Studies show Zika brain damage; feds express deep concern

Zika-infected neural cells
Zika-infected neural cells

Neural progenitor cells are infected with Zika virus (red); cell nuclei appear in blue., © D'Or Institute for Research and Education (IDOR)

The scientific case that the Zika virus damages nerve cells grew stronger over the past few days, with one Brazilian research team linking infection to yet another neurologic condition and another finding more evidence of the virus's potential to damage developing fetal brain cells.

In other developments, federal health officials at a White House press briefing today detailed the efforts that require emergency funding in the wake of a recent administration announcement that it would transfer existing Ebola money until Congress approves President Obama's $1.9 billion Zika funding request.

Zika linked to brain autoimmune disorder

In the first study, Brazilian clinicians followed 151 patients hospitalized in Recife with arbovirus and neurologic symptoms from December 2014 to December 2015, a span that included Brazil's Zika virus outbreak. They suspected autoimmune disorders in 6 of the patients, describing their findings today in a press release in advance of the American Academy of Neurology (AAN) annual meeting in Vancouver.

All six patients had lab-confirmed Zika infections, with tests negative for chikungunya and dengue.

The hospitalized patients had hallmark Zika symptoms, such as fever, rash, joint pain, and conjunctivitis. For the six with neurologic problems, some had those symptoms right away, with others experiencing them up to 15 days later.

Two of the six developed a condition that hasn't been reported in Zika patients before: acute disseminated encephalomyelitis (ADEM), swelling of the brain and spinal cord that attacks the myelin coating around nerve fibers. ADEM typically involves a single attack that patients recover from within 6 months, but it can sometime recur. For both patients, brain scans showed white matter damage.

Four of the patients developed Guillain-Barre syndrome (GBS), and at hospital discharge five of the six patients still had motor function problems.

Brito Ferreira, MD, with Restoration Hospital in Recife, said in the press release that not all people with Zika-related nerve complications will have brain problems, but the findings suggest the possibility of lingering brain-related problems.

James Sejvar, MD, a neurologist and epidemiologist with the US Centers for Disease Control and Prevention (CDC) and a member of the AAN, said in the statement that ADEM cases don't appear to occur as commonly as GBS, but clinicians should be vigilant for that and other brain-related immune conditions.

ADEM is the latest of a handful of neurologic problems besides GBS to be linked to Zika virus infection. In recent reports, clinicians have also reported cases of acute myelitis and meningitis.

More lab evidence of fetal brain damage

Meanwhile, a different Brazilian team found more evidence for fetal brain cell damage in experiments in the lab, not only with neural stem cells but also with complex "minibrain" structures, called neurospheres and brain organoids that give researchers a lab surrogate for studying pathologic developments in fetal brain formation. The researchers, based at the D'Or Institute for Research and Education, published their findings yesterday in Science.

The team observed that Zika virus infects human-derived pluripotent stem neural cells, neurospheres, and cerebral organoids, which led to cell death, malformations, and 40% growth reduction. In similar experiments with dengue virus, the cells were infected, but without damage to neural cells, neurospheres, or organoids.

Patricia Garcez, PhD, first author and researcher at the Federal University of Rio de Janeiro, said in a press release, "these unique results may unravel some key features of ZIKV [Zika virus] infection in the developing brain."

Two other research groups have recently shown similar findings, hinting how Zika virus likely kills or disrupts developing fetal brain cells. One found cell death and changes in gene expression in cortical neural progenitor cells infected with Zika virus, and the other identified a vulnerable receptor location on neural stem cells.

Zika 'scarier than thought'

At today's media briefing, meanwhile, White House press secretary Josh Earnest said the White House still hasn't seen the kind of response that it would expect, and it's useful for the public to know what federal health officials are up against and need.

Anne Schuchat, MD, principal deputy director for the CDC, said Zika virus and its complications are "scarier than thought." She said as more becomes known, it's clear that the virus can cause a broader range of complications in pregnancy and that more US states are at risk from Aedes aegypti mosquitoes, 30 rather than the 12 that the CDC originally believed.

She said the CDC is very worried about Puerto Rico, which is experiencing an outbreak that could result in hundreds of thousands of cases.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), said research and vaccine activities are going full blast with transferred funds, but the efforts won't accomplish their goals without full emergency funding. "When the president asked for $1.9 billion, we needed $1.9 billion."

He added that scientists are learning more about Zika virus every day, with progress being made to understand the damage at the fetal brain cell molecular level and on animal models for studying the disease. Fauci said preliminary work with monkey models suggest that virus levels in pregnant females persist much longer than in those who aren't pregnant.

Congressional Republicans have insisted that the administration use Ebola funds to fight the Zika battle, and though the White House said last week that it has been open to the possibility and would shift $589 million in funds, its original $1.9 billion request remains.

Doug Andres, a spokesman for House speaker Paul Ryan, R-Wisc., today told USA Today that representatives are glad the administration agreed to the request to use existing Ebola money, but he added that, if extra money is needed, it should be addressed through the regular appropriations process.

On Apr 8, however, former Republican presidential candidate and Florida Senator Marco Rubio said he supported Obama's $1.9 billion request to fight Zika virus, according to a Miami Herald report. He added, though, that he wanted to make sure the money was appropriately spent on the targeted goals, with funding prioritized for rapid diagnostic tests, state and local mosquito control, and vaccine development.

See also:

Apr 10 AAN press release

Apr 10 Science study

Apr 10 D'Or Institute press release

Apr 11 White House press briefing

Apr 11 USA Today story

Apr 8 Miami Herald story

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