The UC Davis-M.I.N.D. Institute’s MARBLES study ( Markers of Autism Risk in Babies’ Learning Early Signs) is following some 100 women who have a biological autistic child and who are pregnant, or who are planning on becoming pregnant, to investigate possible biological and environmental agents that children are exposed to prenatally and post-partum. It seems that maternal health during pregnancy—what expecting mothers do or do not do—will remain an area of scrutiny in the search for autism’s causes: A study published in the December Neurology shows that children whose mothers took Epilim, an anti-epileptic drug, during pregnancy were seven times more likely to develop autism, as compared with children whose mothers did not take such a drug, as reported in Reuters. Epilim is known generically as Valproate and is sold as Depakene in the US. Previous studies have reported an association between fetal valproate syndrome and autism.

The woman I spoke to at the birthday party yesterday told me that her brother had been institutionalized at the Cambridge State Hospital. Originally called the Minnesota Colony for Epilectics, it became a state hospital for the developmentally disabled and for those with “mental deficiencies” in 1949; it reached its peak population of 2008 in the 1960s. In 1972, a class action suit was filed against the state’s six State Hospitals by the parents of some of the residents ” who felt that the conditions, care, treatment and training did not meet constitutional standards” (this photo says why). This started a movement to move individuals with developmental disabilities into community settings such as group homes where they might live as independently as possible, and not be shut away for their whole lives.

Today’s Daily Express tells the story of another forgotten child, Prince John, the sixth and youngest child of Queen Mary and George V. John had epilepsy and a “form of autism”:

He suffered his first epileptic fit when he was four and as these gradually became more frequent, it was decided that Johnnie should be hived off to the Sand ringham estate with his devoted nurse Charlotte “Lalla” Bill. Those were the days when little was known about epilepsy, and when treatments included confinement to hot baths in mustard water.

When he visited his doctor in London, the car’s blinds would be drawn so he would not be seen having a fit in public.

Occasionally he would be spotted at Sandring ham, gazing wistfully from a window or playing at soldiers on a wall, paper crown on his head and a wooden sword in his hand.

One observer described him as “a distant figure, tall, muscular but always remote, who would be glimpsed from afar in the woods escorted by his own retainers”.

He was even barred from the royals’ family portraits and photographs, including his parents’ silver wedding photo in July 1918. But this popular myth of the “monster” boy of Sandringham is being challenged by the people who knew him best.

John died in 1919 at the age of 13.

And hearing about his life and that of the older brother of the woman I met last night, makes me more than grateful every day, that Charlie lives with us, goes everywhere with us, in the community and in the world.

Scientists have previously posited that autism’s cause is at the synapse. Mutations in the genes for neuroligins—which ensure that signal transitions between nerve cells function—-have been suggested as a cause of autism.  Neuroscientists at Children’s Hospital Boston have identified what is being called a “master switch” that organizes the functioning of inhibitory synapses. Synapses are the connections between brain cells and enable communication among neurons; they’re essentially for virtually all brain functions, such as memory, sensory perception, motor coordination, learning.

The “master switch” is Npas4, which is a transcription factor, a “switch” that activates or represses other genes; it regulates over 200 genes that play a role in “calming down” over-excited cells. From today’s Science Daily:

At birth, the rapidly developing brain teems with excitatory synapses, which tend to make nerve cells “fire” and stimulate their neighbors. But if the excitation isn’t eventually balanced, it can lead to epilepsy, and diseases like autism and schizophrenia have been associated with an imbalance of excitation and inhibition. The creation of inhibitory connections is also necessary to launch critical periods — windows of rapid learning during early childhood and adolescence, when the brain is very “plastic” and able to rewire itself.

Researchers bred mice that lacked Npas4; these mice appeared anxious and hyperactive as were also prone to seizures and neurological problems. Scientific American has more to say and also notes that findings such as these can be used to “identify people who are genetically at risk for neurological disorders and develop new drugs to prevent and treat them.”

More genetics news today: Researchers have identified the mutated gene that causes childhood absence epilepsy (CAE).

The seizures of childhood absence epilepsy (CAE) are usually staring spells during which the child is not aware or responsive. The child’s eyes may roll up briefly. Each spell lasts about 10 seconds and ends abruptly. The child often is not even aware that anything has happened. These episodes can occur 1 to 50 times per day, often during exercise. Tonic-clonic (grand mal) seizures, with or without fever, may occur for a while before absence seizures develop and may occur from time to time thereafter. [Epilepsy.com]

The Childhood Absence Epilepsy Family Study also notes that CAE is also known as “Petit Mal” or epilepsy with “staring spells.” CAE is an inherited disorder and accounts for 10-12 percent of cases of childhood epilepsy.

