A quest for better treatments with the world-renowned expert on autism spectrum disorders, pediatric neurologist Margaret L. Bauman, MD, at MGH.

Autism Spectrum Disorders | ASDThe week little Neil Buckley lost all his words, Maura and Paul Buckley lost their bearings.  Their oldest, a girl named Gillian, was healthy and vibrant.  Her little brother had been a normal and increasingly talkative toddler until that unforgettable week in 2002.  “In the short span of one week, all his vocabulary disappeared,” recalls his mother, Maura. “He became so frustrated when he had something to say, but all he could do was puff up his cheeks in a struggle to get the words out.”

Maura and Paul rushed Neil to their pediatrician, who referred them to a pediatric neurologist. The neurologist watched Neil and ruled out an autism spectrum disorder; after all, though he had lost his ability to speak, he was still making eye contact, being social with his parents and others and he had normal control over physical movements — all things that often go awry in kids with autism spectrum disorders, or ASD.

But over the next several months, recalls Maura, “everything went downhill, and he lost all those skills too, and more.” Months of despair and hand-wringing brought the couple back to the same specialist, who confirmed a diagnosis of regressive autism, a type of autism in which seemingly normal children begin to show signs of autism, usually at 12-30 months of age. Neil was two.

Another Child Diagnosed

The Buckleys rallied a bevy of specialists to guide them through the challenges of caring for Neil, who soon was also diagnosed with mitochondrial disorder and Crohn’s disease, both serious and progressive diseases that put him in pain that he could not articulate. Then, another son, Tyler, was born. Within minutes of his delivery, his parents and doctors knew something wasn’t right. He was later diagnosed with an even more severe form of mitochondrial disorder than his older brother. A diagnosis of autism spectrum disorder wasn’t far behind.

A family that was once a happy, picture-perfect unit was suddenly upended, with visits to doctors and hospital emergency rooms now more common than trips to the park and the zoo.

A family that was once a happy, picture-perfect unit was suddenly upended, with visits to doctors and hospital emergency rooms now more common than trips to the park and the zoo. On an early quest for better treatments for both of their sons and answers to their many questions, they learned that one of the world-renowned experts on autism spectrum disorders, pediatric neurologist Margaret L. Bauman, MD, at Massachusetts General Hospital had an office minutes from their Lexington, Mass., home.

Distressed parents form long lines to see Dr. Bauman, but  the couple managed to get an appointment. For the last six years, the Buckleys have relied on the care of Dr. Bauman and her colleagues at the Lurie Family Autism Center LADDERS Program for Neil and Tyler. The care, says Maura, “has made our boys’ lives the best that they can be. It has also made our lives, as parents, less stressful because we know we have available to us the best doctors and therapists who are not just keeping up on the cutting-edge ideas about autism, but generating them themselves.”

An Autism Center Poised to Grow

The Lurie Center clinic is only poised to grow. Last summer, MGH received one of the biggest gifts in the hospital’s history, $29 million to expand its existing program in childhood autism. The gift from the Nancy Lurie Marks Family Foundation creates a center beyond the scope of the present MGH Lexington clinic, enabling the recruitment of new clinicians, the funding of new research on autism spectrum disorders and the initiation of education training programs aimed at internists and specialists about the disease. The center will also launch a new program for the growing population of autistic adults.

“In the last two decades, a tsunami of autistic children have been born,” says Ann Neumeyer, MD, a neurologist at the Lurie Center and the center’s medical director. “This rising swell of kids is now getting older, and their needs and challenges are changing, but the medical world is ill-equipped to deal with it.”

Autism Spectrum Disorders | ASDNot too long ago, autism spectrum disorders were viewed as a type of mental retardation. But as instances of autism spectrum disorder have skyrocketed in recent years — not merely attributable to an increase in diagnoses — scientists and physicians have put increased attention to the disorder. Today, autism is behaviorally, rather than medically, defined — that is, it is diagnosed on the basis of physician observation and clinical screening tests, not a blood test or other medical methods. Yet its underlying cause is considered to be neurological and biological, with abnormalities both in the brain and, in  some cases, other organ systems, and it has a strong genetic component.

Questions about Autism Spectrum Disorders

In medical circles, the term autism spectrum disorder largely has come to replace “autism” as scientific understanding of autism has grown and with the recognition that the disorder is heterogeneous both in its causes and clinical characteristics. ASD encompasses a variety of specific diagnoses, with varying degrees of severity, including Asperger syndrome and Pervasive Developmental Disorder. The prevalence of autism spectrum disorders appears to be increasing, affecting close to 1.5 million Americans, mostly boys, according to the Autism Society of America. The Centers for Disease Control and Prevention has reported that an autism spectrum disorder occurs in one in 110 births.

