Charcot-Marie-Tooth disease type 4C associated with myasthenia gravis: coincidental or a foreseeable association?

We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG.

The use of frontalis sling in the management of variable ptosis secondary to congenital myasthenic syndrome.

Congenital myasthenic syndrome (CMS) describes a group of rare inherited disorders caused by impaired neuromuscular transmission at the motor endplate. Common ophthalmic manifestations associated with CMS include ptosis and ophthalmoplegia. A 19-year-old female presented with variable day-to-day ptosis secondary to CMS that was refractory to medical therapy. Bilateral silicone frontalis slings were used to stabilise the upper lid height and reduce fluctuation in severity of ptosis. Blepharoptosis surgery has been performed in patients with chronic myasthenia gravis (MG), but rarely in the setting of CMS. Blepharoptosis surgery in CMS patients with variable ptosis is difficult due to the risk of upsetting the original lid position and developing post-operative exposure keratopathy. Our case demonstrates that the frontalis sling procedure may be considered as an option in the management of variable blepharoptosis secondary to CMS.

Case 261: Thymoma Embedded in Thymus with Pleural Implant in Myasthenia Gravis Lambert-Eaton Overlap Syndrome.

History A 29-year-old woman presented with a 6-month history of progressive general fatigue, fluctuating limb weakness, and difficulty climbing stairs. She initially experienced occasional episodes of transient diplopia that developed while reading in the evening. She subsequently started to experience dry eyes and mouth, difficulty chewing, and mild dysphagia that worsened throughout the day. Her medical history included hypothyroidism from Hashimoto thyroiditis and pneumonia with left pleural effusion. She had no smoking history, and her body mass index was normal (23.8 kg/m2). No medication use was reported at admission. Physical examination revealed mild bilateral ptosis, reduced muscle tone and strength that worsened in proximal leg muscles, and decreased deep tendon reflexes. An edrophonium test revealed improvement in muscle strength and eyelid ptosis. Repetitive nerve stimulation revealed low amplitude of compound muscle action potential at rest (0.21 mV), with a marked increase (700%; normal increase, <60%) at high-rate stimulation (50 Hz). Laboratory work-up was unremarkable except for detection of acetylcholine receptor antibodies in the serum (21.30 nmol/L) and P/Q-type voltage-gated calcium channel antibodies (220 pmol/L). Recent MRI of the brain and spine at an outside hospital showed no abnormal findings. At admission, the patient underwent CT of the chest, abdomen, and pelvis followed by thoracic MRI to further evaluate CT findings.

S1P/S1P Receptor Signaling in Neuromuscolar Disorders.

The bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), and the signaling pathways triggered by its binding to specific G protein-coupled receptors play a critical regulatory role in many pathophysiological processes, including skeletal muscle and nervous system degeneration. The signaling transduced by S1P binding appears to be much more complex than previously thought, with important implications for clinical applications and for personalized medicine. In particular, the understanding of S1P/S1P receptor signaling functions in specific compartmentalized locations of the cell is worthy of being better investigated, because in various circumstances it might be crucial for the development or/and the progression of neuromuscular diseases, such as Charcot-Marie-Tooth disease, myasthenia gravis, and Duchenne muscular dystrophy.

[Myasthenia gravis in dentistry]. / Myasthenia gravis in de tandheelkunde.

In a patient with myasthenia gravis, a life-threatening myasthenic crisis can occur, a complication of myasthenia gravis. The crisis can be triggered by, among other things, emotional stress, pain, infections and a reaction to medication. The policy for invasive dental treatment in a patient with myasthenia gravis must be aimed at preventing a crisis. Prior to the intervention, consultation with the neurologist in charge is necessary because sometimes optimisation of the medication or preventive measures are required. Treatment of a myasthenia gravis patient with amide local analgesic is possible; narcosis is also possible. Local anaesthesia (using amide local analgesic in minimal dosage) is preferred to narcosis. After the dental treatment, optimal pain management is crucial to limit the chance of a crisis.

Excessive daytime sleepiness in a patient with coexisting myotonic dystrophy type 1, myasthenia gravis and Graves' disease.

A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.

