Role of cathepsin K in the development of chronic subdural hematoma.

Despite extensive investigations, the process of development of chronic subdural hematoma (CSDH) is not known. The present study aims to investigate CSDH by measuring biomarkers in it, gas analysis, and immunohistochemical examination. A total of 42 patients with symptomatic CSDH who underwent burr-hole drainage were enrolled. Intraoperatively, hematoma fluid and peripheral venous blood (PVCSDH) were simultaneously collected. As controls, peripheral venous blood (PVControl) and intracranial cerebrospinal fluid (CSF) were collected from other subjects during other surgeries. CatK, lipocalin-type prostaglandin D synthase (PGDS), and cystatin C (CysC) present in these specimens were measured using enzyme-linked immunosorbent assay. Data obtained were statistically analyzed after age correction. In 15 patients, gas analysis was performed for CSDH and PVCSDH. Furthermore, immunohistochemical examination for the outer membrane was performed for four patients. CatK, PGDS, and CysC levels were markedly elevated in the CSF and CSDH. CatK levels in PVCSDH were significantly higher than in PVControl (P<0.0001). In contrast, CysC levels in PVCSDH were significantly lower than in PVControl (P=0.004). The gas analysis revealed that the internal environment of CSDH is characterized by marked hypoxia, hypoglycemia, and lactic acidosis. Furthermore, the outer membrane consistently showed a diffuse staining for CatK. Based on these, CatK was thought to play a role in the development of CSDH, with the levels in peripheral venous blood elevated in patients with CSDH.

Predictive (subtle or overlooked) initial head CT findings in patients who develop delayed chronic subdural hematoma.

With the aging population, the incidence of chronic subdural hematoma (CSDH) is expected to rise. Once symptomatic the morbidity from CSDH is not insignificant. We studied patients who had a minor head injury and CT brain scan prior to developing CSDH to determine if there were any predictors on these scans for subsequent development of a CSDH. A retrospective review was performed on all patients operated for CSDH over a 3-year period and a review performed on those who had imaging studies at the time of a preceding minor head injury. Seven of 37 patients had CT scans prior to developing CSDH. All had evidence of small increases in CSF intensity on the side or sides of the subsequent CSDH. In conclusion, in those patients with a history of minor head injury prior to developing a CSDH, CT brain demonstrated small increases in cerebral spinal fluid (CSF) intensity on the side or sides of the subsequent CSDH. Recognizing this finding may be helpful in monitoring these patients or initiating medical therapy.

Chronic Subdural Hematoma Preceded by High-Impact Trauma: Does the Intensity of Trauma Influence the Pathogenesis of Traumatic Chronic Subdural Hematoma?

AIM: The purpose of this study was to investigate whether the intensity of trauma influences the pathogenesis of traumatic chronic subdural hematoma (CSDH). MATERIAL AND METHODS: Thirty-one patients treated surgically for traumatic CSDH were divided into high-impact and lowimpact groups according to the intensity of trauma. They were respectively evaluated with respect to clinical and radiological findings at presentation, and the subdural concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and beta-trace protein (ΒTP) [a highly specific protein in the cerebrospinal fluid (CSF)] related to the pathogenesis of CSDH. If ΒTP (subdural fluid/serum) was > 2, an admixture of CSF to the subdural fluid was indicated. RESULTS: The ΒTP (subdural fluid/serum) was > 2 in all patients with a traumatic CSDH. The mean concentration of subdural ΒTP in the high-impact group was higher than in the low-impact group (6.1 mg/L versus 3.9 mg/L), and the difference was statistically significant (p=0.02). In addition, mean concentrations of IL-6, IL-8 and VEGF were higher in the high-impact group, as compared to the low-impact group, though the differences did not reach statistical significance. CONCLUSION: Trauma may be related to CSF leakage into the subdural space in CSDH, and the intensity of trauma may influence the amount of CSF leakage. Although there is no direct correlation between the amount of CSF leakage and other subdural molecules, the intensity of trauma may be associated with larger concentrations of molecules in traumatic CSDH.

Limitations of T2*-Gradient Recalled-Echo and Susceptibility-Weighted Imaging in Characterizing Chronic Subdural Hemorrhage in Infant Survivors of Abusive Head Trauma.

A possible misconception among radiologists is that chronic subdural hemorrhage should show some degree of blooming on T2*-gradient recalled-echo or susceptibility-weighted sequences such as SWI and susceptibility-weighted angiography, which is not necessarily true. We present 5 cases of chronic subdural hemorrhages in infants, demonstrating intensity near or greater than that of CSF with variable amounts of hemosiderin staining along the neomembranes. We review the physiology and MR imaging physics behind the appearance of a chronic subdural hemorrhage, highlighting that the absence of a BBB can allow hemosiderin to be completely removed from the subdural compartment. Finally, we stress the importance of reviewing all multiplanar sequences for the presence of neomembranes, which can be quite subtle in the absence of hemosiderin staining and are critical for making the diagnosis of chronic subdural hemorrhage.

Glycosaminoglycans in subdural fluid and CSF after meningeal injury.

