What is Myasthenia Gravis (MG)?

From the Guidelines

Myasthenia gravis should be treated with a multidisciplinary approach, prioritizing the use of acetylcholinesterase inhibitors like pyridostigmine and immunosuppressive therapy, with the goal of reducing morbidity and mortality, and improving quality of life, as outlined in the most recent guidelines 1. The treatment of myasthenia gravis typically involves the use of acetylcholinesterase inhibitors, such as pyridostigmine (Mestinon), starting at 30-60mg three to four times daily and titrating based on symptoms, as well as immunosuppressive therapy, with prednisone being first-line, starting at 15-20mg daily and gradually increasing to 60mg daily if needed 1. Some key points to consider in the management of myasthenia gravis include:

• The use of immunosuppressants, such as azathioprine (2-3mg/kg/day), mycophenolate mofetil (1000mg twice daily), or cyclosporine (3-5mg/kg/day in divided doses) 1
• The consideration of thymectomy for patients with thymoma or generalized myasthenia gravis, especially those under 60 years old 1
• The importance of regular monitoring of respiratory function, as respiratory crisis can occur, and the need for patients to recognize signs of exacerbation, which include increased weakness, difficulty swallowing, or breathing problems requiring immediate medical attention 1
• The goal of treatment is to reduce morbidity and mortality, and improve quality of life, with targeted outcomes including the recognition of the disease, reduction of diplopia, restoration of normal ocular alignment, and improvement of self-image 1.

From the FDA Drug Label

WARNINGS Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of pyridostigmine bromide may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death Myasthenic crisis due to an increase in the severity of the disease is also accompanied by extreme muscle weakness, and thus may be difficult to distinguish from cholinergic crisis on a symptomatic basis The treatment of the two conditions obviously differs radically. Whereas the presence of myasthenic crisis suggests the need for more intensive anticholinesterase therapy, the diagnosis of cholinergic crisis, according to Osserman and Genkins1, calls for the prompt withdrawal of all drugs of this type.

The management of Myasthenia Gravis with pyridostigmine bromide requires careful consideration of the potential for cholinergic crisis versus myasthenic crisis.

• Myasthenic crisis may require more intensive anticholinesterase therapy.
• Cholinergic crisis requires the prompt withdrawal of all drugs of this type and may involve the use of atropine. The diagnosis and management of these conditions should be guided by clinical judgment and potentially the use of edrophonium chloride as a diagnostic tool, as recommended by Osserman and Genkins2.

From the Research

Myasthenia Gravis Treatment Options

• Acetylcholinesterase inhibitors, such as pyridostigmine, are commonly used for symptomatic treatment of myasthenia gravis (MG) 3, 4
• Corticosteroids are the mainstay of immunosuppressive treatment in patients with more than mild MG to induce remission 5
• Immunosuppressive therapies, such as azathioprine, are prescribed in addition to or instead of corticosteroids when background comorbidities preclude or restrict the use of steroids 5
• Rituximab has a role in refractory MG, while plasmapheresis and immunoglobulin therapy are commonly prescribed to treat MG crisis and in some cases of refractory MG 5, 6

Management of Myasthenic Crisis

• Current guidelines recommend intravenous immunoglobulin or plasmapheresis and discontinuation of pyridostigmine during myasthenic crisis 3
• However, intravenous immunoglobulin or plasmapheresis is expensive and frequently not available in developing countries, making continuous intravenous infusion of pyridostigmine or neostigmine a potential substitute 3
• Caution should be observed due to possible complications, such as cardiac arrhythmia and pneumonia, after administration of acetylcholinesterase inhibitor alone 3

Pyridostigmine Effectiveness and Side Effects

• Pyridostigmine is generally considered safe and effective in relieving the symptoms of MG, but provides only partial benefit 4, 7
• Common side effects of pyridostigmine include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 7
• Diarrhea, abdominal cramps, and muscle twitching are the most frequently cited reasons to discontinue pyridostigmine 7

Emerging Treatments

• Novel therapies are being developed and trialed, including ones that inhibit complement-induced immunological pathways or interfere with antibody-recycling pathways 5, 6
• Minimally invasive thymectomy surgery, including robotic-assisted thymectomy surgery, has further revolutionized thymectomy and the management of MG 5