Monday, January 29, 2024

CRELD1 mutation

Colton was born on the 7th June 2021 at 35 weeks after a complicated pregnancy. This included diagnosis of absent ductus venosus at 20 weeks gestation, followed by maternal bedrest, and 3x/week ultrasounds, BPPs and NSTs, partial placental abruption and ultimately too low of fluid triggering emergency c-section.

Colton spent 30 days in NICU with respiratory and feeding distress. After NICU discharge things at home were going well until at around 9-12 weeks old he began having difficulty eating. Colton ultimately had spent 157 days in the hospital during his first year of life.​

Colton became very ill with Respiratory Syncytial Virus (RSV) in October 2021 (when he was 4 months old), where he spent a week in the ICU due to complications. Two days after our return home we noticed Colton starting to do these “twitches”. We immediately brought him back to hospital where he was hooked up to an electroencephalogram (EEG). After a 24 hour scan the neurologist told us that it was likely just developmental “hiccups”. We were sent home with a suggested follow up the following month.

Colton's twitches increased from 3-5 times a day to over a hundred. In our follow up with a neurologist they told us that he would grow out of the twitches and likely something bigger is the issue. We were disappointed in the response because it just didn’t seem right, especially as our other children never presented that way. These twitches continued to progress until our worst day. At the end of November 2021 our whole family had Covid, including Colton. Surprisingly though, Colton had the least amount of symptoms.

As my husband Paul and I took turns taking naps and watching the kids, Colton began to have his twitches, but this time they became very violent then Colton went limp and blue in Paul’s arms. It took an ambulance over 30 minutes to get to our home. Once Colton was hooked up to oxygen his colour slowly returned. Once hooked up to another EEG we got our devastating diagnosis. Not only was Colton having a seizure, his EEG was significantly worse than it was just a month and a half prior. The same doctor who told us not to worry came to tell us that he has infantile spasms and to prepare for a difficult life ahead.

We went months trying to figure out the right medications, all while Colton fought illness after illness. Colton's status seizures always came in conjunction with a respiratory illness. After getting the rhinovirus (common cold) that sent him to month-long hospital stays and several intubations. We demanded for more tests to be done to better understand what was going on.​

Colton was diagnosed with CRELD1 in February 2022. Colton's diagnoses have accumulated over the last year and include infantile spasms/ epilepsy, status epileptics, adrenal insufficiency, failure to thrive, low tone, global developmental delay, moderate to severe bilateral neural hearing loss, G-J placement and eats through J port, submucosal cleft palate, immature eye development, and acute respiratory distress/failure.

Colton had a port-a-catheter placed at 12 months due to difficult IV placements. He has been admitted to PICU several times and has had three emergency intubations for both seizure and pulmonary causes and several respiratory illnesses over his first year of life.​

Due to Colton picking up so many illnesses, he had an immunology panel test done to better understand the level of his immune function. Colton’s IGG and IGB numbers were found to be extremely low - basically his body doesn’t remember when he’s had an illness and so he can’t build immunity because he can’t keep those good cells around. Colton was started on Intravenous Immunoglobulin (IVIg) infusions once a month to help boost his immune system. It's very early days, but Colton has had a positive response to the infusions, in terms of more energy and alertness. We are hoping to see more positive results for Colton with his IGG levels as the infusions continue.

Despite this list of difficulties, Colton is the strongest, most resilient boy we’ve ever met. He smiles and coos, loves to hold our hands and be snuggled. He is adored by his three older siblings. There is no greater love or commitment to creating a pleasurable and positive atmosphere by our family. He - along with the other CRELD1 Warriors - bring absolute joy to our lives. This has been an incredibly difficult year and we couldn’t have done it without the support of our other parents.

Colton's genetics results

Sequencing analysis has shown that Colton is heterozygous for two variants of uncertain significance in the CRELD1 gene. While the CRELD1 gene is typically associated with autosomal dominant inheritance, autosomal recessive inheritance has also been suggested.​

c.959del:p.(GIn320Argfs*25) in exon 9 of the CRELD1 gene (NM_015513.4). The normal sequence with the base(s) that are altered in brackets is: AAGC[delA]GTGT​

The proband's father (GeneDx #2390779) is heterozygous for the p.(Q320Rfs*25) variant in the CRELD1 gene.

Identified in an individual with seizures who also harbored a second CRELD1 variant in published literature.

Frameshift variant predicted to result in protein truncation as the last 101 amino acids are lost and replaced with 24 incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein.

Observed in 84/282702 (0.0297%) alleles in large population cohorts (gnomAD)​

We interpret this as a Variant of Uncertain Significance.​

p.(Cys192Tyr) (TGT>TAT): c.575 G>A in exon 5 of the CRELD1 gene (NM_015513.4)​

The proband's mother (GeneDx #2390769) is heterozygous for the p.(C192Y) variant in the CRELD1 gene. The proband's father (GeneDx #2390779) does not harbor the p.(C192Y) variant in the CRELD1 gene.​

Identified in an individual with seizures who has also harbored a second CRELD1 variant in published literature 

Observed with a likely pathogenic variant on the opposite allele (in trans) in a patient with seizures, poor vision, and hypotonia referred for genetic testing at GeneDx

Observed in homozygous state in a patient referred for genetic testing at GeneDx with failure to thrive, Microcephaly, and seizures and not observed in homozygous state in controls

In silico analysis supports that this missense variant has a deleterious effect on protein structure/ function

Observed in 52/282700 (0.0184%) alleles in large population cohorts (gnomAD)

We interpret this as a Variant of Uncertain Significance.

Jeffries L, Mis EK, McWalter K, Donkervoort S, Brodsky NN, Carpier JM, Ji W, Ionita C, Roy B, Morrow JS, Darbinyan A, Iyer K, Aul RB, Banka S, Chao KR, Cobbold L, Cohen S, Custodio HM, Drummond-Borg M, Elmslie F, Finanger E, Hainline BE, Helbig I, Hewson S, Hu Y, Jackson A, Josifova D, Konstantino M, Leach ME, Mak B, McCormick D, McGee E, Nelson S, Nguyen J, Nugent K, Ortega L, Goodkin HP, Roeder E, Roy S, Sapp K, Saade D, Sisodiya SM, Stals K, Towner S, Wilson W; Deciphering Developmental Disorders; Genomics England Research Consortium; Undiagnosed Disease Network; Khokha MK, Bönnemann CG, Lucas CL, Lakhani SA. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections. Genet Med. 2023 Nov 7;26(2):101023. doi: 10.1016/j.gim.2023.101023. Epub ahead of print. PMID: 37947183.


Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors.

Conclusion: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1.

Friday, January 26, 2024

Neurofibromatosis and giant facial tumors


Hi,everyone amare's chemo medicine that he's been taking since 2012 in which is called rapamune & tamoxifen that he has been taking for about 2 years..we found out he no longer has to take those medications,but he's also started a new medicine called mekinist in which is for cancer patients.we were told by his neurologist in Birmingham al that this medicine has been proven to shrink the tumors in neurofibromatosis patients,so we started amare on this medicine on Wednesday January 27, hoping and praying that this chemo medicine has an dramatic positive change on amare's tumors,only god knows his pain inside,but as a loving and caring parent to amare,I know what he's been threw since the day he came into this world not knowing that the life ahead of him was going to be a great struggle,and I thank god for keeping him on this earth and allowing him to be this sweet,loving and friendly seven year old..he does not see himself any different from others,,but you can only imagine how many rude and ugly stairs that he gets out in public,not to mention the laughter..but threw it all he my son and I would not treat him any differently as I would any other's a lot to handle physically, spiritually, financially and verbally..I pray every waking moment that god heals him and for him to grow older to live the life that he's supposed to have..despite everything amare is always happy!!..and amare's condition requires all of my attention and as well many doctors visits..I admit I want to break down at times but then again ive have to stay strong as a im asking everyone to please keep amare and my family in your prayers.and if you could help in anyway,please do so..we need all the support & love that your willing to give..thank you

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Wednesday, January 24, 2024

Midaortic syndrome and renovascular hypertension in NF1

A mother and father are doing everything they can to help other families avoid the sorrow they went through in 2019 — and they are doing it all in their daughter's name.

