Efficacy of CyberKnife Stereotactic Radiosurgery in Treating Trigeminal Neuralgia: A Single-Institution Study

Keywords

trigeminal neuralgia - CyberKnife - nonisocentric - radiosurgery - rhizotomy

Introduction

Trigeminal neuralgia (TN) is a chronic, persistent, agony state of one or more branches of the trigeminal nerve, which provides sensory innervation to the face and is consistently depicted as “the most exceedingly dreadful pain” by majority of the patients.[1] There are different trigger components for TN attacks, which incorporate biting, shaving, smoking, brushing teeth, or introduction to cold. The pain brought about by these attacks for the most part goes on for few seconds, yet at times, it might last up to few minutes.[2] Severe attacks may lead to inability to eat or speak.[3] TN is rare and can happen at any age, yet over 90% of the cases are reported in patients over the age of 40 years with an occurrence of 12 for every 100,000 individuals with female preponderance.[4]

TN may likewise happen related to certain infections, multiple sclerosis, and hypertension. The etiology might be either idiopathic or symptomatic. The updated ICHD-III (International Classification of Headache Disorders, 3rd edition, β version) classifies TN as classic (essential or idiopathic) and TN without or with accompanying diligent facial pain.[1] [5] Symptomatic TNs are believed to be auxiliary to diseases such as tumors, cardiovascular infarction, and multiple sclerosis. Then again, the reasons for idiopathic TN are not completely understood. It is hypothesized that demyelination along the trigeminal nerve causes pain or aberrant impulse generation secondary to demyelination, which is supposed to happen due to the neurovascular association between the trigeminal nerve and an abnormal venous or arterial vascular structure.[6] The most common causes for severe neurovascular contact were arteries in 98% of cases.[6] [7] [8]

A correct diagnosis is the paramount factor for satisfactory treatment and subsequently a good outcome. Differentiating trigeminal autonomic cephalalgias (cluster headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing [SUNCT], and paroxysmal hemicrania) and other craniofacial pain syndromes or persistent idiopathic facial pain is very important, as treatment is essentially different.[9] [10] Routine head imaging with magnetic resonance imaging (MRI) can detect structural causes. MRI plays a major role in the presurgical assessment to determine the presence of microvascular conflict.[11]

There is no specific consensus on the modality of treatment for TN. When diagnosed, the main aim is to relieve the pain, thus most patients are treated initially with a variety of pain medications (e.g., carbamazepine, phenytoin, gabapentin, lamotrigine, valproic acid, or topiramate) up to the maximal dose they can tolerate. Pharmacological treatment is considered the appropriate initial modality; however, a few patients either do not respond at all or respond inadequately. Only after two failed treatment attempts or in medical treatment-refractory patients, surgical interventions to be considered.[12] [13] No direct randomized studies comparing the medical and surgical treatment exists.

TN surgical management is either ablative (destructive) with the intentional destruction of sensory function of the trigeminal nerve or nondestructive with mere decompression of the trigeminal nerve and preservation of its normal function. Surgical treatment options include microvascular nerve decompression or percutaneous procedures such as balloon compression, glycerol or alcohol rhizotomy, or thermal radiofrequency rhizotomy, but these procedures are associated with neurological complications or side effects.[14] [15] Surgical intervention is a feasible option despite the fact that the best surgical treatment for TN in the general population actually stays dubious. Neuromodulation and repetitive transcranial magnetic stimulation are alternative novel innovations.[16] [17] [18]

Stereotactic radiosurgery (SRS): this procedure is alluded as rhizotomy. A rhizotomy is a procedure wherein select nerve fibers are destroyed to block pain. The principal utilization of SRS for TN is credited to Leksell.[19] Numerous patients with TN are poor candidates for craniotomy or microvascular decompression (MVD) either due to advanced age or due to medical comorbidities. Among this high-risk patient population, SRS is the least invasive treatment option even in TN refractory to prior surgical procedure patients.

