Trigeminal autonomic cephalgia

Brittany Smith knows a thing or two about headaches. The 17-year-old began experiencing migraines at the age of eight. However, in October 2019, the intensity of her headaches escalated and began wreaking havoc on her life.

“Her parents had to pull her out of school because she had missed so much,” said Dana Ionel, D.O., a headache fellow at UK HealthCare’s Kentucky Neuroscience Institute.

“She would just stay in bed. She would not come out of her room, and we would just keep going in there to check on her,” said Brittany’s mom, Tami Smith.

The headaches took on this different force just shy of Brittany’s 14th birthday. The first episode started with her face feeling a bit tight in the morning, and by the time she got home from school, her right eye was swollen and drooping.

“We thought maybe it was something with her eye, so we went to the eye doctor,” said Tami. “They were unsure what was going on, so we went to our local emergency department.”

Doctors there thought Brittany was potentially experiencing Bell’s Palsy, but suggested she go to the emergency department at the University of Kentucky Albert B. Chandler Hospital.

Brittany and her parents made the 90-minute drive from their home in Tollesboro to Lexington. Once at UK, doctors ruled out Bell’s Palsy and suspected it was connected to her migraines. Brittany was admitted and remained in the hospital for five days. During those five days, she underwent numerous tests, but her case proved to be tough in finding definitive answers.

Brittany’s episodes continued and intensified. Each time she would experience a debilitating headache that occurred only on her right side, along with swelling and drooping of her right eyelid. Watching their daughter suffer, Tami and George Smith tirelessly sought answers. Brittany underwent more testing by more doctors, including tests to check for seizures.

“We have been through the wringer with so many different doctors, and nobody had a clue what it was. We just kept hearing complicated migraines or cluster migraines,” said Tami. “Then we were told she would probably lose the use of the right side of her body and not just her face, but still we had no answers. It was just very frustrating.”

Tami and George both work as emergency medical technicians (EMTs). “It is nothing we’ve seen before and when I asked other medics that we work with, they’ve never seen it before either,” said Tami.

As they searched for answers, the frequency of Brittany’s headaches increased. They went from happening once or twice a month, then to once a week, and then to two or three episodes in a single week. She also endured rounds of harsh medications that would leave her with nausea, vomiting, and fatigue in the days that followed. It was hard on the teen who previously loved being outdoors and going to school.

“She had a tough time dealing with the differences,” said Tami. “People didn’t understand and would say things like ‘Oh, it’s just a headache’ or ‘Oh, it’s just a migraine.’ It was not just a migraine.”

Brittany’s parents saw the toll this experience was taking on their daughter, so they helped her begin counseling. Her providers also suggested she start taking medication for depression. The family was desperate for answers and desperate to see Brittany get back to enjoying life.

Shortly after settling into what they thought was their new normal, Brittany received a referral to UK’s Children and Young Adult Headache and Research Program, where she met Dr. Ionel.

“I did not think she had complicated migraines given the failure of all the medications and description of pain,” said Dr. Ionel. “I thought instead that she likely had trigeminal autonomic cephalgia (TAC).”

TACs are a subgroup of headache disorders that include cluster headaches, hemicrania continua, paroxysmal hemicrania, and short unilateral neuralgiform headache attacks (SUNA/SUNCT). They are one-sided headaches that typically include what are called autonomic features on the same side of the headache - some examples are a bloodshot eye, drooping of the eyelid, swelling of the eyelid, a small pupil, and either excessive runniness or stuffiness of the nose. These symptoms can sometimes be confused for Bell's palsy or even a stroke. These symptoms come with the headaches, and typically go away as the headaches are being treated.

According to doctors, TACs are very rare, and even more so rare in children. The specific TAC Brittany was experiencing is known as hemicrania continua.

“For reference, hemicrania continua is thought to represent about 1.7% of all headache disorders,” said Ionel. “It is so rare that a prevalence in the general population cannot be determined.”

Ionel says that TACs are often not recognized and are extremely underdiagnosed. “They have a big burden of disease. Education of these disorders is so important because they can mimic migraines and other conditions which are much more common,” she said.

Following her suspicions about what was going on, Ionel started Brittany on a medication that is only used for TACs. It helps to not only treat the symptoms, but also diagnose the patient. Thankfully, it worked.

“She had resolution of the headache and the facial symptoms,” said Ionel.

