Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial.

Importance: Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective: To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants: This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention: A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures: Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results: The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance: Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration: ClinicalTrials.gov Identifier NCT04112381.

Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility.

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to mechanical stimulus during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. Progesterone treatment of ovariectomized and estrogen-primed mice caused a delayed reduction in the mechanical threshold. Segesterone, a specific agonist of PRs replicated this effect, whereas, the segesterone-induced reduction in mechanical threshold was blocked in the mice lacking PRs in the nervous system. Segesterone treatment also did not alter mechanical threshold in adult male and juvenile female mice. PR activation increased the cold sensitivity but did not affect the heat and light sensitivity. We evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin when administered sequentially, reduced the pain threshold but not when given separately. PRs were expressed in several components of the migraine ascending pain pathway, and their deletion blocked the painful effects of nitroglycerin. PR activation also increased the number of active neurons in the components of the migraine ascending pain pathway. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain and migraine in women. PERSPECTIVE: This article provides evidence for the role of progesterone receptors in regulating pain sensitivity and migraine susceptibility in females. Progesterone receptors may be a therapeutic target to treat chronic pain conditions more prevalent in women than men.

Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation.

OBJECTIVES: The primary objective of this study was to determine whether two neurosurgical procedures, deep brain stimulation (DBS) and focused ultrasound (FUS), to treat essential tremor (ET) of the upper limb also reduce vocal tremor (VT) in patients with comorbid dysphonia. METHODS: Twelve patients with ET and concomitant VT scheduled for neurosurgical intervention (FUS or DBS) or returning for follow-up after DBS implantation were assessed. FUS patients were assessed pre- and post-intervention and DBS patients were assessed with the electrodes turned on and off post-implantation. Three voice recordings of a sustained /a/ were obtained for each participant condition. Percent fundamental frequency variability (FFV) was calculated for each recorded sustained vowel. Additionally, blinded expert perceptual VT rating (VTR) was performed to assess subjective changes in tremors. RESULTS: Of the 12 patients, seven underwent unilateral FUS, and five underwent bilateral DBS. Mean FFV without neurosurgical intervention was 18.3%, SD = 7.8 and with neurosurgical intervention was 6.3%, SD = 3.0 (t (70) =8.7, p < 0.001). Mean FFV decreased in the FUS cohort from 22.0%, SD = 7.1 pre-ablation to 6.7%, SD = 2.4 post-ablation (t (40) = 7.7, p < 0.001). Mean FFV also decreased in the DBS cohort from 15.7%, SD = 7.0 to 6.0%, SD = 3.3 when stimulation was turned on (t (28)=5.7 p < 0.001). In the FUS group, mean VTR decreased from 4.0 to 1.4 post-ablation (Z = 7.8, p < 0.001). In the DBS group, mean VTR decreased from 3.3 to 2.1 with stimulation (Z = 4.1, p < 0.001). CONCLUSION: Neurosurgical interventions for ET (bilateral DBS and unilateral FUS) demonstrate acoustic and perceptual benefits for VT. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:367-373, 2024.

Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study.

OBJECTIVE: Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design. METHODS: This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient's impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively. RESULTS: There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala. CONCLUSIONS: This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.

Progesterone receptor activation regulates sensory sensitivity.

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. We measured the pain threshold daily for four days in ovariectomized, estrogen-primed animals treated with progesterone. The pain threshold was lower 2 days later and stayed that way for the duration of the testing. A specific progesterone-receptor (PR) agonist, segesterone, promoted pain, and mice lacking PR in the brain (PRKO) did not experience lowered pain threshold when treated with progesterone or segesterone. PR activation increased the cold sensitivity but did not affect the heat sensitivity and had a small effect on light sensitivity. Finally, we evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin (NTG) when administered sequentially, reduced pain threshold but not separately. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain in women.

Painful Cutaneous Laser Stimulation for Temporal Summation of Pain Assessment.

Variability in pain sensitivity arises not only from the differences in peripheral sensory receptors but also from the differences in central nervous system (CNS) pain inhibition and facilitation mechanisms. Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation but is susceptible to confounding when elicited with the skin-contact thermode, which adds the responses of touch-related Aß low-threshold mechanoreceptors to nociceptive receptors. In the present study, we evaluate an alternative method involving the use of a contactless cutaneous laser for TSP assessment. We show that repetitive laser stimulations with a one second inter-stimulus interval evoked reliable TSP responses in a significant proportion of healthy subjects (N = 36). Female subjects (N = 18) reported greater TSP responses than male subjects confirming earlier studies of sex differences in central nociceptive excitability. Furthermore, repetitive laser stimulations during TSP induction elicited increased time-frequency electroencephalography (EEG) responses. The present study demonstrates that repetitive laser stimulation may be an alternative to skin-contact methods for TSP assessment in patients and healthy controls. PERSPECTIVE: Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation. We show that contactless cutaneous laser stimulation is a reliable alternative to the skin contact approaches during TSP assessment.