Both cobalt (Gamma Knife) and linear accelerator (CyberKnife)-based radiosurgeries have been advocated. SRS uses modernized computed imaging for target delineation and highly focused beams of radiation, delivering a dose of 70 to 90 Gy as a single maximum dose to the retrogasserian sensory root where the trigeminal nerve exits the brainstem.[20] Such a confined radiation injury ordinarily disrupts the transmission of pain signals to the brain. We have evolved from frame-based stereotaxy to image-guided frameless SRS using noninvasive, nonisocentric treatment techniques, which has resulted in higher rates of pain relief.[21]

The innovative development of CyberKnife radiosurgery technology introduced a new and effective viable restorative alternative. SRS is an outpatient, noninvasive technique alternative to rhizotomies, following the failure of pharmacological pain management or surgery with a lower risk of side effects. Thus, in our study, we analyze the outcomes in this cohort of patients with a median follow-up of 48 months.

Methods

Population Selection

The patients diagnosed with unilateral TN of several years' duration, with a VAS (visual analog scale) score greater than 5 and pain symptoms, either refractory to standard anticonvulsant or surgical interventions, were prospectively included in the study ([Tables 1] and [2])

Table 1 Patient characteristics

Patient characteristics	Number of patients
Total number of patients	30
Sex: male/female	11/19
Mean age (in years)	52.8 (30–78)
Time of TN onset to radiosurgery (mean, range)	1–20 years
Laterality: right side/left side	16/14
Prior pharmacological interventions	30
Prior surgical procedures	8
Microvascular decompression	4
Open rhizotomy	1
Alcohol rhizotomy	1
Radiofrequency ablation	2

Table 2 VAS score

Visual analog scale (VAS) (x-axis)	Number of patients (y-axis)
	Prior to SRS	Post-SRS
0	0	7
1	0	5
2	0	4
3	0	5
4	0	6
5	3	2
6	6	1
7	7	0
8	8	0
9	4	0
10	2	0

Abbreviation: SRS, stereotactic radiosurgery.

Radiosurgical Procedure

Radiosurgery planning was performed with patients in supine position, arms by the side and immobilized with an aquaplast head mask. We systematically performed the planning of MRI imaging to obtain a three-dimensional volume acquisition with 1 mm slice thickness, stereotactic axial T1-T2 weighted MRI with and without gadolinium contrast enhancement followed by planning computed tomographic imaging acquisition. MRI and computed tomographic scans were fused to visualize the retrogasserian portion of the trigeminal nerve across the incisura of the petrous bone apex. The retrogasserian part of the trigeminal nerve was contoured on either FFE or FIESTA axial MRI T2 drive sequences; the target segment of the trigeminal nerve was consistently defined as a 6 to 7 mm length of nerve, approximately 2 to 3 mm distal to the dorsal root entry zone of the brainstem. The final volume of the Vth cranial nerve root was around 0.035 to 0.040 cc, created on the basis of both contours, and was used to define the optimal target. The brainstem, cochlear, and the VII–VIII nerve complexes were contoured. The treatment planning was done using the Multiplan treatment planning system (M/s. Accuray Inc., United States). A dose of 60 Gy, prescribed to 85% median isodose, was delivered to the target. Dose volume histograms were generated. We limit radiation doses to the brainstem to a maximum point dose of 40 Gy, while less than 0.31 cc of brainstem receiving less than 12 Gy and 50% of the isodose line was not infringing into the brain stem. The maximum point dose to cochlea and VII–VIII nerve complexes was limited to 12 Gy.[21]

CyberKnife is a compact X-band LINAC, operating at 11.4 GHz, producing 6 MV X-rays at a dose rate of 800 per minute. Around 45 to 60 nodes and 110 to 120 beams were used to achieve the dose conformity, with each node capable of giving a maximum 12 different beams. The CyberKnife treatment was guided by images acquired from kV X-ray beams. The 6D skull tracking method was used for the treatment. The skull bone was used as a reference for tracking. The images were acquired and compared with the digitally reconstructed radiographs, before each beam was delivered through the continuous monitoring of the alignment ([Figs. 1] [2] [3]). Radiosurgical rhizotomy was performed with the CyberKnife. Additional treatment planning details, detailed figures, and descriptions of the CyberKnife treatment for TN are provided in [Supplementary Material S1] (available in the online version).

