Explore the vast range of titles available.

Myasthenia gravis is a chronic autoimmune disorder caused by antibodies directed against the neuromuscular junction. Some patients may have an associated thymoma, which confers a worse prognosis. Eculizumab, a monoclonal antibody that inhibits the activation of terminal complement, has recently been approved for the treatment of refractory generalized myasthenia gravis. This is an early case report of thymoma-associated refractory myasthenia gravis successfully treated with eculizumab in a real-world setting.

Background Myasthenia gravis is an autoimmune disease mediated by antibodies against proteins associated with the postsynaptic membrane of the neuromuscular junction. Several drugs may trigger an exacerbation of the disease. Melatonin supplements are widely used for the treatment of insomnia as they are well tolerated with few side effects. The role of melatonin in the immune system and its effects in autoimmune disorders remain uncertain. Case presentation We identified three patients in our referral centre from 2014 to 2019 who presented a worsening within days or weeks of starting melatonin. Two of them stopped the treatment without clinical improvement in the next week. Increasing dose of corticosteroids did not lead to clinical improvement in the next month and one of the patients was finally administered intravenous immunoglobulins. Conclusion Melatonin may trigger exacerbations of myasthenia gravis, probably due to an upregulation of the adaptive immune system and an interaction with the corticosteroids and other immunosuppressant treatments. We consider that melatonin should be administered with caution in these patients.

There is no standardized treatment for acquired amyloid polyneuropathy (AAP) in domino liver transplant (DLT) recipients. Our objective is to analyze the efficacy and safety of patisiran for the treatment of AAP in DLT recipients. We performed a postauthorization prospective longitudinal study of DLT recipients with AAP who received patisiran treatment for 22 months. The primary endpoint was change in the Neuropathy Impairment Scale (NIS) from baseline. Other assessments included neurophysiologic study, quantitative sensory testing, 10 m walking test, and quality of life and disability questionnaires. As safety parameters we analyzed evidence of graft rejection, immunosuppression levels, and renal and cardiac adverse effects. Four patients were recruited. The mean NIS at baseline was 8.5 ± 2.08. All patients presented clinical improvement after 22 months of treatment, with a mean NIS of 4.75 ± 2.27 points. The mean change from baseline in the NIS was -3.75 ± 0.71 (95% CI: -0.47 to 7.97). The use of patisiran was not associated with cardiovascular or renal side effects. No patient presented relevant changes in immunosuppression levels or graft rejection. Our study suggests that patisiran may improve neurological manifestations in DLT recipients with AAP, producing no relevant adverse effects.

Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the Drooling Severity Scale (DSS), and the Drooling Frequency Scale (DFS). Patients’ perceptions of clinical benefit were recorded via the Patient Global Impression of Improvement (PGI-I) scale. Following treatment, there was a significant difference in both the DFS and the DSS (p < 0.001). Clinical benefits on the basis of the PGI-I were present in up to 90% of patients.

Background Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. Methods We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient’s standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). Results ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. Conclusions ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.

Myasthenia gravis is an autoimmune disease mediated by antibodies against proteins associated with the postsynaptic membrane of the neuromuscular junction. Several drugs may trigger an exacerbation of the disease. Melatonin supplements are widely used for the treatment of insomnia as they are well tolerated with few side effects. The role of melatonin in the immune system and its effects in autoimmune disorders remain uncertain. Melatonin may trigger exacerbations of myasthenia gravis, probably due to an upregulation of the adaptive immune system and an interaction with the corticosteroids and other immunosuppressant treatments. We consider that melatonin should be administered with caution in these patients.

ABSTRACT Objective Approximately half of patients with hereditary myopathies remain without a definitive genetic diagnosis after DNA next‐generation sequencing (NGS). Here, we implemented transcriptome analysis of muscle biopsies as a complementary diagnostic tool for patients with muscle disease but no definitive genetic diagnosis after exome sequencing. Methods In total, 70 undiagnosed cases with suspected genetic muscular dystrophies or congenital myopathies were included in the study. Muscle RNAseq comprised the analysis of aberrant splicing, aberrant expression, and monoallelic expression. In addition, existing NGS data or variant calling from RNAseq were reanalyzed, and genome sequencing was performed in selected cases. Four aberrant splicing open‐source tools were compared and assessed. Results RNAseq established a diagnosis in 10/70 patients (14.3%) by identifying aberrant transcripts produced by single nucleotide variants (7/10) or copy number variants (3/10). Reanalysis of NGS data allowed the diagnosis in 9/70 individuals (12.9%). Based on this cohort, FRASER was the tool that reported more splicing outlier events per sample while showing the highest accuracy (81.26%). Conclusions We demonstrate the utility of RNAseq in identifying causative variants in muscle diseases. Evaluation of four aberrant splicing tools allowed efficient identification of most pathogenic splicing events, obtaining a manageable number of candidate events for manual inspection, demonstrating feasibility for translation into a clinical setting. We also show how the integration of omic technologies reduces the turnaround time to identify causative variants.

Objectives: To analyze the efficacy and tolerability of diflunisal for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Methods: We performed a retrospective longitudinal study of prospectively collected data for all domino liver transplant recipients with acquired amyloid neuropathy who received diflunisal at our hospital. Neurological deterioration was defined as an score increase of ≥2 points from baseline on the Neurological Impairment Scale/Neurological Impairment Scale-Lower Limbs. Results: Twelve patients who had received compassionate use treatment with diflunisal were identified, of whom seven had follow-up data for ≥12 months. Five patients (71.4%) presented with neurological deterioration on the Neurological Impairment Scale after 12 months ( p = 0.0382). The main adverse effects were cardiovascular and renal, leading to diflunisal being stopped in five patients and the dose being reduced in two patients. Conclusion: Our study suggests that most domino liver transplant recipients with acquired amyloid neuropathy will develop neurological deterioration by 12 months of treatment with diflunisal. This therapy was also associated with a high incidence of adverse effects and low treatment retention. The low efficacy and low tolerability of diflunisal treatment encourage the search for new therapeutic options.

Our aim in this review is to discuss current treatments and investigational products and their effect on patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and provide suggestions for monitoring disease progression and treatment efficacy.