After three years, the Smiths finally received an answer and a treatment that gave Brittany her life back.

“She has not had an episode since we got the diagnosis and started medication in December of 2022,” said Tami. “She doesn’t have to take her depression medicine anymore. She is back to her happy self, just like she was before this all started.”

Brittany also recently obtained her high school degree through an online program – a year ahead of schedule. She’s enjoying doing all the teenage things she was unable to do before, like driving a car. Brittany is thrilled to be back to enjoying time outdoors with her horse, Buttercup, and working hard at her job at a local restaurant.

“It is just amazing. She’s not just in her room all the time,” said Tami.

The Smiths are thankful for Dr. Ionel and all the others at UK Child Neurology who helped them on this long road to an answer. At that first visit, Ionel and others were unable to determine which specific trigeminal Brittany had.

“She kept researching and researching until she came up with the answer to which one Brittany had, which was hemicrania continua,” Tami said. “If she wasn’t calling us to check in, she was sending us messages through our online portal … she was just constantly checking on Brittany.”

That communication and genuine care have continued as Brittany and her family start a new chapter with a TAC diagnosis. It is a diagnosis they are thankful to now know and understand.

“We cannot thank Dr. Ionel and UK HealthCare enough. We were desperate, and they didn’t give up,” said Tami.

https://uknow.uky.edu/uk-healthcare/they-didn-t-give-uk-child-neurologists-help-teen-navigate-rare-headache-disorder

Trofinetide for Rett syndrome

This spring, Acadia Pharmaceuticals Inc. announced that FDA approved DAYBUE (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. DAYBUE is the first and only drug approved for the treatment of Rett syndrome.

The UNC School of Medicine was part of this multi-site clinical trial, led by Yael Shiloh-Malawsky, MD, associate professor of neurology. Co-investigators were Diana Cejas, MD, MPH, and Jane Fan, MD, professor of neurology. The lead study coordinator was Yulissa Gonzalez.

Rett syndrome is a complex, rare, neurodevelopmental disorder typically caused by a genetic mutation on the MECP2 gene. It is characterized by a period of normal development until six to 18 months of age, followed by significant developmental regression with loss of acquired communication skills and purposeful hand use. Symptoms can also include hand wringing and clapping and gait abnormalities. Rett syndrome is believed to affect 6,000 to 9,000 patients in the U.S., with a diagnosed population of approximately 4,500 U.S. patients.

The FDA approval of DAYBUE was supported by results from the pivotal Phase 3 LAVENDER study evaluating the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome five to 20 years of age. In the study, treatment with DAYBUE demonstrated statistically significant improvement compared to placebo on both co-primary efficacy endpoints, as measured by the change from baseline in Rett Syndrome Behavioor Questionnaire and the Clinical Global Impression-Improvement scale score.

“This is a historic day for the Rett syndrome community and a meaningful moment for the patients and caregivers who have eagerly awaited the arrival of an approved treatment for this condition,” said Melissa Kennedy, Chief Executive Officer of the International Rett Syndrome Foundation. “Rett syndrome is a complicated, devastating disease that affects not only the individual patient, but whole families. With the FDA decision, those impacted by Rett have a promising new treatment option that has demonstrated benefit across a variety of Rett symptoms, including those that impact the daily lives of those living with Rett and their loved ones.”

https://news.unchealthcare.org/2023/04/unc-child-neurology-researchers-led-unc-trial-site-for-rett-syndrome-treatment/

Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Peters SU, Jones NE, Youakim JM. Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022 Mar;114:106704. doi: 10.1016/j.cct.2022.106704. Epub 2022 Feb 8. PMID: 35149233.

Abstract

Introduction: Rett syndrome (RTT) is a debilitating neurodevelopmental disorder with no approved treatments. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like growth factor 1. In a phase 2, placebo-controlled trial in 82 females with RTT aged 5-15 years, a significant (p ≤ 0.042) improvement over placebo was observed with the highest trofinetide dose (200 mg/kg twice daily [BID]) on three measures: Rett Syndrome Behaviour Questionnaire (RSBQ), Clinical Global Impression-Improvement (CGI-I), and RTT-Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC-VAS). Trofinetide was well tolerated at all doses (50, 100, and 200 mg/kg BID). A phase 3 trial utilizing disease-specific and novel scales was designed to investigate the efficacy and safety of trofinetide in girls and women with RTT.