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a precise, incisionless approach to cerebral lesioning and an alternative to neuromodulation in movement disorders. Despite rigorous clinical trials, long-term patient-centered outcome data after MRgFUS for tremor-predominant Parkinson's Disease (TPPD) are relatively lacking. OBJECTIVE: To report long-term data on patient satisfaction and quality of life after MRgFUS thalamotomy for TPPD. METHODS: In a retrospective study of patients who underwent MRgFUS thalamotomy for TPPD at our institution between 2015 and 2022, a patient survey was administered to collect self-reported measures of tremor improvement, recurrence, Patients' Global Impression of Change (PGIC), and side effects. Patient demographics, FUS parameters, and lesion characteristics were analyzed. RESULTS: A total of 29 patients were included with a median follow-up of 16 months. Immediate tremor improvement was achieved in 96% of patients. Sustained improvement was achieved in 63% of patients at last follow-up. Complete tremor recurrence to baseline occurred for 17% of patients. Life quality improvement denoted by a PGIC of 1 to 2 was reported by 69% of patients. Long-term side effects were reported by 38% of patients and were mostly mild. Performing a secondary anteromedial lesion to target the ventralis oralis anterior/posterior nucleus was associated with higher rates of speech-related side effects (56% vs 12%), without significant improvement in tremor outcomes. CONCLUSION: Patient satisfaction with FUS thalamotomy for tremor-predominant PD was very high, even at longer term. Extended lesioning to target the motor thalamus did not improve tremor control and may contribute to greater frequency of postoperative motor- and speech-related side effects.

High-Frequency Ultrasound Ablation in Neurosurgery.

Modern transcranial magnetic resonance-guided focused ultrasound is an incisionless, ablative treatment modality for a growing number of neurologic disorders. This procedure selectively destroys a targeted volume of cerebral tissue and relies on real-time MR thermography to monitor tissue temperatures. By focusing on a submillimeter target through a hemispheric phased array of transducers, ultrasound waves pass through the skull and avoid overheating and brain damage. High-intensity focused ultrasound techniques are increasingly used to create safe and effective stereotactic ablations for medication-refractory movement and other neurologic and psychiatric disorders.

Stereotactic and Functional Neurosurgery Convection-Enhanced Delivery of Autologous Cerebrospinal Fluid Enhances Basal Ganglia Visualization during MRI-Guided Deep Brain Stimulation Surgery.

INTRODUCTION: The aim of this study was to determine the safety and feasibility of convection-enhanced delivery of autologous cerebrospinal fluid (CSF) for enhancing intraoperative magnetic resonance imaging (MRI) of the basal ganglia during stereotactic neurosurgery. METHODS: This pilot study was conducted in 4 patients with Parkinson's disease (PD) who underwent MRI-guided deep brain stimulation of the globus pallidus internus (GPi). CSF was obtained via lumbar puncture after general anesthesia and prior to incision. A frameless stereotaxy system was installed, and an infusion catheter was inserted to the GPi using intraoperative MRI. Infusion of autologous CSF was performed at a convective rate of 5 µL/min with a maximum volume of infusion (Vi) of 500 mL. T2-weighted MRI scans were obtained every 15 min up to a maximum of 105 min in order to calculate the volume of distribution (Vd). Safety was assessed with adverse event monitoring, and clinical outcomes were measured with changes in unmedicated UPDRS part III and PDQ-39 scores from baseline to 6 months postoperatively. RESULTS: All four infusions were safe and without adverse events. The mean unmedicated UPDRS part III and PDQ-39 scores improved by 24% and 26%, respectively. The Vd:Vi ratio ranged from 2.2 to 2.8 and peaked 45 min from the onset of infusion, which is when the borders of the GPi could generally be visualized based on T2-weighted MRI. Two patients underwent refinement of the stereotactic targeting based on infusion-enhanced images. CONCLUSIONS: The convective administration of autologous CSF to deep brain structures appears safe and feasible for enhancing intraoperative MRI during stereotactic procedures. Infusion-enhanced imaging with target-specific infusates could be developed to visualize neurochemical circuits or cellular regions that currently are not seen with anatomic/structural MRI.

Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor.

INTRODUCTION: The objectives of this study were to determine long-term patient-reported outcomes with magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET) and to identify risk factors for a poor clinical outcome. METHODS: We administered a telephone or mail-in survey to patients who consecutively underwent unilateral MRgFUS thalamotomy for ET at our institution over an 8-year period. Patients were asked to self-report measures of hand tremor improvement, degree of overall postprocedure improvement, activities of daily life, side effects, and willingness to undergo the procedure again. Specific patient characteristics, ultrasound treatment parameters, and postoperative radiological findings from magnetic resonance imaging performed 1 day after the procedure were analyzed, and multivariable linear regression was used to determine if these factors could serve as predictors of clinical outcome. RESULTS: A total of 85 patients were included in this study with a mean follow-up time of 3.0 years (range 2 months to 1 8.4 years). The mean patient-reported improvement in hand tremor at last follow-up was 66%, and 73% of patients reported meaningful change in their overall condition after the procedure. The percentages of patients reporting normal or only minimal limitations with feeding, drinking, and writing ability at last follow-up were 60%, 71%, and 48%, respectively. In the position of their former selves, 89% of patients would again choose to undergo the procedure. Larger lesions were correlated with a higher risk of adverse events. DISCUSSION/CONCLUSION: While subjective hand tremor improvement declines with time, willingness to undergo the procedure again following MRgFUS thalamotomy for ET remains very high even several years after the procedure.

Medial thalamotomy using stereotactic radiosurgery for intractable pain: a systematic review.

Medial thalamotomy using stereotactic radiosurgery (SRS) is a potential treatment for intractable pain. However, the ideal treatment parameters and expected outcomes from this procedure remain unclear. The aim of this systematic review is to provide further insights on medial thalamotomy using SRS, specifically for intractable pain. A systematic review was performed to identify all clinical articles discussing medial thalamotomy using SRS for intractable pain. Only studies in which SRS was used to target the medial thalamus for pain were included. For centers with multiple publications, care was taken to avoid recounting individual patients. The literature review revealed six studies describing outcomes of medial thalamotomy using SRS for a total of 125 patients (118 included in the outcome analysis). Fifty-two patients were treated for cancer pain across three studies, whereas five studies included 73 patients who were treated for nonmalignant pain. The individual studies demonstrated initial meaningful pain reduction in 43.3-100% of patients, with an aggregate initial meaningful pain reduction in 65 patients (55%) following SRS medial thalamotomy. This effect persisted in 45 patients (38%) at the last follow-up. Adverse events were observed in six patients (5%), which were related to radiation in five patients (4%). Medial thalamotomy using SRS is effective for select patients with treatment-resistant pain and is remarkably safe when modern radiation delivery platforms are used. More posteriorly placed lesions within the medial thalamus were associated with better pain relief. More studies are warranted to shed light on differences in patient responses.

Anterior insula stimulation increases pain threshold in humans: a pilot study.

OBJECTIVE: Chronic pain results in an enormous societal and financial burden. Opioids are the mainstay of treatment, but opioid abuse has led to an epidemic in the United States. Nonpharmacological treatment strategies like deep brain stimulation could be applied to refractory chronic pain if safe and effective brain targets are identified. The anterior insula is a putative mediator of pain-related affective-motivational and cognitive-evaluative cerebral processing. However, the effect of anterior insula stimulation on pain perception is still unknown. Here, the authors provide behavioral and neurophysiological evidence for stimulating the anterior insula as a means of potential therapeutic intervention for patients with chronic pain. METHODS: Six patients with epilepsy in whom intracerebral electrodes had been implanted for seizure localization were recruited to the study. The direct anterior insula stimulations were performed in the inpatient epilepsy monitoring unit while subjects were fully awake, comfortable, and without sedating medications. The effects of anterior insula stimulation were assessed with quantitative sensory testing for heat pain threshold, nociceptive-specific cutaneous laser-evoked potentials, and intracranial electroencephalogram (EEG) recordings. Control stimulation of noninsular brain regions was performed to test stimulation specificity. Sham stimulations, in which no current was delivered, were also performed to control for potential placebo effects. The safety of these stimulations was evaluated by bedside physicians, real-time intracranial EEG monitoring, and electrocardiogram recordings. RESULTS: Following anterior insula stimulations, the heat pain threshold of each patient significantly increased from baseline (p < 0.001) and correlated with stimulation intensity (regression analysis: ß = 0.5712, standard error 0.070, p < 0.001). Significant changes in ongoing intracranial EEG frequency band powers (p < 0.001), reduction in laser pain intensity, and attenuated laser-evoked potentials were also observed following stimulations. Furthermore, the observed behavioral and neurophysiological effects persisted beyond the stimulations. Subjects were not aware of the stimulations, and there were no cardiovascular or untoward effects. CONCLUSIONS: Additional, nonpharmacological therapies are imperative for the future management of chronic pain conditions and to mitigate the ongoing opioid crisis. This study suggests that direct stimulation of the anterior insula can safely alter cerebral pain processing in humans. Further investigation of the anterior insula as a potential target for therapeutic neuromodulation is underway.

Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain.

OBJECTIVE: The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain. METHODS: Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol-5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months. RESULTS: Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8-10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8-10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively. CONCLUSIONS: Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.

In vitro and in vivo characterization of a cranial window prosthesis for diagnostic and therapeutic cerebral ultrasound.

OBJECTIVE: The authors evaluated the acoustic properties of an implantable, biocompatible, polyolefin-based cranial prosthesis as a medium to transmit ultrasound energy into the intracranial space with minimal distortion for imaging and therapeutic purposes. METHODS: The authors performed in vitro and in vivo studies of ultrasound transmission through a cranial prosthesis. In the in vitro phase, they analyzed the transmission of ultrasound energy through the prosthesis in a water tank using various transducers with resonance frequencies corresponding to those of devices used for neurosurgical imaging and therapeutic purposes. Four distinct, single-element, focused transducers were tested at fundamental frequencies of 500 kHz, 1 MHz, 2.5 MHz, and 5 MHz. In addition, the authors tested ultrasound transmission through the prosthesis using a linear diagnostic probe (center frequency 5.3 MHz) with a calibrated needle hydrophone in free water. Each transducer was assessed across a range of input voltages that encompassed their full minimum to maximum range without waveform distortion. They also tested the effect of the prosthesis on beam pressure and geometry. In the in vivo phase, the authors performed ultrasound imaging through the prosthesis implanted in a swine model. RESULTS: Acoustic power attenuation through the prosthesis was considerably lower than that reported to occur through the native cranial bone. Increasing the frequency of the transducer augmented the degree of acoustic power loss. The degradation/distortion of the ultrasound beams passing through the prosthesis was minimal in all 3 spatial planes (XY, XZ, and YZ) that were examined. The images acquired in vivo demonstrated no spatial distortion from the prosthesis, with spatial relationships that were superimposable to those acquired through the dura. CONCLUSIONS: The results of the tests performed on the polyolefin-based cranial prosthesis indicated that this is a valid medium for delivering both focused and unfocused ultrasound and obtaining ultrasound images of the intracranial space. The prosthesis may serve for several diagnostic and therapeutic ultrasound-based applications, including bedside imaging of the brain and ultrasound-guided focused ultrasound cerebral procedures.

Ultrasound Ablation in Neurosurgery: Current Clinical Applications and Future Perspectives.

The concept of focusing high-intensity ultrasound beams for the purpose of cerebral ablation has interested neurosurgeons for more than 70 yr. However, the need for a craniectomy or a cranial acoustic window hindered the clinical diffusion of this technique. Recent technological advances, including the development of phased-array transducers and magnetic resonance imaging technology, have rekindled the interest in ultrasound for ablative brain surgery and have led to the development of the transcranial magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation procedure. In the last decade, this method has become increasingly popular, and its clinical applications are broadening. Despite the demonstrated efficacy of MRgFUS, transcranial thermal ablation using ultrasound is limited in that it can target exclusively the central region of the brain where the multiple acoustic beams are most optimally focused. On the contrary, lesioning of the cortex, the superficial subcortical areas, and regions close to the skull base is not possible with the limited treatment envelope of current phased-array transducers. Therefore, new ultrasound ablative techniques, which are not based on thermal mechanisms, have been developed and tested in experimental settings. This review describes the mechanisms by which these novel, nonthermal ablative techniques are based and also presents the current clinical applications of MRgFUS thermal ablation.

Ablative brain surgery: an overview.

