Study of the Impact of Locus Coeruleus Dysfunction on Cognitive Function in Young Subjects With Ondine Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks.
研究概览
简要总结
This study investigates whether cognitive dysfunction in young patients with congenital central hypoventilation syndrome (Ondine Syndrome) is related to the severity of the disease and dysfunction of the locus coeruleus (a brainstem structure involved in autonomic control and cognition). The investigators will assess cognitive evoked potentials (P300 wave) using high-resolution EEG during attention tasks, pupillometry, brain MRI, neuropsychological tests, and heart rate variability. Patients with different severities of PHOX2B gene mutation (alanine expansions <27 vs. ≥27) will be compared.
详细描述
Ondine Syndrome (congenital central hypoventilation syndrome) is a rare autosomal dominant genetic disorder caused by mutations in PHOX2B. Patients require lifelong nocturnal ventilation and often have cognitive impairments. The cause of cognitive deficits is uncertain: possible hypoxic brain injury or direct effects of PHOX2B mutations on brain regions like the locus coeruleus.
This cross-sectional study includes 21 patients aged 7-20 years with Ondine Syndrome and PARM-type (polyalanine repeat mutation) PHOX2B mutations, divided into moderate (<27 alanine expansions) and severe (≥27 expansions) groups. During routine hospitalization, participants undergo:
High-resolution EEG with evoked potentials during auditory and visual attention tasks to measure P300 wave amplitude.
Pupillometry during the same tasks to assess locus coeruleus function.
3T (3 Tesla magnetic resonance imaging) MRI (anatomical and diffusion imaging) without sedation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 7 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonatal diagnosis of Ondine Syndrome.
- •PARM-type PHOX2B mutation.
- •Age 7 to 20 years.
- •Receiving nocturnal ventilation.
- •Consent obtained. Affiliated with social security.
排除标准
- •Severe autism spectrum disorder preventing test completion.
- •Legal guardianship or curatorship.
结局指标
主要结局
Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks.
时间窗: 24 hours
Measurement of cognitive evoked potential P300 amplitude using a 64-electrode EEG system during Flanker and oddball paradigms to assess locus coeruleus function.
次要结局
- Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.(24 hours)
- Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry.(24 hours)
- Heart rate variability parameters from Holter ECG monitoring.(24 hours)
- Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.(24 hours)
- Scores of socio-adaptive behavior from the Vineland neuropsychological test (Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning).(24 hours)