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

Sheikh, Shuja; Alvi, Usman; Soliven, Betty; Rezania, Kourosh

doi:10.3390/jcm10071537

Cited by 87 publications

(72 citation statements)

References 182 publications

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“…Many drugs of everyday practice have been found capable of inducing neuromuscular dysfunction or exacerbating a smoldering myasthenic syndrome in case reports, but only few targeted anticancer agents were included (3,7,25). Here, we presented the first case with anti-MuSK(+)MG after long-term exposure to BRAF/MEK inhibitors, where the reactivation of myasthenia after dabrafenib/trametinib rechallenge further supports that the TKI association may be more than coincidental.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, the emergence of MG after administration of targeted anticancer agents is occasionally reported in the literature. Thus, these medications cannot significantly influence the already low incidence (0.3-2.8 per 100,000) and prevalence (5.35-35 per 100,000) of MG, and counting their clinical benefit, there is no clear contraindication of using them (7,53). However, physicians and healthcare providers should be aware of such rare but possible neurological complications following TKI administration and should also be on alert for the need of a multidisciplinary approach and a multimodality treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical diagnosis of MG can be confirmed by the serological detection of these autoantibodies and by the electrophysiological testing of nerve-to-muscle conduction [e.g., repetitive nerve stimulation (RNS) and single-fiber electromyography (EMG)] (1). Few neoplasms are associated with MG with thymoma being the most common among them (10-15%) (2), while many drugs of everyday clinical practice have been accused to cause or unmask myasthenic manifestations, such as anesthetic agents, antibiotics or antivirals (e.g., aminoglycosides, fluoroquinolones, macrolides, or antiretrovirals) (3), anticonvulsants (e.g., gabapentin, phenobarbital, and phenytoin), statins (e.g., atorvastatin, pravastatin, rosuvastatin, and simvastatin) (3), psychiatric drugs (e.g., haloperidol, chlorpromazine, and prochlorperazine), and other drugs such as D-penicillamine (4), chemotherapies (e.g., cisplatin, fludarabine) even new immune checkpoint inhibitors such as nivolumab, pembrolizumab, and ipilimumab (5)(6)(7). However, all these abovementioned medications have been pinpointed in low evidence level studies and with no clear pathophysiological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

et al. 2021

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More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with “off-target” impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians’ awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

et al. 2021

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“…Only one patient received hydroxychloroquine, another drug that has shown in vitro antiviral activity but has failed to demonstrate clinical bene t [26]. Chloroquine and hydroxychloroquine also have the potential to exacerbate MG symptoms [24,25].…”

Section: Discussionmentioning

confidence: 99%

Myasthenia Gravis Exacerbation and Myasthenic Crisis Associated With COVID19: Case Series and Literature Review.

Rodrigues

Freitas

Lima

et al. 2021

Preprint

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Myasthenia Gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID19. Management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID19 and discuss prognosis and treatment based on a literature review. Most patients were female (7/8), with an average age of 47.1 years. Treatment was immunoglobulin (IVIG) in 3 patients, plasma exchange (PLEX) in 2 patients, and adjustment of baseline drugs in 3. In-hospital mortality was 25% and 37.5% in 2-month follow-up. This is the largest case series of MG exacerbation or myasthenic crisis due to COVID19 to this date. Mortality was considerably higher than in myasthenic crisis of other etiologies. Previous treatment for MG or acute exacerbation treatment did not seem to interfere with prognosis, although sample size was too small to draw definitive conclusions. Further studies are needed to understand the safety and effectiveness of interventions in this setting, particularly of PLEX, IVIG, rituximab and tocilizumab.

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“…There are various medications utilized intraoperatively that can either exacerbate MG symptoms or cause CNS depression and respiratory distress [46]. Thus, careful consideration should be taken in the intraoperative management of patients with MG.…”

Section: Intraoperative Carementioning

confidence: 99%

Narrative Review of Surgery for Myasthenia Gravis

Dezube¹,

Deeb²,

Jaklitsch³

2021

obm neurobiol

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Myasthenia Gravis (MG) is a rare autoimmune disorder characterized by antibody mediated blockade of neuromuscular transmission. Up until the last decade, evidence suggesting benefit of thymectomy for myasthenia gravis has been based on non-randomized control studies. Our paper serves as an expert narrative review of new literature pertaining to surgical management of myasthenia gravis based on review of articles from PubMed and Cochrane database from date of inception through June 14, 2021. We used the MeSH search terms: “myasthenia gravis”; “thymectomy”; “thymoma”; and “surgery” to identify any new relevant articles for inclusion in our review. The results of these studies are summarized below. We reviewed multiple articles including two randomized control trials. As a result of these studies over the past decade, the American Academy of Neurology’s most recent practice advisory, published online March 25, 2020, gives a level ‘B’ recommendation for thymectomy for MG in patients with acetylcholine receptor antibody-positive generalized MG age 18-65 years old. They additionally noted the need for further discussion surrounding the benefits and risks of surgery and whether minimally invasive approaches to thymectomy would provide the same benefits as the traditional transsternal approach. Evidence recommending thymectomy during pregnancy remains limited due to lack of available data. Emerging evidence suggests that performance of video-assisted or robotic-assisted thymectomy is feasible, but further study is needed due to a lack of randomized control trials.

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

Cited by 87 publications

References 182 publications

Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

Myasthenia Gravis Exacerbation and Myasthenic Crisis Associated With COVID19: Case Series and Literature Review.

Narrative Review of Surgery for Myasthenia Gravis

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