Tuesday, April 27, 2021

Modified Atkins diet for the treatment of epileptic spasms refractory to hormonal therapy

Sharma S, Goel S, Kapoor D, et al. Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial. Journal of Child Neurology. April 2021. doi:10.1177/08830738211004747



We aimed to evaluate the efficacy of the modified Atkins diet in children with epileptic spasms who had failed hormonal therapy.


Children aged 9 months to 3 years having daily epileptic spasms despite a trial of ACTH or oral prednisolone and 1 additional anticonvulsant medication were enrolled. Children were randomly assigned to receive the modified Atkins diet either immediately or after a delay of 4 weeks. The ongoing anticonvulsant medications were continued unchanged. The primary outcome variable was the proportion of children who achieved spasm freedom as per parental reports at 4 weeks. Secondary outcomes included time to spasm cessation, proportion of children with electroclinical remission, the proportion of children with >50% reduction of spasms at 4 weeks, and adverse effects of the diet. (ClinicalTrials.gov Identifier: NCT03807141). 


A total of 91 children were enrolled in the study; 46 in the diet group and 45 in the control group. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤ .001). The median time to achieve spasm cessation was 10 days (interquartile range 9-20). Nine of these had resolution of hypsarrhythmia on electroencephalography (EEG). Thirty (65.2%) in the diet group had >50% reduction in spasms, compared with none in the control group (P < .001). The most common side effect was constipation, noted in 34.8% of the children. 


The modified Atkins diet was found to be effective and well tolerated in children with epileptic spasms refractory to hormonal therapy.

Courtesy of:  https://www.mdlinx.com/journal-summary/evaluation-of-the-modified-atkins-diet-for-the-treatment-of-epileptic-spasms-refractory-to-hormonal/3B2CTUOHgbiAZf1vGkp3WS

Monday, April 12, 2021

Mosaic embryo

My husband and I were sitting in an Upper East Side office with deep-toned velvet couches and fluffy throw pillows, surrounded by photos of smiling babies, as the fertility doctor gave his spiel. He told us that after age 35, a woman’s chances of getting pregnant drop. Older women produce few normal embryos even with fertility treatment. But we’d have a healthy baby in our arms within a year — if we tested the embryos. 

By testing the chromosomes in my embryos, he said, we could weed out the abnormal embryos that may lead to miscarriage or a child with disabilities and only use viable ones. 

I’ve always been a late bloomer — I met my husband at 37 and married at 39. I was in good health but pushing 40, with diminishing egg count and quality. After six months of trying to conceive on our own, we wanted all the help we could get. My husband and I jumped at the embryo testing suggestion. 

After two long rounds of in vitro fertilization, we had five embryos, but the genetic testing deemed four of them “abnormal,” meaning they contained extra or missing chromosomes. Our fifth embryo, a girl, was what our genetic counselor called “mosaic,” meaning it had both abnormal and normal cells. 

Starting in the late 1990s, doctors testing fertilized eggs classified them as normal or abnormal, then added the classification “mosaic” in 2015. Mosaic embryos can be either low- or high-level, depending on the number of abnormal cells. Twenty percent of tested embryos are mosaic. 

Ours was a low-level mosaic embryo, with a few cells having an extra 22nd chromosome. Scientists are still trying to understand mosaicism, but this meant our embryo could be normal and lead to a healthy baby; she could have genetic abnormalities that would lead to miscarriage; or she could be born with congenital heart defects, asymmetrical development (meaning one side of her body could look like it was melting while the opposite side looked normal) or other disabilities that would cause her to use a wheelchair for life. It was like rolling the dice, except for someone you’ve never met.

It turns out there are a lot of online communities for mosaic kids and their families, including one on Facebook dedicated specifically to mosaics with an extra 22nd chromosome. Some adults lived normal lives and only find they have mosaic +22 later in life. Some women who were pregnant with babies with mosaic +22 miscarried. Children — ranging from newborns to young adults — had varying developmental challenges. 

What scared me most was that in girls, the extra 22nd chromosome could cause infertility. I felt selfish for wanting her so desperately that I would allow her into the world without this same opportunity. 

