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Abstract Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933

Background: The COVID-19 pandemic has affected acute stroke care, resulting in a decrease in stroke admissions worldwide. We examined trends in stroke severity at hospital admission, including (1) probable need for rehabilitation (National Institutes of Health Stroke Scale score > 6 points) and (2) probable need for assistance (modified Rankin Scale score > 2 points), and discharge to rehabilitation after acute care among inpatients with acute ischemic stroke and intracerebral hemorrhage., Methods: We compared quality assurance data for acute ischemic stroke and intracerebral hemorrhage during the pandemic with the period before the pandemic in Hesse, Germany, using logistic regression analyses., Results: Fewer inpatients with a probable need for rehabilitation were present at the beginning of the second wave of the COVID-19 pandemic in September 2020 (adjusted OR (aOR) 0.85, 95% CI [0.73, 0.99]), at the end of the second national lockdown in May 2021 (aOR 0.81, 95% CI [0.70, 0.94]), and at the approaching peak of COVID-19 wave 4 in November 2021 (aOR 0.79, 95% CI [0.68, 091]). Rates of probable need for assistance were significantly lower at the beginning of COVID-19 wave 2 in August 2020 (aOR 0.87, 95% CI [0.77, 0.99]) and at the beginning of COVID-19 wave 3 in March 2021 (aOR 0.80, 95% CI [0.71, 0.91]). Rates of discharge to rehabilitation were lower from the beginning in October 2020 to the peak of COVID-19 wave 2 in December 2020 (aOR 0.83, 95% CI [0.77, 0.90]), at the beginning and end of COVID-19 wave 3 in March 2021 and May 2021 (aOR 0.86, 95% CI [0.79, 0.92]), respectively, and at the beginning of COVID-19 wave 4 in October 2021 (aOR 0.86, 95% CI [0.76, 0.98])., Conclusions: The results suggest that the COVID-19 pandemic had an impact on stroke management during the pandemic, but the absolute difference in stroke severity at hospital admission and discharge to rehabilitation was small., (© 2024. The Author(s).)

The ability of some artificial intelligence (AI) systems to autonomously evolve and the sometimes very limited possibilities to comprehend their decision-making processes present new challenges to our legal system. At a European level this has led to reform efforts, of which the proposal for a European AI regulation promises to close regulatory gaps in existing product safety law through cross-sectoral AI-specific safety requirements. A prerequisite, however, would be that the EU legislator does not only avoid duplications and contradictions with existing safety requirements but also refrains from imposing exaggerated and unattainable demands. If this were to be taken into consideration, the new safety requirements could also be used to specify the undefined standard of care in liability law. Nevertheless, challenges in the context of provability continue to remain unresolved, posing a risk of rendering the legal protection efforts of the aggrieved party ineffective. It remains to be seen whether the EU legislator will address this need for reform with the recently proposed reform of product liability law by the Commission., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Mild traumatic brain injuries (mTBI) sustained during contact sports like amateur boxing are found to have long-term sequelae, being linked to an increased risk of developing neurological conditions like Parkinson's disease. The aim of this study was to assess differences in volume of anatomical brain structures between amateur boxers and control subjects with a special interest in the affection of deep grey matter structures., Methods: A total of 19 amateur boxers and 19 healthy controls (HC), matched for age and intelligence quotient (IQ), underwent 3T magnetic resonance imaging (MRI) as well as neuropsychological testing. Body mass index (BMI) was evaluated for every subject and data about years of boxing training and number of fights were collected for each boxer. The acquired 3D high resolution T1 weighted MR images were analyzed to measure the volumes of cortical grey matter (GM), white matter (WM), cerebrospinal fluid (CSF) and deep grey matter structures. Multivariate analysis was applied to reveal differences between groups referencing deep grey matter structures to normalized brain volume (NBV) to adjust for differences in head size and brain volume as well as adding BMI as cofactor., Results: Total intracranial volume (TIV), comprising GM, WM and CSF, was lower in boxers compared to controls (by 7.1%, P = 0.009). Accordingly, GM (by 5.5%, P = 0.038) and WM (by 8.4%, P = 0.009) were reduced in boxers. Deep grey matter showed statistically lower volumes of the thalamus (by 8.1%, P = 0.006), caudate nucleus (by 11.1%, P = 0.004), putamen (by 8.1%, P = 0.011), globus pallidus (by 9.6%, P = 0.017) and nucleus accumbens (by 13.9%, P = 0.007) but not the amygdala (by 5.5%, P = 0.221), in boxers compared to HC., Conclusion: Several deep grey matter structures were reduced in volume in the amateur boxer group. Furthermore, longitudinal studies are needed to determine the damage pattern affecting deep grey matter structures and its neuropsychological relevance., (© 2022. The Author(s).)