Fig. 1 Treatment planning image from the CyberKnife workstation showing the target, organs at risk, and contouring for trigeminal neuralgia. The isodose lines represent the prescribed radiation dose, with the target area and adjacent critical structures clearly delineated.

Fig. 2 Detailed treatment plan for trigeminal neuralgia as visualized on the CyberKnife treatment planning system. The figure highlights the precise targeting of the trigeminal nerve with focused stereotactic radiosurgery, dose volume histograms, and beam placements.

Fig. 3 6D Skull tracking system used during CyberKnife treatment delivery. This figure demonstrates the real-time monitoring and adjustment of patient positioning to ensure accurate radiation delivery to the intended target.[21]

Screen shots were taken from the CyberKnife (Accuray) treatment planning workstation, illustrating the treatment plan for TN ([Figs. 1] and [2]) and 6D skull tracking ([Fig. 3]) during the treatment delivery.[21]

Follow-Up

All patients went through subsequent clinical assessments and were re-evaluated for pain response at 1, 2, 6, 9, and 12 monthly intervals and thereafter yearly for a median follow-up of 48 months. Any relapse of pain or the development of facial numbness was clinically re-evaluated at our outpatient department. During the initial month after the radiosurgery, the patients were advised to continue on their preoperative pain medications and later the medications were gradually tapered off. The follow-up evaluation was done through mail/telephone regarding pain control, medication, and any trigeminal dysfunction. Pain outcomes were grouped into two categories based on the VAS score: satisfactory (VAS ≤ 3 with pain free and off medication) and unsatisfactory (VAS > 3 with partial pain relief and on medication). The presence and timing of facial numbness were also recorded and classified according to the Barrow Neurological Institute (BNI) Facial Numbness Scale score. Success rate in our study was defined as patients who achieved complete pain relief and were off medications.

We analyzed the pain relief rate and symptoms for trigeminal nerve dysfunction like hypesthesia or paresthesia; anesthesia dolorosa, dry eye syndrome, or dysgeusia were addressed in detail. The significance of trigeminal dysfunction was classified in two groups, mild or bothersome, on the basis of the request from the patient to use medication to alleviate the symptoms. Statistical analysis was performed with the commercially available software SPSS (version 24).

Results

All the patients achieved some level of relief from discomfort; they were subsequently followed for a median time period of 48 months. Pain assessment was done using the VAS score. Some went off medications and some required medication with reduced dosing. Out of the above-mentioned 30 patients, 21 of them achieved satisfactory pain relief (VAS score ≤ 3). The sequence of pain relief achieved by our study population with time interval are: 1 patient achieved pain relief at the 1st month, 1 patient at 2nd month, 2 patients at 6th month, 5 patients at 9th month, 6 patients at 12th month, 2 patients at 24th month, 3 patients at 36th month, and 1 patient at 48th month; 9 patients had partial pain relief (VAS > 3) and were still on medications. A patient had a recurrence and was re-irradiated at the 36th month ([Figs. 4] [5] [6]). All the patients post-SRS treatment were on medical management with carbamazepine, gabapentin, and mecobalamin until adequate pain relief was achieved ([Table 3]). Facial numbness was assessed by the BNI Facial Numbness Scale score; 10 out of 30 patients had developed some form of facial numbness with a latency period of 10 months ([Table 4]).

Fig. 4 The figure illustrates the change in VAS pain scores, representing the intensity of pain experienced by patients, prior to CyberKnife stereotactic radiosurgery. Pretreatment scores indicate severe pain levels, with most patients reporting scores in the higher range, reflecting significant baseline discomfort associated with trigeminal neuralgia. VAS, visual analog scale.

Fig. 5 The figure illustrates the change in VAS pain scores, representing the intensity of pain experienced by patients, following CyberKnife stereotactic radiosurgery. Posttreatment scores reveal a marked reduction in pain, showcasing the effectiveness of radiosurgery in achieving pain relief, reinforcing the role of stereotactic radiosurgery as a viable noninvasive treatment modality for managing trigeminal neuralgia. VAS, visual analog scale.

Fig. 6 This figure evaluates the clinical outcomes post-radiosurgery by assessing patient response. The graph visualizes the number of patients achieving complete, partial, or no response, highlighting the treatment's overall responses. Series 1 depicts patients achieving complete pain relief and no longer requiring medication and Series 2 depicts patients experiencing partial pain relief but remaining dependent on medications for symptom management.

