Sub-study of the NEURODOC Project : Neurophysiological Evaluation of a Routine Care Open Label tDCS Session (Neurodoc)

Groupe Hospitalier Pitie-Salpetriere

Status: Completed

Conditions: Traumatic Brain Injury; Stroke; Disorder of Consciousness; Anoxic Brain Injury

Treatments: Diagnostic Test: Electrophysiological recordings; Behavioral: Coma Recovery Scale - revised

Study type: Interventional

Funder types: Other

Identifiers

NCT04035655

2013-A01385-40

Details and patient eligibility

About

Limited treatments are available to improve consciousness in severely brain injured patients. Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed evidence of efficacy to increase level of consciousness and functional communication in some Minimally Conscious State (MCS) patients, and in some Vegetative State (VS) patients.

However the mechanisms by which tDCS improves consciousness are poorly understood and the electrophysiological effects of such a stimulation have never been studied in disorders of consciousness patients.

In this study, the investigators will use detailed clinical examinations and electrophysiological assessments (quantitative high-density EEG and event-related potentials) to assess the effect of a open-label single session of left dorsolateral prefrontal cortex tDCS stimulation administered as routine care.

Full description

Limited treatments are available to improve consciousness in severely brain injured patients. Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed evidence of efficacy to increase level of consciousness and functional communication in some Minimally Conscious State (MCS) patients, and in some Vegetative State (VS) patients (1, 2, 3, 4), with no side effects reported.

However the mechanisms by which tDCS improves consciousness are poorly understood and the electrophysiological effects of the stimulation have never been studied in disorders of consciousness patients.

In this study, the investigators will use detailed clinical examinations (Coma Recovery Scale - Revised (5)) and electrophysiological assessments (quantitative high-density EEG and event-related potentials) (6, 7) and event-related potentials (8, 9) together with a standard morphological MRI to assess the effect of a open-label single session of left dorsolateral prefrontal cortex tDCS stimulation administered as routine care.

The primary goal is to investigate electrophysiological response to tDCS and its relation to behavioral response to better understand how tDCS affects consciousness in disorders of consciousness patients.

References:

1. Angelakis, E. et al. Transcranial Direct Current Stimulation Effects in Disorders of Consciousness. Arch. Phys. Med. Rehabil. 95, 283-289 (2014).
2. Thibaut, A., Bruno, M.-A., Ledoux, D., Demertzi, A. & Laureys, S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology 82, 1112-1118 (2014).
3. Thibaut, A. et al. Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state. Brain Inj. 1-9 (2017). doi:10.1080/02699052.2016.1274776
4. Martens, G. et al. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimulat. (2018). doi:10.1016/j.brs.2018.04.021
5. Giacino, J. T. & Kalmar, K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol. Rehabil. 15, 166-174 (2005).
6. Sitt, J. D. et al. Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state. Brain 137, 2258-2270 (2014).
7. Engemann, D. A. et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain J. Neurol. 141, 3179-3192 (2018).
8. Bekinschtein, T. A. et al. Neural signature of the conscious processing of auditory regularities. Proc. Natl. Acad. Sci. 106, 1672-1677 (2009).
9. Faugeras, F. et al. Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness. Neuropsychologia 50, 403-418 (2012).

Enrollment: 66 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age between 18 and 80 years
• Disorder of consciousness assessed by CRS-R (VS, MCS, exitMCS)
• Patients with stable clinical examination (even in intensive care unit)
• Structural brain injury confirmed by cerebral imaging (MRI or TDM)

Exclusion criteria

• Refractory status epilepticus
• Known preexisting severe neurodegenerative disease (ie: Alzheimer disease, Lewy body dementia, ...)
• MRI contraindication: metallic intra-cranial implants, pacemaker or implantable cardioverter-defibrillator, cranial prosthesis
• Pregnant, parturient or breastfeeding women

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 1 patient group

Clinical and electrophysiological evaluation of tDCS session

Experimental group

Description:

In this prospective case-control study, the investigator's main goal was to evaluate the impact of a single standard-care tDCS session on brain activity (EEG). The effect of a single 20 minutes 2 mA tDCS session with the anode placed over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital cortex administered as routine care were evaluated by combined behavioral and electrophysiological assessments immediately before and after the stimulation. The study consisted of the following interventions, administered immediately before and after the stimulation session: * detailed behavioral assessment by the Coma Recovery Scale-Revised (CRS-R) * 5 minutes resting state high-density EEG recordings and 6 minutes auditory oddball paradigm immediately. Additionally, clinical anatomical MRI (T1) acquired as routine care were used to model the estimated tDCS-induced electric fields in the entire head of patients, based on available T1-weighted MRI.

Treatment:

Behavioral: Coma Recovery Scale - revised

Diagnostic Test: Electrophysiological recordings