Lambert-Eaton Myasthenic Syndrome; Pathogenesis, Diagnosis, and Therapy

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare disease with a well-characterized pathogenesis. In 50% of the patients, LEMS is a paraneoplastic manifestation and caused by a small cell lung carcinoma (SCLC). Both LEMS patients with SCLC and those without this tumour have in 85% of cases pathogenetic antibodies of very high LEMS specificity against voltage-gated calcium channels (VGCCs) in the cell membrane of the presynaptic motor nerve terminal. Better understanding of LEMS pathogenesis has lead to targeted symptomatic therapy aimed at the neuromuscular junction and to semispecific immuno-suppression. For SCLC LEMS, tumour therapy is essential

Physical training and exercise in myasthenia gravis

Under embargo until: 2021-12-18Myasthenia gravis is characterized by muscle weakness and fatigue. As sustained muscle use increases the weakness, the value of physical training programs has previously been questioned. This is a review to clarify the safety and usefulness of systematic training in myasthenia gravis, based on a systematic search in available databases using the relevant key words. Ten intervention studies including 159 patients with generalized disease have been published regarding the effect of systematic physical training, three of them on respiratory muscles. Muscle strength improved, and in the majority of the studies also daily function and quality of life. The feeling of fatigue not directly related to actual muscle weakness was less influenced by physical training. Continuous training was necessary to maintain the improved function. Physical training and exercise are safe in myasthenia gravis. This can improve both muscle strength and daily function. Type and intensity of systematic training should be adapted in the individual patient. A minimum of 150 min of exercise per week is recommended for myasthenia gravis patients with mild and moderate disease.acceptedVersio

Post-secular religion and the therapeutic turn: three Norwegian examples

The focus of this article is three contemporary Norwegians, who claim that they communicate with superhuman beings and/or promote therapeutic practices based on superhuman intervention. They come from different walks of life: Margit Sandemo is a best-selling author and housewife; Joralf Gjerstad is now retired, but was a dairy assistant and a bell-ringer in the local church; Märtha Louise is a princess and trained as a physiotherapist and Rosen ther­apist.What sorts of religion do they promote? How do they relate to the Church? How do they reflect the situation of post-secular religion in Norway? They personify in different ways the therapeutic turn of contemporary culture and religion, which challenges traditional religion as well as the field of medicine/science. Sandemo, Gjerstad and Märtha Louise and Samnøy try to solve everyday problems—illness, difficulties in mastering life and personal relations, the need for safety, feelings of unease in one’s house—problems that are basic in human life, but in some cases neglected by the expert fields or not able to be solved within them

Founding Fathers, Turtles and the Elephant in the Room: The Quest for Origins in the Scientific Study of Religion

The theme of the present article is the quest for origins, founding fathers and the never-ending search for identity in the scientific study of religion. Because the quest for origins and for founding fathers is intertwined with the complex relationship to theology, theology is frequently made into the significant other. The elephant is a metaphor for the preoccupation with theology. The article discusses the longing for origins, and it discusses good fathers and bad fathers, and especially Max Müller’s contribution to the study of religion. It also takes up the new quest for historical origins as well as the quest for generative mechanisms of religion and asks why the study of religion needs the metaphysical boosts of origins. A permanent preoccupation with universal patterns in the study of religion, recent developments in science, contemporary processes of globalization, a renewed general interest in religion, a wish to control the field and the continuous struggle to be different from theology are pointed out as reasons for the never-ending quest for origins. The article suggests that it might be fruitful to let go of the preoccupation with theology, and further that grand-scale comparative studies and universal claims need to be matched by small-scale studies of religion on the ground and by embracing complexity and reflexivity

Myasthenia gravis, respiratory function, and respiratory tract disease

Myasthenia gravis (MG) is characterized by muscle weakness caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction and impair acetylcholine receptor function. Weakness of respiratory muscles represents the most severe MG manifestation, and 10–15% of all patients experience an MG crisis with the need of mechanical ventilatory support at least once in their life. MG patients with respiratory muscle weakness need active immunosuppressive drug treatment long term, and they need regular specialist follow-up. Comorbidities affecting respiratory function need attention and optimal treatment. Respiratory tract infections can lead to MG exacerbations and precipitate an MG crisis. Intravenous immunoglobulin and plasma exchange are the core treatments for severe MG exacerbations. High-dose corticosteroids, complement inhibitors, and FcRn blockers represent fast-acting treatments that are effective in most MG patients. Neonatal myasthenia is a transient condition with muscle weakness in the newborn caused by mother’s muscle antibodies. In rare cases, treatment of respiratory muscle weakness in the baby is required.publishedVersio