Jessica and Dan Roomberg, from Lafayette Hill, Pennsylvania, launched the Magical Mila Foundation in honor of their daughter, Mila, who died from Neurofibromatosis (NF) type 1 when she was just over a year old.

When Mila was born on Sept. 16, 2017, the doctors discovered a heart murmur, which they said was not a concern and that it would go away within a year, Jessica Roomberg told Fox News Digital.

During the next few weeks following Mila's birth, Jessica Roomberg and her husband noticed some birthmark-looking patches on Mila's back, so they went to a pediatrician in the Philadelphia area to see what exactly this was.

The pediatrician they met with did not seem concerned about the patches — and told the couple to "just enjoy their time with her," Jessica Roomberg recalled.

"That raised an immediate red flag for me and Dan, so we just started googling everything … and Neurofibromatosis came up."

The parents went back to the pediatrician asking if she had this "on her radar" — but the doctor did not seem concerned.

The couple were still worried about what they'd found on their daughter's back, so they consulted with the genetics and dermatology teams at Children's Hospital of Philadelphia (CHOP).

After a geneticist examined Mila, the child was diagnosed with Neurofibromatosis type 1 (NF) – a genetic disorder that occurs in about one in every 3,000 live births, according to the Magical Mila Foundation's webpage.

"NF1 is characterized by multiple café au lait (light brown) skin spots ... Children with NF1 can have very mild to more severe manifestations. These include learning differences and delays, early puberty, hypertension, scoliosis and tumors. Some children develop tumors in the brain or on the optic nerve. These tumors are generally not cancerous, but they can cause significant health issues or vision impairment," the site continued.

Dan Roomberg said, "When you hear ‘genetic disease,’ you always think one of the parents has it or is a carrier."

He added, "But neither of us had heard of it [or] had it, so with her case, it was a spontaneous mutation."

After receiving the news, the parents were "totally crushed," but immediately began doing research on the disease and looking for the best care for their little girl, they said.

Mila was under baseline surveillance with the NF team at CHOP, so the team could keep regularly check in on her.

"At this point, Mila is going through life great. She is meeting all of her milestones," Jessica Roomberg commented.

"She was just such a joy. The sweetest girl in the world."

When Mila was 14 months old, the Roombergs took her into see doctors for a follow-up visit for the heart murmur that was present at her birth.

"How do we continue to parent Mila? How do we continue her legacy?"

The doctors determined the murmur was no longer there, but they said they needed more imaging because they saw something else, Jessica Roomberg stated.

"They left it at that, and we were just paralyzed," she added.

The family returned to the hospital the following Monday.

Mila received a sedated MRI — and the doctors were stunned at what they found.

Mila's blood pressure was reading 240/110 mmHg, the highest CHOP had ever seen for a child under age three, Dan and Jessica Roomberg noted.

Mila was quickly admitted and physicians began working to lower her blood pressure.

"The reason her blood pressure was so high was because she had a narrowing of her aorta," Jessica Roomberg said.

The point near her belly button was the size of a point on a pencil, she continued.

"All the blood in her body was trying to rush through this really, really tiny space, and it was causing her blood pressure to be astronomical and her heart to balloon," the mom said.

Mila and her parents were at CHOP for over five weeks when physicians finally diagnosed her with Midaortic Syndrome and Renovascular Hypertension — a very rare result of her having NF 1.

The Roombergs and their daughter were released from the hospital before Christmas, but would return each week.

"The plan was in the short term, medicine — and then, in the long term, until she was a little bit older and stronger like three or four years old, to do a major [vascular] surgery," Jessica Roomberg stated.

CHOP does not have pediatric vascular surgeons, so the hospital team shared Mila's case with specialists at the University of Michigan, she continued.

The doctors at CHOP notified the Roombergs that the medicine was not working, and that Mila was in need of emergency surgery in Michigan.

Mila underwent an eight-to-nine-hour revascularization surgery of her aorta and kidney arteries, Jessica Roomberg said.

The surgery was deemed a success, she added.

"The feeling of relief was amazing — however, we had a long road ahead."

After spending the evening by her side, the doctors told the Roombergs that something was wrong.

Mila was rushed into an emergency surgery but went into cardiac arrest during her time in the operating room.

She was put on life support, but the physicians did not see improvement.

They told the Roombergs, "It's time to say goodbye," Jessica Roomberg recalled.

"They turned everything off, and she passed away in our arms," said the heartbroken mom.

Jessica and Dan Roomberg remember going into "the deepest, darkest hole" after their daughter's passing.

They needed to find a new purpose in their life — and they wanted Mila to still be a part of it.

"We wanted to channel our grief into doing something. We needed things just to have scheduled on the calendar the next day to have a reason to get out of bed," Dan Roomberg shared.

Six weeks after Mila died, the Roombergs reconnected with her doctors at CHOP and told them they wanted to do something in her honor.

"How do we continue to parent Mila? How do we continue her legacy?" Jessica Roomberg said she and her husband asked themselves.

In May 2019, Dan and Jessica Roomberg brainstormed with the staff at CHOP. They came up with the angle of their foundation: blood pressure monitoring.

They wanted to come up with something that was specific to Mila's case, but could also impact the lives of children who had similar needs.

"There's a whole list of other genetic conditions that require children under three to have their blood pressure taken," Dan Roomberg said.

"BP [blood pressure] should be measured annually in children and adolescents ≥3 y of age," according to the American Academy of Pediatrics (AAP).

Jessica Roomberg noted that for children under the age of three who have health issues, blood pressure monitoring is required.

Along with the help of Dr. Kevin Meyers, director of the hypertension clinic at CHOP, and Dr. Rachel Hachen, medical director of the Neurofibromatosis program at CHOP, Dan and Jessica Roomberg created the "BP under 3."

"They are wanting to help kids who require a blood pressure measurement [to] get it taken and get it taken properly," Jessica Roomberg said.

"We are really proud of how far we've come, but we have so much to do."

A successful clinical trial was completed at CHOP in which a variety of blood pressure technology was used on children under three who needed a blood pressure measurement; it came up with an accurate reading of their blood pressure.

The technology that is being used measures the blood pressure on the way up, so that it is less painful and stressful for the child, the Roombergs said.

The Magical Mila Foundation funded educational trainings for the staff at CHOP on how to obtain accurate readings on children who are under three, and they've already seen a 200% increase in accurate readings, Dan Roomberg shared.

They just finished a video project with the AAP and the CHOP team sharing Mila's story and the importance of accurate blood pressured on children under three that will now be seen by all providers who are part of the AAP.

"We are really proud of how far we've come, but we have so much to do," Jessica Roomberg continued.

"Nothing will ever hold us back from fighting for her," she added.

The Magical Mila Foundation not only allows the Roombergs to help kids who are in need of pediatric care, but it also helps them feel attached to their daughter, they said.

"This is our way of always being able to parent Mila," Dan Roomberg said.

Since the foundation's creation in 2019, the organization has raised over $500,000 for CHOP.

"Even though she has been gone a lot longer than she was here, we still do things for her every single day," Jessica Roomberg shared.

"She is the heartbeat of our family," Dan Roomberg added.

To learn more about Mila's story and about the Magical Mila Foundation, check out

Dana-Farber corrections/retractions

Dana-Farber expands studies to be retracted to 6, plus 31 to be corrected over mishandled data

A review of alleged data manipulation in studies involving four top scientists at Dana-Farber Cancer Institute has led to plans to retract six papers and correct 31 manuscripts, the institute confirmed on Monday.

