Myasthenia Gravis May Follow Infection by West Nile Virus

Daniel M. Keller, PhD

July 02, 2013

BARCELONA, Spain — West Nile virus infection (WNV) is now linked to the development of myasthenia gravis (MG) some months later, a series of case reports indicates. Residual deficits of WNV, such as weakness or fatigue, may confound or delay the diagnosis of MG.

WNV "is the poliomyelitis of the 21st century," Arturo Leis, MD, from the Methodist Rehabilitation Center and the University of Mississippi in Jackson told Medscape Medical News here at the 23rd Meeting of the European Neurological Society (ENS).

He explained that WNV is an RNA neurotropic arthropod-borne flavivirus that can cause neuroinvasive disease manifesting as meningitis, encephalitis, or poliomyelitis. The Centers for Disease Control and Prevention (CDC) 2012 national surveillance data for WNV activity, released in May, showed that a total of 5674 cases in people, including 286 deaths, were reported from 48 states, the highest numbers reported since 2003. Of these cases, 54% were classified as neuroinvasive, including cases of meningitis, encephalitis, or acute flaccid paralysis. The outbreak last summer is thought to be related to factors including higher-than-normal temperatures, the CDC reported.

There is no evidence that the virus directly damages the neuromuscular junction, suggesting that host factors are involved in the development of MG, Dr. Leis noted.

At this meeting, he reported on 6 cases of MG, all with similar features, that developed 3 to 7 months after acute infection with WNV and after initial neurologic deficits had stabilized. Patients ranged in age from 56 to 76 years, and they had various combinations of symptoms of fluctuating ptosis, diplopia, dysarthria, dysphagia, fatigue, and generalized weakness. Computed tomography of the chest revealed a 5 x 3 cm thymoma in 1 patient.

All patients had serologically confirmed infection, neuroinvasive disease with electromyographic evidence of poliomyelitis, and markedly elevated acetylcholine receptor antibodies (35 to 201 nmol/L vs laboratory normal of <0.4 nmol/L). Results of antibody tests for anti-MuSK, a muscle-specific kinase that is a cause of MG, were negative. None of the patients had any evidence of MG before the WNV infection.

"After performing EMG [electromyography] and nerve action studies, our impression is that these patients have an asymmetric neuropathic process affecting anterior horn cells or motor axons. Clinically, this is a poliomyelitis," Dr. Leis said.

Treatments consisted of various combinations of pyridostigmine, prednisone, methylprednisolone, intravenous immune globulin, mycophenolate, and azathioprine. The patient with the thymoma underwent plasma exchange and thymectomy for recurrent MG crises.

Dr. Leis speculated that the MG was probably caused by molecular mimicry by the virus, "although some colleagues don't necessarily agree."

Shares Proteins

One who does agree is session moderator Guido Stoll, professor and vice chairman of the Department of Neurology at the University of Würzburg in Germany.

"I would suspect...that the virus shares proteins that are also present in the [acetylcholine] receptor and then you generate the immune response against the virus and there's cross-reactivity to an antigen that's present in the body," he commented to Medscape Medical News. "A second possibility would be that something changes within the thymus because acetylcholine receptors are expressed within the thymus, and the thymus is important for the genesis of myasthenia gravis."

He said the clinical message is to be aware of the possibility of MG if a patient has secondary weakness. "Usually the patients get better, and when you are facing secondary problems in terms of fatigue, muscle weakness you should think of myasthenia. ... You have to recognize that something new occurred. And that's the key point," he advised.

Dr. Stoll said the term poliomyelitis relates to a clinical picture that does not have to be caused by the typical enteric polio virus. It describes a condition in which an infectious agent or an immune attack destroy anterior horn cells.

Dr. Leis noted that he is seeing more cases of WNV and predicts an increasing number as time goes on. So far, he has treated as many as 70 cases and has just received 3 more case referrals of MG from colleagues, for a total of 9. He has published this work in an article online in Muscle & Nerve, and it will later appear in print.

There was no commercial funding for the study. Dr. Leis and Dr. Stoll (who was not involved in the study) have disclosed no relevant financial relationships.

23rd Meeting of the European Neurological Society (ENS). Abstract O339. Presented June 10, 2013.


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