Advances and challenges in the treatment of myasthenia gravis

Myasthenia gravis (MG) is a chronic autoimmune disease with fluctuating muscle weakness and fatigability. Standard immunomodulatory treatment may fail to achieve sufficient improvement with minimal symptom expression or remission of myasthenic symptoms, despite adequate dosing and duration of treatment. Treatment-resistant MG poses a challenge for both patients and treating neurologists and requires new therapeutic approaches. The spectrum of upcoming immunotherapies that more specifically address distinct targets of the main immunological players in MG pathogenesis includes T-cell directed monoclonal antibodies that block the intracellular cascade associated with T-cell activation, monoclonal antibodies directed against key B-cell molecules, as well as monoclonal antibodies against the fragment crystallizable neonatal receptor (FcRn), cytokines and transmigration molecules, and also drugs that inhibit distinct elements of the complement system activated by the pathogenic MG antibodies. The review gives an overview on new drugs being evaluated in still ongoing or recently finished controlled clinical trials and drugs of potential benefit in MG due to their mechanisms of action and positive effects in other autoimmune disorders. Also, the challenges associated with the new therapeutic options are discussed briefly.publishedVersio

From the History of Religions to the Science of Religion in Norway

The focus in this article is on the developments in the study of religion in Norway during the last fifty years, reflecting over continuities and breaks with the past, over changes in themes, theories and methods as well as over relations to the surrounding world.

A New Score for Sharp Discharges in the EEG Predicts Epilepsy

Purpose: A challenge in EEG interpretation is to correctly classify suspicious focal sharp activity as epileptiform or not. A predictive score was developed from morphologic features of the first focal sharp discharge, which can help in this decision. Methods: From a clinical standard EEG database, the authors identified 2,063 patients without a previous epilepsy diagnosis who had a focal sharp discharge in their EEG. Morphologic features (amplitude, area of slow wave, etc.) were extracted using an open source one-click algorithm in EEGLAB, masked to clinical classification. A score was developed from these features and validated with the clinical diagnosis of epilepsy over 2 to 6 years of follow-up. Independent external validation was performed in Kural long-term video-EEG monitoring dataset. Results: The score for the first focal sharp discharge had a moderate predictive performance for the clinical designation as the EEG being epileptiform (area under the receiver operating characteristics curve = 0.86). Best specificity was 91% and sensitivity 55%. The score also predicted a future epilepsy diagnosis (area under the receiver operating characteristics curve = 0.70). Best specificity was 86% and sensitivity 38%. Validation on the external dataset had an area under the receiver operating characteristics curve = 0.80. Clinical EEG identification of focal interictal epileptiform discharges had an area under the receiver operating characteristics curve = 0.73 for prediction of epilepsy. The score was based on amplitude, slope, difference from background, slow after-wave area, and age. Interrater reproducibility was high (ICC = 0.91). Conclusions: The designation of the first focal sharp discharge as epileptiform depends on reproducible morphologic features. Characteristic features were amplitude, slope, slow after-wave area, and difference from background. The score was predictive of future epilepsy. Halford semiquantitative scale had similar diagnostic performance but lower reproducibility.publishedVersio

Interictal epileptiform discharges vary across age groups

Objective To investigate whether the occurrence and morphology of interictal epileptiform discharges (IEDs) in scalp-EEG change by age. Methods 10,547 patients who had a standard or sleep deprived EEG recording reported using the SCORE standard were included. 875 patients had at least one EEG with focal IEDs. Focal IED morphology was analyzed by age using quantitative measures in EEGLAB and by visual classification based on the SCORE standard. We present distributions of IED measures by age group, with medians, interquartiles, 5th and 95th percentiles. Results Focal IEDs occurred most frequently in children and elderly. IED morphology and localization depended on age (p < 0.001). IEDs had higher amplitudes, sharper peaks, larger slopes, shorter durations, larger slow-wave areas and wider distributions in children. These morphological characteristics diminished and the IEDs became more lateralized with increasing age. Spike asymmetry was stable across all age groups. Conclusions IEDs have age-dependent characteristics. A spike detector, human or computer, should not operate with the same set of thresholds for patients at various age. With increasing age, focal IEDs are less sharp, have lower amplitudes, have less prominent slow-waves and they become more lateralized. Our findings can help EEG readers in detecting and correctly describing IEDs in patients of various age. Significance EEG readers should always consider patient age when interpreting interictal epileptiform discharges.publishedVersio