Major motor-functional determinants associated with poor self-reported health-related quality of life in myasthenia gravis patients.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which disabling muscle weakness may affect health-related quality of life (HRQoL). The aim of this study was to investigate which common motor-functional deficits and corresponding severity are most determinant of poor HRQoL in these patients. In 41 patients, the dichotomized first item of the Italian Myasthenia Gravis Questionnaire (IMGQ), categorizing patients who report "good" and "poor" HRQoL, was chosen as dependent-outcome variable. All items composing the myasthenia gravis-specific scale (MG-ADL), i.e. talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to rise from chair, double vision, and eyelid droop were acquired as independent variables and dichotomized. Stepwise backward LR multivariable logistic regression analysis was performed. In addition, the main characteristics of patients were compared. MG-ADL items "chewing" ≥1, i.e. "fatigue chewing solid food", and "breathing" ≥2, i.e. "shortness of breath at rest" proved to be significant determinants. Higher dose of corticosteroid therapy was significantly (p = 0.027; r s  = -0.35), correlated with poor HRQoL. At diagnosis, a decremental response to repetitive nerve stimulation (RNS) from the abductor pollicis brevis was significantly more frequent in patients with poor HRQoL. In conclusion, impaired "chewing" and "breathing" functions indicate the need for careful planning of rehabilitation, re-education and patient management. Moreover, decremental response to RNS at diagnosis may identify patients at risk for poor HRQoL.

Application of digital technology in the prosthodontic management of a patient with myasthenia gravis: A clinical report.

Application of digital technology in the treatment of a patient with myasthenia gravis and an excessively resorbed mandibular residual alveolar ridge is presented. The patient requested replacement of worn maxillary and mandibular prostheses. Treatment involved fabricating a new maxillary complete denture that was similar in appearance to the one being replaced and rebasing the existing and clinically acceptable mandibular fixed framework. The interim phase of treatment involved fabricating a mandibular milled prosthesis similar in morphology to the existing fixed complete denture with computer-aided design and computer-aided manufacturing technology. This facilitated conversion of an interim prosthesis by using an orientation device and eliminated the need for the patient to adapt to an interim removable complete denture.

[Contribution of Perioperative Oral Health Care and Management for Patients who Underwent General Thoracic Surgery].

Due to the recent advances in radiological diagnostic technology, the role of video-assisted thoracoscopic surgery in thoracic disease has expanded, surgical indication extended to the elderly patients. Cancer patients receiving surgery, radiation therapy and/or chemotherapy may encounter complications in conjunction with the oral cavity such as aspiration pneumonia, surgical site infection and various type of infection. Recently, it is recognized that oral health care management is effective to prevent the postoperative infectious complications, especially pneumonia. Therefore, oral management should be scheduled before start of therapy to prevent these complications as supportive therapy of the cancer treatment. In this background, perioperative oral function management is highlighted in the remuneration for dental treatment revision of 2012,and the importance of oral care has been recognized in generally. In this manuscript, we introduce the several opinions and evidence based on the recent previous reports about the perioperative oral health care and management on thoracic surgery.

Association Between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities.

INTRODUCTION: For patients with generalized myasthenia gravis (gMG), the association between symptom severity, often measured with the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument, and utility values is unknown. METHODS: Data was analyzed from the phase 3 ADAPT trial, which included adult patients with gMG randomly assigned to treatment with efgartigimod + conventional therapy (EFG + CT) or placebo + CT (PBO + CT). MG-ADL total symptom scores and the EQ-5D-5L, a measure of health-related quality of life (HRQoL), were collected biweekly up to 26 weeks. Utility values were derived from the EQ-5D-5L data with the United Kingdom value set. Descriptive statistics were reported for MG-ADL and EQ-5D-5L at baseline and follow-up. A normal identity-link regression model estimated the association between utility and the eight MG-ADL items. A generalized estimating equations (GEE) model was estimated to predict utility based on the patient's MG-ADL score and treatment received. RESULTS: A total of 167 patients (84 EFG + CT, 83 PBO + CT) contributed 167 baseline and 2867 follow-up measurements of MG-ADL and EQ-5D-5L. EFG + CT-treated patients experienced more improvements than PBO + CT-treated patients in most MG-ADL items and EQ-5D-5L dimensions, with the largest improvements observed in chewing, brushing teeth/combing hair, eyelid droop (MG-ADL); self-care, usual activities, mobility (EQ-5D-5L). The regression model indicated that individual MG-ADL items contributed differently to utility values, with the largest impact from brushing teeth/combing hair, rising from a chair, chewing, and breathing. The GEE model showed that each unit improvement in MG-ADL led to a statistically significant utility increase of 0.0233 (p < 0.001). In addition, a statistically significant improvement of 0.0598 (p = 0.0079) in utility was found for patients in the EFG + CT group compared to the PBO + CT group. CONCLUSION: Among patients with gMG, improvements in MG-ADL were significantly associated with higher utility values. MG-ADL scores alone were not sufficient to capture the utility gained from efgartigimod therapy.

