Management of spontaneous intracranial hypotension - Transorbital ultrasound as discriminator.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) is most commonly caused by cerebrospinal fluid (CSF) leakage. Therefore, we hypothesised that patients with orthostatic headache (OH) would show decreased optic nerve sheath diameter (ONSD) during changes from supine to upright position. METHODS: Transorbital B-mode ultrasound was performed employing a high-frequency transducer for ONSD measurements in the supine and upright positions. Absolute values and changes of ONSD from supine to upright were assessed. Ultrasound was performed in 39 SIH patients, 18 with OH and 21 without OH, and in 39 age-matched control subjects. The control group comprised 20 patients admitted for back surgery without headache or any orthostatic symptoms, and 19 healthy controls. RESULTS: In supine position, mean ONSD (±SD) was similar in patients with (5.38±0.91 mm) or without OH (5.48±0.89 mm; p=0.921). However, in upright position, mean ONSD was different between patients with (4.84±0.99 mm) and without OH (5.53±0.99 mm; p=0.044). Furthermore, the change in ONSD from supine to upright position was significantly greater in SIH patients with OH (-0.53±0.34 mm) than in SIH patients without OH (0.05±0.41 mm; p≤0.001) or in control subjects (0.01±0.38 mm; p≤0.001; area under the curve: 0.874 in receiver operating characteristics analysis). CONCLUSIONS: Symptomatic patients with SIH showed a significant decrease of ONSD, as assessed by ultrasound, when changing from the supine to the upright position. Ultrasound assessment of the ONSD in two positions may be a novel, non-invasive tool for the diagnosis and follow-up of SIH and for elucidating the pathophysiology of SIH.

Optic Nerve Sheath Diameter Measurement to Identify High-Risk Patients for Spinal Ischemia after Endovascular Thoracoabdominal Aortic Aneurysm Repair.

BACKGROUND & PURPOSE: Thoracic endovascular aortic repair (TEVAR) is associated with a reasonable risk of spinal ischemia. As cerebrospinal fluid pressure (CSFP) is correlated with the rate of paraplegia, a non-invasive method to estimate CSFP could help to estimate the patient's individual risk and guide the therapeutic approach. The quantification of the optic nerve sheath diameter (ONSD) using ocular sonography (OS) could be a suitable technique and was examined in the present study. METHODS: 28 patients with TEVAR were included. Five consecutive measurements of the ONSD were performed in each patient. The first before the intervention ("baseline"), the next immediately postinterventional at the intensive care unit (post1), measurements 3, 4 (post2, post3) on day 1 and 2 after the intervention and number 5 (post4) before discharge. Statistical analysis was done using the Wilcoxon-test. A p-value < 0.05 was considered statistically significant. RESULTS: A significant increase between baseline and post1-measurements (right eye: p = 0.006; left eye: p = 0.02) could be detected. A significant decrease was detected between post1 and post3 (right eye: p = 0.02; left eye: p < 0.01). A group of 5 patients had an additional increase of ONSD from post1 to post2, one of these patients developed a permanent paraplegia. Patients with spinal catheters had significantly lower ONSDs at nearly all time points. CONCLUSION: The present study is the first to prospectively examine and prove the possibility to monitor CSFP changes in patients with TEVAR associated transient spinal edema using OS. Systematic factors as artificial ventilation and body positioning did not have a significant effect.

Low endogenous recanalization in embolic central retinal artery occlusion--the retrobulbar "spot sign".

BACKGROUND AND PURPOSE: Central retinal artery occlusion (CRAO) is most often indirectly diagnosed by lack of retinal perfusion. Direct embolus characterization may help to understand the natural course and low response to treatment. In a previous study we identified a hyperechoic signal within the optic nerve and in the central retinal artery ("spot sign"). METHODS: In this study we performed a follow-up investigation in 7 patients with CRAO and positive spot sign indicating the embolic cause of the occlusion after a median interval of 17 months (range 11-38 months) using a battery of tests (ocular color-coded sonography, optic coherence tomography [OCT], fundoscopy, amongst others). RESULTS: The spot sign persisted in all patients, none had high-grade internal carotid artery stenosis, stroke or transient ischemic attacks. Four patients were completely blind, 3 patients were able to recognize hand movements. OCT demonstrated retinal atrophy, and fundoscopy revealed only minimal arterial perfusion. CONCLUSIONS: The hyperechoic spot sign may be an important predictive prognostic marker for persistent loss of vision. Its persistence may indicate calcified or cholesterol emboli and may explain the low therapeutic success rate to thrombolysis. Further studies on their origin and significance in atherosclerotic disease are warranted.

Comparative expression pattern of Matrix-Metalloproteinases in human glioblastoma cell-lines and primary cultures.

BACKGROUND: Glioblastomas (GBM), the most frequent malignant brain tumors in adults, are characterized by an aggressive local growth pattern and highly invasive tumor cells. This invasion is facilitated by expression of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases. They mediate the degradation of protein components of the extracellular matrix. Twenty-three family members are known. Elevated levels of several of them have been reported in GBM. GBM cell-lines are used for in vitro studies of cell migration and invasion. Therefore, it is essential to know their MMP expression patterns. Only limited data for some of the cell-lines are published, yet. To fill the gaps in our knowledge would help to choose suitable model systems for analysis of regulation and function of MMPs during GBM tumorigenesis, cell migration and invasion. FINDINGS: We analysed MMP-1, -8, -9, -10, -11, -13, -17, -19, -20, -21, -23, -24, -26, -27, and MMP-28 expression in seven GBM cell-lines (SNB-19, GaMG, U251, U87, U373, U343, U138) and in four primary cell cultures by semiquantitative RT-PCR, followed changes in the MMP expression pattern with increasing passages of cell culture and examined the influence of TNF-α and TGF-ß1 stimulation on the expression of selected MMPs in U251 and U373 cells.MMP-13, -17, -19 and -24 were expressed by all analyzed cell-lines, whereas MMP-20 and MMP-21 were not expressed by any of them. The other MMPs showed variable expression, which was dependent on passage number. Primary cells displayed a similar MMP-expression pattern as the cell-lines. In U251 and U373 cells expression of MMP-9 and MMP-19 was stimulated by TNF-α. MMP-1 mRNA expression was significantly increased in U373 cells, but not in U251 cells by this cytokine. Whereas TGF-ß1 had no impact on MMP expression in U251 cells, it significantly induced MMP-11 and MMP-24 expression in U373 cells. CONCLUSIONS: Literature-data and our own results suggest that the expression pattern of MMPs is highly variable, dependent on the cell-line and the cell-culture conditions used and that also regulation of MMP expression by cytokines is cell-line dependent. This is of high impact for the transfer of cell-culture experiments to clinical implementation.