Methods: This 12-week, double-blind, randomized, placebo-controlled study (LAVENDER; NCT04181723) will evaluate trofinetide in 187 females, aged 5-20 years, with RTT. Co-primary endpoints are the RSBQ and CGI-I scales. Clinical domains of the CGI-I include communication, ambulation, hand use, seizures, attentiveness, and social (eye contact) and autonomic (breathing) aspects. Secondary endpoints will leverage four novel RTT-specific clinician ratings (derived from the RTT-DSC-VAS) of hand function, ambulation, ability to communicate, and verbal communication, and existing scales, to evaluate other core symptoms of RTT, quality of life and caregiver burden. A 40-week, open-label extension study will follow.

Discussion: This study was designed using disease-specific scales optimized to demonstrate changes in core symptoms of RTT and may provide the first phase 3 data demonstrating drug efficacy in individuals with RTT.

See: https://childnervoussystem.blogspot.com/2019/04/trofinetide-in-pediatric-rett-syndrome.html

https://childnervoussystem.blogspot.com/2018/10/trofinetide-in-treatment-of-rett.html

Gelastic seizures

https://www.youtube.com/shorts/kDIKCfsMqkg

https://www.youtube.com/shorts/be8AIjYXUI8

https://www.youtube.com/watch?v=dnRTt34wAhk

Screening for congenital CMV

ST PAUL, Minn. — At barely a day old, newborn Ny'aire went through what most babies in Minnesota do shortly after birth: Getting his blood spotted for the state's newborn screening panel.

With mom and dad by his side at M Health Fairview Southdale Hospital, Ny'aire barely made a sound as his pricked heel was placed on a paper to smear his blood sample, which would then be sent to the Minnesota Department of Health.

But Ny'aire is among the first babies in the country to be universally screened for congenital cytomegalovirus, known as CMV. In February, Minnesota became the first state in the country to universally screen for CMV, after the 2021 passing of a law named the Vivian Act.

Cytomegalovirus is a common virus, frequently going undetected in adults and older children. However, if a pregnant woman contracts it and transfers it to her unborn baby, it can lead to developmental issues later on in the child's life.

Ask Leah Henrikson, mother of now 8-year-old Vivian Henrikson, for whom the Minnesota law was named.

"She already lost hearing at birth in her left ear, but she could also lose hearing in right," Henrikson said. "So we have to kind of monitor and lots of doctor's appointments and things."

Henrikson says in addition to hearing loss, Vivian has cerebral palsy, epilepsy and learning challenges.

Vivian contracted CMV in utero. Henrikson credits doctors with realizing something was wrong, leading Vivian to be diagnosed with CMV while just a few days old.

The early diagnosis allowed the Henriksons to plan and prepare for Vivian's potential health issues, something that Henrikson wants all families to have.

"It makes all the difference in the world to know right away," she said. "Early is always better for treatment... there are options, but if you don't know, you can't treat what you don't know. So then you've missed your window and it's hard to make up that valuable time."

The Department of Health estimates that of the 65,000 babies born each year in Minnesota, up to 300 will be born with CMV. Of that number, 20% will develop symptoms.

While that may not seem like a lot, the health department says the virus is more prevalent than some of the other disorders for which it screens.

"Some of the other conditions we might see one or two per year for those rare conditions, but with this, we do expect to see quite a few more positive results," said Jill Simonetti, manager of MDH's newborn screening program.

A component of the Vivian Act is education about CMV.

Many women have never even heard of the virus, let alone know how it spreads through bodily fluid.

"So you might think twice before you finish your child's sandwich, for example. Or not share a cup with your toddler, because the virus is transferred through saliva," Henrikson said.

Dr. Mark Schleiss, a Professor of Pediatrics at the U of M Medical School who has long studied CMV, continues to research a possible vaccine for it. He supports the newborn screening, citing the importance of early intervention.

"The window for intervention, especially hearing loss, is really narrow," he said. "If a child has undiagnosed hearing loss in the first three years of life and they don't get early intervention, then their speech and language development can really be impaired in the long term. So it's an important diagnosis to try to identify."

https://www.kare11.com/article/news/local/kare11-sunrise/the-new-screening-in-mn-affecting-every-newborn-in-the-state/89-903c3e32-eecc-4c2b-91e9-ae95c8b121e3

NGN-401 for the treatment of Rett syndrome

NEW YORK, January 23, 2023 – Neurogene Inc., a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for NGN-401 for the treatment of Rett syndrome.

