Krishna, Vibhor

OBJECTIVE Essential tremor (ET) is common and disabling in older adults. Many patients aged ≥ 80 years are ineligible for deep brain stimulation due to medical comorbidities. Data on noninvasive alternatives, such as MR-guided high-intensity focused ultrasound (MRgHIFU), remain limited in this population. The aim of this study was to evaluate the safety and efficacy of unilateral MRgHIFU thalamotomy targeting the ventral intermediate nucleus (VIM) for the treatment of ET in patients ≥ 80 years of age. METHODS This retrospective multicenter cohort study included consecutive patients aged ≥ 80 years with medically refractory ET treated with unilateral MRgHIFU VIM thalamotomy between 2016 and 2023 at five academic neurosurgical centers. All patients met skull density ratio criteria and underwent standardized targeting. Clinical assessments were conducted at baseline, immediately posttreatment, and at the 3-month follow-up. The primary outcome was change in tremor severity assessed by using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS). Secondary outcomes included the Clinical Rating Scale for Tremor (CRST) score, Dynamic Gait Index score, patient-reported tremor relief, and adverse events. RESULTS One hundred twenty-nine patients (76 male, mean age 84 years) were included. At 3 months, the mean TETRAS score improved by 9.2 points (p < 0.001). CRST scores also showed significant improvement. The mean patient-reported tremor relief was 81%. Adverse events were mild and transient, with a 1.6% rate of nonsurgical adverse events. Subgroup analysis comparing patients 80–84 years versus those ≥ 85 years of age showed no significant differences in treatment response. Gait outcomes improved modestly but were not significant in the age ≥ 85 years group. CONCLUSIONS Unilateral MRgHIFU thalamotomy is a safe and effective noninvasive treatment for ET in patients ≥ 80 years of age. It results in significant improvements in tremor and disability, with a low complication rate. These findings support its consideration for older patients who are ineligible for invasive procedures and highlight the importance of age-specific metrics in neuromodulation outcomes research.

TPS2094 Background: Liquid biopsy in glioblastoma (GBM) is hindered by a lack of requisite circulating tumor (ct) and cell-free (cf) DNA levels in blood due to the blood-brain barrier (BBB). This limits the identification of blood-based tumor biomarkers along with the development and use of biomarker-driven systemic therapies. Low intensity focused ultrasound combined with intravenously administered microbubble oscillators (MB-FUS), leads to non-invasive BBB opening. This trial aims to evaluate the utility of LIFU for bolstering blood ctDNA and cfDNA for enhance liquid biopsy in patients with GBM. Methods: LIBERATE is an ongoing, prospective, multi-center, self-controlled, pivotal trial evaluating safety and technical efficacy of transcranial MR-guided MB-FUS for increasing blood ctDNA and cfDNA levels in adults, aged 18-80 years with GBM. Patients with suspected GBM planned for tumor biopsy or resection at 17 centers in US and Canada are being enrolled. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered IV microbubbles for enhanced sonication, after which MR-guided BBB opening using a 220 kHz device, with 1024-element phased array transducer, is performed with real-time acoustic feedback control for effective cavitation. Pre- and post-procedure, phlebotomy and MRI brain are done. Patients are offered optional 2 nd procedure during adjuvant chemotherapy phase if willing. Primary efficacy endpoint is correlation between biomarker patterns in tumor tissue collected during surgery/biopsy and blood collected following MB-FUS procedure. Confirmatory secondary efficacy endpoint is ratio between greatest yield of cfDNA in blood post-MB-FUS compared to cfDNA level in blood pre-MB-FUS. The primary study hypothesis is that agreement rate on biomarker pattern between resected/biopsied tumor tissue and blood is > 70%. The secondary hypothesis is that MB-FUS BBBO leads to a ≥2-fold rise in blood cfDNA. Assuming the true agreement rate expected is 89%, a sample of N = 50 patients will provide 90% power to meet the primary endpoint (Exact test, Binomial Proportion, one-sided Alpha = 0.025). Exploratory endpoints include (1) sensitivity of detection of known specific somatic mutations in ctDNA from blood samples collected before and after MB-FUS, (2) estimation of ctDNA levels in samples collected at 30-minutes, 1-hour, 2-hour, and 3-hour post-MB-FUS to determine time of greatest yield, (3) correlation of MRI parameters related to grading of BBB opening and ctDNA-based biomarkers from post-MB-FUS blood samples, (4) biomarker correlation between plasma cfDNA sampled during adjuvant chemotherapy phase and tumor tissue harvested at surgery. Patient enrollment commenced in 2022 and is ongoing (NCT05383872). Clinical trial information: NCT05383872 .

AbstractObjectiveFocused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open‐label, single‐center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment‐refractory epilepsy.MethodsTwo adult subjects with treatment‐refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy.ResultsThe patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure‐free at 12 months, and in the second patient, the frequency reduced from 90–100 seizures per month to 3–6 seizures per month.SignificanceThis is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment‐refractory focal onset epilepsy.