Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage.

There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N = 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6-8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0-14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N = 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0-1, 2-3, 4-5, 6-8, and 10-14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p = 0.0003) and neutrophil (p = 0.0002) counts during post-SAH days 0-14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2-3, p = 0.018), blood MMP-9 (post-SAH days 4-5, p = 0.045), and CSF MMP-9 (post-SAH days 2-3, p = 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6-8, R = 0.39; p = 0.055; post-SAH days 10-14, R = 0.79; p < 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4-5, R = 0.72; p = 0.0002). Elevation of CSF MMP-9 during post-SAH days 0-14 is associated with poor 3-month outcome (p = 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.

[The war invalid laws of 1920 on support for disabled soldiers and their surviving relatives in the provinces of southern Jutland, and the disabled soldiers' board of Sønderborg]. / Krigsinvalidelovene af 1920 om understottelse til militaere invalider og sadannes efterladte i de sønderjyske landsdele og Invalidenaevnet i Sønderborg.

After the reunion between Denmark and Southern Jutland in 1920, the Danish state took over the obligations towards disabled soldiers and surviving relatives to dead soldiers from this province, serving in the German army during World War I. In 1920, the regulations were fixed by law, giving rise to Invalide-noevnet (disabled soldiers' board) in Sonderborg. The board dealt with altogether 6400 applications for invalidity pension and 4000 applications from surviving relatives. In Sonderborg an institution for disabled soldiers (Krigsinvalideskolen) was founded, including a hospital department and workshops for training and rehabilitation as well as production of bandages. A survey is given of these activities. The author next uncovers the story behind one of 9 names on a war memorial tablet, representing soldiers from the parish of Lebol, Sydals, who died in German war service during World War I. The medical record for this dead soldier is given and the family's fruitless efforts for 18 years to obtain pension are reported in details.