Table 3 Response assessment

Follow-up	1st Month	2nd month	6th month	9th month	12th month	24th month	36th month	48th month
Pain relief and off medications (Series 1)	1	2	4	9	15	17	20	21
Partial pain relief and on medications (Series 2)	29	28	26	21	15	13	10	9

Table 4 Barrow Neurological Institute Facial Numbness Score[21]

Grade	Description	Number of patients
I	No facial numbness	20
II	Mild facial numbness, not bothersome	6
III	Facial numbness, somewhat bothersome	4
IV	Facial numbness, very bothersome	0

Discussion

The exact biological mechanism causing the cessation of TN pain after radiosurgical rhizotomy is still poorly understood. Some researchers have opined that the clinical response to radiosurgery correlates with the development of facial numbness.[19] [21] This further suggests that these two phenomena are interdependent and there may be a common underlying mechanism. However, the onset of pain relief and facial numbness appears to have a different time interval. TN pain relief is relatively rapid and appears to be an acute or subacute event after a radiosurgical rhizotomy, whereas facial numbness is clearly a delayed event (6–10 months or more after radiosurgery). Various contrast MRI studies post-radiosurgical rhizotomies have reported a latency of changes at the root entry zone, the latter being consistent with breakdown in the blood–brain barrier, which strongly suggests that facial numbness may have arisen from the injury to the microvasculature of the trigeminal nerve and the adjacent brainstem. It is an intriguing phenomenon, which raises a question regarding the use of radioprotectors like amifostine at the time of radiosurgery might provide relative radioprotection to the endothelium and limit the incidence of delayed microvascular injury. Hypothetically, such an agent would not alter the biological mechanism underlying the therapeutic benefits of radiosurgery. Thus, a randomized trial to investigate such a possibility may define the answer in future.[22]

The evolution of radiosurgery from Gamma Knife to nonisocentric CyberKnife treatment planning techniques with greater technical expertise has given a new vision in the treatment outcomes. The optimal dosing and the target volume are the most defining criteria for the end results. Innumerable experimental studies in primate models demonstrated focal axonal degeneration of the trigeminal nerve at a dose of 80 Gy and partial nerve necrosis at higher doses (100 Gy).[23] Various studies conducted by researchers (Régis et al,[24] Flickinger et al,[25] Villavicencio et al,[26] Dvorak et al,[27] Dhople et al,[28] Riesenburger et al,[29] Kondziolka et al[30]) using Gamma Knife advocated a maximum dose of 90 Gy to the retrogasserian portion of the nerve with a median length of 6 mm (5–12 mm range) for the radiosurgery target of TN. The authors observed that with a maximum dose of 75 to 90 Gy, 80 to 87% of patients initially were pain-free, but however, they reported a 50 to 54% rate of permanent trigeminal nerve dysfunction in patients treated at the maximum dose of 90 Gy, compared with previous reports of a 10% rate of trigeminal nerve dysfunction at doses closer to 80 Gy. Posttreatment numbness occurred in 45 to 47% of the patients treated and the overall rate of complications was 15 to 18%. A cumulative dose >130 Gy was more likely to result in successful (>50%) pain control, but was also more likely (>20%) to result in development of new nerve dysfunction. The other studies conducted by Di Carlo et al,[31] Patil et al,[32] and Adler et al[21] with CyberKnife radiosurgery reported treatment of TN with frameless SRS where a segment of the trigeminal nerve (5–8 mm range) was targeted in a single radiosurgical prescribed dose of 60 to 65 Gy delivered at the 80% isodose line with a 70% short-term response rate and the latency period of pain relief increased to 2 months.

The aim of the current prospective single-institution study is to address the advantages of radiosurgical rhizotomy for TN using nonisocentric CyberKnife radiosurgery. A retrospective study conducted by Sudahar et al to assess the dosimetry of CyberKnife radiosurgery heralded the need for clinical response assessment. [33] The overall response rate observed in the study appears satisfactory. The outcomes in our study show that 70% of patients experienced good to excellent pain relief. Twenty-one patients had the optimal result of being pain-free and were off medications. The other nine patients had partial pain relief but were on reduced doses of medications and one among them had a recurrence of pain and was irradiated with a dose of 45 Gy, not exceeding the brain stem constraints (maximum point dose of 15 Gy and 1 mL of brainstem volume receiving less than 10 Gy).

