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Ailish Coblentz, Gavin J. B. Elias, Alexandre Boutet, Jurgen Germann, Musleh Algarni, Lais M. Oliveira, Clemens Neudorfer, Elysa Widjaja, George M. Ibrahim, Suneil K. Kalia, Mehr Jain, Andres M. Lozano, and Alfonso Fasano

OBJECTIVE

The objective of this study was to report the authors’ experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques.

METHODS

A retrospective analysis was conducted in 11 pediatric patients (6 girls and 5 boys, mean age 12 ± 4 years) with medically refractory dystonia who underwent GPi-DBS implantation between June 2009 and September 2017. Using pre- and postoperative MRI, volumes of tissue activated were modeled and weighted by clinical outcome to identify brain regions associated with clinical outcome. Functional and structural networks associated with clinical benefits were also determined using large-scale normative data sets.

RESULTS

A total of 21 implanted leads were analyzed in 11 patients. The average follow-up duration was 19 ± 20 months (median 5 months). Using a 7-point clinical rating scale, 10 patients showed response to treatment, as defined by scores < 3. The mean improvement in the Burke-Fahn-Marsden Dystonia Rating Scale motor score was 40% ± 23%. The probabilistic map of efficacy showed that the voxel cluster most associated with clinical improvement was located at the posterior aspect of the GPi, comparatively posterior and superior to the coordinates of the classic GPi target. Strong functional and structural connectivity was evident between the probabilistic map and areas such as the precentral and postcentral gyri, parietooccipital cortex, and brainstem.

CONCLUSIONS

This study reported on a series of pediatric patients with dystonia in whom GPi-DBS resulted in variable clinical benefit and described a clinically favorable stimulation site for this cohort, as well as its structural and functional connectivity. This information could be valuable for improving surgical planning, simplifying programming, and further informing disease pathophysiology.

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Ailish Coblentz, Gavin J. B. Elias, Alexandre Boutet, Jurgen Germann, Musleh Algarni, Lais M. Oliveira, Clemens Neudorfer, Elysa Widjaja, George M. Ibrahim, Suneil K. Kalia, Mehr Jain, Andres M. Lozano, and Alfonso Fasano

OBJECTIVE

The objective of this study was to report the authors’ experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques.

METHODS

A retrospective analysis was conducted in 11 pediatric patients (6 girls and 5 boys, mean age 12 ± 4 years) with medically refractory dystonia who underwent GPi-DBS implantation between June 2009 and September 2017. Using pre- and postoperative MRI, volumes of tissue activated were modeled and weighted by clinical outcome to identify brain regions associated with clinical outcome. Functional and structural networks associated with clinical benefits were also determined using large-scale normative data sets.

RESULTS

A total of 21 implanted leads were analyzed in 11 patients. The average follow-up duration was 19 ± 20 months (median 5 months). Using a 7-point clinical rating scale, 10 patients showed response to treatment, as defined by scores < 3. The mean improvement in the Burke-Fahn-Marsden Dystonia Rating Scale motor score was 40% ± 23%. The probabilistic map of efficacy showed that the voxel cluster most associated with clinical improvement was located at the posterior aspect of the GPi, comparatively posterior and superior to the coordinates of the classic GPi target. Strong functional and structural connectivity was evident between the probabilistic map and areas such as the precentral and postcentral gyri, parietooccipital cortex, and brainstem.

CONCLUSIONS

This study reported on a series of pediatric patients with dystonia in whom GPi-DBS resulted in variable clinical benefit and described a clinically favorable stimulation site for this cohort, as well as its structural and functional connectivity. This information could be valuable for improving surgical planning, simplifying programming, and further informing disease pathophysiology.

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Alexandre Boutet, Gavin J. B. Elias, Robert Gramer, Clemens Neudorfer, Jürgen Germann, Asma Naheed, Nicole Bennett, Bryan Li, Dave Gwun, Clement T. Chow, Ricardo Maciel, Alejandro Valencia, Alfonso Fasano, Renato P. Munhoz, Warren Foltz, David Mikulis, Ileana Hancu, Suneil K. Kalia, Mojgan Hodaie, Walter Kucharczyk, and Andres M. Lozano

OBJECTIVE

Many centers are hesitant to perform clinically indicated MRI in patients who have undergone deep brain stimulation (DBS). Highly restrictive guidelines prohibit the use of most routine clinical MRI protocols in these patients. The authors’ goals were to assess the safety of spine MRI in patients with implanted DBS devices, first through phantom model testing and subsequently through validation in a DBS patient cohort.

METHODS

A phantom was used to assess DBS device heating during 1.5-T spine MRI. To establish a safe spine protocol, routinely used clinical sequences deemed unsafe (a rise in temperature > 2°C) were modified to decrease the rise in temperature. This safe phantom-based protocol was then used to prospectively run 67 spine MRI sequences in 9 DBS participants requiring clinical imaging. The primary outcome was acute adverse effects; secondary outcomes included long-term adverse clinical effects, acute findings on brain MRI, and device impedance stability.

RESULTS

The increases in temperature were highest when scanning the cervical spine and lowest when scanning the lumbar spine. A temperature rise < 2°C was achieved when 3D sequences were modified to 2D and when the number of slices was decreased by the minimum amount compared to routine spine MRI protocols (but there were still more slices than allowed by vendor guidelines). Following spine MRI, no acute or long-term adverse effects or acute findings on brain MR images were detected. Device impedances remained stable.

CONCLUSIONS

Patients with DBS devices may safely undergo spine MRI with a fewer number of slices compared to those used in routine clinical protocols. Safety data acquisition may allow protocols outside vendor guidelines with a maximized number of slices, reducing the need for radiologist supervision.

Clinical trial registration no.: NCT03753945 (ClinicalTrials.gov).

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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.