Switch to double positive late onset MuSK myasthenia gravis following thymomectomy in paraneoplastic AChR antibody positive myasthenia gravis

IntroductionThe aim of our study was to establish if there were any clinical and immunological differences between early (EOMG) and late onset myasthenia gravis (LOMG).Methods and resultsWe recruited 150 patients with myasthenia gravis making this the largest prospective cohort study in MG to date. Most (74%) patients have LOMG. Of these, 8 (5.33%) are seronegative. Most (88%) are positive for AChR Abs, 4% have MuSK, 2% LRP4 and 10% are double positive to AChR and MuSK Ab on CBA.The incidence of LOMG is higher than EOMG. There is a statistically significant fall in AChR titre levels on serial measurement (p <0.0001). LOMG pts have higher AChR titres at recruitment compared to EOMG (p=0.0498) with higher MG composite scores (p=0.0287). Significantly higher numbers of LOMG pts are positive for AChR Ab on RIA in generalised MG compared to EOMG. A third of the pts with Early Onset Generalised MG are positive for MuSK Abs on CBA. There is no significant difference in clinical presentation between single seropositive pts Vs double seropositive pts. AChR Ab titres are lower in ocular EOMG versus ocular LOMG and titres in ocular patients are lower than in generalised patients.Flow cytometric analysis of PBMCs showed a significantly reduced percentage of Treg cells in our patient cohort compared to healthy controls (p<0.0001) and a significant difference in the levels of TNFa, IL10 and IL17 produced.ConclusionOur study has shown that there are clinical and immunological differences between early onset and late onset myasthenia gravis, both respond well to treatment with an improvement in composite scores and a fall in antibody titres. We are continuing to study this cohort of MG patients with extended follow-up.

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Effective Early Treatment of AChR Antibody-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country

Journal of Central Nervous System Disease ◽

10.1177/11795735211016080 ◽

2021 ◽

Vol 13 ◽

pp. 117957352110160

Author(s):

Thomas Mathew ◽

Kurian Thomas ◽

Saji K John ◽

Shruthi Venkatesh ◽

Raghunandan Nadig ◽

...

Keyword(s):

Observational Study ◽

Myasthenia Gravis ◽

Treatment Option ◽

Early Treatment ◽

Early Stage ◽

Tertiary Care ◽

Response To Treatment ◽

Myasthenic Crisis ◽

Achr Antibody ◽

Significant Difference

Background: Rituximab is reserved for treating refractory myasthenia gravis (MG) patients. Here we report our experience with rituximab in AChR antibody positive generalized MG (gMG) and impending myasthenic crisis (IMC). Methods: This retrospective, observational study, conducted at a tertiary care, neuroimmunology clinic, analyzed the data of patients with AChR antibody positive gMG, treated with rituximab between 1st January 2016 and 30th October 2018. Results: Eleven patients with AChR antibody positive gMG received rituximab. Mean age of the cohort was 50.54 ± 18.71 years with 9 males. Seven out of 11 patients received rituximab in the early stage (<2 years from onset) and had good response to treatment. Four of the 5 patients with IMC improved with rituximab alone. In the 10 patients who regularly followed up, there was a significant difference between the QMG scores at baseline and at 1, 2, 6, 12, and 18 months ( P < .0001). Conclusion: Rituximab appears to be a potentially effective early treatment option for AChR antibody positive generalized MG and impending myasthenic crisis.

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Post-thymectomy myasthenia gravis: a case report and systematic review of literature

BMJ Case Reports ◽

10.1136/bcr-2021-246005 ◽

2021 ◽

Vol 14 (12) ◽

pp. e246005

Author(s):

Louise Gurowich ◽

Gabriel Yiin ◽

Adam Maxwell ◽

Alexandra Rice

Keyword(s):