The incidence of trigeminal dysfunction after the radiosurgical procedure and the pain relief rate correspond with the amount of radiation delivered along the nerve root. As addressed in the studies observed by Di Carlo et al,[31] Patil et al,[32] and Adler et al,[21] the longer the length of the nerve irradiated, the higher the dose, leading to higher incidence of facial numbness. In our study analysis, the most common complication that was experienced by a few patients was post-rhizotomy delayed facial numbness (10 patients out of 30). Consequently, the overall incidence and characteristics of sensory loss experienced by some of the patients in the current study seem comparable to what has been reported previously.[21]

The frequency and intensity of facial numbness observed in the current study represents a generous improvement over what was previously reported for CyberKnife rhizotomy.[21] [26] For instance, in our analysis around 13% had bothersome facial numbness (BNI III) and none reported very bothersome facial numbness (BNI IV) when compared with the study results observed by Villavicencio et al.[26] Likewise, none in our study series developed any more serious complications, such as anesthesia dolorosa, trismus, masticator weakness, diplopia, decreased hearing, dry eye syndrome, or paresis. As a consequence, it appears that the dose volume parameters being used with the present nonisocentric technique make for a better clinical outcome. The median overall follow-up was 48 months and the mean time for the occurrence of facial numbness was 10 months. Due to the latency period between radiosurgery and the onset of facial numbness, it is quite possible that, with the further follow-up, additional patients may develop sensory symptoms. Ultimately, it seems clear that numbness is significantly less likely using the optimized treatment parameters. In addition, 70% of population in our study series were pain-free and off medication with excellent clinical outcome and the observed relapse rate was 0.03%. Although the rate of long-term likelihood of TN recurrence when both the length of nerve and dose have been optimized still remains unknown.

It is worth pointing out that TN pain when compared with other pain syndromes has some degree of exceptions. As a consequence, the large majority of patients with complete relief were easy to categorize as such. In contrast, the nature of symptoms, side effects, and results among patients with only partial pain relief was more intricate and less conducive to the relatively simplistic measuring tools used in this investigation. Besides, some of these patients also eventually developed post-rhizotomy delayed facial numbness, and it was often difficult to recognize new sensory symptoms from their prior pain condition. It is reasonable to suggest that this high rate of response is owing to the significant specialized technical differences that could clarify the difference in morbidity associated with Gamma Knife radiosurgery and CyberKnife radiosurgery for TN. CyberKnife treatments are designed through inverse treatment plans, for which beam intensity for each field can be modified to obtain the desired dose distribution, and are thus easier to fit to the clinical requirements of dose conformity compared with Gamma Knife treatment plans, which are based on a forward treatment planning and modulating the beam-on time for each field and each shot individually is quite difficult. Therefore, CyberKnife, with its greater number of modulation factors, can meet the clinical requirements of dose conformity more easily than Gamma Knife.

Microvascular Decompression

MVD shows high success rates, with approximately 90% of patients experiencing immediate pain relief and 70 to 80% maintaining relief at 5 years. Pain recurrence can occur in 10 to 30% of patients over the long term. MVD carries moderate risks, including facial numbness (10–15%), hearing loss (5–10%), and less common complications like CSF leaks and cranial nerve deficits. MVD is recommended for younger or healthier patients due to the need for general anesthesia and a more intensive recovery process compared with noninvasive options ([Table 5]).[31]