On the path to evidence-based therapy in neuromuscular disorders.

Neuromuscular disorders encompass a diverse group of acquired and genetic diseases characterized by loss of motor functionality. Although cure is the goal, many therapeutic strategies have been envisioned and are being studied in randomized clinical trials and entered clinical practice. As in all scientific endeavors, the successful clinical translation depends on the quality and translatability of preclinical findings and on the predictive value and feasibility of the clinical models. This chapter focuses on five exemplary diseases: childhood spinal muscular atrophy (SMA), Charcot-Marie-Tooth (CMT) disorders, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), acquired autoimmune myasthenia gravis (MG), and Duchenne muscular dystrophy (DMD), to illustrate the progress made on the path to evidenced-based therapy.

A case of Lambert-Eaton myasthenic syndrome with possible myasthenia gravis.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission (NMJ) that shares many clinical features with myasthenia gravis (MG). We report a 73 year-old lady who presented 10 years previously with stiffness of both calves, dry mouth, fatigue, proximal weakness and areflexia in lower limbs. Neurophysiological studies were consistent with LEMS. Her work up for an underlying neoplasm was negative. She recently developed unilateral ptosis and diplopia which dramatically improved with pyridostigmine suggesting concomitant MG.

Decreased salivary α-amylase activity responding to citric acid stimulation in Myasthenia gravis with malnutrition.

OBJECTIVES: Malnutrition, defined according to Nutritional risk screening (NRS 2002), is commonly observed in patients of Myasthenia gravis (MG), a neuromuscular disorder manifested by varied degrees of skeletal muscle weakness. Because biochemical composition of saliva changes in correspondence to alterations in nutritional status, we tested our hypothesis that a certain saliva component(s) might serve as a biomarker(s) for nutrition status of MG, particularly for those MG patients with high risk of malnutrition. MATERIALS AND METHODS: 60 MG patients and 60 subjects belonging to the healthy control group (HCG) were enrolled in this case-control study. The salivary α-amylase (sAA) activity, salivary flow rate (SFR), pH, total protein density (TPD), and the concentrations of chloride and calcium ions in MG group with or without malnutrition were measured before and after citric acid stimulation. Thereafter, the relationship between sAA activity and BMI was determined in MG and HCG. RESULTS: Compared with HCG, more patients with malnutrition, increased TPD and chloride and calcium concentrations but decreased pH value and SFR both before and after acid stimulation, as well as reduced sAA activity, pH and TPD responses to acid stimulation. MG with malnutrition showed decreased sAA activity and TPD responding to acid stimulation compared with those without malnutrition. Compared with normal BMI, sAA activity response to acid stimulation was reduced in low BMI. There was a significant strong positive correlation between the ratio of sAA activity and BMI in MG. CONCLUSIONS: Salivary biochemical characteristics are abnormally altered in MG with malnutrition. Altered sAA activity responding to acid stimulation was associated with malnutrition. CLINICAL RELEVANCE: Decreased sAA activity responding to acid stimulation can reflect malnutrition state and may be one potential screening marker for MG patients with high risk of malnutrition.

Jaw muscle weakness: a differential indicator of neuromuscular weakness--preliminary observations.

