Application of digital tools and artificial intelligence in the Myasthenia Gravis Core Examination.

Background: Advances in video image analysis and artificial intelligence provide opportunities to transform how patients are evaluated. In this study, we assessed the ability to quantify Zoom video recordings of a standardized neurological examination- the Myasthenia Gravis Core Examination (MG-CE)-designed for telemedicine evaluations.

Methods: We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis (MG) who underwent the MG-CE.

Clinical Reasoning: A 65-Year-Old Woman With Isolated Macroglossia as the Initial Presentation of a Rare Disease.

Macroglossia can be seen in multiple conditions, but its evaluation becomes more challenging when approached as an isolated presenting symptom. This is a case of a 65-year-old patient with isolated progressive tongue hypertrophy of unclear etiology for 5 years. We navigate the causes of macroglossia and discuss the clinical and diagnostic procedures that helped us narrow the differential diagnoses for our patient.

Application of Digital Tools and Artificial Intelligence to the Myasthenia Gravis Core Examination.

Background: Advances in video image analysis and artificial intelligence provide the opportunity to transform the approach to patient evaluation through objective digital evaluation.

Objectives: We assessed ability to quantitate Zoom video recordings of a standardized neurological examination the myasthenia gravis core examination (MG-CE), which had been designed for telemedicine evaluations.

Methods: We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis undergoing the MG-CE.

Intermuscular coherence as an early biomarker for amyotrophic lateral sclerosis: The protocol for a prospective, multicenter study.

Objective: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

Methods: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines.

Added load increases the peak frequency of intermuscular coherence.

Cortical motor neuron activity appears to drive lower motor neurons through two distinct frequency bands: the β range (15-30 Hz) during weak muscle contractions and γ range (30-50 Hz) during strong contractions. It is unknown whether the frequency of cortical drive shifts continuously or abruptly between the β and γ frequency bands as contraction strength changes. Intermuscular coherence (IMC) between synergistic arm muscles was used to assess how the frequency of common neuronal drive shifts with increasing contraction strength.

Long-term effects of pancreatic islet transplantation on polyneuropathy in patients with brittle diabetes: A single-center experience.

Introduction/aims: Pancreatic islet transplantation (ITx) is increasingly used in patients with brittle type 1 diabetes (T1D). If successful, ITx results in insulin-free euglycemia, but its application is limited by a need for lifelong immunosuppression. The aim of this study was to assess the long-term effects of ITx on the occurrence and course of polyneuropathy in a cohort of patients with brittle T1D.

Technetium-pyrophosphate bone scan: A potential biomarker for the burden of transthyretin amyloidosis in skeletal muscle: A preliminary study.

Introduction/aims: Transthyretin amyloidosis (ATTR) proteins can infiltrate skeletal muscle and infrequently cause a myopathy. Technetium-pyrophosphate ( Tc-PYP) is a validated biomarker for cardiac involvement in variant and wild-type ATTR (ATTRv and ATTRwt, respectively). The aim of this study was to test the hypothesis that Tc-PYP is a biomarker for muscle burden of ATTR.

Current Treatment of Myasthenia Gravis.

Myasthenia gravis (MG) is the most extensively studied antibody-mediated disease in humans. Substantial progress has been made in the treatment of MG in the last century, resulting in a change of its natural course from a disease with poor prognosis with a high mortality rate in the early 20th century to a treatable condition with a large proportion of patients attaining very good disease control. This review summarizes the current treatment options for MG, including non-immunosuppressive and immunosuppressive treatments, as well as thymectomy and targeted immunomodulatory drugs.

Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation.

Valine 122 isoleucine (V122I) is the most common mutation associated with familial transthyretin-related amyloidosis (fATTR) in the metropolitan United States. V122I-related fATTR usually presents with cardiomyopathy. When polyneuropathy is encountered, it is usually mild, distal, and axonal in nature.

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations.

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million.

Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder which is characterized by presence of antibodies against acetylcholine receptors (AChRs) or other proteins of the postsynaptic membrane resulting in damage to postsynaptic membrane, decreased number of AChRs or blocking of the receptors by autoantibodies. A number of drugs such as immune checkpoint inhibitors, penicillamine, tyrosine kinase inhibitors and interferons may induce de novo MG by altering the immune homeostasis mechanisms which prevent emergence of autoimmune diseases such as MG. Other drugs, especially certain antibiotics, antiarrhythmics, anesthetics and neuromuscular blockers, have deleterious effects on neuromuscular transmission, resulting in increased weakness in MG or MG-like symptoms in patients who do not have MG, with the latter usually being under medical circumstances such as kidney failure.

Modulation of immune responses by bile acid receptor agonists in myasthenia gravis.

Bile acids bind to multiple receptors, including Takeda G protein-coupled receptor 5 (TGR5) and farnesoid-X-receptors alpha (FXRα). We compared the response of PBMCs to the activation of these receptors in healthy controls and myasthenic patients. We found that TGR5 is a more potent negative regulator of T cell cytokine response than FXRα in both groups.

Myasthenia gravis induced by avelumab.

Neurological immune-related adverse events are potentially life-threatening complications of immune checkpoint inhibitors. Myasthenia gravis (MG) is a rare complication of treatment with inhibitors of programmed cell death protein 1 (PD)-1 and PD ligand 1 (PD-L1). We present a patient who developed seronegative MG resulting in respiratory failure while being treated with avelumab for metastatic, treatment-refractory ovarian cancer.