Viral diseases of the nervous system are ancient and poliomyelitis was described in Egypt as early as 2000 BC. They can cause a wide range of neurological symptoms, such as meningitis, encephalitis, meningoencephalitis, Guillain-Barré-like syndrome and stroke, often leaving mild to severe residuals. Depending on the pathogen, the symptoms appear quickly within hours, or lead to increasing chronic symptoms within 1 week or months. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was newly identified in January 2020 and occurs worldwide, illustrates the sequelae of a phenomenon that has been known for centuries, the possible rapid spread of pathogen-related infectious diseases. Due to vaccination programs some pathogens are becoming rarer or are considered to be eradicated. Nevertheless, vaccination programs, especially in the poorer regions, are repeatedly interrupted, for example by wars. The most recent example is the interruption of vaccination against poliomyelitis in Ukraine. As life expectancy continues to rise and years of life lost to infectious diseases decrease, the new infectious disease threat is likely to come from emerging and re-emerging infections; however, according to a recent analysis of population data from 29 countries, life expectancy during the corona pandemic has decreased, e.g., by 28 months in the USA and by 6 months in Germany. Climate change, rapid urbanization and changing land-use patterns could increase the risk in the coming decades. In particular, the climate change can alter the spectrum of global pathogens and especially vector-borne infections can spread to new areas. A sustained increase in travel, trade and mobility enables the pathogens to spread quickly., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Southeast Asia harbors a young population of more than 600 million people. Socioeconomic transition within the last decades, driven by globalization and rapid economic growth, has led to significant changes in lifestyle and nutrition in many countries of this region. Hence, an increase in the number of non-communicable diseases is seen in most populations of Southeast Asia. Brunei Darussalam is the smallest country in this region, with a population of around 400,000 inhabitants. Vast hydrocarbon resources have transformed Brunei into a wealthy industrialized country within the last few decades. We compared the age distribution and prevalence of cardiovascular risk factors in ischemic stroke patients between the only stroke unit in Brunei Darussalam and a tertiary stroke center from Frankfurt/Germany. Between 2011 and 2016, a total number of 3877 ischemic stroke patients were treated in both institutions. Even after adjusting for age due to different population demographics, stroke patients in Brunei were younger compared to their German counterparts. The prevalence of hypertension and diabetes mellitus was significantly higher in young age groups in Brunei, whereas no difference was observed for older patients. The rapid socioeconomic transition might be a significant risk factor for the development of non-communicable diseases, including stroke.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland)., (© 2021. The Author(s).)