The news comes as the famed cancer research and treatment center is now reviewing scores of studies co-authored by some of its leading researchers, including CEO Laurie Glimcher, COO William Hahn, and prominent scientists Irene Ghobrial and Kenneth Anderson.

Dana-Farber confirmed the retractions and corrections in progress in an email to STAT, which reported on Friday that researchers were preparing to retract one paper and correct others. The higher numbers were first reported by the Wall Street Journal, which also reported that Dana-Farber concluded three papers needed no corrective action. But the institute did not say precisely which studies would be retracted or corrected.

“Correcting the scientific record is a common practice of institutions with strong research integrity processes at which basic research is conducted. Some of the potential errors that blogger Sholto David flagged had come up in our ongoing reviews,” Dana-Farber told STAT.

During a conversation with STAT last week, the institute’s research integrity officer, Barrett Rollins, said that all of the cases that have been assessed thus far appear “credible,” a term meaning the allegation carried enough scientific merit to warrant more investigation. STAT did not receive immediate clarification regarding whether Dana-Farber had recently decided to retract or correct additional papers.

The institute’s review of past research involving these four scientists grew after David, a molecular biologist who blogs about research integrity, wrote a Jan. 2 post flagging issues with dozens of studies and the Harvard Crimson covered it. The cancer institute, a teaching affiliate of Harvard Medical School, noted in a statement that Dana-Farber had taken “prompt and decisive action” in many of the cases flagged by David for which data now under scrutiny were generated in a Dana-Farber lab.

The corrections in progress include correction submissions that are currently being prepared for submission, awaiting acceptance from journals, and corrections that journals have already accepted. An additional manuscript with a potential error is still under examination, according to Dana-Farber.

Moving to correct errors and retract papers with falsified or incorrect data is the first step to restoring trust in a researcher and their reputation in the face of misconduct allegations, said Steven Salzberg, a computational biologist at Johns Hopkins University who spoke on scientific misconduct more generally but not these specific cases.

“I know professors who found out [scientific misconduct] was happening in their labs and retracted the papers,” he said. “It’s a black mark on your record, but if you’re a scientist with integrity then that’s what you do and you recover from it.”


Batten disease

For the three out of every 100,000 children who are born with Batten disease, the diagnosis is one of the most devastating that a family can receive.

Emily Blackburn, 32, found out in March 2023 that her 7-year-old son, Grayson Naff, has the rare, genetic, fatal disorder.

Now, the Ohio family is faced with the harsh reality that Naff will ultimately lose his sight, then his cognitive abilities and motor skills.

The life expectancy for children with Batten disease is usually five or six years after symptoms begin.

Shortly before her son started first grade, Blackburn took him to the eye doctor for what she thought was a routine visual exam.

She’d noticed it was more difficult for him to see the TV screen, so she assumed he needed glasses.

During the exam, the doctor noticed something concerning in Naff's retina and sent the family to a retina specialist in Cincinnati.

"At first, they thought it was a disease called Stargardt, which causes you lose your central vision and become legally blind," Blackburn told Fox News Digital in an interview.

That was heartbreaking in itself, she said — "enough to send you into a spiral" — but things got even worse when the doctors decided to do some genetic testing to confirm the diagnosis.

It turned out the first diagnosis was incorrect. And with tears in their eyes, the geneticists informed Blackburn during a Zoom call that her son actually had Batten disease.

"We went from thinking our son would become legally blind to finding out that he has this fatal disease with no cure," Blackburn said. "I really don't have words for it. It's unbelievable. It’s soul-crushing."

What is Batten disease?

A fatal genetic disorder, Batten disease interferes with the body's ability to eliminate cellular waste, per Cleveland Clinic's website.

As the excess lipids and proteins build up, they cause vision loss, seizures, cognitive decline, impaired mobility and death.

There is currently no cure for the disorder.

"It's unbelievable. It’s soul-crushing."

Batten disease is usually diagnosed through genetic testing, when an abnormal change is found in one of the several genes associated with the disease, noted Christelle Moufawad El Achkar, M.D., a neurologist in the Division of Epilepsy and Clinical Neurophysiology at Boston Children's Hospital. (Achkar is not involved in Naff's care.)

There are 13 different types of Batten disease, each involving a different gene. Naff was diagnosed with CLN3.

"Within each gene, there can be different clinical subtypes with different ages of onset and severity, starting from infancy until adulthood," Moufawad El Achkar told Fox News Digital.

"This can make diagnosis harder, especially in the early stages of the disease."

Early diagnosis is very important, the doctor emphasized, especially because some types of disease can be slowed with therapies.

Initial symptoms of Batten include loss of balance, falls and slurring of speech.

Epilepsy or seizures can be an early sign in some subtypes, but might only happen later in the course of the disease for some patients, said Moufawad El Achkar.

Gradual loss of vision is seen in almost all cases.

"It is crucial to suspect and test for Batten disease in any child who has loss of skills, especially if accompanied by seizures, at any age," the doctor said.

As her son's vision had already declined considerably at the time of his diagnosis, it is now 20/200, which qualifies as legally blind, Blackburn shared.

Only Naff's vision has been impacted so far, but doctors have warned Blackburn of what’s to come over the next couple of years — including dementia, decline in motor skills and seizures.

As of now, Naff only knows about his vision struggles — Blackburn has not told him about the Batten disease diagnosis.

"We try to keep him as educated as we can on his vision while still allowing him to be the same little boy he is now," Blackburn told Fox News Digital.

"We feel like the weight of all the other symptoms is just too hard, too much for him to carry."

Naff still attends the same public school, where he works with a teacher for the visually impaired.

"We have amazing teachers and amazing friends in our community," Blackburn said.

Multidisciplinary care

Patients affected by Batten disease need a multidisciplinary team to help manage their symptoms and design a plan to provide the best quality of life possible, Moufawad El Achkar noted.

Naff’s primary care team is at Nationwide Children’s Hospital in Columbus, Ohio.

Twice a year, the family drives to the University of Iowa Hospitals & Clinics to see an eye doctor, who prescribes an experimental medicine to help preserve Naff's vision for as long as possible.

They also travel to Texas Children’s Hospital in Houston to see a neurologist.

Naff will have an EEG (electroencephalography) each year to monitor his brain waves for seizure activity.

He is currently taking a medication called Miglustat, which could help to ease or slow down symptoms. Although the drug is FDA-approved for another condition called Gaucher disease, it is not yet approved for Batten.

"Since it's not FDA approved, it has a hefty copay cost — if insurance doesn’t cover it, it’s about $100 a pill, or $9,000 a month," Blackburn said.

Through an initiative called Guiding Grayson, the family has held events to help raise money for Naff’s costly care.

"Having the support from our community and our friends has been one of the best things to come out of this," said Blackburn.

All the funds raised for Naff have gone toward the cost of the Miglustat.

"We feel like the weight of all the other symptoms is just too hard, too much for him to carry."

Blackburn, who used to work as a project manager, has opted not to return to a full-time job so she can take care of Naff and her younger son.

"There are a lot of unknowns and a lot of scary things, but we hope that the medication can hold off Grayson’s symptoms for as long as possible until there's a cure," she added.

Clinging to hope

Because each gene involved in the various types of Batten disease has a different mechanism, finding treatment for each one has been a very difficult process, noted Moufawad El Achkar.

"There have been some oral medications that over time might have shown some delay in the progression of the disease, but none have been shown to affect the course of the disease," she said.

Through an initiative called Guiding Grayson, the family has held fundraising events to help collect money for Naff’s costly care. (Emily Blackburn)

A drug called Cerliponase Alpha has been shown to significantly slow down symptoms of Batten disease type 2, noted Moufawad El Achkar.