NGN-401 is the first investigational adeno-associated virus (AAV) gene therapy candidate to be administered to pediatric patients using Neurogene’s proprietary Expression Attenuation via Construct Tuning (EXACT) gene regulation technology. EXACT, developed in collaboration with the University of Edinburgh, is a self-contained, transgene regulation technology that can be tuned to deliver a desired level of transgene expression within a narrow range, and is compatible with viral and non-viral delivery platforms. Embedding EXACT technology into NGN-401 is an important advancement in gene therapy for Rett syndrome, specifically because the disorder requires a treatment approach that safely regulates MECP2 transgene expression without causing toxic effects associated with overexpression.

Intracerebroventricular (ICV) delivery of NGN-401 was evaluated in multiple preclinical models, including the male MECP2 knock out mouse model for efficacy, the female MECP2 mouse model for tolerability, and non-human primates (NHPs) for toxicity. Notably, the efficacy profile for NGN-401 was robust, demonstrating a significant survival benefit with concomitant improvements in Rett syndrome-like phenotypes compared to untreated control animals. Importantly, expression data for NGN-401 demonstrated well-controlled MeCP2 protein levels in key brain regions affected by Rett syndrome, while conventional gene therapy, without EXACT regulation, generated more variable and undesirable higher MeCP2 levels. While comparable doses of NGN-401 in female mice and in NHPs were safe and well-tolerated, in stark contrast, conventional MECP2 gene therapy without EXACT regulation showed severe toxicity in mice and early signs of toxicity in NHPs.

“Rett syndrome is a particularly challenging disorder for gene therapy because of the requirement to deliver therapeutic levels of MECP2, without also triggering significant side effects associated with too much gene expression,” said Rachel McMinn, Ph.D., CEO and Founder of Neurogene. “We believe the preclinical profile for NGN-401 is highly compelling, with the strongest results generated to date across multiple animal models. FDA clearance of NGN-401 represents a significant milestone for Neurogene and the Rett syndrome community and underscores our commitment to turn devastating neurological diseases into treatable conditions, and to improve the lives of patients and families impacted by these rare diseases.”

“Rett syndrome is a debilitating disease with a devastating impact on children and their families, with no disease-modifying treatments available,” said Dr. Bernhard Suter, Assistant Professor of Pediatrics and Neurology at Baylor College of Medicine and neurologist at Texas Children’s Hospital. “The upcoming clinical study of NGN-401, which has a mechanism of action aimed at addressing the root cause of disease, offers hope for improving the lives of those suffering from Rett syndrome.”

Neurogene recognizes the U.S. Rett syndrome patient advocacy organizations, the Rett Syndrome Research Trust (RSRT) for funding foundational Rett syndrome research at the University of Edinburgh, and the International Rett Syndrome Foundation (IRSF). We appreciate both the RSRT and the Clinical Trial Committee of the IRSF for their extensive collaboration and significant input into the clinical trial design, as well as the large number of caregivers and expert clinicians who provided their unique insights into the key disease manifestations of Rett syndrome. Feedback from all stakeholders, including the FDA, is incorporated into the Phase 1/2 clinical trial design.

IND clearance enables Neurogene to initiate a Phase 1/2 trial to assess the safety, tolerability and efficacy of NGN-401 in female pediatric patients with Rett syndrome. The open-label, single-arm, multi-center clinical trial will evaluate a single dose of NGN-401 delivered using a one-time ICV procedure. More details about the trial design will become available on www.clinicaltrials.gov.

About NGN-401
NGN-401 is an adeno-associated virus (AAV) gene therapy investigational product that is the first to deliver the full-length human MECP2 gene, under the control of Neurogene’s EXACT self-contained gene regulation technology. EXACT enables therapeutic levels of the protein MeCP2 while avoiding overexpression related toxicities. NGN-401 has received FDA clearance to be dosed in a one-time administration using the ICV procedure, which Neurogene has shown achieves broad vector distribution to key regions of the brain affected in Rett syndrome. NGN-401 has undergone extensive preclinical study and has demonstrated a robust efficacy profile, coupled with lack of MeCP2 protein related toxicities, even at high doses not intended for human use. NGN-401 is manufactured at Neurogene’s GMP manufacturing facility, located in Houston, TX.

