Meeting the challenges of myasthenia gravis at Mayo Clinic in Florida
With the addition of Juan J. Figueroa, M.D., there are now five neurologists specializing in neuromuscular disease at Mayo Clinic in Florida. "Each of us in the neuromuscular practice routinely treats patients with early diagnosis of myasthenia gravis, as well as those with more-complicated symptoms that may be difficult to diagnose or may be refractory to standard treatments," says Devon I. Rubin, M.D.
The management of myasthenia gravis (MG) can be challenging. Response to treatment can vary widely within and across patients. While some patients have classic symptoms and respond well to first line medications, others present with unusual distributions of weakness or test negative for the typical antibodies, which can complicate the diagnosis.
Even for patients with a definitive diagnosis, MG may vary over time in its response to medication. Management requires careful monitoring of the potency, duration and type of medication offered. Experienced neuromuscular clinicians can help determine the best combination of therapies for routine care and specialized treatments of symptom exacerbation and crisis management.
Study from a patient with generalized myasthenia gravis
Single fiber EMG study
Mayo Clinic pioneered discoveries in the mechanisms of MG, distinguishing it from other, related neurologic autoimmune disorders, and developed many of the clinical tools to manage it. Across Mayo, diagnosis integrates the expertise of:
- Neurologists to conduct the physical examination and EMG testing
- Neuro-ophthalmologists to distinguish ocular muscle symptoms of MG from other ocular muscle conditions
- Immunologists to detect the serum antibodies associated with MG
- Radiologists to interpret imaging studies of the thymus
- Thoracic surgeons to help determine whether thymectomy is a necessary or viable treatment option
Neuromuscular neurologists at Mayo conduct repetitive stimulation studies, as well as single fiber EMG, considered the most sensitive electrodiagnostic test of neuromuscular transmission. Both tests require specialized skill not only to administer but also to interpret.
"Single fiber studies are very helpful in diagnosing mild disease when other tests fail to demonstrate abnormalities," explains Dr. Rubin. "For example, if someone has a slight eyelid droop or a mild case of double vision, the single fiber EMG is extremely valuable in helping to confirm the diagnosis of mild MG."
His neurology colleague Elliot L. Dimberg, M.D., adds, "Most patients with MG have ocular findings — ptosis or diplopia — regardless of whether or not they have weakness in the extremities or extensor muscles or difficulty in speech, swallowing or respiration. We're fortunate to have Paul W. Brazis, M.D., our neuro-opthalmologist, to differentiate ocular muscle symptoms suspicious for MG from other types of ocular conditions."
Diagnosis includes testing for antibodies associated with MG, such as acetylcholine receptor antibodies (AChR), which block acetylcholine receptors at the postsynaptic neuromuscular junction. In patients who test seronegative for AChR, further antibody analysis may include a test for muscle-specific kinase (MuSK), a relatively new antibody associated with MG.
Patients who test positive for MuSK respond less consistently to traditional therapies and often have more bulbar than extremity involvement in their symptom presentation. In discussing the resources available for patients with uncertain diagnosis, Kathleen D. Kennelly, M.D., Ph.D., cites Vanda A. Lennon, M.D., Ph.D., director of the Neuroimmunology laboratory at Mayo Clinic in Rochester, Minn.
Dr. Lennon and her colleagues developed many of the antibody tests for MG, some of which are available only through Mayo laboratories. Dr. Kennelly says, "When we have patients with a questionable diagnosis who test negative for both MuSK and AChR, Dr. Lennon is very aggressive in conducting testing for other antibodies that may be associated with different neurologic disorders that cause weakness, such as Lambert-Eaton syndrome, and in working with and going the extra measure for the clinician. It is truly individualized diagnostic testing. She has more than once made the difference for our patients."
Meeting treatment challenges
Patients with MG have variability in response to treatment. At Mayo Clinic, immunomodulatory medications are often prescribed to enhance immunosuppression against the antibodies causing the disease. For patients with complex disease — those who test seronegative or who have an unusual distribution of weakness — MG management can be a difficult balance.
As Dr. Kennelly says, "We are advocates for the patient. For those with severe disease, we try novel therapies and medication combinations."
Depending on the health of the patient, severity of the disease, response to treatment, or if a thymic tumor is present, a thymectomy may be recommended. John A. Odell, M.D., the thoracic surgeon who works with the neurology team in Florida, has years of experience in thymectomy for patients with MG.
With the new hospital now open on Mayo's campus in Florida, care of patients with diagnosed and undiagnosed MG has become streamlined. Dr. Dimberg notes that many patients with undiagnosed MG present to the hospital's emergency room. With the EMG laboratory located in close proximity to the inpatient service, diagnosis can be rendered, emergent management offered, and follow-up care provided in a seamless process.
Ambulatory infusion center
For patients in an acute MG crisis, intravenous immunoglobulin or plasma exchange may be prescribed. And, although rare, there are some patients who require ongoing treatments of this type. "It is critical that you have an experienced ambulatory infusion center where this type of treatment can be administered on an outpatient basis," says Dr. Rubin.
Mayo's infusion center in Florida is open on weekends, and both it and the plasma exchange unit are staffed by nurses and technicians who are experienced in treating patients with MG.
Muscular Dystrophy Association clinic
Mayo Clinic in Florida is a designated site of the Muscular Dystrophy Association (MDA). Although the common perception is that the MDA is focused only on hereditary muscular dystrophies, it also advocates for patients with acquired neuromuscular diseases, such as MG and polymyositis.
The Florida team monitors a number of patients through the MDA-sponsored neuromuscular clinic, people who for insurance reasons might not otherwise be able to receive care through Mayo. As Dr. Kennelly points out, "We often share patients with neurologists at a distance who send patients for additional treatment advice. MDA support can make it easier for some of those patients to be seen here."