title: Neurofilament heavy chain and heat shock protein 70 as markers of seizure-related brain injury.
abstract: OBJECTIVE
  Status epilepticus (SE) has deleterious effects on brain tissue, but whether brief recurrent seizures may also damage neurons represents a matter of controversy. Therefore, it remains a central area of epilepsy research to identify individuals at risk where disease progression can be potentially prevented. Biomarkers may serve as tools for such identification. Thus the present study aimed at analyzing the levels of heat shock protein 70 (HSP-70, also designated as HSPA1A) and neurofilament heavy chain protein (NfH(SMI35) ) in cerebrospinal fluid (CSF) of patients with seizures of different severity.
  
  
  METHODS
  Forty-one patients were included, of whom 20 patients had a single generalized tonic-clonic seizure (GTCS) episode (SS), 11 had repetitive GTCS (RS), and 10 experienced convulsive SE. The control group consisted of 18 subjects. HSP-70 levels were measured using a conventional enzyme-linked immunosorbent assay (ELISA), whereas the NfH(SMI35) protein levels were detected by an electrochemiluminescence (ECL) immunoassay.
  
  
  RESULTS
  Patients with SE (p < 0.001) and RS (p < 0.05) had significantly higher NfH(SMI35) levels than controls, and SE was associated with increased concentrations when compared with SS (p < 0.001). NfH(SMI35) levels in SS did not differ from controls. Patients with SE had significantly raised HSP-70 levels compared to RS (p < 0.05), SS (p < 0.05), and controls (p < 0.001). SS and RS did not differ from each or from controls. Levels of NfH(SMI35) and HSP-70 showed a significant correlation (r = 0.34; p = 0.007) in the group of all study subjects, which was not apparent when controls and patients with seizures were considered separately. The correlation between NfH(SMI35) and HSP-70 tended to be inverse in patients with SE, but it did not reach statistical significance (r = -0.3; p > 0.05).
  
  
  CONCLUSIONS
  Studying biochemical markers as additional quantitative tools for the measurement of neuronal damage (especially subclinical), complementary to available techniques of imaging, and clinical assessment might prove useful for identifying patients at risk of accumulating neuronal injury resulting from uncontrolled seizures. NfH(SMI35) and HSP-70 are of potential value as sensitive and specific biomarkers of seizure-related pathologic events. Future longitudinal studies are needed to monitor such patients by correlating biochemical, neuroimaging, and clinical methods of assessment.
authors.affiliation: Department of Neurology, Medical University of Lublin, Jaczewskiego 8, Lublin, Poland. krejdak@europe.com
authors.forename: Konrad
authors.initials: K
authors.lastname: Rejdak
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Stephan
authors.initials: S
authors.lastname: Rüegg
authors.forename: Raija L P
authors.initials: RL
authors.lastname: Lindberg
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Dorota
authors.initials: D
authors.lastname: Sulejczak
authors.forename: Ewa
authors.initials: E
authors.lastname: Papuc
authors.forename: Robert
authors.initials: R
authors.lastname: Rejdak
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Stelmasiak
authors.forename: Paweł
authors.initials: P
authors.lastname: Grieb
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000627:therapeutic use; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000209:etiology*; D004569:Electroencephalography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D012640:Seizures / Q000150:complications* / Q000188:drug therapy; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018840:HSP70 Heat-Shock Proteins; D016900:Neurofilament Proteins; C051774:neurofilament protein H