Abstract
BackgroundClinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage. At present, there are no valid tests for assessing organic damage to the brain associated with seizure. The aim of this study was to investigate cerebrospinal fluid (CSF) and plasma concentrations of Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a sensitive indicator of acute injury to brain neurons, in patients with tonic–clonic or partial secondarily generalized seizures due to various etiologies.MethodsCSF and plasma concentrations of UCH-L1 were assessed in 52 patients within 48 hours after epileptic seizure and in 19 controls using ELISA assays.ResultsCSF obtained within 48 hours after seizure or status epilepticus (SE) presented significantly higher levels of UCH-L1 compared to controls (p = 0.008). Plasma UCH-L1 concentrations were negatively correlated with time to sample withdrawal. An analysis conducted using only the first 12 hours post-seizure revealed significant differences between concentrations of UCH-L1 in plasma and controls (p = 0.025). CSF and plasma concentrations were strongly correlated with age in patients with seizure, but not in control patients. Plasma UCH-L1 levels were also significantly higher in patients after recurrent seizures (n = 4) than in those after one or two seizures (p = 0.013 and p = 0.024, respectively).ConclusionOur results suggest that determining levels of neuronal proteins may provide valuable information on the assessment of brain damage following seizure. These data might allow clinicians to make more accurate therapeutic decisions, to identify patients at risk of progression and, ultimately, to provide new opportunities for monitoring therapy and targeted therapeutic interventions.
Highlights
Clinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage
Recent experimental studies have shown that seizures, whether continuous or sporadic, can cause molecular and cellular responses resulting in neuronal damage or death, gliosis, and axonal and dendritic remodeling [1,2]
Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) concentrations in cerebrospinal fluid (CSF) were significantly higher in patients within 48 hrs after epileptic seizure than in controls
Summary
Clinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage. The aim of this study was to investigate cerebrospinal fluid (CSF) and plasma concentrations of Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a sensitive indicator of acute injury to brain neurons, in patients with tonic–clonic or partial secondarily generalized seizures due to various etiologies. After TBI, blood UCH-L1 level correlates with injury severity, outcome at discharge and 6 months after injury [10,11] This neuronal protein can be readily detected in CSF and blood very early after injury [11], which provides a valuable time-window for potential neuroprotective strategies. Because of its clinically relevant characteristics and high brain specificity, UCH-L1 has been recently recognized as a novel and promising biomarker of neuronal injury and BBB disruption
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