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

NCT ID: NCT05645874

Last Updated: 2022-12-12

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 240 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2024-12-30

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.

Conditions

Mitochondrial Diseases; Developmental Delay Disorder; Small Fiber Neuropathy; Cerebral Palsy

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Control (no underlying neurological disorder)

Skin biopsy

Intervention Type: DIAGNOSTIC_TEST

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.

Neurodevelopmental disorder_Genetic cause known

Skin biopsy

Intervention Type: DIAGNOSTIC_TEST

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.

Neurodevelopmental disorder_Acquird (cause known)

Skin biopsy

Intervention Type: DIAGNOSTIC_TEST

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.

Neurodevelopmental disorder_Cause unknown

Skin biopsy

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

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

• 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

• Clinical signs of polyneuropathy, autonomic dysfunction
• Skin inflammation, scar, skin disease, other known chronic diseases that can cause small fiber pathology

Neurodevelopmental patients

• Known polyneuropathy
• Skin inflammation, scar, skin disease, other known chronic diseases that can cause small fiber pathology

• Minimum Eligible Age: 0 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital Düsseldord, Department of General Pediatrics, Neonatology and Pediatric Cardiology

Düsseldorf, , Germany

Site Status: RECRUITING

Countries

Germany

Facility Contacts

Luisa Averdunk, MD

Role: primary

Felix Distelmaier, MD

Role: backup

References

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.

Reference Type: BACKGROUND

PMID: 21040142 (View on PubMed)

Other Identifiers

2021-1556

Identifier Type: OTHER

Identifier Source: secondary_id

SFN children

Identifier Type: -

Identifier Source: org_study_id