Background: Ablative therapies have been used for the treatment of neurological disorders for many years. They have been used both for creating therapeutic lesions within dysfunctional brain circuits and to destroy intracranial tumors and space-occupying masses. Despite the introduction of new effective drugs and neuromodulative techniques, which became more popular and subsequently caused brain ablation techniques to fall out favor, recent technological advances have led to the resurgence of lesioning with an improved safety profile. Currently, the four main ablative techniques that are used for ablative brain surgery are radiofrequency thermoablation, stereotactic radiosurgery, laser interstitial thermal therapy and magnetic resonance-guided focused ultrasound thermal ablation. Object: To review the physical principles underlying brain ablative therapies and to describe their use for neurological disorders. Methods: The literature regarding the neurosurgical applications of brain ablative therapies has been reviewed. Results: Ablative treatments have been used for several neurological disorders, including movement disorders, psychiatric disorders, chronic pain, drug-resistant epilepsy and brain tumors. Conclusions: There are several ongoing efforts to use novel ablative therapies directed towards the brain. The recent development of techniques that allow for precise targeting, accurate delivery of thermal doses and real-time visualization of induced tissue damage during the procedure have resulted in novel techniques for cerebral ablation such as magnetic resonance-guided focused ultrasound or laser interstitial thermal therapy. However, older techniques such as radiofrequency thermal ablation or stereotactic radiosurgery still have a pivotal role in the management of a variety of neurological disorders.

Gamma Knife Radiosurgery for Trigeminal Neuralgia Reduces Neurovascular Compression: A Case Report after 11 Years.

BACKGROUND: Trigeminal neuralgia (TN) is a rare and debilitating craniofacial pain syndrome often caused by vascular compression of the trigeminal nerve. Gamma Knife radiosurgery (GKRS) has been shown to offer a less invasive yet effective treatment method for pain reduction in TN. In this case report, we observed radiological evidence of resolved neurovascular compression after 11 years for a patient with recur-rent TN and prior GKRS. CASE REPORT: A 72-year-old -female presented with TN and radiological evidence of neurovas-cular compression on the affected side. She had complete resolution of her pain for 7 years after treatment with GKRS. The patient experienced recurrence and underwent repeat GKRS, this time resulting in another 3 years of pain relief. After the second recurrence, repeat intracranial imaging demonstrated resolution of neurovascular compression. DISCUSSION: GKRS is an important treatment option for TN, although the mechanisms behind pain relief from this procedure still remain unclear. While prior histological and radiological studies point to ablative mechanisms for pain relief, this case report suggests that GKRS may result in a decompressive effect in TN due to changes in neurovascular architecture. Despite this finding, TN is known to occur and recur in the absence of neurovascular compression; thus, further work is necessary to understand the etiology of TN and its treatments. CONCLUSION: In this case, we demonstrate that vessel-nerve relationships may change over time in TN patients treated with GKRS, which raises the possibility that GKRS could ease a neurovascular compression.

Deep brain stimulation of the posterior limb of the internal capsule in the treatment of central poststroke neuropathic pain of the lower limb: case series with long-term follow-up and literature review.

OBJECTIVE: Central poststroke neuropathic pain is a debilitating syndrome that is often resistant to medical therapies. Surgical measures include motor cortex stimulation and deep brain stimulation (DBS), which have been used to relieve pain. The aim of this study was to retrospectively assess the safety and long-term efficacy of DBS of the posterior limb of the internal capsule for relieving central poststroke neuropathic pain and associated spasticity affecting the lower limb. METHODS: Clinical and surgical data were retrospectively collected and analyzed in all patients who had undergone DBS of the posterior limb of the internal capsule to address central poststroke neuropathic pain refractory to conservative measures. In addition, long-term pain intensity and level of satisfaction gained from stimulation were assessed. Pain was evaluated using the visual analog scale (VAS). Information on gait improvement was obtained from medical records, neurological examination, and interview. RESULTS: Four patients have undergone the procedure since 2001. No mortality or morbidity related to the surgery was recorded. In three patients, stimulation of the posterior limb of the internal capsule resulted in long-term pain relief; in a fourth patient, the procedure failed to produce any long-lasting positive effect. Two patients obtained a reduction in spasticity and improved motor capability. Before surgery, the mean VAS score was 9 (range 8-10). In the immediate postoperative period and within 1 week after the DBS system had been turned on, the mean VAS score was significantly lower at a mean of 3 (range 0-6). After a mean follow-up of 5.88 years, the mean VAS score was still reduced at 5.5 (range 3-8). The mean percentage of long-term pain reduction was 38.13%. CONCLUSIONS: This series suggests that stimulation of the posterior limb of the internal capsule is safe and effective in treating patients with chronic neuropathic pain affecting the lower limb. The procedure may be a more targeted treatment method than motor cortex stimulation or other neuromodulation techniques in the subset of patients whose pain and spasticity are referred to the lower limbs.