OBJECTIVE Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation. METHODS Patients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39). RESULTS Thirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46-87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2-30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6-24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14-45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13-24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850-23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°-60°C). CONCLUSIONS MRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse event...

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As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life.

Background. Thalamotomy is effective in alleviating tremor in Parkinson's disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46–74) with a mean disease duration of 5.4 ± 2.8 years (range, 2–10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3), dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved), and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety.

OBJECTIVEThe authors report their experience in treating patients suffering from medication-resistant essential tremor (ET) with MR-guided focused ultrasound (MRgFUS) thalamotomy over a 5-year period.METHODSForty-four ET patients treated with unilateral MRgFUS ventral intermediate nucleus (VIM) thalamotomy were assessed using the Clinical Rating Scale for Tremor (CRST) score and the Quality of Life in Essential Tremor Questionnaire (QUEST) over a 5-year span.RESULTSTremor was significantly improved immediately following MRgFUS in all patients and ceased completely in 24 patients. CRST scores in the treated hand at baseline (median 19; range 7–32, 44 patients) improved by a median of 16 at 1 month (44 patients; p < 0.0001), 17 at 6 months (31 patients; p < 0.0001), 15 at 1 year (24 patients; p < 0.0001), 18 at 2 years (15 patients; p < 0.0001), 19 at 3 years, (10 patients; p < 0.0001), 21 at 4 years (6 patients; p < 0.01), and 23 at 5 years (2 patients, significance not tested). Return of tremor that impacted activities of daily living was reported in 5 patients (11%). QUEST scores showed significant improvement, with median change of 35 points (p < 0.0001; 44 patients) at 1 month, 33 (p < 0.0001; 31 patients) at 6 months, 27 (p < 0.0001; 24 patients) at 1 year, 26 (p < 0.001; 15 patients) at 2 years, 25 (p < 0.001; 10 patients) at 3 years, 33 (p < 0.001; 6 patients) at 4 years, and 28 (significance not tested, 2 patients) at 5 years. Adverse events after the procedure were reversible in all but 5 patients (11%).CONCLUSIONSMRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor. Additional studies with a larger group of patients is needed to substantiate these favorable results.