West Nile Mimics Polio

Image: Erica P. Johnson MORE MOSQUITO MAYHEM: The list of symptoms now associated with West Nile virus includes a condition reminiscent of paralytic poliomyelitis. The background is an electron micrograph of the poliovirus. When the West Nile virus arrived in the United States in 1999, its route of infection was the bite of an infected mosquito. Since then, WNV has proven its versatility: During the 2002 season, delivery came courtesy of transplants, transfusions, and breast milk. Now, the list of symptoms is growing to include a condition reminiscent of paralytic poliomyelitis. In August, the Centers for Disease Control and Prevention (CDC) reported the first six cases--three from Mississippi, three from Louisiana.1 The number is now at least 15. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told a joint Senate Committee Hearing on Sept. 24 that the new link was a surprise. "Clinically, if you were to open a textbook and look up West Nile virus and its manifestations, you wouldn't see anterior horn cells mentioned. That is novel for this flavivirus. There is now concern that the range of disease manifestations is broader than originally thought." West Nile is not exactly rampant: only one in five people with WNV will have fever; of those, only 1 in 150 will manifest associated symptoms of meningitis or encephalitis. However, the newly recognized weakness and paralysis reminiscent of polio are being treated with respect. "If this infection is similar to poliovirus infection, then probably there will be long-term consequences," says Dobrivoje S. Stokic, director of neuroscience and neurological recovery at Mississippi Methodist Rehabilitation Center in Jackson, where the first polio-West Nile link was made. DISCOVERY IN A REHAB CENTER It was at the rehab center that senior scientist A. Arturo Leis detected antibodies to the virus in several patients who had experienced unusually rapid onset of the asymmetric muscle weakness that is the hallmark of post-polio syndrome. This condition develops when neurons that sprout to compensate for cells killed by the poliovirus become overburdened years later. "Dr. Leis looked back in the literature, and found that many animal species present with poliomyelitis as the leading symptom when infected with WNV," recalls Stokic. In fact, a 1956 report links WNV to polio-like symptoms in primates.2 In the Mississippi patients, electromyograms identified damaged motor neurons (also called anterior horn cells) in the gray matter of the spinal cord--exactly where poliovirus is found. "So we reinterpreted the patients according to the animal data, made the link, then alerted the CDC," Stokic adds.3 The Mississippi cases were not alone. A woman who had traveled to Atlanta from Louisiana appeared at Emory University School of Medicine on July 3, reporting a worsening headache, muscle pain, and weakness.4 She had a fever but was alert. The weakness progressed and by the sixth day, she was unable to move her limbs or lift her head. Respiration therapy was started, yet her reflexes and senses remained normal. On day 12, WNV antibodies were detected in her cerebrospinal fluid. Two months later, she was still in rehab with respiratory assistance, reports Jonathan D. Glass, professor of neurology and pathology at the Emory Center for Neurodegenerative Disease. Photo: Courtesy of The CDC, Meredith Hickson LET IT BE: Ugly reminders of what polio once meant to victims and their families decades ago. NEW, OR NOT? Researchers are careful when they use the term "poliomyelitis-like syndrome" or the more descriptive "acute flaccid paralysis," because poliovirus and WNV are not the only pathogens that cause these symptoms. "Coxsackie virus, other enteroviruses, and Japanese encephalitis virus can cause the symptoms too," says Glass. The clinical presentation is similar, whatever the viral cause. "In real polio, limpness and weakness are asymmetric, such as the upper part of one leg," says Stokic. "Only some muscles are affected. This is typical of the old days of poliovirus or symptoms that polio vaccine produced in a small percentage of people," he adds. In past seasons, weakness and paralysis linked to WNV were symmetrical, resembling Guillan-Barre syndrome, which strips myelin from peripheral nerves. "We are saying now that it is not primarily the fibers in the peripheral nervous system, but the cell bodies in the gray matter of the spinal cord," relates Stokic. Because peripheral nerves can heal, recovery from Guillan-Barre is usually rapid. Not so for poliomyelitis. "This isn't a new presentation of WNV itself; it did not mutate. The poliomyelitis is newly recognized. The site of action for the muscle weakness is in the [central nervous system]," he adds. CLINICAL CONSEQUENCES Although there is no treatment at present, the new information will help; clinicians who note the patterns of weakness and paralysis will lessen the likelihood of inappropriate therapy. Treatments for Guillan-Barre (anticoagulants, corticosteroids, plasmapheresis) could be dangerous for a patient with a polio-like syndrome. The same is true for mistakenly treating a patient for stroke. The expanded case definition may lead to more diagnoses. "Being aware of the polio-like symptoms will raise the index of suspicion for WNV in patients with fever and weakness," says Glass. And new cases may not drop off, as is usual with winter, thanks to the southern migration of virus-carrying mosquitoes. Meanwhile, state health officials and CDC researchers continue to monitor patients with poliomyelitis-like syndrome for signs of returning neuromuscular function. As of early October, WNV caused symptoms in 2,530 people, killing 125, in 32 states. Virus-laden birds and mosquitoes are now more widespread. But Fauci put the illness into perspective for the Senate, comparing it with the 20,000 annual influenza deaths. "It would be extraordinarily unlikely that the impact of West Nile would ever get to the same radar screen as influenza and AIDS. Having said that, this disease needs to be taken seriously. It is not trivial. It is an evolving disease. We need to keep an eye on it and be ready for the worst." Ricki Lewis (rickilewis@nasw.org) is a contributing editor. References 1. A. Leis et al., "Acute flaccid paralysis syndrome assoc-iated with West Nile virus infection--Mississippi and Louisiana, July-August 2002," The Morbidity and Mortality Weekly Report, 51:825-8, Sept. 20, 2002. 2. E.E. Manuelidis, "Neuropathology of experimental West Nile virus infection in monkeys," Journal of Neuro-pathology and Experimental Neurology, 15:448-60, 1956. 3. A. Leis et al., "A poliomyelitis-like syndrome from West Nile virus infection," The New England Journal of Medicine (NEJM), 347:1279-80, Oct. 17, 2002. 4. J.D. Glass et al., "Poliomyelitis due to West Nile virus," NEJM, 347:1280-1, Oct. 17, 2002.

West Nile Mimics Polio

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Image: Erica P. Johnson
MORE MOSQUITO MAYHEM: The list of symptoms now associated with West Nile virus includes a condition reminiscent of paralytic poliomyelitis. The background is an electron micrograph of the poliovirus.