We had to make a fast choice: do a third cycle of I.V.F., hoping to get a normal embryo, or risk transferring the mosaic. Should we first try the mosaic embryo or risk having more nonviable embryos to agonize over? Because of the risks to the fetus and the developmental challenges our baby might face, the genetic counselor advised us to not transfer…

It was a lot to take in. I wasn’t scared that my life would be curtailed if I brought up a child with special needs — I was ready to dedicate myself to a child. But I worried that my wanting a child was blinding me to some of my potential shortcomings. Was I capable of giving up everything to concentrate on this person who would need me in ways I couldn’t even fathom yet? I was terrified that I couldn’t handle having a child with special needs and would take it out on her…

A recently published study of 1,000 mosaic embryos found those that progressed into a late-term pregnancy and full term birth had similar odds of being born without any discernible genetic differences to a normal embryo. But there were no guarantees. 

I didn’t want to try another I.V.F. cycle. In late February 2020, we decided to transfer the embryo into my uterus — just in time for New York City to shut down during the pandemic.

Five months later, I got a call from a physician who was filling in for my doctor; she canceled my appointment, claiming she was uncomfortable transferring a mosaic embryo. I was livid and overcome with grief. 

“The larger question that emerges with embryo testing is who gets to take on the risk of possibly bringing a child with potential disabilities into the world,” Dr. Taylor [Dr. Hugh Taylor, chairman of the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine]  said. “The decision should not be left to physicians. Patients should be given the freedom to decide, and properly counseled in cases where there are abnormalities that will inevitably lead to death.” 

Parents I had met online described wheeling or driving their frozen abnormal and mosaic embryos in unwieldy metal tanks to other clinics when their physicians refused to transfer. Fortunately, my regular doctor came back and scheduled a new appointment for the following month…

At three months, my doctor recommended a blood test that checked the baby’s DNA fragments in my blood to see if she was at risk for genetic abnormalities. At this point, my husband and I had begun to notice families in the dog park whose children had genetic disabilities. We quietly found acceptance that we would add variety to the families in our community and decided that we wouldn’t terminate the baby — no matter the result. 

They came back as normal. But like embryo testing, the blood test couldn’t diagnose a fetus’s genetic condition with certainty. Our doctor offered a more accurate amniocentesis test, but we had already made our decision. I decided to leave it there.

Now, during ultrasounds, our daughter hides her face behind her hands or presses hard against the placenta, as if asking us to let her grow in privacy. The last time I glimpsed her full profile, at five months gestation, her nose, long and sharp, was prominent and unmistakable. I wondered if it was one of the characteristics of the extra 22nd chromosome or if she’d simply inherited my husband’s nose. As my due date draws nearer, her genetic profile is less of a concern. I’m thrilled we’ve made it this far.



Sunday, April 4, 2021

The world's most expensive drug.

For the first few months of her life, Ayah Lundt was the picture of health. 

Born in January last year at a whopping 8.3 pounds, the bubbly baby girl with dark curls and bright brown eyes hit all her developmental milestones. 

By six months, she was crawling and trying new foods. Bananas and mushy broccoli were her favorites. Avocados, not so much. 

Then at nine months, her progress suddenly reversed. She could not lift her head while lying down, sit on her own or clap -- all things she'd excitedly done before. Her legs caved when she tried to crawl or stand. The key red flag came when she was unable to eat oatmeal with a spoon -- something she'd done numerous times. 

For a baby who loves her food, that was especially worrisome, her mother, Mary Mithika, told CNN by phone from their home in Bornholm, Denmark. 

Ayah was diagnosed with spinal muscular atrophy, a genetic disease found in one in 10,000 children born worldwide. She's now 14 months old and her parents are in a race against time to raise $2 million for a one-time, potentially life-saving treatment before she turns 2. 

The treatment is called Zolgensma. At $2.1 million a dose, it's referred to as the world's most expensive drug. 

