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Aim: With the resolution from April 28, 2014, the Bavarian state government in Germany decided to found a new medical school at Augsburg University, thereby requiring the development of a competency-based medical curriculum.Methods: Two interdisciplinary groups developed a spiral curriculum (following Harden) employing the model of Thumser-Dauth & Öchsner. The curriculum focuses on specifically defined competencies: medical expertise, independent scientific reasoning, argumentation and scholarship, as well as communication skills.Results: The spiral curriculum was developed as a hybrid curriculum. Its modular structure incorporates the mandatory subjects required by the German regulations for medical licensure (Approbationsordnung) into organ- and system-centered blocks which are integrated both horizontally and vertically. Basic preclinical sciences are covered in the blocks “Movement,” “Balance” and “Contact.” The clinical sciences are organized according to six pillars (conservative medicine, surgical medicine, men’s-women’s-children’s medicine, the senses, the nervous system and the mind, and general medicine) which students revisit three times each over the course of the program. A longitudinal clinical course incorporates interdisciplinary education. A particular focus is on scientific education encompassing a longitudinal course in the sciences (including interdisciplinary classes with other university departments), block practicums, and two scientific projects.Conclusion: It is not only the degree of integration und intensity of the Augsburg University undergraduate medical degree program, but also its targeted advancement of academic, social and communication skills that have not yet been realized to such an extent elsewhere in Germany. On July 8, 2016, the German Council of Science and Humanities unanimously gave this concept a positive evaluation. Future research will examine and evaluate the Augsburg medical curriculum and the impact of the new medical school on the hospital and university in Augsburg.

The main causes for cerebrospinal fluid (CSF) leaks are known to be traumatic, iatrogenic, neoplastic, a meningoencephalocele, congenital bone defects, and spontaneous. Off-label intrathecal administration of fluorescein is widely used to localize a CSF leak. Complications are rare and low dose administration is described to be safe. In this case report, we present a case of a patient, who showed a CSF leak due to an encephalocele. Low dose fluorescein was applied intrathecally via lumbar catheter, the CSF leaks could be identified, and multilayered closure was performed. Postoperatively, the patient presented with motor and sensory deficits in the lower limbs which regressed only partially within 2 months. A possible explanation may be an increased local concentration of fluorescein, possibly on the basis of a preexisting lumbar spinal canal stenosis. To our knowledge, this is the first case in which a dose as low as 20 mg of fluorescein (2% saline mixture) led to persisting paraplegia. Therefore, the potential benefits and risks of the intrathecal fluorescein use in the detection of a CSF leak have to be discussed comprehensively prior to surgery. [ABSTRACT FROM AUTHOR]

Background and Aims In recent decades, nighttime temperatures have increased faster than daytime temperatures. The increasing prevalence of nocturnal heat exposure may pose a significant risk to cardiovascular health. This study investigated the association between nighttime heat exposure and stroke risk in the region of Augsburg, Germany, and examined its temporal variations over 15 years. Methods Hourly meteorological parameters, including mean temperature, relative humidity, and barometric pressure, were acquired from a local meteorological station. A data set was obtained consisting of 11 037 clinical stroke cases diagnosed during warmer months (May to October) between the years 2006 and 2020. The average age of cases was 71.3 years. Among these cases, 642 were identified as haemorrhagic strokes, 7430 were classified as ischaemic strokes, and 2947 were transient ischaemic attacks. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the stroke risk associated with extreme nighttime heat, as measured by the hot night excess (HNE) index after controlling for the potential confounding effects of daily maximum temperature and other climatic variables. Subgroup analyses by age group, sex, stroke subtype, and stroke severity were performed to identify variations in susceptibility to nighttime heat. Results Results suggested a significant increase in stroke risk on days with extreme nighttime heat (97.5% percentile of HNE) (odds ratio 1.07, 95% confidence interval 1.01–1.15) during the full study period. When comparing the results for 2013–20 with the results for 2006–12, there was a significant increase (P <.05) in HNE-related risk for all strokes and specifically for ischaemic strokes during the more recent period. Furthermore, older individuals, females, and patients with mild stroke symptoms exhibited a significantly increased vulnerability to nighttime heat. Conclusions This study found nocturnal heat exposure to be related to elevated stroke risk after controlling for maximum daytime temperature, with increasing susceptibility between 2006 and 2020. These results underscore the importance of considering nocturnal heat as a critical trigger of stroke events in a warming climate. [ABSTRACT FROM AUTHOR]

