ABBREVIATIONS:
- BNI
- Barrow Neurological Institute
- CLp
- posterior part of the central lateral nucleus
- MRgFUS
- MR-guided focused ultrasound
- NRS
- Numeric Pain Rating Scale
- RFTA
- radiofrequency thermal ablation
- SRS
- stereotactic radiosurgery.
Chronic neuropathic pain can be severely disabling and is difficult to treat. An array of invasive procedures has been used to reduce pain in patients who are refractory to or intolerant of conservative and noninvasive management.1,2 Notably, neurosurgeons have developed some ablative interventions to interrupt neural circuits that process or modulate pain.3 Medial thalamotomy involves the ablation of medial thalamic nuclei which encode information related to the affective-motivational dimension of pain.4 Within the medial thalamus, the centromedian/parafascicular complex has been the most common target for lesioning,5 whereas the posterior part of the central lateral nucleus (CLp) has been targeted for ablation in few studies.6-8 The CLp is believed to have an intermediate functional role between the medial diffuse and lateral specific sensory thalamic nuclei and to project to large cortical domains, including brain areas mediating discriminative, affective-motivational, cognitive, and motor aspects of pain.6,9-11 Thus, lesioning the CLp is believed to have a multimodal effect on pain and possibly greater efficacy than ablating classic medial thalamic targets, as shown in some recent studies.7-9
Central lateral thalamotomy, which involves the stereotactic lesioning of the CLp, has been performed using various stereotactic ablative techniques, including radiofrequency thermal ablation (RFTA),7 MR-guided focused ultrasound (MRgFUS)8 thermal ablation, and stereotactic radiosurgery (SRS).6 We previously reported the early results observed in the first cohort of patients with neuropathic pain who were treated with central lateral thalamotomy using Gamma Knife radiosurgery (GKRS). The initial results in 8 patients were favorable for pain reduction rates and safety.6 This retrospective study aims to describe the results observed in a larger group of patients who were followed up clinically for a longer period and, ultimately, to determine whether central lateral thalamotomy using GKRS is safe and effective in reducing pain in patients with medically intractable neuropathic pain syndromes.
METHODS
Patient Population
This study is a retrospective, single-center case series of all patients who underwent central lateral thalamotomy using GKRS for intractable chronic neuropathic pain syndromes between 2014 and 2021. Eight patients were previously reported.6 All patients had not responded to trials of adequately dosed medications for chronic pain, including antiepileptics and antidepressants, or invasive treatments for at least 1 year. All 21 patients provided informed consent on the risks and benefits of radiosurgery before treatment. Permission from our institutional ethics committee was obtained for this historical cohort study. This study conforms to the STROBE reporting criteria.12
Stereotactic Radiosurgery Procedure
Radiosurgery was performed using the Leksell Gamma Knife models Perfexion (2014-2020) and Icon (2021; Elekta). After headframe fixation, 3-dimensional MRI was acquired and stereotactic targets were chosen on T2 and precontrast and postcontrast T1-weighted sequences using dedicated planning software (Gammaplan, Elekta). A single 4-mm isocenter was placed on the CLp using an indirect targeting method based on stereotactic brain atlases. The intended target was 6 mm lateral to the medial thalamic border, 0 to 2 mm anterior to the posterior commissure, and 6 mm above the intercommissural line. Small adjustments were made according to individual anatomy as seen on stereotactic MRI. A maximal dose of 130 to 140 Gy was delivered to the target. The selection of the dose was guided by a dose-volume analysis based on prior experience with parenchymal tolerance to GKRS13-15 and on earlier reports of other authors investigating GKRS medial thalamotomy for pain.4 Unilateral thalamotomy was performed in most of the initial patients. Subsequently, bilateral lesions were made, based on a putative greater efficacy of bilateral lesions, as supposed by Jeanmonod and Morel7 and Jeanmonod et al.8 The radiosurgical plans were devised in a multidisciplinary fashion with a neurosurgeon, radiation oncologist, and medical physicist.