Table 5 Comparison of CyberKnife SRS, micro-neurosurgery, and Gamma Knife

Parameter	CyberKnife SRS	Micro-neurosurgery (microvascular decompression)	Gamma Knife radiosurgery
Procedure type	Noninvasive, frameless radiosurgery	Invasive surgical procedure	Noninvasive, frame-based radiosurgery
Primary mechanism	Targeted radiation causing nerve lesion	Physical decompression of neurovascular conflict	Targeted radiation causing nerve lesion
Anesthesia requirement	No	General anesthesia required	Local anesthesia for frame placement
Hospital stay	Outpatient	Inpatient (1–3 days)	Outpatient
Recovery time	Minimal, often same-day recovery	Extended recovery, 2–6 weeks	Minimal, often same-day recovery
Pain relief onset	Gradual (weeks to months)	Immediate to rapid onset	Gradual (weeks to months)
Long-term pain relief	∼70–80% pain relief at 2–3 years	∼80–90% pain relief at 2 years	∼70–80% pain relief at 2–3 years
Complication rate	Low (e.g., sensory changes in <10%)	Higher (e.g., hearing loss, facial numbness)	Moderate (e.g., facial numbness, sensory changes)
Risk of facial numbness	∼5–10%	∼10–15%	∼10–15%
Suitability for elderly/comorbid patients	Highly suitable due to noninvasiveness	Limited due to invasiveness and anesthesia risks	Suitable, though frame placement may be challenging
Cost	Moderate to high	High	Moderate to high

Abbreviation: SRS, stereotactic radiosurgery.

Conclusion

Compared with previous reports that describe the clinical outcome after nonisocentric radiosurgical rhizotomy in patients with TN, the present study demonstrates both high rates of pain relief and an acceptable incidence of facial numbness. Nearly 70% rate of success after SRS was achieved in our study series and is still comparable to or better than that achieved with any other modality in the treatment of TN. The exact mechanism of cessation of pain through SRS is unclear, some claim due to the nerve root ablation and some due to break in the blood–brain barrier leading to the microvascular injury and facial numbness. Furthermore, CyberKnife SRS appears to be a safe, effective treatment modality for TN and increasing the durability of pain relief. Further study is warranted, and, ideally, a randomized trial comparing various treatment modalities should be conducted.