Background: High throughput technologies provide new opportunities to further investigate the pathophysiology of ischemic strokes. The present cross‐sectional study aimed to evaluate potential associations between the etiologic subtypes of ischemic stroke and blood‐based proteins. Methods: We investigated the associations between ischemic stroke subtypes and a panel of circulating inflammation biomarkers in 364 patients included in the Stroke Cohort Augsburg (SCHANA). Stroke etiologies were categorized according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Serum concentrations of 52 biomarkers were measured using the Bio‐Plex Pro™ Human Cytokine Screening Panel, ICAM‐1 set and VCAM‐1 set, plus the Pro™ Human TH17 cytokine sCD40L set and IL31 set (all Bio‐Rad, USA). Multivariable linear regression models were used to examine associations. Point estimates were calculated as the mean difference in σ‐standardized cytokine levels on the log2‐scale. Results: Stromal‐cell‐derived‐factor 1 alpha (SDF‐1a) showed significantly higher serum levels in cardioembolic compared with large vessel atherosclerotic stroke (β = 0.48; 95% CI 0.22; 0.75; Padj = 0.036). Significantly lower levels of interleukin‐6 (IL‐6) (β = −0.53; 95% CI −0.84; −0.23; Padj = 0.036) and macrophage migration inhibitory factor (MIF) (β = −0.52; 95% CI −0.84; −0.21; Padj = 0.043) were found in the small vessel versus large vessel stroke subtype. Conclusions: Immune dysregulations observed in different stroke subtypes might help uncover pathophysiological mechanisms of the disease. Further studies are needed to validate identified biomarkers in diverse study populations before they can potentially be used in clinical practice to further improve stroke management and patient outcomes. [ABSTRACT FROM AUTHOR]

Approximately one-third of patients with stroke show depressive symptoms. The so-called post-stroke depression (PSD) has a negative influence on mortality as well as physical and mental conditions. The aim of this study was to analyse the association between PSD and health-related quality of life (HRQOL) in patients with stroke. The analysis was based on data of 326 patients from the Stroke Cohort Augsburg (SCHANA Study) collected after the stroke event by interview and three months later using a postal survey. Depressive symptoms were measured with the Patient-Health Questionnaire (PHQ-9), subjective health status with the EuroQol 5D visual analogue scale (EQ-5D VAS), and HRQOL with the Stroke Impact Scale (SIS). Patients with depressive symptoms were compared to those without depressive symptoms in terms of sociodemographic characteristics and scores of the SIS and the EQ-5D VAS. Multiple linear regression models were calculated to investigate the association between PSD and subjective health status and HRQOL. Three months after the stroke, 17.8% of patients had depressive symptoms. Patients with PSD showed significantly worse SIS and EQ-5D VAS scores. In addition, an independent negative linear association between PSD and subjective health status and between PSD and all domains of SIS could be found. The study confirmed that PSD is common in patients with mild stroke and negatively related to all stroke-specific HRQOL domains. The results underline the importance of early screening for PSD in stroke patients since it may hinder a successful rehabilitation. [ABSTRACT FROM AUTHOR]

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and post-treatment was tested and examined for impact on clinical safety and efficacy. Overall, 27 of the 5876 evaluable subjects (0.5%) developed NAbs after onabotulinumtoxinA treatment. At study exit, 16 of the 5876 subjects (0.3%) remained NAb positive. Due to the low incidence of NAb formation, no clear relationship was discernable between positive NAb results and gender, indication, dose level, dosing interval, treatment cycles, or the site of injection. Only five subjects who developed NAbs post-treatment were considered secondary nonresponders. Subjects who developed NAbs revealed no other evidence of immunological reactions or clinical disorders. This comprehensive meta-analysis confirms the low NAb formation rate following onabotulinumtoxinA treatment across multiple indications, and its limited clinical impact on treatment safety and efficacy. [ABSTRACT FROM AUTHOR]