Treatment Outcomes
Relevant clinical data were obtained from electronic medical records and telephone conversations with the patients or their relatives. All patients underwent at least 1 neurological assessment during follow-up. Dosimetric data were obtained from the treatment planning software. Average pain was rated on the Numeric Pain Rating Scale (NRS) in the range of 0 to 10 (NRS: 0 is no pain and 10 is the maximum pain imaginable). Patients achieving meaningful pain reduction after treatment were defined as those patients with at least 50% reduction in NRS. Initial pain reduction was defined as a reduction of NRS ≥ 50% during the follow-up assessment period, irrespective of the final pain outcome. Final pain reduction was defined as a reduction of NRS ≥ 50% at the last follow-up.
Pain was also assessed using the Barrow Neurological Institute (BNI) pain intensity score (Table 1). BNI pain scores of I-III indicated treatment success. NRS was estimated before GKRS and during clinical follow-up visits, whereas the BNI pain score was estimated at the last clinical assessment. Postprocedural MRI was acquired between 6 and 9 months after GKRS to confirm lesion development.
TABLE 1. -
BNI Pain Intensity Score
| Score |
Pain description |
| I |
No pain, no medication |
| II |
Occasional pain, no medication |
| III |
Some pain, adequately controlled with medication |
| IV |
Some pain, not adequately controlled with medication |
| V |
Severe pain or no pain relief |
BNI, Barrow Neurological Institute.
BNI scores of 1, 2, and 3 were considered to indicate treatment success, whereas BNI scores of 4 or 5 indicated treatment failure.
Statistical Analysis
Patient and treatment characteristics were summarized with descriptive statistics. Meaningful pain reduction rates were estimated using the Kaplan-Meier method, and stratified survival outcomes were compared with the log-rank test for categorical variables. Univariate Cox regression was used for continuous variables. Preoperative and postoperative NRS were compared using the Wilcoxon signed-rank test. Nonparametric tests, including the Fisher exact test, the Kolmogorov-Smirnov test, and the Spearman rank correlation coefficient, were used to assess the correlation between NRS percent decrease after GKRS, initial and final meaningful pain reduction rates, and several variables (age, sex, volume of the lesion contralateral to pain side, lesion's side [contralateral vs bilateral], and neuropathic pain syndrome [trigeminal deafferentation pain vs all other neuropathic pain syndromes]). P values < .05 were considered statistically significant. Stata MP (StataCorp LP) software, version 14.0, was used for the statistical analysis.
RESULTS
Demographics and SRS Characteristics
A total of 21 patients underwent central lateral thalamotomy using GKRS for intractable neuropathic pain syndromes. Detailed demographic data are presented in Table 2. The median pain duration time before GKRS was 4 years (IQR 8-10 years). The mean preradiosurgery NRS in this cohort of 21 patients was 9 (range 8-10). Treatment parameters and stereotactic coordinates are presented in Tables 3 and 4, respectively. Postoperative MRI confirmed accurate lesions formation in all patients (Figure 1). The mean lesions' volume, as assessed on postoperative MRI scans, was 190 mm3 (range 120-600 mm3). Two patients expired during the follow-up assessment period for causes unrelated to GKRS.
