Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions.

OBJECTIVE: Medial thalamotomies were introduced in the late 1940s. Pain relief was shown to be achieved for all body locations. With some exceptions, these early relatively small series showed frequent, more or less complete recurrence of the original pain. The posterior part of the central lateral nucleus in the human medial thalamus was identified in the 1990s using multiarchitectonic studies and intraoperative single-cell recordings and was confirmed as a surgical target. This retrospective patient series extended over 11 years. Its goal was to demonstrate the efficacy and risk profile of the MR-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) against chronic and therapy-resistant neuropathic (i.e., neurogenic) pain. METHODS: In this single-center, nonrandomized retrospective cross-sectional analysis of consecutive patients, 63 consecutive MRgFUS CLT interventions were performed in 55 patients. RESULTS: The mean follow-up duration was 55 months. A total of 112 CLT targets were performed, and the CLT was applied bilaterally in 48 patients and contralateral to their pain in 7 patients. Repeat MRgFUS interventions were performed in 8 patients. One serious adverse event with numbness of the upper lip was recorded. The mean pain relief rated by patients was 42% ± 32% at 3 months, 43% ± 36% at 1 year, and 42% ± 37% at the last follow-up (n = 63). The proportions of cases with ≥ 30% pain relief were 65% at 3 months, 63% at 1 year, and 61% at the last follow-up. Good outcomes (≥ 50% pain relief) were found in 54% of patients at 3 months, 49% at 1 year, and 51% at the last follow-up. The reduction in mean VAS scores showed similar percentage reductions as those for pain relief (-41% for continuous pain and -49% for pain attacks) at the 1-year follow-up. The mean frequency of pain attacks was reduced by 92%. Allodynia was reduced or suppressed in 68% of patients and never appeared de novo after MRgFUS CLT. CONCLUSIONS: These results suggest that MRgFUS CLT against neuropathic pain is a safe approach and its results are stable over time. At a mean follow-up duration of 55 months, the mean pain relief was 42% and more than 50% of patients still reported ≥ 50% pain relief. Patients with classical and idiopathic trigeminal neuralgia reported a higher mean pain relief compared with the whole patient group.

Complete resolution of chronic cluster headache following central lateral thalamotomy using incisionless MRI-guided focused ultrasound with 6 years of follow-up: illustrative case.

BACKGROUND: The authors reported the case of a 66-year-old male patient with a 14-year history of right-sided severe episodic and therapy-resistant cluster headache (CH) who underwent bilateral central lateral thalamotomy (CLT) using incisionless transcranial magnetic resonance imaging-guided focused ultrasound (MRgFUS). OBSERVATIONS: The patient experienced a single cluster headache attack 5 weeks after the procedure. There were no more pain attacks over the next 6 years of follow-up. LESSONS: This treatment success may indicate a common pathophysiology for CH and neurogenic (neuropathic) pain, which has been treated with CLT for more than 30 years. Further experience is needed to assess the reproducibility of this case.

Bilateral MR-Guided Focused Ultrasound Pallidothalamic Tractotomy for Parkinson's Disease With 1-Year Follow-Up.

Objective: Bilateral stereotactic neurosurgery for advanced Parkinson's disease (PD) has a long history beginning in the late 1940s. In view of improved lesioning accuracy and reduced bleeding risk and in spite of long-standing caveats about bilateral approaches, there is a need to investigate bilateral MR-guided focused ultrasound (MRgFUS) interventions. We hereby present the clinical results of bilateral pallidothalamic tractotomy (PTT), i.e., targeting of pallidal efferent fibers below the thalamus at the level of Forel's field H1, followed for 1 year after operation of the second side. Methods: Ten patients suffering from chronic and therapy-resistant PD having received bilateral PTT were followed for 1 year after operation of the second side. The primary endpoints included the Unified Parkinson's Disease Rating Scale (UPDRS) scores in on- and off-medication states, dyskinesias, dystonia, sleep disturbances, pain, reduction in drug intake, and assessment by the patient of her/his global symptom relief as well as tremor control. Results: The time frame between baseline UPDRS score and 1 year after the second side was 36 ± 15 months. The total UPDRS score off-medication at 1 year after the second PTT was reduced by 52% compared to that at baseline on-medication (p < 0.007). Percentage reductions of the mean scores comparing 1 year off- with baseline on-medication examinations were 91% for tremor (p = 0.006), 67% for distal rigidity (p = 0.006), and 54% for distal hypobradykinesia (p = 0.01). Gait and postural instability were globally unchanged to baseline (13% improvement of the mean, p = 0.67, and 5.3% mean reduction, p = 0.83). Speech difficulties, namely, hypophonia, tachyphemia, and initiation of speech, were increased by 58% (p = 0.06). Dyskinesias were suppressed in four over four, dystonia in four over five, and sleep disorders in three over four patients. There was 89% pain reduction. Mean L-Dopa intake was reduced from 690 ± 250 to 110 ± 190. Conclusions: Our results suggest an efficiency of bilateral PTT in controlling tremor, distal rigidity, distal hypobradykinesia, dyskinesias, dystonia, and pain when compared to best medical treatment at baseline. Larger series are of course needed.