Background: Chronic fatigue is a common symptomafter a stroke. Studies suggested that chronic fatigue is caused by inflammatory or immunological processes but data are limited and contradictory. Thus, the present study aimed to identify specific biomarkers associated with fatigue in post-stroke patients and replicated the findings in a population-based study. Methods: We investigated associations between 39 circulating biomarkers of inflammation and fatigue in 327 patients after an ischemic stroke included in the Stroke Cohort Augsburg (SCHANA) study and the "Metabolism, Nutrition and Immune System in Augsburg" (MEIA) study (n = 140). The Fatigue Assessment Scale (FAS) was used to assess the severity of fatigue. The serum concentrations of the biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel (Bio-Rad, USA). Multiple linear regression models adjusted for possible confounders were used to examine associations. Results: In patients with stroke, SCGFb was inversely associated [-1.67, 95% confidence interval (CI) (-3.05; -0.29) p = 0.018], and in healthy subjects, G-CSF was positively associated [1.56, 95% CI (0.26; 2.87), p = 0.020] with an increasing FAS- score, while SCF was positively related in both samples [1.84, 95% CI (0.27; 3.42), p = 0.022 and 1.40, 95% CI (0.29; 2.52), p = 0.015]. However, after correction for multiple testing, all of these associations lost statistical significance. Conclusion: The present findings suggested an association between the growth factor SCF and fatigue. Future research on cytokines as possible markers of fatigue should focus on a longitudinal design including a sufficiently large number of study participants to enable testing associations between certain cytokines and sub-groups of chronic fatigue. [ABSTRACT FROM AUTHOR]

Background and purpose: Acute stroke treatment and secondary prevention have tremendously improved functional outcomes after stroke. However, this does not always imply a likewise improvement in health‐related quality of life (HRQoL). Knowledge on factors influencing HRQoL after stroke is still scarce, especially regarding social aspects like the level of education and the presence of migration background. Methods: In the present stroke cohort study, participants were interviewed during their hospital stay and completed a postal questionnaire at 3 and 12 months post stroke. Functional outcomes were assessed by the modified Rankin Scale and HRQoL by evaluating the detailed Stroke Impact Scale (SIS). Logistic regression models were used to determine associations between education, migration background and quality of life end‐points. Results: A total of 945 (mean age 69 years; 56% male) stroke patients were enrolled. After adjusting for confounders, a lower educational level was associated with worse functional outcomes in the SIS domain 'strength' (odds ratio 2.67, 95% confidence interval 1.6–4.4, p < 0.001). Migration background was associated with worse outcomes in the SIS domain 'emotion' (p = 0.007, odds ratio 1.71, 95% confidence interval 1.2–2.5). Additionally, for female patients worse HRQoL outcomes were found in multiple other SIS domains. Conclusions: Migration background and a lower educational level were significantly associated with lower long‐term HRQoL after stroke. These aspects should be considered in targeted rehabilitation programmes and follow‐up support of stroke patients. [ABSTRACT FROM AUTHOR]

The clinical efficacy and safety of bilateral pallidal deep-brain stimulation for severe primary dystonia in a series of 40 patients who participated in a prospective trial of neurostimulation is reported. In this randomized comparison of the effects of neurostimulation and sham stimulation it was found that bilateral high-frequency stimulation of the internal globus pallidus is efficacious in the reduction of movement impairment and disability in patients with primary generalized or segmental dystonia.

