Muscle weakness and functional disability in patients with myasthenia gravis

2018 ◽  
Vol 59 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Lotte Vinge ◽  
Johannes Jakobsen ◽  
Henning Andersen
Keyword(s):  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Functional Disability

scholarly journals AB0854 A CASE REPORT OF BROWN SYNDROME COMPLICATING THE MANAGEMENT OF SCLEROMYOSITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1451.1-1451
Author(s):  
P. Arora ◽  
L. Croot
Keyword(s):  
Case Report ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Tendon Sheath ◽  
Motility Disorder ◽  
Ocular Motility ◽  
Muscle Involvement ◽  
Eye Muscle ◽  
Brown Syndrome ◽  
Superior Oblique

Background:Brown syndrome is a rare ocular motility disorder which has been reported in JRA, RA and SLE but never in a patient with scleromyositis.Objectives:To report the first case of Brown syndrome in a patient with scleromyositis and increase awareness of this condition.Methods:A case report and discussion.Results:The patient was diagnosed with scleromyositis, at the age of 34, after presenting with arthralgia, sclerodactyly, skin pigmentation, Raynaud’s phenomenon, mild muscle weakness and dyspnoea. His labs were CRP 47 mg/L, CK 868 IU/L, ANA strongly positive; anticentromere Ab negative and Anti-PM/Scl-75 and Anti- PM/Scl-100 Ab positive. HRCT chest showed extensive pulmonary fibrosis with lower lobe honeycombing. TLCO was 3.98 (33% of predicted).He was initially managed with high dose steroids and pulsed IV cyclophosphamide with azathioprine for maintenance therapy. His lung disease stabilised and myositis resolved but he continued to develop calcinosis cutis so was switched to 6 monthly IV rituximab.6 years later, he developed morning headaches with intermittent diplopia, described as double vision in vertical gaze with one image being above the other. Episodes lasting 10 minutes to 2 hours. Examination showed normal visual acuity and fundoscopy, no peripheral or eye muscle weakness.Investigations to exclude myasthenia gravis, cerebral vasculitis and atypical infection were organised (MRI, AChR antibody, lumbar puncture, MRA) and were normal.Because of intermittent nature of his episodes, his eye examination was always normal but he captured images in disconjugate gaze with right eye looking upwards and outwards when trying to look straight (Figure 1). Occasionally this was associated with orbital pain and an audible click. These features are suggestive of Brown syndrome.He continues to have recurrent episodes despite immunosuppression but prednisolone 20mg daily for 1-2 days at onset of each attack causes rapid resolution of symptoms.Figure 1.Right eye looking upwards and outwards when trying to look straightConclusion:Scleromyositis is an overlap syndrome of scleroderma and dermatomyositis. Muscle involvement is mild and clinical presentation can be variable. The PM/Scl antibodies are highly characteristic of the syndrome. (1)Brown syndrome is an ocular motility disorder, first described in 1950, characterized by the inability to fully elevate the affected eye in adduction due to pathology of the superior oblique tendon sheath. (2)It can be congenital or acquired, viz, trauma, surgery or sinusitis and also been described in RA, JIA and SLE. (3)If superior oblique tendon cannot relax or slide freely through the trochlea then the affected eye cannot depress completely, leading to diplopia on upward gaze. (4) In inflammatory disease it is thought that swelling of the posterior part of the superior oblique tendon or tenosynovitis are likely causes of the tendon sheath abnormality. (4) This is likely to be the case in this patient because his symptoms are recurrent, respond to steroids and tend to occur more towards the end of rituximab cycles.Recognition of this syndrome is important because invasive investigations can be avoided. Also, intermittent diplopia in a patient with autoimmune disease is suggestive of myasthenia gravis which maybe incorrectly diagnosed.Finally, this case demonstrates the syndrome can be easily managed with short courses of oral steroids, although patients who are already on immunosuppressant treatment may need this in addition.References:[1]Török L, Dankó K, Cserni G, Szûcs G. PM-SCL autoantibody positive scleroderma with polymyositis (mechanic’s hand: clinical aid in the diagnosis). JEADV 2004; 18: 356–359[2]Brown H W. Congenital structural muscle anomalies. In:Alien J H, ed. Strabismus ophthalmic symposium I. St Louis:CV Mosby, 1950: 205-6.[3]Cooper C, Kirwan JR, McGill NW, Dieppe PA. Brown’s syndrome: an unusual ocular complication of rheumatoid arthritis. Ann Rheum Dis 1990; 49:188-9.[4]Sandford-Smith JH. Superior oblique tendon syndrome and its relationship to stenosing tenosynovitis. Br JOphthalmol 1973; 57:859-65.Disclosure of Interests:None declared