INTRODUCTION: Flaccid quadriparesis is a common neurological problem. Guillain-Barré syndrome Guillain-Barre syndrome (GBS), polymyositis/dermatomyositis (PM/DM), generalized myasthenia gravis (MG), and hypokalemic periodic paralysis (HPP) constitute the majority of cases of flaccid quadriparesis. Few patients from any of these disease groups lack the cardinal clinical features. We established clinical marker(s) that might have significant discriminating power for diagnosis. METHODS: Forty-six patients satisfied all of our criteria. Cases were evaluated clinically followed by laboratory and electrophysiological study, and, in selected cases, muscle histopathology. RESULTS: Twenty-four patients had GBS, 9 had MG, 7 had PM/DM, and 6 had HPP. Jaw-opening weakness was found in 71.4% of PM/DM, 83.3% of HPP, and 4.1% of GBS cases. Jaw-closing weakness was found in 88.8% of MG cases. CONCLUSIONS: Presence of jaw-closing weakness pointed toward MG, whereas presence of jaw-opening weakness suggested muscle disease (PM/DM and HPP). GBS patients very rarely had jaw muscle weakness.

Myasthenia Gravis Associated With Programmed Death-1 (PD-1) Receptor Inhibitor Pembrolizumab: A 40-day Case Report.

PURPOSE: This case report describes myasthenia gravis-like symptoms after treatment with a programmed cell death 1 inhibitor, pembrolizumab, the treatment modalities utilized, and associated patient outcomes. SUMMARY: A 76-year old male treated with pembrolizumab for palliative therapy for metastatic melanoma presented with increasing weakness, neck pain, diplopia in the left eye, abducens palsy, periorbital edema, and decreased appetite. The patient was diagnosed with acetylcholine receptor antibody (AChR) negative myasthenia gravis. The patient was started on prednisone 1 mg/kg/day, followed by pyridostigmine 60 mg by mouth 3 times a day, and IVIg for 5 days. Due to minor improvements in myasthenia gravis symptoms, 5 cycles of plasmapheresis were ordered. The patient was successfully treated for aspiration pneumonia after cardiopulmonary arrest. On day 28, the patient was diagnosed with ventilator associated pneumonia and received appropriate therapy. Due to ICU agitation and delirium, VAP, and long duration of treatment, the patient requested withdrawal of care and passed. CONCLUSION: Programmed cell death inhibitors, such as pembrolizumab, can provide great benefit to patients but can also be associated with rare but serious adverse events. With new reports of MG after use, providers should continually weigh the benefits versus harm in using these products and monitor patients closely for such adverse events.

A Case Report of Subclinical Myasthenia Gravis Associated with Castleman's Disease.

BACKGROUND Castleman's disease is defined as a benign lymphoproliferative disorder of uncertain origin. It is most commonly found in the area of mediastinum. Castleman's disease is classified based on pathological features into hyaline-vascular, plasma cell, and mixed variants, which the hyaline-vascular variant is the commonest in association with Myasthenia Gravis. Castleman's Disease have been very rarely reported in Myasthenia Gravis, as it is associated with various clinical abnormalities. The enlarged localized lymph node is mainly diagnosed by incidental radiological findings due to the enlargement of thymus gland or by compression symptoms. CASE REPORT Here we report a case revolves around a 31-year-old Saudi woman who presented with a 2 years history of exertional dyspnea associated with mouth and eye ulcers. There were no other associated symptoms such as muscular weakness, rapid fatigue or drooping of the eyelids. She was referred to our institution for further investigations and management. She was diagnosed with a mediastinal thymoma that was detected based on a positive serology of antibody anti-acetylcholine receptor (AChR) testing and a computed tomography (CT) scan findings, she eventually underwent a bilateral thoracoscopic thymectomy. CONCLUSIONS The aim of this case report is to add more to the literature by reporting a rare case of an asymptomatic subclinical Myasthenia Gravis associated with Castleman's disease. It highlights the importance of considering a Castleman's Disease in an asymptomatic case who presented with a mediastinal mass and in order to avoid an unusual intraoperative finding such as massive bleeding by performing a biopsy and an angiography preoperatively.

Swallowing dysfunction in myasthenia gravis patients examined with high-resolution manometry.

