Autism research shows signs of inflammation in brain tissue of patients

Inflammation in the brain is clearly a feature of autism, according to a new study published November 15, 2004, in online edition of Annals of Neurology, the scientific journal of the American Neurological Association. The researchers found strong evidence that certain immune system components that promote inflammation are consistently activated in people with autism.

"These findings reinforce the theory that immune activation in the brain is involved in autism, although it is not yet clear whether it is destructive or beneficial, or both, to the developing brain," said senior author Carlos A. Pardo-Villamizar, M.D., at the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Autism is a disorder of the developing brain that appears in early childhood. It is estimated to afflict between 2 and 5 of every 1000 children and is four times more likely to strike boys than girls. Children with autism have difficulties in social interaction and communication and may show repetitive behaviors and have unusual attachments to objects or routines.

Autism has a strong genetic component, and in some families, autism tends to be more prevalent. In identical twins with autism both are usually affected. However, the number of children with autism appears to be increasing more than expected for a genetic disorder. This suggests to scientists that genetic abnormalities require the influence of other factors to cause the disorder. Birth complications, toxins, diet, and viruses and other pathogens have been suggested, though there is no strong evidence for any of these.

In recent years, there have been scientific hints of immune system irregularities in children with autism, but not all studies have confirmed this. Pardo and his colleagues sought a more definitive answer by looking not at the immune system overall, but at immune components inside the relatively sealed environment of the nervous system.

Led by first author Diana L. Vargas, MD, a post-doctoral fellow working in Pardo's laboratory, the researchers examined brain tissue from 11 people with autism, aged 5 to 44 years, who had died of accidents or injuries. Compared with normal control brains, the brains of the people with autism featured immune system activation and inflammation in the brain. "This ongoing inflammatory process was present in different areas of the brain and produced by cells known as microglia and astroglia," said Pardo.

When the researchers measured brain levels of immune system proteins called cytokines and chemokines, they found abnormal patterns consistent with inflammation. "The pattern of cellular and protein findings indicate that they are part of the 'innate' immune system in the brain, and do not appear to be caused by immune abnormalities from outside the brain," said Pardo.

The findings in the brain tissue were corroborated by studies of cerebrospinal fluid obtained from six children with autism (ages 5 to 12 years), in which cytokines that promote inflammation were found to be elevated. It is conceivable that signs of inflammation in the cerebrospinal fluid could one day be used to diagnose autism, or even that doctors could treat inflammation to prevent or combat autism, however this is still speculative, according to Andrew W. Zimmerman, a pediatric neurologist at the Kennedy-Krieger Institute in Baltimore and co-author of the paper. For one thing, it is possible that the inflammation represents the brain's efforts to combat some other process damaging to brain cells.

"These findings open new possibilities for understanding the dynamic changes that occur in the brain of autistic patients during childhood and adulthood. Although they may lend themselves to development of new medical treatments for autism, much more research would be needed to establish the validity of this approach," said Pardo.

"Currently, there are no biological tests that support the diagnosis of autism", says Dr. Heba Ismail from The Doctors Lounge. "One would hope that the possible detection of signs of inflammation in the brain or cerebrospinal fluid could one day be used for the earlier diagnosis of autism, and therefore earlier intervention plans."

Among the next steps in this line of research, Pardo and colleagues are studying how the genetic background of patients and families may influence the development of immunological reactions in the brain that confer susceptibility to autism.

Sources

Article: "Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism," Diana L. Vargas, Caterina Nascimbene, Chitra Krishnan, Andrew W. Zimmerman, and Carlos A. Pardo; Annals of Neurology; Published Online: November 15, 2004 (DOI: 10.1002/ana.20315).

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Chronically ventilated premature infants need continued surfactant

Monday, 15^th November 2004

	Research shows that even after premature infants produce surfactant, it often fails to function and they may develop lung disease.
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Physicians have known for decades that many premature babies suffer respiratory problems stemming from insufficiency of a lung substance called surfactant during their first few weeks of life. The standard treatment has been to provide replacement surfactant immediately after birth. A new study has found that even after infants begin producing their own surfactant, it often fails to function properly in premature infants who continue to have lung disease after their first week.

The study also raises the question of whether additional replacement surfactant treatment may benefit such infants, just as it does in the week after birth.

Neonatology researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania published the study in the October 20 online edition of the journal Pediatric Research. It was the first study of surfactant dysfunction in infants beyond the first week of life.

"We studied premature babies who require mechanical ventilation to breathe after one week of age," said Philip L. Ballard, M.D., Ph.D., director of Neonatology Research at The Children's Hospital of Philadelphia. "We found that three-quarters of these high-risk infants have episodes of surfactant dysfunction, and these episodes are associated with worsening of their respiratory status."

Surfactant is a naturally produced mixture of proteins and lipids (fats) that lowers surface tension within alveoli, the tiny air sacs within the lungs. By doing so, it prevents the alveoli from collapsing during exhalation, and eases the work of breathing. Premature infants have underdeveloped respiratory systems and do not produce enough of their own surfactant. Therefore, physicians have found that supplying replacement surfactant may improve infants' lung function during the earliest period after birth.

Replacement surfactant is discontinued after babies begin to produce enough surfactant on their own. However, infants with persistent lung disease may develop a condition called bronchopulmonary dysplasia (BPD), in which chronic respiratory distress makes it necessary for infants to breathe through a mechanical ventilator. BPD can cause long-term disability or death.

In this study, the researchers analyzed samples of fluid from the windpipes of 68 premature infants who had breathing tubes between one to 12 weeks after birth. Seventy-five percent of the infants on at least one occasion had abnormal surfactant function, and diminished amounts of an important component of surfactant, called surfactant protein B. In addition, these surfactant abnormalities were significantly more likely to occur during periods of respiratory infection and worsened respiratory status.