Gene therapies have also been developed for some types and are in early clinical trial stages, but have not yet been administered in the U.S.

"Research is ongoing to look for therapies for virtually all of the subtypes, but most are at the pre-clinical stage at this time," said Moufawad El Achkar.

"A lot of strides have been made, but we need a lot more treatment options to be developed, tailored to each subtype, and we need them as soon as possible."

"Collaboration between scientists, medical teams and family associations all over the world is absolutely necessary to make any meaningful progress in treating these extremely rare disorders," the doctor added.

Blackburn said she is holding out hope for a cure in her son's lifetime.

"Scientists are working tirelessly to try to find a cure for this disease," she said. "It just takes a while for gene therapy to be approved, so that’s what is scary."

"One of our main goals is to raise awareness for research and funds for a cure — and just to let Grayson know how much we love him."

"Some days, I’m really hopeful and I feel like Grayson can beat this, and then some days it's just debilitating and gut-wrenching — it feels like we’re in a nightmare," Blackburn went on.

"One of our main goals is to raise awareness for research and to raise funds for a cure — and just to let Grayson know how much we love him."

Anyone can learn more about the family's struggle at

Monday, January 22, 2024

Ecchordosis physaliphora

Inspired by a patient

Ecchordosis physaliphora
Last revised by Yoshi Yu on 9 Nov 2023

Ecchordosis physaliphora is a congenital benign hamartomatous lesion derived from notochord remnants, usually located in the retroclival prepontine region, but can be found anywhere from the skull base to the sacrum.

There has been some controversy as to whether intradural chordoma and large ecchordosis physaliphora are different entities. Some authors (such as Wolfe et al.) proposed the name 'intradural chordoma' for all intradural notochordal remnant lesions. Others (such as Rodriguez et al.) proposed that all intradural notochordal remnant lesions should be called ecchordosis physaliphora, until chordoma are pathologically proven to arise from the intradural compartment. However, they are currently considered distinct pathologies with a common origin.
Clinical presentation

Unlike chordomas which are often symptomatic due to brainstem or cranial nerve compression, patients with ecchordosis physaliphora are usually asymptomatic. They are found in ~2% of autopsies.

Ecchordosis physaliphora arise from remaining notochord cells along the axis of the spine after embryogenesis. Unfortunately, ecchordosis physaliphora and chordoma are histologically indistinguishable, other than by examining the margins, the latter demonstrating infiltrative growth.
Radiographic features


CT is generally not sensitive for such lesions, mainly because of posterior fossa artifacts and the near CSF density of the mass. The bony clival defect is, however, visible as a well-demarcated smoothly corticated region, without aggressive features.

Occasionally an osseous stalk is seen at the base of the lesion which is said to be pathognomonic in this context.

A stalk-like connection to the clivus is usually seen if high-resolution images are obtained.

Apart from the characteristic location (retroclival, prepontine, and intradural), MRI findings are non-specific, with signal similar to CSF:

T1: hypointense

T2: hyperintense

T1 C+ (Gd): ​variable; however, most cases have not shown substantial enhancement 1
History and etymology

Rudolf Virchow (1821-1902), a German physician and pathologist first described a similar lesion in 1857 and mistook it as a degenerative process affecting the spheno-occipital synchondrosis with cartilaginous components and termed it "ecchondrosis physaliphora" which comes from the Greek "chondros" meaning cartilage and "physalis" meaning bubble. Friedrich von Muller suggested a notochordal origin in 1858. In 1898 Ribbert confirmed its notochordal origin and coined the modern term of "ecchordosis physaliphora".

Differential diagnosis

The differential diagnosis of retroclival intradural lesions consists mainly of :

chordoma: generally symptomatic and enhances after contrast administration

benign notochordal cell tumor (BNCT)

skull base metastasis

dermoid cyst

epidermoid cyst

arachnoid cyst: communicates with subarachnoid space, follows CSF intensity pattern and no enhancement

Sunday, January 21, 2024

Approval of omaveloxolone for Friedreich ataxia

Subramony SH, Lynch DL. A Milestone in the Treatment of Ataxias: Approval of Omaveloxolone for Friedreich Ataxia. Cerebellum. 2023 May 23. doi: 10.1007/s12311-023-01568-8. Epub ahead of print. PMID: 37219716.


The exciting news about the US FDA approval of omaveloxolone as the first-ever drug to be approved for an inherited ataxia is welcome news for patients and families that deal with this devastating disease as well as for health care providers and investigators with an interest in this and other rare diseases. This event is the culmination of long and fruitful collaboration between patients, their families, clinicians, laboratory researchers, patient advocacy organizations, industry, and regulatory agencies. The process has generated intense discussion about outcome measures, biomarkers, trial design, and the nature of approval process for such diseases. It also has brought hope and enthusiasm for increasingly better therapies for genetic diseases in general.

Lee A. Omaveloxolone: First Approval. Drugs. 2023 Jun;83(8):725-729. doi: 10.1007/s40265-023-01874-9. PMID: 37155124.


Omaveloxolone (SKYCLARYS™) is an orally active, small molecule semi-synthetic triterpenoid drug that increases antioxidant activity, which is being developed by Reata Pharmaceuticals, Inc. for the treatment of Friedreich's ataxia. In patients with Friedreich's ataxia, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is suppressed, which is associated with oxidative stress, mitochondrial dysfunction and damage to cells, including central and peripheral neurones. The Nrf2 pathway may be activated by omaveloxolone as it blocks the ubiquitination and degradation of Nrf2. Omaveloxolone was approved in February 2023 in the USA for the treatment of Friedreich's ataxia. This article summarizes the milestones in the development of omaveloxolone leading to this first approval for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.

Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, Boesch S, Nachbauer W, Mariotti C, Mathews KD, Giunti P, Wilmot G, Zesiewicz T, Perlman S, Goldsberry A, O'Grady M, Meyer CJ. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021 Feb;89(2):212-225. doi: 10.1002/ana.25934. Epub 2020 Nov 5. Erratum in: Ann Neurol. 2023 Dec;94(6):1190. PMID: 33068037; PMCID: PMC7894504.

Erratum inCorrection to Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study).
Lynch D.Ann Neurol. 2023 Dec;94(6):1190. doi: 10.1002/ana.26808. Epub 2023 Oct 5.PMID: 37795909 No abstract available.


Objective: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.

Methods: We conducted an international, double-blind, randomized, placebo-controlled, parallel-group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015-002762-23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks.

Results: One hundred fifty-five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (-1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of -2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone.

Interpretation: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA.

Lynch DR, Johnson J. Omaveloxolone: potential new agent for Friedreich ataxia. Neurodegener Dis Manag. 2021 Apr;11(2):91-98. doi: 10.2217/nmt-2020-0057. Epub 2021 Jan 12. PMID: 33430645.


Friedreich ataxia is a slowly progressive neurodegenerative disorder leading to ataxia, dyscoordination, dysarthria and in many individuals vision and hearing loss. It is associated with cardiomyopathy, the leading cause of death in Friedreich ataxia (FRDA), diabetes and scoliosis. There are no approved therapies, but elucidation of the pathophysiology of FRDA suggest that agents that increase the activity of the transcription factor Nrf2 may provide a mechanism for ameliorating disease progression or severity. In this work, we review the evidence for use of omaveloxolone in FRDA from recent clinical trials. Though not at present approved for any indication, the present data suggest that this agent acting though increases in Nrf2 activity may provide a novel therapy for FRDA.

Sunday, January 14, 2024

Safety and efficacy of supratherapeutic doses of clobazam

Gedela S, Freedman DA, Gedela S, Glynn P, Salvator A, Patel AD. Safety and Efficacy of Supratherapeutic Doses of Clobazam. J Child Neurol. 2019 Oct;34(12):735-738. doi: 10.1177/0883073819856834. Epub 2019 Jun 19. PMID: 31215313.


