Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

Bernadette T Gillick, Adam Kirton, Jason B Carmel, Preet Minhas, Marom Bikson, Bernadette T Gillick, Adam Kirton, Jason B Carmel, Preet Minhas, Marom Bikson

Abstract

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation.

Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial.

Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process.

Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm(2) with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events.

Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials.

Keywords: hemiparesis; modeling; pediatrics; stroke; transcranial direct current stimulation.

Figures

Figure 1
Figure 1
Conceptual methodology for determination of dose. Theoretical 7-step compartmentalization of decision workflow (left column) and implementation considerations specific to this case study of a 10 year-old child with hemiparesis due to perinatal stroke (right column). Incorporation of prior experience in the dose decision process coupled with modeling allows value-determination of subject-specific dose decisions for implementation.
Figure 2
Figure 2
Current flow predictions during tDCS in individual pediatric model for the M1-SO and Lateralized Temporal montages. M1-SO- The center of anode (red) was positioned on the motor strip and the cathode (black) was positioned over the contraletral supraorbital area. At 0.7 mA applied current, the peak electric field was 0.23 V/m. C3-C4- The center of anode (red) was positioned over the left temporal lobe and the cathode (black) was positioned contralateral to the anode (M-O). At 0.7 mA applied current, the peak electric field was 0.29 V/m. EF plots in the left, right and top views, are shown respectively (A.1a–c, B.1a–c). Cross-sectional coronal electric field plots were taken from the center of the anode (A.1.b1, B.1.b1). Directionality plots were also plotted. The red corresponds to current flowing inwards, the green corresponds to a net flow of zero, and the blue corresponds to current flowing outwards (B.1–B.2).

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