Marian Christoph Neidert

Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fishers exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8-14 (8-14 versus 3-7, p = 0.016; 15 versus 3-7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8-14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3-7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8-14. To clarify and strengthen these observations, prospective, randomized trials are needed.

Soluble α-klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas.

OBJECTIVE Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. DESIGN Prospective controlled study. METHODS We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. RESULTS Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P<0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. CONCLUSION High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

Hydrocephalus after resection and adjuvant radiochemotherapy in patients with glioblastoma

OBJECTIVE Glioblastomas are the most common primary malignant brain tumors in adults with a poor prognosis. The current study sought to identify risk factors in glioblastoma patients that are closely associated with communicating hydrocephalus. METHODS We retrospectively analyzed data from 151 patients who were diagnosed with a glioblastoma between 2007 and 2011 and underwent complete surgical resection closely followed by adjuvant radiochemotherapy. RESULTS We observed a significant tendency toward communicating hydrocephalus in cases of ventricular opening during surgical tumor resection (Fishers exact test p<0.001) and a noticeable, although not statistically significant, correlation between the onset of communicating hydrocephalus and evidence of leptomeningeal tumor dissemination (Fishers exact test p=0.067). Additionally, there was a trend toward frontal tumor location and a larger tumor volume in patients with communicating hydrocephalus. The majority of patients suffering from communicating hydrocephalus received a cerebrospinal fluid (CSF) shunt implantation after radiation therapy (63.6%, Fishers exact test p=0.000). CONCLUSION We identified the following risk factors associated with the onset of communicating hydrocephalus in glioblastoma patients: ventricular opening during tumor resection and leptomeningeal tumor dissemination. Shunt implantation seems to be safe and effective in these patients.

Reduction of Thromboembolic Events in Meningioma Surgery: A Cohort Study of 724 Consecutive Patients

Background Meningiomas are associated with the highest postoperative rate of venous thromboembolic events (VTE) among all intracranial tumors. The aim of this study is to compare two entirely different VTE prophylaxis regimens in 724 consecutive patients undergoing meningioma surgery. Methods Two cohorts at a single institution treated with different regimens to prevent VTE were reviewed retrospectively. Cohort A (n = 482; 314 females, mean age 57 years, range: 11–87 years) received our institutional regimen during the years 1999–2006, consisting of low-molecular-weight heparin (LMWH) and compression stockings. For cohort B (n = 242; 163 females, mean age 56.8 years, range: 16–90 years), during the years 2008–2010, the management included intraoperative 10°–20° leg elevation with intermittent pneumatic compression (IPC), heparin and LMWH administration. We compared the incidence of the endpoints pulmonary embolism (PE), deep venous thrombosis (DVT), hemorrhage and death, taking into account several known associated risk factors. Results For all endpoints, we observed a more favorable outcome with the new regimen. The difference in incidence of PEs (cohort A: 38/482, 8%; cohort B: 6/242, 2.5%) reached statistical significance (p = 0.002). In general, patients with skull base meningiomas had a higher risk for PE (OR 2.77). Regarding VTE prophylaxis, an adjusted subgroup analysis suggests that the new regimen is particularly beneficial for patients with skull base meningiomas. Conclusions We recommend perioperative prophylaxis using a management composed of intraoperative leg-elevation, IPC, early heparin administration and LMWH to reduce the risk for PE.

Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome

The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2±standard error of the mean [SEM] 13.0ml) was significantly higher compared to patients without ACE inhibitors (140.4±SEM 6.2ml; p=0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p=0.079), especially in patients older than 80years (6/23, 26% versus 3/45, 7%; p=0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH.

Synchronous pituitary adenoma and pituicytoma.

Pituicytoma is a rare benign neoplasm arising in the sellar region, usually found in the posterior lobe and/or pituitary stalk. Here, we report the case of a 67-year-old woman who presented with bitemporal hemianopsia and visual impairment accompanied by mildly elevated prolactin. Pathologic and molecular examination of the tissue removed transsphenoidally revealed 2 distinct tumors: pituitary adenoma and pituicytoma. To the best of our knowledge, histologically proven pituicytoma and pituitary adenoma have never been reported together.