Clobazam is a commonly used long-acting benzodiazepine approved by the US Food and Drug Administration (FDA) to treat seizures associated with Lennox Gastaut syndrome. The FDA approved maximum dosage of clobazam is 1 mg/kg/d or a total of 40 mg a day. Many providers exceed this dosage but there is limited data on the safety, tolerability, and efficacy of supratherapeutic doses. We reviewed retrospective data at our institution and compared patients on supratherapeutic doses to patients on therapeutic doses. A total of 133 patients met inclusion criteria (65 supratherapeutic, 67 therapeutic). There was no statistically significant difference in terms of seizure control, health care utilization, or side effects between patients on supratherapeutic doses and those on therapeutic doses. This study lends further support to the safety and tolerability of supratherapuetic doses of clobazam.

Co-morbid tics and stereotypies

Cavanna AE, Purpura G, Riva A, Nacinovich R. Co-morbid tics and stereotypies: a systematic literature review. Neurol Sci. 2023 Sep 29. doi: 10.1007/s10072-023-07095-y. Epub ahead of print. PMID: 37775


Background: Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are characterised by a complex co-morbidity profile, however little is known about the co-occurrence of these hyperkinetic disorders in the same patient population.

Objective: This review aimed to assess the relationship between tics and stereotypies when these conditions present in co-morbidity.

Methods: We conducted a systematic literature review of original studies on co-morbid tics and stereotypies, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Our literature search identified six studies of suitable sample size (n ≥ 40) presenting data on the association between tics and stereotypies in otherwise typically developing patients. A considerable proportion (23%) of patients diagnosed with stereotypic movement disorder present with co-morbid tics (range 18-43%). Likewise, the prevalence of primary stereotypies is increased in patients with tic disorders such as Tourette syndrome (8%, range 6-12%).

Discussion: Tics and stereotypies can often develop in co-morbidity. The association of tics and stereotypies in the same patient has practical implications, in consideration of the different treatment approaches. Future research should focus on the assessment and management of both conditions, particularly in special populations (e.g. patients with pervasive developmental disorders).

Thursday, January 11, 2024

Hyperventilation induced seizures in focal epilepsy

Milan A, Alzahrany M, Gupta A. Hyperventilation Induced Seizures in Focal Epilepsy: Two Cases and a Review of Literature. Clin EEG Neurosci. 2024 Jan 2:15500594231222982. doi: 10.1177/15500594231222982. Epub ahead of print. PMID: 38166403.


We report two cases of temporo-perisylvian epilepsy with habitual seizures consistently inducible by hyperventilation (HV). One case was non-lesional, while the other was a lesional temporo-perisylvian epilepsy. Both underwent surgical resection and were seizure-free or nearly seizure-free thereafter. We discuss the pathophysiological changes evoked by HV in healthy brains, and those with generalized and focal epilepsy. We provide a comprehensive and critical review of the literature on the role of HV in focal epilepsy. We suggest HV should be considered an activation method for patients with focal epilepsy during epilepsy monitoring unit admissions and may help in the localization of the epileptogenic network/zone.

Early vigabatrin treatment in tuberous sclerosis infants and neurocognitive outcome

Bebin EM, Peters JM, Porter BE, McPherson TO, O'Kelley S, Sahin M, Taub KS, Rajaraman R, Randle SC, McClintock WM, Koenig MK, Frost MD, Northrup HA, Werner K, Nolan DA, Wong M, Krefting JL, Biasini F, Peri K, Cutter G, Krueger DA; PREVeNT Study Group. Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial. Ann Neurol. 2023 Aug 28. doi: 10.1002/ana.26778. Epub ahead of print. PMID: 37638552.


Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.

Interpretation: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms.

Wednesday, January 10, 2024

Antiseizure medication-Induced alopecia: A literature review

Pitton Rissardo J, Fornari Caprara AL, Casares M, Skinner HJ, Hamid U. Antiseizure Medication-Induced Alopecia: A Literature Review. Medicines (Basel). 2023 Jun 9;10(6):35. doi: 10.3390/medicines10060035. PMID: 37367730; PMCID: PMC10301592.


Background: Adverse effects of antiseizure medications (ASMs) remain one of the major causes of non-adherence. Cosmetic side effects (CSEs) are among the most commonly reported side effects of ASMs. In this context, alopecia is one of the CSEs that has a high intolerance rate leading to poor therapeutical compliance. Methods: We performed a literature review concerning alopecia as a secondary effect of ASMs. Results: There are 1656 individuals reported with ASM-induced alopecia. Valproate (983), lamotrigine (355), and carbamazepine (225) have been extensively reported. Other ASMs associated with alopecia were cenobamate (18), levetiracetam (14), topiramate (13), lacosamide (7), vigabatrin (6), phenobarbital (5), gabapentin (5), phenytoin (4), pregabalin (4), eslicarbazepine (3), brivaracetam (2), clobazam (2), perampanel (2), trimethadione (2), rufinamide (2), zonisamide (2), primidone (1), and tiagabine (1). There were no reports of oxcarbazepine and felbamate with drug-induced alopecia. Hair loss seen with ASMs was diffuse and non-scarring. Telogen effluvium was the most common cause of alopecia. A characteristic feature was the reversibility of alopecia after ASM dose adjustment. Conclusions: Alopecia should be considered one important adverse effect of ASMs. Patients reporting hair loss with ASM therapy should be further investigated, and specialist consultation is recommended.

Inside the booming business of cutting babies’ tongues

Tess Merrell had breastfed three babies and never expected trouble with her fourth. But after a month of struggling with her newborn, she hired Melanie Henstrom for help.

Ms. Henstrom, a lactation consultant, identified a culprit: The infant’s tongue was tethered to the bottom of her mouth. It was a common problem, she said, and could be fixed with a quick procedure at a dentist’s office

“It was touted as this miracle cure,” said Ms. Merrell, a high school soccer coach in Boise, Idaho.

Ms. Henstrom recommended a dentist, who in December 2017 cut under the baby’s tongue with a laser. Within days, the infant, Eleanor, was refusing to eat and had become dangerously dehydrated, medical records show. She spent her first Christmas on a feeding tube.

For centuries, midwives and doctors have been cutting such “tongue-ties” to ease breastfeeding. But the procedure’s popularity has exploded over the past decade as women face intensifying pressure to nurse.

Lactation consultants and dentists have aggressively promoted the procedures, even for babies with no signs of genuine tongue-ties and despite a slight risk of serious complications, a New York Times investigation found.

A small fraction of babies are born with a bundle of tissue that attaches the tip of their tongue to the bottom of their mouth. In some pronounced cases, doctors snip that tissue. But many tongue-ties are harmless, and the evidence that cutting them improves feeding is scant.

Yet some lactation consultants and dentists pitch laser surgery to anxious and exhausted mothers like Ms. Merrell as a cure-all that will improve breastfeeding and prevent a litany of health problems, including sleep apnea, speech impediments and constipation, according to dozens of parents, dentists, doctors and consultants.

Tongue-tie evangelists recommend lasering not only the tissue under the tongue but also the webbing that connects the lips and cheeks to the gums. Diagnosing and cutting these “oral ties” — often for hundreds of dollars — has become a niche industry.

One well-known dentist in Manhattan takes in millions of dollars a year from his tongue-tie practice. Lactation consultants who refer patients and assist dentists get paid, too. And companies that make lasers are also jumping on the trend.

It is difficult to tally the volume of surgeries, which are often not covered by insurance. But by all accounts the numbers are soaring.

Tongue releases done in hospitals — a small proportion of the total — grew more than 800 percent nationally between 1997 and 2012, to more than 12,000, one study found. Ear, nose and throat specialists in 25 states said they had seen sharp increases in requests for tongue-tie consultations, sometimes overwhelming their schedules. And searches for “tongue tie” on Google reached a record in June, more than doubling over the last five years.

