The Role of CSF in Chiari II Brain Malformation
NCT Number: NCT06560788
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Myelomeningocele|Brain Malformation|Chiari Malformation Type 2
Interventions: OTHER: collection of cerebrospinal fluid
Sponsor: University College, London
Collaborators: Great Ormond Street Hospital for Children NHS Foundation Trust|University College London Hospitals
Sex: ALL
Age: CHILD
Enrollment: 18
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-01
Completion Date: 2027-08-01

Summary:
Spina bifida, particularly its most severe form known as open spina bifida (myelomeningocele), is a significant congenital disorder that results in profound neurological impairments, including Chiari II malformation. This malformation is associated with the downward displacement of the cerebellum and brainstem into the spinal canal, often leading to hydrocephalus, a condition where cerebrospinal fluid (CSF) accumulates in the brain1. These conditions can result in a range of complications, including cognitive and motor disabilities, learning difficulties, and, in severe cases, early mortality1,2.

While surgical interventions, including prenatal and postnatal surgeries, have been developed to manage the physical manifestations of spina bifida and Chiari II malformation, these procedures have not been fully successful in addressing the associated brain anomalies3. This study aims to explore the hypothesis that the composition of CSF plays a critical role in the development of these brain defects. Specifically, it is hypothesized that the rapid replenishment of CSF, due to its leakage from the open spine in spina bifida, results in a "less mature" fluid composition, which negatively affects neurogenesis and neuronal migration during critical periods of brain development.

Primary Outcome Measures: Identification of Proteins in Cerebrospinal Fluid (CSF), The presence of specific proteins in cerebrospinal fluid (CSF) will be identified through proteomic analysis. This outcome will focus on categorizing which proteins are present in the CSF samples from patients with spina bifida and control participants., 1 year|Quantification of Protein Concentrations in Cerebrospinal Fluid (CSF), The concentration of each identified protein in cerebrospinal fluid (CSF) will be measured using proteomic analysis. This outcome will report the amount of each protein present in the CSF, expressed in micrograms per milliliter (µg/mL) or nanograms per milliliter (ng/mL), allowing for comparison between patients with spina bifida and controls., 1 year
Secondary Outcome Measures: Measurement of Neurogenesis in Median Ganglionic Eminence (MGE) Cultures, The rate of neurogenesis in the median ganglionic eminence (MGE) of embryonic brain slice cultures will be measured following exposure to cerebrospinal fluid (CSF) from patients with Chiari II malformation and control subjects. The outcome will focus on the number of proliferating neurons per unit area, measured in cells per square millimeter (cells/mm²)., 1 year|Measurement of Neuronal Migration in Median Ganglionic Eminence (MGE) Cultures, The distance of neuronal migration in the median ganglionic eminence (MGE) of embryonic brain slice cultures will be measured following exposure to cerebrospinal fluid (CSF) from patients with Chiari II malformation and control subjects. The outcome will report the migration distance of neurons, measured in micrometers (µm)., 1 year