Reference Values of Intraepidermal Nerve Fiber Density in Children and Small Fiber Neuropathy in Children With Acquired and Genetic Neurodevelopmental Disorders - An Unrecognized Cause of Pain and Window Into Brain Pathology ? -
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 203
- 试验地点
- 1
- 主要终点
- Part 1 - Cutoff for reduced intraepidermal nerve fiber density (IENFD) in children
研究概览
简要总结
Background: Small-Fiber-Neuropathy describes the degeneration of mildly or unmyelinated nerve fibers and causes neuropathic pain and autonomic dysfunction. Gold standard for the diagnosis is a small skin punch biopsy from the lower leg and the histological quantification of the intraepidermal nerve fiber density (IENFD). In children, the normal IENFD has not been systematically assessed and normal reference values are needed. In Parkinson´s disease, the neurodegeneration also affects the peripheral nerves and SFN is present already in the early stages. Whether neurodevelopmental disorders (NDDs) in childhood are likewise associated with SFN is largely unknown. The IENFD is age-dependent and declines with age.
Aims: In this study, we are establishing the reference values for the physiological IENFD in children from 0-18 years. Moreover, we are investigating if children with NDDs have a reduced IENFD and if SFN is a clinically relevant cause of pain and autonomic dysfunction.
详细描述
In the first part of the study, skin biopsies will be collected from the leg from children with a normal neurological development (healthy children) in the setting of elective orthopedic surgery (during general anesthesia; from surgical crop margins).
The IENFD is determined by staining and quantification of PGP9.5-positive intraepidermal nerve fibers on 40 µm thick skin sections.
The skin biopsies will be collected from the site of orthopedic surgical procedure. For example, if the child is undergoing corrective osteotomy of genu valgum, the skin biopsy is drawn from the most distal part of surgical incision sides (distal leg); if the child is undergoing orthopedic surgery in the context of epiphyseolysis capitis femoris, the skin biopsy is drawn from the thigh (proximal leg):
In adults, the IENFD is higher in specimens derived from the proximal leg than in skin from the distal leg. Because in small fiber neuropathy the small nerve fiber degeneration often starts distally, the recommended sampling site for the quantification of IENFD in adults is the distal leg. That is why the calculation of the 5th percentile as the cutoff for reduced IENFD in children will be based on skin biopsies collected from the distal leg.
Due to the limited number of surgeries on the distal leg and distal biopsies in certain age groups of healthy participants (e.g. 4-8), cases with skin biopsies taken from the proximal leg will also be included. The IENFD from cases drawn from the proximal leg and cases from the distal leg will be compared. The samples drawn from the distal or proximal leg will be labelled accordingly. If the IENFD is comparable between the distal and proximal cases, a pooled analysis including proximal and distal cases will be performed.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Elective surgical intervention from lower leg
- •Interest to participate in the study, informed consent
- •Unremarkable neurological development
排除标准
- •Clinical signs of polyneuropathy, autonomic dysfunction
- •Skin inflammation, scar, skin disease, other known chronic diseases that can cause small fiber pathology
- •Neurodevelopmental patients
- •Inclusion Criteria:
- •Neurodevelopmental problems (developmental delay, muscular hypotonia, seizures, ataxia,...) with age of onset before the age of 18 years
- •Interest to participate in the study, informed consent
- •Exclusion Criteria:
- •Known polyneuropathy
- •Skin inflammation, scar, skin disease, other known chronic diseases that can cause small fiber pathology
结局指标
主要结局
Part 1 - Cutoff for reduced intraepidermal nerve fiber density (IENFD) in children
时间窗: 2 years
Age- and sex-specific 5th percentile of IENFD in the distal leg of neurologically healthy children aged 0-18 years (controls) as the cutoff for reduced IENFD.
Part 2 - Proportion of children with reduced IENFD among children with neurodevelopmental disorders (NDDs).
时间窗: 2 years
Proportion of children with genetic, acquired NDDs or NDDs of initially unexplained etiology whose IENFD falls below the predicted, age- and sex-specific 5th percentile (cutoff) that was calculated in part 1.
次要结局
未报告次要终点