Cerebrospinal fluid and blood biomarkers of status epilepticus.
Aurélie HaninVirginie LambrecqJérôme Alexandre DenisFrançoise Imbert-BismutBenoît RuchetonFoudil LamariDominique Bonnefont-RousselotSophie DemeretVincent NavarroPublished in: Epilepsia (2019)
Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron-specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100-beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.
Keyphrases
- brain injury
- cerebral ischemia
- subarachnoid hemorrhage
- cerebrospinal fluid
- intensive care unit
- resting state
- end stage renal disease
- blood brain barrier
- ejection fraction
- chronic kidney disease
- oxidative stress
- white matter
- newly diagnosed
- young adults
- cardiovascular disease
- type diabetes
- transcription factor
- cardiovascular events
- mechanical ventilation
- binding protein
- patient reported outcomes
- early onset
- protein protein
- extracorporeal membrane oxygenation
- high density