Background: The current Libyan civil war has originated many casualties, imposing medical challenges. War injuries are complex, requiring specialized knowledge and interdisciplinary assessment for adequate patient and intercultural management., Methods: This retrospective study analyzed records of 78 Libyan patients admitted from July 2016 to November 2017 to neurological and trauma surgical departments of Krankenhaus Nordwest, Frankfurt, Germany. Issues of system preparation of the hospital, demographics, injury patterns and therapies were analyzed. The chi-squared test was used to analyze differences in injury patterns in explosion and gunshot injuries., Results: Seventy-seven of seventy-eight patients were male (mean age 30.6 years). The patients received primary and secondary treatment in Tunisia (n = 39), Libya (n = 36) and Turkey (n = 23). Forty-eight patients had gunshot injuries, 37 explosion injuries, 11 both. Preparation for management of injuries included hygienic and isolation protocols, organization of interpreters and intercultural training. Patients presented with a broad variety of neurological, psychiatric and trauma surgical injuries. Fifty-six patients had sensory, 47 motor deficits. Nine reported headache, 5 vertigo, 13 visual impairment, 28 psychiatric symptoms. Eighteen patients had central nervous damage, 50 peripheral nervous damage. Central nervous damage was significantly more common in gunshot than explosion injuries (p = 0.015). Peripheral nervous damage was more common in explosion than gunshot injuries (p < 0.1). Fifty-one patients had polytrauma and 49 suffered from fractures. Therapy included surgical interventions (n = 56) and physiotherapy. Structured rehabilitation programs were often indicated., Conclusion: Specialized knowledge about war injuries and their management including hospital preparation and planning regarding infrastructure may be required anytime. Injuries include a broad variety of neurological, psychiatric and trauma surgical injuries. Therefore, an interdisciplinary approach is crucial.

Competing Interests: Erklärung zu finanziellen InteressenForschungsförderung erhalten: Nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: Nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: Nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): Nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht-Sponsor der Veranstaltung): Nein.Erklärung zu nichtfinanziellen InteressenDie Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Emerging and re-emerging viruses may cause meningitis, encephalitis, meningoencephalomyelitis, encephalitis, Guillian-Barré-like-syndromes as well as strokes. Most important viruses belong to the family of Adenoviridae, Arbovirus, Arenaviridae, Herpesviridae, Picornaviridae, Paramyxoviridae as well as Togaviridae . Clinical presentation usually consists of a biphasic presentation. Non-specific febrile illnesses may be accompanied by rash, headache, arthralgia and myalgia. Thereafter focal neurological signs may evolve. Diagnostic strategies for the detection of emerging and re-emerging viruses may be difficult due to the short viraemic period. Pitfalls in serology may be due to antibody crossreactivity. Arboviruses are transmitted by arthropods. Aedes mosquitos are one of the vectors for arboviruses like Chikungunya-virus, Dengue-virus, Japanese-Encephalitis-B-virus and West-Nile-virus. Since the last centuries Aedes mosquitos have spread from their naturally habitat in Africa to America as well as Europe. The arboviruses risk profile depend essentially on the occurrence, the activity of the respective vector, this may be the key to fight the disease and its spread. Due to global shifts in the ecological balance but also as a result of more or less successful control measures, some diseases have become rarer, others are more common. The viruses persist in the respective vector months to years; in ticks they may persist for years and in mosquitoes 1 to 4 months. In order to survive bad climatic conditions unscathed, the viruses partially overwinter in arthropods., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Arboviruses are transmitted by arthropods, more than 100 of them are human pathogens and many of the arboviruses have neurotropic characteristics such as dengue viruses (DENV) and Japanese encephalitis virus (JE-V). Both DENV and JE-V belong to the genus Flavivirus. Climatic changes, food imports from the tropics and travel behavior have also increased the number of cases of diseases caused by tropical or subtropical viruses in Europe. Due to the close degree of relationship of the flaviviruses, coinfections with several arboviruses can occur. The DENV and JE-V are mosquito-borne infections caused by the genus Aedes spp. In cases of involvement of the central nervous system, the virus often reaches the brain via the blood-brain barrier. The DENV is a single-stranded RNA-positive virus with four known serotypes, DENV-1 to DENV-4. The DENV infections are usually asymptomatic and are known as classical dengue fever, the more severe courses are dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), usually with fatal outcome. Both DHF and DSS are classical second infections. A vaccination is not approved in Germany but has been approved for endemic regions since 2015. The course of an infection with JE-V initially runs characteristically and it is only characterized by encephalitis a few days later. For the JE-V a vaccine is approved even in Germany.

