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BACKGROUND Telemedicine practice for neurological diseases has grown significantly during the COVID-19 pandemic. Telemedicine offers an opportunity to assess digitalization of examinations and enhances access to modern computer vision and artificial intelligence processing to annotate and quantify examinations in a consistent and reproducible manner. The Myasthenia Gravis Core Examination (MG-CE) has been recommended for the telemedicine evaluation of patients with myasthenia gravis. OBJECTIVE We aimed to assess the ability to take accurate and robust measurements during the examination, which would allow improvement in workflow efficiency by making the data acquisition and analytics fully automatic and thereby limit the potential for observation bias. METHODS We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis undergoing the MG-CE. The core examination tests required 2 broad categories of processing. First, computer vision algorithms were used to analyze videos with a focus on eye or body motions. Second, for the assessment of examinations involving vocalization, a different category of signal processing methods was required. In this way, we provide an algorithm toolbox to assist clinicians with the MG-CE. We used a data set of 6 patients recorded during 2 sessions. RESULTS Digitalization and control of quality of the core examination are advantageous and let the medical examiner concentrate on the patient instead of managing the logistics of the test. This approach showed the possibility of standardized data acquisition during telehealth sessions and provided real-time feedback on the quality of the metrics the medical doctor is assessing. Overall, our new telehealth platform showed submillimeter accuracy for ptosis and eye motion. In addition, the method showed good results in monitoring muscle weakness, demonstrating that continuous analysis is likely superior to pre-exercise and postexercise subjective assessment. CONCLUSIONS We demonstrated the ability to objectively quantitate the MG-CE. Our results indicate that the MG-CE should be revisited to consider some of the new metrics that our algorithm identified. We provide a proof of concept involving the MG-CE, but the method and tools developed can be applied to many neurological disorders and have great potential to improve clinical care.

Background Telemedicine practice for neurological diseases has grown significantly during the COVID-19 pandemic. Telemedicine offers an opportunity to assess digitalization of examinations and enhances access to modern computer vision and artificial intelligence processing to annotate and quantify examinations in a consistent and reproducible manner. The Myasthenia Gravis Core Examination (MG-CE) has been recommended for the telemedicine evaluation of patients with myasthenia gravis. Objective We aimed to assess the ability to take accurate and robust measurements during the examination, which would allow improvement in workflow efficiency by making the data acquisition and analytics fully automatic and thereby limit the potential for observation bias. Methods We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis undergoing the MG-CE. The core examination tests required 2 broad categories of processing. First, computer vision algorithms were used to analyze videos with a focus on eye or body motions. Second, for the assessment of examinations involving vocalization, a different category of signal processing methods was required. In this way, we provide an algorithm toolbox to assist clinicians with the MG-CE. We used a data set of 6 patients recorded during 2 sessions. Results Digitalization and control of quality of the core examination are advantageous and let the medical examiner concentrate on the patient instead of managing the logistics of the test. This approach showed the possibility of standardized data acquisition during telehealth sessions and provided real-time feedback on the quality of the metrics the medical doctor is assessing. Overall, our new telehealth platform showed submillimeter accuracy for ptosis and eye motion. In addition, the method showed good results in monitoring muscle weakness, demonstrating that continuous analysis is likely superior to pre-exercise and postexercise subjective assessment. Conclusions We demonstrated the ability to objectively quantitate the MG-CE. Our results indicate that the MG-CE should be revisited to consider some of the new metrics that our algorithm identified. We provide a proof of concept involving the MG-CE, but the method and tools developed can be applied to many neurological disorders and have great potential to improve clinical care.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

We recently demonstrated that hepatic stellate cells (HSC) induce myeloid derived suppressor cells (MDSC) differentiation from myeloid progenitors. In this report, we found that adoptive transfer of the MDSC was effective in reversing disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell-dependent, and B cell-mediated model for myasthenia gravis (MG). In accordance with ameliorated disease severity, the MDSC-treated EAMG mice showed suppressed AchR-specific T cell responses, decreased levels of serum anti-AChR IgGs and reduced complement activation at the neuromuscular junctions. We also discovered that the MDSC inhibited the proliferation of, and antibody production from B cells activated by anti-IgM or anti-CD40 antibodies in vitro, and inhibited the production of antibodies against a T cell-independent antigen in vivo, indicating that in addition to their T cell inhibitory activities, MDSC also directly inhibit B cells. These results demonstrated that HSC-induced MDSC concurrently suppress T- and B- cell autoimmunity, leading to effective treatment of established EAMG. These data also suggest that the MDSC could be further developed as a novel approach for MG treatment, and even more broadly, for other diseases in which T and B cells are involved in the pathogenesis.

