Saturday, October 29, 2016

Acute flaccid myelitis

Erin Olivera waited weeks for doctors to tell her why her youngest son was paralyzed.

Ten-month-old Lucian had started crawling oddly — his left leg dragging behind his right — and soon was unable to lift his head, following Erin only with his eyes.

She took him to a hospital in Los Angeles, but doctors there didn’t know how to treat what they saw.

Lucian’s legs felt soft as jelly and he couldn’t move them. His breathing became rapid. The left side of his smile drooped as his muscles weakened.

Physicians ran test after test, and Erin began spending her nights on a hospital room couch. After Lucian fell asleep, during her only minutes alone between working and visiting her three other kids, she cried.

A terrifying reality was taking hold: Doctors wouldn’t be able to give her a diagnosis for her paralyzed child….

“How can I make a decision for him when I don’t even know what’s wrong?” she said. “What can I do to help him?”

So one morning in July of 2012, Erin lifted Lucian out of his hospital bed, his body limp and heavy. She rested his cheek on her shoulder, the way he liked to be held since he’d become weak.

Erin returned home to Ventura County with a child she thought might never learn to walk.

In the years since, hundreds of children across the country have shown up at hospitals unable to move their arms or legs. Dozens of kids have become paralyzed in the past few months alone.

They suffer from a mysterious illness that continues to alarm and puzzle scientists. This kind of sudden and devastating paralysis hasn’t been widespread since the days of polio. Lucian, one of the disease’s earliest victims, set off a hunt among doctors to discover its cause….

Now the future felt upended by questions about their youngest son — whether he’d ever be able to drive a car, get married, have kids.

They took him to more doctors, but that failed to bring a diagnosis, let alone a treatment.

Through months of physical therapy, Lucian eventually regained strength in most of his limbs, but still couldn’t move his left leg at all. When he crawled, it dragged behind…

Then one day, she came across an article online about a dozen paralyzed kids. She immediately thought of Lucian.

The article mentioned Dr. Keith Van Haren, a Stanford University child neurologist who had diagnosed many of the other cases.

She called him…

A handful of physicians had seen patients with similar symptoms and asked Dr. Carol Glaser to test them for polio.

“I thought, ‘Well that’s crazy. We don’t have polio here,” said Glaser, then head of the encephalitis and special investigations section at the California Department of Public Health. Glaser quickly determined the patients weren’t suffering from polio. She also tested for pathogens that can sometimes cause such paralysis, including West Nile virus. All negative.

Then she decided to check for other viruses in the same family as poliovirus, known as enterovirus. And in some of the paralyzed patients, she found a possible culprit: enterovirus D-68. 

Enterovirus D-68 was incredibly rare, almost never seen after it was first discovered in 1962 in four California children who had pneumonia. Though a cousin of poliovirus, it was only supposed to cause a runny nose and cough.

Van Haren had never heard of it…

One, two, three or four limbs paralyzed. Sudden onset. No cognitive changes.

Lucian fit the bill.

Within minutes, Van Haren delivered the diagnosis: polio-like paralysis likely caused by enterovirus D-68...

In late summer of 2014, enterovirus D-68 started sending kids struggling to breathe to emergency rooms around the country. News reports called it a rare, cold-causing virus, a danger to children with asthma.

But then an 11-year-old boy in Texas with a seemingly normal fever lost the ability to walk and move his right arm.

A 17-year-old girl in Santa Barbara experienced severe neck pain at her birthday party and ended up in the hospital, paralyzed from the neck down.

In Oregon, a 13-year-old boy’s diaphragm stopped working, so he needed a ventilator to breathe. He was completely paralyzed, able only to wiggle his toes and his right hand.

Whatever was happening to these children was “pretty much, literally, exactly, what polio did,” said Dr. Jean-Baptiste Le Pichon, a child neurologist who treated four such patients in 2014 at Children’s Mercy Hospital in Kansas City, Mo.

Glaser watched from California as the numbers of paralyzed kids grew. She became horrified that her theory about enterovirus D-68 might be correct...

Erin hoped the new cases would lead to a cure for her son.