Background: Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10-14% of the infected individuals suffer from long-term disability and in 1.5-3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT)., Methods: A case series of 11 patients with a prior history of vaccination, part of a recently published lager cohort of 111 TBE cases. Evaluation included clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of CSF and serum samples. Furthermore, metadata for extended analysis on clinical outcome of TBE with VBT were analysed., Results: One patient had a clear VBT and ten of them had irregular vaccinations schedules (IVS). Infection severity did not differ in patients with IVS as compared to a non-vaccinated control cohort (median mRS: both 3.0) but these patients showed a stronger cellular immune response as measured by CSF pleocytosis (IVS, 205 cells/μL versus non-vaccinated control, 114 cell/μL, P < 0.05) and by differential pattern of CSF (intrathecal) immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by-linear association revealed a more serious course of TBE in patients with VBT than in a non-vaccinated control cohort (χ 2  = 9.95, P = 0.002). Furthermore, ordinal logistic regression analysis showed that VBT patients had an age-corrected, 2.65 fold (CI: 1.110-6.328; χ 2  = 4.813; p = 0.028) significant higher risk to suffer from moderate or severe infections, respectively., Conclusion: A history of IVS surprisingly seems to have no impact on the clinical course of TBE but may leave marks in the specific brain immune response. VBT patients, however, carry an age-independent, significant risk to experience a severe infection., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Despite recent advances in multiple sclerosis (MS) care, many patients only infrequently access health care services, or are unable to access them easily, for reasons such as mobility restrictions, travel costs, consultation and treatment time constraints, and a lack of locally available MS expert services. Advances in mobile communications have led to the introduction of electronic health (eHealth) technologies, which are helping to improve both access to and the quality of health care services. As the Internet is now readily accessible through smart mobile devices, most people can take advantage of eHealth apps. The development of digital applications and remote communication technologies for patients with MS has increased rapidly in recent years. These apps are intended to complement traditional in-clinic approaches and can bring significant benefits to both patients with MS and health care providers (HCPs). For patients, such eHealth apps have been shown to improve outcomes and increase access to care, disease information, and support. These apps also help patients to participate actively in self-management, for example, by tracking adherence to treatment, changes in bladder and bowel habits, and activity and mood. For HCPs, MS eHealth solutions can simplify the multidisciplinary approaches needed to tailor MS management strategies to individual patients; facilitate remote monitoring of patient symptoms, adverse events, and outcomes; enable the efficient use of limited resources and clinic time; and potentially allow more timely intervention than is possible with scheduled face-to-face visits. These benefits are important because MS is a long-term, multifaceted chronic condition that requires ongoing monitoring, assessment, and management. We identified in the literature 28 eHealth solutions for patients with MS that fall within the four categories of screening and assessment, disease monitoring and self-management, treatment and rehabilitation, and advice and education. We review each solution, focusing on any clinical evidence supporting their use from prospective trials (including ASSESS MS, Deprexis, MSdialog, and the Multiple Sclerosis Performance Test) and consider the opportunities, barriers to adoption, and potential pitfalls of eHealth technologies in routine health care., (©Martin Marziniak, Giampaolo Brichetto, Peter Feys, Uta Meyding-Lamadé, Karen Vernon, Sven G. Meuth. Originally published in JMIR Rehabilitation and Assistive Technology (http://rehab.jmir.org), 24.04.2018.)

Background and Purpose: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT., Methods: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184)., Results: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001)., Conclusions: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network., (© 2018 S. Karger AG, Basel.)

Background: To meet the requirements imposed by the time-dependency of acute stroke therapies, it is necessary 1) to initiate structural and cultural changes in the breadth of stroke-ready hospitals and 2) to find new ways to train the personnel treating patients with acute stroke. We aimed to implement and validate a composite intervention of a stroke team algorithm and simulation-based stroke team training as an effective quality initiative in our regional interdisciplinary neurovascular network consisting of 7 stroke units., Methods: We recorded door-to-needle times of all consecutive stroke patients receiving thrombolysis at seven stroke units for 3 months before and after a 2 month intervention which included setting up a team-based stroke workflow at each stroke unit, a train-the-trainer seminar for stroke team simulation training and a stroke team simulation training session at each hospital as well as a recommendation to take up regular stroke team trainings., Results: The intervention reduced the network-wide median door-to-needle time by 12 minutes from 43,0 (IQR 29,8-60,0, n = 122) to 31,0 (IQR 24,0-42,0, n = 112) minutes (p < 0.001) and substantially increased the share of patients receiving thrombolysis within 30 minutes of hospital arrival from 41.5% to 59.6% (p < 0.001). Stroke team training participants stated a significant increase in knowledge on the topic of acute stroke care and in the perception of patient safety. The overall course concept was regarded as highly useful by most participants from different professional backgrounds., Conclusions: The composite intervention of a binding team-based algorithm and stroke team simulation training showed to be well-transferable in our regional stroke network. We provide suggestions and materials for similar campaigns in other stroke networks.

