Biomarkers and methods for detection of seizures and epilepsy

Abstract

Epileptic seizures are difficult to diagnose and are often difficult to distinguish from several conditions with similar presentations, and therefore, diagnosis of seizures is often a long, expensive, and unreliable process. This invention provides biomarkers for identifying seizures and epilepsy, assays for measuring and assessing biomarker concentration, predictive models based on biomarkers and computer systems for detecting, assessing and diagnosing phasic and tonic changes associated with seizures and epilepsy in all clinical and healthcare settings. Diagnostic methods, kits and predictive models provided herein provide quantitative and/or qualitative assessment in order to allow patients to proceed immediately to diagnostic and/or treatment protocols, and assess therapeutic treatment effectiveness.

1 - 18 . (canceled) 
     
     
         19 . A method for diagnosing a seizure disorder in a patient comprising the steps of:
 obtaining a blood plasma or blood serum sample from the patient;   measuring or detecting the concentration of thymus and activation-regulated chemokine (TARC) in the blood plasma or blood serum sample via at least one selected from the group of enzyme-linked immunoassay (ELISA), Indirect ELISA, Sandwich ELISA, Competitive Elisa, Multiple and Portable (M&P) ELISA, and combinations thereof;   measuring or detecting the concentration of tumor necrosis factor alpha (TNF-α) in the blood plasma or blood serum sample via at least one selected from the group of enzyme-linked immunoassay (ELISA), Indirect ELISA, Sandwich ELISA, Competitive Elisa, Multiple and Portable (M&P) ELISA, and combinations thereof;   comparing concentrations of TARC and TNF-α to normal control concentrations of TARC and TNF-α, respectively;   determining at least one of the following: i) the concentration of TARC in the blood plasma or blood serum sample obtained from the patient is increased compared to the normal control concentration of TARC; and ii) the concentration ratio of TNF-α to TARC in the blood plasma or blood serum sample obtained from the patient is decreased compared to the normal control concentration ratio of TNF-α to TARC; and   diagnosing the seizure disorder in the patient.   
     
     
         20 . The method of  claim 19 , wherein the normal control concentrations of TARC and TNF-α are obtained from a subject that has at least one characteristic selected from (i)-(iii):
 (i) the same sex as the patient, 
 (ii) the same age or a similar age as the patient, or 
 (iii) the same race as the patient. 
 
     
     
         21 . The method of  claim 19 , further comprising using electroencephalography (EEG) to diagnose the seizure disorder in the patient. 
     
     
         22 . The method of  claim 19 , further comprising using magnetic resonance imaging (MRI), complete blood count (CBC), chemistry metabolic panel (CMP), a toxicology screen test, a positron emission tomography (PET) scan, a lumbar puncture, or a combination thereof to diagnose the seizure disorder in the patient. 
     
     
         23 . The method of  claim 19 , further comprising:
 measuring or detecting the concentration of soluble intercellular adhesion molecule 5 (sICAM-5) in the blood plasma or blood serum sample via at least one selected from the group of enzyme-linked immunoassay (ELISA), Indirect ELISA, Sandwich ELISA, Competitive Elisa, Multiple and Portable (M&P) ELISA, and combinations thereof; and   comparing the concentration of sICAM-5 to a normal control concentration of sICAM-5.   
     
     
         24 . The method of  claim 23 , wherein an algorithm is used to compare the concentrations of TARC, TNF-α, and sICAM-5 in the blood plasma or blood serum sample obtained from the patient to the normal control concentrations of TARC, TNF-α, and sICAM-5, respectively;
 wherein the algorithm comprises: i) a first step of comparing the concentration ratio of TNF-α to TARC in the blood plasma or blood serum sample obtained from the patient to the normal control concentration ratio of TNF-α to TARC, and ii) a second step, to be performed if the concentration ratio of TNF-α to TARC in the blood plasma or blood serum sample obtained from the patient is less than the normal control concentration ratio of TNF-α to TARC, the second step comprising comparing the concentration of sICAM-5 in the blood plasma or blood serum sample obtained from the patient to the normal control concentration of sICAM-5; 
 and wherein the algorithm provides a score indicative of a diagnosis of the seizure disorder in the patient. 
 
     
     
         25 . The method of  claim 24 , wherein the algorithm uses logistic regression to classify a clinical event in the patient as an epileptic or non-epileptic event and to provide the score indicative of the diagnosis of the seizure disorder in the patient. 
     
     
         26 . The method of  claim 23 , further comprising determining the concentration of sICAM5 in the blood plasma or blood serum sample obtained from the patient is increased compared to the normal control concentration of sICAM5. 
     
     
         27 . The method of  claim 23 , further comprising determining the concentration ratio of TNF-α to sICAM5 in the blood plasma or blood serum sample obtained from the patient is decreased compared to the normal control concentration ratio of TNF-α to sICAM5.