But doctors say that though the disabled children can regain strength in some limbs, there’s usually also some paralysis that cannot be reversed — just like with polio.

Scientists think a virus travels to the spinal cord and damages motor function there, irreversibly…

Between June and August this year, another 30 children nationwide became paralyzed, and scientists still don’t know why.

Dr. Manisha Patel, who heads the acute flaccid myelitis team for the U.S. Centers for Disease Control and Prevention, said the agency is concerned by the increase and its resemblance to 2014. Experts think case numbers for September and October will be even higher.

But there’s not much public health officials can do, because the paralysis officially remains a medical mystery.

Many suspect that enterovirus D-68 — which gave hundreds of people a severe cold in 2014 — also caused the paralysis outbreak that year. Some of the paralyzed children had enterovirus D-68 in their system, and researchers have found that injecting mice with enterovirus D-68 paralyzes them.

But to confirm the link, doctors need to find enterovirus D-68 in the paralyzed children’s cerebrospinal fluid, to show that the virus traveled to the spinal cord and created the injury there — which they haven’t yet…

And physicians are still baffled that no one had noticed the possible risk of paralysis before.

Some think there hadn’t ever been enough cases of enterovirus D-68 to unmask the horrifying side effect; only 26 people tested positive for the virus in 36 years. Another possibility is that enterovirus D-68 recently mutated to become more likely to paralyze those infected.

For now, experts say that enterovirus D-68 isn’t enough of a threat to make a vaccine and that many people now have immunity to the virus from the 2014 outbreak. Plus, it will probably mutate again, rendering a vaccine that protects against the current strain useless.

“You kind of hold your breath and hope it doesn’t get worse,” Van Haren said.

Courtesy of Doximity 


  1. As feared by pediatric neurologists during the 2014 outbreak of acute flaccid myelitis, a second outbreak of the illness is underway this year, with 50 cases in 24 states confirmed as of August by the Centers for Disease Control and Prevention (CDC), and more cases continuing to be reported by neurologists across the country. [The CDC was due to release updated statistics this month.]

    The spate of new cases has prompted the CDC and neurologists experienced in treating the disorder to urge clinicians to be on the lookout this fall for any case they come across of acute, unexplained flaccidity, and to report them immediately to their state or local health authorities based on the case definition and specimen collection procedure outlined by the CDC. [The CDC case definition and procedure is here:]

    “The trend seems to be pretty much on par with what we saw in 2014,” Manisha Patel, MD, the leader of the CDC team investigating the outbreak, told Neurology Today. “We're working with the health departments to continue to raise awareness about this. As the surveillance system matures, we'll be able to understand these trends a little better.”...

    Neurologists breathed a sigh of relief when only 26 cases in 16 states were confirmed for all of 2015. But after beginning slowly this year, with seven cases through April, a surge began that has yet to show signs of peaking: five more in May, eight in June, 12 in July, and 18 in August.

    Dr. Patel declined to name the 24 states where cases have been identified, saying it is up to each individual state health department to reveal that information. But neurologists around the country identified cases in Massachusetts, California, Colorado, Florida, New Jersey, New York, Pennsylvania, Virginia, and Texas...

    The largest cluster by far this year has been in the Philadelphia area, where Children's Hospital of Philadelphia (CHOP) has treated nine affected children, according to Sarah Hopkins, MD, MSPH, a pediatric neurologist there...

    Multiple studies have provided strong epidemiological evidence and biological plausibility linking the 2014 outbreak to enterovirus D68 (EV-D68), although the pathogen was not detected in the cerebrospinal fluid of any patients two years ago or even this year. Adding to the mystery, the nationwide outbreak of respiratory illnesses associated with EV-D68 that occurred concurrently with the 2014 AFM outbreak has not recurred this year.

    For now, the most difficult challenge for clinicians treating AFM is what to tell the parents of affected children.“You know that for a lot of these kids, most of these kids, they're not going to get back to where they were before,” Dr. Hopkins said. “That's really hard for some of these families to come to terms with, understandably. With our 2014 cases, most of them still aren't back to where they were before. A lot of them have made progress, but it's a long road to recovery.”,_Reports_of_Acute_Flaccid.1.aspx


  3. Researchers developing drugs against polio and other polio-like viruses say those drugs could potentially be effective against a mysterious, polio-like condition called acute flaccid myelitis (AFM).