Background: What is telescience? Is it feasible to transfer academic information with the help of telematics to educate and teach young scientists over large distances? The term telescience has so far not been defined but covers a variety of possibilities, which could be successfully implemented worldwide. This article gives examples and highlights the feasibility analysis of telescience., Methods: We have carried out feasibility analyses for neurological functional diagnostics, an epidemiological cross-sectional study as well as a laboratory study for detection of thrombocyte function during dengue fever with the help of telemedicine. The basis for all these projects was a telemedical transcontinental cooperation over a distance of 12,000 km., Results: All performed studies demonstrated the feasibility. With the help of telematics the laboratory techniques, planning, conduction and interpretation of results as well as publication skills can be transferred., Discussion: Telescience is feasible. Our studies showed that telescience is a very promising option to transfer knowledge, which will help to enable professional expertise to be transferred directly to the region/country without a brain drain. All too often young motivated scientists are enticed to move to well-known institutions, which involves the danger of a brain drain. Brain drain can be avoided in favor of local implementation of scientific projects. Our results illustrate that it is feasible to educate and guide scientists with the help of telematics infrastructures.

Due to the world-wide aging population, there is a need for specialist neurological knowledge, treatment and care. Stroke treatment is effective in reducing mortality and disability, but it is still not available in many areas of the world. We describe the set-up process of a specialized Neuroscience, Stroke and Rehabilitation Centre in Brunei Darussalam (BNSRC) in cooperation with a German hospital. This study details the setup of a stroke-, neurological intensive care- and neurorehabilitation unit, laboratories and a telemedical network to perform all evidence-based stroke treatments. All neurological on-site services and the telemedical network were successfully established within a short time. After setup, 1386 inpatients and 1803 outpatients with stroke and stroke mimics were treated. All evidence-based stroke treatments including thrombolysis and hemicraniectomy could be performed. It is possible to establish evidence-based modern stroke treatment within a short time period by a transcontinental on-site and telemedical cooperation.

Background: Specialized neurological treatment decreases the mortality and morbidity of stroke patients. In many regions of the world an extensive coverage is not available. The cooperation between the Krankenhaus Nordwest (KHNW, Frankfurt, Germany) and the Government of Brunei Darussalam describes the set-up process of a specialized neurological center, including stroke unit, science and rehabilitation center., Aim: The aim of this project called to teach to treat - to treat to teach was to set up a center of excellence in neurology in Brunei Darussalam over a distance of 12,000 km. Treatment options were elucidated by teaching and taught by case examples., Material and Methods: The construction of the Brunei Neuroscience Stroke and Rehabilitation Center (BNSRC) began in July 2010. To overcome the large distance between the department of neurology and neuroradiology at the KHNW and the BNSRC, a telemedical network was established. We provided daily teleteaching for all professions involved in patient care as well as 24/7 availability of teleneurological services from Germany to support the local team on site., Results: In the BNSRC unit over 1000 patients with ischemic and hemorrhagic stroke and all the various acute neurological conditions were treated from July 2010 until July 2016 as inpatients and over 5000 were treated as outpatients. Since 2010, a total of 52 patients with stroke were treated by thrombolysis within the thrombolytic window and 81 hemicraniectomies were performed., Conclusion: The project has shown that it is possible to convey specialized neurological knowledge over large distances to provide significant benefits for patients and caregivers.

