αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients.
In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] score <or=8) who underwent ventriculostomy. Patients requiring CSF drainage for other medical reasons served as controls. CSF samples were taken at admission and every 6 h thereafter for a maximum of 7 days and assessed using novel quantitative fragment-specific ELISAs for SBDPs. Outcome was assessed using the 3-month Glasgow Outcome Scale. Mean CSF levels of SBDPs were significantly higher in TBI patients than in controls at all time points examined. Different temporal release patterns of CSF SBDP145 and SBDP120 were observed. SBDP145 provided accurate diagnoses at all time points examined, while SBDP120 release was more accurate 24 h after injury. Within 24 h after injury, SBDP145 CSF concentrations significantly correlated with GCS scores, while SBDP120 levels correlated with age. SBDP levels were significantly higher in patients who died than in those who survived. SBDP145 levels (>6 ng/mL) and SBDP120 levels (>17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.
Mondello
Stefania
S
Department of Clinical Programs and Center of Innovative Research, University of Florida, Gainesville, Florida, USA.
Robicsek
Steven A
SA
Gabrielli
Andrea
A
Brophy
Gretchen M
GM
Papa
Linda
L
Tepas
Joseph
J
Robertson
Claudia
C
Buki
Andras
A
Scharf
Dancia
D
Jixiang
Mo
M
Akinyi
Linnet
L
Muller
Uwe
U
Wang
Kevin K W
KK
Hayes
Ronald L
RL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D011379:Prognosis; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D012720:Severity of Illness Index; D013049:Spectrin / Q000134:cerebrospinal fluid*; D015996:Survival Rate; D055815:Young Adult
D015415:Biomarkers; D010446:Peptide Fragments; D020033:Protein Isoforms; D013049:Spectrin
N Engl J Med. 2007 Nov 29;357(22):2277-84
18046031
Lancet. 1974 Jul 13;2(7872):81-4
4136544
J Neurotrauma. 2007 Feb;24(2):354-66
17375999
Lancet. 1978 Jan 21;1(8056):113-5
87549
Neurosurgery. 1999 Sep;45(3):477-83
10493369
Acta Paediatr. 1996 Apr;85(4):485-9
8740311
Brain Res. 1971 May 7;28(2):351-4
5113526
Lancet. 1991 Mar 2;337(8740):535-8
1671900
J Trauma. 2002 Apr;52(4):798-808
11956409
J Neurotrauma. 1997 Jun;14(6):369-83
9219852
J Neurotrauma. 1995 Aug;12(4):565-72
8683607
J Neurotrauma. 2000 Aug;17(8):641-7
10972241
JAMA. 2004 Jun 2;291(21):2531-2
15173131
J Neurotrauma. 1997 Jul;14(7):419-40
9257661
Br J Neurosurg. 1999 Feb;13(1):56-9
10492686
Neurosurgery. 2001 Dec;49(6):1490; author reply 1492-3
11859838
J Neurotrauma. 2009 Apr;26(4):471-9
19206997
Epilepsia. 2003;44(s10):2-10
14511388
J Neuropathol Exp Neurol. 2009 Mar;68(3):241-9
19225412
Stroke. 1991 Oct;22(10):1254-8
1926235
J Neurotrauma. 2007 Feb;24(2):270-80
17375991
Acta Neurochir (Wien). 1976;34(1-4):45-55
961490
Brain Inj. 2000 Oct;14(10):851-7
11076132
Pediatr Radiol. 2003 Jul;33(7):442-9
12743660
J Neurosurg. 2003 Oct;99(4):666-73
14567601
Sheng Li Ke Xue Jin Zhan. 2000 Jul;31(3):217-21
12545707
J Cell Biol. 1986 Jun;102(6):2088-97
3519621
J Neurosurg. 1981 Jun;54(6):751-62
7241184
J Cereb Blood Flow Metab. 2003 Jan;23(1):34-42
12500089
J Neurotrauma. 2004 Sep;21(9):1131-40
15453984
Arch Neurol. 1991 Jun;48(6):580-5
2039378
Acta Neurochir Suppl. 1998;71:117-9
9779161
Br J Neurosurg. 1996 Oct;10(5):471-6
8922706
Neurosurgery. 2001 Jun;48(6):1255-8; discussion 1258-60
11383727
J Biol Chem. 1998 Aug 28;273(35):22490-7
9712874
J Cardiothorac Vasc Anesth. 1996 Jan;10(1):120-6
8634377
J Cereb Blood Flow Metab. 2004 Jan;24(1):98-106
14688621
J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):161-2
14707332
Lancet. 2000 Sep 9;356(9233):923-9
11036909
Brain Inj. 1996 Jan;10(1):47-54
8680392
J Neurotrauma. 2005 Feb;22(2):252-65
15716631
J Neurotrauma. 1995 Aug;12(4):555-64
8683606
BMJ. 2007 Dec 8;335(7631):1182-4
18063642
J Neurosurg. 2007 Oct;107(4):792-6
17937225
Neurosci Lett. 1993 Oct 1;160(2):139-44
8247344
J Neurotrauma. 2007 Jun;24(6):960-78
17600513
Acta Neurochir (Wien). 2005 Aug;147(8):855-61
15924207
Expert Rev Proteomics. 2005 Aug;2(4):603-14
16097892
J Neurochem. 2000 Sep;75(3):1264-73
10936210
Lancet. 1977 Apr 23;1(8017):878-81
67287
Annu Rev Neurosci. 1987;10:269-95
3551759
J Neurotrauma. 2004 Oct;21(10):1443-56
15672634
J Neurosurg Sci. 2006 Jun;50(2):25-31
16841024
J Neurotrauma. 2007 Feb;24(2):259-69
17375990
J Neurosurg. 1999 Nov;91(5):875-7
10541249
J Neurochem. 2001 Sep;78(6):1297-306
11579138
J Trauma. 1999 Dec;47(6):1126-30
10608545
J Head Trauma Rehabil. 1999 Dec;14(6):602-15
10671706
J Neuropsychiatry Clin Neurosci. 2007 Winter;19(1):5-20
17308222
Neurochem Res. 2007 Dec;32(12):2006-14
17401646
Neurosurgery. 1990 Sep;27(3):429-32
2234337
Expert Opin Med Diagn. 2008 Aug;2(8):937-45
23495867
Mol Chem Neuropathol. 1993 Apr;18(3):247-56
8507303
Acta Neurochir (Wien). 1997;139(12):1161-4; discussion 1165
9479423
Neuropathol Appl Neurobiol. 1996 Dec;22(6):509-13
9004238
J Neurol Neurosurg Psychiatry. 1998 Dec;65(6):930-2
9854976
Neurosurgery. 2000 Jan;46(1):70-5; discussion 75-7
10626937
Neurosurgery. 2001 Dec;49(6):1490-1; author reply 1492-3
11859837
Neurosurgery. 2005 Dec;57(6):1173-82; discussion 1173-82
16331165
J R Coll Physicians Lond. 1975 Apr;9(3):231-7
1142324
Crit Care Med. 2010 Jan;38(1):138-44
19726976
Trends Neurosci. 2000 Feb;23(2):59
10652545
J Neurotrauma. 1999 Sep;16(9):749-61
10521135
Clin Chim Acta. 1978 Jan 16;82(3):259-70
563780
J Neuropathol Exp Neurol. 1996 Jul;55(7):850-60
8965100
Lancet. 1994 Oct 15;344(8929):1055-6
7523810