Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.

Novel neurointerventions present innovative therapeutic approaches to a range of treatment-refractory disorders. We sought to characterize factors that inform and define translational readiness for first-in-human (FIH) neuromodulatory trials.

We used a two-part methodology involving a scoping review of the biomedical literature on the readiness of FIH trials for both neurological and non-neurological applications, and semi-structured interviews with stakeholders about decision-making for neuromodulation using magnetic resonance-guided focused ultrasound as a case example.

One hundred and thirty factors relevant to FIH readiness were identified in the scoping review. Trial design, adequacy of preclinical evidence, and risk were ubiquitous across biotechnologies. Target organ, target function, and inadequacy of animal models were dominant in the neurointervention literature. Interview results on the relative importance of these factors reveal divergent values, priorities, and understandings both between patients and clinicians and between patients affected by different conditions.

Readiness of neurotechnology for FIH trials is defined by a multitude of interacting factors that pertain to clinical and nonclinical priorities, perceptions, and values.