Systematic Review ◽

Case Report ◽

Myasthenia Gravis ◽

Early Onset ◽

Late Onset ◽

High Morbidity ◽

Review Of Literature ◽

Prompt Treatment ◽

Autoimmune Condition ◽

Anti Acetylcholine

Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction characterised by weakness and fatiguability, carrying a high morbidity if treatment is delayed. A clear association with thymoma has led to management with thymectomy as a common practice, but MG presenting post-thymectomy has rarely been reported. We present a case of an 82- year-old woman developing fatigue, ptosis and dysarthria 3 months after thymectomy. After a clinical diagnosis of MG was made, she responded well to prompt treatment with prednisolone and pyridostigmine. Her anti-acetylcholine receptor antibody (anti-AChR) subsequently came back positive. Our systematic review reveals that post-thymectomy MG can be categorised as early-onset or late-onset form with differing aetiology, and demonstrated correlation between preoperative anti-AChR titres and post-thymectomy MG. The postulated mechanisms for post-thymectomy MG centre around long-lasting peripheral autoantibodies. Clinicians should actively look for MG symptoms in thymoma patients and measure anti-AChR preoperatively to aid prognostication.

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Late onset myasthenia gravis: A review and report of 24 cases

Brain and Nerves ◽

10.15761/jbn.1000119 ◽

2018 ◽

Vol 3 (1) ◽

Author(s):

Andrea L. Porras-Yaurivilca ◽

Tulio E. Bertorini ◽

Victor J. Duenas-Vicuna ◽

William H. Mays

Keyword(s):

Myasthenia Gravis ◽

Late Onset

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A Case of COVID-19 Vaccine Associated New Diagnosis Myasthenia Gravis

Journal of Primary Care & Community Health ◽

10.1177/21501327211051933 ◽

2021 ◽

Vol 12 ◽

pp. 215013272110519

Author(s):

Augustine Chavez ◽

Charlotte Pougnier

Keyword(s):

Myasthenia Gravis ◽

Late Onset ◽

Severe Exacerbation ◽

Presenting Symptoms ◽

Immune Mediated ◽

Peg Tube ◽

New Diagnosis

An 82-year-old man presented with intermittent episodes of slurred speech during his evening meals after receiving the BNT162b2 COVID-19 vaccine. Thorough evaluation was conducted including lab work and EMG confirming a new diagnosis of late-onset myasthenia gravis. Despite treatment, the patient progressed rapidly to severe exacerbation requiring intubation and placement of a PEG tube. Infections provoking new diagnosis and exacerbations of myasthenia gravis have been reported. New diagnosis of myasthenia gravis associated with the COVID-19 vaccine is rarely reported. This case highlights the need for clinicians to be aware of the uncommon presenting symptoms in late-onset myasthenia gravis and the possibility of vaccine provoked diagnoses of immune mediated diseases.

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Vestibular assessment of a patient with myasthenia gravis: case report

Journal of Otolaryngology-ENT Research ◽

10.15406/joentr.2020.12.00458 ◽

2020 ◽

Vol 12 (3) ◽

pp. 65-70

Author(s):

Kenneth Chua ◽

Sakumura J

Keyword(s):

Myasthenia Gravis ◽

Late Onset ◽

Vestibular Function ◽

Symptom Checklist ◽

Test Results ◽

Functional Impairments ◽

Clinical Value ◽

Vestibular Assessment ◽

Vestibular Function Testing ◽

Function Testing

Vestibular Assessment in patients with Myasthenia Gravis (MG) is challenging, as diagnostic evaluation requires good recording of eye movements. Reports on Vestibular Function Testing (VFT) in MG patients have been scant and it is arguable that VFT will have little clinical value in the MG population. A 75-year-old man, with late onset acquired autoimmune MG presented with dizziness for evaluation. He completed VFT with no significant abnormalities in all tests and was elated to have vestibular ruled out as a contributing factor to his dizziness and imbalance. However, his functional impairments were still addressed and managed regardless of the test results. MG is a heterogenous condition that may be well-controlled with treatment. Patients with dizziness can still be diagnostically evaluated to rule in or out a vestibular involvement and should not be precluded from VFT. Patients should also be assessed for their functional impairments and not based on symptom checklist and objective test results alone. Hence, patients with normal VFT results can still benefit from a hybrid of vestibular rehabilitation therapy (VRT) with focus on habituation.

