[Telemedicine and international projects: from Asia to Africa: chances for the future?] / Telemedizin und internationale Projekte: von Asien nach Afrika ­ Chancen der Zukunft?

Although the morbidity and mortality of neurological diseases in many Asian and African countries is high and are predicted to increase even further in the coming decades, in many areas there is a shortage of medical personnel and high-quality treatment options. This shortage, together with a frequently insufficient healthcare infrastructure, limits the access of many patients to medical treatment. The possibilities of telemedicine are multifarious. It provides new, so far unused possibilities in the diagnostics and treatment of neurological diseases, totally independent of geographical boundaries. In the future it could also be used for the education and training of physicians and medical personnel and to close the existing gaps in healthcare, especially in developing countries.

[Telerehabilitation: from the virtual world to reality-Medicine in the twenty-first century : Video-assisted treatment in times of COVID-19]. / Telerehabilitation: von der virtuellen Welt zur Realität ­ Medizin im 21. Jahrhundert : Videogestützte Therapie in Zeiten von COVID-19.

Neurological diseases are the most common cause of disability worldwide. In addition to physical limitations, they often lead to cognitive deficits that make active participation in professional and social life difficult. Due to physical and cognitive deficits, it is often difficult for neurological patients to gain access to specialized knowledge or to receive specialized treatment and is associated with greatly increased effort. Neurological diseases account for 11.6% of global disability-adjusted life years (DALYs, a measure for quantifying disease burden) and 16.5% of deaths, and remain the leading cause of DALYs and the second leading cause of death worldwide. Neurorehabilitation encompasses the goal of reintegrating patients with neurological dysfunctions into everyday life. The ongoing situation in the context of the COVID-19 pandemic poses new challenges for the healthcare system. Social distancing and quarantine have deprived many people with neurological disorders of access to routine medical care. The corona pandemic is a catalyst for the widespread use of telemedicine in the field of neurology and neurorehabilitation. Projects such as the Brunei project of the Nordwest Krankenhaus Frankfurt as well as an MS clinic in Canada show that highly specialized medicine and neurorehabilitation can be delivered to remote areas or in the living room of patients or any doctor's office. Telemedical, telerehabilitative and teletherapeutic applications offer the opportunity to supplement and optimize existing care structures and with modern technology to make a new and contemporary interpretation of old-fashioned medical and therapeutic home visits.

The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.

[Winners of globalization: dengue viruses and Japanese encephalitis virus-Diseases in neurology]. / Gewinner der Globalisierung: Dengue-Viren und Japanisches Enzephalitisvirus ­ Erkrankungen in der Neurologie.

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.

[Mission (im)possible : Setting up a neurological center 12,000 km away with telemedicine]. / "Mission (im)possible" : Aufbau eines neurologischen Zentrums 12.000 km entfernt mittels Telemedizin.

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.

[Telescience : Feasibility studies, definition and a fair answer to the scientific brain drain]. / Telewissenschaft ­ Telescience : Machbarkeitsstudie, Definition und eine faire Antwort zum Wissenschafts-Braindrain.

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.

Setting up a Neuroscience Stroke and Rehabilitation Centre in Brunei Darussalam by a transcontinental on-site and telemedical cooperation.

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.

CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

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.

[Neurocysticercosis]. / Neurozystizerkose.

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.

[Acute viral and emerging viral CNS infections]. / Akute virale und importierte virale Entzündungen des ZNS.

The morbidity and mortality of viral CNS infections can be reduced through early initiation of therapy, which could be specific or in most cases symptomatic. This in turn requires the physician to consider meningoencephalitis as a differential diagnosis.Increasing climate changes, global air travel and changing immune responses contribute to the emergence of rather rare viral pathogens on our continent. Thus, neurologists in Europe are facing an enormous challenge due to lacking knowledge and experience of these new germs, which needs to be taken care of.Novel therapeutic approaches with e.g. monoclonal antibodies awaken the hope of mitigating the partially lethal courses of these diseases.

[Vasculitis of the nervous system in infectious diseases]. / Vaskulitis des Nervensystems bei Infektionserkrankungen.

Vasculitis and vasculopathies of the central and peripheral nervous system can be caused by infectious diseases. Vasculitis can lead to stenosis, occlusion and aneurysm formation of blood vessels which may result in stroke or cerebral haemorrhage. In cases of peripheral nervous system involvement mononeuritis multiplex and symmetric peripheral neuropathy are possible. The diagnosis is based on clinical presentation, serology, cerebrospinal fluid analysis and neuroradiologic examinations. In cases of peripheral neuropathy neurophysiologic examinations and biopsy of the sural nerve can lead to the diagnosis. A fast and efficient antimicrobial therapy is the most important treatment option. In cases of peripheral neuropathies short-term treatment with corticosteroids and plasma exchange may be helpful.

Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time.

