Microcephaly

Microcephaly means "smallheadedness", whereas "Microencephaly" means "small brain". Because the size of the brain is mostly determined by the size of the head, microencephaly is implied when discussing microcephaly. Microcephaly is a neurodevelopmental disorder. It serves as an important neurological indication or warning sign, but no uniformity exists in its definition. It is usually defined as a head circumference (HC) more than two standard deviations below the mean for age and sex. Some academics advocate defining it as head circumference more than three standard deviations below the mean for the age and sex. Microcephaly may be congenital or it may develop in the first few years of life. The disorder may stem from a wide variety of conditions that cause abnormal growth of the brain, or from syndromes associated with chromosomal abnormalities. In general, life expectancy for individuals with microcephaly is reduced and the prognosis for normal brain function is poor. The prognosis varies depending on the presence of associated abnormalities.


Figure 1: Zika fever symptoms of babies born with microcephaly.

Affected newborns generally have striking neurological defects and seizures. Severely impaired intellectual development is common, but disturbances in motor functions may not appear until later in life. Infants with microcephaly are born with either a normal or reduced head size. Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled scalp. As the child grows older, the smallness of the skull becomes more obvious, although the entire body also is often underweight and dwarfed. Development of motor functions and speech may be delayed. Hyperactivity and intellectual disability are common occurrences, although the degree of each varies. Convulsions may also occur. Motor ability varies, ranging from clumsiness in some to spastic quadriplegia in others.

In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority. Some may experience ongoing difficulty with walking, painful symptoms, and some require long-term breathing support. Guillain–Barré syndrome is rare, at one to two cases per 100,000 people every year. The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who described it with André Strohl in 1916.

Generally, no specific cure is known for microcephaly. Treatment is symptomatic and supportive. The spread of mosquito-borne Zika virus has been implicated in increasing levels of congenital microcephaly by the CDC.


Figure 2: A baby with microcephaly (left) compared to a baby with a typical head size.


Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness as a result of damage to the peripheral nervous system. Many experience changes in sensation or develop pain, followed by muscle weakness beginning in the feet and hands. The symptoms develop over half a day to four weeks. During the acute phase, the disorder can be life-threatening with about a quarter developing weakness of the breathing muscles and requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.

This autoimmune disease is caused by the body's immune system mistakenly attacking the peripheral nerves and damaging their myelin insulation. Sometimes this immune dysfunction is triggered by an infection. The diagnosis is usually made based on the signs and symptoms, through the exclusion of alternative causes, and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid. Various classifications exist, depending on the areas of weakness, results of nerve conduction studies, and the presence of antiganglioside antibodies. It is classified as an acute polyneuropathy.

In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority. Some may experience ongoing difficulty with walking, painful symptoms, and some require long-term breathing support. Guillain–Barré syndrome is rare, at one to two cases per 100,000 people every year. The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who described it with André Strohl in 1916.

Symptoms
The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over four weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the cranial nerves which supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include back pain, painful tingling, muscle pain and pain in the head and neck relating to irritation of the lining of the brain.

Causes
Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks prior to the onset of the neurological symptoms. These may consist of upper respiratory tract infection (rhinitis, sore throat) or diarrhea. In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.

Two thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly these are episodes of gastroenteritis or a respiratory tract infection. The Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3 and the bacterium Mycoplasma pneumoniae have been associated with GBS. The tropical viral infection dengue fever has been associated with episodes of GBS. Previous hepatitis E virus infection has been found to be more common in people with Guillain–Barré syndrome. Zika virus has been linked to Guillain–Barré syndrome.


Treatment
Plasmapheresis and intravenous immunoglobulins (IVIg) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the body's attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIg neutralizes harmful antibodies and inflammation. These two treatments are equally effective and a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIg works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIg is usually used first because of its ease of administration and safety. Its use is not without risk; occasionally it causes liver inflammation, or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery.

Prognosis
Guillain–Barré syndrome can lead to death as a result of a number of complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care this occurs in about 5% of cases. There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be chronic inflammatory demyelinating polyneuropathy which is treated differently. The health-related quality of life (HRQL) after an attack of Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience chronic pain, fatigue and difficulty with work, education, hobbies and social activities.


Zika Virus Signs & Clinical Symptoms

Clinical facts about Zika virus infection:

 
  • About 1 in 5 people infected with Zika virus become ill.
  • The most common symptoms of Zika are fever, rash, joint pain, or red eyes.
  • Other symptoms include muscle pain, headache, pain behind the eyes, and vomiting.
  • The illness is usually mild with symptoms lasting for several days to a week.
  • Severe disease requiring hospitalization is uncommon.
  • Deaths due to Zika have not been reported.

The first well documented case of Zika virus was in 1964, beginning with a mild headache and progressing to a maculopapular rash, fever, and back pain. Within 2 days, the rash was fading, and within 3 days, the fever was gone and only the rash remained. So, the most common symptoms of Zika virus disease are mild fever, rash, conjunctivitis, headaches and arthralgia, which appears between three and twelve days after the mosquito vector bite. One out of four people may not develop symptoms, but among those who are affected, the disease is usually mild with symptoms that can last between two and seven days. Severe disease requiring hospitalization is uncommon. Complications (neurological, autoimmune) are rare, but have been described in the outbreaks in Polynesia.


Figure 1: Zika fever symptoms. The most common symptoms of Zika are fever, rash, joint pain, or red eyes


The symptoms of zika fever are similar to other flaviviruses such as Dengue fever or chikungunya (see figure 2), which means that it can be easily mistaken for one of those illnesses. The majority of cases (60-80%) are asymptomatic. The main clinical symptoms in patients are low-grade fever, conjunctivitis, transient arthritis/arthralgia (mainly in the smaller joints of the hands and feet) and maculopapular rash that often starts on the face and then spreads throughout the body. Hemorrhagic manifestations have been documented in only one instance, hematospermia (red–brown fluid in ejaculate). During the outbreak in French Polynesia there was also noted to be a concomitant increase in cases of Guillain-Barré Syndrome which could have been due to Zika but has not been proven.


Figure 2: Comparisment of Dengue, Zika and Chikungunya symptoms. You can also download the original image in high resolution as jpg, tiff or powerpoint file.


Video 1. Brazil links fast-spreading Zika virus to birth defects.


A pregnant woman can pass Zika virus to her fetus during pregnancy. Zika is a cause of microcephaly and other severe fetal brain defects in northeast Brazil (see video 1).

The CDC has issued a travel alert for people traveling to regions and certain countries where Zika virus transmission is ongoing: Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Suriname, and Venezuela. See all the CDC and WHO guidelines. The CDC recommends special precautions for pregnant women and women trying to become pregnant:

  • Pregnant women in any trimester should consider postponing travel to the areas where Zika virus transmission is ongoing. Pregnant women who do travel to one of these areas should talk to their doctor or other healthcare provider first and strictly follow steps to avoid mosquito bites during the trip.
  • Women trying to become pregnant should consult with their healthcare provider before traveling to these areas and strictly follow steps to prevent mosquito bites during the trip.


Figure 2: Zika fever symptoms of babies born with microcephaly.