Three cases of congestive cardiomyopathy complicating the acquired immune deficiency syndrome (AIDS) are reported. In one case, acute cardiac decompensation resulted in prolonged but ultimately reversible cardiogenic shock. In the second case, clinical signs of cardiac disease were precipitated by acute renal failure and fluid overload. In the third, congestive heart failure developed spontaneously and responded promptly to administration of diuretics but the patient died suddenly, apparently due to an arrhythmia. The etiology of cardiomyopathy in AIDS is unclear and the manifestations of cardiomyopathy in this setting range from subclinical to life threatening.

We report that the addition of human macrophage inflammatory protein-3 beta (MIP-3 beta) to cultures of human PBMCs that have been activated with LPS or PHA results in a significant enhancement of IL-10 production. This effect was concentration-dependent, with optimal MIP-3 beta concentrations inducing more than a 5-fold induction of IL-10 from LPS-stimulated PBMCs and a 2- to 3-fold induction of IL-10 from PHA-stimulated PBMCs. In contrast, no significant effect on IL-10 production was observed when 6Ckine, the other reported ligand for human CCR7, or other CC chemokines such as monocyte chemoattractant protein-1, RANTES, MIP-1 alpha, and MIP-1 beta were added to LPS- or PHA-stimulated PBMCs. Similar results were observed using activated purified human peripheral blood monocytes or T cells. Addition of MIP-3 beta to nonactivated PBMCs had no effect on cytokine production. Enhancement of IL-10 production by MIP-3beta correlated with the inhibition of IL-12 p40 and TNF-alpha production by monocytes and with the impairment of IFN-gamma production by T cells, which was reversed by addition of anti-IL-10 Abs to the cultures. The ability of MIP-3 beta to augment IL-10 production correlated with CCR7 mRNA expression and stimulation of intracellular calcium mobilization in both monocytes and T cells. These data indicate that MIP-3 beta acts directly on human monocytes and T cells and suggest that this chemokine is unique among ligands binding to CC receptors due to its ability to modulate inflammatory activity via the enhanced production of the anti-inflammatory cytokine IL-10.

The CC chemokine known as 6Ckine (SLC, Exodus-2, or TCA4) has been identified as a ligand for CCR7. Mouse 6Ckine has also been shown to signal through mouse CXCR3 and share some of the activities of IFN-gamma inducible protein 10 and monokine induced by IFN-gamma. Nonetheless, human 6Ckine has not been shown to bind CXCR3 receptor or have angiostatic activity. In this study, we report that human 6Ckine does not induce a calcium flux in either human CXCR3 or mouse CXCR3 transfected cells, although it is an equally potent agonist as mouse 6Ckine and human macrophage inflammatory protein-3beta in human CCR7 transfected cells. Mouse 6Ckine (but not human 6Ckine) is capable of competing with radiolabeled IFN-gamma inducible protein 10 for human CXCR3. In addition, radiolabeled human 6Ckine does not bind to either human CXCR3 or mouse CXCR3. Together these data suggest that human CC chemokine 6Ckine is not a ligand for the human or mouse CXC chemokine receptor CXCR3.

To determine the expression of fetal and adult acetylcholine receptor (AChR) isoforms among extraocular muscle (EOM) en plaque and en grappe endplates.Antibodies against peptide fragments of the gamma- and epsilon-subunits of the fetal and adult AChRs and alpha-bungarotoxin were used in immunofluorescence experiments to stain rat neonatal leg, adult diaphragm, and extraocular rectus muscle endplates.Anti-epsilon antibodies intensely stained diaphragm endplates weakly stained rare neonatal endplates. Anti-gamma antibodies stained neonatal, but not diaphragm, endplates. Anti-epsilon antibodies bound to all en plaque and en grappe endplates of extraocular muscle. Anti-gamma antibodies bound to global and orbital en grappe endplates. All en plaque endplates of the orbital region and a subset of endplates in the global region stained with anti-gamma antibodies.All en grappe endplates and certain en plaque endplates of EOM are the only mature endplates that coexpress the adult and fetal AChR isoforms. The expression of both isoforms may be important to determine contractile properties, protein expression regulation, and EOM susceptibility to myasthenia gravis.