Thymectomy in Myasthenia Gravis

In recent years much progress has been made in the investigation of the pathophysiology, characterizing subgroups, and extension of multimodal treatment of myasthenia gravis (MG). This applies especially to the role of thymectomy (Thx). Thymectomy is always indicated for thymoma-associated myasthenia gravis. Furthermore, based on large cohort studies, during recent decades thymectomy has also become a central part of immune-modulating MG therapy in patients without thymoma. The lack of randomized studies, however, caused a certain persistent reluctance as to the significance of thymectomy. The current MGTX trial has shown the effectiveness of thymectomy. A significant improvement of myasthenic complaints and the reduction of immunosuppressive medication was primarily shown for acquired early-onset MG (EOMG) with complete resection of all thymic tissue. Because the MGTX study only included patients younger than 65 years with generalized MG and positive for acetylcholine-receptor antibodies, at present the significance of Thx for other relevant subgroups as juvenile MG, MG in older patients, ocular MG, as well as seronegative patients is under investigation. Even the prevailing opinion of no benefit of thymectomy for MuSk-positive patients probably needs reevaluation based on ambiguous findings. With respect to surgery, based on the exclusive performance of extended median sternotomy for MG in the MGTX, the value of thoracoscopic modifications for thymectomy as a minimally-invasive alternative is currently under evaluation. For clinical reasons further judgment regarding different minimally-invasive thymectomy techniques compared to the conventional open procedures in the form of randomized comparative studies would be required. Currently, however, an experience-based robotic-assisted thoracoscopic unilateral approach to thymectomy meets all requirements related to surgical, clinical-neurological and patient aspects. Ethical reasons, therefore, will lead to other strategies for comparison of different surgical techniques.

Modern Techniques of Radiation Therapy in the Treatment of Brain Tumors and Tumors of the Skull Base

Today the choice of radiation oncology technique and treatment concept is highly individualized. Modern techniques enable the use of high local doses with significant sparing of normal tissue. This has significantly improved the therapeutic window. Molecular markers guide therapy decisions within the interdisciplinary context, for primary as well as secondary brain tumors. Skull base tumors benefit from highly precise radiation techniques; often, radiation therapy can be seen as a treatment alternative to surgery in this region.

Treatment Standards and Individualized Therapy of Myasthenia Gravis

A wide range of established treatment options is currently available for myasthenia gravis. These include cholinesterase inhibitors for symptomatic treatment and a broad spectrum of immunosuppressive, immunomodulating or cell-depleting options to modify the underlying immunological process. Appropriate use allows the great majority of patients to lead a normal life. Specialized centers integrating outpatient and in-hospital resources as well as interdisciplinary competences offer important advantages for optimum individualized therapy.

Diagnosis of Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. The diagnosis of myasthenia gravis (MG) is based on clinical features, combined with neurophysiological and immunological parameters. Autoantibodies against the nicotinic acetylcholine receptor are the main finding in about 80% of the patients. More recently, autoantibodies against muscle-specific kinase (MuSK) and lipoprotein receptor-associated protein 4 (LRP4) have been identified in a subset of MG patients. Additionally, anti-titin autoantibodies can point to an underlying thymoma in younger MG patients. Neurophysiological examination includes a repetitive stimulation to detect a possible decrement as the electrical correlate of pathological muscle fatigability. Single-fiber electromyography can identify neuromuscular transmission disturbances in otherwise unclear cases.

Off-Label Use in Rare Diseases: Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenic Syndromes

The off-label use of licensed drugs is widespread, and the risk of adverse events is elevated, especially if the scientific evidence is low. The treatment of rare diseases (<5/10,000) therefore may increase the risk of off-label use. The optimized standard treatment is primarily based on the regulatory decisions of the German Federal Joint Committee. The valid guidelines and the regulations of the German health system are discussed in this article. The criteria for indication and monitoring of off-label use are shown, especially focused on the problem of refractory myasthenia gravis. Escalation of treatment results regularly in off-label use. The arguments within the applicable guidelines should be followed. Some new aspects of the European regulations are likewise discussed.

Physiotherapy and Occupational Therapy in Acute Neurology

Therapy of neurological patients comprises, beyond medical treatment, the treatment of functional deficits which result from a neurological disease such as stroke. Physiotherapy aims at enabling bedridden neurological patients to become mobile again using training of movement and coordination. In cooperation with occupational therapists, patients are trained to become able to perform activities of daily living again. In addition, multimodal activating/assisting exercises are mandatory to counteract the deficit-related development of joint contractures. The rationale for these exercises are neurophysiological findings about postlesional cerebral plasticity. Moreover, parametric scales have been developed to assess neurological disturbances and to monitor their resolution in an observer-independent fashion. This allows communication across institutions and to assess the efficacy of physiotherapy and occupational therapy.