"I think about the cost every day, and it weighs me down," Mithika said through tears before taking a break to compose herself. "And then I look at Ayah and see her getting worse. As a parent, what would you do if you knew there's something out there that can save your child?"…

Zolgensma, the gene therapy treatment, is not a guaranteed cure. Ayah's mother says she will never walk again. But a one-time intravenous dose delivers a fully functional copy of the gene into the target nerve cells, altering the child's biology and improving muscle movement and function.

The drug is not approved under universal health care in Denmark, the small Scandinavian nation of about 6 million people. So Ayah's parents are raising money to get her treated in the United States, where Zolgensma was approved in 2019 for use on children under age 2.

They've started talks with Boston Children's Hospital to get her treated there once they've raised enough money for the drug and the additional costs of tests and doctor visits in the US.

The race to get the funds has spanned continents. Mithika, Ayah's mom, is from Kenya while her husband, Frank Lundt, is Danish. Friends and others from their respective homelands have helped by organizing fundraisers. But in a year marked by a pandemic and economic hardships, the family is struggling to meet their goal before Ayah turns 2.

As of late March they had only raised about $60,000.

"We just want what every parent wants -- the best for their child," Lundt said. Ayah has one other sibling, Amira, who's 2…

"All we heard from the doctor was SMA, SMA," she said. "We had so many questions. We went on the internet to find out how bad it was. We called doctors we knew. We just wanted to find out as much as we could."

A week later, Ayah's doctor started her on medication approved in Denmark. But her parents said it hasn't helped much.

The drug's maker says its high cost is based on its value

There have been numerous cases of children showing immediate improvement after getting Zolgensma.

"The potential for gene therapy products to change the lives of those patients who may have faced a terminal condition, or worse, death, provides hope for the future," the FDA wrote in its approval letter. "Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood."

But why is the drug so expensive?

Dave Lennon, president of Novartis Gene Therapies, the Illinois company which developed Zolgensma, says the treatment's price is relative to the value it brings to the health care system -- and the cost of long-term care for children with SMA.

"Treating and caring for patients with SMA can cost up to $6 million in the first 10 years of a patient's life," he told CNN.

The therapy is approved for use in at least 35 countries. But in Denmark, the Danish Medicines Council is assessing whether its cost should be reimbursed under the country's universal health care system.

"Zolgensma received conditional approval in the EU in May 2020 for specific patients with SMA," Lennon said. "We are working closely with the Danish authorities as they assess whether Zolgensma should be reimbursed as a treatment for SMA."

Last year, Novartis launched a lottery-style program to provide the treatment for free to SMA patients under age 2. It has since allocated 100 free doses, and plans to provide a similar number worldwide this year. To prioritize those with the greatest need, the company says it excludes patients from countries -- including those in the EU -- where the drug is approved.

Because Ayah's parents are not eligible for the lottery program, they are pinning their hopes on Denmark agreeing to cover the cost of Zolgensma -- or raising the $2.1 million themselves.

In the family home, a normal day starts with Ayah getting breathing treatments twice a day. Her parents use continuous positive airway pressure, known informally as a CPAP machine, as a preventative form of therapy on her lungs, her father said.

Ayah's not a fan of the treatment. To calm her down, her mother softly sings "You Are My Sunshine" as she puts the breathing apparatus over her daughter's nose and mouth.

Ayah also gets a different medicine via a lumbar puncture every few months. They also try to do activities, such as crawling, to strengthen her little muscles.

"She's like a four-month-old trapped in a 14-month-old's body," Mithika said.

In the months since her diagnosis, Ayah's symptoms have worsened, leaving her unable to sit on her own, lift her head while lying down or bear weight on her legs. She uses a small green wheelchair with straps to keep her safe.

"She gets frustrated she cannot move. When her older sister dances around her, she tries to join her from the wheelchair but she can't," Mithika said. "Every patient is different. But in just the last few weeks, she's deteriorated so much."

The setbacks haven't sapped Lundt's and Mithika's determination to save their child. They've launched a social media campaign dubbed "Friends of Little Ayah," where they share videos of her progress and urge their followers to tag anyone who can help donate via various platforms, such as this GoFundMe.

