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Daniel Mendelsohn, Nir Lipsman, and Mark Bernstein

alternative to thermocoagulation, further transformed the field, culminating in several trials demonstrating successful treatment of refractory depression and OCD. 3 Despite early successes, it is unclear to what extent the public and the neurosurgical community support neuromodulation for treating psychiatric diseases. The ability of clinicians to alter pathological thinking and behavior has led ethicists to predict substantial public health and societal consequences for functional neurosurgery. 8–10 Due to the intimate relationship between the mind and personal

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Nir Lipsman, Michael Ellis, and Andres M. Lozano

. Conclusions Pediatric patients will certainly benefit from the continued development of DBS technology for the management of refractory neurological, and with time, psychiatric conditions. Currently, several studies support the use of DBS for movement disorders in highly selected patients, with ongoing research exploring additional, exciting indications. The future of pediatric functional neurosurgery will focus on the development of safer, smaller, and more flexible technology that will improve the child's quality of life, while minimizing exposure to surgical risk

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Ryan M. Jones, Shona Kamps, Yuexi Huang, Nadia Scantlebury, Nir Lipsman, Michael L. Schwartz, and Kullervo Hynynen

T ranscranial MRI-guided focused ultrasound (MRgFUS) is being clinically investigated for thermal ablation of tumors and functional neurosurgery applications. 32 To date, most of the clinical experience with MRgFUS in the brain has been obtained in treating essential tremor, one of the most prevalent movement disorders worldwide. 25 Subsequent to the previously developed radiofrequency ablation 40 and deep brain stimulation approaches, 43 several groups have shown that unilateral lesioning in the ventral intermediate (VIM) nucleus of the thalamus via MRgFUS

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Ying Meng, Christopher B. Pople, Suneil K. Kalia, Lorraine V. Kalia, Benjamin Davidson, Luca Bigioni, Daniel Zhengze Li, Suganth Suppiah, Karim Mithani, Nadia Scantlebury, Michael L. Schwartz, Clement Hamani, and Nir Lipsman

in these patients may be more resistant to dopaminergic replacement therapy and thus potentially amenable to surgical strategies targeting the ventrointermediate nucleus (VIM) of the thalamus with deep brain stimulation (DBS) or lesioning. 5 The development of transcranial MR-guided focused ultrasound (MRgFUS) has revitalized the practice of lesioning procedures in functional neurosurgery. Performed with the patient awake in an MRI scanner, MRgFUS allows for real-time clinical and radiological feedback. These features promise to render lesioning safer and more

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Benjamin Davidson, Karim Mithani, Yuexi Huang, Ryan M. Jones, Maged Goubran, Ying Meng, John Snell, Kullervo Hynynen, Clement Hamani, and Nir Lipsman

, López-Aguirre M , Letter: The role of skull thickness beyond the skull density ratio on MRgFUS thalamotomy feasibility: which patients should we exclude? Neurosurgery . 2020 ; 86 ( 5 ): E477 – E479 . 13 Gallay MN , Moser D , Jeanmonod D . Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments . J Neurosurg . 2019 ; 130 ( 4 ): 1234 – 1243 . 14 Kim SJ , Roh D , Jung HH , A study of novel bilateral thermal capsulotomy with focused

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Jetan H. Badhiwala, Brij Karmur, Lior M. Elkaim, Naif M. Alotaibi, Benjamin R. Morgan, Nir Lipsman, Philippe De Vloo, Suneil K. Kalia, Andres M. Lozano, and George M. Ibrahim

research efforts he oversees from the following: Medtronic, Boston Scientific, St. Jude Medical–Abbott, Helaers Foundation, and the European Society for Stereotactic and Functional Neurosurgery. Dr. Kalia reports receiving speaker and teaching fees from Medtronic. Dr. Lozano reports being a consultant for Medtronic, St. Jude, and Boston Scientific. Author Contributions Conception and design: Ibrahim. Acquisition of data: Ibrahim, Elkaim. Analysis and interpretation of data: Badhiwala, Karmur, Elkaim, Alotaibi, Morgan, De Vloo. Drafting the article: Ibrahim, Badhiwala

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Marie-Andrée Coulombe, Lior M. Elkaim, Naif M. Alotaibi, Daniel A. Gorman, Alexander G. Weil, Aria Fallah, Suneil K. Kalia, Nir Lipsman, Andres M. Lozano, and George M. Ibrahim

OBJECTIVE

Gilles de la Tourette syndrome (GTS) is a disorder characterized by motor and vocal tics. Although by definition the onset of GTS is before age 18 years, clinical trials of deep brain stimulation (DBS) have been conducted only in adults. Using individual participant data (IPD) meta-analysis methodology, the current study investigated the safety and efficacy of DBS as a treatment for GTS in children and youth.