Expecting the unexpected.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Blessie Elizabeth Nelson ◽  
Adrian Gerard Murphy ◽  
Jacquelyn W. Zimmerman
Keyword(s):  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
De Novo ◽  
Early Recognition ◽  
Compound Muscle Action Potential ◽  
Care Center ◽  
Tertiary Care ◽  
Sudden Onset ◽  
Shoulder Abduction ◽  
Myasthenic Crisis

e14066 Background: Myasthenia gravis is an autoimmune neuro-muscular disorder traditionally seen in bi-modal distribution in young women or older men. Discovery of immunotherapy has brought hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo. Methods: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day. One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. He was started on antibiotics for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Results: Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine. Conclusions: There is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management. It highlights need for the oncological world and our colleagues in various other disciplines of healthcare to identify and mitigate the effects of immunotherapy which has become our hope in beating cancer.

Muscle Weakness and Diabetes Jointly Exacerbate the Rate of Functional Disability among Older Mexican Americans

2017 ◽  
Vol 49 (5S) ◽  
pp. 69-70
Author(s):  
Ryan P. McGrath ◽  
Brenda M. Vincent ◽  
Brad P. Dieter ◽  
Kate A. Duchowny ◽  
Kyriakos S. Markides ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Mexican Americans ◽  
Functional Disability

scholarly journals Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis: A Neuromuscular Surprise

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Hassam Ali ◽  
Rahul Pamarthy ◽  
Nayab Ahsan ◽  
WashmaAwan ◽  
Shiza Sarfraz
Keyword(s):  
Neuromuscular Junction ◽  
Tyrosine Kinase ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Acetylcholine Receptors ◽  
Muscular Contraction ◽  
Skeletal Muscle Weakness ◽  
Hypoxic Respiratory Failure ◽  
Receptor Antibodies

Myasthenia gravis is a neuromuscular autoimmune disease that results in skeletal muscle weakness that worsens after periods of activity and improves after rest. Myasthenia gravis means “grave (serious), muscle weakness.” Although not completely curable, it can be managed well with a relatively high quality of life and expectancy. In myasthenia gravis, antibodies against the acetylcholine receptors at the neuromuscular junction interfere with regular muscular contraction. Although most commonly caused by antibodies to the acetylcholine receptor, antibodies against MuSK (muscle-specific kinase) protein can also weaken transmission at the neuromuscular junction. Muscle-specific tyrosine kinase myasthenia gravis (MuSK-Ab MG) is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. Diagnosis can be challenging due to its atypical presentation as compared to seropositive myasthenia gravis. It responds inconsistently to steroids, but plasma exchange and immunosuppressive therapies have shown promising results. We report a case of a 49-year-old female who presented with acute hypoxic respiratory failure. Our patient experienced progressive, undiagnosed MuSK-Ab MG for years without a diagnosis.

scholarly journals Myasthenia Crisis Vs Cholinergic Crisis: Challenges in Crisis Management Without Plasmapheresis or Intravenous Immunoglobulin (IVIG)

2020 ◽  
Vol 2 (2) ◽  
pp. 53
Author(s):  
Lila Tri Harjana ◽  
Hardiono Hardiono
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Spontaneous Breathing Trial ◽  
Ventilatory Support ◽  
Clinical Signs ◽  
Autoimmune Disorder ◽  
High Dose ◽  
Respiratory Compromise

