Generalized myasthenia gravis with acetylcholine receptor antibodies: A guidance for treatment.

BACKGROUND: Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. METHODS: MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. RESULTS: Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. CONCLUSIONS: Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.

Thymectomy in Juvenile Myasthenia Gravis Is Safe Regarding Long Term Immunological Effects.

Thymectomy is an established treatment in adult MG and also recommended for the treatment of post-pubertal onset juvenile MG. Whether the youngest children should be thymectomized is still debated. Signs of premature aging of the immune system have been shown in studies on early perioperative thymectomy in children with congenital heart defect. In this retrospective cohort study the objective was to investigate the long-term effects of treatment related thymectomy on T cell subsets and T cell receptor rearrangement excision circles (TRECs) in peripheral blood of juvenile myasthenia gravis (MG) patients, as well as clinical occurrence of autoimmune disorders, malignancies and infectious diseases. Forty-seven patients with onset of myasthenia gravis before the age of 19 years were included; 32 (68.1%) had been thymectomized and 15 (31.8%) had not. They were studied at varying times after thymectomy (7-26 years). We found a significant lower number of naïve helper T cells (CD4+CD45RA+) with an increased proportion of memory helper T cells (CD4+CD45RO+), and a significant lower number of naïve cytotoxic T cells (CD8+CD27+CD28+) in the thymectomized patients. In addition they showed a significant reduction in the number of TRECs and proportion of recent thymic emigrants (RTE) compared to non-thymectomized patients. In none of them an increased frequency of malignancies or infections was found. Our findings indicate a premature aging of the immune system after thymectomy in juvenile MG, but associated clinical consequences could not be verified.

Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19.

OBJECTIVE: To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. METHODS: Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. RESULTS: In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10-7) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). CONCLUSION: Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.

A Middle-Aged Man Presenting With Progressive Heart Failure, Myopathy, and Monoclonal Gammopathy of Uncertain Significance.

A 48-year-old man presented with rapidly progressive heart failure and monoclonal gammopathy of uncertain significance. No specific cause was detected on endomyocardial biopsy. As the heart failure worsened, he also developed progressive skeletal myopathy. This provided the clue to the diagnosis, and cardiac function recovered rapidly with cause-directed therapy. (Level of Difficulty: Intermediate.).

A painful foot with diagnostic and therapeutic consequences.

Background A wide range of patients are referred to multidisciplinary pain clinics. An important part of the work-up is a thorough pain analysis that might reveal a specific cause for chronic pain. Method We describe a patient with chronic pain in one foot after a light trauma and repeated surgery. However, careful examination revealed symptoms and clinical finings in both feet. This led to referral to a University Hospital and the diagnosis of a chronic neurologic condition explaining both symptoms and findings. The diagnosis of this condition has implications both for further follow-up for this patient and possibly also other family members. Implications Professionals working in the pain-field should be aware of diagnosis that might partly explain increased pain or complications after surgery.

Geographical Distribution of Myasthenia Gravis in Northern Europe--Results from a Population-Based Study from Two Countries.

OBJECTIVES: To compare the prevalence of myasthenia gravis (MG) subgroups based on immunological markers and clinical presentation in two geographically complete MG populations in northern Europe. METHODS: This cross-sectional study included all living MG patients in Norway and a regional cohort from the Netherlands. Patients were identified using their hospital registration codes. Medical charts of subjects >16 years were reviewed. Inclusion criteria were clinical MG, a positive antibody test for acetylcholine receptor (AChR MG) or muscle-specific kinase (MuSK MG), or if seronegative MG, confirmed by an electrophysiological test. RESULTS: 1,205 MG patients (534 Norwegians and 671 Dutch) fulfilled the criteria, giving a higher point prevalence in the Netherlands (167/million, 95% CI 155-180) than in Norway (138/million, 95% CI 126-150). In particular, rates of AChR MG (143 vs. 111/million), MuSK MG (6.5 vs. 0.5/million), and ocular phenotype (62 vs. 24/million) were higher in the Netherlands. CONCLUSION: Novel findings are an AChR MG geographical north-south gradient and a 2.6-fold more ocular MG patients in the Netherlands than in Norway. The MuSK MG latitudinal gradient supports the notion of a north-south gradient in Europe, with a higher prevalence in the south. The variation is probably explained by genetic differences between the populations, in addition to environmental interactions.

[Drugs that may trigger or exacerbate myasthenia gravis]. / Medikamenter som kan utløse og forverre myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease causing muscle weakness due to impaired transmission at the neuromuscular junction. MG or a MG-like condition may be triggered or exacerbated by several drugs used for treatment of other diseases. Drugs may interfere with the neuromuscular transmission through several mechanisms, either by affecting pre- or postsynaptic ion channels or by affecting acetylcholinesterase. Based on a literature search in PubMed and the authors' own clinical experiences, we provide an overview focusing on the most frequently used drugs that may exacerbate weakness in patients with MG. In our experience, symptomatic MG-patients who have a generalised disease are especially vulnerable to drug-induced exacerbations, while stable MG patients with few symptoms more seldom are. Nevertheless, patients with MG must receive treatment for co-existing conditions. It is important to be aware of a possible increase in muscle weakness when introducing a new drug. If the patient deteriorates, the new treatment must be withdrawn or the dose reduced.

An unusual case of the syndrome of cervical rib with subclavian artery thrombosis and cerebellar and cerebral infarctions.

BACKGROUND: Cerebellar and cerebral infarctions caused by the syndrome of cervical rib with thrombosis of subclavian artery are very unusual. CASE PRESENTATION: We report the case of a 49-year-old male patient with a right cervical rib compression leading to subclavian arterial thrombosis and both cerebellar and cerebral infarctions secondary to retrograde thromboembolisation. Follow-up imaging revealed partial resolution of the thrombosis after combined anti-coagulant and anti-platelet therapy. The cervical rib and first costa were surgically removed to prevent additional events. CONCLUSION: Cervical rib vascular compression should be promptly diagnosed and treated in order to avoid further complications, including cerebrovascular ischemic events.