MR-Guided Focused Ultrasound Central Lateral Thalamotomy for Trigeminal Neuralgia. Single Center Experience.

Background: Trigeminal neuralgia (TN) is a recognized pain condition the treatment of which can be very challenging. Various surgical interventions can be applied in cases of therapy-resistance to drug treatments. The central lateral thalamotomy (CLT) against neurogenic (or neuropathic) pain is based on multiarchitectonic histological as well as physiopathological studies, and integrates the nucleus in a large thalamocortical (TC) and corticocortical network responsible for the sensory, cognitive and affective/emotional components of pain. The advent of the magnetic resonance imaging guided high intensity focused ultrasound (MRgFUS) brought a strong reduction in morbidity and increase in accuracy compared to penetration techniques. Objective: This study was aimed at analyzing the outcome of bilateral MRgFUS CLT for chronic therapy-resistant trigeminal pain, all performed in one single center. Methods: Patients were categorized in Classical, Idiopathic and Secondary TN. By definition, paroxysms lasted for seconds up to 2 min. All patients were screened for trigeminal neurovascular conflict. In case of classical TN, microvascular decompression was proposed. Therapy-resistance and thus indication for MRgFUS CLT was based on the lack of efficacy and/or side effects of antiepileptic and antidepressant drugs. Good outcome was defined by a pain relief ≥50%. Results: Eight patients suffering from chronic therapy-resistant trigeminal neuralgia were treated. All suffered from pain with paroxysmal character. Six patients reported additionally continuous pain. Mean follow-up was 53 months (range: 12-92, median: 60 months). The mean pain relief assessed by patients was 51% (median: 58%, range: 0-90%) at 3 months, 71% (median: 65%, range: 40-100%) at 1 year and 78% (median: 75%, range: 50-100%) at their longest follow-up. This represents 63% good outcomes at 3 months, 88% at 1 year and 100% at last follow-up. Frequency of the mean pain paroxysms decreased from 84 per day preoperative to 3.9 at 1 year postoperatively. There were no serious adverse events in this series. Conclusion: Our study provides preliminary support for the safety and efficacy of MRgFUS CLT, a histologically and pathophysiologically based medial thalamotomy against chronic therapy-resistant trigeminal neuralgia.

MR-guided focused ultrasound cerebellothalamic tractotomy for chronic therapy-resistant essential tremor: anatomical target reappraisal and clinical results.

OBJECTIVE: In addition to the well-recognized ventral intermediate nucleus (Vim) thalamotomy for the treatment of chronic therapy-resistant essential tremor (ET), an alternative approach targeting the posterior part of the subthalamus was proposed in the 1960s and early 1970s and then was reactualized as cerebellothalamic tractotomy (CTT) with the advent of MR-guided focused ultrasound (MRgFUS) surgery. The goal of this study was to improve target coverage and thus efficacy (i.e., tremor control and its consistency). The authors undertook a histological reappraisal of the CTT target and proposed a targeting strategy of the MRgFUS CTT based on 1) the MR visualization of the center of the red nucleus and 2) the application of preplanned target subunits realized with short sonications under thermal dose control. This study was aimed at demonstrating the efficacy and risk profile of this approach against chronic therapy-resistant ET. METHODS: Ten consecutive patients suffering from chronic therapy-resistant ET benefited from a unilateral MRgFUS CTT and were followed over the course of 1 year. Primary endpoints were subjective tremor relief, Clinical Rating Scale for Tremor (CRST) score, activities of daily living (ADL) score, and the hand function (HF) scores HF16 and HF32. Histological reappraisal of the target led the authors to propose a standardized targeting protocol for MRgFUS CTT. Thermal doses for 18 and 240 cumulative equivalent minutes at 43°C were calculated and correlated with intraoperative and 2 days postoperative T2-weighted MR images. RESULTS: The mean ± SD for the baseline CRST score was 48 ± 12; the score was 16 ± 7 at 3 months, and 17 ± 8 at 1 year. The mean tremor relief rated by the patients for the operated side was 95% after 2 days, 96% at 3 months, and 93% at 1 year. The mean HF16 was 11.0 ± 2.1 at baseline, 0.7 ± 0.7 at 3 months, and 0.8 ± 0.9 at 1 year (93% mean reduction). The minimum reduction for the HF16 at 1 year was 78%. There was a 51% reduction of the mean ADL score at 1 year. There was no bleeding or infection. Gait difficulties, only detectable on tandem gait, were increased in 3 patients and reduced in 2 patients at 1 year. There was no dysarthria. CONCLUSIONS: The authors' results suggest that MRgFUS CTT is a very effective treatment option for therapy-resistant ET.