Introduction: Myasthenia gravis (MG) is an acquired autoimmune disorder clinically characterized by skeletal muscle weakness & fatigability on exertion with prevalence as high as 2–7 in 10,000 and women are affected more frequently than men (~3:2). Over 12-16% of generalized MG patients experience crisis once in their lifetime. A serious complication of myasthenia gravis is respiratory failure. This may be secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment with excess doses of a cholinesterase inhibitor (cholinergic crisis). Case Report: Thirty-two years old woman refereed from a private hospital to ED for further treatment with myasthenia in crisis, after nine days of treatment in the previous ICU. Patient already in intubation with mechanical ventilation and history of the treatment of a high dose of multiple anticholinesterase drugs and steroids without plasmapheresis or immunoglobulin intravenous. During admission, diarrhea was present, with no sign of GI infection. On the third day of admission, the patient performed a Spontaneous Breathing Trial and was a success then extubated. Then two day after extubation, the patient falls to respiratory failure and need mechanical ventilation. Anticholinesterase test was performed, and it shows no improvement in clinical signs, and diagnose as Cholinergic Crisis. After re-adjustment of anticholinesterase drug with a lower dose, clinically, the respiratory condition improved, and on the 10th day of admission, the patient was succeed extubated. At 12nd days of ICU admission, patient discharge from ICU. Discussion: Myasthenia and Cholinergic Crisis is a severe and life-threatening condition characterized by generalized muscle weakness with a respiratory compromise that requires ventilatory support. Respiratory failure may be present in the cholinergic crisis without cholinergic symptoms (miosis, diarrhea, urinary incontinence, bradycardia, emesis, lacrimation, or salivation). The most important management aspect of Myasthenia patients in crisis is the recognition and treatment of myasthenia vs cholinergic crisis.

scholarly journals Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sophie Cleanthous ◽  
Ann-Christin Mork ◽  
Antoine Regnault ◽  
Stefan Cano ◽  
Henry J. Kaminski ◽  
...  
Keyword(s):  
Literature Review ◽  
Myasthenia Gravis ◽  
Rare Disease ◽  
Outcome Measures ◽  
Patient Experience ◽  
Muscle Weakness ◽  
Symptom Severity ◽  
Test Theory ◽  
Concept Elicitation

Abstract Background Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease, characterised by fluctuating muscle weakness which makes it challenging to assess symptom severity. Mixed methods psychometrics (MMP), which combines evidence from qualitative research and modern psychometrics, is a versatile approach to the development of patient-centred outcome measures (PCOM) in the context of rare disease. Our objective was to develop the MG Symptom patient-reported outcome (PRO) to assess key aspects of MG severity from the patient perspective. Methods We used MMP to develop a novel PRO instrument in a multi-step process. An initial conceptual model for MG patient experience was developed and expanded based on preliminary literature review and two waves of concept elicitation interviews with people with MG (Step 1). Based on this, the novel PRO instrument, the MG Symptoms PRO, was drafted. The draft instrument was refined by combining qualitative and quantitative data collected in a Phase 2 clinical study (Step 2). Results Findings from the literature review and concept elicitation interviews (n = 96) indicated that patient experience in MG includes proximal muscle weakness symptoms related to several body parts, along with muscle weakness fatigability and general fatigue. Then, a set of 42 items across five scales (ocular-, bulbar-, and respiratory muscle weakness, physical fatigue, and muscle weakness fatigability) was developed. Qualitative evidence endorsed its relevance, clarity, and ease of completion; quantitative analysis with Rasch measurement theory methods demonstrated strong measurement properties, including good targeting and high reliability. Classical test theory analyses showed adequate reliability of the instrument and mild to moderate correlations with other widely used MG-specific outcome measures. Conclusions The MG Symptoms PRO has potential to be used both to measure treatment benefit in clinical trials and monitor symptom severity in clinical practice. Its component scales were purposefully designed to stand alone, enhancing interpretability of scores given the heterogeneity of MG, and enabling modular use. Compared with existing MG PROs, it contains more detailed assessments of muscle weakness and muscle weakness fatigability symptoms, which are of key importance to people with MG. The MMP approach used may serve as a case study for developing PCOMs across rare disease indications.

scholarly journals Myasthenia Gravis in Patients with Histopathologically Diagnosed Thymoma at Sanglah General Hospital: A Case Series

