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.

Convergent Morphological Evolution in Silene Sect. Italicae (Caryophyllaceae) in the Mediterranean Basin.

Recent divergence can obscure species boundaries among closely related taxa. Silene section Italicae (Caryophyllaceae) has been taxonomically controversial, with about 30 species described. We investigate species delimitation within this section using 500 specimens sequenced for one nuclear and two plastid markers. Despite the use of a small number of genes, the large number of sequenced samples allowed confident delimitation of 50% of the species. The delimitation of other species (e.g., Silene nemoralis, S. nodulosa and S. andryalifolia) was more challenging. We confirmed that seven of the ten chasmophyte species in the section are not related to each other but are, instead, genetically closer to geographically nearby species belonging to Italicae yet growing in open habitats. Adaptation to chasmophytic habitats therefore appears to have occurred independently, as a result of convergent evolution within the group. Species from the Western Mediterranean Basin showed more conflicting species boundaries than species from the Eastern Mediterranean Basin, where there are fewer but better-delimited species. Significant positive correlations were found between an estimation of the effective population size of the taxa and their extent of occurrence (EOO) or area of occupancy (AOO), and negative but non-significant correlations between the former and the posterior probability (PP) of the corresponding clades. These correlations might suggest a lower impact of incomplete lineage sorting in species with low effective population sizes and small distributional ranges compared with that in species inhabiting large areas. Finally, we confirmed that S. italica and S. nemoralis are distinct species, that S. nemoralis might furthermore include two different species and that S. velutina from Corsica and S. hicesiae from the Lipari Islands are sister species.

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.

Effects of Cerebellothalamic Tractotomy on Cognitive and Emotional Functioning in Essential Tremor: A Preliminary Study in 5 Essential Tremor Patients.

Background: Subthalamic stereotactic interventions have recently caught renewed interest as a treatment for essential tremor (ET). However, it is not clear whether these interventions are associated with neurocognitive, mood or personality changes. Objective: To investigate neurocognition, neuropsychiatric functions and personality variables in patients with ET and to explore the neurocognitive and neuropsychiatric effects of cerebellothalamic tractotomy (CTT), a form of subthalamotomy. Methods: In our study, we investigated cognitive functions, frontal functions, mood and personality variables in 5 patients with intractable ET. Patients were tested before and 3 months after surgery using neuropsychological tests, clinical scales for depression, anxiety, anger regulation and a personality test. Results: Before surgery, ET patients showed normal neurocognitive function, a slightly elevated frontal lobe score in the dimensions mental control and memory, without being indicative of a frontal lesion, and no elevated depression or anxiety scores compared to norm values. After surgery, there was no change in neurocognitive function and no increase in depression or anxiety scores. Conclusion: In this exploratory study on 5 ET patients, CTT was not associated with alterations of mood or neurocognitive functions. © 2015 S. Karger AG, Basel.

First experience with MR-guided focused ultrasound in the treatment of Parkinson's disease.

BACKGROUND: Radiofrequency (RF) subthalamotomies have been proposed since the 1960s to treat patients suffering from Parkinson's disease (PD). Recently, the magnetic resonance (MR)-guided focused ultrasound technology (MRgFUS) offers the possibility to perform subthalamic thermocoagulations with reduced risks and optimized accuracy. We describe here the initial results of the MRgFUS pallidothalamic tractotomy (PTT), an anatomical and physiological update of the earlier subthalamotomies. METHODS: Thirteen consecutive patients suffering from chronic (mean disease duration 9.7 years) and therapy-resistant PD were treated unilaterally with an MRgFUS PTT. Primary relief assessment indicators were the score reduction of the Unified Parkinson Disease Rating Scale (UPDRS) and the patient estimation of global symptom relief (GSR) taken at 3 months follow-up. Final temperatures at target were between 52°C and 59°C. The MR examinations were performed before the treatment, 2 days and 3 months after it. The accuracy of the targeting was calculated on 2 days post-treatment MR pictures for each PTT lesion. RESULTS: The first four patients received a PTT using the lesional parameters applied for thalamotomies. They experienced clear-cut recurrences at 3 months (mean UPDRS relief 7.6%, mean GSR 22.5%), and their MR showed no sign of thermal lesion in T2-weighted (T2w) images. As a consequence, the treatment protocol was adapted for the following nine patients by applying repetition of the final temperatures 4 to 5 times. That produced thermocoagulations of larger volumes (172 mm(3) against 83 mm(3) for the first four patients), which remained visible at 3 months on T2w images. These nine patients enjoyed a mean UPDRS reduction of 60.9% and a GSR of 56.7%, very close to the results obtained with radiofrequency lesioning. The targeting accuracy for the whole patient group was 0.5, 0.5, and 0.6 mm for the anteroposterior (AP), mediolateral (ML), and dorsoventral (DV) dimensions, respectively. CONCLUSIONS: This study demonstrated the feasibility, safety, and accuracy of the MRgFUS PTT. To obtain similar results as the ones of RF PTT, it was necessary to integrate the fact that white matter, in this case, the pallidothalamic tract, requires repeated thermal exposition to achieve full lesioning and thus full therapeutic effect.

