Blood biomarker that predicts persistent cognitive dysfunction after concussion

1. A method for diagnosing and treating a computed tomography (CT)-negative mild traumatic brain injury (mTBI) in a subject, said method comprising:

(a) obtaining a blood, serum, or plasma sample from said subject within 24 hours of the injury;

(b) contacting said sample with an antibody that specifically binds to a calpain-generated neoepitope of calpain-cleaved all-spectrin N-terminal fragment (SNTF) to form an antibody-SNTF complex;

(c) measuring the amount of the antibody-SNTF complex, to determine SNTF concentration in the subject's serum or plasma;

(d) comparing said serum or plasma concentration of SNTF in the subject to that of a pre-determined standard;

(e) diagnosing said mTBI in said subject, wherein an elevated SNTF level relative to the standard indicates the severity of mTBI; and

(f) treating said mTBI in said subject.

2. The method of claim 1 , wherein said standard is determined by measuring SNTF concentration in a subject having sustained an orthopedic injury or in a normal uninjured subject.

3. The method of claim 1 , wherein said standard is determined by measuring SNTF concentrations in a subject or pool of subjects having sustained an orthopedic injury or in a normal uninjured subject or pool of subjects.

4. The method of claim 1 , further comprising the step of assessing the subject by diffusion tensor imaging (DTI).

5. The method of claim 4 , wherein said diffusion tensor imaging (DTI) measures the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC).

6. The method of claim 1 , further comprising the step of assessing the subject by diffusion tensor imaging (DTI) and by neurobehavioral analyses.

7. The method of claim 1 , wherein said mTBI is a concussion.

8. The method of claim 1 , wherein said mTBI is caused by a head injury.

9. The method of claim 8 , wherein said head injury is blunt trauma, acceleration, or deceleration forces.

10. The method of claim 1 , further comprising the steps of:

(g) obtaining a blood, serum, or plasma sample from said subject, during or after treatment of said subject for mTBI;

(h) repeating steps (b)-(d), for the sample obtained during or after treatment of said subject; and

(i) monitoring the response to the treatment in the subject having suffered from mTBI, wherein decreasing SNTF levels indicates a subsequent decreased risk of brain damage, long-term functional disability, or long-term neurological dysfunction.

11. A method for identifying and treating a subject at risk of suffering from a mild traumatic brain injury (mTBI)-associated abnormality in white matter structure or a long-term dysfunction, said method comprising:

(a) obtaining a blood, serum, or plasma sample from said subject within 24 hours of the injury;

(b) contacting said sample with an antibody that specifically binds to a calpain-generated neoepitope of calpain-cleaved all-spectrin N-terminal fragment (SNTF) to form an antibody-SNTF complex;

(c) measuring the amount of the antibody-SNTF complex, to determine SNTF concentration in the subject's serum or plasma;

(d) comparing said serum or plasma concentration of SNTF in the subject to that of a pre-determined standard;

(e) identifying a subject at risk of suffering from a mild traumatic brain injury (mTBI)-associated abnormality in white matter structure or a long-term dysfunction, wherein an elevated SNTF level relative to the standard indicates an elevated risk of suffering from a mild traumatic brain injury (mTBI)-associated abnormality in white matter structure or a long-term dysfunction; and

(f) treating said mTBI in said subject.

12. The method of claim 11 , wherein said standard is determined by measuring SNTF concentration in a subject having sustained an orthopedic injury or in a normal uninjured subject.

13. The method of claim 11 , further comprising the steps of:

(g) obtaining a blood, serum, or plasma sample from said subject, during or after treatment of said subject for mTBI;

(h) repeating steps (b)-(d), for the sample obtained during or after treatment of said subject; and

(i) monitoring the response to the treatment in the subject having suffered from mTBI, wherein decreasing SNTF levels indicates a subsequent decreased risk of brain damage, long-term functional disability, or long-term neurological dysfunction.

14. A method for providing a prognosis for and treating a subject having suffered from a computed tomography (CT)-negative mild traumatic brain injury (mTBI), said method comprising:

(a) obtaining a blood, serum, or plasma sample from said subject within 24 hours of the injury;

(b) contacting said sample with an antibody that specifically binds to a calpain-generated neoepitope of calpain-cleaved all-spectrin N-terminal fragment (SNTF) to form an antibody-SNTF complex;

(c) measuring the amount of the antibody-SNTF complex, to determine SNTF concentration in the subject's serum or plasma;

(d) comparing said serum or plasma concentration of SNTF in the subject to that of a pre-determined standard;

(e) providing a prognosis for said subject having suffered from said mTBI, wherein an elevated SNTF level relative to the standard indicates an elevated risk of long-term neurological dysfunction of the mTBI evolving to brain damage; and

(f) treating said mTBI in said subject.

15. The method of claim 14 , further comprising the steps of:

(g) obtaining a blood, serum, or plasma sample from said subject, during or after treatment of said subject for mTBI;

(h) repeating steps (b)-(d), for the sample obtained during or after treatment of said subject; and

(i) monitoring the response to the treatment in the subject having suffered from mTBI, wherein decreasing SNTF levels indicates a subsequent decreased risk of brain damage, long-term functional disability, or long-term neurological dysfunction.