The General and Social Health Long-Term Outcome of Adult Epilepsy Patients at the Kork Epilepsy Center

Objectives The majority of epidemiological studies show that there is an increased burden of somatic comorbidities among people with epilepsy (PWE) compared with the general population. We sought that in the subgroup of patients with satisfactory and stable seizure situation and healthy style of living, the general health and quality of life might be similar to people without epilepsy and investigated the long-term outcome and the prevalence of comorbidities and the social outcome of adult patients who had been continuously treated at our center for at least 25 years. Material and methods We consecutively collected our adult out-patients for 10 months and identified those patients who had been treated at our center for at least 25 years. Among this group we assessed demographic data, epilepsy syndrome, seizure situation, antiepileptic therapy, the number of previous AEDs, the socioeconomic situation and co-morbidities. Results Out of a total of 1672 patients, 14.4 % (n = 241) patients fulfilled our inclusion criterion. In 200 the files allowed an appropriate analysis of the data. Mean treatment duration in Kork was 36 years (25 – 52). 60% of patients were seizure-free for more than one year. 80% of the seizure-free patients did not complain of adverse events. Adverse events were more often among patients with ongoing seizures. Somnolence, gait disturbances and tremor were the leading symptoms. Better seizure outcome correlated with higher education, better professional education and lower unemployment rates. Diseases such as cardiovascular diseases or diabetes mellitus were not more frequent than in the general population. PWE do not have necessarily an impaired prognosis of their general health.

Myasthenia Gravis: Family Planning, Pregnancy and Delivery

Myasthenia gravis affects women younger than 40 about three times more frequently than men. Therefore, questions about family planning, pregnancy and delivery are common for these patients and their treating physicians. The outcome for mother and child depends a good deal on knowledge of the influence of pregnancy on myasthenia, therapy options, the relationship between the disease and delivery and the newborn. This paper provides an overview of these situations to support women with myasthenia gravis and their physicians in their decision-making regarding desire for children, the course of pregnancy and delivery and neonatal considerations. With thorough advice, good preparation and support of partners and families, the desire for a child can come true for patients with myasthenia gravis. Taking special precautions and with interdisciplinary treatment, the risks for mother and child can be minimized.

Juvenile Myasthenia Gravis

Juvenile myasthenia gravis (JMG) is an autoimmune disorder of neuromuscular transmission caused by production of antibodies against the postsynaptic membrane of the neuromuscular junction. Clinical signs in young children and adolescents range from isolated ocular symptoms to general muscular weakness and respiratory insufficiency. Clinical presentation of JMG in young children and adolescents shows distinct features compared to adults. Young children may show generalized muscular weakness already during the first two years of life, and in this group specific antibodies can be only slightly increased. Because of existing therapeutic options, an early diagnosis is important. In case of negative specific antibodies and onset of the first symptoms during infancy or early childhood, the diagnosis of a congenital myasthenic syndrome (CMS) must be considered and is not always clear to differentiate. Clinical symptoms, diagnostic procedures and therapeutic strategies with consideration of specificities of this age group are discussed.

Neuroimmunological Registries in Germany

Several neuroimmunological registries have been established in Germany during the last 10 years. The common aim is to investigate the course of different diseases, mainly under various therapeutic conditions, to identify predictive factors as well as the side effects of immunomodulating therapies. Six nationwide neuroimmunological registries will be presented in this article. The German Network for Research on Autoimmune Encephalitis (GENERATE) with more than 40 participating clinical centers and 570 documented patients (September 2016) collects data and biomaterials of autoimmune encephalitis with known and unknown antibodies. The registry coordinates and mediates between scientists and clinicians and acts as a platform for the development of guidelines and procedures. The neuromyelitis optica study group (NEMOS) has established a national registry for patients with neuromyelitis optica and neuromyelitis optica spectrum disorders. In addition to 22 academic hospitals, 17 regional hospitals and several practices are participating. Currently, 250 patients are enrolled. Moreover, NEMOS is now establishing a prospective patient cohort (NationNMO) within the competence network multiple sclerosis. Current research focuses on treatment strategies for relapses and interval therapy of neuromyelitis optica. The competence network multiple sclerosis has initiated a multi-center, prospective cohort study of patients with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (MS) (NationMS), with the aim of long-term follow-up and clinical and paraclinical characterization of the patients. Between August 2010 and December 2014, 1,212 patients in 22 university und non-university centers were enrolled in the NationMS cohort. Standardized clinical data as well as biomaterial and MRI images were collected and stored. The German MS Society (DMSG, Bundesverband e.V.) established in 2001 a long-term project to obtain a consistent and reliable overview of MS patients in Germany. Since 2014 the registry has been revised comprehensively, with the main purpose of establishing a permanent data repository for healthcare research while ensuring the collection, storage and provision of data over decades and enabling the description of long-term outcomes. Currently, more than 170 German centers are participating and over 48,000 patients are enrolled in the registry. Since 2013, the competence network multiple sclerosis has established the immunotherapy registry REGIMS with the objective to obtain information on incidence, type and characteristics of adverse events of new immunomodulating therapies for patients with multiple sclerosis or clinical isolated syndrome. As of January 2017 more than 700 patients have been recruited from 36 active centers. The German Multiple Sclerosis and Pregnancy Registry aims to obtain safety information of disease modifying drug exposure during pregnancy. In addition to safety aspects, disease course during pregnancy and postpartum and the identification of predictors of disease activity are investigated. During the last ten years 1,500 pregnant MS patients were prospectively enrolled in the registry and at least 250 new pregnancies are followed every year. These six registries make an important epidemiological and scientific contribution. Numerous colleagues from clinics and practice support these registries. The objective is the closer understanding of the disease course, the influence of therapeutic decisions and thus the improvement of counseling and care.