Subscribe to eTOC

News from the AAN Annual Meeting
Widespread Neurologic Complications Detected in Wake of Ebola Outbreak

ARTICLE IN BRIEF

Figure

A COLORIZED electron micrograph of Ebola virus, the cause of Ebola hemorrhagic fever.

A new report, released ahead of the AAN Annual Meeting, found that a majority of Ebola survivors in Liberia experience neurologic complications.

A six-month follow-up of Ebola survivors in Liberia found that the majority of them had neurological problems suggestive of central nervous system damage, including headache, weakness, hearing and vestibular dysfunction, parkinsonism, myalgia, and memory loss.

While the original response to the deadly outbreak of Ebola in West Africa focused on stemming the spread of the virus and treating its horrific symptoms, the new study suggests that the neurological fallout from Ebola will present another very difficult challenge for health workers even now as the epidemic is over.

“People have been focused on the diarrhea, the kidney failure,” and other immediate consequences of Ebola virus infection, said Avindra Nath, MD, FAAN, the study's senior author and clinical director of the National Institute of Neurological Disorders and Stroke (NINDS). “Once you clear that out, you are still stuck with what happens within the brain.”

The abstract, released February 24 by the AAN ahead of a scheduled presentation in April at the AAN Annual Meeting in Vancouver, focused on 82 Ebola survivors in Liberia, though researchers have now assessed more than 160 survivors in that country, Dr. Nath said.

“We found that the vast majority of Ebola survivors have pretty profound neurological complications,” Dr. Nath told Neurology Today. He said the findings suggest that there may be reservoirs of virus in the brains of Ebola survivors, “causing neurologic dysfunction” long after the initial threat is over. It's already known that the Ebola virus can linger in the eye globe and semen for months after Ebola infection.

“The pathogenesis of neurologic complications in patients with Ebola virus disease and in survivors is largely unknown,” said Tim Uyeki, MD, MPH, a medical officer at the US Centers for Disease Control and Prevention who has worked on clinical issues related to Ebola virus disease.

Dr. Nath said that no autopsies have been performed because of the highly infectious nature of the infection. The virus is present in the sweat, tears, diarrheal fluid, and every bodily secretion, he noted.

SURVIVORS POST-EBOLA

Dr. Nath, who has travelled to Liberia to work on the NINDS-funded study, said families of Ebola survivors will often make a comment like “he's just not the same as he was before.” He said eye doctors had noticed that survivors have trouble with following commands for eye tracking and suspected that the patients have cognitive dysfunction.

The researchers focused on 82 of 87 recruited survivors (five were excluded from the study), nearly 70 percent of whom had been treated at an Ebola treatment unit (ETU) for more than 14 days. The average age of the survivors was 34.6 years and 53 percent of them were female.

Six-month standardized assessments of the survivors found, among other observations:

  • The most common new neurological symptoms during or after ETU admission were headache, depressed mood, weakness, myalgia and memory loss.
  • Severe neurological manifestations included hallucinations, meningitis and coma.
  • Severe neurological manifestations were found in half of the survivors, and the remaining half had moderate manifestations.
  • The most commonly reported ongoing symptoms included weakness, headaches, depressed mood, memory loss and myalgia.
  • Two patients were actively suicidal and one had active hallucinations.
  • Nearly two-thirds had abnormalities of eye pursuits and saccades.
  • One-third had tremor and abnormal reflexes and abnormal sensory findings.
  • One-sixth of patients had frontal release signs.
  • All survivors had some neurologic disability as measured by the Modified Rankin Scale.

“Neurologic abnormalities following Ebola virus disease involved subcortical structures, cerebellar pathways, and sensory peripheral nerves and were present in all survivors,” the researchers reported.

NEXT STEP: ASSESSING UNINFECTED CONTACTS

Dr. Nath said the research team now plans to evaluate uninfected contacts of people who had Ebola to gain added insight into the neurological problems experienced by survivors. It is possible that some of the neurological symptoms were present before Ebola infection.

Dr. Nath said his research team is also evaluating serum and CSF samples from survivors to look for antibodies and the virus by PCR. He hopes to eventually get an MRI machine in place to look for brain changes that may be due to Ebola.

