Letters to the Editor: Nonresponsive myasthenia is suspicious for congenital myasthenic syndrome or myopathy

| October 1, 2020

Dear Editor:

We read the excellent article by Diaz-Abad et al1 about a 54-year-old male patient with double seronegative myasthenia gravis. In the article, Diaz et al1 explained the patient did not tolerate pyridostigmine or steroids and did not respond sufficiently to immunoglobulins or plasmapheresis. However, respiratory failure (due to involvement of the respiratory muscles), as well as fatigue, daytime sleepiness, and sleep quality, improved upon application of noninvasive ventilation (NIV) with the volume-assured pressure support (VAPS) mode.1 Regardless of this improvement, the study has a number of shortcomings.

The main shortcoming of the study is that the diagnosis of myasthenia gravis remains unproven. Results of low- and high-frequency repetitive nerve stimulation were not provided, and single-fiber electromyography has not been carried out. Additionally, the authors did not mention if antibodies against agrin or anti-low-density lipoprotein receptor-related protein 4 (LRP4) were elevated or not. Diagnosing myasthenia gravis solely upon the clinical presentation and the response to pyridostigmine is insufficient, as several differential diagnoses might present with a similar clinical picture and also respond to pyridostigmine.2,3

The authors do not mention if chewing weakness, ptosis, dysphagia, blurred vision, and chronic fatigue showed diurnal fluctuations or not. Myasthenic symptoms typically increase during daytime to reach a nadir in the evening.4

Another shortcoming is that no explanation is provided, except for gastrointestinal compromise, and why the patient did not tolerate pyridostigmine dosages 90mg/d or more. It should be known which gastrointestinal side effects occurred, and if these side effects developed upon intravenous administration of neostigmine as well. For example, did the patient develop diarrhea, cramps, or tenesmes?

The next shortcoming is that heart failure was not excluded as a cause of exertional dyspnoea. We should be informed about the echocardiography findings and the titers of serum creatine-kinase, proBNP, and troponine values. Since myasthenia gravis can trigger the Takotsubo syndrome (TTS),5 it is crucial to be convinced that exertional dyspnoea was not due TTS.

Additionally, family history was not provided. In patients with seronegative myasthenia, congenital mysthenic syndrome (CMS) has to be excluded. Since the family history is positive in the majority of the cases with CMS,6 it is crucial to disclose if first-degree relatives of the index patient ever developed similar clinical manifestations or had been diagnosed with a neuromuscular disorder.

The authors should have explained why only some of the myasthenic manifestations responded favorably to NIV-VAPS. Weakness of respiratory muscles improved upon NIV but obviously not weakness of the limb muscles; daytime sleepiness, fatigability, and sleep quality improved, whereas ptosis, double vision, chewing difficulty, and dysphagia did not. Since weakness of the extra-ocular eye muscles, limb muscles, respiratory muscles, and the axial muscles progressed, we are interested in the long-term follow-up of the patient. Did he lastly require mechanical ventilation, for example?

The patient is reported to have had experienced an episode of transient global amnesia (TGA).1 Since TGA needs to be delineated from ischemic stroke, a stroke-like episode (SLE), and seizures,7 we should be informed about the results of cerebral magnetic resonance imaging (MRI) and the electroencephalograph recordings. It is also crucial to know the trigger of the TGA. Was it physical or psychological stress?

An explanation regarding why azathioprin was not tried should also be provided, as azathioprin is approved as first-line immunosuppressant for myasthenia in some of the European countries.8 Lastly, it should be explained why the patient experienced an episode of blurred vision. Intolerance to steroids suggests that the patient had developed myopathy. In addition to weakness, did the patient develop muscle cramps or muscle stiffness?

Overall, this interesting case report has a number of shortcomings that should be addressed before concluding that NIV-VAPS is beneficial for muscular respiratory failure in myasthenia gravis. Before administering long-term immunosuppression in a patient with bulbar and muscle weakness, the diagnosis of myasthenia gravis needs to be unequivocally established.

References

  1. Diaz-Abad M, Todd N, Zilliox L, Sanchez A, Hafer-Macho C. Use of noninvasive ventilation with volume-assured pressure support for treatment-refractory myasthenia gravis. Innov Clin Neurosci. 2019;16:11–13.
  2. Finsterer J. Mitochondrial disorder mimicking ocular myasthenia. Acta Neurol Belg. 2010;110:110–112.
  3. Yang K, Cheng H, Yuan F, et al. CHRNE compound heterozygous mutations in congenital myasthenic syndrome: a case report. Medicine (Baltimore). 2018;97:e0347.
  4. Inoue Y. [Midbrain ptosis with diurnal fluctuation like myasthenia]. No To Shinkei. 19;50:387–392.
  5. Rathish D, Karalliyadda M. Takotsubo syndrome in patients with myastheni a gravis: a systematic review of previously reported cases. BMC Neurol. 2019;19:281.
  6. Finsterer J. Congenital myasthenic syndromes. Orphanet J Rare Dis. 2019;14(1):57.
  7. Sajeev J, Koshy A, Rajakariar K, Gordon G. Takotsubo cardiomyopathy and transient global amnesia: a shared aetiology. BMJ Case Rep. 2017;2017:bcr2017219472.
  8. Pedersen EG, Hallas J, Pottegård A, et al. Oral immunosuppressive treatment of myasthenia gravis in Denmark: a nationwide drug utilization study 1996–2013. Basic Clin Pharmacol Toxicol. 201;123486–123493.

With regards,

Josef Finsterer, MD, PhD

Klinik Landstrasse, Messerli Institute in Vienna, Austria.

Fulvio A. Scorza, MD, and  Carla A. Scorza
Paulista School of Medicine, Neuroscience, Federal University of São Paulo(EPM / UNIFESP) in São Paulo, Brazil.

Funding/financial disclosures. The authors have no conflict of interest relevant to the content of this letter. No funding was received for the preparation of this letter.

Tags: , , , ,

Category: Current Issue, Letters to the Editor, Neurology

Comments are closed.