Many families swear by the procedures. But the tongue-tie boom has unnerved pediatricians across the country.

In 2020, a large practice in New Jersey sent an email to families warning that babies were “being clipped, snipped and lasered at an alarming rate.” Last year, an office in Kentucky issued a similar alert, citing babies who refused to eat and were in “severe pain” after laser procedures. Dr. Charles Cavallo told The Times he wrote that alert in response to what he saw as a “money grab” by local dentists and lactation consultants.

Serious complications are rare. But doctors said they had seen the cuts cause such pain that babies refused to eat, becoming dehydrated and malnourished. A few said newly floppy tongues blocked infants’ airways.

Some parents said their guilt from seeing their babies suffer tipped them into depression. Others spent thousands of dollars on chiropractors and speech therapists who claimed their services were necessary for successful recoveries.

Unlike most medical specialties in America, the tongue-tie world operates with little oversight. State dental boards accept complaints from the public, but they rarely suspend dentists’ licenses. And only three states regulate lactation consultants.

Ms. Henstrom, for example, has continued to practice as a lactation consultant in Boise, despite health care workers and clients repeatedly filing complaints about her.

In a brief phone call, Ms. Henstrom said she gave careful attention to each client. “I have literally thousands of people who are thrilled with what I’m doing,” she said. She did not respond to a list of detailed questions.

The idea that tongue-ties can interfere with breastfeeding has been around for centuries. Midwives once used a long, sharp fingernail to rip the tissue beneath a baby’s tongue. In 1601, a royal surgeon cut the tongue-tie of Louis XIII, the future king of France.

But doctors have also long raised alarms about the procedure. “Frequently the parents are deceived, for profit, greed and ignorance,” a German obstetrician wrote in 1791. “This aid is abused, and one unties where nothing is tied.”

With the arrival of mass-produced formula in the 20th century, breastfeeding fell out of favor, and tongue-ties were rarely discussed. That began to change in the 1970s, as breastfeeding made a comeback.

Sucking from a bottle is easy. But to breastfeed, infants must learn to use their tongues to extract milk.

Specialized lactation consultants like Alison Hazelbaker emerged to teach nursing techniques. Some babies she saw in the 1980s had obvious tongue-ties that prevented them from nursing, she said, but pediatricians knew little about the condition. In 1993, she developed an assessment tool for tongue-ties that is still in use.

At the time, pediatricians carried out the releases with scissors, typically on babies with ties under the front of their tongues.

But in 2004, an article in the newsletter of the American Academy of Pediatrics suggested that a wider range of babies might benefit. A pediatric surgeon and a lactation consultant wrote that some patients had subtle tethers at the back of their tongues. Others had tissue tightly connecting their lips to their gums. Any of these ties, the authors warned, could impede breastfeeding.

Despite relying on anecdotes, the article became influential. Ms. Hazelbaker said she watched with alarm as the diagnosis of tied tongues, cheeks and lips accelerated. Before long, Facebook groups about tongue-ties gained thousands of members. “Everything started to go to hell in a handbasket,” she said in an interview with The Times.

In 2020, a panel of 16 leading ear, nose and throat specialists published guidelines warning that tongue-ties were being over-diagnosed and that cheek-tie releases simply “should not be performed.”

With or without surgery, breastfeeding often improves over time, making it hard to sort out cause and effect. Many women credit the procedures for making nursing easier.

Before the release, “I was sob-crying, it was so painful,” said Adrianne Parkey of Little Rock, Ark., whose baby was born this month. After, she said, she felt immediate relief. Some research has shown that the procedure reduces nipple pain.

The procedures appear to be more popular than ever. Even some of their original proponents now worry the releases are performed too often.

“I have huge concerns,” said Catherine Watson Genna, a lactation consultant in New York who co-wrote the 2004 newsletter article. Newer research, she said, has shown that some babies might be mistaken for having tongue-ties when in fact they have other conditions that restrict the tongue. “Everything looks like a nail because everybody’s got a hammer now.”

While lasting problems from oral releases are rare, they can be wrenching for families.

In Montana, a dentist released lip and tongue-ties on Clara Reck’s infant daughter in November 2022. Ms. Reck said her baby lost the ability to suck. Medical records show that she dropped from the 97th to the 15th percentile for weight in three months. Until last month, her daughter was still getting feeding therapy.

In Delaware, Dr. Nicole Aaronson, a pediatric ear, nose and throat surgeon, said that last week, she saw an 11-day-old boy who was hospitalized for weight loss because of tongue damage from a laser procedure. “He will heal and eventually do fine, but my point is that these procedures are not without risk,” she said.

And in Texas, Satina Bolton said she was pitched on “how we’re going to save your breastfeeding journey.” After two tongue-tie procedures, her daughter was hospitalized and needed a feeding tube.

Dr. Scott Siegel of Manhattan has been cutting babies’ tongues for two decades, ever since he took over the practice of one of the authors of the 2004 article.

He said he sees up to 100 patients a week, charging $900 for a five-minute procedure to release oral ties.

In November, Times reporters watched Dr. Siegel perform releases on three babies.

Before each procedure, he met with the parents, listing what he described as tongue-tie symptoms, including spitting up, gas and falling asleep while trying to breastfeed.

One mother came in because of trouble breastfeeding. Another had a fussy baby, and the third was hoping to avoid future health issues. Dr. Siegel told one family that the release could prevent problems like sleep apnea. “We’re looking at being proactive,” he said.

Working with two assistants, he swaddled the babies and covered their eyes with protective glasses. The laser released a plume of white vapor as it cut tissue.

Dr. Siegel acknowledged that few medical studies supported releasing oral ties. But his experience had convinced him that the procedures improved feeding and had other benefits. He has hundreds of five-star reviews online.

Not every family has been satisfied. Lainie Goldwert’s lactation consultant referred her to Dr. Siegel because her newborn was constantly nursing, never seeming satiated. After the tongue release, she said, her daughter’s mouth became weak. Ms. Goldwert had to squeeze her cheeks to help her suck, even when using a bottle.

“We went from a child who was breastfeeding voraciously to one who was not able to breastfeed,” she said. “It felt like, what the hell did I just do to my child?”

Dr. Siegel said he had very low complication rates. As for Ms. Goldwert’s baby, “this is a case that I would most likely treat differently now,” he said, including by warning parents that the recovery process might be long and complicated.

Companies that manufacture the lasers used by Dr. Siegel and other dentists are catering to this new market.

One company, Biolase, sells an $80,000 laser machine. In April, it hosted a conference at a resort in Scottsdale, Ariz., for more than 100 pediatric dentists and their colleagues. It was called “Tequila and Tongue Ties.”

Before rounds of tequila shots and margaritas, attendees were trained on how to perform tongue-tie releases and use social media to build their businesses. Dentists posed for photos with bottles of tequila against a backdrop that read, “Nacho average dental meeting.”

Biolase’s chief executive, John Beaver, said he thought tongue-tie releases were beneficial to patients. He said the company’s financing plan meant dentists needed to perform only three procedures a month to break even and could generate a “huge” return on investment by doing more.

Dr. Soham Roy, chair of the pediatric ear, nose and throat practice at Children’s Hospital Colorado, has operated on babies injured by lasers. “There are some folks out there who either buy or rent these lasers and they use them as cash-making machines,” he said.

Ms. Henstrom, the lactation consultant in Idaho, was converted to the benefits of tongue-tie releases after undergoing the procedure herself in her 40s. She claimed that it improved her scoliosis and that she stopped getting migraines and acid reflux. “I immediately felt a release of tension not just in my mouth, but throughout my entire body,” she wrote on her website.

After arriving in Boise in 2017, Ms. Henstrom got to work establishing her lactation consulting business, Baby Bonds, taking midwives out to lunch and offering free breastfeeding classes. Undiagnosed tongue-ties were always her focus.

