The ongoing Zika virus outbreak in South America has brought media and research attention to several rare neurological disorders.
Early reports suggested links between Zika infection and microcephaly (abnormal smallness of the head) in newborn infants. These were quickly followed by reports of increased rates of auto-immune disorder Guillain-Barre syndrome in Zika-infected adults. The most recent reports propose a connection between Zika infection and acute disseminated encephalomyelitis (ADEM).
These three rare conditions all cause damage to the nervous system, which includes the brain, spinal cord and nerves. Our nervous system functions to send signals throughout the body to co-ordinate movement, sense our environment and regulate body function.
What is acute disseminated encephalomyelitis (ADEM)?
ADEM is a rare autoimmune disease that causes lesions in the brain and spinal cord. Disease is usually triggered by a previous infection or vaccination, although why this occurs is not well understood. For example, one in 1,000 people infected with measles goes on to develop ADEM. Rates of disease have decreased in developed countries, due to reduced rates of infection.
Immune cells normally protect our body against disease, by killing invading viruses and bacteria. In ADEM, these immune cells attack our nerves within the brain and spinal cord and cause damage. Damage destroys the insulating coating on our nerve cells, called myelin, and interferes with signalling in the nervous system.
Early symptoms include fever, low energy, headache nausea and vomiting. Within several days, symptoms escalate and can range from low energy to coma, with weakness along one side of the body or in the legs (hemiparesis/paraparesis). Symptoms can also include loss of control of body movements (ataxia) and other movement disorders. Anti-inflammatory drugs are usually used to try to reduce damage.
Symptoms can start to improve quickly (within days) and people usually fully recover within six months. Most people experience no long-term symptoms. However, some individuals do “relapse”, meaning they go on to experience another round of symptoms.
If patients continue to having recurring symptoms, they may be diagnosed with multiple sclerosis. Multiple sclerosis causes similar damage and symptoms to ADEM and is a life-long disease. It is currently unclear whether ADEM leads to multiple sclerosis in some people or whether ADEM is simply confused for the first episode of multiple sclerosis.
How do you show Zika causes neurological disease?
Last week, the Centers for Disease Control and Prevention (CDC) concluded that Zika infection causes microcephaly. Microcephaly is a birth defect that causes abnormally small head size in infants and is associated with brain defects.
CDC researchers have also provided evidence for a strong link between Zika infection and Guillain-Barre syndrome. Guillain-Barre syndrome, which causes temporary paralysis and can lead to death, has increased in 12 countries currently experiencing a Zika virus outbreak.
Demonstrating Zika infection actually causes disease requires extensive study and consideration of a range of data. This was done in the recent publication connecting Zika infection and microcephaly. These conclusions required data showing individuals who develop disease are infected with Zika, as well as population data showing that rates of disease increased in Zika-affected areas and ruling out other possible causes.
The conclusions were also supported by laboratory data demonstrating that Zika virus can infect and kill nerve cells. These functional studies in the lab provide a logical connection between Zika virus and neurological disease.
Is ADEM linked to Zika virus infection?
A possible link between Zika infection and ADEM has been proposed based on recent study findings from Brazil. In 151 patients with confirmed arbovirus infection (a group of viruses that includes Zika), six developed neurological symptoms.
All six patients were infected by Zika virus and four developed Guillain-Barre syndrome. The remaining two developed ADEM. ADEM is well known to develop after infection by a range of viruses, so it’s entirely possible Zika virus will be added to this list. However, it should be noted that even among people infected with Zika virus, a very small number will develop ADEM.
While a link between Zika infection and ADEM is cause for concern, it remains to be formally proven. It may take months or years of study to confirm whether Zika actually causes ADEM. The hope is that through continued study we can better understand both Zika infection and ADEM disease and develop better ways of treating both.
Steven Maltby receives funding from the NHMRC Centre of Excellence in Severe Asthma (www.severeasthma.org.au) and the Hunter Medical Research Institute (www.hmri.org.au). He is affiliated with The University of Newcastle and the HMRI.