Is Myasthenia Gravis (MG) still a consideration in patients with intact extraocular movements?

From the Guidelines

Yes, Myasthenia Gravis (MG) should still be considered in patients with intact extraocular movements. While ocular symptoms like ptosis and diplopia are common early manifestations of MG, affecting up to 90% of patients at some point, not all MG patients present with ocular involvement. Some patients may initially or primarily experience bulbar symptoms (difficulty speaking, chewing, or swallowing), limb weakness, or respiratory muscle weakness without any ocular manifestations. The pathophysiology involves autoantibodies targeting acetylcholine receptors or related proteins at the neuromuscular junction, which can affect any voluntary muscle group. When evaluating a patient with suspected MG, physicians should perform a comprehensive assessment including the ice pack test, edrophonium test, acetylcholine receptor antibody testing, and electromyography with repetitive nerve stimulation 1. Additionally, MuSK antibody and LRP4 antibody testing may be warranted in seronegative cases 1. The hallmark clinical feature of MG is fatigable weakness that worsens with repeated use and improves with rest, which can occur in any muscle group regardless of extraocular involvement. According to the most recent study 1, Pyridostigmine bromide administered orally two to four times a day is the first line of treatment for myasthenia gravis, but about half of patients with strabismus-associated myasthenia show minimal response. In contrast, about 66% to 85% of patients show a positive response to corticosteroids. For some patients, various forms of immunosuppressive therapy with azathioprine, which is known to be effective, and other agents under current investigation such as efgartigimod alfa-fcab may be offered by treating neurologists. Efgartigimod alfa-fcab has recently been FDA approved for patients who test positive for the anti-acetylcholine receptor. Key points to consider in the management of MG include:

• Comprehensive assessment including ice pack test, edrophonium test, acetylcholine receptor antibody testing, and electromyography with repetitive nerve stimulation
• MuSK antibody and LRP4 antibody testing in seronegative cases
• Treatment with Pyridostigmine bromide, corticosteroids, and immunosuppressive therapy
• Consideration of thymectomy in some cases
• Surgical management of strabismus may be considered after remission or stabilization of the disease.

From the FDA Drug Label

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 For detailed information on the management of patients with myasthenia gravis, the physician is referred to one of the excellent reviews such as those by Osserman and Genkins2, Grob3 or Schwab4,5.

Myasthenia Gravis (MG) is still a consideration in patients, as it is a condition that requires management and can be affected by the use of pyridostigmine bromide. The presence of intact extraocular movements does not rule out MG, as the disease can manifest in various ways. However, the differential diagnosis of myasthenic crisis and cholinergic crisis is crucial, as the treatment approaches differ significantly 2.

From the Research

Myasthenia Gravis Consideration

• Myasthenia Gravis (MG) is a neuromuscular disorder that can present with extraocular muscle weakness, leading to symptoms such as diplopia and ptosis 3, 4, 5, 6, 7.
• The presence of intact extraocular movements does not rule out MG, as some patients may have mild or fluctuating symptoms 3, 7.
• Studies have shown that patients with ocular myasthenia gravis (OMG) can have abnormal single-fiber electromyography (SFEMG) results, which may predict the development of generalized myasthenia gravis (GMG) 3.
• Treatment options for OMG include pyridostigmine, immunosuppression, intravenous immunoglobulin, plasmapheresis, thymectomy, lid crutches, ptosis surgery, and extraocular muscle surgery 4, 6.
• Corticosteroids, such as prednisone, have been shown to be effective in reducing diplopia, ocular motor dysfunction, and ptosis in patients with OMG 6.

Diagnostic Considerations

• The diagnosis of MG can be challenging, and a thorough differential diagnosis is necessary to rule out other conditions that may mimic MG 5.
• The detection of serum antibodies against the acetylcholine receptor (AChR) is a critical diagnostic test, but may be negative in some patients with purely ocular MG 7.
• Electromyographic studies and the Tensilon test can be useful in diagnosing MG, but may have limitations in purely ocular myasthenia 7.

Treatment Response

• Treatment response to corticosteroids and anti-cholinesterase agents can be satisfactory in many patients with ocular MG, but other immunosuppressive drugs may also be needed 7.
• The optimal treatment of OMG remains unknown, and further studies are needed to compare the efficacy of different treatment options 4, 6.