Babies are defined as premature if they are born before 37 weeks of gestation. Most premature babies have symptoms of respiratory distress, with the risk increasing with greater prematurity. The infants in this study were very premature, having been born at 23 to 30 weeks gestation.

"Premature infants with continuing respiratory failure and abnormal surfactant may benefit from treatment with replacement surfactant--or from strategies to increase their own production of surfactant," said Dr. Ballard, who has been studying infant lung development for more than 30 years. He and his colleagues are currently carrying out a pilot trial of surfactant therapy in preterm infants older than 7 days, and they are planning a clinical trial to investigate short- and long-term safety and effectiveness of surfactant treatment in these infants.

Sources

JEFFREY D. MERRILL, ROBERTA A. BALLARD, AVITAL CNAAN, ANNA MARIA HIBBS, RODOLFO I. GODINEZ, MARYE H. GODINEZ, WILLIAM E. TRUOG, and PHILIP L. BALLARD. Dysfunction of Pulmonary Surfactant in Chronically Ventilated Premature Infants. Pediatr Res 2004, DOI: 10.1203/01.PDR.0000145565.45490.D9.
 

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Toxoplasmosis screening recommended for newborns, pregnant women

Monday 21st February, 2005

	Physicians found that symptoms and risk factors are absent in more than half of the mothers of infants with congenital toxoplasmosis.
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Physicians found that signs, symptoms and identifiable risk factors are absent in more than half of the mothers of infants with congenital toxoplasmosis in a national study of children with this disease.

More than half of the pregnant women who were at risk for acute infection with Toxoplasma gondii could not be identified by history or routine examination. Therefore, the physicians recommend that systematic screening for acute acquired toxoplasmosis for all pregnant women in the United States during prenatal visits, as well as screening for congenital toxoplasmosis in all newborns, become standard medical practice. The group also emphasizes that confirmation of test results in reference laboratories and informed counseling are essential parts of the process.

An infection caused by the parasite Toxoplasma gondii, toxoplasmosis can be harmful and potentially lethal to the children of women who acquire the infection during pregnancy.

In the February issue of the The American Journal of Obstetrics and Gynecology, the researchers report that current clinical practice -- taking a careful history and performing a physical examination -- would identify only half of the at-risk mothers who have acquired the infection during pregnancy and have had infants with congenital toxoplasmosis. Screening through blood tests could have identified the rest, the researchers said.

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Mayo Clinic study suggests no link between autism and immunizations

Friday, 21^st January 2005

	Over the past 20 years, there has been speculation about a connection between immunizations and an increase in autism.
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ROCHESTER, Minn. -- Over the past 20 years, there has been speculation about a connection between immunizations and an increase in autism. However, a study by Mayo Clinic researchers published in the January issue of Archives of Pediatrics and Adolescent Medicine suggests the increase may be due to improved awareness, changes in diagnostic criteria and availability of services, not environmental factors or immunizations.

"This study is the first to measure the incidence -- the occurrence of new cases -- of autism by applying consistent, contemporary criteria for autism to a specific population over a long period of time," says William Barbaresi, M.D., a Mayo Clinic developmental pediatrician and one of the study authors. "In doing so, the study accounts for improvements in the diagnostic criteria for autism, the medical community's improved understanding of this disease and changes in federal special education laws."

The study found that the increase in the incidence of autism in Olmsted County, Minn. coincided with broadening of the diagnostic criteria for autism and new federal special education laws including autism as a disability category. Both events occurred many years after immunizations were mandated for school entry. Broader, more precise diagnostic criteria for autism were introduced in 1987. Prior to these new criteria, children with autism may have been given less precise diagnoses such as "developmental delay" or "mental retardation," and children with milder symptoms of autism may not have been identified at all. The 1991 federal special education laws improved the availability of educational services for children with autism.

The study used data from the Rochester Epidemiology Project, a database of all inpatient and outpatient records in Olmsted County, Minn. The database diagnoses are indexed for computerized retrieval, allowing researchers to identify subjects with any developmental disorder. Researchers found 3,000 children with at least one of 80 diagnoses related to autism. Of the 3,000 children, 124 actually met the current diagnostic criteria for autism. Reviewing the medical and school history of this group showed that the incidence of autism was stable until 1988-1991, then increased after new laws and new diagnostic criteria were implemented.

Sources

Mayo Clinic.

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Early warning signs for meningitis in children identified

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Researchers have identified a number of early symptoms for meningococcal disease in children that could substantially speed up diagnosis, reporting their findings online in The Lancet today (Wednesday January 11, 2005).

Meningococcal disease is the most common infectious cause of  death in children in many developed countries. The disease can progress from initial symptoms to death within hours, so early diagnosis is crucial. However, the classic symptoms of the disease ? rash, headache, stiff neck, sensitivity to light, and impaired consciousness ? occur late in the pre-hospital illness and currently parents and doctors are over-reliant on these for diagnosis.

To investigate the early clinical features of the disease, Matthew Thompson (University of Oxford, UK) and colleagues sent questionnaires to parents of 448 children with meningococcal disease. They also looked at the children's medical records. They found that the classic symptoms of the disease developed late, with an average onset of 13-22 hours. By contrast, 72% of the children had early symptoms of infection (sepsis) ? leg pain, cold hands and feet, and abnormal skin color - that developed at an average of 8 hours. These early clinical features should be promoted to parents and doctors to substantially speed up diagnosis of this potentially fatal infection in children, state the authors.

Dr Thompson states: "Recognizing early symptoms of sepsis [infection] could increase the proportion of children identified by primary-care physicians and shorten the time to hospital admission. The framework within which meningococcal disease is diagnosed should be changed to emphasize identification of these early symptoms by parents and clinicians."

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