TABLE 2. -
Demographic and Symptom Characteristics for All Patient Who Underwent Central Lateral
Thalamotomy in This Study
| Variable |
N |
Median (IQR)/% |
| Sex |
|  Male |
10 |
48 |
|  Female |
11 |
52 |
| Age at the time of GKRS, y |
|
61 (55-66) |
| Indication for GKRS |
|  Trigeminal deafferentation pain |
12 |
57 |
|  Central poststroke neuropathic pain |
3 |
14 |
|  Brachial plexus injury
a
|
3 |
14 |
|  Postherpetic neuralgia |
2 |
10 |
|  Phantom limb pain |
1 |
5 |
| Pain quality |
|  Proprioceptive |
8 |
38 |
|  Electrical discharges |
7 |
33 |
|  Thermal |
11 |
52 |
|  Exteroceptive |
3 |
14 |
|  Allodynia |
12 |
57 |
| NRS before GKRS |
|  8 |
7 |
33 |
|  9 |
6 |
29 |
|  10 |
8 |
37 |
| Side of pain |
|  Left |
11 |
52 |
|  Right |
10 |
48 |
|  Pain duration before GKRS, y |
|
4 (8-10) |
| Preoperative medications |
|  Antidepressants |
16 |
76 |
|  Antiepileptics |
16 |
76 |
|  Opioids |
13 |
62 |
|  NSAIDs |
3 |
14 |
|  Benzodiazepines |
5 |
24 |
|  Lidocaine patch |
3 |
14 |
| Prior surgical treatments for neuropathic pain |
|  None |
14 |
67 |
|  MCS |
1 |
5 |
|  SCS |
3 |
14 |
|  DREZ ablation |
1 |
5 |
|  Stellate ganglion glycerolization |
1 |
5 |
|  Nerve blocks |
1 |
5 |
|  Nerve RF ablation |
3 |
14 |
| Pain location |
|  Arm |
4 |
19 |
|  Face |
13 |
62 |
|  Shoulder |
1 |
5 |
|  Trunk and limbs |
3 |
14 |
DREZ, dorsal root entry zone; GKRS, Gamma Knife radiosurgery; MCS, motor cortex stimulation; NRS, Numeric Pain Rating Scale; NSAIDs, nonsteroidal anti-inflammatory drugs; RF, radiofrequency; SCS, spinal cord stimulation.
aThe 2 patients with postherpetic neuralgia had facial and arm and shoulder pain, respectively. Some patients reported a combination of pain qualities.
TABLE 3. -
Side of Lesions and Dosimetric Data of Gamma Knife Radiosurgery
| Variable |
N (%) |
| Maximum dose, Gy |
|  130 |
10 (2 unilateral, 8 bilateral) |
|  140 |
11 (3 unilateral, 8 bilateral) |
| Side of lesion |
|  Bilateral |
16 (76) |
|  Right |
1 (5) |
|  Left |
4 (19) |
TABLE 4. -
Stereotactic Coordinate of the Functional Lesions in the Medial Thalamus for Each Patient
| Patient, no. |
Side of lesion |
Stereotactic coordinates of the lesion center (mm) |
Pain syndrome |
Daily medications before GKRS |
Daily medications at the last assessment |
| Lateral |
Anteroposterior |
Vertical |
| 1 |
Left |
10 |
0 |
6.3 |
BPI |
Gabapentin 900 mg; opioids as needed |
Gabapentin 150 mg |
| 2 |
Right |
8.4 |
1 |
6 |
BPI |
Gabapentin 1200 mg; opioids as needed; duloxetine 60 mg |
Gabapentin 1200 mg; opioids as needed; duloxetine 60 mg |
| 3 |
Left |
7 |
1 |
6.3 |
TDP |
Amitriptyline 50 mg; gabapentin 600 mg |
Amitriptyline 50 mg |
| 4 |
Right |
12 |
2 |
4 |
TDP |
Amitriptyline 50 mg; pregabalin 200 mg; opioids as needed |
Amitriptylyie 50 mg; pregabalin 200 mg; opioids as needed |
| Left |
12 |
2 |
4 |
|
| 5 |
Right |
7 |
1 |
6 |
TDP |
Amitriptyline 50 mg; pregabalin 200 mg; opioids as needed |
– |
| Left |
7 |
1 |
6 |
|
| 6 |
Right |
8 |
1 |
5 |