2021 ◽  
Vol 15 (2) ◽  
pp. 91
Author(s):  
Desak Putu Gayatri Saraswati Seputra ◽  
I Gusti Ayu Sri Mahendra Dewi
Keyword(s):  
Myasthenia Gravis ◽  
General Hospital ◽  
Muscle Weakness ◽  
Histopathological Examination ◽  
Early Recognition ◽  
Regional Lymph Node ◽  
Case Series ◽  
Epithelial Tissue ◽  
Muscle Involvement ◽  
Female Ratio

Introduction: Thymoma is a neoplasm of the thymus gland which arises from the epithelial tissue. Thymoma is frequently related to various paraneoplastic syndromes, most commonly myasthenia gravis. Up to 50% of patients with thymoma are reported to develop myasthenia gravis, whereas 10–15% of patients with myasthenia gravis are found to have thymoma. Case Presentation: This case series reported 3 patients with myasthenia gravis which co-occurred with thymoma at Sanglah General Hospital from 2018 to 2019. The patients’ ages range from 33 to 61 years (mean age 46 ± 11 years) with a 2:1 male-to-female ratio. The diagnosis of myasthenia gravis was made by the presentation of typical myasthenia gravis appearances, the fluctuating intensity of ocular and bulbar muscle weakness (all three cases), and limbs and axial muscle weakness (one case); no respiratory muscle involvement was found. Physical and supporting examinations including electroneuromyography results were coherent with myasthenia gravis. The diagnosis of thymoma was made by highly suggestive appearance in Thorax Multi Sliced Computed Tomography (MSCT) scan examination and histopathologic findings. MSCT scan examination showed a well-circumscribed ovoid solid mass in the mediastinum (left anterosuperior, superior, and anterior to middle right mediastinum) sized from 1.8x1.5x2.9 cm to 8.1x9.9x9.7 cm, enhanced with contrast injection with areas of calcification and central necrotic (1 case) and no dissemination to regional lymph node and neighboring organs. All cases received acetylcholinesterase inhibitors and underwent extended thymectomy. Histopathological examination showed accordance with thymoma features of subtype A, AB, and B1.Conclusions: Clinicians should be aware of the thymoma and myasthenia gravis co-existence possibility to ensure early recognition and appropriate management.

scholarly journals Two patients with a neuroendocrine tumour of the small intestine and paraneoplastic myasthenia gravis

2014 ◽  
Vol 2014 ◽  
Author(s):  
M A W Hermans ◽  
B M L Stelten ◽  
H R Haak ◽  
W W de Herder ◽  
M W Dercksen
Keyword(s):  
Small Intestine ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Muscle Weakness ◽  
Neuroendocrine Tumour ◽  
Stage Iv ◽  
List Type ◽  
Bulbar Symptoms ◽  
Receptor Antibodies ◽  
Learning Points

Summary This paper reports on two patients with a long-standing diagnosis of an ENETS stage IV neuroendocrine tumour (NET) of the small intestine who developed neurological symptoms. The first patient only had bulbar symptoms and tested positive for acetylcholine receptor antibodies. The second patient had more classical symptoms of fatigable diplopia and muscle weakness of the legs, but no detectable antibodies. The diagnosis of paraneoplastical myasthenia gravis (MG) was postulated. Both patients were treated with pyridostigmine for MG and octreotide for the NETs. Interestingly, treatment of the NETs resulted in improvement of myasthenic symptoms. Paraneoplastic MG has been described to occur with certain malignancies, mainly thymoma. Herein, we prove that the association with gastrointestinal NETs, however, rare, is also one to be considered by clinicians dealing with either of these diseases. The pathogenesis has yet to be elucidated. Learning points NETs are rare malignancies with a wide variety of symptoms. Paraneoplastic MG can occur with various types of malignancies. Herein, we provide evidence of paraneoplastic MG in association with a grade IV NET of the small intestine. Treatment of the NETs resulted in remission of myasthenic symptoms in one patient.

scholarly journals Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

2021 ◽  
Vol 118 (13) ◽  
pp. e2020635118
Author(s):  
Dana L. E. Vergoossen ◽  
Jaap J. Plomp ◽  
Christoph Gstöttner ◽  
Yvonne E. Fillié-Grijpma ◽  
Roy Augustinus ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Binding Sites ◽  
Antiinflammatory Activity ◽  
Autoimmune Response ◽  
Cross Link ◽  
Muscle Specific Kinase ◽  
Opposing Effects

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

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