Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

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  • 1 Intensive Care Department,
  • 2 Fundación Instituto de Investigación Sanitaria Islas Baleares (IdISBa), and
  • 3 Department of Neurological Surgery, Son Espases University Hospital, Palma de Mallorca, Spain; and
  • 4 The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida
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OBJECTIVE

The objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury.

METHODS

This is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended.

RESULTS

A total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI.

CONCLUSIONS

In this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

ABBREVIATIONS ASC = apoptosis-associated speck-like protein containing a caspase recruitment domain; AUC = area under the curve; ELISA = enzyme-linked immunosorbent assay; GCS = Glasgow Coma Scale; GOSE = Glasgow Outcome Scale–Extended; ICP = intracranial pressure; IL = interleukin; NICU = neurosurgical ICU; NLR = nucleotide oligomerization domain–like receptor; TBI = traumatic brain injury.

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Contributor Notes

Correspondence Juan Pablo de Rivero Vaccari: Lois Pope LIFE Center, Miami, FL. jderivero@med.miami.edu.

INCLUDE WHEN CITING Published online May 1, 2020; DOI: 10.3171/2020.2.JNS193079.

Disclosures Dr. de Rivero Vaccari is a cofounder and managing member of InflamaCORE, LLC, and has licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. He is a scientific advisory board member of ZyVersa Therapeutics.

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