METHODS

A systematic review with no date or language restrictions was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Three electronic databases were searched: PubMed, EMBASE, and Web of Science. From 843 articles screened, the IPD of 58 children and youth (ages 12–21 years) extracted from 21 articles were collected and analyzed. A mixed-effects univariable analysis followed by multivariable hierarchical regression was performed using change in the Yale Global Tic Severity Scale (YGTSS) score as the primary outcome and reported measures of comorbidities as secondary outcomes.

RESULTS

The authors’ results showed an average improvement of 57.5% ± 24.6% across studies on the YGTSS. They also found that comorbid depression and stimulation pulse width each correlated negatively with outcome (p < 0.05). In patients with less severe GTS, greater improvements were evident following thalamic stimulation. More than one-quarter (n = 16, 27.6%) of participants experienced side effects, the majority of which were minor.

CONCLUSIONS

DBS in the pediatric population may be an effective option with a moderate safety profile for treatment of GTS in carefully selected children and youth. Large, prospective studies with long-term follow-up are necessary to understand how DBS influences tic symptoms and may alter the natural course of GTS in children.

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Michael L. Schwartz, Robert Yeung, Yuexi Huang, Nir Lipsman, Vibhor Krishna, Jennifer D. Jain, Martin G. Chapman, Andres M. Lozano, and Kullervo Hynynen

OBJECTIVE

One patient for whom an MR-guided focused ultrasound (MRgFUS) pallidotomy was attempted was discovered to have multiple new skull lesions with the appearance of infarcts on the MRI scan 3 months after his attempted treatment. The authors conducted a retrospective review of the first 30 patients treated with MRgFUS to determine the incidence of skull lesions in patients undergoing these procedures and to consider possible causes.

METHODS

A retrospective review of the MRI scans of the first 30 patients, 1 attempted pallidotomy and 29 ventral intermediate nucleus thalamotomies, was conducted. The correlation of the mean skull density ratio (SDR) and the maximum energy applied in the production or attempted production of a brain lesion was examined.

RESULTS

Of 30 patients treated with MRgFUS for movement disorders, 7 were found to have new skull lesions that were not present prior to treatment and not visible on the posttreatment day 1 MRI scan. Discomfort was reported at the time of treatment by some patients with and without skull lesions. All patients with skull lesions were completely asymptomatic. There was no correlation between the mean SDR and the presence or absence of skull lesions, but the maximum energy applied with the Exablate system was significantly greater in patients with skull lesions than in those without.

CONCLUSIONS

It is known that local skull density, thickness, and SDR vary from location to location. Sufficient energy transfer resulting in local heating sufficient to produce a bone lesion may occur in regions of low SDR. A correlation of lesion location and local skull properties should be made in future studies.

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Manish Ranjan, Gavin J. B. Elias, Alexandre Boutet, Jidan Zhong, Powell Chu, Jurgen Germann, Gabriel A. Devenyi, M. Mallar Chakravarty, Alfonso Fasano, Kullervo Hynynen, Nir Lipsman, Clement Hamani, Walter Kucharczyk, Michael L. Schwartz, Andres M. Lozano, and Mojgan Hodaie

OBJECTIVE

Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients.

METHODS

T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced (“translated”) by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy.

RESULTS

T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the “final” indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant.

CONCLUSIONS

T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

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Marissa D’Souza, Kevin S. Chen, Jarrett Rosenberg, W. Jeffrey Elias, Howard M. Eisenberg, Ryder Gwinn, Takaomi Taira, Jin Woo Chang, Nir Lipsman, Vibhor Krishna, Keiji Igase, Kazumichi Yamada, Haruhiko Kishima, Rees Cosgrove, Jordi Rumià, Michael G. Kaplitt, Hidehiro Hirabayashi, Dipankar Nandi, Jaimie M. Henderson, Kim Butts Pauly, Mor Dayan, Casey H. Halpern, and Pejman Ghanouni

OBJECTIVE

Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.

METHODS

In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.

RESULTS

Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.

CONCLUSIONS

MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.