Purpose: Recurrent laryngeal nerve palsy in thyroid surgery is still a threatening complication. Our aim was to analyze the impact of prolonged tensile stress on the recurrent laryngeal nerve (RLN) in an animal model using continuous intraoperative neuromonitoring (C-IONM)., Methods: Constant tensile stress was applied to left and right RLNs in 20 pigs (40 RLN). In a pilot study, five animals were subjected to a tensile force of 0.34 ± 0.07 N for 10 min and changes in amplitude were documented using C-IONM. In the main study, a force of 1.2 N was applied until the signal amplitude was reduced by 85 %, in 15 pigs. Nerve conductivity was analyzed by threshold current measurements., Results: Good correlation was found between stress and amplitude decrease in the pilot study as well as between signal decrease and duration of trauma in the main study. Great variations were found inter- and intra-individually. These variations were most prominent at 85 % signal reduction (median 36 min, range 0.3-171 min). There was no side specificity (left 0.3-171 min, right 0.3-168 min, respectively, p = 0.19). However, in each individual animal, there was a sensitive (0.3-98.9 min) and less sensitive nerve (26.8-171 min). These differences became highly significant at 85 % of signal reduction (p = 0.008), where the vulnerability is 1.4 to 146.4 times higher on one side (mean 4.3)., Conclusions: Our study demonstrates the presence of a sensitive RLN that was 4.3 times more vulnerable than the contralateral nerve (range 1.4-146.4 times, p = 0.008). Thus, the right and the left nerves cannot be assumed to be of equal sensitivity to trauma. In our data, the more sensitive nerve does not occur predominantly on one side and was named the "weepy nerve."

Introduction: Professional boxing can lead to chronic traumatic encephalopathy, a variant of traumatic brain injury (TBI). Its occurrence in amateur boxers is a matter of debate since amateur boxing is considered to be less harmful due to more strict regulations. However, several studies using different methodological approaches have revealed subtle signs of TBI even in amateurs. Diffusion tensor imaging (DTI) is sensitive to microscopic white matter changes and has been proven useful in TBI when routine MR imaging often is unrevealing., Methods: DTI, with tract-based spatial statistics (TBSS) together with neuropsychological examination of executive functions and memory, was used to investigate a collective of 31 male amateur boxers and 31 age-matched controls as well as a subgroup of 19 individuals, respectively, who were additionally matched for intellectual performance (IQ)., Results: All participants had normal findings in neurological examination and conventional MR. Amateur boxers did not show deficits in neuropsychological tests when their IQ was taken into account. Fractional anisotropy was significantly reduced, while diffusivity measures were increased along central white matter tracts in the boxers group. These changes were in part associated with the number of fights., Conclusions: TBSS revealed widespread white matter disturbance partially related to the individual fighting history in amateur boxers. These findings closely resemble those in patients with accidental TBI and indicate similar histological changes in amateur boxers.

Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Objectives: Hypertension is the most important known risk factor for cardiovascular diseases. A cross-sectional study was conducted in Brunei Darussalam to estimate the prevalence of hypertension and its association with socioeconomic and life-style factors and impact on stroke incidence., Methods: Five thousand and sixty-three participants aged above 18 years from 2103 randomly selected households in the Brunei-Muara district of Brunei Darussalam were surveyed. Hypertension was defined as mean SBP at least 140 mmHg, DBP at least 90 mmHg, or taking antihypertensive medication and blood pressure was measured twice. Logistic regression models are used to analyze the association between hypertension/medication for hypertension and sex, age, overweight, education, smoking, family history of hypertension, and employment., Results: A total of 48.3% [95% confidence interval (CI): 46.9-49.7%] of all respondents were identified as hypertensive. Prevalence of hypertension was higher in men (52.8%; 95% CI: 50.7-54.9%) compared to women (45.0%; 95% CI: 43.2-46.8%) and women seek treatment more often than men. Age, overweight, lower levels of education, and a family history of high blood pressure are positively associated with the prevalence of hypertension. The prevalence of overweight (57.3%) and obesity (23.7%) is high and the attributable risk of hypertension for stroke is large., Conclusion: The prevalence of hypertension in Brunei is high in both women and men. Information campaigns and prevention programs are needed to be able to cope with the increasing problem of hypertension and resulting diseases like stroke in Brunei in the near future.

