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.
Background The role of deep brain stimulation (DBS) in the management of motor symptoms in patients with Parkinson's disease is well defined. However, it is becoming increasingly clear that DBS can either improve or worsen a number of non‐motor phenomena. Objectives We examined the published literature to better understand the effects on autonomic symptoms following DBS of the subthalamic nucleus and the globus pallidus interna. Methods We conducted a PubMed search of studies regarding the effects of DBS on the autonomic system published from January 2001. We searched for the following terms and their combinations: Parkinson's disease, deep brain stimulation, subthalamic nucleus, globus pallidus interna, autonomic dysfunction. Results Most studies reported in the literature focus on DBS targeting the subthalamic nucleus, with particular emphasis on favorable outcomes regarding gastrointestinal function and bladder control. However, the emergence or worsening of autonomic symptoms in subgroups of patients has also been documented. More controversial is the effect of stimulation on the cardiovascular, pulmonary, and thermo‐regulatory systems as well as sexual functioning. Data regarding the influence of DBS on the autonomic system when the target is the globus pallidus interna is less forthcoming, with target selection varying according to centre and clinical indication. Conclusions DBS appears to affect the autonomic nervous system, with varying degrees of influence, which may or may not be clinically beneficial for the patient. A better understanding of these effects could help personalize stimulation for individual patients with autonomic disorders and/or avoid autonomic symptoms in susceptible patients.
Background Deep brain stimulation (DBS) is an established treatment for dystonia and tremor. However, there is no consensus about the best surgical targeting strategy in patients with concomitant tremor and dystonia. Both the thalamic ventral intermediate nucleus (VIM) and the globus pallidus pars interna (GPi) have been proposed as targets. Few cases using them together in a double-target approach have also been reported. Methods We reviewed the literature on this topic, summarizing results of different target choices. Additionally, we retrospectively report a case series of nine patients with sporadic dystonia and severe tremor treated with a double-target strategy at our center. Outcome measures were the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) and Eq-5d scale. Results In published studies of patients with dystonia and tremor, VIM-DBS is highly effective on tremor but raise some concerns about dystonia’s control, while GPi-DBS is more effective on dystonia but does not always relieve tremor. GPi + VIM-DBS shows good efficacy but is rarely reported and reserved for selected patients. In our patients, the double-target strategy obtained a significant and durable improvement in tremor, dystonia, and quality of life. Additionally, compared with a cohort of patients with tremor treated with VIM-DBS only, significantly lower frequency and intensity of VIM stimulation were required to control tremor. Conclusion Our findings and published evidence seem to support the double-targeting approach as a safe and effective option in selected patients with tremor-dominant dystonia. This strategy appears to provide a more extensive control of either dystonia or tremor and may have a potential for limiting stimulation-related side effects.
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