OBJECTIVE: To prospectively compare oropharyngeal swallowing dysfunction in myasthenia gravis (MG) patients presenting with difficulty in swallowing between the neutral and chin-down positions, based on the results of high-resolution manometry (HRM) examination. METHODS: We prospectively compared the HRM results of swallowing studies of seven MG patients showing difficulty in swallowing (neutral and chin-down positions) at the Department of Neurology of our institution during the period February-December 2018. The HRM assessment parameters were as follows: maximum swallowing pressure (SP) at the soft palate, meso­hypopharynx, and upper esophageal sphincter (UES), and the duration of relaxation pressure at the UES. These parameters were compared between the two positions and their correlations with the results of neurological evaluations, such as the Quantitative Myasthenia Gravis (QMG) score (total and neck muscles alone), and grip strength, were also analyzed. RESULTS: In comparison with the neutral position, in the chin-down position the maximum SP at the meso­hypopharynx was significantly increased (p < 0.05), the maximum SP at the UES was significantly decreased (p < 0.05), and the duration of relaxing SP at the UES was significantly increased (p < 0.05). Interestingly, there were no correlations between the SP at any location and the results of the neurological evaluations. CONCLUSIONS: The chin-down position appears useful for improving pharyngeal clearance in MG patients, by promoting increased SP at the meso­hypopharynx, relaxing SP at the UES, and increasing the duration of relaxation pressure at the UES.

Patient-reportedimpact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG).

INTRODUCTION: Myasthenia gravis (MG) is a rare, chronic, autoimmune disease, mediated by immunoglobulin G antibodies, which causes debilitating muscle weakness. As with most rare diseases, there is little patient-reported data with which to understand and address patient needs. This study explores the impact of MG in the real world from the patient perspective. METHODS AND ANALYSIS: This is a 2-year prospective, observational, digital, longitudinal study of adults with MG, resident in the following countries: the USA, Japan, Germany, France, the UK, Italy, Spain, Canada and Belgium. The planned sample size is 2000. Recruitment will be community based, via patient advocacy groups, social media and word of mouth. Participants will use a smartphone application (app) to check eligibility, provide consent and contribute data. Planned data entry is as follows: (1) personal profile on enrollment-covering demographics, MG characteristics and previous care; (2) monthly event tracker-current treatments, healthcare visits, treatment-related adverse events, productivity losses; (3) monthly selection of validated generic and disease-specific patient-reported outcomes instruments: EQ-5D-5L, Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Quality of Life 15-item revised scale, Hospital Anxiety and Depression Scale and Health Utilities Index III. Analyses are planned for when the study has been running in most countries for approximately 6, 12, 18 and 24 months. ETHICS AND DISSEMINATION: The study protocol has been reviewed and granted ethics approval by Salus IRB for participants resident in the following countries: Germany, the UK and the US. Local ethics approval is being sought for the following study countries: Belgium, Canada, France, Italy, Japan and Spain. Study results will be communicated to the public and participants via conference presentations and journal publications, as well as regular email, social media and in-application communication. TRIAL REGISTRATION NUMBER: NCT04176211.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

BACKGROUND: In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. OBJECTIVE: To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. METHODS: The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). RESULTS: Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. CONCLUSIONS: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Systemic lupus erythematosus after thymectomy for myasthenia gravis: a case report and review of the literature.

Here, we report a case of systemic lupus erythematosus in a 13-year-old girl who developed the disease 3 years after thymectomy performed for the treatment of myasthenia gravis. The presenting symptoms were fever, generalized fatigability, bilateral loin pain, weight loss, arthralgia, hair loss, and recurrent painless mouth ulcers. Laboratory findings revealed proteinuria, hematuria, anemia, leucopenia, a high titer of antinuclear antibodies (ANA), anti-dsDNA, and decreased complement (C3 and C4) levels. There was minimal ascitis and pericardial effusion. Renal biopsy showed lupus nephritis class IV. The diagnosis of systemic lupus erythematosus was established based on the clinical and laboratory findings. The activity of systemic lupus erythematosus was controlled by pulsed treatment with methyl prednisolone followed by long-term oral glucocorticoid and immunosuppressive therapy. This study highlights the immune system derangement following thymectomy. It also examines the relevant literature.