The efficacy of gamma knife radiosurgery in patients with trigeminal neuralgia: The initial experience of the Bezmialem Vakif University
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.258009
Source of Support: None, Conflict of Interest: None
Keywords: Gamma Knife, stereotactic radiosurgery, trigeminal neuralgia
Trigeminal neuralgia (TN), a disorder which is characterized by pain of a short duration, is caused by compression of one of the branches of the fifth cranial nerve. The pain is often described as a sharp-lancinating one and is present in intervals. The incidence of TN is 4.3/100,000 per year, and female subjects are more commonly affected than the male ones. TN can be divided into two subgroups as primary and secondary. The primary form of TN is idiopathic and there is no clear reason or disease that could explain this form. The secondary form of TN is a result of other diseases, such as multiple sclerosis, a tumor, or a cyst. Medical treatment is the first-line treatment for these patients to treat the underlying disease. If the treatment fails, local treatments such as retrogasserian rhizotomy or balloon microcompression can be used. If the local therapy does not result in pain reduction or if there is a compression on the fifth nerve, microvascular decompression (MVD) is performed. Beside the surgical treatment, gamma knife radiosurgery is an alternative treatment option for treating TN. Studies have reported a significant pain reduction in patients treated with gamma knife. The advantages of the gamma knife radiosurgery as compared with surgical treatment are that it is a less invasive procedure, the patients are discharged from the hospital on the same day of the treatment, and the procedure avoids the risks of open surgery.
The purpose of our study was to retrospectively investigate the effect of gamma knife radiosurgery in patients with TN at the Bezmialem Vakif University Hospital.
We retrospectively collected data of the patients who underwent gamma knife radiosurgery treatment for their TN between June 2014 and January 2017. Characteristics such as age, gender, complaints, and clinical findings were reported.
The location of the pain, an assessment of the visual analog scale (VAS) for the pain severity (from 0 to 10), local treatment used before the application of radiosurgery, the time interval between the time when the complaints had first started and when the gamma knife radiosurgical treatment was administered, were reported. Before the gamma knife treatment, patients underwent magnetic resonance imaging (MRI) with and without contrast and MR angiography. After gamma knife treatment, the follow-up of the patients was performed 1 week after the procedure and then every 3 months afterwards. The complications and the change in the VAS score were reported during the follow-up period.
Gamma knife radiosurgical technique
Leksell gamma knife model C (Elekta, Stockholm, Sweden) was used for the treatment of the patients. Before the treatment, patients received sedation and analgesia to place the frame on the head of the patient. Then, the patients underwent a magnetic resonance imaging (MRI) with and without contrast (1 mm thickness, axial and coronal T1, and axial T2 constructive interference in steady state [CISS] MRI sequences). The magnetic resonance images were used to make a treatment plan. All patients were treated by a marginal dose of 40 Gy to 50% isodose, where the maximum treatment dose was 80 Gy. The maximum limited dose to the brain stem was 15 Gy. Briefly, trigeminal nerve was detected on T1- and T2-weighted images [Figure 1]a. A single 4-mm isocenter was used for targeting. The target is placed 2–4 mm anterior from the junction of the trigeminal nerve and pons, so that brainstem surface was irradiated at the 20–30% isodose line [Figure 1]b. This meant that the brainstem received less than 15 Gy, which is the critical toxic dose for the brainstem. This method provided an effective protection of the brainstem from radiation and kepts the radiation dose to the brainstem below the critical dose. Therefore, there was no need to perform an extra shielding of the brainstem. GammaPlan software was used for dose planning and calculations. The details of this method of radiosurgery have been described previously. The patients were discharged on the same day of the treatment.
The primary endpoint of the statistical analysis was pain control and the secondary endpoint was the development of a complication. To identify if there was any correlation between demographic data such as age, gender, location of the pain and the pain control, and the development of complications, we performed the statistical analysis using the Statistical Package for the Social Sciences software for Windows, version 23.0 (IBM Corp., Armonk, NY, USA). In case of normal distribution, unpaired t-tests were used, and non-normally distributed data were tested with regression analysis. A P value of 0.05 or lower was considered as being statistically significant.
Twenty-four patients (10 males) with TN were treated with gamma knife radiosurgery. The median age of the patients was 62.5 years (range, 34–91 years). The median time interval between the first complaint and the gamma knife radiosurgical treatment was 5 years (range, 1–21 years). Pain was on the right side in 14 (58%) patients, on the left side in 9 (38%) patients, and bilateral in one (4%) patient (In the latter patient, the left sided TN, where the pain was more severe, was treated). All the patients received medical treatment for their TN before gamma knife treatment. The median duration of the medical treatment before gamma knife radiosurgical treatment was administered was 5 years (range: 1–18 years). Despite temporary relief of symptoms following the administration of medical treatment such as carbamazepine and gabapentine, the severity of the pain had increased progressively in these patients.
Clinical follow-up of the patients was performed by recording their status at the clinical visits or by phone. The median follow-up period of the patients after gamma knife radiosurgical treatment was 11 months (range: 1–27 months). The median VAS score was 10 (range: 5–10) at the time of gamma knife treatment. The median VAS score decreased to 1 (range: 0–10) during the last follow-up visit. The pain decreased in 16 (67%) patients, while it was stable in 5 (21%) patients. Three (12%) patients were lost during the follow-up duration [Table 1].