PHN |
Gabapentin 600 mg; oxcarbazepine 600 mg; duloxetine 60 mg; paroxetine 20 mg; lidocaine patches, opioids as needed |
Pregabalin 200 mg; duloxetine 60 mg; lamotrigine 100 mg; opioids as needed |
| left |
7 |
1 |
5 |
|
| 7 |
Left |
7 |
1 |
6.3 |
TDP |
Clomipramine 95 mg; amitriptyline 25 mg; gabapentin 1200 mg; tapentadol 600 mg |
Clomipramine 95 mg; amitriptyline 25 mg; gabapentin 1200 mg; tapentadol 600 mg |
| 8 |
Left |
11 |
2 |
6.3 |
CPSP |
Lidocaine patches; duloxetine 60 mg; opioids as needed |
Lidocaine patches; opioids as needed |
| 9 |
Right |
10 |
1 |
6 |
PHN |
Amitriptyline 75 mg; gabapentin 900 mg; carbamazepine 400 mg; opioids as needed |
Duloxetine 60 mg; gabapentin 900 mg; carbamazepine 400 mg; opioids as needed |
|
Left |
10 |
1 |
6 |
|
| 10 |
Right |
8 |
0 |
6 |
TDP |
Gabapentin 900 mg; amitriptyline 25 mg; clonazepam 4 mg; opioids as needed |
Gabapentin 900 mg; amitriptyline 25 mg |
|
Left |
10 |
1 |
6 |
|
| 11 |
Right |
8 |
1 |
6 |
TDP |
Carbamazepine 900 mg; tapentadol 600 mg; amitriptilyne 75 mg |
Carbamazepine 900 mg; tapentadol 600 mg; amitriptilyne 75 mg |
|
Left |
9 |
1 |
6 |
|
| 12 |
Right |
8 |
0 |
7 |
BPI |
Pregabalin 1800 mg; amitriptyline 75 mg; clonazepam 4 mg; opioids as needed |
Pregabalin 1800 mg; amitriptyline 75 mg; clonazepam 4 mg; opioids as needed |
|
Left |
8 |
0 |
7 |
|
| 13 |
Right |
13 |
0 |
6 |
TDP |
Phenytoin 300 mg; nimesulide 400 mg |
Phenytoin 300 mg; nimesulide 100 mg |
|
Left |
12 |
1 |
5 |
|
| 14 |
Right |
9 |
1 |
7 |
TDP |
Pregabalin 225 mg; ibuprofen 600 mg; amitriptyline 75 mg |
Pregabalin 225 mg; ibuprofen 600 mg; amitriptyline 75 mg |
|
Left |
8.8 |
0.8 |
7 |
|
| 15 |
Right |
8 |
0 |
7 |
CPSP |
Amitriptyline 75 mg; gabapentin 1200 mg |
Amitriptyline 75 mg; gabapentin 1200 mg |
|
Left |
8 |
0 |
7 |
|
| 16 |
Right |
9 |
1 |
7 |
TDP |
Amitriptyline 75 mg; opioids as needed |
Amitriptyline 75 mg; opioids as needed |
|
Left |
10 |
2 |
7 |
|
| 17 |
Right |
8.5 |
0 |
6.5 |
TDP |
Tramadol 400 mg; clonazepam 4 mg |
Tramadol 400 mg; clonazepam 4 mg |
|
Left |
9 |
2 |
6.5 |
|
| 18 |
Right |
9.5 |
0 |
6 |
TDP |
Clonazepam 14 mg; indometacin 50 mg; morphine 100 mg; further opioids as needed |
Clonazepam 2 mg; indometacin 50 mg; morphine 100 mg |
|
Left |
8.5 |
0 |
6 |
|
| 19 |
Right |
12 |
0 |
7 |
PLP |
Gabapentin 2400 mg; duloxetine 60 mg; clonazepam 2 mg; oxycodone 35 mg |
Gabapentin 2400 mg; duloxetine 60 mg; clonazepam 2 mg; oxycodone 35 mg; medical cannabis |
|
Left |
14 |
0 |
7 |
|
| 20 |
Right |
9 |
0 |
7 |
CPSP |
Pregabalin 100 mg; clonazepam 4 mg; tapentadol 200 mg |
Pregabalin 100 mg; clonazepam 4 mg; |
|
Left |
8 |
0 |
7 |
|
| 21 |
Right |
8 |
0 |
6 |
TDP |
Duloxetine 60 mg; carbamazepine 600 mg; ketorolac 30 mg |
Duloxetine 60 mg; carbamazepine 600 mg; ketorolac 30 mg |
|
Left |
8 |
0 |
6 |
|
BPI, brachial plexus injury; CPSP, central poststroke neuropathic pain; GKRS, Gamma Knife radiosurgery; PHN, postherpetic neuralgia; PLP, phantom limb pain; TDP, trigeminal deafferentation pain.
