The thymus in myasthenia gravis: Site of “innate autoimmunity”?

Myasthenia gravis (MG) is an autoimmune disorder caused, in most cases, by autoantibodies against components of the neuromuscular junction, frequently the acetylcholine receptor (AChR), and less often the muscle-specific kinase receptor. The thymus plays a major role in the pathogenesis of MG with anti-AChR antibodies: it shows marked pathologic alterations (hyperplastic or tumoral) in most AChR-positive patients and contains the elements required to initiate and sustain an autoimmune reaction (AChR autoantigen, AChR-specific T cells, and autoantibody-secreting plasma cells). In this study we review early and more recent findings implicating the thymus as site of AChR autosensitization in MG and briefly discuss the therapeutic role of thymectomy. We also summarize data showing that the MG thymus is in a state of chronic inflammation, and we review emerging evidence of a viral contribution to the onset and maintenance of the thymic autoimmune response.     

Combined Guillain–Barré syndrome and myasthenia gravis

Background: Guillain–Barré syndrome and myasthenia gravis both lead to muscle weakness but the two combined is uncommon. Detection of these entities can help identify forms of autoimmune neuromuscular diseases that may respond to immunotherapy. This report sought to characterize the clinical features of these two entities when combined. Methods: This report is of a case of combined Guillain–Barré syndrome and myasthenia gravis. The clinical features were analyzed and correlated to those published in English literature from 1960 to 2012. Ten reports and 12 cases, including the present case, were reviewed. Results: There were 12 patients (4 women and 8 men), aged 17 to 84 years, with combined Guillain–Barré syndrome and myasthenia gravis. Four had post-infectious Guillain–Barré syndrome followed by the development of myasthenia gravis concurrently or concomitantly within one month. All cases had symptoms of ptosis and areflexia. The other common presentations were limb weakness, oculobulbar weakness, and respiratory involvement. Functional outcome was mentioned in 10 patients and seven had good outcome (Hughes scale ?2). Conclusion: Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing combined Guillain–Barré syndrome and myasthenia gravis. The early recognition of this combination of peripheral nervous and neuro-muscular junction inflammation is important for initial treatment and prognosis.     

Impact of myasthenia gravis on family planning: How do women with myasthenia gravis decide and why?

Introduction: We analyzed the impact of myasthenia gravis (MG) on decision‐making in family planning by women with the disease. Methods: In a cross‐sectional, anonymous survey, a standardized questionnaire was sent or handed out to 1,637 women with MG. Results: In total, 801 questionnaires were eligible for analysis. Over fifty percent of the patients had abstained from having children due to MG. The concern mentioned most often was the possible influence of MG medication on the unborn child (87.1%). Spouses/partners (91.8%) and MG treating physicians (82.9%) were the most important persons involved in the decision‐making process. Higher age and personal experience of intensive‐care treatment for MG were independently associated with the decision to abstain from having children. Lower level of knowledge was independently associated with the probability of discouraging other MG patients from having children. Conclusions: Women with MG need specific guidance about family planning issues, which may lead to lower rates of voluntary childlessness. On the basis of our data, more specific hypotheses can be generated that require prospective investigation. Muscle Nerve 52:371–379, 2015     

Linaclotide – a secretagogue and antihyperalgesic agent – what next?

Ongoing clinical trials suggest that linaclotide, a first‐in‐class, 14‐amino acid peptide guanylate cyclase‐C (GC‐C) receptor agonist and intestinal secretagogue is an effective treatment for chronic constipation. A study in this issue of the Journal suggests that linaclotide also has antihyperalgesic effects in three common rat models of inflammation‐ and stress‐induced hypersensitivity (i.e., acute trinitrobenzene sulfonic acid colitis, water avoidance stress [WAS], and restraint‐induced stress) but not in naïve animals. In mice, linaclotide at least partly reduces hyperalgesia via GC‐C receptors. Dose–effect relationships of linaclotide were complicated and non‐linear. This viewpoint discusses human clinical trials with linaclotide and the results of this study. Potential mechanisms and clinical significance of these findings are explored. Collectively, these data suggest that GC‐C receptors exert other, as yet poorly understood, effects on gastrointestinal sensitivity in conditions associated with inflammation and/or stress‐induced increased intestinal permeability. However, the data need to be confirmed in humans and in long‐term animal models. Further studies are also necessary to elucidate the mechanisms as these effects cannot be explained by linaclotide’s known effects on epithelial GC‐C receptors.     

Amyotrophic lateral sclerosis and myasthenia gravis: association or chance occurrence?

Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/10⁹), compared to our findings (1.87/10⁷) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events.     

Can mycophenolate mofetil be tapered safely in myasthenia gravis? A retrospective,multicenter analysis

Introduction: Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well‐controlled patients. Methods: This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed. Results: Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months). Conclusions: Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended. Muscle Nerve 52 : 211–215, 2015     

Acupuncture: does it work and, if so, how?

This article is intended to assist physicians in giving advice to their patients about acupuncture. Despite 20 years of research, the efficacy of acupuncture in general is not established. One of the difficulties with drawing conclusions from the existing literature is that the term acupuncture is used to describe a variety of treatments that differ in many important aspects, both theoretical and technical. This article critically reviews the existing evidence supporting the various effects that have been proposed to result from acupuncture treatments. The evidence is classified according to level of effect (eg, local, segmental, generalized) and type of acupuncture treatment (eg, manual v electrical acupuncture).     

Brain imaging technologies: how, what, when and why?

OBJECTIVE: Innovations in physics and computing technology over the past two decades have provided a powerful means of exploring the overall structure and function of the brain using a range of computerised brain imaging technologies (BITs). These technologies offer the means to elucidate the patterns of pathophysiology underlying mental illness. The aim of this paper is to explore the current status and some of the future directions in the application of BITs to psychiatry. METHOD: Brain imaging technologies provide unambiguous measures of brain structure (computerised tomography and magnetic resonance imaging [MRI]) and also index complementary measures of when (electroencephalography, event related potentials, magnetoencephalography) and where (functional MRI, single photon emission computed tomography, positron emission tomography) aspects of brain activity occur. RESULTS: The structural technologies are primarily used to exclude a biological cause in cases of a suspected psychiatric disorder. The functional technologies show considerable potential to delineate subgroups of patients (that may have different treatment outcomes), and evaluate objectively the effects of treatment on the brain as a system. What is seldom emphasised in the literature are the numerous inconsistencies, the lack of specificity of findings and the simplistic interpretation of much of the data. CONCLUSION: Brain imaging technologies show considerable utility, but we are barely scratching the surface of this potential. Simplistic over-interpretation of results can be minimised by: replication of BIT findings, judicious combination of complementary methodologies, use of appropriate activation tasks, analysis with respect to large normative databases, control for performance, examining the data'beyond averaging', delineating clinical subtypes, exploring the severity of symptoms, specificity of findings and effects of treatment in the same patients. The technological innovation of BITs still far outstrips the sophistication of their use; it is essential that the meaning and mechanisms underlying BIT measures are always evaluated with respect to prevailing models of brain function across disciplines.