    The Centers for Disease Control and Prevention has confirmed 89 cases of the paralyzing disease in the United States through September. A 6-year-old boy suspected of having AFM died in Seattle on Sunday, the first death believed to be caused by the disease.

    One of the drugs in development, pocapavir, was used briefly on a few patients during a 2014 outbreak of AFM under a compassionate-use exception that allows extremely sick patients to be given unapproved drugs without the usual kinds of placebo-controlled trials required by the Food and Drug Administration.

    “There were a couple of kids who got pocapavir in the Colorado outbreaks,” said Benjamin Greenberg, a neurologist who has treated children with AFM at the University of Texas Southwestern in Dallas. “It had relatively weak but measurable impact on viral replication. A larger study would definitely be warranted. We'll take anything we can get.”

    Although the CDC says no cause has been conclusively linked to AFM, many researchers suspect a family of viruses known as enteroviruses.

    “I have been studying enteroviruses for 40 years now,” said John Modlin, deputy director of the polio eradication program at the Bill and Melinda Gates Foundation. “If I had a child with acute flaccid myelitis, I would be on the phone in a second to the companies making these drugs.”

    None of the drugs is approved by the Food and Drug Administration. Even pocapavir is currently unavailable on any basis because the FDA has required the small company studying it to submit a New Drug Application before it would consider allowing the drug to be offered on a compassionate-use basis again, said Marc Collett, president of the company, ViroDefense of Chevy Chase, Md.

    Even if the drugs could reach patients, Modlin said, they would be effective — if they work at all — only in the few days or hours when the condition first strikes.

    Despite those considerable drawbacks, not to mention the fact that no enterovirus has been proved to cause AFM, the CDC official in charge of its polio research says he understands the logic in trying to make the drugs available on a compassionate-use basis.

    “It is true there are a number of drugs that have been through safety trials,” said Steve Oberste, chief of the CDC's Polio and Picornavirus Laboratory Branch. “Some have been through phase 2 efficacy trials, and some have previously been used in other compassionate-use cases. But in those cases, at least we knew there was an infectious agent, we knew what it was, so it was easier to justify. Still, I can certainly understand why someone might say, well, this drug is proven safe, what have I got to lose?”

    Marijo De Guzman, whose son Daniel died Sunday following a tentative diagnosis of AFM, said that if her child had been offered the opportunity to receive one of the experimental drugs, “I would have said, let's try it, whatever we can do to try to save my son.”

    Courtesy of Doximity

  4. Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR. Acute flaccid myelitis: A clinical review of US cases 2012-2015. Ann Neurol. 2016 Sep;80(3):326-38.

    This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States.

  5. Kim YM, Orvedahl A, Morris S, Schmidt R, Mar S. A 12-Year-Old Girl With Encephalopathy and Acute Flaccid Paralysis: A Neuropathological Correlation and Cohort Review. Pediatr Neurol. 2016 Sep 8. pii: S0887-8994(16)30365-4. doi:10.1016/j.pediatrneurol.2016.08.004. [Epub ahead of print]

    Olive G, Clarke A, Doerholt K, Gowda V, Siddiqui A, Lim MJ. Acute flaccid weakness with myelopathy and peripheral nerve involvement in 2 children: Recent characterization of a previously observed phenomenon. Eur J Paediatr Neurol. 2016 Nov;20(6):948-952.

    Acute flaccid weakness may be the first presentation of acute transverse myelitis (ATM), an immune-mediated central nervous system disorder or may be the first presentation of anterior horn cell syndrome or peripheral nervous system disease.
    We describe two previously healthy female infants who presented with acute flaccid paralysis and encephalopathy. Neuroimaging revealed central cord signal changes in both cases and surprisingly electrophysiological studies performed revealed a generalized axonal motor neuropathy as well.
    Clinical, radiological and neurophysiological assessment are important to aid in the diagnosis and subsequent management of children with overlapping inflammatory peripheral and central nervous system syndromes.