BACKGROUND: The diagnosis of multiple sclerosis (MS) is based on dissemination in space (DIS) and time (DIT). The aim of the study was to assess the impact of spinal cord (SC) imaging on the evidence of DIS and DIT. METHODS: Thirty-five treatment-naive patients with a first clinical symptom suggestive of MS were examined in a 2-year prospective longitudinal follow-up assessment. Brain and SC magnetic resonance imaging (MRI), Expanded Disability Status Scale and multiple sclerosis functional composite were analysed at baseline and after 1 and 2 years. RESULTS: At study entry, 21 patients were classified as clinically isolated syndrome suggestive of MS (CIS) and 14 patients as possible early MS. SC lesions were detected at baseline in 14 CIS patients (67%, median: 1.0, enhancing 29%) and in 11 patients with possible early MS (79%, median: 2.0, enhancing 29%). DIS as depicted by additive SC imaging was detected in two additional individuals according to the revised versus the 2001 McDonald criteria. All patients with emerging cord lesions showed new brain lesions. Five individuals developed clinically asymptomatic cord lesions. CONCLUSIONS: Spinal cord abnormalities are frequent in CIS patients and in patients with possible early MS. SC imaging slightly improved the establishment of DIS, but had no impact on the evidence of DIT.

Prevalence of cerebral microhemorrhages in amateur boxers as detected by 3T MR imaging.

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.

Quantitative diffusion tensor imaging in herpes simplex virus encephalitis.

Diffusion-weighted imaging (DWI) has been employed in many brain pathologies, but with few studies only and heterogeneous results in herpes simplex virus encephalitis (HSVE). Diffusion tensor imaging (DTI) in comparison to DWI yields additional directional diffusion data, adding information and enabling a more differentiated description of brain pathologies. The authors addressed the question whether tissue changes as identified on T2-weighted magnetic resonance imaging (MRI) could be further characterized by DTI, in particular whether different forms of edema may occur in HSVE. Six patients with HSVE confirmed by positive polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) samples were studied. Patients were examined with MRI including DTI in the early stage of the infection. Conventional MRI- and DTI-derived parameter maps were analyzed for signal change qualitatively and by region-of-interest (ROI) analysis of the affected brain parenchyma. All patients showed typical clinical characteristics of HSVE and lesions in the mediobasal temporal structures and insula. In two cases hemorrhagic inflammatory tissue changes were found. DTI analysis showed slightly reduced mean diffusivity (MD) and increased fractional anisotropy (FA) values in the earliest phase. Patients scanned at day 14 or later had lesions with increased MD and reduced FA in accordance with inflammatory vasogenic edema. This study confirms signal change consistent with the presence of inflammatory vasogenic edema in HSVE as the most prominent DTI finding. In the early stage slight reductions of MD may be found, which might be due to a specific mechanism of viral infection.

Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis.

Structural damage of the central nervous system (CNS) often leads to severely disabling residual symptoms despite effective antiviral therapy during Herpes simplex virus encephalitis (HSVE). Edematous space-occupying lesions are pathological and neuroradiological well-known phenomena for this disease. The molecular mechanisms of brain edema development in HSVE are poorly understood, the regulation of water brain-blood barrier (BBB) permeability might be disturbed. Aquaporin 4 (AQP4) is the predominant aquaporin expressed in the brain. Aquaporin 1 (AQP1) plays a role in cerebrospinal fluid modulation. Previous studies suggest that alterations of AQP expression play an important role in the development of brain edema. The mRNA expression of AQP4, AQP1, of their physiologically associated proteins Alpha-syntrophin and KIR 4.1 and of the structural glial protein glial fibrillary acid protein (GFAP) was analyzed in a well-established mice model simulating the human disease. Our data demonstrate a significant down-regulation of AQP4 in the acute phase of disease and an up-regulation of AQP4 and AQP1 in the long term. These results reveal the complex transcription pattern of AQP4, AQP1, KIR 4.1, alpha-syntrophin, and GFAP during HSVE and suggest a role for AQP4 regulation in the pathophysiology of acute and long-term HSVE. AQP4 modulation could be a potential target for brain edema treatment during HSVE.

[Acute cerebral circulation problems]. / Akute zerebrale Durchblutungsstörung.

Acute stroke is the third most common cause of death and also the most common cause of permanent disability in industrialized countries. Ischemic stroke is caused by occlusion of a cerebral artery leading to a critical reduction in brain perfusion in the respective brain area (penumbra). Most acute stroke treatment strategies are based on the penumbra concept: attaining rapid and persistent reperfusion is followed by the protection of critically ischemic and not yet infarcted (penumbral) tissue by, e.g., neuroprotection. Examination of the acute stroke patient includes a brief history, neurostatus and imaging (CT or MRI) for the exclusion of intracerebral hemorrhage. The diagnostic standard is CT; modern stroke MRI protocols provide an improved selection in later time windows. Intravenous thrombolysis with rt-PA within 3 h of symptom onset is the only approved therapy with a proven significant benefit for the patient. The effect is smaller but still significant if treatment occurs up to 4.5 h, and may still be present in MRI selected patients up to 9 h. More aggressive forms of therapy include interventional reperfusion techniques and therapy of malignant MCA infarction such as hemicraniectomy and hypothermia, which at present, however, are not routine and are only performed in specialized centers.