“If your baby is super fussy, chances are your babe has a missed tongue tie,” her website states.

While the group that grants credentials for lactation consultants says they should not diagnose tongue-ties if they don’t have medical degrees, Ms. Henstrom often unequivocally tells parents that their infants are tongue-tied, sometimes without examining them in person, according to parents and her social media posts.

“According to pics and video, babe is for sure tied,” Ms. Henstrom wrote in 2020 in response to a parent’s post on a tongue-tie Facebook group.

In 2017, Ms. Merrell, fed up with trying to get Eleanor to nurse comfortably, contacted the local chapter of La Leche League, a well-known organization that promotes breastfeeding. Ms. Henstrom, a volunteer with the group, responded in a Facebook message that Eleanor’s problem was “likely” a tongue-tie.

Ms. Merrell replied that her pediatrician, a physical therapist and a previous lactation consultant had all said that wasn’t the issue.

“Trust me,” Ms. Henstrom said later in the exchange. “I have seen this hundreds of times and a revision always fixes it.”

“I hope so,” Ms. Merrell responded. “It would be nice to have an easy fix.”

After the surgery, Eleanor initially seemed to be improving. But then she stopped eating and became dehydrated. Her pediatrician sent her to the hospital. “We felt really stupid afterward because we paid to hurt our baby,” Ms. Merrell said.

“I feel terrible for what the Merrell family had to endure,” said Dr. Joel Whitt, the dentist who performed the procedure. He said this was the only bad outcome of nearly 800 such surgeries he had performed. He referred The Times to two past clients, who confirmed that their babies had benefited from surgery.

Dr. Whitt said he later dramatically reduced the volume of surgeries he was performing, in part because he worried that the benefits of releasing lip ties were being overstated.

By early 2020, Ms. Henstrom was exclusively referring patients to another dentist, Dr. Samuel Zink. She also assisted during the procedures, holding babies down while Dr. Zink cut their numbed mouths with a laser, according to a recent podcast interview and interviews with her clients.

Ms. Henstrom’s clients said she charged $150 for attending the tongue-tie release session, with optional follow-up visits. Parents said Dr. Zink’s fee was usually about $600. Insurance rarely covered the costs.

Dr. Zink did not respond to requests for comment.

Several of Ms. Henstrom’s clients said that when they expressed trepidation about the releases, she warned that untreated tongue-ties could lead to learning disabilities, scoliosis and sleep apnea.

Lauren Lavelle hired Ms. Henstrom to help with breastfeeding before giving birth to her daughter, June. Without even meeting the 3-day-old baby, Ms. Henstrom warned that, absent laser surgery, “she will never breastfeed,” according to Ms. Lavelle. “She will never eat solids.”

Two days after Dr. Zink performed the procedure, Ms. Henstrom visited Ms. Lavelle’s home and swept her fingers around June’s sore mouth. After that, the baby’s crying intensified and she began clawing at her face. Ms. Lavelle took her to the emergency room, where she said a doctor asked how such a tiny baby had such a large wound in her mouth and gave her pain medication.

Ms. Lavelle said the experience made her question her ability as a mother.

Several other parents said Ms. Henstrom also placed her fingers inside their babies’ mouths to prevent the tissue from reattaching, and she instructed the parents to do the same every six hours.

There is no research supporting the use of such techniques, which some specialists said can cause babies to fear eating because they associate their mouth with pain.

Courtney Wambeke tried to keep up with Ms. Henstrom’s instructions, prying her fingers into her daughter’s clenched mouth. But at a follow-up appointment, Ms. Henstrom said the tongue-tie had reattached. Ms. Wambeke was shocked when the consultant reached into the crying baby’s mouth and broke open the wound with her finger.

Last summer, an employee at St. Luke’s contacted the Boise police department, asking officers to check on the well-being of a 2-month-old who was being treated “for injuries from a tongue-tie,” according to a police report. The baby had lost weight “due to pain during eating.”

Ms. Henstrom had recommended the procedure and later “put her fingers in the infant’s mouth to manipulate the area recently operated on,” the police report said.

The investigation did not proceed, according to the report, because the baby had recovered and the parents said they were satisfied with Ms. Henstrom’s care.

It wasn’t the first time that health care workers had raised concerns about her.

In 2018, Ms. Henstrom worked part-time at a Boise midwifery practice. Soraya Mazloomi, a doula who also worked there, said several mothers complained about Ms. Henstrom’s pressuring them to get surgery for their babies. She was encouraged to leave. (The practice, Treasure Valley Midwives, is under new management, and a representative declined to comment.)

Most states, including Idaho, do not regulate lactation consultants. But more than 19,000 of the consultants have credentials from the International Board of Lactation Consultant Examiners. That group has received at least three complaints about Ms. Henstrom since 2020.

Kathy Strickland, a pediatric physical therapist, filed one that February. “I was getting referred to parents who were uncomfortable, who went in for follow-up and said it was traumatic, that she pushed so hard on their baby’s mouth,” she said in an interview.

Later in 2020, Ms. Lavelle also complained to the board, describing how she had been traumatized by her daughter’s tongue-tie release.

The lactation board, which reports its disciplinary decisions, has not taken action against Ms. Henstrom. A spokeswoman for the board, Susan Brayshaw, declined to comment on the complaints, citing a policy of confidentiality. “Some complaints take significantly longer than others due to the nature of the allegations and related investigations,” she said.

Since 2002, the board has revoked the certifications of only three lactation consultants.

Ms. Lavelle also filed a complaint against Dr. Zink with the Idaho board of dentistry. The board collected medical records and statements from Ms. Lavelle and Dr. Zink. Dr. Zink told the board that June’s procedure was “uneventful” but that an extremely small percentage of patients do not respond well to the procedure. He said none of his hundreds of other tongue-tie patients had previously complained.

The board’s executive director informed Ms. Lavelle via email that the group “didn’t feel that further investigation was warranted.” It found that Dr. Zink was not at fault.

Late last year, Ms. Henstrom recommended tongue, lip and cheek tie releases for an infant named Vivi. Sitting in Dr. Zink’s waiting room a few days later, Vivi’s mother, Aubrey Nobili, could hear her baby’s screams over the muffling hum of a noise machine.

When Ms. Henstrom brought Vivi back into the room, the wailing infant couldn’t catch her breath. Ms. Nobili pulled her daughter close and smelled charred flesh.

Vivi never breastfed again.

Six months later, a specialist at St. Luke’s assessed Vivi because she was having difficulty swallowing and would sometimes choke while drinking from a bottle. The specialist wrote in her medical records afterward that the problems were “likely due to” the laser surgery.

Ms. Nobili is a stay-at-home mother, and her husband, Ryan, works at Costco. They have four other young children. They said they ran up more than $5,000 in credit card debt paying for Vivi’s feeding therapies.

She turned 1 in November. Her family decorated their home with red and pink balloons and dressed her up as a strawberry.

Only one thing was missing: a birthday cake. Vivi still can't eat solid food.

A new investigational gene therapy, NGN-401, for Rett syndrome

Texas Children’s Hospital, an internationally recognized, top-ranked children’s hospital and pediatric research center affiliated with Baylor College of Medicine, is the first to deliver a novel gene therapy to treat Rett syndrome in pediatric patients. Two female patients with Rett syndrome were the first children worldwide to receive this promising treatment.

This exciting milestone is part of an ongoing first-in-human Phase I/II trial of a new investigational gene therapy, NGN-401, conducted by Neurogene Inc., a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases. Texas Children’s is currently the first clinical trial site to recruit and dose patients in the U.S. for this multicenter study.