Patients 1, 3, 4, 5, 6, 7, 10, 11, 13, 17, 18, and 21 had initial meaningful pain reduction after radiosurgery. Pain recurred during follow-up in patients 4, 6, 7, 11, and 21. Pain syndromes and medications taken preradiosurgery and postradiosurgery for each patient are listed in the right most columns.
;)
FIGURE 1.: Prescribed 50% isodose lines have been superimposed on the postoperative T1-weighted postcontrast MR images acquired in the axial
A, coronal
B, and sagittal
C, planes. The correspondence between the prescribed isodose lines and the actual lesions demonstrates the targeting accuracy of the GKRS lesioning technique. Lesions' size, defined as the extension of the gadolinium-enhanced area, clustered around volumes of 200 mm
3, corresponding to the volume of the oblate spheroidal 4-mm isocenter of the Perfexion and Icon Gamma Knife models.
28 These stereotactic lesions are more extended in the X dimension and cover the medio-lateral dimension for about 6 mm, whereas the lesion's
Y and
Z dimensions are of approximately 4-5 mm. GKRS, Gamma Knife radiosurgery.
Pain Outcomes
Meaningful initial pain reduction, defined as a NRS decrease ≥50% and BNI I-III status, was achieved in 12 patients (57%) after a median period of 3 months (IQR 3-6 months). Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (83% vs 22%, P = .009). The median follow-up time was 28 months (IQR 12-48 months). Among patients who had initial pain reduction, pain recurred in 5 patients (24%), for a total of 7 patients (33%) with pain reduction at the last follow-up evaluation. The median time to pain recurrence was 36 months (IQR 7-36 months). For all patients, estimated rates of meaningful pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively (Figure 2). Meaningful pain reduction time curves did not significantly differ between the trigeminal deafferentation pain group and all other patients (P = .06; Figure 3). Overall, the mean NRS at the last clinical assessments was 6.9 (range 0-10), for an average reduction of 23% (P = .001). When distinguishing change in pain scores by pain etiology, the average percent decrease in NRS at the last assessments was significantly greater for patients with trigeminal deafferentation pain than for patients with all other neuropathic pain syndromes (35% and 7.5%; P = .046). BNI and NRS pain outcomes are summarized in Table 5. For all patients, age, sex, lesion's side (contralateral vs bilateral), size of the lesion contralateral to pain side, and duration of pain before GKRS did not predict initial or final meaningful pain reduction or correlate with a greater percent decrease in NRS at last assessments or during follow-up. At the last assessment, 8 patients (including the 7 responders) had reduced the preoperative intake of medications for pain and 1 was able to stop medication.
FIGURE 2.: Kaplan-Meier survival curve for patients attaining meaningful pain reduction (baseline NRS score reduction ≥50%) after Gamma Knife central lateral thalamotomy. Estimated rates of patients attaining meaningful pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. NRS, Numeric Pain Rating Scale.
FIGURE 3.: Kaplan-Meier survival curves comparing meaningful pain reduction rates after Gamma Knife central lateral thalamotomy in patients with trigeminal deafferentation pain (continue line) and other neuropathic pain syndromes (dotted line). Estimated rates of patients attaining meaningful pain reduction for patients with trigeminal deafferentation pain at 1, 2, 3, and 5 years were 66%, 66%, 22%, and 22%, respectively. Estimated rates of patients attaining meaningful pain reduction for patients with neuropathic pain syndromes different than trigeminal deafferentation pain at 1, 2, 3, and 5 years were 22%, 22%, 11%, and 11%, respectively. TDP, trigeminal deafferentation pain.
