Base. 2011;21:287–294
6)

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.
7)

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.
8)

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.
10)

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:
11)

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.

Tumor associated trigeminal neuralgia

Tumor associated trigeminal neuralgia

Trigeminal neuralgia pathogenesis is uncertain. What is nominated as typically TN is idiopathic, but may be due to a structural lesion:

Posterior fossa tumor1) 2) 3) 4) 5), contralateral posterior fossa tumors, 6) 7)ipsilateral and contralateral supratentorial tumor8) 9) 10) 11) 12).

Trigeminal neuralgia in vestibular schwannoma 13).

Trigeminal neuralgia as the initial manifestation of temporal glioma 14).

A supratentorial tumor can initiate TN even without a direct involvement of the trigeminal ganglion or nerve. Such tumors may lead to increased intracranial pressure and brain shift generating a pressure cone that distorts the brain stemand displaces an adjacent vessel, compressing the trigeminal nerve root.

Another explanatory mechanism in a patient with supratentorial tumor and hydrocephalus can be that pressure over the trigeminal sensory root rather than stretching of the nerve fiber leads to TN 15).

References

1) , 6)

Deshmukh VR, Hott JS, Tabrizi P, Nakaji P, Feiz-Erfan I, Spetzler RF. Cavernous malformation of the trigeminal nerve manifesting with trigeminal neuralgia: Case report. Neurosurgery. 2005;56:E623.
2) , 9)

Deshpande S, Kaptain GJ, Pobereskin LH. Temporal glioblastoma causing trigeminal neuralgia. J Neurosurg. 1999;91:515.
3)

Gnanalingham K, Joshi SM, Lopez B, Ellamushi H, Hamlyn P. Trigeminal neuralgia secondary to Chiari’s malformation–treatment with ventriculoperitoneal shunt. Surg Neurol. 2005;63:586–8. discussion 588-9.
4) , 7) , 10)

Goel A, Sham A. Trigeminal neuralgia in the presence of ectatic basilar artery and basilar invagination: Treatment by foramen magnum decompression: Case report. J Neurosurg. 2009;111:1220–2.
5)

Peñarrocha-Diago M, Mora-Escribano E, Bagán JV, Peñarrocha-Diago M. Neoplastic trigeminal neuropathy: Presentation of 7 cases. Med Oral Patol Oral Cir Bucal. 2006;11:E106–11.
8)

Cirak B, Kimaz N, Arslanoglu A. Trigeminal neuralgia caused by intracranial epidermoid tumor: Report of a case and review of different therapeutic modalities. Pain Physician. 2004;7:129–32.
11)

Guttal KS, Naikmasur VG, Joshi SK, Bathi RJ. Trigeminal neuralgia secondary to epidermoid cyst at the cerebellopontine angle: Case report and brief review. Odontology. 2009;97:54–6.
12)

Love S, Coakham HB. Trigeminal neuralgia: Pathology and pathogenesis. Brain. 2001;124:2347–60.
13)

Apostolakis S, Karagianni A, Mitropoulos A, Filias P, Vlachos K. Trigeminal neuralgia in vestibular schwannoma: Atypical presentation and neuroanatomical correlations. Neurochirurgie. 2019 Mar 21. pii: S0028-3770(19)30024-4. doi: 10.1016/j.neuchi.2019.01.001. [Epub ahead of print] PubMed PMID: 30905383.
14)

Khalatbari M, Amirjamshidi A. Trigeminal neuralgia as the initial manifestation of temporal glioma: Report of three cases and a review of the literature. Surg Neurol Int. 2011;2:114. doi: 10.4103/2152-7806.83734. Epub 2011 Aug 13. PubMed PMID: 21886887; PubMed Central PMCID: PMC3162802.
15)

Cirak B, Kimaz N, Arslanoglu A. Trigeminal neuralgia caused by intracranial epidermoid tumor: Report of a case and review of different therapeutic modalities. Pain Physician. 2004;7:129–32.

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Significant pain reduction after initial SRS: 80–96% 1) 2) 3) 4) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 5).

Recurrent pain occurs within three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Favorable prognosticators: higher radiation doses, previously unoperated patient, absence of atypical pain component, normal pre-treatment sensory function 6).

Side effects: Hypesthesia occurred in 20% after initial SRS, and in 32% of those requiring repeat treatment 7) (higher rates associated with higher radiation doses) 8).


Outcome prediction of this modality is very important for proper case selection. The aim of a study was to create artificial neural networks (ANN) to predict the clinical outcomes after gamma knife radiosurgery (GKRS) in patients with TN, based on preoperative clinical factors.

