Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial

Autor: James Gratwicke, Ludvic Zrinzo, Joshua Kahan, Amy Peters, Una Brechany, Ann McNichol, Mazda Beigi, Harith Akram, Jonathan Hyam, Ashwini Oswal, Brian Day, Laura Mancini, John Thornton, Tarek Yousry, Sebastian J. Crutch, John-Paul Taylor, Ian McKeith, Lynn Rochester, Jonathan M. Schott, Patricia Limousin, David Burn, Martin N. Rossor, Marwan Hariz, Marjan Jahanshahi, Thomas Foltynie
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Brain Stimulation, Vol 13, Iss 4, Pp 1031-1039 (2020)
Druh dokumentu: article
ISSN: 1935-861X
DOI: 10.1016/j.brs.2020.04.010
Popis: Background: Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias. Objective: To assess the safety and tolerability of low frequency (20 Hz) NBM DBS in DLB patients and explore its potential effects on both clinical symptoms and functional connectivity in underlying cognitive networks. Methods: We conducted an exploratory randomised, double-blind, crossover trial of NBM DBS in six DLB patients recruited from two UK neuroscience centres. Patients were aged between 50 and 80 years, had mild-moderate dementia symptoms and were living with a carer-informant. Patients underwent image guided stereotactic implantation of bilateral DBS electrodes with the deepest contacts positioned in the Ch4i subsector of NBM. Patients were subsequently assigned to receive either active or sham stimulation for six weeks, followed by a two week washout period, then the opposite condition for six weeks. Safety and tolerability of both the surgery and stimulation were systematically evaluated throughout. Exploratory outcomes included the difference in scores on standardised measurements of cognitive, psychiatric and motor symptoms between the active and sham stimulation conditions, as well as differences in functional connectivity in discrete cognitive networks on resting state fMRI. Results: Surgery and stimulation were well tolerated by all six patients (five male, mean age 71.33 years). One serious adverse event occurred: one patient developed antibiotic-associated colitis, prolonging his hospital stay by two weeks. No consistent improvements were observed in exploratory clinical outcome measures, but the severity of neuropsychiatric symptoms reduced with NBM DBS in 3/5 patients. Active stimulation was associated with functional connectivity changes in both the default mode network and the frontoparietal network. Conclusion: Low frequency NBM DBS can be safely conducted in DLB patients. This should encourage further exploration of the possible effects of stimulation on neuropsychiatric symptoms and corresponding changes in functional connectivity in cognitive networks. Trial registration number: NCT02263937.
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