Background: Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the influence of pro-inflammatory cytokine activation on the coagulation system in extremely preterm infants and its impact on the development of IVH. Objective: To determine the interaction between serum interleukin-6 (IL-6) and the coagulation system in preterm infants predisposed to the development of IVH. Methods: Vitamin K-dependent coagulation factors were examined retrospectively in 132 extremely preterm infants prior to vitamin K administration at the first day of life. Patients were grouped according to the occurrence of IVH and serum concentration of IL-6 >/<100 pg/ml. Results: Occurrence of IVH was associated with clinical diagnosis of chorioamnionitis, low gestational age, high CRIB score, air leak, catecholamine treatment, low initial hematocrit and increased serum concentration of IL-6. Infants developing IVH showed a diminished coagulation profile. Multivariable logistic regression analysis revealed decreased activity of coagulation factor VII, development of pneumothorax and low hematocrit as independent risk factors for the development of IVH. An increased IL-6 serum concentration was associated with a significantly decreased activity of coagulation factor VII and increased levels of fibrinogen. Conclusions: The association of elevated IL-6 levels with alterations of the coagulation profile and development of IVH found in our study supports the assumption of a close pathophysiological relation between inflammation and IVH.

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In this prospective cohort study we aimed to investigate the trajectory of the cognitive performance of patients after discharge from an intensive care unit (ICU). Special consideration was given to patients with suspected premorbid cognitive impairment who might be at risk for the development of dementia. Clinical characteristics were collected until discharge. The premorbid cognitive state was estimated by a structured interview with a close relative. Cognitive outcome was assessed using the Consortium to Establish a Registry of Alzheimer’s Disease (CERAD) Plus battery and the Stroop Color and Word Test at the time of discharge from ICU and 9 months later. The results of the study group were compared to an established healthy control group and to normative data. A total number of 108 patients were finally included. At the time of discharge, patients underperformed the healthy control group. In linear regression models, delirium during the ICU stay and the factor premorbid cognitive impairment were associated with poorer cognitive outcome (p = 0.047 and p = 0.001). After 9 months, in 6% of patients without evidence of premorbid cognitive impairment long-lasting deficits were found. In patients with suspected premorbid cognitive impairment, performance in tests of executive function failed to improve.

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Background Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group. Methods We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest. Discussion ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease. Trial registration The trial has been registered at the German Clinical Trials Register on 3 July, 2020 (DRKS00022308, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022308).

Essential tremor (ET) is a progressive movement disorder whose pathophysiology is not fully understood. Current evidence supports the view that the cerebellum is critically involved in the genesis of the tremor in ET. However, it is still unknown whether cerebellar dysfunction affects not only the control of current movements but also the prediction of future movements through dynamic adaptation toward a changed environment. Here, we tested the capacity of 28 patients with ET to adapt in a visuomotor adaptation task known to depend on intact cerebellar function. We found specific impairments in that task compared to age-matched healthy controls. Adaptation to the visual perturbation was disrupted in ET patients, while de-adaptation, the phase after abrupt removal of the perturbation, developed similarly to control subjects. Baseline tremor-independent motor performance was as well similar to healthy controls, indicating that adaptation deficits in ET patients were not rooted in an inability to perform goal-directed movements. There was no association between clinical severity scores of ET and early visuomotor adaptation abilities. These results provide further evidence that the cerebellum is dysfunctional in ET.

Zusammenfassung Hintergrund Akut-symptomatische epileptische Anfälle treten in engem zeitlichem Zusammenhang mit einer akuten Störung der Hirnfunktion auf. Sie sind mit einem niedrigen Risiko späterer unprovozierter Anfallsrezidive assoziiert. Daher empfehlen aktuelle Leitlinien keine längerfristige medikamentöse Anfallsprophylaxe. Dennoch werden im klinischen Alltag oft langfristige sekundärprophylaktische Therapien begonnen. Die Anfallsprognose nach leitliniengerecht nicht oder nur kurzzeitig behandelten akut-symptomatischen Anfällen ist bisher unbekannt. Hypothese Nach einem akut-symptomatischen Erstanfall struktureller Ätiologie ist das 1‑Jahres-Risiko für unprovozierte Rezidivanfälle nicht höher als 25 %, auch wenn keine oder nur eine kurzfristige medikamentöse Anfallsprophylaxe eingesetzt wird. Methoden Das PROSA-Register ist eine einarmige, offene, prospektive, multizentrische Beobachtungsstudie. Eingeschlossen werden 115 volljährige Personen mit strukturell bedingtem akut-symptomatischem, epileptischem Erstanfall, sofern dieser kein Status epilepticus war. Der intrahospitale Verlauf wird der Krankenakte entnommen. Nach 3, 6 und 12 Monaten finden telefonische Nachbefragungen statt. Diskussion Das PROSA-Register wird als Beobachtungsstudie die derzeitige Behandlungspraxis nach akut-symptomatischem Anfall und die tatsächliche Anfallsprognose innerhalb eines Jahres beleuchten. Die Ergebnisse sollen die vorhandene Evidenz unterstreichen, dass eine medikamentöse Anfallsprophylaxe über die akute Phase der zugrunde liegenden Erkrankung hinaus nicht notwendig ist. Registrierung Die Studie wurde prospektiv im Deutschen Register Klinischer Studien unter der ID DRKS00017811 registriert.