- The biennial meeting of ASSFN was held June 4–7 in Atlanta.
- Many of the presentations were made by neurosurgeons using focused ultrasound in their clinical practices.
- This report was recently updated with additional information.
The biennial meeting of the American Society for Stereotactic and Functional Neurosurgery (ASSFN) was held June 4–7 in Atlanta. The conference, which is primarily attended by neurosurgeons, was designed with daily plenary sessions followed by topic-based parallel sessions on adult and pediatric neuromodulation, functional neuro-oncology, movement disorders, epilepsy, and pain management.
Several clinicians who use focused ultrasound in their practices presented at the meeting, including:
- Michael Kaplitt, MD, from Weill Cornell Medicine, New York, NY
- Vibhor Krishna, MD, from the University of North Carolina, Chapel Hill, NC
- Jose Obeso, MD, PhD, from HM Cinac, Madrid, Spain
- Ali Rezai, MD, from the West Virginia University School of Medicine in Morgantown, WV
“At ASSFN this year, discussion of focused ultrasound was no longer reserved for specific sessions,” said Dr. Krishna. “It was included in the plenary sessions and many attendees were curious about focused ultrasound and how to incorporate it into their clinical practices.”
Dr. Krishna also noted that the meeting was in person, so there was much social discussion about focused ultrasound. The neurosurgeons were curious about using focused ultrasound to treat epilepsy, especially temporal lobe epilepsy. They also asked whether one focused ultrasound device could be used for both blood-brain barrier (BBB) opening and ablation, indicating that they would be particularly interested in adopting the technology if both were offered in one treatment platform (not right now). Several attendees asked about other companies in the field – about what they are doing and whether they were developing platforms to treat epilepsy or provide neuromodulation.
The sessions that included focused ultrasound, and a few notes on each session, are listed below.
Dr. Kaplitt gave a well-attended talk on using focused ultrasound for BBB opening, covering the fundamentals and the breadth of the therapeutics that can be delivered (e.g., small molecules, nanoparticles, viruses). He shared some unpublished preclinical and clinical data from his laboratory work delivering gene therapy for Parkinson’s disease.
Prof. Obeso’s group presented two papers on using unilateral, MRI-guided, high-intensity focused ultrasound subthalamotomy (FUS-STN) for the treatment of Parkinson’s Disease (PD).
- One study reported the long-term safety and efficacy of FUS-STN to treat the motor signs of PD. Thirty-two patients were evaluated 2 to 3 years after treatment. The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III score for the treated side of the body while off-medication improved by 54.3% from baseline to 2 to 3 years (19.0 ± 3.2 to 8.6 ± 3.3, p<0.001), and no disabling or delayed adverse events were encountered at 2 to 3 years. In addition, seven patients evaluated at 5 years also kept their clinical benefit. These data show that the motor improvement conveyed by FUS-STN in PD patients is sustained without medical management complications. Admittedly, the open-label nature of the study and limited number of patients obliges us to be cautious regarding definitive conclusions. However, the experience is clearly positive and in keeping with the predominant role of the STN as a target for PD.
- The second study enrolled 12 patients (mean age of 52.9±7.1 years) with PD who were treated with unilateral FUS-STN within 5 years of diagnosis (the “Early Focus I” project). Parkinsonian motor signs were extremely asymmetrical in all cases. The study aimed to ascertain the safety of FUS-STN for this specific patient population. No major neurological deficits were encountered immediately after treatment. Within the first 2 weeks after treatment, two patients presented mild dyskinesia on the treated side while off-medication; another 4 patients presented mild dyskinesia while on medication. In all cases, the dyskinesias resolved after levodopa reduction. Indeed, at 6 months, no patient showed dyskinesias, but two patients had developed a toe dystonic posture. No other severe adverse event was present. One patient had facial asymmetry and mild slurred speech. In terms of motor improvement at 6 months, the off-medication MDS-UPDRS III score for the most affected side had improved by 71% (from 14.8 ± 2.9 to 4.4 ± 2.7 [p<0.01]), and the total motor MDS-UPDRS was also reduced by 50%. This pilot study indicated that unilateral FUS-STN in early PD patients appears to be safe and effective for improving motor manifestations. A larger confirmatory trial is currently being organized.
Altogether, Prof. Obeso and the group at HM-CINAC’s current experience indicates that FUS-STN provides the best therapeutic profile for patients with asymmetrical PD. This ongoing experience demonstrates that the historical fear of hemiballism associated with STN ablation is unwarranted.
Dr. Krishna discussed leveraging neuroimaging to define the therapeutic target and measure the tissue response after focused ultrasound brain treatments. His data show that diffusion MRI is a reliable way to measure treatment response, and he recently received a grant from the National Institutes of Health to optimize ultrasound treatment parameters by measuring tissue response after ablation. The audience of more than 100 attendees asked questions that demonstrated excitement in the field. The questions were about the precision of ultrasound ablation, how the target shape and location affect the surgeon’s ability to ablate, and whether MR integration could be used to further optimize the technique. Dr. Krishna noted that focused ultrasound has truly entered the active thinking process of neurosurgeons.
Targeted Drug Delivery
During a plenary session on targeted drug delivery, Dr. Krishna described how focused ultrasound is being leveraged to deliver therapeutics to the brain. He also shared the fundamentals of BBB opening with focused ultrasound, such as how treatment parameters (frequency, duty cycle, amplitude, bubble size) influence the degree of opening. He covered the current state of the field for human translation of BBB opening research. Attendee questions included: “When you think about the wide range of therapeutics (small to large molecules) for the treatment of neurological disorders, where do you see ultrasound fit in the best?” “Does ultrasound influence the potency of the therapeutics?” “Do the therapeutics stay in the brain or leach out…is it a two-way street?” It was a well-attended and interesting session.
This session included a debate between Dr. Krishna and Joshua M. Rosenow, MD, from Northwestern University on the use of tractography for stereotactic targeting versus standard of care. Dr. Krishna advocated for leveraging tractography to identify ablation targets in the brain, such as the ventral intermediate (VIM) nucleus, reduce the risk of treatment-related side effects, and improve outcomes. Audience members were interested in improving currently available techniques, and the thought leaders seemed to be on board with improving tractography technology.
BBB Opening for Alzheimer’s Disease
Dr. Rezai presented his initial safety experience in a clinical trial using focused ultrasound to open the BBB in nine patients with Alzheimer’s disease. The session was well attended, and he received questions about repeated and consistent BBB opening and imaging findings. Dr. Rezai reported that some of the participants in the clinical trial have had measurable amyloid reduction.
Dr. Albert Kim presented “Focused Ultrasound, Liquid Biopsy, and Chemotherapy Potentiation.”
We thank Dr. Krishna and Prof. Obeso for their assistance with this meeting report.