Biomarkers in the Etiology of Idiopathic Intracranial Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- intracranial pressure (ICP) blood biomarker correlation
研究概览
简要总结
Idiopathic intracranial hypertension (IIH) is a condition characterized by an increase in intracranial pressure (ICP), papilledema with a risk of permanent visual loss, and severe headaches that profoundly affect quality of life.
To date the exact pathophysiology of IIH remains unknown. IIH is considered a complex neurometabolic and neuroendocrine disorder, favored by female gender, and obesity.
In the majority of patients (80% of the cases) IIH is associated with obstruction of cerebral venous drainage with stenosis of the transverse sinus. This stenosis may be the main underlying cause in the so-called "venogenic" form of IIH. Equally, in the absence of a stenosis, obstruction may occur when otherwise normal venous sinuses are compressed by the increased ICP, the so-called "non-venogenic" form of IIH. An innovative treatment of IIH with associated venous stenosis includes stenting of the transverse sinus stenosis. This strategy may allow resolution of papilledema and ICP reduction rates up to 80%.
Although the pathogenesis of IIH is still poorly understood, inflammatory mechanisms, autoimmune reactions, and hormonal abnormalities of notably androgens, have been proposed to contribute to its pathophysiology. The function of the blood-brain barrier (BBB) has been studied by determining the prevalence of extravasation of endogenous proteins such as fibrinogen.
A growing body of the literature shows a correlation between increased ICP and metabolic/hormonal changes.
The improvement of IIH treated with acetazolamide and/or stenting appears to correlate with the reduction of ICP. Yet the association of this reduction with metabolic changes at the peripheral and central blood level as well as the CSF remains unclear. The search for specific inflammatory, immunological and hormonal biomarkers in patients with IIH and their variation in relation to the ICP should provide a better understanding of its etiology.
详细描述
Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure (ICP) of unknown cause, papilledema with the risk of permanent visual impairment, and severe headaches that profoundly impair quality of life, often becoming irreversible despite resolution of the IIH and disappearance of the papilledema.
IIH is diagnosed using the modified Dandy criteria,based on increased ICP (>25 cm H2O on lumbar puncture (LP) performed in the lateral decubitus), papilledema, normal cerebrospinal fluid (CSF) and brain imaging that rules out all other causes of intracranial hypertension.
IIH is attracting growing interest among clinicians as its incidence and prevalence increases. IIH predominates in women of childbearing age with increased body mass index (BMI) . In the United Kingdom its incidence has doubled in 14 years, rising from 3.5 per 100,000 to 7.69 per 100,000 in the female population between 2002 and 2016 (+ 108%)
To date, the exact pathophysiology of IIH remains unknown. IIH is considered to be a complex neurometabolic and neuroendocrine disorder favored by female gender and obesity. Hypothesized mechanisms include inflammatory, autoimmune and hormonal abnormalities, of notably androgens.
In the majority of patients (80% of the cases) IIH is associated with obstruction of cerebral venous drainage with bilateral stenosis of the transverse sinus. This stenosis may be the main underlying cause in the so-called "venogenic" form of IIH. Equally, in the absence of a stenosis, obstruction may occur when otherwise normal venous sinuses are compressed by the increased ICP, the so-called "non-venogenic" form of IIH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years and older
- •Patients with newly diagnosed untreated HII (following the modified Dandy criteria) with normal CSF composition, abnormal CSF pressure at the lumbar puncture (>25 cm H2O), and significant pressure gradient at the level of the stenosis (≥8 mmHg)
- •Presence of bilateral transverse sinus stenosis (or unilateral with hypoplastic contralateral sinus).
排除标准
- •Allergy to contrast media (nickel, titanium)
- •Allergy or contraindication to antiplatelet agents
- •Patient on anti-inflammatory treatment
- •Chronic inflammatory disease
- •History of intracranial venous thrombosis, cerebral hemorrhage, thrombophilia
- •History of intracranial tumor
- •Fulminant IIH with acute visual loss
- •Optic nerve atrophy with papilledema (chronic IIH)
- •Female being pregnant, breastfeeding, or planning to become pregnant in the next 3 months
- •Major comorbidities with high procedural risk
- •Life expectancy < 6 months
- •Adult under guardianship or conservatorship or incapacitated
- •Refusal of consent after receiving all necessary information
- •Not covered by or not a beneficiary of the French social security system
结局指标
主要结局
intracranial pressure (ICP) blood biomarker correlation
时间窗: Change over time before (at inclusion) and 3 months after IIH treatment (follow-up)
The correlation (Pearson's r) between blood biomarkers and ICP measured before and after IIH treatment. Pearson's r will be calculated with a multivariate stepwise linear regression to identify those biomarkers that can explain a change in ICP. The blood biomarkers are extracted from peripheral and central venous blood. The ICP is measured at torcular level. The blood biomarkers include: * Inflammatory markers (pg/mL): * Osteopontin, γ\&β-chain fibrinogen, α1-acid glycoprotein 2 et haptoglobin * Inflammatory cytokines : INFγ, IL-2, IL-10, IL-4, IL-12p70, IL-6, IL-13, IL-8, IL-1β, TNF-α, IL-17, IL-23, IGF-1, TGFβ1 * Chemokines: Fractalkine, SDF-1, CX3CL1, MCP-1, CCL3, CCL5 * BBB integrity markers (pg/mL): S100b, GFAP, Neurofilament light-chain, Neuronal specific enolase, Uch-L1 * Headache associated markers (pg/mL): Calcitonin Gene Related-Peptide, Glucagon-Like Peptide * Hormonal markers (ng/mL): 11β-HSD1, Glucagon-like peptide-1, DHEAS, Leptin, estradiol, and testosterone
次要结局
- Headache severity(change over time before (at inclusion) and 3 months after IIH treatment (follow-up))
- Body mass index (BMI)(change over time before (at inclusion) and 3 months after IIH treatment (follow-up))
- Optic fibre layer (RNF) thickness(Before (at inclusion) and 3 months after treatment (follow-up))
- Transverse sinus stenosis(change over time before (at inclusion) and 3 months after IIH treatment (follow-up))
- Cerebral blood flow(change over time before (at inclusion) and 3 months after IIH treatment (follow-up))
- MRI contrast enhancement(change over time before (at inclusion) and 3 months after IIH treatment (follow-up))