Neurosurgeons at Barrow Neurological Institute in Phoenix are involved with testing the viability of deep brain stimulation (DBS) to treat Alzheimer’s disease, a disorder that currently has few treatment options. Results from the Phase 2 study, reported in the Journal of Neurosurgery on Dec. 18, 2015, demonstrated the safety of DBS in Alzheimer’s patients.
A neurosurgical procedure in which an implanted neurostimulator delivers electrical signals to specific areas of the brain to help regulate abnormal signals, DBS is currently only approved in the U.S. for the treatment of Parkinson’s disease and essential tremor. However, its use is being researched for a number of conditions, including epilepsy, depression and bipolar disorder. Francisco Ponce, MD, Director of the Barrow Center for Neuromodulation, believes there are potential applications for Alzheimer’s disease – the most common form of dementia – as well. Whereas in Parkinson’s disease and essential tremor, the target for the electrodes are nodes within the motor circuits, the Alzheimer’s study targeted the fornix, which is part of the memory pathway.
“There are more than five million Americans living with Alzheimer’s, and yet there are few promising pharmacologic treatment options for this progressive disease,” says Dr. Ponce. “Previous pilot studies researching the use of DBS in Alzheimer’s have indicated the potential to slow cognitive decline in some patients, and have even shown metabolic changes in the brain that may slow the progression of the disease.” Barrow Neurological Institute is part of Dignity Health St. Joseph’s Hospital in Phoenix.
The ADvance Trial, using a device from Functional Neuromodulation, Inc., is aimed at evaluating the safety, efficacy and tolerability of DBS in this patient population. Initial research took place between 2012 and 2014 at six hospitals throughout the U.S., including Banner Alzheimer’s Institute in Phoenix and Banner Sun Health Research Institute in Sun City, as well as one institution in Canada. During the trial, 42 patients with mild Alzheimer’s disease underwent the surgical procedure and were closely monitored for adverse effects.
Overall, there were no programming-related adverse effects, unanticipated adverse device effects, reported neurological deficits or instances of mortality in the study population. Adverse effects such as headache and infection occurred in 11.9% (5 of 42) of the patients in this study, consistent with rates reported in other DBS trials.
“The first phase of this study was designed to evaluate the 90-day postoperative safety of this particular surgical method. While the study was relatively small, we believe the data suggest that DBS surgery targeting the fornix can be performed safely in this patient population. The hope is that our positive surgical experience will help pave the way for future research into DBS and Alzheimer’s,” says Dr. Ponce.
Dr. Ponce adds that the next step is evaluating the efficacy and longer-term safety of the treatment, which will not be known until the last patient completes the two-year evaluation later this year.
Source: Lynne Reaves – St. Joseph’s Hospital and Medical Center
Image Source: The image is credited to Barrow.
Original Research: Abstract for “Bilateral deep brain stimulation of the fornix for Alzheimer’s disease: surgical safety in the ADvance trial” by Francisco A. Ponce, MD, Wael F. Asaad, MD, PhD, Kelly D. Foote, MD, William S. Anderson, MD, PhD, G. Rees Cosgrove, MD, Gordon H. Baltuch, MD, PhD, Kara Beasley, DO, MBe, Donald E. Reymers, Esther S. Oh, MD, Steven D. Targum, MD, Gwenn S. Smith, PhD, Constantine G. Lyketsos, MD, MHS, and Andres M. Lozano, MD, PhD for The ADvance Research Group in Journal of Neurosurgery. Published online December 18 2015 doi:10.3171/2015.6.JNS15716
Abstract
Bilateral deep brain stimulation of the fornix for Alzheimer’s disease: surgical safety in the ADvance trial
OBJECT
This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer’s disease (AD).
METHODS
The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure.
RESULTS
Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0–79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0–7.9 mm), y = 9.6 ± 0.9 mm (range 8.0–11.6 mm), z = −7.5 ± 1.2 mm (range −5.4 to −10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2–4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported.
CONCLUSIONS
Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD.
Clinical trial registration no.: NCT01608061
“Bilateral deep brain stimulation of the fornix for Alzheimer’s disease: surgical safety in the ADvance trial” by Francisco A. Ponce, MD, Wael F. Asaad, MD, PhD, Kelly D. Foote, MD, William S. Anderson, MD, PhD, G. Rees Cosgrove, MD, Gordon H. Baltuch, MD, PhD, Kara Beasley, DO, MBe, Donald E. Reymers, Esther S. Oh, MD, Steven D. Targum, MD, Gwenn S. Smith, PhD, Constantine G. Lyketsos, MD, MHS, and Andres M. Lozano, MD, PhD for The ADvance Research Group in Journal of Neurosurgery. Published online December 18 2015 doi:10.3171/2015.6.JNS15716