Rett syndrome is a rare neurodevelopmental disorder that primarily affects girls, most of whom develop normally until 6-18 months of age when they begin to experience progressive regression in acquired motor and verbal skills and develop constant hand-wringing behavior. Eventually, this condition causes severe impairments that affect nearly every aspect of their daily lives, including their ability to speak, walk, eat, and breathe.

In 1999, a team led by Dr. Huda Zoghbi, a distinguished service professor at Baylor College of Medicine, founding director of the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and Howard Hughes Medical Institute investigator, made the transformational discovery that mutations in methyl cytosine binding protein 2 (MECP2) gene causes Rett syndrome.

It is, therefore, particularly momentous that 25 years following that discovery, the first gene therapy trial for Rett syndrome is now underway in the same site under the guidance of Dr. Bernhard Suter, associate professor of Pediatrics and Neurology at Baylor College of Medicine and medical director of the Blue Bird Circle Rett Center at Texas Children’s.

Doctor refused to help in mid-air emergency

A medical doctor has received support online after sharing that he had refused to help a passenger in need of clinical attention on a long-haul flight.

The 30-year-old man opened up about the experience on social media eight days ago. He wrote that the alcoholic drinks he had enjoyed a few hours earlier were the reason why he then backed out of the mid-air emergency. "I'm working as an internal medicine hospitalist at a major hospital," the man wrote.

"Recently, I was on a long-haul international flight. Usually, I sleep on flights, but this was during my waking hours so I decided to spend my time enjoying the inflight entertainment and free drinks. I had already been drinking even before the flight while I was in the lounge," the doctor added.

"I was trying to watch [a] movie and enjoy my drinks when an announcement was made asking if there was a doctor on flight. Normally, I would present myself to the cabin crew and help out, but after several hours of boozing, I was pretty drunk. I was not able to think clearly and probably would have done more harm than good. I didn't react to the announcement at all," he added.

The doctor had shared further down the post that the female passenger sitting next to him had tapped him on the shoulder to alert him to the announcement from the galley.

The doctor had simply replied that another passenger would be able to help or that the cabin crew would receive instructions from a medical team on the ground. The Reddit user wrote about the woman's reaction to his decision to give the emergency a miss. "She said I was an unbelievable a****** and that if the passenger died it was my fault," the doctor added.

"[I responded that] just because I'm a doctor doesn't mean that I'm on call 24/7 to provide medical care on demand. I work when I'm at the hospital, outside I'm just like everyone else and I'm entitled to drink and relax. She had a disgusted look on her face and didn't talk to me after that," he wrote.

Although his co-passenger was displeased with his decision, thousands of Reddit users have backed the medic over his refusal to help out.

Newsweek consulted travel agency owner Elisa Karen Bell for her take on the awkward situation.

"Having traveled extensively for over three decades, I believe that the man handled the situation appropriately. The only suggestion I can add is that he could have told his seatmate that he's over the limit, with regard to the cocktails based on his professional standards," Bell said.

"Therefore, as he said, he could do more harm than good. Sometimes, it simply takes a brief explanation to shut someone up, even though it's none of their business," Bell, who is also a Medicare insurance adviser, added.

Since it had been shared to the social-media platform on December 21 by u/ThrowAwayFoodie22, the Reddit post has been upvoted by 86 percent of the users that engaged with it and commented on more than 2,800 times.

"You are [not the] a****** for not volunteering after you'd been drinking, but why did you not just tell your co-passenger that? The way you describe it you have appeared to just not want to help, and that comes across as really cold and callous," one user wrote.

"Not the A****** for not volunteering, but kind of an idiot for saying oh, someone else will help. If you had just said, 'I can't I've been drinking'. That would be the end of it," another added.

Tuesday, January 9, 2024

Electromagnetic source imaging predicts surgical outcome in children with focal cortical dysplasia

Chikara RK, Jahromi S, Tamilia E, Madsen JR, Stufflebeam SM, Pearl PL, Papadelis C. Electromagnetic source imaging predicts surgical outcome in children with focal cortical dysplasia. Clin Neurophysiol. 2023 Sep;153:88-101. doi: 10.1016/j.clinph.2023.06.015. Epub 2023 Jul 5. PMID: 37473485; PMCID: PMC10528204.


Objective: To evaluate the diagnostic accuracy of electromagnetic source imaging (EMSI) in localizing spikes and predict surgical outcome in children with drug resistant epilepsy (DRE) due to focal cortical dysplasia (FCD).

Methods: We retrospectively analyzed magnetoencephalography (MEG) and high-density (HD-EEG) data from 23 children with FCD-associated DRE who underwent intracranial EEG and surgery. We localized spikes using equivalent current dipole (ECD) fitting, dipole clustering, and dynamical statistical parametric mapping (dSPM) on EMSI, electric source imaging (ESI), and magnetic source imaging (MSI). We calculated the distance from the seizure onset zone (DSOZ) and resection (DRES). We estimated receiver operating characteristic (ROC) curves with Youden's index (J) to predict outcome.

Results: EMSI presented shorter DSOZ (15.18 ± 9.06 mm) and DRES (8.56 ± 6.24 mm) compared to ESI (DSOZ: 25.04 ± 16.20 mm, p < 0.009; DRES: 18.88 ± 17.30 mm, p < 0.03) and MSI (DSOZ: 23.37 ± 8.98 mm, p < 0.03; DRES: 15.51 ± 10.11 mm, p < 0.02) for clustering in patients with good outcome. Clustering showed shorter DSOZ and DRES compared to ECD fitting and dSPM (p < 0.05). EMSI had higher performance as outcome predictor (J = 70.63%) compared to ESI (J = 41.27%) and MSI (J = 33.33%) for clustering.

Conclusions: EMSI provides superior localization and improved predictive performance than individual modalities.

Significance: EMSI can help the surgical planning and facilitate the localization of epileptogenic foci.


Christos Papadelis, Ph.D., founding director of Neuroscience Research at Cook Children’s, and his team recently published an article in the scientific journal, Clinical Neurophysiology, entitled "Electromagnetic source imaging predicts surgical outcome in children with focal cortical dysplasia." Rupesh Kumar Chikara, Ph.D., a postdoctoral research fellow, served as first author. Due to significant interest in this article, the editor-in-chief selected a figure for the cover of the journal.

Focal cortical dysplasia (FCD) is the most common pathology in children with drug resistant epilepsy. Surgical resection of FCD can lead to seizure freedom or a significant decrease in the number of seizures. Several electrophysiological methods are currently used in the presurgical evaluation of these patients. The goal of these methods is to identify noninvasively, with high precision, the brain area that is responsible for the generation of clinical seizures. Among others, magnetoencephalography (MEG) and high-density electroencephalography (HD-EEG) contribute significantly to this process. MEG and HD-EEG measure the magnetic and electric activity that is generated by the human brain; yet, these methods present limitations when they are used in isolation. For example, MEG is unable to localize epileptic activity generated in deep areas of the brain. On the other hand, HD-EEG presents lower localization precision compared to MEG.

In the present article, Dr. Papadelis and his team propose the development of a novel electrophysiological method that combines information from these two neuroimaging modalities into a single fused solution. The research team analyzed data of simultaneous MEG and HD-EEG electrophysiological recordings from 23 children with FCD who were unable to control their seizures with drugs. They showed that the combined information from MEG and HD-EEG provides superior accuracy in localizing the epileptic activity compared to using the modalities in isolation. This accuracy was comparable to invasive methods, such as intracranial electroencephalography recordings. This new method will potentially have significant clinical impact since it may offer a precise localization of the brain area that is responsible for the generation of seizures. Also, it may predict the surgical outcomes of children who are unable to control their seizures with medication alone. The findings of this study are particularly important for patients who cannot handle invasive examinations, such as infants or young children with epilepsy.

The study is funded by Dr. Papadelis' RO1 grant from the National Institute of Neurological Disorders and Stroke and is in collaboration with Boston Children's Hospital and Harvard Medical School.