• References

• 1 Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 (1, Suppl 1): 9-160
• 2 De Simone R, Marano E, Brescia Morra V. et al. A clinical comparison of trigeminal neuralgic pain in patients with and without underlying multiple sclerosis. Neurol Sci 2005; 26 (Suppl. 02) s150-s151
• 3 Cheshire WP. Trigeminal neuralgia feigns the terrorist. Cephalalgia 2003; 23 (03) 230
• 4 De Toledo IP, Conti Réus J, Fernandes M. et al. Prevalence of trigeminal neuralgia: a systematic review. J Am Dent Assoc 2016; 147 (07) 570-576.e2
• 5 Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33 (09) 629-808
• 6 Thomas KL, Vilensky JA. The anatomy of vascular compression in trigeminal neuralgia. Clin Anat 2014; 27 (01) 89-93
• 7 Heinskou TB, Rochat P, Maarbjerg S. et al. Prognostic factors for outcome of microvascular decompression in trigeminal neuralgia: a prospective systematic study using independent assessors. Cephalalgia 2019; 39 (02) 197-208
• 8 Maarbjerg S, Wolfram F, Gozalov A, Olesen J, Bendtsen L. Significance of neurovascular contact in classical trigeminal neuralgia. Brain 2015; 138 (Pt 2): 311-319
• 9 Cohen AS, Matharu MS, Goadsby PJ. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA)–a prospective clinical study of SUNCT and SUNA. Brain 2006; 129 (Pt 10): 2746-2760
• 10 Zakrzewska JM, Linskey ME. Trigeminal neuralgia. BMJ Clin Evid 2014; 2014: x
• 11 Gronseth G, Cruccu G, Alksne J. et al. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology 2008; 71 (15) 1183-1190
• 12 Cruccu G, Gronseth G, Alksne J. et al; American Academy of Neurology Society, European Federation of Neurological Society. AAN-EFNS guidelines on trigeminal neuralgia management. Eur J Neurol 2008; 15 (10) 1013-1028
• 13 Obermann M. Recent advances in understanding/managing trigeminal neuralgia. F1000 Res 2019;8:F1000 Faculty Rev-505
• 14 Sandell T, Eide PK. Effect of microvascular decompression in trigeminal neuralgia patients with or without constant pain. Neurosurgery 2008; 63 (01) 93-99 , discussion 99–100
• 15 Hagenacker T, Bude V, Naegel S. et al. Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia. J Headache Pain 2014; 15 (01) 78
• 16 Kustermans L, Van Buyten J-P, Smet I, Coucke W, Politis C. Stimulation of the Gasserian ganglion in the treatment of refractory trigeminal neuropathy. J Craniomaxillofac Surg 2017; 45 (01) 39-46
• 17 Jakobs M, Unterberg A, Treede R-D, Schuh-Hofer S, Ahmadi R. Subcutaneous trigeminal nerve field stimulation for refractory trigeminal pain: a cohort analysis. Acta Neurochir (Wien) 2016; 158 (09) 1767-1774
• 18 Klein J, Sandi-Gahun S, Schackert G, Juratli TA. Peripheral nerve field stimulation for trigeminal neuralgia, trigeminal neuropathic pain, and persistent idiopathic facial pain. Cephalalgia 2016; 36 (05) 445-453
• 19 Leksell L. Sterotaxic radiosurgery in trigeminal neuralgia. Acta Chir Scand 1971; 137 (04) 311-314
• 20 Sheehan J, Pan H-C, Stroila M, Steiner L. Gamma knife surgery for trigeminal neuralgia: outcomes and prognostic factors. J Neurosurg 2005; 102 (03) 434-441
• 21 Adler Jr JR, Bower R, Gupta G. et al. Nonisocentric radiosurgical rhizotomy for trigeminal neuralgia. Neurosurgery 2009; 64 (2, Suppl): A84-A90
• 22 A Study of Amifostine for Prevention of Facial Numbness in Radiosurgery Treatment of Trigeminal Neuralgia - Study Results - ClinicalTrials.gov [Internet]. [cited 2020 Nov 28]. Accessed December 20, 2024 at: https://clinicaltrials.gov/ct2/show/results/NCT01364259
• 23 Kondziolka D, Lacomis D, Niranjan A. et al. Histological effects of trigeminal nerve radiosurgery in a primate model: implications for trigeminal neuralgia radiosurgery. Neurosurgery 2000; 46 (04) 971-976 , discussion 976–977
• 24 Régis J, Metellus P, Dufour H. et al. Long-term outcome after gamma knife surgery for secondary trigeminal neuralgia. J Neurosurg 2001; 95 (02) 199-205
• 25 Flickinger JC, Pollock BE, Kondziolka D. et al. Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind, randomized study. Int J Radiat Oncol Biol Phys 2001; 51 (02) 449-454
• 26 Villavicencio AT, Lim M, Burneikiene S. et al. Cyberknife radiosurgery for trigeminal neuralgia treatment: a preliminary multicenter experience. Neurosurgery 2008; 62 (03) 647-655 , discussion 647–655
• 27 Dvorak T, Finn A, Price LL. et al. Retreatment of trigeminal neuralgia with Gamma Knife radiosurgery: is there an appropriate cumulative dose? Clinical article. J Neurosurg 2009; 111 (02) 359-364
• 28 Dhople AA, Adams JR, Maggio WW, Naqvi SA, Regine WF, Kwok Y. Long-term outcomes of Gamma Knife radiosurgery for classic trigeminal neuralgia: implications of treatment and critical review of the literature. Clinical article. J Neurosurg 2009; 111 (02) 351-358
• 29 Riesenburger RI, Hwang SW, Schirmer CM. et al. Outcomes following single-treatment Gamma Knife surgery for trigeminal neuralgia with a minimum 3-year follow-up. J Neurosurg 2010; 112 (04) 766-771
• 30 Kondziolka D, Zorro O, Lobato-Polo J. et al. Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg 2010; 112 (04) 758-765
• 31 Di Carlo DT, Benedetto N, Perrini P. Clinical outcome after microvascular decompression for trigeminal neuralgia: a systematic review and meta-analysis. Neurosurg Rev 2022; 46 (01) 8
• 32 Patil CG, Veeravagu A, Bower RS. et al. CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurg Focus 2007; 23 (06) E9
• 33 Sudahar H, Kurup PGG, Murali V, Velmurugan J. Comparative analysis between 5 mm and 7.5 mm collimators in CyberKnife radiosurgery for trigeminal neuralgia. J Med Phys 2013; 38 (03) 120-124