Radiological and Thermal Dose Correlations in Pallidothalamic Tractotomy With MRgFUS.

Background: MR-guided focused ultrasound (MRgFUS) offers the possibility of safe and accurate lesioning inside the brain. Until now, most MRgFUS thermal applications have been based on temperature or energy protocols. Experimental studies support however an approach centered on thermal dose control. Objective: To show the technical feasibility and lesion size predictability of a thermal dose approach during MRgFUS pallidothalamic tractotomy (PTT) against chronic therapy-resistant Parkinson's disease (PD). Methods: MR and thermal dose data were analyzed in 31 MRgFUS interventions between January and December 2017 in patients suffering from chronic therapy-resistant Parkinson's disease (PD) using a standardized PTT target covered by 5 to 7 target lesion sub-units. Results: Good correlations were found between (1) the mean axial T2 lesion diameter intraoperatively and the mean 240 cumulative equivalent min at 43°C (240 CEM) thermal dose diameter (r = 0.52), (2) the mean axial T2 diameter 48 h post-treatment and the mean 18 CEM thermal dose diameter (r = 0.62), and (3) the mean axial T2 diameter intraoperatively and 48 h post-treatment (r = 0.62). Conclusion: Our current approach using a thermal dose steering for multiple target lesion sub-units could be reproduced in 31 interventions with a good lesion size predictability.

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note.

Background: MR-guided focused ultrasound (MRgFUS) offers new perspectives for safe and efficient lesioning inside the brain. The issue of target coverage remains primordial and sub-optimally addressed or solved in the field of functional neurosurgery. Objective: To provide an optimized planning and operative strategy to perform a pallidothalamic tractotomy (PTT) in chronic therapy-resistant Parkinson's disease (PD) with the technology of MRgFUS. Methods and results: Histological sections and maps from 6 human brain hemispheres were analyzed and outlines of the pallidothalamic tract on Myelin-stained sections were drawn and superimposed. We determined a standardized PTT target coverage characterized by 5 to 7 preplanned target lesion sub-units of 1.5 × 1.5 × 3.0 mm, which were placed using focal point displacements and shortest possible times, under thermal dose control. Conclusion: We hereby present our current approach to the MRgFUS PTT on the basis of a histological reappraisal and optimized heat application to the pallidothalamic tract in the H1 field of Forel.

MRgFUS Pallidothalamic Tractotomy for Chronic Therapy-Resistant Parkinson's Disease in 51 Consecutive Patients: Single Center Experience.

Background: There is a long history, beginning in the 1940s, of ablative neurosurgery on the pallidal efferent fibers to treat patients suffering from Parkinson's disease (PD). Since the early 1990s, we undertook a re-actualization of the approach to the subthalamic region, and proposed, on a histological basis, to target specifically the pallidothalamic tract at the level of Forel's field H1. This intervention, the pallidothalamic tractotomy (PTT), has been performed since 2011 using the MR-guided focused ultrasound (MRgFUS) technique. A reappraisal of the histology of the pallidothalamic tract was combined recently with an optimization of our lesioning strategy using thermal dose control. Objective: This study was aimed at demonstrating the efficacy and risk profile of MRgFUS PTT against chronic therapy-resistant PD. Methods: This consecutive case series reflects our current treatment routine and was collected between 2017 and 2018. Fifty-two interventions in 47 patients were included. Fifteen patients received bilateral PTT. The median follow-up was 12 months. Results: The Unified Parkinson's Disease Rating Scale (UPDRS) off-medication postoperative score was compared to the baseline on-medication score and revealed percentage reductions of the mean of 84% for tremor, 70% for rigidity, and 73% for distal hypobradykinesia, all values given for the treated side. Axial items (for voice, trunk and gait) were not significantly improved. PTT achieved 100% suppression of on-medication dyskinesias as well as reduction in pain (p < 0.001), dystonia (p < 0.001) and REM sleep disorders (p < 0.01). Reduction of the mean L-Dopa intake was 55%. Patients reported an 88% mean tremor relief and 82% mean global symptom relief on the operated side and 69% mean global symptom improvement for the whole body. There was no significant change of cognitive functions. The small group of bilateral PTTs at 1 year follow-up shows similar results as compared to unilateral PTTs but does not allow to draw firm conclusions at this point. Conclusion: MRgFUS PTT was shown to be a safe and effective intervention for PD patients, addressing all symptoms, with varying effectiveness. We discuss the need to integrate the preoperative state of the thalamocortical network as well as the psycho-emotional dimension.

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments.

