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Randomized Controlled Trial
. 2025 Feb 17;26(1):35.
doi: 10.1186/s10194-025-01967-8.

Safety and feasibility of deep brain stimulation of the anterior cingulate and thalamus in chronic refractory neuropathic pain: a pilot and randomized study

Denys Fontaine  1   2   3 , Aurélie Leplus  4   5   6 , Anne Donnet  6   7   8 , Nelly Darmon  5   9 , Anne Balossier  10 , Bruno Giordana  5   9 , Benoit Simonet  4   5   6 , Petru Isan  4   5   6 , Jean Regis  10 , Michel Lanteri-Minet  5   6   8   11
Affiliations
Randomized Controlled Trial

Safety and feasibility of deep brain stimulation of the anterior cingulate and thalamus in chronic refractory neuropathic pain: a pilot and randomized study

Denys Fontaine et al. J Headache Pain. .

Abstract

Background: Deep Brain Stimulation (DBS) of the anterior cingulum has been recently proposed to treat refractory chronic pain but its safety and its efficacy have not been evaluated in controlled conditions. Our objective was to evaluate the respective feasibility and safety of sensory thalamus (Thal-DBS) combined with anterior cingulate (ACC-DBS) DBS in patients suffering from chronic neuropathic pain.

Methods: We conducted a bicentric study (clinicaltrials.gov NCT03399942) in patients suffering from medically-refractory chronic unilateral neuropathic pain surgically implanted with both unilateral Thal-DBS and bilateral ACC-DBS, to evaluate successively: Thal-DBS only; combined Thal-DBS and ACC-DBS; ACC-DBS "on" and "off" stimulation periods in randomized cross-over double-blinded conditions; and a 1-year open phase. Safety and efficacy were evaluated by repeated neurological examination, psychiatric assessment, comprehensive assessment of cognitive and affective functioning. Changes on pain intensity (Visual Analogic Scale) and quality of life (EQ-5D scale) were used to evaluate DBS efficacy.

Results: All the patients (2 women, 6 men, mean age 52,1) completed the study. Adverse events were: epileptic seizure (2), transient motor or attention (2), persistent gait disturbances (1), sleep disturbances (1). No patient displayed significant cognitive or affective change. Compared to baseline, the quality of life (EQ-5D utility score) was significantly improved during the ACC-DBS "On" stimulation period (p = 0,039) and at the end of the study (p = 0,034).

Conclusion: This pilot study confirmed the safety of anterior cingulate DBS alone or in combination with thalamic stimulation and suggested that it might improve quality of life of patients with chronic refractory neuropathic pain.

Trial registration: The study has been registered on 20,180,117 (clinicaltrials.gov NCT03399942).

Keywords: Chronic Pain; Cingulate cortex; Deep brain stimulation; Neuropathic pain; Thalamus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by a Ethical Medical Committee (“Comité de Protection de Personnes Sud Méditerranée”, ID-IRB 2017-A00032-51) and registered (clinicaltrials.gov NCT03399942). All the patients signed an informed consent before inclusion. Safety data were supervised by an independent Data Monitoring Committee. Competing interests: This academic study has been sponsored and funded by the CHU de Nice (grant number: 16-AOIP-01). The hardware (leads and generators) was provided free of charge by Abbott which was not involved in the design and analysis of the study. DF is consultant for Medtronic, Abbott, and Boston Scientific, companies that manufacture and commercialize DBS devices, and received research grant from Medtronic and Abbott. MLM is consultant for Medtronic and received research grant from Medtronic. AL received speaker fees from Boston Scientific. AB has received consultant fees from Medtronic. Other authors declare no conflict of interest related to the study.

Figures

Fig. 1
Fig. 1
Study design. The study design consists of a 1-month pre-treatment evaluation phase, a phase of thalamic stimulation alone (1 month), then thalamic and anterior cingulate (ACC) stimulation (3 months), followed by a cross-over randomized phase comparing ACC stimulation “On” (3 months) and “Off” (3 months) periods, and then an open phase (12 months)
Fig. 2
Fig. 2
Location of electrodes. A. 3D representation of bilateral electrodes within the antérior cingulate cortex (ACC), from a left superior anterior point of view. B, C, D Patient’s C1P2 properative T1 weighted MRI merged with post operative CT showing the respective locations of the electrodes within the left sensory thalamus (B) and the ACC (C, D)
Fig. 3
Fig. 3
Evolution of main cognitive and affective performances along the study compared to baseline. The graphs indicate the differences of scores between baseline and every other time of measure. Indiviuals patients’ values are indicated by blue points, mean are displayed by red points. No patient showed a variation in performance greater than two standart deviations. Executive function score has been computed by the mean of standardized scores of several test including: the Trail Making Test B, Stroop interference, Stroop Interference– Naming, Six Elements, Phonological fluency, Categorical fluency, Modified Wisconsin card sorting test– perseverative error, Brixton, Double task. Episodic memory has been computed by the mean of standardized scores of the Free recalls 1, 2, 3 and 4 of the Free and Selective Cued Recall Test. The working memory score has been computed by the mean of standardized scores of WAIS IV digit span subtest. The score assessing the “Theory of Mind” has been computed as the mean of standardized score of the Reading the mind in the eyes test. The Emotion Recognition score has been computed as the mean of standardized score of the Facial expression of emotion, stimuli and test (FEEST). Apathy has been assessed by the Lille Apathy Rating Scale
Fig. 4
Fig. 4
Evolution of pain intensity and quality of life scores according to study period and stimulation status. VAS: Visual Analogic Scale; EQ-5D: EuroQoL EQ-5D-3 L health questionnaire including two scores: the utility score and the VAS score. QoL: quality of life
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