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Outcome measures and treatment effectiveness in late onset myasthenia gravis

Neurological Research and Practice ◽

10.1186/s42466-020-00091-z ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Francesca Pasqualin ◽

Silvia V. Guidoni ◽

Mario Ermani ◽

Elena Pegoraro ◽

Domenico M. Bonifati

Keyword(s):

Side Effects ◽

Myasthenia Gravis ◽

Outcome Measures ◽

Clinical Features ◽

Early Onset ◽

Treatment Effectiveness ◽

Late Onset ◽

Positive Outcome ◽

Response To Treatment

Abstract Background Recently different subtypes of myasthenia gravis (MG) have been described. They differ for clinical features and pathogenesis but the prognosis and response to treatment is less clear. The aim of the study was to evaluate outcome and treatment effectiveness including side effects in late onset MG (LOMG) compared with early onset MG (EOMG). Methods We analysed retrospectively 208 MG patients. Clinical features were recorded as well as treatment and side effects. Outcome at the last follow-up was evaluated with MGSTI and MGPIS scales. Results The 208 patients included were classified as follow: 36 ocular MG, 40 EOMG, 72 LOMG, 25 thymoma-associated, 14 anti-MuSK and 21 double seronegative. Similar positive outcome was achieved in either early and late onset subgroup. We found pharmacological remission and minimal manifestations at the MGFA-PIS in the 95% and 94,4% of EOMG and LOMG respectively but in LOMG a lower dose of immunosuppressors (MGSTI< 2) was required compared to EOMG (p = 0,048). Severe side effects were present in a small percentage of patients in both group but diabetes was more frequent in LOMG vs EOMG (2,2% vs 5%, p = 0.017). Conclusions Despite LOMG has more comorbidities that might interfere with treatment and outcome, therapeutic management does not seem to differ between EOMG and LOMG. A similar positive outcome was seen in both subgroups but LOMG group seems to require lower doses of medication to control symptoms.

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Clinical and therapeutic features of myasthenia gravis in adults based on age at onset

Neurology ◽

10.1212/wnl.0000000000008903 ◽

2020 ◽

Vol 94 (11) ◽

pp. e1171-e1180 ◽

Cited By ~ 8

Author(s):

Elena Cortés-Vicente ◽

Rodrigo Álvarez-Velasco ◽

Sonia Segovia ◽

Carmen Paradas ◽

Carlos Casasnovas ◽

...

Keyword(s):

Myasthenia Gravis ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Neuromuscular Diseases ◽

Cross Sectional ◽

Life Threatening ◽

Onset Group ◽

Anti Acetylcholine

ObjectiveTo describe the characteristics of patients with very-late-onset myasthenia gravis (MG).MethodsThis observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late-onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed.ResultsA total of 939 patients from 15 hospitals were included: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men (p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti–acetylcholine receptor (anti-AChR) antibodies (p < 0.0001) was higher and fewer patients had thymoma (p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening (p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset (p = 0.002), they required fewer drugs (p < 0.0001) and were less frequently drug-refractory (p < 0.0001).ConclusionsPatients with MG are primarily ≥65 years of age with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, they achieve a good outcome with fewer immunosuppressants when diagnosed and treated properly.

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Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis—A Multicenter Analysis

Journal of Intensive Care Medicine ◽

10.1177/0885066620967646 ◽

2020 ◽

pp. 088506662096764

Author(s):

Klemens Angstwurm ◽

Amelie Vidal ◽

Henning Stetefeld ◽

Christian Dohmen ◽

Philipp Mergenthaler ◽

...

Keyword(s):

Myasthenia Gravis ◽

Late Onset ◽

Retrospective Chart Review ◽

Health Condition ◽

Myasthenic Crisis ◽

Early Tracheostomy ◽

Ventilation Time ◽

Data Rates ◽

Multicenter Analysis ◽

The Impact

Background: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. Methods: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. Results: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). Conclusion: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.

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