Perhaps the world’s biggest breakthrough in autism was Dr. Bauman’s discovery in the mid-1980s of distinct abnormalities in the brains of autistic patients.

Though understanding of autism spectrum disorders has improved dramatically in the last two decades — with many of those discoveries having emerged from Mass General labs and clinics — many questions are still unanswered. Are environmental factors to blame for the explosion of autism spectrum disorder cases? To what extent do genes play a role? What parts of the brain and body are malfunctioning and why? Why are boys more susceptible than girls? And why do so  many autistic individuals suffer from other debilitating medical problems?

Perhaps the world’s biggest breakthrough in autism was Dr. Bauman’s discovery in the mid-1980s of distinct abnormalities in the brains of autistic patients. Her groundbreaking finding was based on work parsing through a postmortem autistic brain of a young man, donated by the boy’s family after his untimely death, and comparing it to a normal brain. It took her all of one intensive summer to do — a nanosecond in research terms, but no one had tried it before.

Discovery in a Mentor’s Lab

The discovery happened in the lab of her colleague and mentor, Thomas L. Kemper, MD, at Boston Medical Center. “I didn’t know what I was looking for,” she recalls. “I was interested in studying the human brain and there happened to be an autistic brain available that had been sitting in a lab drawer. We started to study this case systematically and by the fall, knew that this brain was anatomically abnormal in specific brain regions that are important for learning, behavior, emotion and memory.”

The news made the front page of The Boston Globe in 1984 and took the medical world by storm. Until then, the prevailing explanation for the underlying cause of autism spectrum disorders was the “refrigerator mother” theory — that distant and inattentive  mothers were to blame for their children’s autism.

Building on her existing patient base of children with learning disabilities, Dr. Bauman gradually established a thriving practice for children with a spectrum of developmental disabilities, based at two area hospitals. She founded the LADDERS program in 1981 at Youville Hospital in Cambridge, Mass. In 1997, the program joined the pediatric service at Mass General. The new affiliation with MassGeneral Hospital for Children (MGHfC) meant the program could expand to include research and teaching, critical components for a still poorly understood disorder.

Autism Spectrum Disorders | ASDSince then, she has recruited additional staff with expertise in neurology, child psychiatry and gastroenterology, as well as psychology, social work, nursing, special education, and, in association with Spaulding Rehabilitation Hospital, occupational and physical therapy and speech and audiology therapy.

A Model for Comprehensive Care

Resource coordinators have also joined to help families navigate the overwhelming interactions with insurance companies, schools and services. More recently, the clinic formed the basis of what is now known as the Autism Treatment Network (ATN), a group of academic hospitals and physicians dedicated to developing a model of comprehensive medical care for children and adolescents with autism spectrum disorders.

The Lurie Center LADDERS program emphasizes early diagnosis and intensive intervention, since early identification and treatment of autism spectrum disorders are known to improve developmental outcomes. “Often,  we can make diagnoses now at six months of age because the  first sign now appears to be head lag,” a lack of neck control.  In healthy children, neck control kicks in by four months of age, enabling a baby to hold up his head, says Dr. Bauman.

Indeed, Maura Buckley attests that Tyler had the benefit of his older brother’s diagnosis in that she, her husband and physicians were vigilant for signs of autism from the moment of birth. She believes that early treatment for Tyler, who is now six, is to thank for the fact that “he defies his diagnosis.” He communicates relatively effectively using sign language and he just began using his first sentences, while his older brother is completely nonverbal.

Another hallmark of the program is thorough medical work-ups and attention to co-existing medical conditions.

Chronic Pain Issues

“So many of these children have chronic pain issues or other medical problems that prevent them from learning and maximally benefiting from their therapies and interventions,” says Dr. Neumeyer. Some have hearing loss, which inhibits language development; others have epilepsy, motor disorders, food allergies, metabolic disorders and psychiatric disorders. Many have sleep disorders, and some defined syndromes such as Fragile X Syndrome, Rett syndrome or Tuberous Sclerosis are complex. “Once you take away those underlying medical problems, or mitigate them,” she says, “development blossoms.”

 Dr. Buie and collaborators have published studies showing that many autistic individuals possess  a specific genetic abnormality implicated in GI disorders, but  more studies need to be done, he says.