They used the clinical findings of 155 patients who were underwent GKRS (from March 2000 to march 2015) at Iran Gamma Knife center, TehranIran. Univariate analysis was performed for a long list of risk factors, and those with P-Value < 0.2 were used to create back-propagation ANN models to predict pain reduction and hypoesthesia after GKRS. Pain reduction was defined as BNI score 3a or lower and hypoesthesia was defined as BNI score 3 or 4.

Typical trigeminal neuralgia (TTN) (P-Value = 0.018) and age>65 (P-Value = 0.040) were significantly associated with successful pain reduction and three other variables including radiation dosage >85 (P-Value = 0.098), negative history of diabetes mellitus (P-Value = 0.133) and depression (P-Value = 0.190). On the other hand, radio dosage > 85 (P-Value = 0.008) was significantly associated with hypoesthesia, other related risk factors (with p-Value < 0.2), were history of multiple sclerosis (P-Value = 0.106), pain duration more than 10 years before GKRS (P-Value = 0.115), history of depression (P-Value = 0.139), history of percutaneous ablative procedures (P-Value = 0.148) and history of diabetes mellitus (P-Value = 0.169).ANN models could predict pain reduction and hypoesthesia with the accuracy of 84.5% and 91.5% respectively. By mutual elimination of each factor in this model we could also evaluate the contribution of each factor in the predictive performance of ANN.

The findings show that artificial neural networks can predict post operative outcomes in patients who underwent GKRS with a high level of accuracy. Also the contribution of each factor in the prediction of outcomes can be determined using the trained network 9).

Case series

The long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up.

The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia.

The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN 10).


Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications.

The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery.

The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options 11).


From 1994 to 2009, 40 consecutive patients with typical, intractable TN received GKRS. Among these, 22 patients were followed for >60 months. The mean maximum radiation dose was 77.1 Gy (65.2-83.6 Gy), and the 4 mm collimator was used to target the radiation to the root entry zone.

The mean age was 61.5 years (25-84 years). The mean follow-up period was 92.2 months (60-144 months). According to the pain intensity scale in the last follow-up, 6 cases were grades I-II (pain-free with or without medication; 27.3%) and 7 cases were grade IV-V (<50% pain relief with medication or no pain relief; 31.8%). There was 1 case (facial dysesthesia) with post-operative complications (4.54%).

The long-term results of GKRS for TN are not as satisfactory as those of microvascular decompression and other conventional modalities, but GKRS is a safe, effective and minimally invasive technique which might be considered a first-line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable 12).


Kondziolka et al., evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery.

All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients.

After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity.

Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted 13).

References

1)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
2) , 8)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gor- man DA. High-dose trigeminal neuralgia radiosur- gery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
3)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
4)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotchi J, Levivier M. Gamma knife surgery for idi- opathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
5) , 7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vlady- 1982 ka V. Treatment of essential trigeminal neuralgia with gamma knife surgery.JNeurosurg.2005; 102 Suppl:29–33
6)

Maesawa S, Salame C, Flickinger JC, Pirris S, Kond- ziolka D, Lunsford LD. Clinical outcomes after ster- eotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2001; 94:14–20
9)

Ertiaei A, Ataeinezhad Z, Bitaraf M, Sheikhrezaei A, Saberi H. Application of an artificial neural network model for early outcome prediction of gamma knife radiosurgery in patients with trigeminal neuralgia and determining the relative importance of risk factors. Clin Neurol Neurosurg. 2019 Feb 12;179:47-52. doi: 10.1016/j.clineuro.2018.11.007. [Epub ahead of print] PubMed PMID: 30825722.
10)

Régis J, Tuleasca C, Resseguier N, Carron R, Donnet A, Yomo S, Gaudart J, Levivier M. The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia. Stereotact Funct Neurosurg. 2016;94(1):24-32. doi: 10.1159/000443529. Epub 2016 Feb 17. PubMed PMID: 26882097.
11)

Karam SD, Tai A, Wooster M, Rashid A, Chen R, Baig N, Jay A, Harter KW, Randolph-Jackson P, Omogbehin A, Aulisi EF, Jacobson J. Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up. J Radiat Oncol. 2014;3:125-130. Epub 2013 Nov 20. PubMed PMID: 24955219; PubMed Central PMCID: PMC4052001.
12)

Lee JK, Choi HJ, Ko HC, Choi SK, Lim YJ. Long term outcomes of gamma knife radiosurgery for typical trigeminal neuralgia-minimum 5-year follow-up. J Korean Neurosurg Soc. 2012 May;51(5):276-80. doi: 10.3340/jkns.2012.51.5.276. Epub 2012 May 31. PubMed PMID: 22792424; PubMed Central PMCID: PMC3393862.
13)

Kondziolka D, Perez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998 Dec;55(12):1524-9. PubMed PMID: 9865796.
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