Cerebrospinal fluid concentrations of polyols following traumatic brain injury

Traumatic brain injury is the leading cause of death and disability in children
and adults aged 1 to 44 years. The direct consequences of a single traumatic
brain injury (TBI) or repetitive insults can result in various secondary
pathological conditions.
Under normal circumstances, the brain uses glucose as an obligate energy
source. However, during glucose excess, neurotoxic polyols are generated. The
brain uses glucose as an obligate energy source and generates polyols during
glucose excess. Following TBI, the brain utilizes less glucose due to sedative
medications, the injury itself and because of a hyperglycaemic stress response.
As such we hypothesise that the brain produces increased amounts of neurotoxic
polyols after TBI.
We propose to conduct a prospective observational cohort study to describe the
polyol concentrations in the cerebrospinal fluid (CSF) in participants admitted
to the intensive care unit following TBI, who have required insertion of an
External Ventricular Drain (EVD) as part of their clinical management, and
determine associations between CSF polyol concentration, plasma glucose and
markers of neuroinflammation.

Primary objective:
i. Investigate cerebrospinal fluid (CSF) polyol concentrations in patients
following traumatic brain injury

Secondary objectives:
i. Investigate the association between plasma glucose, CSF glucose and CSF
polyols following traumatic brain injury.
ii. Investigate the relationship between CSF polyol concentration and plasma
and CSF markers of neuroinflammation (S100-beta, neuron specific enolase,
neurofilament light, IL-6, TNF-alpha, Il-10, interferon-gamma) in patients with
TBI.

Prospective monocenter cohort study with an expected duration of 2 years. This
study will be conducted at the Amsterdam UMC, location AMC.

This study has no additional risks beyond standard care, as there are no
additional blood or liquor collection moments for research purposes. Patients
will undergo three times a week blood and liquor tests for this study. The
blood collection will involve 1 tube of blood of 4 ml at a time, with a maximum
collection of 40 ml of blood per patient. This blood collection will take place
at the same time as the department's blood collection. The liquor examination
takes place in the liquor drained from the Extra Ventricular Drain (EVD). There
will be no additional liquor collection. Therefore, the burden on the subject
is minimal and the risks are similar to those of standard care.