Subcortical lesions due to cobalamin deficiency: an unusual MRI lesion pattern.

We present a 44-year-old male patient with new onset of right focal epilepsy and bilateral hand hypesthesia. Cerebral MRI showed bilateral T2w/DWI hyperintense subcortical lesions in the cingulate gyrus, insula, and amygdala, whereas spinal MRI revealed a cervical posterior column lesion, corresponding to subacute combined degeneration. Laboratory workup revealed a cobalamin deficiency due to type A gastritis, and no evidence of antibodies associated with limbic encephalitis. After sufficient cobalamin substitution, the cerebral and spinal lesions gradually regressed. Our case represents a unique cerebral subcortical MRI lesion pattern in a patient with epilepsy and cobalamin deficiency. Thus, the latter represents an important differential diagnosis for autoimmune encephalitis.

Beyond growth rate 0.6: What drives Corynebacterium glutamicum to higher growth rates in defined medium.

In a former study we showed that Corynebacterium glutamicum grows much faster in defined CGXII glucose medium when growth was initiated in highly diluted environments [Grünberger et al. (2013b) Biotechnol Bioeng]. Here we studied the batch growth of C. glutamicum in CGXII at a comparable low starting biomass concentration of OD ≈ 0.005 in more detail. During bioreactor cultivations a bi-phasic growth behavior with changing growth rates was observed. Initially the culture grew with µË†=0.61±0.02 h-1 before the growth rate dropped to µË†=0.46±0.02 h-1. We were able to confirm the elevated growth rate for C. glutamicum in CGXII and showed for the first time a growth rate beyond 0.6 in lab-scale bioreactor cultivations on defined medium. Advanced growth studies combining well-designed bioreactor and microfluidic single-cell cultivations (MSCC) with quantitative transcriptomics, metabolomics and integrative in silico analysis revealed protocatechuic acid as a hidden co-substrate for accelerated growth within CGXII. The presented approach proves the general applicability of MSCC to investigate and validate the effect of single medium components on microorganism growth during cultivation in liquid media, and therefore might be of interest for any kind of basic growth study.

Recurrent Stroke in a Young Patient with Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Quo Vadis?

So far, there has been no generally accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). As recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation and the concept of ESUS comprises heterogeneous subgroups of patients, including a wide age range, concomitant patent foramen ovale (PFO), variable cardiovascular risk factors as well as a variable probability for atrial fibrillation (AF), an individualized clinical approach is needed. In this context, we here present a case of recurrent stroke in a young patient with ESUS and PFO. During treatment according to our Catch-up-ESUS registry study, prolonged cardiac monitoring diagnosed AF, and PFO closure was omitted.

Drip and ship for mechanical thrombectomy within the Neurovascular Network of Southwest Bavaria.

OBJECTIVE: To determine feasibility and safety of stroke care organization within our Neurovascular Network of Southwest Bavaria (NEVAS) in a rural area with distances of up to 100 kilometers, we compared patients who underwent mechanical thrombectomy (MT) in large vessel occlusion admitted directly to our center (direct to center [DTC]) to patients who were transferred for MT via NEVAS (drip and ship [DS]). METHODS: This is a retrospective analysis of prospectively collected data of all MT patients between January 2015 and May 2018. Successful recanalization was defined as a thrombolysis in cerebral infarction score of 2b-3. Symptomatic intracerebral hemorrhage (sICH) was defined according to European Cooperative Acute Stroke Study 3. Modified Rankin Scale (mRS) score of 0-2 at 3 months indicated good outcome. RESULTS: MT was performed in 410 patients: 221 DTC and 189 DS. Median NIH Stroke Scale (NIHSS) score was 16 and premorbid mRS score was 0. Thrombolysis was applied in 62.2% with the same time from symptom onset in both groups (94.5 vs 95 minutes). Successful recanalization (79.3% vs 77.8%) and NIHSS score reduction from admission to discharge (16-7 vs 17-6) were comparable. Time delay from onset to revascularization was 96 minutes in DS (212 vs 308 minutes, p = 0.001). At follow-up, DTC patients had a trend to better outcome (33.5% vs 24.3%, p = 0.056). Neither sICH (6.3% vs 5.9%, p = 0.840) nor mortality (31.2% vs 34.4%, p = 0.387) differed between the groups. CONCLUSION: DS patients benefit from MT without relevant safety concerns, but with a trend to unfavorable outcome compared to DTC patients. These results suggest that DS is suitable to provide MT in rural areas where DTC is not possible.

