Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
试验速览
- 阶段
- 不适用
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Cortical Inhibitory Tone
研究概览
简要总结
Dravet syndrome (DS) is an epileptic encephalopathy caused by pathogenic variants in the SCN1A gene resulting in medically refractory epilepsy and psychomotor delays.
As a pilot study assessing for feasibility, the investigators aim to test whether alterations in cortical excitatory:inhibitory ratio can be reliably recorded. The investigators will utilize transcranial magnetic stimulation (TMS) metrics of cortical excitatory and inhibitory tone as an initial step towards translating findings from rodent genetic models of DS into disease-specific biomarkers and offer future measures of therapeutic target engagement in this patient population.
Participants will complete two visits, each consisting of a TMS session and an EEG session. Visits will be scheduled 4-8 weeks apart.
详细描述
This is a single site study to be conducted at Boston Children's Hospital (BCH) investigating the neurophysiological biomarkers of epilepsy and developmental disability in children and young adults with Dravet Syndrome.
Mechanistically, the features of the DS phenotype are attributable to a loss of cortical inhibition. TMS is a non-invasive form of focal cortical stimulation in which an external powerful magnet induces an electrical field intracranially over the stimulated region that is used to interrogate or modulate states of cortical excitation or inhibition.
Accordingly, the investigators propose to test whether metrics of cortical excitability and inhibition can be obtained by transcranial magnetic stimulation (TMS) and EEG in patients with DS.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Months 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 6 months - 30 years
- •Ability to obtain informed consent with the participant or legally authorized representative
- •DS confirmed by pathogenic variant in SCN1A gene
- •Medical history consistent with clinical phenotype of DS
排除标准
- •Comorbid conditions such as a second genetic diagnosis which may confound interpretation.
- •Current or planned participation in a clinical drug or device trial.
- •Previous participation in a gene therapy or gene editing trial
- •Allergy to adhesives used for surface EMG electrodes
- •Contraindications to TMS (e.g. implanted devices for which there is no TMS safety data)
结局指标
主要结局
Cortical Inhibitory Tone
时间窗: 1 year
Power in the gamma (30-80 Hz) frequency band.
Durations of cortical silent period (ms)
时间窗: 1 year
Cortical Silent Period (CSP) is a single-pulse TMS measure of GABA-mediated cortical inhibition, in which stimulation is applied to the motor cortex while subjects are activating a target muscle (here, abductor pollicis brevis and deltoid muscles), resulting in a pause in muscle contraction. The time between stimulation and the return of voluntary muscle activity is the CSP, measured in milliseconds (ms).
Resting motor threshold (% machine output)
时间窗: 1 year
Resting motor threshold (rMT) is obtained by single-pulse TMS and measures voltage-gated sodium-channel-mediated cortical excitability. It is the minimum intensity of stimulation needed to reliably evoke a motor evoked potential (MEP) of at least 50 microvolts in over 50% of trials. It is reported as a percentage of total machine output.
Ratio of motor evoked potential amplitudes (no units)
时间窗: 1 year
Facilitation (ICF) are paired-pulse TMS metrics of cortical inhibition and excitability, respectively. A short interval interstimulus (1-5 ms) leads to cortical inhibition reflective of GABAergic neurotransmission; a longer interval interstimulus of 10-20 ms leads to a cortical facilitation, which reflects glutamatergic neurotransmission; an even longer interstimulus interval of 50-300 ms reflects GABAB-mediated local inhibition and likely GABAA-mediated network inhibition. The ratio of the peak-to-peak amplitude (in mm) of the second MEP to the first (or control) MEP will be calculated for each of these stimulation protocols.
次要结局
未报告次要终点
研究者
Alexander Rotenberg
Associate, Department of Neurology; Director, Neuromodulation Program; Associate Professor of Neurology, Harvard Medical School
Boston Children's Hospital