OBJECTIVE: Since the first clinical application of the incisionless magnetic resonance-guided focused ultrasound (MRgFUS) technology only small series of patients have been reported, and thus only extrapolations of the procedure-related risks could be offered. In this study, the authors analyze side-effects and targeting accuracy in 180 consecutive treatments with MRgFUS for chronic therapy-resistant idiopathic Parkinson's disease (PD), essential tremor (ET), cerebellar tremor (CT), and neuropathic pain (NP), all performed in their dedicated center. METHODS: A total of 180 treatments with MRgFUS for chronic therapy-resistant idiopathic PD, ET, CT, and NP were prospectively assessed for side-effects and targeting accuracy. Monitoring for later side-effects was continued for at least 3 months after the procedure in all but 1 case (0.6%); in that single case, the patient was lost to follow-up after an uneventful early postoperative course. The surgical targets were the pallidothalamic tract (pallidothalamic tractotomy, n = 105), the cerebellothalamic tract (cerebellothalamic tractotomy, n = 50), the central lateral nucleus (central lateral thalamotomy, n = 84), the centrum medianum (centrum medianum thalamotomy, n = 12), and the globus pallidus (pallidotomy, n = 2). Cognitive testing was performed before, 1-2 days after, and 1 year after the procedure. The Mini-Mental State Examination (MMSE) was used for the first 29 cases and was then replaced by the Montreal Cognitive Assessment (MoCA). Lesion reconstruction and measurement of targeting accuracy were done on 2-day posttreatment MR images for each performed target. To determine targeting accuracy measurement, 234 out of the 253 lesions depicted in the 2-day postoperative MR examination could be 3D-reconstructed. RESULTS: The mean MoCA score was slightly improved 2 days postoperatively (p = 0.002) and remained stable at 1-year follow-up (p = 0.03). The mean MMSE score was also slightly improved 2 days postoperatively and at 1-year follow-up, but the improvement was not statistically significant (p = 0.06 and p = 0.2, respectively). The mean (± SD) accuracy was 0.32 ± 0.29 mm, 0.29 ± 0.28 mm, and 0.44 ± 0.39 mm for the mediolateral, anteroposterior, and dorsoventral dimensions, respectively. The mean 3D accuracy was 0.73 ± 0.39 mm. As to side-effects, 14 events over 180 treatments were documented. They were classified into procedure-related (n = 4, 2.2%), effect on neighboring structures (n = 3, 1.7%), and disease-related (n = 7, 3.9%). There was no bleeding. CONCLUSIONS: The incisionless transcranial MRgFUS technology demonstrates a higher targeting accuracy and a lower side-effect profile than techniques requiring cerebral penetration. In the absence of penetration brain shift, this technique avoids the placement of a thermolesion away from the chosen target, thus suppressing the need for reversible therapeutic energy application. With the use of proper physiopathology-based targets, definitive therapeutic effects can be coupled with sparing of sensory, motor, and paralimbic/multimodal thalamocortical functions. Clinical efficacy, not analyzed in this investigation, will ultimately rest in proper target selection and optimized thermolesional coverage of the target.

Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy.

BACKGROUND: Already in the late 1960s and early 1970s, targeting of the "posterior subthalamic area (PSA)" was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT). METHODS: Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others' (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion. RESULTS: The mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up. CONCLUSIONS: CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.

Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery.

Anatomical knowledge of the structures to be targeted and of the circuitry involved is crucial in stereotactic functional neurosurgery. The present study was undertaken in the context of surgical treatment of motor disorders such as essential tremor (ET) and Parkinson's disease (PD) to precisely determine the course and three-dimensional stereotactic localisation of the cerebellothalamic and pallidothalamic tracts in the human brain. The course of the fibre tracts to the thalamus was traced in the subthalamic region using multiple staining procedures and their entrance into the thalamus determined according to our atlas of the human thalamus and basal ganglia [Morel (2007) Stereotactic atlas of the human thalamus and basal ganglia. Informa Healthcare Inc., New York]. Stereotactic three-dimensional coordinates were determined by sectioning thalamic and basal ganglia blocks parallel to stereotactic planes and, in two cases, by correlation with magnetic resonance images (MRI) from the same brains prior to sectioning. The major contributions of this study are to provide: (1) evidence that the bulks of the cerebellothalamic and pallidothalamic tracts are clearly separated up to their thalamic entrance, (2) stereotactic maps of the two tracts in the subthalamic region, (3) the possibility to discriminate between different subthalamic fibre tracts on the basis of immunohistochemical stainings, (4) correlations of histologically identified fibre tracts with high-resolution MRI, and (5) evaluation of the interindividual variability of the fibre systems in the subthalamic region. This study should provide an important basis for accurate stereotactic neurosurgical targeting of the subthalamic region in motor disorders such as PD and ET.