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 .- 14 . (canceled) 
     
     
         15 . A method for diagnosing epilepsy in a mammalian subject comprising the steps of:
 (a) contacting a blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of TARC;   (b) contacting said blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of TNF-α;   (c) comparing the concentrations of TARC and TNF-α to normal control concentrations; and   (d) diagnosing epilepsy in the mammalian subject.   
     
     
         16 . The method of  claim 15 , further comprising contacting a blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of soluble ICAM-5 (sICAM-5) and comparing the concentration of sICAM5 to normal concentrations. 
     
     
         17 . A method for diagnosing a seizure disorder in a mammalian subject comprising the steps of:
 (a) contacting a blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of TARC;   (b) contacting said blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of TNF-α;   (c) comparing concentration ratios of TARC and TNF-α to normal control concentration ratios; and   (d) diagnosing the seizure disorder in the mammalian subject.   
     
     
         18 . The method of  claim 17 , further comprising contacting a blood plasma or blood serum sample obtained from the mammalian subject with a diagnostic reagent that can measure or detect the expression level of soluble ICAM-5 (sICAM-5) and comparing the concentration of sICAM5 to normal concentrations. 
     
     
         19 . The method of  claim 17 , wherein prolactin or other biomarker diagnostic test is used in combination to diagnose the seizure disorder. 
     
     
         20 . A kit for generating quantitative data for a patient comprising:
 (a) a diagnostic reagent that can measure an expression level of soluble ICAM-5 (sICAM-5) in a blood plasma or blood serum sample taken from the patient;   (b) a diagnostic reagent that can measure an expression level of TARC in the blood plasma or blood serum sample taken from the patient;   (c) a diagnostic reagent that can measure an expression level of TNF-α in the blood plasma or blood serum sample taken from the patient; and   (d) an analysis unit for comparison of the expression levels of sICAM-5, TARC, and TNF-α to expression levels of normal controls.   
     
     
         21 . A method of treating a seizure disorder in a patient diagnosed with a seizure disorder in accordance with the method of  claim 18 , the method comprising administering a therapy for epilepsy to the patient. 
     
     
         22 . The method of  claim 21 , wherein the normal control is selected based on a characteristic selected from the group consisting of sex, age, race, and combinations thereof. 
     
     
         23 . The method of  claim 21 , wherein the therapy for epilepsy is a therapeutically effective dose of an anti-epileptic compound selected from the group consisting of phenytoin, fosphenytoin, carbamazepine, clobazam, clonazepam, diazepam, divalproex, eslicarbazepine acetate, ethosuxemide, ezogabine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, lorazepam, oxcarbazepine, phenobarbital, primidone, tiagabine, topiramate, valproic acid, zonisamide and pharmaceutically acceptable salts, prodrugs, and derivatives thereof. 
     
     
         24 . The method of  claim 21 , further comprising using EEG to treat a patient with seizure disorder. 
     
     
         25 . The method of  claim 21 , further comprising using MM or other diagnostic test to treat a patient with seizure disorder.