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

Cerebral Palsy Clinical Trial

— SFN_children  

Official title:

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 ? -

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05645874
• Other study ID #: SFN children
• Secondary ID: 2021-1556
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: November 2022
• Source: Heinrich-Heine University, Duesseldorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Years and older

Eligibility

control patients

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

Related Conditions & MeSH terms

• Cerebral Palsy
• Developmental Delay Disorder
• Developmental Disabilities
• Mitochondrial Diseases
• Neurodevelopmental Disorders
• Small Fiber Neuropathy

Intervention

Diagnostic Test:
• Skin biopsy
Control skin biopsies from children without a chronic underlying disease are drawn from surgical crop margins during elective orthopedic surgery of the lower leg (n<80). Skin punch biopsies from children with acquired (n<80) or genetic NDD (n<80) or unknown etiology (N<80) are drawn in the setting of elective interventions during sedation or after local anesthesia. IENFD is quantified by immunohistochemistry and compared between the control and NDD group.

Locations

Country	Name	City	State
Germany	University Hospital Düsseldord, Department of General Pediatrics, Neonatology and Pediatric Cardiology	Düsseldorf

Sponsors (1)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Lauria G, Bakkers M, Schmitz C, Lombardi R, Penza P, Devigili G, Smith AG, Hsieh ST, Mellgren SI, Umapathi T, Ziegler D, Faber CG, Merkies IS. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010 Sep;15(3):202-7. doi: 10.1111/j.1529-8027.2010.00271.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intraepidermal nerve fiber density		2 years
Secondary	Pathological protein deposits, morphological alterations of cell organells		2 years