Dr. Nath said he has concerns about addressing these neurological problems in Liberia. In Liberia, “there is no neurologist in the entire country and a lot of physicians died during the epidemic,” he said, noting that there are few available medications to treat specific neurologic conditions, such as tremor or seizures.

According to the World Health Organization (WHO), there were 28,639 confirmed cases of Ebola from 2014 to February 2016, nearly all of them in Guinea, Liberia, and Sierra Leone. Deaths from Ebola totaled 11,316. WHO last month issued a clinical guide for care of Ebola survivors.

While the epidemic has been declared over, public health officials continue to monitor for new cases. The abstract findings are part of a larger study called PREVAIL III, which is a US-Liberian collaboration to track the long-term health consequences of Ebola. The researchers want to determine if survivors develop immunity that will protect against future Ebola infection and whether survivors can transmit infection to close contacts and sexual partners. There is also work to develop and test an Ebola vaccine.

Before Dr. Nath's group released its abstract findings, there were already suggestions in the medical literature that the Ebola virus may damage the central nervous system. There was a case reported in January of a Sierra Leona woman who developed late-onset encephalitis following Ebola infection. Another reported case involved a Scottish nurse who developed meningitis after recovering from Ebola infection.

“Studies published in 2015 and 2016 suggest that survivors of Ebola virus disease may experience a wide range of complications, including neurologic signs and symptoms, of variable severity, and unknown duration,” Dr. Uyeki said in an email to Neurology Today.

MORE TO BE LEARNED

How Ebola may take a long-term toll on the brain is not known, and multiple factors could be to blame. For instance, in addition to the possibility of a direct viral hit, it is possible that the ongoing neurological symptoms are due to an immune response to the initial infection, experts say.

“Systemic inflammation can also lead to immune activation in the brain that could lead to memory dysfunction and other neurological problems,” said Robyn Klein, MD, PhD, a professor of internal medicine, pathology and immunology and neuroscience at Washington University, who commented on the findings. “The physical and emotional toll of being critically sick with Ebola could also take a toll.”

“We are just beginning to learn about the ways that viruses and inflammatory diseases can affect the brain,” Dr. Klein said. “Many of the mechanisms that promote normal brain development, including sculpting of neural connections, use molecules thought previously to be only involved in immune function during peripheral responses to pathogens. We are now observing that these mechanisms may be triggered during recovery from infections, altering neural connections in the fully developed brain.”

Joseph R. Berger, MD, FAAN, a professor of neurology at University of Pennsylvania, said the abstract findings suggest that the “central nervous system is widely” affected by Ebola, but how that happens is not clear. He said the virus could have a “hit-and-run effect” that causes the neurologic damage or it may be the result of ongoing viral infection. Previous reports have shown that the Ebola virus can persist in certain areas of the body for nine months or longer.

Dr. Berger said it is important to track survivors of Ebola survivors to learn more about how the virus operates and perhaps find ways to prevent or minimize problems in future outbreaks. He said lessons can also be learned from Ebola about other emerging viral diseases.

“We look at these obscure viruses that affect people in poor countries and we think that they are unlikely to cause problems that will ever affect the US,” Dr. Berger said. But he cautioned that probably “it is only a matter of time before we see anther pandemic like we did with HIV.”

EXPERTS: ON EBOLA-RELATED NEUROLOGIC COMPLICATIONS

Figure

DR. ROBYN KLEIN: “Systemic inflammation can also lead to immune activation in the brain that could lead to memory dysfunction and other neurological problems. The physical and emotional toll of being critically sick with Ebola could also take a toll.”

Figure

DR. JOSEPH R. BERGER said the findings suggest that the “central nervous system is widely” affected by Ebola, but how that happens is not clear. He said the virus could have a “hit-and-run effect” that causes the neurologic damage or it may be the result of ongoing viral infection. Previous reports have shown that the Ebola virus can persist in certain areas of the body for nine months or longer.

LINK UP FOR MORE INFORMATION:

•. WHO clinical care for survivors of Ebola virus disease—Interim guidance: http://bit.ly/WHO-clinicalcare