The new study that points to a genetic cause for CAE appears in the May 29th online edition of the American Journal of Human Genetics. The study’s authors are from the David Geffen School of Medicine at UCLA and the Epilepsy Genetics/Genomics Laboratory, Epilepsy Center at the VA-Greater Los Angeles Healthcare System in West Los Angeles.

UCLA/VA research scientist Dr. Miyabi Tanaka studied the DNA of 48 patients with CAE and discovered that four patients had a genetic mutation occurring in a receptor called GABAR which binds to a neurotransmitter of the brain called GABA that inhibits the excitation of nerve cells in child and adult brains. When this regulation is lost or reduced, seizures develop.

“We identified this genetic mutation in eight percent of study patients with CAE, which is significant,” said Richard W. Olsen, Ph.D., study author and professor, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA.

Scientists also found that the genetic mutation was caused by an “alternative signal peptide called exon 1a, which is richly expressed in the fetus and developing brain, but as the child matures and becomes an adult, the expression of exon 1a is reduced”—-and this is why CAE “disappears” in adolescence and in adults.

We have wondered about the possibility of my son having seizures like the “absence seizures” noted above. Charlie’s pediatric neurologist specializes in epilepsy and seizures and (based on our descriptions of Charlie’s behavior) does not think he is having these types of seizures. Since my son’s language is very limited, we can never be 100% certain about anything, though—-hence the continuing interest in the possibility of medical signs and/or tests to detect conditions; to find answers.

Up until last week, posts about “mercury” and “Jenny McCarthy” had the most comments—-after last week, the topic of religion and the restraining order filed against the parents of Adam Race generated a torrent of discussion that’s still going on).

• Priest Files Restraining Order Against Parents of Autistic 13-year-old
  Some 250-plus comments about Adam Race and the parish of St. Joseph’s in Bertha, Minnesota.
• A Mother and a Housewife
  Mothers and housewives can be pretty accomplished—-one whom I know (via the internet) is Kathleen Seidel, who writes the Neurodiversity weblog.
• Read with Care: New Study on Thimerosal and Neurodevelopmental Disorders
  A new study published in the Journal of Neurological Sciences that reports an association between increased mercury (Hg) exposure from thimerosal-containing vaccines and neurodevelopmental disorders; two of the co-authors are Mark and David Geier.
• 5-year-old girl drowns in bathtub
  5-year-old Carlee Bennett of Pleasant Prairie, Wisconsin, apparently drowned in her bathtub on the evening of May 17th.
• So Is It Really Autism?: The search for medical signs
  According to Dr. Fernando Miranda of the Bright Mind Institute, maybe not. A report in the May 19th Good Morning America/ABC News describes some children who were initially diagnosed with autism, and later found to have Landau-Kleffner Syndrome. For some of the children, anti-seizure medication has produced dramatic results.
• Timeout Rooms and Physical Restraints
  Put in a timeout room more than 90 times?—coming home from school with cuts, bumps, and bruises?—-being held on the floor on his stomach by two adults?: All of these happened to 9-year-old Matthew Montgomery in Oldham County, Kentucky.
• Excluded?: On Keeping the Faith
  Does a fear of rejection, of being excluded, too often lead parents of autistic children and autistic individuals, and individuals who are “different,” not to seek out communities and experiences that they still feel drawn to?
• Insurance Doesn’t Pay For Groceries—What About Autism?
  Two comments by officials in two Utah insurance companies suggest how much is still not known about autism
• It’s Ok to be Disabled Until—-
  Oscar Pistorius, the runner from South Africa who is a double amputee, recently won a decision to be allowed to compete in the Olympic trials.

According to Dr. Fernando Miranda of the Bright Mind Institute, maybe not. A report in the May 19th Good Morning America/ABC News describes some children who were initially diagnosed with autism, and later found to have Landau-Kleffner Syndrome. For some of the children, anti-seizure medication has produced dramatic results and Dr. Miranda is said to insist that “you have to look inside the brain to determine what’s wrong,” via MRIs and EEGs.

The ABC report portrays parents as greatly relieved to know that there is a medical issue for their child’s disorder, and that the child does not have autism:

To watch Beckett [Kavanaugh] today, you might think he has a bit of trouble speaking, but it’s minor. You’d never think he was autistic. He’s being mainstreamed in kindergarten, in a school that he attends with his brother.

But that is yet another thing [his mother, Sarah Kavanaugh] has had to fight for, because the autism label stuck for so long it was hard to remove.