Background and Objectives: Tick-borne encephalitis (TBE) still represents a considerable medical and health economic problem in Europe and entails a potential threat to travellers. The aim of this study was to characterise the conditions of severe TBE by precisely recording its clinical variants, the related neuroimaging features, and the variant-specific long-term outcome and by identifying predictors for severe courses., Methods: A cohort of 111 TBE patients (median age 51, range 17-75 years; 42% females) was analysed prospectively. Data were acquired from the department of neurology, University Hospital Heidelberg, and the infectious diseases registry of the Robert-Koch institute Berlin. Neurological status was ascertained by protocol at admission and discharge and the degree of disability was scored using the modified RANKIN Scale (mRS; clinical score addressing neurological disability, range from 0, healthy to 6, dead) at admission and at follow-up. Follow-up examination was conducted by means of a telephone interview. To identify independent predictors for severe TBE and functional outcome, modelled logistic regression was performed. MRI changes were correlated with infection variants. To assess alpha-motor neuron injury patterns, we used high-resolution magnetic resonance neurography (hrMRN). Analyses were performed at the Department of Neurology, University Hospital, University of Heidelberg from April 2004 through September 2014., Results: Acute course: 3.6% of patients died during the acute infection. All patients with a lethal course suffered from meningoencephaloradiculitis (MER, 14.4% of the cohort), which is associated with a significantly higher risk of requiring intensive care (p = 0.004) and mechanical ventilation (p<0.001) than menigoencephalitis (ME, 27.9% of the cohort). At admission, both MER and ME groups were severely affected, with the MER group having a statistically higher mRS score (median of 5 in the MER groups versus 4 in the ME group; p<0.001). Long-term outcome: outcome for MER was considerably worse (median mRS = 4) than for ME (mRS = 1, p<0.0001) and meningitis (mRS = 0, 57.7% of the cohort)., Risk Factors: advanced age (p<0.001) and male gender (p = 0.043) are independent risk factors for a severe infection course. Furthermore, we identified pre-existing diabetes mellitus (p = 0.024) as an independent risk factor for MER. In MER, alpha-motor neuron injury accounts for the poor prognosis confirmed by hrMRN., Conclusion and Relevance: These data provide critical information for neurologists and other health professionals to use in evaluating TBEV patients who live in or travel to endemic areas. This information can be used to classify clinical presentation and estimate infection-associated complications and individual prognosis. Furthermore, the risk for severe, disabling infections in older patients should prompt general practitioners to recommend and encourage vaccination to those patients living in or travelling to endemic areas.

Neurocysticercosis is a leading cause of acquired epilepsy worldwide and endemic in underdeveloped and developing regions. As a result of increased migration and traveling, cases of neurocysticercosis reach Europe more frequently. Neurological symptoms are multifarious and often nonspecific, so that neurocysticercosis poses a diagnostic challenge. We report a case of a patient in whom the diagnosis of neurocysticercosis was achieved quickly via the patient's history, neuroimaging and serology., (© Georg Thieme Verlag KG Stuttgart · New York.)

The blood-brain barrier is morphologically composed of cerebral microcapillary endothelium through its tight junctions. It serves as a mechanical, metabolic and cellular barrier and can also protect the brain from pathogen invasion. Many brain diseases involve a disturbance of blood-brain barrier function either as a consequence of a noxa or as primary failure. In vitro models of the blood-brain barrier are suitable tools to study drug transport, pathogen transmigration and leukocyte diapedesis across the cerebral endothelium. Such models have previously been derived mainly from porcine or bovine brain tissues. We describe here a simple method by which rat cerebral microcapillaries and cells of glial origin can be quickly and simultaneously purified. By using a capillary fragment size restriction method based on glass bead columns different fractions can be separated: vital, long capillary fragments for ex vivo uptake studies and smaller capillary fragments for endothelial culture. Furthermore, fractions can be obtained for astroglial and oligodendroglial cell cultures. With this method both microcapillary enrichment and glial cell purification are quickly achieved, which reduces expenditure, number of required animals and laboratory working time., (Copyright © 2013. Published by Elsevier B.V.)

