Improving tremor response to focused ultrasound thalamotomy.

MRI-guided high-intensity focused ultrasound thalamotomy is an incisionless therapy for essential tremor. To reduce adverse effects, the field has migrated to treating at 2 mm above the anterior commissure-posterior commissure plane. We perform MRI-guided high-intensity focused ultrasound with an advanced imaging targeting technique, four-tract tractography. Four-tract tractography uses diffusion tensor imaging to identify the critical white matter targets for tremor control, the decussating and non-decussating dentatorubrothalamic tracts, while the corticospinal tract and medial lemniscus are identified to be avoided. In some patients, four-tract tractography identified a risk of damaging the medial lemniscus or corticospinal tract if treated at 2 mm superior to the anterior commissure-posterior commissure plane. In these patients, we chose to target 1.2-1.5 mm superior to the anterior commissure-posterior commissure plane. In these patients, post-operative imaging revealed that the focused ultrasound lesion extended into the posterior subthalamic area. This study sought to determine if patients with focused ultrasound lesions that extend into the posterior subthalamic area have a differnce in tremor improvement than those without. Twenty essential tremor patients underwent MRI-guided high-intensity focused ultrasound and were retrospectively classified into two groups. Group 1 included patients with an extension of the thalamic-focused ultrasound lesion into the posterior subthalamic area. Group 2 included patients without extension of the thalamic-focused ultrasound lesion into the posterior subthalamic area. For each patient, the percent change in postural tremor, kinetic tremor and Archimedes spiral scores were calculated between baseline and a 3-month follow-up. Two-tailed Wilcoxon rank-sum tests were used to compare the improvement in tremor scores, the total number of sonications, thermal dose to achieve initial tremor response, and skull density ratio between groups. Group 1 had significantly greater postural, kinetic, and Archimedes spiral score percent improvement than Group 2 (P values: 5.41 × 10-5, 4.87 × 10-4, and 5.41 × 10-5, respectively). Group 1 also required significantly fewer total sonications to control the tremor and a significantly lower thermal dose to achieve tremor response (P values: 6.60 × 10-4 and 1.08 × 10-5, respectively). No significant group differences in skull density ratio were observed (P = 1.0). We do not advocate directly targeting the posterior subthalamic area with MRI-guided high-intensity focused ultrasound because the shape of the focused ultrasound lesion can result in a high risk of adverse effects. However, when focused ultrasound lesions naturally extend from the thalamus into the posterior subthalamic area, they provide greater tremor control than those that only involve the thalamus.

Focused ultrasound using a novel targeting method four-tract tractography for magnetic resonance-guided high-intensity focused ultrasound targeting.

Magnetic resonance-guided high-intensity focused ultrasound thalamotomy is a Food and Drug Administration-approved treatment for essential tremor. The target, the ventral intermediate nucleus of the thalamus, is not visualized on standard, anatomic MRI sequences. Several recent reports have used diffusion tensor imaging to target the dentato-rubro-thalamic-tract. There is considerable variability in fibre tracking algorithms and what fibres are tracked. Targeting discrete white matter tracts with magnetic resonance-guided high-intensity focused ultrasound is an emerging precision medicine technique that has the promise to improve patient outcomes and reduce treatment times. We provide a technical overview and clinical benefits of our novel, easily implemented advanced tractography method: four-tract tractography. Our method is novel because it targets both the decussating and non-decussating dentato-rubro-thalamic-tracts while avoiding the medial lemniscus and corticospinal tracts. Our method utilizes Food and Drug Administration-approved software and is easily implementable into existing workflows. Initial experience using this approach suggests that it improves patient outcomes by reducing the incidence of adverse effects.

Tubulinopathies.

Mutations causing dysfunction of the tubulins and microtubule-associated proteins, otherwise known as tubulinopathies, are a group of recently described entities, that lead to complex brain malformations. An understanding of the fundamental principles of operation of the cytoskeleton and compounds in particular microtubules, actin, and microtubule-associated proteins, can assist in the interpretation of the imaging findings of tubulinopathies. Somewhat consistent morphological imaging patterns have been described in tubulinopathies such as dysmorphic basal ganglia-the hallmark (found in 75% of cases), callosal dysgenesis, cerebellar hypoplasia/dysplasia, and cortical malformations, most notably lissencephaly. Recognizing the common imaging phenotypes present in tubulinopathies can prove invaluable in directing the genetic workup for a patient with brain malformations.