In the videos Ayah sits in her wheelchair, blows kisses and says "tak." It's Danish for "thanks."


Thursday, April 1, 2021

Infanticide vs. inherited cardiac arrhythmias 2

"Manipulative" is how prison officers once described Kathleen Megan Folbigg, the convicted serial baby killer who has just cost the state of NSW millions trying - and failing - to prove her innocence.

Behind bars in the country's toughest maximum security women's prison, Folbigg would manipulate other female inmates and try mental tricks with the prison officers.

As Australia's worst female serial killer, and a killer of babies, Folbigg endured a status as the most reviled type of offender and always claimed "I didn't do it".

Unsurprisingly, behind bars this familiar assertion doesn't cut the mustard.

But on the outside, Folbigg managed to convince swathes of lawyers, scientists and doctors that she really didn't kill her four infant children over the space of a decade.

In perhaps her most manipulative act to date, Folbigg has managed to put whole factions of the legal fraternity at loggerheads.

But on Wednesday, the NSW Court of Appeal found that "no error of law" had been made by the 2019 inquiry which found Folbigg's conviction 18 years ago had been not only correct, but reinforced.

Now it is likely the 53-year-old prison inmate will remain behind bars until her 2028 release.

And she will walk out of prison only as a paroled criminal, not the cruelly wronged saint her supporters believe her to be.

There's no happy ending for Kathleen Folbigg's violent and troubled life, which began as a baby when her father murdered her mother by stabbing her in the street.

And there's no pretending that the sinister words in Folbigg's secret diaries weren't about her culpability in murdering three of her children and unlawfully killing the other.

The diaries, which Folbigg claimed in2019 were only about her struggling to cope with motherhood, included entries which said her infant daughter made her "snap her cog".

Take the entry scrawled in one of the diaries, which Folbigg had kept since she was young in exercise books, one of which Folbigg had taken the trouble to cover with a picture of a teddy bear.

It is dated November 9, 1997 and, Folbigg writes, it is a Sunday night at 8pm.

By this time Kathleen had given birth to four children with husband Craig Folbigg.

The first three were already dead: Caleb, aged 19 days, Patrick, eight months, then Sarah, 10 months and the fourth, Laura, was just three months old.

Folbigg writes: "Craig was pretty drunk Friday nite. In his drunken stupor he admitted that his (sic) not really happy.

"There' a problem with his security level with me. He has a morbid fear about Laura.

"Well I know there's nothing wrong with her.

"Nothing out of the ordinary anyway. Because it was me not them.

"Think I can handle her fits of crying better than I did with Sarah …

"With Sarah, all I wanted was for her to shut up. And one day she did."

In another entry, Folbigg wrote four years after Sarah's death that "I miss her … but I am not sad that Laura is here and she isn't."

Sixteen months after this, on March 1, 1999, Laura Elizabeth Folbigg died, as the other children had, while home alone with their mother.

Kathleen called an ambulance and performed CPR on the toddler until paramedics arrived, but the 19-month-old couldn't be saved.

Laura was too old to have suffered Sudden Infant Death Syndrome (SIDS) and a GP who attended the scene informed police.

Police would seize her diaries and find Folbigg's private musings.

These included the 1996 entry made after the deaths of her first three children, in which she wrote, "obviously, I am my father's daughter".

Kathleen Folbigg was born illegitimately on June 14, 1967 to Kathleen May Donovan and immigrant hoist driver and petty criminal, Thomas Jack "Taffy" Britton.

When she was 18 months old, Britton stabbed Ms Donovan 24 times in a street in the inner-western Sydney suburb of Annandale, and she died before an ambulance arrived.

Britton would serve 15 years in prison and then be deported to Britain.

Kathleen was made a ward of the state after appearing in Minda Children's Court as a "neglected destitute child".

She was fostered out to relatives, but they had difficulties with her, complaining that aged between two and three she had severe temper tantrums, aggression and crying fits.

According to report by forensic psychiatrist Michael Diamond, the foster relatives made distressing observations about young Kathleen.

