Proenkephalin as marker for severity of aneurysmal subarachnoid hemorrhage: a pilot study

Objective: Several biomarker have shown associations with severity, vasospasm, ischemic events or outcome in aneurysmal subarachnoid hemorrhage. Yet no biomarker is used in daily clinical routine. Previously encephalin peptides were described as new biomarkers in ischemic stroke and traumatic brain injury. We sought to evaluate the usefulness of Proenkephalin A, a precursor protein of encephalin peptides, as biomarker in aneurysmal subarachnoid hemorrhage. Method: Eighteen consecutive patients with aSAH had plasma PENK A levels measured with a validated chemiluminescence sandwich immunoassay. The association of PENK A levels at admission with severity of SAH according to the World Federation of Neurological Surgeons (WFNS) grade after resuscitation was the primary endpoint. Levels of PENK A are analyzed with respect to different clinical and radiological scores as well as between patients with ICH, intraventricular hemorrhage, hydrocephalus, brain edema, vasospasm and ischemia. Results: Good grade patients showed median PENK A levels of 73.9pmol/l (IQR 69-80.4) and poor grade patients 117pmol/l (IQR 86-149). PENK A levels are significantly associated with severity of SAH as graded on the WFNS scale (p=0.03). No other parameter had a significant association. Conclusions: PENK A might be a useful serum marker in aSAH. Yet, larger trials also with serial PENK A assessments are needed.

Is intracranial aneurysm rupture related to solar activity?

Objective: A number of intrinsic and extrinsic risk factors for the rupture of intracranial aneurysms have been identified. Still, the cause precipitating aneurysm rupture remains unknown in many cases. In addition, it has been observed that aneurysm ruptures are clustered in time but the trigger mechanism remains obscure. As solar activity has been associated with cardiovascular mortality and morbidity we decided to study ist association to aneurysm rupture in the Swiss population. Method: Patient data was extracted from the Swiss SOS database, at time of analysis covering 918 patients with angiography-proven aSAH treated at seven Swiss neurovascular centers between 01/01/2009 – 12/31/2011. The number of aneurysm rupture per day, week, month (Daily/Weekly/Monthly Rupture Frequency = RF) was measured and correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux (F10.7 index), solar proton flux, solar flare occurrence, planetary K-index/planetary A-index) using Poisson regression analysis. Results: Of a consecutive series of 918 cases of SAH, precise determination of the date of symptom onset was possible in 816 (88.9%). During the period of interest there were 517 days without recorded aneurysm rupture. There were 398, 139, 27 and 12 days with 1, 2, 3, and 4 ruptures per day. Five or 6 ruptures were only noted on a single day each. Poisson regression analysis demonstrated a significant correlation of F10.7 index and aneurysm rupture (incidence rate ratio (IRR) = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719 – 1.008894; p<0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. As the F10.7 index is known to correlate well with the Space Environment Services Center (SESC) sunspot number, we performed additional analyses on SESC sunspot number and sunspot area. Here, a likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95%CI 1.001864 – 1.004965; p<0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95%CI 1.000249 – 1.000589; p<0.001) emerged. All other variables analyzed showed no correlation with RF. Conclusions: Using valid methods, we found higher radioflux, sunspot number and sunspot area to be associated with an increased count of aneurysm rupture. Since we were using rupture frequencies rather than incidences and because we cannot explain the physiological basis of this statistical association, the clinical meaningfulness of this statistical association must be interpreted carefully. Future studies are warranted to rule out a type-1 error.

Clinical herniation – how to improve differentiation between WFNS grade IV and V

Objective: Current data show a favorable outcome after poor grade subarachnoid hemorrhage (SAH) in up to 50% of patients. This limits the use of the WFNS scale for drawing treatment decisions. We therefore analyzed how clinical signs of herniation might improve the existing WFNS grading. Therefore we compared the current WFNS grading and a modified WFNS grading with respect to outcome. Method: We performed a retrospective study including 182 poor grade SAH patients. Patients were graded according to the original WFNS scale and additionally into a modified classification the “WFNS herniation” (WFNSh grade IV: no herniation; grade V clinical signs of herniation). Outcome was compared between these two grading systems with respect to the dichotomized modified Rankin scale after 6 months. Results: The WFNS and WFNSh showed a positive predictive value (PPV) for poor outcome of 74.3% (OR 3.79, 95% confidence interval [CI]=1.94, 7.54) and 85.7% (OR 8.27, 95% CI=3.78, 19.47), respectively. With respect to mortality the PPV was 68.3% (OR 3.9, 95% CI=2.01, 7.69) for the WFNS grade V and 77.9% (OR 6.22, 95% CI=3.07, 13.14) for the WFNSh grade V. Conclusions: Using positive clinical signs of herniation instead of “no response to pain stimuli” (motor Glasgow Coma Scale Score) can improve WFNS V grading. Using this modification, prediction of poor outcome or death improves.

Die Blutzeugen der deutschen Volkserhebung, oder Scenen aus dem tragischen Ende der neu'sten Volksaufstände in Deutschland

Boberach: Knappen Darstellungen der Ereignisse in Baden, der Pfalz und Dresden 1849 und der Wiener Oktoberrevolution 1848 folgen Beiträge über Max Dortu, Gustav Schlöffel, Blum, August Bernigau, Messenhäuser [sic!], Lamartine, Bem, Graf Batthyani, Struve, Greiner, P. Fries, Reichard, Hepp, Hanitz, Nikolaus Schmitt, Cullmann [sic!], Goldmark, d'Ester, Franz Umbscheiden, Blenker, Raquillet [sic!], Sznayder [sic!], Zitz, Eisenstuck, Crzeriak, Fr. Ludwig Krahn, Dr. Sander, Jodokus Temme, Schulze-Delitzsch, Carl Vogt; eingefügt sind Briefe und Aufzeichnungen über die Prozesse in Rastatt, die Prager Unruhen im Juni 1848, die Kämpfe in Ungarn und die Lage der Emigranten, ferner Gedichte, u.a. von Herwegh

Hochwichtiges der Gegenwart in Sieben Bildern, betreffend die gegenwärtigen gedrückten Verhältnisse des Mittelstandes : nämlich: der Handwerker und Arbeiter, so wie des Handels und aller Gewerbe in Deutschland, und wie diesem wichtigen Stand des deutschen Volks geholfen werden kann

Boberach: Im Interesse der allgemeinen Wohlfahrt wird [die] Gründung einer deutschen Kriegsflotte, eines Deutschen Handelskongresses, einer Nationalbank und von Kolonien in Übersee gefordert; das Staatsoberhaupt soll Exekutivgewalt haben

An die hohe Nationalversammlung von Deutschland zu Frankfurt am Main: Mitten unter den politischen Stürmen des Augenblicks ...

Boberach: Aus dem Entwurf der Grundrechte des deutschen Volkes soll sich ergeben: Die gesamte Volkserziehung soll Staatssache sein. Die Volksschullehrer sollen an der Universität ausgebildet und wie Angehörige wissenschaftlicher Berufe besoldet werden. Die Schule soll von der Kirche getrennt, aber der Religionsunterricht beibehalten werden.