Human herpesviruses may cause infections of the central nervous system during primary infection or following reactivation from a latent state. Especially in immunosuppressed patients the infection can take a life-threatening course, and therefore early diagnosis of herpesvirus-associated neurological diseases should have high priority. Clinical presentation in these patients is usually without typical features, making diagnosis even more challenging. Therefore general broad testing for different herpesviruses in cerebrospinal fluid samples is highly recommended. In addition, determination of the virus DNA level in the cerebrospinal fluid by quantitative assays seems to be of high importance to determine prognosis. Moreover, it might help to differentiate between specific virus-associated disease and unspecific presence of virus in the cerebrospinal fluid, especially in immunocompromised patients. Polymerase chain reaction analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses. This review summarizes the role human herpesviruses play in central nervous system infections in immunocompromised patients, with a focus on the clinical manifestation of encephalitis.

Background: The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question., Design: GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage., Conclusion: 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients., Trial Registration: Current Controlled TrialsISRCTN45122933.

Background: A variety of tools has been developed to identify nerve structures and to lower the risk of nerval injury during thyroid surgery. These tools are usually based on intermittent electrophysiological tracing of the nerves, but its use is still associated with permanent recurrent laryngeal nerve (RLN) injury. We are now presenting the results of the implementation of a novel real-time nerve monitoring system, based on a new vagal nerve cuff electrode., Methods: Nineteen consecutive patients scheduled for thyroid surgery (17 with benign, 2 with malignant disease), were enrolled in this observational trial. The flexible cuff electrode was implanted during each operation and atraumatically surrounded the vagal nerve. The evoked potentials were sensed by standard thyroid electrodes. Electrical stimulation and recording were achieved through a multichannel electromyography (EMG) system. The signal analysis was performed in real-time by specially designed software., Results: The cuff electrode did not cause any complications during or after the surgery. In all patients, stable and reproducible signals were easily evoked. The mean time required to place the electrode was 6.5 min. The mean overall vagal nerve stimulation time was 65 min. No permanent RLN lesions were detected in any patient. One patient with a postoperative bleeding from a strap muscle vein required a wound revision, which was performed without nerve monitoring. This patient experienced a temporary partial impairment of the left vocal cord. No hypoparathyroidism was observed in any patient postoperatively., Conclusions: The presented technique of real-time continuous RLN monitoring by stimulation of the vagal nerve is feasible, safe, reproducible, and easy to perform. In addition, this new system is compatible with existing equipment and can be used as an add-on with conventional nerve monitoring devices during thyroid surgery.

Background and Purpose: The evidence for traumatic brain injury in amateur boxers is controversial. Hypothetically, sudden acceleration of the head due to the impact of the blow during the boxing fight might result in diffuse axonal injury or contusion. We wanted to determine whether cerebral microhemorrhages occur more often in amateur boxers than in nonboxers., Materials and Methods: In 42 male, classical amateur boxers and in 37 healthy, nonboxing male volunteers we performed cranial MR imaging at 3T. The study protocol included a transverse dual spin-echo MR imaging sequence, a 3D sagittal magnetization-prepared rapid acquisition of gradient echo sequence, a coronal T2*-weighted sequence, and an axial time-of-flight MR angiography sequence. MR imaging data were made anonymous before 2 neuroradiologists independently evaluated the images. In addition, the following risk factors were assessed: total numbers of fights and knockouts, weight division, and duration of boxing. We compared the group proportions of microhemorrhages with Fisher test of exact probability., Results: There was a statistically higher prevalence of cerebral microhemorrhages in the group of boxers (3 of 42; 7.1%) than in nonboxing persons (0 of 37; 0%). This difference was not statistically significant, however (P = .2479; Fisher exact test)., Conclusion: Although we detected more microhemorrhages in amateur boxers than in nonboxing persons, this difference did not prove to be significant.