Two (8%) patients developed complications related to gamma knife treatment. One patient developed hypoesthesia in the dermatome of the maxillary branch of the fifth cranial nerve. Another patient developed facial paresis (House-Brackman grade 2) 2 months after the treatment. This patient received steroid therapy and recovered within 3 weeks. There was no correlation between the patients' characteristics and the development of complication.
No clinical factors (gender, age, and location of the pain) of the patients recruited, significantly correlated with the pain relief, with the P values of the association of these factors with pain relief being 0.365, 0.232, and 0.365, respectively.
We evaluated 24 patients who were treated with gamma knife radiosurgery for TN at the Bezmialem Vakıf University Hospital. We showed that 76% of the patients during their follow-up visit had a reduction in pain and there was no change in 24% of the patients after the gamma knife treatment. Lars Leksell was the first who used gamma knife radiosurgery for patients with TN in 1951. The study by Kondziolka et al., investigated the effectiveness of gamma knife radiosurgery on TN in a multicenter cohort of 50 patients. In this study, the maximum target dose varied between 60 and 90 Gy and the isodose was 50%. They reported a median follow-up period of 18 months (range: 11–36 months) and 29 (58%) patients were pain-free after treatment. Three (6%) patients developed a facial paralysis. Regis et al., reported in their study that, of the 100 patients who were treated with gamma knife radiosurgery for TN, 83 were pain-free. Six (6%) patients developed facial paralysis and 4 (4%) patients developed facial hypoesthesia. The mean follow-up period was 12 months and the median maximum prescription dose was 85 Gy (range: 70–90Gy) with 50% isodose line. The degree of pain relief and the incidence of complications in our study were consistent with the data present in the current literature. In earlier reports, to identify the optimal effective and safe dose for TN, several dosing schemas had been tried. Finally, 40 Gy to 50% isodose line was found to be an effective dose (with the maximum dose being 80 Gy). We followed this treatment schedule and treated TN using a dose of 40 Gy to the 50% isodose line, where the maximum permissible treatment dose was limited to 80 Gy.
The treatment options for patients with TN are microvascular decompression of the trigeminal nerve, various ablative procedures including gamma knife radiosurgery, and local percutaneous procedures such as radiofrequency thermocoagulation, glycerol rhizolysis, and balloon compression. In a meta-analysis by Lopez et al., comparing the ablative neurosurgical treatments for TN, the authors reported that among all other techniques, radiofrequency thermocoagulation was associated with the highest rate of complications. Although most of these complications were transient, 29% of the patients analyzed in this study developed complications. The complication rate was 24.8% in patients treated with glycerol rhizolysis, 16.1% in those treated with balloon compression, and 12.1% in those treated with gamma knife radiosurgery. These results suggested that gamma knife radiosurgery was the safest technique among other ablative procedures. Furthermore, perioperative mortality has been reported following all of the percutaneous techniques; however, death or radiation-related malignancy has not been seen with the use of gamma knife in patients treated for TN.
Studies have shown that an immediate response to treatment is usually not seen after the treatment of gamma knife radiosurgery. Regis et al., reported that the pain relief was seen after a median delay of 10 days (range: 0–25 weeks). This period of time is important in deciding further treatment for the patient. If an immediate response is desired, an MVD, or a local treatment including percutaneous glycerol rhizotomy, thermocoagulation, or balloon microcompression may be used as a preferred treatment option instead of radiosurgical treatment. In our study, the pain relief was seen after a median time of 1 month (range: 1 week–6 months) after gamma knife radiosurgery. This suggests that gamma knife radiosurgery provides pain relief in a clinically acceptable time frame in patients with TN.
Dieckmann et al., and Steiger et al., reported that 91% and 84% of the patients, respectively, were pain-free after treatment with percutaneous glycerol rhizotomy. The two series, however, reported the risk of developing complications, including facial hypoesthesia in 45% and 44% of their patients, respectively. This shows that the treatment with percutaneous glycerol rhizotomy is associated with a relatively high risk of complications. Also, the duration of pain relief was not found to be a long-lasting one with the local procedures. Compared to these local procedures, gamma knife radiosurgery may provide an effective treatment option with a low risk for the patients.
The standard therapy of TN with a vascular compression of the fifth cranial nerve is MVD. Tyler-Kabara et al., investigated 1185 patients with TN who underwent MVD. The mean follow-up duration of the patients was 6.2 years. After 1 year of treatment, 80% of the patients were pain-free. After a follow-up duration of 10 years, 70% of the patients were pain-free. MVD therapy is more invasive compared with radiosurgery, but shows a higher control rate of the disease and a faster time to recovery from the TN.,, On the contrary, older patients and those with comorbidities would have a higher risk of surgical complications. Gamma knife radiosurgery provides an effective and a noninvasive treatment option for this group of patients.
We report our preliminary results on patients with TN treated with gamma knife radiosurgery. Our study has some limitations. The number of patients in our recruited cohort was limited and we did not have a long-term follow-up of these patients. Also, we did not compare the outcome of gamma knife radiosurgery with that of other treatment options including MVD and local procedures.
Our results suggest that gamma knife radiosurgery provides an effective treatment option in patients with TN with an acceptable complication risk rate. Further studies with larger cohorts are warranted to assess the long-term results of gamma knife treatment in patients with TN.
The authors declare no conflict of interest and no financial support was received.
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