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Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial

Francisco A. Ponce Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; 

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Wael F. Asaad Departments of Neurosurgery and
Neuroscience, Brown University and Rhode Island Hospital, Providence, Rhode Island;

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Kelly D. Foote Department of Neurosurgery, University of Florida, Gainesville, Florida; 

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William S. Anderson Departments of Neurological Surgery,

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G. Rees Cosgrove Departments of Neurosurgery and

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Gordon H. Baltuch Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania;

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Kara Beasley Boulder Neurosurgical & Spine Associates, Boulder, Colorado;

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Donald E. Reymers Functional Neuromodulation Ltd., Minneapolis, Minnesota; and

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Esther S. Oh Medicine, and
Psychiatry, Johns Hopkins University, Baltimore, Maryland;

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Steven D. Targum Functional Neuromodulation Ltd., Minneapolis, Minnesota; and

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Gwenn S. Smith Psychiatry, Johns Hopkins University, Baltimore, Maryland;

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Constantine G. Lyketsos Psychiatry, Johns Hopkins University, Baltimore, Maryland;

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Andres M. Lozano Division of Neurosurgery, University of Toronto, Ontario, Canada

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Page Range:
75–84
Volume/Issue:
Volume 125: Issue 1
DOI link:
https://doi.org/10.3171/2015.6.JNS15716
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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 (clinicaltrials.gov)

ABBREVIATIONS

ADAS-cog-11 = Alzheimer's Disease Assessment Scale cognitive subscale ; AD = Alzheimer's disease ; AE = adverse event ; DBS = deep brain stimulation ; DBS-f = deep brain stimulation of the fornix ; IPG = internal pulse generator ; PD = Parkinson's disease ; SAE = serious adverse event .
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Contributor Notes

Drs. Ponce and Asaad contributed equally to this work.

INCLUDE WHEN CITING Published online December 18, 2015; DOI: 10.3171/2015.6.JNS15716.

Correspondence Francisco A. Ponce, c/o Neuroscience Publications, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013. email: neuropub@dignityhealth.org.
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