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.

The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson's disease.

MR-guided focused ultrasound is a novel, minimally invasive surgical procedure for symptomatic treatment of PD. With this technology, the ventral intermediate nucleus, STN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions. © 2019 International Parkinson and Movement Disorder Society.

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.

The neurosurgical treatment of craniofacial pain syndromes: current surgical indications and techniques.

Craniofacial pain syndromes are comprised of multiple pathological entities resulting in pain referred to the scalp, face, or deeper cranial structures. In a small subset of patients affected by those syndromes, pharmacological and physical therapies fail in alleviating pain. In some of those refractory patients surgical procedures aimed at relieving pain are indicated and have been adopted with variable results and safety profiles. In this review, the authors describe craniofacial pain syndromes that most commonly fail to respond to pharmacological therapies and may be amenable to tailored surgical procedures. In particular, trigeminal, glossopharyngeal, and occipital neuralgias are considered, as well as some primary headache syndromes such as cluster headache, short unilateral neuralgiform headache with conjunctival injection and tearing/short unilateral neuralgiform headache with autonomic symptoms, and migraine. Surgical techniques, including the implantation of deep brain or peripheral nerve electrodes with subsequent chronic stimulation, microvascular decompression of neurovascular conflicts, and percutaneous lesioning of neural structures are described. Finally, surgical indications, outcomes, and safety of these procedures are presented.

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.

Ganglioglioma Arising from the Septum Pellucidum: Case Report and Review of the Literature.

BACKGROUND: Gangliogliomas are low-grade neoplasms that typically affect patients under the age of 30 and present with epilepsy and symptoms of mass effect. Here, we report a case of an intraventricular ganglioglioma involving the septum pellucidum in a pediatric patient with history of optic glioma. Only one other pediatric intraventricular ganglioglioma arising from the septum pellucidum has been reported previously. CASE REPORT: The patient initially presented at 9 months of age with a pilocytic astrocytoma centered on the optic chiasm, treated with chemotherapy and radiation at 3 years of age. Routine follow-up imaging at 13 years of age revealed the development of a mass in the septum pellucidum, which was subtotally resected endoscopically because of its proximity to the fornices. Pathology confirmed a ganglioglioma positive for the BRAF V600E mutation. The tumor residual progressed and was treated with stereotactic radiosurgery. The patient was asymptomatic at her 6-month follow-up visit and the size of the nodule remained stable. LITERATURE REVIEW: Our review of the 25 previously reported intraventricular gangliogliomas found that their pre-surgical diagnoses were often incorrect, reflecting the difficulty of making the diagnosis with signs, symptoms, and imaging alone. Patients can be reassured that the prognosis is generally favorable following uncomplicated neurosurgical resection.

Thalamic Deep Brain Stimulation Salvages Failed Focused Ultrasound Thalamotomy for Essential Tremor: A Case Report.

BACKGROUND: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. METHODS: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. RESULTS: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. CONCLUSION: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.

Deep brain stimulation for the treatment of drug addiction.

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.

Transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy for tremor: technical note.

Although the use of focused ultrasound (FUS) in neurosurgery dates to the 1950s, its clinical utility was limited by the need for a craniotomy to create an acoustic window. Recent technological advances have enabled efficient transcranial delivery of US. Moreover, US is now coupled with MRI to ensure precise energy delivery and monitoring. Thus, MRI-guided transcranial FUS lesioning is now being investigated for myriad neurological and psychiatric disorders. Among the first transcranial FUS treatments is thalamotomy for the treatment of various tremors. The authors provide a technical overview of FUS thalamotomy for tremor as well as important lessons learned during their experience with this emerging technology.

Volume-staged versus dose-staged radiosurgery outcomes for large intracranial arteriovenous malformations.

OBJECT: The aim in this paper was to compare the outcomes of dose-staged and volume-staged stereotactic radio-surgery (SRS) in the treatment of large (> 10 cm(3)) arteriovenous malformations (AVMs). METHODS: A systematic literature review was performed using PubMed. Studies written in the English language with at least 5 patients harboring large (> 10 cm(3)) AVMs treated with dose- or volume-staged SRS that reported post-treatment outcomes data were selected for review. Demographic information, radiosurgical treatment parameters, and post-SRS outcomes and complications were analyzed for each of these studies. RESULTS: The mean complete obliteration rates for the dose- and volume-staged groups were 22.8% and 47.5%, respectively. Complete obliteration was demonstrated in 30 of 161 (18.6%) and 59 of 120 (49.2%) patients in the dose- and volume-staged groups, respectively. The mean rates of symptomatic radiation-induced changes were 13.5% and 13.6% in dose- and volume-staged groups, respectively. The mean rates of cumulative post-SRS latency period hemorrhage were 12.3% and 17.8% in the dose- and volume-staged groups, respectively. The mean rates of post-SRS mortality were 3.2% and 4.6% in dose- and volume-staged groups, respectively. CONCLUSIONS: Volume-staged SRS affords higher obliteration rates and similar complication rates compared with dose-staged SRS. Thus, volume-staged SRS may be a superior approach for large AVMs that are not amenable to single-session SRS. Staged radiosurgery should be considered as an efficacious component of multimodality AVM management.

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.

Future Directions of MR-guided Focused Ultrasound.

MR-guided focused ultrasound (MRgFUS) allows for the incisionless treatment of intracranial lesions in an outpatient setting. While this is currently approved for the surgical treatment of essential tremor and Parkinson's disease, advancements in imaging and ultrasound technology are allowing for the expansion of treatment indications to other intracranial diseases. In addition, these advancements are also making MRgFUS treatments easier, safer, and more efficacious.

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.

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.

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.

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.

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.