Catch-up-ESUS - follow-up in embolic stroke of undetermined source (ESUS) in a prospective, open-label, observational study: study protocol and initial baseline data.

INTRODUCTION: So far there is no uniform, commonly accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). Recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation. As ESUS comprises heterogeneous subgroups including a wide age-range, concomitant patent foramen ovale (PFO), and variable probability for atrial fibrillation (AF), an individualised approach is urgently needed. This prospective registry study aims to provide initial data towards an individual, structured diagnostic and therapeutic approach in ESUS patients. METHODS AND ANALYSIS: The open-label, investigator-initiated, prospective, single-centre, observational registry study (Catch-up-ESUS) started in 01/2018. Consecutive ESUS patients ≥18 years who give informed consent are included and will be followed up for 3 years. Stratified by age <60 or ≥60 years, the patients are processed following a standardised diagnostic and treatment algorithm with an interdisciplinary design involving neurologists and cardiologists. Depending on the strata, patients receive a transesophageal echocardiogram; all patients receive an implantable cardiac monitor. Patients <60 years with PFO and without evidence of concomitant AF are planned for PFO closure within 6 months after stroke. The current diagnostic and therapeutic workup of ESUS patients requires improvement by both standardisation and a more individualised approach. Catch-up-ESUS will provide important data with respect to AF detection and PFO closure and will estimate stratified stroke recurrence rates after ESUS. ETHICS AND DISSEMINATION: The study has been approved by the responsible ethics committee at the Ludwig Maximilian University, Munich, Germany (project number 17-685). Catch-Up-ESUS is conducted in accordance with the Declaration of Helsinki. All patients will have to give written informed consent or, if unable to give consent themselves, their legal guardian will have to provide written informed consent for their participation. The first observation period of the registry study is 1 year, followed by the first publication of the results including follow-up of the patients. Further publications will be considered according the predefined individual follow-up dates of the stroke patients up to 36 months. TRIAL REGISTRATION NUMBER: Clinicaltrialsregister.gov registry (NCT03820375).

Bioavailability of Dietary Omega-3 Fatty Acids Added to a Variety of Sausages in Healthy Individuals.

A low Omega-3 Index (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes) is associated with cardiac, cerebral, and other health issues. Intake of EPA and DHA, but not of alpha-linolenic acid (ALA), increases the Omega-3 Index. We investigated bioavailability, safety, palatability and tolerability of EPA and DHA in a novel source: a variety of sausages. We screened 96 healthy volunteers, and recruited 44 with an Omega-3 Index <5%. Participants were randomly assigned to receive a variety of sausages enriched with approximately 250 mg EPA and DHA per 80 g (n = 22) daily for 8 weeks, or matching placebo sausages (n = 22). All sausages contained approximately 250 mg ALA/80 g. In the verum group, the mean Omega-3 Index increased from 4.18 ± 0.54 to 5.72 ± 0.66% (p < 0.001), while it remained unchanged in the placebo group. While ALA levels increased only in the placebo group, DPA levels increased in both groups. Inter-individual variability in the response was large. The mean increase of the Omega-3 Index per intake of EPA and DHA we observed was higher than for other sources previously studied, indicating superior bioavailability. As increasing production of EPA and DHA is difficult, improvements of bioavailability can facilitate reaching the target range for the Omega-3 Index (8-11%).

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model.

Vascularization still remains an obstacle to engineering of bone tissue with clinically relevant dimensions. Our aim was to induce axial vascularization in a large volume of a clinically approved biphasic calcium phosphate ceramic by transferring the arteriovenous (AV) loop approach to a large animal model. HA/beta-TCP granula were mixed with fibrin gel for a total volume of 16 cm(3), followed by incorporation into an isolation chamber together with an AV loop. The chambers were implanted into the groins of merino sheep and the development of vascularization was monitored by sequential non-invasive magnetic resonance imaging (MRI). The chambers were explanted after 6 and 12 weeks, the pedicle was perfused with contrast agent and specimens were subjected to micro-computed tomography (micro-CT) scan and histological analysis. Sequential MRI demonstrated a significantly increased perfusion in the HA/beta-TCP matrices over time. Micro-CT scans and histology confirmed successful axial vascularization of HA/beta-TCP constructs. This study demonstrates, for the first time, successful axial vascularization of a clinically approved bone substitute with a significant volume in a large animal model by means of a microsurgically created AV loop, thus paving the way for the first microsurgical transplantation of a tissue-engineered, axially vascularized bone with clinically relevant dimensions.