The German healthcare system

The foundation of Germany’s healthcare system is derived from Germany’s Basic Law (Grundgesetz), which obliges the state to provide social services to its citizens (Articles 20, 28 of the Basic Law). Specifically, the state must ensure sufficient, needs-based ambulatory and inpatient medical treatment, in qualitative and quantitative terms, as well as guarantee the provision of medicine. The federal government may assume this duty itself or delegate it to state governments and institutions in the form of service guarantee contracts (§ 72, German Social Insurance Code, Book V). The following paper provides an overview of the structural organization, individual components and funding of the German healthcare system, which, in its current form, is extremely complex and which even experts find difficult to grasp

Visualizing the Central Nervous System: Imaging Tools for Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are autoimmune central nervous system conditions with increasing incidence and prevalence. While MS is the most frequent inflammatory CNS disorder in young adults, NMOSD is a rare disease, that is pathogenetically distinct from MS, and accounts for approximately 1% of demyelinating disorders, with the relative proportion within the demyelinating CNS diseases varying widely among different races and regions. Most immunomodulatory drugs used in MS are inefficacious or even harmful in NMOSD, emphasizing the need for a timely and accurate diagnosis and distinction from MS. Despite distinct immunopathology and differences in disease course and severity there might be considerable overlap in clinical and imaging findings, posing a diagnostic challenge for managing neurologists. Differential diagnosis is facilitated by positive serology for AQP4-antibodies (AQP4-ab) in NMOSD, but might be difficult in seronegative cases. Imaging of the brain, optic nerve, retina and spinal cord is of paramount importance when managing patients with autoimmune CNS conditions. Once a diagnosis has been established, imaging techniques are often deployed at regular intervals over the disease course as surrogate measures for disease activity and progression and to surveil treatment effects. While the application of some imaging modalities for monitoring of disease course was established decades ago in MS, the situation is unclear in NMOSD where work on longitudinal imaging findings and their association with clinical disability is scant. Moreover, as long-term disability is mostly attack-related in NMOSD and does not stem from insidious progression as in MS, regular follow-up imaging might not be useful in the absence of clinical events. However, with accumulating evidence for covert tissue alteration in NMOSD and with the advent of approved immunotherapies the role of imaging in the management of NMOSD may be reconsidered. By contrast, MS management still faces the challenge of implementing imaging techniques that are capable of monitoring progressive tissue loss in clinical trials and cohort studies into treatment algorithms for individual patients. This article reviews the current status of imaging research in MS and NMOSD with an emphasis on emerging modalities that have the potential to be implemented in clinical practice

Accelerating clinical research in neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders are rare relapsing inflammatory central nervous system diseases with a heterogenous immunological and clinical spectrum. International collaborations are required to: (i) reach a better understanding of the disease and its subtypes; (ii) develop laboratory and imaging biomarkers; and (iii) ultimately improve treatments

Imaging the Visual Pathway in Neuromyelitis Optica

The focus of this paper is to summarize the current knowledge on visual pathway damage in neuromyelitis optica (NMO) assessed by magnetic resonance imaging (MRI) and optical coherence tomography (OCT)

Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies

Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies

Break up of heavy fermions at an antiferromagnetic instability

We present results of high-resolution, low-temperature measurements of the Hall coefficient, thermopower, and specific heat on stoichiometric YbRh2Si2. They support earlier conclusions of an electronic (Kondo-breakdown) quantum critical point concurring with a field induced antiferromagnetic one. We also discuss the detachment of the two instabilities under chemical pressure. Volume compression/expansion (via substituting Rh by Co/Ir) results in a stabilization/weakening of magnetic order. Moderate Ir substitution leads to a non-Fermi-liquid phase, in which the magnetic moments are neither ordered nor screened by the Kondo effect. The so-derived zero-temperature global phase diagram promises future studies to explore the nature of the Kondo breakdown quantum critical point without any interfering magnetism.Comment: minor changes, accepted for publication in JPS

The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice

Background There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates. Fat-1 mice express an n-3 desaturase, which allows them to convert n-6 PUFAs into n-3 PUFAs. Results CNS lipid profiles in fat-1 mice showed a significant increase of eicosapentaenoic acid (EPA) levels but similar docosahexaenoic acid levels compared to wt littermates. This was also reflected in significantly higher levels of monohydroxy EPA metabolites such as 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 brain tissue. Feeding fat-1 mice and wt littermates 0.2% cuprizone for 5 weeks caused a similar degree of CNS demyelination in both groups; remyelination was increased in the fat-1 group after a recovery period of 2 weeks. However, at p = 0.07 this difference missed statistical significance. Conclusions These results indicate that n-3 PUFAs might have a role in promotion of remyelination after toxic injury to CNS oligodendrocytes. This might occur either via modulation of the immune system or via a direct effect on oligodendrocytes or neurons through EPA- derived lipid metabolites such as 18-HEPE

Exercise in multiple sclerosis -- an integral component of disease management

Multiple sclerosis (MS) is the most common chronic inflammatory disorder of the central nervous system (CNS) in young adults. The disease causes a wide range of symptoms depending on the localization and characteristics of the CNS pathology. In addition to drug-based immunomodulatory treatment, both drug-based and non-drug approaches are established as complementary strategies to alleviate existing symptoms and to prevent secondary diseases. In particular, physical therapy like exercise and physiotherapy can be customized to the individual patient's needs and has the potential to improve the individual outcome. However, high quality systematic data on physical therapy in MS are rare. This article summarizes the current knowledge on the influence of physical activity and exercise on disease-related symptoms and physical restrictions in MS patients. Other treatment strategies such as drug treatments or cognitive training were deliberately excluded for the purposes of this article

Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis

Neuromyelitis optica spectrum disorders (NMOSD) are autoantibody mediated chronic inflammatory diseases. Serum antibodies (Abs) against the aquaporin-4 water channel lead to recurrent attacks of optic neuritis, myelitis and/or brainstem syndromes. In some patients with symptoms of NMOSD, no AQP4-Abs but Abs against myelin-oligodendrocyte-glycoprotein (MOG) are detectable. These clinical syndromes are now frequently referred to as "MOG-encephalomyelitis" (MOG-EM). Here we give an overview on current recommendations concerning diagnosis of NMOSD and MOG-EM. These include antibody and further laboratory testing, MR imaging and optical coherence tomography. We discuss therapeutic options of acute attacks as well as longterm immunosuppressive treatment, including azathioprine, rituximab, and immunoglobulins