High-Frequency Intra-operative Ultrasound-Guided Surgery of Superficial Intra-cerebral Lesions via a Single-Burr-Hole Approach

The study described here examined the feasibility of using high-frequency intra-operative ultrasound (hfioUS) guidance to resect superficial intra-cerebral lesions through a single burr hole. A cohort of 23 consecutive patients with a total of 24 intra-cerebral lesions (9 intra-cerebral metastases, 8 gliomas, 4 infections, 2 lymphomas and 1 cavernoma) were studied. All lesions could be localized and successfully resected, biopsied or aspirated, and histopathological diagnoses were obtained in all cases. The mean operating time was 59.6 ± 23.9 min. The mean cross-sectional lesion size was 6.4 ± 7.6 cm(2), and the mean cortex surface-to-lesion distance was 0.6 ± 0.8 cm. Our results illustrate the feasibility of identifying and resecting superficial intra-cerebral lesions under hfioUS guidance via a single-burr-hole approach. We were able to achieve short resection times with no post-operative complications in all patients, favorable conditions under which to start adjuvant therapy when indicated.

Third-generation cephalosporins as antibiotic prophylaxis in neurosurgery: what's the evidence?

To analyze the role of third-generation cephalosporins as prophylactic antibiotics in neurosurgery. We reviewed the literature for data from randomized controlled trials (RCTs) on third-generation cephalosporins compared to other antibiotic regimen in neurosurgery. End point of the RCTs was the occurrence of surgical site infections (SSIs)--data were pooled in a fixed-effects meta-analysis. Five randomized controlled trials enrolling a total of 2209 patients were identified. The pooled odds ratio for SSIs (overall) with third-generation cephalosporins prophylaxis in the five RCTs was 0.94 (95% CI, 0.59-1.52; P=0.81). No significant difference between third-generation cephalosporins and alternative regimen was identified. When analyzing organ SSIs (osteomyelitis, meningitis, and others intracranial infections) in data derived from four RCTs (1596 patients), third-generation cephalosporins failed to show superiority (pooled odds ratio 0.88; 95% CI 0.45-1.74; P=0.72). Third-generation cephalosporin antibiotic prophylaxis fails to show superiority over conventional regimens regarding both incisional and organ related SSIs in neurosurgery.

Growth hormone secreting pituitary microadenomas and empty sella – An under-recognized association?

OBJECTIVE To describe an association of growth hormone (GH) secreting pituitary microadenomas and empty sella (ES), which has been described in case reports - the underlying mechanisms are unclear. METHODS We retrospectively analyzed patients operated for GH-producing pituitary adenomas between February 2004 and February 2009. Magnetic resonance imaging (MRI), computed tomography (CT) imaging, and pituitary function testing were performed. All cases underwent transsphenoidal surgery (TSS). Mean follow up was 38 months (range 12-80 months). RESULTS Out of 152 patients with acromegaly due to GH-producing pituitary adenomas (female:male=73:79; age range 17-63 years), 69 patients had microadenomas (45.4%; 38 females, 31 males). We found 14 cases (14/69, 20.3%), all microadenomas, with presurgical evidence of ES - 10 females (71%) and 4 males (29%) (female:male=2.5:1). When compared with 103 patients with GH-negative microadenomas treated in the same time period (ES in 4 of 103; 3.9%), ES was highly significantly associated with GH production by the microadenoma (p=0.001). In acromegalics with empty sella, no cases of ectopic adenoma were found. Postoperatively, GH and IGF-1 levels fell in all patients, and 7 cases had random GH and IGF-1 levels consistent with cure. CONCLUSION The combination of GH-producing microadenomas and empty, enlarged sella is not rare. In this setting, preoperative CT scans are very useful and the transsphenoidal approach is efficient and safe. The mechanism underlying the association of GH-producing microadenomas and empty sella remains unclear and requires further studies.

Interferon-β Modulates the Innate Immune Response against Glioblastoma Initiating Cells.

Immunotherapy targeting glioblastoma initiating cells (GIC) is considered a promising strategy. However, GIC are prone to evade immune response and there is a need for potent adjuvants. IFN-β might enhance the immune response and here we define its net effect on the innate immunogenicity of GIC. The transcriptomes of GIC treated with IFN-β and controls were assessed by microarray-based expression profiling for altered expression of immune regulatory genes. Several genes involved in adaptive and innate immune responses were regulated by IFN-β. We validated these results using reverse transcription (RT)-PCR and flow cytometry for corresponding protein levels. The up-regulation of the NK cell inhibitory molecules HLA-E and MHC class I was balanced by immune stimulating effects including the up-regulation of nectin-2. In 3 out of 5 GIC lines tested we found a net immune stimulating effect of IFN-β in cytotoxicity assays using NKL cells as effectors. IFN-β therefore warrants further investigation as an adjuvant for immunotherapy targeting GIC.