title: Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.
abstract: 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 ).
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona;
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Ponce
authors.affiliation: Departments of 2 Neurosurgery and.|Neuroscience, Brown University and Rhode Island Hospital, Providence, Rhode Island;
authors.forename: Wael F
authors.initials: WF
authors.lastname: Asaad
authors.affiliation: Department of Neurosurgery, University of Florida, Gainesville, Florida;
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.affiliation: Departments of 5 Neurological Surgery.
authors.forename: William S
authors.initials: WS
authors.lastname: Anderson
authors.affiliation: Departments of 2 Neurosurgery and.
authors.forename: G
authors.initials: G
authors.lastname: Rees Cosgrove
authors.affiliation: Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Baltuch
authors.affiliation: Boulder Neurosurgical & Spine Associates, Boulder, Colorado;
authors.forename: Kara
authors.initials: K
authors.lastname: Beasley
authors.affiliation: Functional Neuromodulation Ltd., Minneapolis, Minnesota; and.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Reymers
authors.affiliation: Medicine, and.|Psychiatry, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Esther S
authors.initials: ES
authors.lastname: Oh
authors.affiliation: Functional Neuromodulation Ltd., Minneapolis, Minnesota; and.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Targum
authors.affiliation: Psychiatry, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Gwenn S
authors.initials: GS
authors.lastname: Smith
authors.affiliation: Psychiatry, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: Division of Neurosurgery, University of Toronto, Ontario, Canada.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D020712:Fornix, Brain; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D013238:Stereotaxic Techniques; D016896:Treatment Outcome
keywords: AD = Alzheimer's disease; ADAS-cog-11 = Alzheimer's Disease Assessment Scale cognitive subscale; AE = adverse event; Alzheimer's disease; DBS = deep brain stimulation; DBS-f = deep brain stimulation of the fornix; IPG = internal pulse generator; PD = Parkinson's disease; SAE = serious adverse event; deep brain stimulation; dementia; fornix; functional neurosurgery; memory