Dr Diamond assessed Folbigg and examined her historical case file specifically for the special judicial inquiry sparked by her supporters attempting to prove her innocence.

In his report, which was made public online in May 2019, the relatives said she had "a preoccupation with sexual problems".

The report said a medical officer considered it likely the girl had been sexually abused by her father during infancy.

The situation further deteriorated after Kathleen turned three years old, and it was concluded "she was a very disturbed little girl" who "became aggressive" towards other children.

She was fostered out, aged three, as a child with specific needs to the Marlborough family at Kotara near Newcastle.

She later had no memory of the violent and turbulent times before her mother's murder, but official files refer to her "catastrophic early life experiences and disruption of attachments within a violent and abusive family of origin".

In her foster family, little Kathy had a much older brother and sister, and a mother she claimed was cold and controlling, Dr Diamond's report said.

She was very close to the sister, who would later tell Folbigg's trial that Kathleen was "capable of looking someone in the eye and lying outright to them".

Kathleen's child welfare services file also noted she had "problematic sexualised behaviours as a very young child" and "difficulty regarding her intellectual functioning".

Young Kathleen would be "domineering towards the other children" fostered by Marlboroughs and "difficult" when they were around.

Kathleen was told she had been "chosen" by the Marlboroughs and was doted upon by their biological children.

She was a loner at school and preferred playing with boys rather than girls, felt socially isolated from others and trusted no-one.

At the age of 15 she had a boyfriend and via him was able to make friendships with girls for the first time.

Due to a breakdown with her relationship with her mother, she left school six months before sitting her HSC.

At the age of 18 she met Craig Folbigg, who was five years older than her, on a disco dance floor.

They married in 1988, when she was 20, and the couple set up home in a Newcastle suburb.

Craig worked as a clerk for the mining and steel giant BHP and Kathleen worked as a waitress for an Indian restaurant.

Craig came from a large family and expected they would have children.

Kathleen had no trouble conceiving their first child, Caleb Gibson Folbigg.

After he died aged 19 days in February 20, 1989, they placed a death notice in the paper which said "Take care of him Nanny".

It was a reference to the fact he'd be joining his late grandmother, Esme Folbigg, in the afterworld.

Kathleen fell pregnant with her second child in September the same year and after Patrick was born in June 1990, Craig took three months off work to help care for him.

Aged four months, Patrick had what Kathleen described as a "terrifying" incident.

After putting his son to bed, Craig woke to his wife screaming by the baby's cot because she had found him "limp".

He would later be diagnosed with epilepsy but what had caused it was unexplained.

Four months later, Kathleen phoned Craig to say "it's happening again" after Patrick had died, from a seizure.

It was February 13, 1991.

Dr Diamond's report says Folbigg spoke of her devastation after finding Craig in a romantic clinch in their home with a friend of hers, who was drunk.

She felt "rejection … abandonment and betrayal". Craig left BHP and started selling cars.

Kathleen started work in a babywear store, BabyCo, and became pregnant with her third child, although she was depressed and anxious.

After Sarah Kathleen Folbigg's birth on October 14, 1992, Kathleen had trouble bonding with the child and was full of fear.

Sarah died aged 10 months, on August 30, 1993 and, thereafter, Craig Folbigg became deeply depressed.

He wanted to bring the ashes of the three children home and after arguing against it, Kathleen agreed.

Their relationship reached "rock bottom", but they moved house, made amends and again, Kathleen became pregnant.

Craig sought out experts to advise them on the safety measures of having a healthy baby.

According to police statements by Craig Folbigg cited in Dr Diamond's report, he described his wife's response to the deaths of their children as "relatively detached and disengaged".

This came after "acute distress" at the time of their deaths.

Laura was born on August 7, 1997, a blonde baby with a cherubic face.

Kathleen wrote in her diary: "I think Laura is beautiful compared to Sarah … her slight difference in looks gives her a beautiful face … gorgeous and beautiful, well so far anyway.

"Looking at the video Sarah was boyish looking. Laura has definitely feminine features.

"They are chalk and cheese. And truthfully, just as well.

"Wouldn't have handled another one like Sarah."