“Many medical problems cause odd behaviors or exacerbate them like head-banging or large twitches, because many autistic patients are nonverbal so they act out physically what they are feeling inside,” says Lurie Center gastroenterologist Timothy Buie, MD. “In the past, the medical world thought, ‘autistic kids just behave that way,’ and doctors would try to address the behavior. But now we can identify an underlying medical condition, and if we can treat the medical problem, the behaviors frequently either diminish or go away altogether.”

Indeed, Dr. Buie and his colleagues at MGHfC and elsewhere have plenty of anecdotal evidence to suggest a significant link between gastrointestinal (GI) disorders and autism spectrum disorders. Some experts believe that up to 50 percent of autistic individuals have  GI disorders like gastro-esophageal reflux, inflammatory bowel disease such as Crohn’s disease and functional issues like irritable bowel syndrome and constipation. Dr. Buie and collaborators have published studies showing that many autistic individuals possess  a specific genetic abnormality implicated in GI disorders, but  more studies need to be done, he says.

Discovering a Set of Mutations

Another piece of the autism spectrum disorder puzzle is beginning to come together, as its genetic underpinnings are coming to light. In December, an international team led by scientists at Mass General, Johns Hopkins University and the Massachusetts Institute of Technology announced its discovery of a set of mutations on a particular gene active in the nerve cells of autistic patients. The finding followed an earlier discovery by the same team of abnormalities on chromosome 16 that were associated with autism spectrum disorders. Mark J. Daly, PhD, a member of the Center for Human Genetic Research at MGH, was the senior author of these groundbreaking studies.

The group found that the brain’s “white matter” is enlarged in children both with and without autism who have language problems.

Meanwhile, with increasingly advanced imaging, researchers are focusing in on the architecture, brain waves and chemistry of the autistic brain. Scientists from the MGH-TRANSCEND Research Laboratory, which conducts research at the Lexington site, have made a series of discoveries in this area. The group found that the brain’s “white matter” is enlarged in children both with and without autism who have language problems. Now, the team,  led by Martha R. Herbert, MD, PhD, a pediatric neurologist and TRANSCEND’s director, is investigating how this starts early  in life.

Such studies are shedding light not only on why autistic individuals have trouble communicating, but also on what is  malfunctioning in their bodies and brains. “Ultimately, I expect we will learn broadly about the biological basis for human communication and also how the brain and the body affect each other,” says Dr. Herbert. “That’s a tremendous ‘side benefit’ to these studies and I expect that they may be helpful in expanding our understanding of other diseases like Alzheimer’s, dementia and other neuro-degenerative disorders.”

Despite the advances, patients and their families today face tremendous challenges in staying healthy and overcoming the many roadblocks related to autism spectrum disorders.

Despite the advances, patients and their families today face tremendous challenges in staying healthy and overcoming the many roadblocks related to autism spectrum disorders. One is the paucity of clinicians with expertise in autism and the challenge schools  face in coping with the growing number of autistic children; the Lurie grant includes a mandate to address those needs.

“The wonderful thing about the Lurie gift is that it will enable  us to augment the care we have offered at LADDERS, which  has a unique capability to support medical problems in children with autism,” says Dr. Neumeyer. While many other programs evaluate children and send them back to their pediatrician for care, “we have the ability to offer life-long care surrounding their disability, which also provides us with an opportunity to learn more about autism and care for autistic adults.”

The Lurie Family Autism Center: What’s Happening Next

The $29 million gift from the Nancy Lurie Marks Family Foundation for the formation of the Lurie Family Autism Center will go towards recruiting a director, hiring new staff and expanding clinical research and educational initiatives. Some of the specific near-term goals include:

  • Recruitment of physicians with expertise in neurology, gastroenterology, psychiatry and psychopharmacology, and experts in audiology, nutrition and adult internal medicine
  • Formation of audiology and phlebotomy labs and potentially an electoencephalography (EEG lab), and labs for specialized testing
  • The development of a program designed to assess autistic children, adolescents and adults with regard to their needs for assisted technology and alternative means of communication
  • A fellowship program for young investigators and physicians-in-training
  • In coordination with MassGeneral Hospital for Children’s Child and Adolescent Health Policy Program, headed by James M. Perrin, MD, a wide-sweeping advocacy and education program that will educate caregivers at Mass General and beyond about autism and how best to recognize signs of autism and treat patients with autism
  • Establishment and augmentation of behavioral programs for psychiatric inpatient care at McLean Hospital’s inpatient autism program
  • Recruitment of a neuropsychologist and neuropsychology fellow to the Lurie Center LADDERS program in collaboration with McLean Hospital
  • Expansion of research infrastructure and development of new studies on the origins, course and treatment of autism
  • Establishment of a family support center that offers resources and referrals to schools, vocational counseling and social service agencies