BACKGROUND: Inflammatory mechanisms have an acknowledged role in the progression of chronic subdural hematoma (CSDH) and in tissue response after subarachnoid hemorrhage (SAH). The participation of extracellular matrix, especially glycosaminoglycans, in the cellular events during tissue repair is known to be important. We studied the production of glycosaminoglycans after two types of meningeal injury-one caused by rupture of the dural border cell layer after head injury, and the other caused by SAH. METHODS: Patients with CSDH (n = 28), subdural effusion (n = 8), and SAH (n = 33) were included in the study. Samples from subdural fluid or cerebrospinal fluid (CSF) were assayed for hyaluronic acid (HA) with an enzyme-linked assay and for sulfated glycosaminoglycans (sGAGs) with a dye-binding assay. RESULTS: The median HA concentration was 3021 (range, 408-14,012) ng/ml in the CSDH fluid, 668 (392-3607) ng/ml in the effusion fluid, and 21.7 (5.8-195) ng/ml in the serum. In lumbar CSF after SAH, the median HA concentration was 246 (47-3686) ng/ml being 1.5-fold higher than that in control CSF. The median sGAG concentration was 52.8 (0-144) µg/ml in CSDH fluid, but only 5.32 (0-20.5) µg/ml in the effusion fluid, where the concentration was similar to that in the serum. CONCLUSIONS: We found high, but variable, concentrations of sGAGs and HA in the CSDH and effusion fluid after head injury and HA in the CSF after SAH. Our results show that HA and sGAGs are induced after meningeal injury and that these proteins may participate in a reactive process.

Chronic subdural haematoma evolving from traumatic subdural hydroma.

OBJECTIVE: This study aimed to investigate the incidence and clinical characteristics of chronic subdural haematoma (CSDH) evolving from traumatic subdual hydroma (TSH). METHODS: The clinical characteristics of 44 patients with CSDH evolving from TSH were analysed retrospectively and the relevant literature was reviewed. RESULTS: In 22.6% of patients, TSH evolved into CSDH. The time required for this evolution was 14-100 days after injury. All patients were cured with haematoma drainage. CONCLUSIONS: TSH is one possible origin of CSDH. The clinical characteristics of TSH evolving into CSDH include polarization of patient age and chronic small effusion. The injuries usually occur during deceleration and are accompanied by mild cerebral damage.

Cerebrospinal fluid leakage into the subdural space: possible influence on the pathogenesis and recurrence frequency of chronic subdural hematoma and subdural hygroma.

OBJECT: The purpose of this study was to clarify whether cerebrospinal fluid (CSF) leakage into the subdural space is involved in the genesis of chronic subdural hematoma (CSDH) and subdural hygroma (SH) and to clarify whether this leakage of CSF into the subdural space influences the postoperative recurrence rate of CSDH and SH. METHODS: In this prospective observational study, 75 cases involving patients treated surgically for CSDH (67 patients) or SH (8 patients) were evaluated with respect to clinical and radiological findings at presentation, the content of beta -trace protein (beta TP) in the subdural fluid (betaTPSF) and serum (betaTPSER), and the CSDH/SH recurrence rate. The betaTPSF was considered to indicate an admixture of CSF to the subdural fluid if betaTPSF/betaTPSER>2. RESULTS: The median beta TPSF level for the whole patient group was 4.29 mg/L (range 0.33-51 mg/L). Cerebrospinal fluid leakage, as indicated by betaTPSF/betaTPSER>2, was found to be present in 93% of the patients with CSDH and in 100% of the patients with SH (p=0.724). In patients who later had to undergo repeated surgery for recurrence of CSDH/SH, the betaTPSF concentrations (median 6.69 mg/L, range 0.59-51 mg/L) were significantly higher (p=0.04) than in patients not requiring reoperation (median 4.12 mg/L, range 0.33-26.8 mg/L). CONCLUSIONS: As indicated by the presence of betaTP in the subdural fluid, CSF leakage into the subdural space is present in the vast majority of patients with CSDH and SH. This leakage could be involved in the pathogenesis of CSDH and SH. Patients who experience recurrences of CSDH and SH have significantly higher concentrations of betaTPSF at initial presentation than patients not requiring reoperation for recurrence. These findings are presented in the literature for the first time and have to be confirmed and expanded upon by further studies.

Specific pattern of growth factor distribution in chronic subdural hematoma (CSH): evidence for an angiogenic disease.

BACKGROUND: The aim of this prospective study was to evaluate the significance of growth factors as determinants of the pathological degree of neovascularisation found in the parietal neomembrane of chronic subdural hematoma (CSH). Thus far the pathogenesis of the vascularisation has not been elucidated. METHOD: The concentrations of growth factors, i.e. vascular endothelial derived growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) were determined using ELISA technique in hematoma fluid and serum of 20 patients with uni- or bilateral CSH. For comparison, growth factor concentrations were determined in cerebrospinal fluid (CSF) of patients undergoing diagnostic myelography. FINDINGS: Concentrations of VEGF and bFGF were significantly (p < 0.001) increased in the hematoma fluid as compared with serum (VEGFh = 8.142 pg/ml, bFGFh = 8.7 pg/ml versus VEGFS = 368 pg/ml, bFGF, = 1.8 pg/ml). In contrast, PDGF concentration was significantly (p < 0.001) lower in the hematoma (PDGFh = 3,456 pg/ml versus PDGF, = 31,937 pg/ml). The serum levels for VEGF, bFGF and PDGF in CSH patients lay within the range of normal volunteers. No growth factors were found in normal CSF. INTERPRETATION: These results reveal a specific distribution pattern of growth factors in CSH patients. This pattern suggests that CSH may be considered a member of the angiogenic disease family.