Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

ABBREVIATIONS ACC = anterior cingulate cortex; AD = Alzheimer's disease; ADAS-Cog = Alzheimer's Disease Assessment Scale, Cognitive Subscale; ALIC = anterior limb of the internal capsule; ANT = anterior nucleus of the thalamus; area LC = locus of the caudate neurons; BNST = bed nucleus of the stria terminalis; CMPfc = centromedian-parafascicular complex; DBS = deep brain stimulation; ET = essential tremor; GPi = globus pallidus pars interna; ITP = inferior thalamic peduncle; NAc = nucleus accumbens; nbM = nucleus basalis of Meynert; OCD = obsessive-compulsive disorder; PAG/PVG = periaqueductal gray/periventricular gray; PD = Parkinson's disease; PTSD = posttraumatic stress disorder; STN = subthalamic nucleus; VC/VS = ventral capsule/ventral striatum; Vim = ventral intermediate thalamic nucleus; VPL/VPM = ventral posterior lateral nucleus/ventral posterior medial nucleus.Deep brain stimulation (DBS) has evolved considerably over the past 4 decades. Although it has primarily been used to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia, recently it has been approved to treat obsessive-compulsive disorder and epilepsy. Novel potential indications in both neurological and psychiatric disorders are undergoing active study. There have been significant advances in DBS technology, including preoperative and intraoperative imaging, surgical approaches and techniques, and device improvements. In addition to providing significant clinical benefits and improving quality of life, DBS has also increased the understanding of human electrophysiology and network interactions. Despite the value of DBS, future developments should be aimed at developing less invasive techniques and attaining not just symptom improvement but curative disease modification.https://thejns.org/doi/abs/10.3171/2019.4.JNS181761

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment‐resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high‐resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above‐mean and below‐mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient‐specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426–443

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