Cognitive functioning, emotional processing, mood, and personality variables before and after stereotactic surgery: a study of 8 cases with chronic neuropathic pain.

BACKGROUND: Stereotactic central lateral thalamotomy (CLT) has been applied as a treatment for chronic intractable neuropathic pain. However, it is not clear whether this intervention influences the emotional and cognitive impairments observed in patients who have chronic neuropathic pain. OBJECTIVE: To investigate neuropsychological functions and emotional processing in patients with chronic neuropathic pain compared with healthy volunteers and to explore the neuropsychiatric effect of the CLT. METHODS: We investigated pain ratings, cognitive functions, emotional processes, and personality variables before and after surgery in 8 patients with intractable neuropathic pain. Patients were tested before and 3 months after CLT by the use of neuropsychological tests; clinical scales for depression, anxiety, anhedonia, and anger regulation; a personality test; and 2 experimental tasks testing the theory of mind as well as the ability to recognize facial emotional expressions. Nine age- and sex-matched control subjects were tested once using the same procedure. RESULTS: The comparison of the patient group before surgery with the control group evidenced significant differences on the cognitive assessments, the depression and anxiety scores, as well as on the somatic complaint subscale of the personality test. Three months after CLT, patients experienced a significant improvement in their depression scores. There were no additional postsurgical cognitive impairments. CONCLUSION: For our patients with chronic neuropathic pain, CLT provided pain relief and reduction of their depression scores without causing postsurgical cognitive impairments.

MR-guided focused ultrasound technique in functional neurosurgery: targeting accuracy.

BACKGROUND: The purpose of this study was to describe targeting accuracy in functional neurosurgery using incisionless transcranial magnetic resonance (MR)-guided focused ultrasound technology. METHODS: MR examinations were performed before and 2 days after the ultrasound functional neurosurgical treatment to visualize the targets on T2-weighted images and determine their coordinates. Thirty consecutive targets were reconstructed: 18 were in the central lateral nucleus of the medial thalamus (central lateral thalamotomies against neurogenic pain), 1 in the centrum medianum thalamic nucleus (centrum medianum thalamotomy against essential tremor), 10 on the pallido-thalamic tract (pallido-thalamic tractotomies against Parkinson's disease), and 1 on the cerebello-thalamic tract (cerebello-thalamic tractotomy against essential tremor). We describe a method for reconstruction of the lesion coordinates on post-treatment MR images, which were compared with the desired atlas target coordinates. We also calculated the accuracy of the intra-operative target placement, thus allowing to determine the global, planning, and device accuracies. We also estimated the target lesion volume. RESULTS: We found mean absolute global targeting accuracies of 0.44 mm for the medio-lateral dimension (standard deviation 0.35 mm), 0.38 mm for the antero-posterior dimension (standard deviation 0.33 mm), and 0.66 mm for the dorso-ventral dimension (standard deviation 0.37 mm). Out of the 90 measured coordinates, 83 (92.2%) were inside the millimeter domain. The mean three-dimensional (3D) global accuracy was 0.99 mm (standard deviation 0.39 mm). The mean target volumes, reconstructed from surface measurements on 3D T1 series, were 68.5 mm(3) (standard deviation 39.7 mm(3)), and 68.9 mm(3) (standard deviation 40 mm(3)) using an ellipsoidal approximation. CONCLUSION: This study demonstrates a high accuracy of the MR-guided focused ultrasound technique. This high accuracy is due not only to the device qualities but also to the possibility for the operator to perform on-going real-time monitoring of the lesioning process. A precise method for determination of targeting accuracy is an essential component and basic requirement of the functional neurosurgical activity, allowing an on-going control of the performed therapeutic work indispensable for any target efficiency analysis and the maintenance of a low risk profile.

Correction: MR-guided focused ultrasound technique in functional neurosurgery: targeting accuracy.

[This corrects the article on p. 3 in vol. 1, PMID: 24761224.].