TABLE 5. -
Pain Outcomes After GKRS
| Variable |
N (%) |
Median (range) |
| Initial meaningful pain reduction |
|  All |
12 (57) |
|
|  TDP |
10 (83) |
|
|  Other pain causes |
2 (22) |
|
|  Time to meaningful pain reduction, mo |
|
28 (8-81) |
| Final meaningful pain reduction |
|  All |
7 (33) |
|
|  TDP |
6 (50) |
|
|  Other pain causes |
1 (11) |
|
| During follow-up best recorded post-GKRS NRS |
|  10 |
1 |
|
|  9 |
3 |
|
|  8 |
2 |
|
|  7 |
1 |
|
|  6 |
2 |
|
|  5 |
3 |
|
|  4 |
6 |
|
|  2 |
1 |
|
|  0 |
2 |
|
| Last recorded post-GKRS NRS |
|  10 |
3 |
|
|  9 |
4 |
|
|  8 |
6 |
|
|  7 |
1 |
|
|  5 |
2 |
|
|  4 |
3 |
|
|  2 |
1 |
|
|  0 |
1 |
|
| Time to pain recurrence, mo |
|
36 (2-36) |
| BNI pain scores at last assessment |
|  V |
7 |
|
|  IV |
7 |
|
|  III |
6 |
|
|  II |
0 |
|
|  I |
1 |
|
BNI, Barrow neurological Institute; GKRS, Gamma Knife radiosurgery; NRS, numeric pain rating scale; TDP, trigeminal deafferentation pain.
Safety
No patient included in this study suffered an adverse event because of central lateral thalamotomy using GKRS.
DISCUSSION
In this single-center retrospective series, we demonstrated that central lateral thalamotomy using GKRS was safe and initially effective in reducing pain in a subset of patients with neuropathic pain; however, pain recurred frequently over time, and only 1 patient experienced complete pain relief. Patients with facial deafferentation pain were significantly more likely to experience pain reduction than those with other neuropathic pain syndromes. Pain reduction was usually delayed with respect to the GKRS procedure, likely because of the time necessary for the lesions to mature.
Within the past decades, there have been several reports of lesioning the medial thalamus for the treatment of chronic pain. Recently, the interest of neurosurgeons has focused on central lateral thalamotomy.6-8 This procedure was introduced by Jeanmonod et al,7,8 who consistently observed favorable results after performing central lateral thalamotomy in a large group of patients. Those authors postulated that ablating the CLp was successful as it restored some thalamocortical dynamics that had been altered by neuropathic pain states.9 Initially, Jeanmonod's7 group generated lesions in the CLp using RFTA, with 53% of the 96 patients with neuropathic pain having sustained pain reduction (more than 50% from baseline) after treatment. Subsequently, those authors created lesions using MRgFUS. In their most recent study using MRgFUS ablation for neuropathic pain, which included 12 patients, 5 of the 8 patients who were assessed at 1 year after the procedure had meaningful pain reduction (mean pain reduction of 57% at the 1-year follow-up).8 Their studies' outcomes compared favorably with other studies of medial thalamotomy for neuropathic pain.16,17 Of note, a review of the literature related to medial thalamotomy by Tasker5 reported that only 29% of patients with neuropathic pain had successful pain reduction after lesioning the medial thalamic nuclei.
Since 2014, we have performed central lateral thalamotomy in patients with neuropathic pain using GKRS. Our early results compared with those of Jeanmonod et al8,9 using MRgFUS because 5 of the 8 patients who underwent GKRS reported meaningful pain reduction after an average follow-up of 2 years.6 By contrast, the results of the present follow-up study showed frequent pain recurrence over time and compare with those reported by other groups investigating medial thalamotomy using SRS.5,17-19 A recent systematic review of the literature about medial thalamotomy using SRS showed that only 38% of patients had meaningful pain reduction at their last assessment,4 which is similar to the 33% observed in the present investigation. These less favorable results are likely because of the longer follow-up periods of many patients; in a similar way, previous reports of patients undergoing interventional ablative or neuromodulatory therapies of the central nervous system for pain, including medial thalamotomy, demonstrated that pain reduction weans over time.4,20
Consistent with our previous report, pain reduction was more frequent in patients with trigeminal deafferentation pain than in those with other neuropathic pain syndromes. As a matter of fact, all but 1 of the treatment-responder patients of our study suffered from trigeminal deafferentation pain. This observation is consistent with those of Lovo et al,21 who used SRS for performing medial thalamotomy. Hitchcock and Texeira,22 Mark et al,23,24 and Steiner et al25 also observed that patients with pain located in the upper body had better pain outcomes after medial thalamotomy, although the reason for such predilection is still unclear.
