Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha (TNF alpha). Increased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebrospinal fluid (CSF) samples were collected from 22 consecutively enrolled patients with SAH and from 10 non-SAH patients (controls). The CSF samples were studied using immunoassays for IL-1Ra and TNF alpha to investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra levels were significantly higher in patients with SAH who were in poor clinical condition on admission than in those who were in good condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra and TNF alpha were detected during Days 4 through 10 in patients suffering from SAH who eventually had a poor outcome (p < 0.05). Patients with good outcomes and control patients had low levels of these cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. This finding indicates that patients in poor clinical condition have a labile biochemical state in the brain that is reflected in increased cytokine levels following the surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise, leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic brain injuries. The present study shows that levels of these cytokines increase after SAH occurs and that high cytokine levels correlate with brain damage. It is therefore likely that fever, leukocytosis, and nitric oxide synthesis are also mediated by IL-1 in patients suffering from SAH and it is probable that the inflammatory mediators contribute to brain damage.
Gamma knife surgery is an effective treatment for DAVSs, with a low risk of complications. Major disadvantages of this therapy include the time elapsed before obliteration and the possibility that not all shunts will be obliterated. Cortical venous drainage from a DAVS, a risk factor for intracranial hemorrhage, is therefore a relative contraindication. Consequently, GKS can be used in the treatment of both benign DAVSs with subjectively intolerable bruit and aggressive DAVSs not responsive to endovascular treatment or surgery.
Object. The purpose of this study was to assess the long-term treatment efficacy and morbidity of patients who undergo gamma knife radiosurgery (GKS) for craniopharyngioma. Methods. Twenty-one consecutive Swedish patients were evaluated retrospectively: 11 children (≤ 15 years) and 10 adults. The time from diagnosis to the most recent follow-up imaging study was 6.3 to 34.3 years (mean 18.2 years, median 16.8 years). Tumor volumes and morbidity from GKS or other treatments were assessed at the time of the most recent imaging study or at the time of a subsequent new treatment. The observation period ranged from 0.5 to 29 years (mean 7.5 years, median 3.5 years). The prescription dose ranged from less than 3 Gy to 25 Gy. The mean tumor volume was 7.8 cm3 (range 0.4–33 cm3). There were 22 tumors in 21 patients treated with GKS. Five of these tumors were reduced in size, three were unchanged, and 14 increased. Tumor progression correlated with a low dose to the tumor margin. Eleven (85%) of 13 tumors that received a dose of less than 6 Gy to the margin increased in size, whereas only three (33%) of nine tumors that received 6 Gy increased. This difference was statistically significant (p = 0.01). In five of six patients tumors that became smaller after GKS there were no recurrences within a mean follow-up period of 12 years. Nine (82%) of 11 tumors in children ultimately increased after GKS, compared with five (50%) of 10 in adults. In eight patients there was a deterioration of visual function. In all except one this could be related to a volume increase but radiation-induced damage could not be excluded as a factor in any of them. Four patients developed pituitary deficiencies. Conclusions. Gamma knife radiosurgery is effective in controlling growth of craniopharyngiomas with a minimum dose of 6 Gy. The findings also suggest that other stereotactic techniques, such as cyst aspiration and intracystic treatment, are only of value in reducing tumor volume in preparation for safe GKS.
Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10−12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.
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