On March 1, 1999, Laura Folbigg died after what Kathleen described was a coughing fit the little girl had while in bed.

After a suspicious GP called police, what would become a two-year investigation began.

They placed listening devices (LDs) into the Folbigg's' Singleton home.

They took in Kathleen Folbigg for questioning and began interviewing friends and relatives.

Detectives would later say the LDs recorded Kathleen Folbigg walking around the home "basically rehearsing her evidence for court".

She was heard practising "whether she cried at the right occasions" and gave the "right" evidence.

In April 2001, police arrested Kathleen Folbigg and charged her with the murders of her four children.

The deaths of the children had been passed off as SIDS and epilepsy, but pathology experts from the UK and US consulted by the police said the children had all been smothered by their mother.

Kathleen Folbigg was the only person to locate the dead children, although Craig Folbigg was present in the house and woken by his wife's screams at the death of Caleb.

The same happened on the first occasion when Patrick "died", only to be resuscitated and then die months later.

None of the children had coexisted with any of their siblings.

Folbigg had never thought her diaries would see the light of day, writing in one of them, "tell you what don't think anyone could read this and find out all my secrets. I write like a 5-year-old."

Folbigg pleaded not guilty, and was eventually granted bail while she awaited trial and was reportedly confident she would be acquitted.

However, in 2003 she was convicted of the manslaughter of Caleb, and of the murders of Patrick, Sarah and Laura between 1989 and 1999.

She is serving a maximum 30 years and is 18 years into her 25-year minimum jail term, with an earliest possible release date of 2028. 

In prison, Folbigg was at first held in a segregated protection area, because her crimes meant she was in serious danger of being hurt or killed by other women inmates.

Baby killing is regarded as "the lowest of the low" and Folbigg copped abuse, threats and physical assaults.

Eventually she worked in prison jobs, and with some inmates became something of an inmate "den mother".

She continued to claim her innocence and by 2010 a group began mounting a petition to free Folbigg.

Eventually, more than 90 eminent persons including respected scientists would sign a document which said "no reasonable person" could accept she was guilty if presented with the facts.

They rejected the findings of Folbigg's trial and scoffed at then crown prosecutor Mark Tedeschi's case, saying circumstantial evidence wasn't a proper argument.

Circumstantial evidence cases are a legitimate and legal part of the NSW criminal justice system.

The petition claims a genetic mutation called CALM2 G114R was found in Sarah and Laura's DNA, inherited from their mother, which can cause sudden cardiac arrest in infants.

Eventually, the Justice for Kathleen Folbigg petition led to the special inquiry in 2019, presided over by former NSW district court chief judge Reginald Blanch, QC.

Judge Blanch found significant investigations had failed to find a reasonable natural explanation for any of the Folbigg children's deaths.

He instead concluded that Folbigg's explanations before the inquiry made "her guilt of these offences even more certain"

Folbigg appealed the finding in the NSW Court of Appeal, claiming Blanch had failed in his obligation to conduct an inquiry about the potential for the deaths to have been natural.

In dismissing this appeal on Wednesday, the NSW Court of Appeal ordered Folbigg pay for the cost of its two-day hearing.

Folbigg's supporters now want NSW Governor Margaret Beazley to pardon her and immediately release her from jail, to end the "miscarriage of justice'' they say Folbigg has suffered.

In 2017, Folbigg was convicted of bashing another inmate inside Silverwater Women's Correctional Centre in a fight over a toaster.

She punched the inmate in the stomach for carrying the toaster into a cell - forbidden, as it is a fire hazard, telling the inmate, "You're not allowed to take the f***ing toaster in the room". 

Folbigg immediately asked for CCTV footage of the incident.

Barrister Isabel Reed told the NSW District Court that this was evidence of Folbigg's instant "shock, horror and embarrassment" after the assault.

But Judge Tanya Bright rejected this and Folbigg's appeal against the severity of a four month sentence imposed for the assault.

Judge Bright said she accepted that Folbigg had an "exemplary record" since her incarceration in 2003, but that she had a very long way to go until her maximum sentence expired in 2033.