Medial thalamotomy using SRS is a safe procedure, and reported adverse events are low. The few reported radiation-related complications are from early studies that used higher radiation doses, large collimator helmets, and multiple isocenters plans.4 The use of contemporary SRS delivery platforms and lower radiation doses obviated radiation-induced adverse events in recent studies. As a matter of fact, many patients included in this study were treated with simultaneous bilateral single 4-mm isocenter lesions using 130 or 140 Gy, without suffering adverse events after long-term assessment. This same dose prescription has been used for bilateral thalamotomies in patients with movement disorders without observing radiation-related complications.26 The CLp's large dimension and position distant from eloquent areas make central lateral thalamotomy particularly safe. In support of this claim, studies investigating central lateral thalamotomy with MRgFUS and RFTA reported few complications, which were generally related to the surgical procedures rather than neurological sequelae of the lesions.7,8 This study confirms the high safety profile of central lateral thalamotomy performed with GKRS. No adverse event was recorded during the follow-up assessments of all patients.
The advantages of GKRS over MRgFUS are that patients do not require head shaving and do not need to be in an MRI environment. The advantages of using MRgFUS for central lateral thalamotomy are the immediate pain reduction effect and that lesions can be repeated in the case of pain recurrence, without dose-accumulation effect. The volume of a single 4-mm isocenter radio lesion is too small to cover the whole extent of the CLp, especially in its dorsoventral size, possibly limiting the efficacy of the procedure. As a matter of fact, Gallay et al27 recently showed that large MRgFUS-mediated lesions covering a greater extension of the CLp are remarkably effective in patients with medically intractable trigeminal neuralgia (in their study, all the 8 patients treated had pain intensity reduction of 50% or more from baseline after a median period of 60 months).
Limitations
The results of this study should be interpreted in the context of several limitations. Pain was evaluated with subjective measures not assessing the affective-emotional and cognitive-attentive dimensions of pain and patients' health-related quality of life. In addition, we have not systematically collected information about changes in pain quality after GKRS. Cognitive changes that occurred after thalamotomy were not assessed with validated neuropsychological scales. The heterogeneous indications to GKRS and the uneven size of patients' subpopulations limited analyses between subgroups. The retrospective design and single-center nature of this study limit its power and generalizability. Finally, the lack of a control group and randomization does not allow us to rule out the influence of a placebo effect in patients' reported results.
CONCLUSION
Our findings demonstrate that central lateral thalamotomy using GKRS is remarkably safe, even if bilateral lesions are performed concurrently. Pain reduction occurs in a subset of patients with neuropathic pain, more frequently with trigeminal deafferentation pain; however, pain reduction is usually partial, pain recurrences are frequent over time, and complete pain relief is rare. Our pain reduction rates compare with those of other studies investigating medial thalamotomy using SRS in patients with intractable pain.4 The role of central lateral thalamotomy using GKRS for the treatment of neuropathic pain syndromes is not established, and randomized studies will have to be conducted to establish its actual safety and efficacy. Some trials of central lateral thalamotomy using MRgFUS are ongoing worldwide (NCT05122403, NCT03309813, NCT04579692, and NCT01699477). The results of these studies will provide more information on the outcomes of central lateral thalamotomy in patients with chronic pain.
Acknowledgments
We would like to acknowledge Dr Shayan Moosa (University of Virginia) for his assistance in proofreading the manuscript.
Funding
This study did not receive any funding or financial support.
Disclosures
The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
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