Authors :
Presenting Author: Marytery Fajardo, MD – Nicklaus Children's Hospital
Matt Lallas, MD – Nicklaus Children’s Hospital
Puck Reeders, PhD – Nicklaus Children's Hospital
Trevor Resnick, MD – Nicklaus Children's Hospital Comprehensive Epilepsy Center
Michael Duchowny, MD – Nicklaus Children's Hospital
Prasanna Jayakar, MD, PhD – Nicklaus Children's Hospital
Robert Keating, MD – Nicklaus Children's Hospital
Nolan Altman, MD – Nicklaus Children's Hospital
Magno Guillen, PhD – Nicklaus Children's Hospital
John Ragheb, MD – Nicklaus Children's Hospital
Rationale:
Magnetic resonance guided focused ultrasound ablation (FUS) is approved for thalamotomy and pallidotomy in adults with essential tremor and Parkinson’s disease. The use of FUS ablation in children is of intense interest and study but is unproven as safe or effective. We present the safety, technical challenges and clinical response to FUS ablation in a cohort of 10 patients. The results from the first 5 patients treated were previously published.
Methods:
Ten pediatric patients with benign central brain lesions were treated between 2018 and 2024 by MRI guided focused ultrasound ablation in a prospective, single-arm trial ( NCT03028246 ). All patients were treated using the Insightec ExAblate 4000 protocol that included nine patients at Nicklaus Children’s Hospital, Miami, FL and one at Children’s National Medical Center, Washington, D.C. All FUS procedures were performed under general anesthesia. Eight patients had hypothalamic hamartomas (HH), one had a subependymal giant cell astrocytoma, and one had a low grade astrocytoma of the right parietal white matter. Tumor volumes ranged from 0.14 cc to 4.58 cc.
Results:
All patients tolerated the procedure well and were discharged home on the first or second post operative day. Three patients had scalp swelling from the FUS procedure beyond what would be expected from stereotactic pin placement alone, and which lasted a few days to over two weeks. Nine patients completed their six-month follow-ups; the 10th was treated in late July, 2024. The final HH patient developed diabetes insipidus 36 hours after treatment that required re-admission to the hospital and medical management. She remains on dDAVP 6 months post ablation. Otherwise, no patient experienced any endocrine, visual, or neurologic complications. All HH patients had an immediate, and to date sustained clinical response. Five HH patients had complete resolution of their gelastic seizures and one a greater then 90% reduction. The two patients with hypothalamic hyperphagia had an immediate and sustained response to FUS. All the HH patients had family or self-reported improvement in behavior, school performance and concentration. The SEGA patient could not be treated due to cavitation from microscopic and macroscopic calcification and was restarted on medical therapy. The low-grade astrocytoma patient had a stable residual, which the family elected to have removed 2 years post ablation.
FUS treatment volumes 3 months post ablation ranged from 0.08 cc to 0.49 cc. Procedure lengths decreased from approximately 12 hours for the first subject, to under 4 hours for the final patient. Peak target temperatures ranged from 51· to 61· C in all treatments except the SEGA for which therapeutic temperatures could not be reached.
Conclusions:
FUS ablation is feasible in children to at least age 10 years of age and is generally well tolerated. HH may be an optimal target for FUS ablation and warrants further study in a larger pivotal trial. Funding:
The Focused Ultrasound Foundation (grant no. FUS 530 to T.S.T.) funded this trial (clinicaltrials.gov identifier no. NCT03028246). The device manufacturer, InSightec Ltd., is our FDA regulatory sponsor