Pain ratings, psychological functioning and quantitative EEG in a controlled study of chronic back pain patients.

OBJECTIVES: Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chronic back pain, and we compared patients with neuropathic and non-neuropathic pain components. We furthermore assessed the presence of psychopathology and the degree of psychological functioning and examined whether the strength of the TCD-related EEG markers is correlated with psychological symptoms and pain ratings. DESIGN: Controlled clinical trial with age and sex matched healthy controls. METHODS: Spontaneous EEG was recorded in 37 back pain patients and 37 healthy controls. RESULTS: We were not able to observe a statistically significant TCD effect in the EEG data of the whole patient group, but a subsample of patients with evidence for root damage showed a trend in this direction. Pain patients showed markedly increased psychopathology. In addition, patients' ratings of pain intensity within the last 1 to 12 months showed strong correlations with EEG power, while psychopathology was correlated to the peak frequency. CONCLUSION: Out of several possible interpretations the most likely conclusion is that only patients with severe pain as well as root lesions with consecutive thalamic deafferentation develop the typical TCD pattern. Our primary method of defining 'neuropathic pain' could not reliably determine if such a deafferentation was present. Nevertheless the analysis of a specific subsample as well as correlations between pain ratings, psychopathology and EEG power and peak frequency give some support to the TCD concept. TRIAL REGISTRATION: ClinicalTrials.gov NCT00744575.

Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain.

OBJECT: Recent technological developments open the field of therapeutic application of focused ultrasound to the brain through the intact cranium. The goal of this study was to apply the new transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain. METHODS: In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was proposed. In 11 patients, precisely localized thermal ablations of 3-4 mm in diameter were produced in the posterior part of the central lateral thalamic nucleus at peak temperatures between 51 ° C and 64 ° C with the aid of real-time patient monitoring and MR imaging and MR thermometry guidance. The treated neuropathic pain syndromes had peripheral (5 patients) or central (6 patients) origins and covered all body parts (face, arm, leg, trunk, and hemibody). RESULTS: Patients experienced mean pain relief of 49% at the 3-month follow-up (9 patients) and 57% at the 1-year follow-up (8 patients). Mean improvement according to the visual analog scale amounted to 42% at 3 months and 41% at 1 year. Six patients experienced immediate and persisting somatosensory improvements. Somatosensory and vestibular clinical manifestations were always observed during sonication time because of ultrasound-based neuronal activation and/or initial therapeutic effects. Quantitative electroencephalography (EEG) showed a significant reduction in EEG spectral overactivities. Thermal ablation sites showed sharply delineated ellipsoidal thermolesions surrounded by short-lived vasogenic edema. Lesion reconstructions (18 lesions in 9 patients) demonstrated targeting precision within a millimeter for all 3 coordinates. There was 1 complication, a bleed in the target with ischemia in the motor thalamus, which led to the introduction of 2 safety measures, that is, the detection of a potential cavitation by a cavitation detector and the maintenance of sonication temperatures below 60 ° C. CONCLUSIONS: The authors assert that tcMRgFUS represents a noninvasive, precise, and radiation-free neurosurgical technique for the treatment of neuropathic pain. The procedure avoids mechanical brain tissue shift and eliminates the risk of infection. The possibility of applying sonication thermal spots free from trajectory restrictions should allow one to optimize target coverage. The real-time continuous MR imaging and MR thermometry monitoring of targeting accuracy and thermal effects are major factors in optimizing precision, safety, and efficacy in an outpatient context.

Measurement of targeting accuracy in focused ultrasound functional neurosurgery.

The object of this study was to describe a method of measuring targeting accuracy in functional neurosurgery using MR imaging and the Stereotactic Atlas of the Human Thalamus and Basal Ganglia. This method should be useful for any functional procedure using these tools or similar ones, and is described here in the specific context of focused ultrasound surgery. The authors describe the atlas coordinate system used, the different relevant targeting and accuracy definitions, the tools used, the intraoperative target determination, the postoperative target reconstructions, and the calculation of the therapeutic lesion volume. The proposed method has been applied to the specific situation of measuring targeting accuracy in focused ultrasound functional neurosurgery. The authors found mean absolute global targeting accuracies between 0.54 and 0.72 mm (SDs between 0.34 and 0.42 mm), with 85% of measured coordinates within 1 mm. The proposed method may be particularly useful in the context of functional neurosurgical procedures implying therapeutic ablations, be they through radiofrequency, focused ultrasound, or any other technique. This method allows an ongoing control of the targeting precision, a basic requirement in any functional neurosurgical procedure.