She’s also had to battle conventional wisdom in the medical community. Despite the EEG results, other doctors she’d seen in the past told her Beckett’s seizures didn’t meet the standard criteria for treatment. He wasn’t having enough seizures, in other words.

Doctors told her to take Beckett off the anti-seizure drugs, and Kavanaugh did without telling anyone.

A few weeks later, Beckett’s speech therapist called, very concerned. Beckett was sliding backward quickly, Sarah was told, so she put him back on the drugs.

Typically with anti-seizure medicine, the course of treatment is no more than four years. In that amount of time, the seizures usually clear up as the brain is literally retrained to stop seizing.

Many types of anti-seizure medicine are in use for other symptoms, such as bipolar disorder. But there is great debate within the autism medical community about when anti-seizure drugs should be used and about how severe the seizures have to be before they are treated.

Further complicating things, these seizures can often be completely invisible to the naked eye, or mistaken for staring or daydreaming — symptoms typical of autism.

We’ve speculated again and again that a seizure might be behind some of Charlie’s difficulties. Charlie’s had two MRIs and an EEG (not a sleep one) and there’s been no sign of seizure activity. By coincidence, the pediatric neurologist who Charlie sees specializes in seizures and epilepsy and he’s been very sure that Charlie is not having seizures. We’ve a few friends whose children do have Landau-Kleffner and/or epilepsy and there are differences in the types of teaching and other treatments that a child best responds to.

There’s something about finding a medical, biological, physical cause for a child screaming over and over or knocking his head on the car window that is reassuring. If you know that it’s a bad stomachache—or constipation from eating too much of certain things, perhaps—-plus a bad headache that is the reason for a tough day, a parent tends to feel that he or she can do something to “fix” it. I was reminded of this yet again this afternoon: Charlie asked to go swimming, got dressed in his swimsuit, sat in a chair unmoving. My suggestion to put on his shoes so that we could go brought on a bout of crying which continued in the car. I had to stop—-once at a major intersection—-three times and try to talk and calm down Charlie, who was almost in the back of our stationwagon at one point.

Jim and I think that Charlie’s having definitely entered puberty has a lot to do with these seemingly sudden outbursts of crying, anxiety, and head-swinging. I have been trying to recall my own adolescence, which was not happy; Jim has similar memories of being a miserable pre-teen. We know we’ve entered a new stage on the long road with Charlie. And when I think back to how I struggled to explain what I was feeling when I was 13, and think of how limited Charlie’s speech is, I hear how much he’s trying to say, even though the words aren’t there. I hope that we can sometimes pinpoint an actual reason for why Charlie is upset; I know that too often we may not, and we have to keep listening and learning.

The ABC News suggests that autism is a “label” better lost and one certainly feels some relief to find out the reason for a child’s illness. But: In the very recent past—sadly and terribly—a local mother here in New Jersey killed her middle-school son, who had been recently diagnosed with epilepsy. Families need to know that there is a lot of help and support for children with special needs and/or serious health issues and that there much that can be done.

And that, any label is just a label, and that it’s just the first step in trying to figure out how best to truly help one’s child.

Researchers at Adelaide’s Women’s & Children’s Hospital and the University of Adelaide, Australia, have found that a mutant gene causes epilepsy and intellectual disabilities specific to women. As noted in Science Daily, the study links a “large family of genes known as protocadherins with a condition known as ‘epilepsy and mental retardation limited to females’ (EFMR).” EFMR is described as “relatively uncommon” and also hereditary,

…….with successive generations of women affected. In just one of seven families studied across the world, 23 women were affected by the disorder across five generations. This discovery will now enable such families to benefit from genetic counselling, including screening for the genetic mutation at pregnancy.

“This is the first time this type of gene has been found to be involved in epilepsy,” Dr [Leanne] Dibbens [one of the leaders of the study] says.

“One of the most important discoveries we’ve made is that women in families affected by EFMR carry both a ‘good’ gene and a ‘bad’ (mutated) gene, while the men carry only the bad gene. For some reason, the men remain unaffected by the condition,” Dr Dibbens says.

“We suspect this may have something to do with the male Y chromosome, but more research will be needed to find out exactly how or why.”

Of course, epilepsy and intellectual disabilities are not found in all autistic women, but these are among the co-morbid conditions that can occur with autism. Dibbens will be continuing her research by studying “larger groups of patients with epilepsy, intellectual disability, and a number of the females affected in these families have autistic features and obsessive features,” as she notes in a May 12th interview with The World Today.

The study is published in Nature Genetics.