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 (clinicaltrials.gov)

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Deep brain stimulation of the fornix as a therapeutic approach for Alzheimer’s disease: Systematic Review

10.5327/1516-3180.168 ◽

2021 ◽

Author(s):

Paloma Abrantes de Oliveira ◽

Diogo Abrantes de Oliveira ◽

Isabelle Magalhães Guedes Freitas

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Randomized Clinical Trials ◽

Anterior Commissure ◽

Brain Network ◽

Double Blind ◽

Alzheimer Dementia ◽

Deep Brain

INTRODUCTION: Alzheimer’s disease (AD) is a disorder characterized by cognitive impairment. The brain network in DA can be interrupted by deficiencies in glucose metabolismo. Deep brain stimulation (DBS) is used in Parkinson’s disease (PM), once it modulates motor circuits. Considering this potential, the benefits of this approach in DA must be evaluated1,2. OBJECTIVE: To investigate the potential benefit of stimulating the cerebral fornix (CF) through DBS for patients with AD. METHODS: Controlled and randomized clinical trials (ECCR), in English, performed on humans, in the last 5 years, indexed on PubMed, were selected from the keywords “Deep brain Stimulation” and “Alzheimer Dementia”. This review was registered on PROSPERO by protocol 254506 and the PRISMA recommendation was used to improve its organization. RESULTS: Deeb W et al. (2019) conducted an ECCR on 42 patients with AD receiving DBS in CF, anterior commissure, corpus and sub-corpus callosum, demonstrating that in 48% of them, old experiences were reported. Furthermore, the memories became better as the stimulation increased. Lozano AM et al. (2016), in turn, developed an ECCR on 6 patients receiving DBS in CF, showing increases in glucose metabolism in some cerebral areas after 12 months, contrasting to the expected reduction in AD, especially in > 65 years. It’s noteworthy that the multicenter and double-blind ECCR by Ponce FA (2016) showed the safety of DBS in CF as therapy for AD, similar to that verified in the MP. CONCLUSION: The analyzed evidences suggest a potential cognitive benefit of DBS in the therapeutic management of AD.

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