Background: Much is known about the association between physical activity and the occurrence of stroke. However, the evidence about the correlation between pre-stroke physical activity and post-stroke quality of life remains inconsistent. Thus, there is a high public health relevance to the topic. Aim: The aim of this study was to investigate the association between pre-stroke physical activity and physical quality of life after three months. Methods: Data arises from 858 patients with stroke included a prospective single-centre observational cohort study in Augsburg, Germany, between September 2018 and November 2019. The participants were recruited at the Department of Neurology and Clinical Neurophysiology, University Hospital of Augsburg after their stroke event. The level of physical activity was determined following the short form of the International Physical Activity Questionnaire at baseline. Physical quality of life was assessed three months after hospital discharge using the German version of the Stroke Impact Scale (SIS). A multiple linear regression model and a quantile regression were carried out. Results: A total of 497 patients were included in the analysis (mean age 69.6, 58.8% male), 26.2% had a high, 18.9% a moderate and 54.9% a low level of pre-stroke physical activity. Patients with high pre-stroke physical activity had a significantly better physical quality of life three months after stroke in the SIS physical domain (beta = 4.1) and in the SIS subdomains hand function (beta = 5.6), mobility (beta = 4.1) and activities of daily living (beta = 3.7). In the physical domain and the subdomain mobility, the effect was especially strong for persons with low physical quality of life after three months. Conclusion: Pre-stroke physical activity seems to have an important and positive association with physical quality of life after three months in patients with mild disability. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Prolonged-release fampridine (PR-FAM), a potassium channel blocker, is approved for improving walking ability in patients with multiple sclerosis (MS). Beyond this, positive effects on other MS symptoms like fatigue, cognition, and tremor have been described. To our knowledge, a positive effect of PR-FAM on spinal myoclonus has not been described so far. Here, we report a 32-year-old female with myoclonus after cervical myelitis affecting both hands which markedly improved after administration of PR-FAM. Treatments used before such as carbamazepine or levetiracetam had to be withdrawn because of intolerable side effects or lack of efficacy. The positive effect of PR-FAM could be confirmed by transient suspension. PR-FAM may be considered as a treatment option in refractory spinal myoclonus after myelitis in selected cases. [ABSTRACT FROM AUTHOR]

Background: Post-stroke fatigue is a common symptom after stroke. However, studies on the factors associated with early and late fatigue are scarce. The objective of this study was to identify variables associated with early and late fatigue. Methods: In the German Stroke Cohort Augsburg (SCHANA) study, participants were interviewed during their hospital stay and completed a postal questionnaire 3 and 12 months post-stroke. Fatigue was assessed using the Fatigue Assessement Scale (FAS). In addition, depression was measured by the Patient Health Questionnaire (PHQ-9), general health status by the EQ-5D visual analog scale, and physical activity by the International Physical Activity Questionnaire (IPAQ). Multivariable regression models were used to determine the associations between FAS scores at 3 and 12 months post-stroke and demographic, psychosocial and health-related covariables. Results: Among 505 participants, the frequency of fatigue was 31.1% 3 months and 29.1% 12 months post-stroke. Prior stroke (ß = 2.37, p = 0.0076), prior diagnosis of depression (ß = 5.04, p = 0.0001), higher NIHSS (ß = 0.25, p = 0.0360) and higher PHQ-9 scores (ß = 0.55, p < 0.0001) were significantly associated with higher fatigue levels 3 months post-stroke. Additionally, younger age (ß = −0.07, p = 0.0219), a worse rating of general health at baseline (ß = −0.04, p = 0.0287) and low pre-stroke physical activity (ß = −0.0004, p = 0.0089) were significantly associated with higher fatigue levels 12 months after stroke. Conclusions: Fatigue is a common and persisting symptom even in patients with mild impairment. Prior depressive disorder and early depressive symptoms were the most relevant predictors of both early and late fatigue. [ABSTRACT FROM AUTHOR]

Background: Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature. Objective: Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied. Methods: A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included. Results: Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization. Conclusions: Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT. [ABSTRACT FROM AUTHOR]

Prolonged-release fampridine (PR-FAM), a potassium channel blocker, is approved for improving walking ability in patients with multiple sclerosis (MS). Beyond this, positive effects on other MS symptoms like fatigue, cognition, and tremor have been described. To our knowledge, a positive effect of PR-FAM on spinal myoclonus has not been described so far. Here, we report a 32-year-old female with myoclonus after cervical myelitis affecting both hands which markedly improved after administration of PR-FAM. Treatments used before such as carbamazepine or levetiracetam had to be withdrawn because of intolerable side effects or lack of efficacy. The positive effect of PR-FAM could be confirmed by transient suspension. PR-FAM may be considered as a treatment option in refractory spinal myoclonus after myelitis in selected cases. [ABSTRACT FROM AUTHOR]