Severe Relapse of Vaccine-Induced Guillain-Barré Syndrome After Treatment With Nivolumab.

Cancer immunotherapy with checkpoint inhibitors may result in neuromuscular immune-related adverse reactions, including Guillain-Barré syndrome (GBS)-like disease. On the other hand, checkpoint inhibitor therapy may result in exacerbation of underlying autoimmune diseases such as myasthenia gravis and multiple sclerosis. We present a patient who developed a severe and fatal relapse of postvaccination GBS after he was treated with nivolumab, a monoclonal antibody directed to programmed death-1 (PD-1), during a GBS treatment-related fluctuation.

Facial Palsy Induced by Checkpoint Blockade: A Single Center Retrospective Study.

The augmented immune response caused by immune checkpoint inhibitors leads to the emergence of a class of side effects called immune-related adverse events (irAEs). Facial palsy (FP) is rarely reported as an irAE. In this retrospective study, we reviewed the records of 353 patients treated with immunotherapy in our center from 2015-2018.

Neonatal Hypoxia Results in Peripheral Nerve Abnormalities.

Although the adverse effects of neonatal hypoxia associated with premature birth on the central nervous system are well known, the contribution of hypoxic damage to the peripheral nervous system (PNS) has not been addressed. We demonstrate that neonatal hypoxia results in hypomyelination and delayed axonal sorting in mice leading to electrophysiological and motor deficits that persist into adulthood. These findings support a potential role for PNS hypoxic damage in the motor impairment that results from premature birth and suggest that therapies designed to protect the PNS may provide clinical benefit.

Head-drop: A frequent feature of late-onset myasthenia gravis.

Introduction: Head-drop is often encountered in myasthenia gravis (MG) patients, but its frequency and clinical course have not been studied systematically.

Methods: In a retrospective study of a cohort of MG patients seen over a period of 11 years in a tertiary medical center, we assessed the clinical characteristics of patients who had head-drop.

Results: Of 146 generalized MG patients, 15 had head-drop during the course of their disease.

Gastrostomy tube placement is safe in advanced amyotrophic lateral sclerosis.

Objectives: To evaluate the safety and effect on survival of insertion of a gastrostomy tube (G-tube) in patients with amyotrophic lateral sclerosis (ALS) who have upright forced vital capacity (uFVC) ≤ 50% predicted. Current guidelines, which are based on higher rates of post-procedure complications in ALS patients with advanced respiratory dysfunction, have led to a recommendation to perform G-tube insertion before the FVC drops to <50% predicted, even when the patient has no significant dysphagia.

Methods: We assessed 41 ALS patients who received a G-tube, mostly by insertion of a percutaneous endoscopic gastrostomy (PEG) tube by a dedicated team that included a gastroenterologist and one of two anesthesiologists using Monitored Anesthesia Care with deep sedation, and 61 patients who did not receive a G-tube.

Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary assessment.

Introduction: Simple laboratory tests of upper motor neuron involvement in amyotrophic lateral sclerosis (ALS) are not available. Intermuscular coherence has been shown to distinguish patients with primary lateral sclerosis, a pure upper motor neuron disorder, from normal subjects, suggesting it could be useful for assessing ALS. We aimed to determine whether intermuscular coherence can distinguish ALS patients from normal subjects.

Impaired regulatory B cells in myasthenia gravis.

Regulatory B cells (Bregs) attenuate the severity of experimental autoimmune myasthenia gravis (EAMG) in an interleukin-10 (IL-10)-dependent manner. The goal of this study was to investigate the role of human Bregs in MG focusing on CD19(+)CD1d(hi) CD5(+) and CD19(+)CD24(hi)CD38(hi) subsets. We found that MG patients exhibited a decrease in the frequency of both Breg subsets and IL-10 producing B cells within each subset, which correlated with disease severity.

Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS.

The tumor suppressor protein adenomatous polyposis coli (APC) is multifunctional - it participates in the canonical Wnt/β-catenin signal transduction pathway as well as modulating cytoskeleton function. Although APC is expressed by Schwann cells, the role that it plays in these cells and in the myelination of the peripheral nervous system (PNS) is unknown. Therefore, we used the Cre-lox approach to generate a mouse model in which APC expression is specifically eliminated from Schwann cells.

Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy.

B7-2(-/-) non-obese diabetic (NOD) mice develop a spontaneous autoimmune polyneuropathy (SAP) that mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, we focused on the role of regulatory T cells (Tregs ) and regulatory B cells (Bregs ) in SAP. We found that deletion of B7-2 in female NOD mice led to a lower frequency and number of Tregs and Bregs in spleens and lymph nodes.

S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination.

Sphingosine 1-phosphate (S1P) receptors are G protein-coupled receptors expressed by many cell types, including cells of oligodendrocyte (OLG) lineage. We had previously shown that targeted deletion of S1P1 in OLG lineage cells did not result in obvious clinical phenotype or altered number of OLGs at 3 months, but there were subtle abnormalities in myelin. In this study, we examined the role of S1P1 in developmental myelination and cell survival, focusing on age 3 weeks.