Reference Values of Intraepidermal Nerve Fiber Density in Children and Small Fiber Neuropathy in Neurometabolic and Neurodevelopmental Disorders in Children

Recruiting

• Conditions: Small Fiber Neuropathy; Mitochondrial Diseases; Developmental Delay Disorder; Cerebral Palsy
• Interventions: Diagnostic Test: Skin biopsy

• Registration Number: NCT05645874
• Lead Sponsor: Heinrich-Heine University, Duesseldorf

Brief Summary

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 SNF is a clinically relevant cause of pain and autonomic dysfunction.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-01
• Status Verified: 2022-11
• Study First Submitted: 2022-11-30
• Study First Submitted QC: 2022-11-30
• Last Update Submitted: 2022-11-30
• Study First Posted: 2022-12-12
• Last Update Posted: 2022-12-12
• Primary Completion: 2023-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Elective surgical intervention from lower leg
• Interest to participate in the study, informed consent
• Unremarkable neurological development

Exclusion Criteria

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control (no underlying neurological disorder)	Skin biopsy	-
Neurodevelopmental disorder_Cause unknown	Skin biopsy	-
Neurodevelopmental disorder_Genetic cause known	Skin biopsy	-
Neurodevelopmental disorder_Acquird (cause known)	Skin biopsy	-

Primary Outcome Measures

Name	Time	Method
Intraepidermal nerve fiber density	2 years

Secondary Outcome Measures

Name	Time	Method
Pathological protein deposits, morphological alterations of cell organells	2 years

Trial Locations

Locations (1)

University Hospital Düsseldord, Department of General Pediatrics, Neonatology and Pediatric Cardiology; 🇩🇪 Düsseldorf, Germany