Clinical trial NCT05645874: Reference Values of Intraepidermal Nerve Fiber Density in Children and Small Fiber Neuropathy in Neurometabolic and Neurodevelopmental Disorders in 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 ? -
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Mitochondrial Diseases
Developmental Delay Disorder
Small Fiber Neuropathy
Cerebral Palsy
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2022-12-12
Enrollment: 240
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Control (no underlying neurological disorder) individuals
2. Neurodevelopmental disorder_Genetic cause known
3. Neurodevelopmental disorder_Acquired (cause known, for example perinatal asphyxia or intracranial bleeding)
4. Neurodevelopmental disorder_Cause unknown

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.


Eligibility criteria: 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

Primary outcomes:
measure: Intraepidermal nerve fiber density
timeFrame: 2 years
Secondary outcomes:
measure: Pathological protein deposits, morphological alterations of cell organells
timeFrame: 2 years
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldord, Department of General Pediatrics, Neonatology and Pediatric Cardiology
Study officials:
References:
citation: 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.