About EXACT
Expression Attenuation via Construct Tuning (EXACT) is Neurogene’s proprietary gene regulation platform technology, developed in collaboration with the University of Edinburgh. EXACT was created to address key limitations of conventional gene therapy, in which cells receiving multiple copies of an AAV therapeutic are “overdosed” with transgene, resulting in transgene related toxicities. EXACT is a self contained gene regulation platform technology that can be tuned to deliver a desired level of transgene expression within a narrow range, thus avoiding transgene toxicities. EXACT is compatible with viral and non-viral delivery platforms, and as delivery methods improve, it may prove to be an important safety tool in gene therapy designs across disease areas.

About Rett Syndrome
Rett syndrome is an X-linked, progressive, neurodevelopmental disorder. Rett syndrome has an estimated incidence of 1 in 10,000 live female births, making it one of the most common genetic causes of developmental and intellectual impairment in females. The incidence in males is currently unknown.

Rett syndrome is caused by mutations in the MECP2 gene that lead to deficiency of the methyl cytosine binding protein 2 (MeCP2), an important protein responsible for normal function in the brain and other parts of the nervous system. Females with Rett syndrome typically have normal development up until 6-18 months of age. However, females then experience rapid regression of previously acquired milestones including speech, gross and fine motor skills, and develop stereotypical, repetitive hand movements that prevent them from purposeful hand movement or function. Over time females may develop muscle contractures, rigidity, and debilitating scoliosis, along with periods of recurrent seizures, burdensome gastrointestinal abnormalities, breathing abnormalities and cognitive decline.

There are no approved disease-modifying therapies for Rett syndrome. Current treatments for Rett syndrome include symptom management and supportive care.

https://www.neurogene.com/press-releases/neurogene-announces-fda-clearance-of-ind-for-ngn-401-gene-therapy-for-children-with-rett-syndrome/

AstraZeneca COVID-19 vaccine related death

A British coroner recently determined that a healthy, young doctor in the United Kingdom died from a rare reaction to AstraZeneca's COVID-19 vaccine.

Dr. Stephen Wright, 32, passed away in January 2021 ten days after receiving his first dose. He worked as a psychologist in London, according to the BBC.

Wright suffered a cerebral blood clot after getting inoculated. He was described as "fit and healthy" before falling ill.

Coroner Andrew Harris said it was a "very unusual and deeply tragic case."

"Dr Wright was a fit and healthy man who had the AstraZeneca covid vaccination on 16 January 2021, awoke with a headache on the 25th and later developed left arm numbness," Harris explained at London Inner South Coroner's Court. "He attended an emergency department just after midnight, where he was found to have high blood pressure and a sagittal sinus venous thrombosis."

"He was transferred to King’s College Hospital at 6:39 am but, because of the extent of the bleed and very low platelets, was unfit for surgery, dying at 6:33 pm," the coroner added. "My conclusion as to the cause of death is unintended complications of vaccination."

Wright's widow, Charlotte, is suing AstraZeneca. She has been trying to get the wording on her husband's death certificate changed from "natural causes."

"It was made clear that Stephen was fit and healthy and that his death was by vaccination of AstraZeneca. For us, it allows us to be able to continue our litigation against AstraZeneca. This is the written proof," Wright said to the BBC.

An AstraZeneca spokesperson said that they extended their "deepest sympathies" to Wright's family.

"Patient safety is our highest priority and regulatory authorities have clear and stringent standards to ensure the safe use of all medicines, including vaccines," the spokesperson said.

https://www.foxnews.com/health/young-healthy-british-doctor-died-severe-reaction-astrazeneca-covid-vaccine-coroner

What voice disorder does Robert F. Kennedy Jr. have?

What voice disorder does Robert F. Kennedy Jr. have?

According to ABC News, Robert F. Kennedy Jr. suffers from "spasmodic dysphonia, a specific form of an involuntary movement disorder called dystonia that affects only the voice box." This is not a life-threatening illness but it can certainly affect one's quality of life.

Other people who have it say "losing your voice hits people in their primary, intimate connection to the outside world and affects nearly every aspect of their lives."

In a conversation with Oprah Winfrey for the February 2007 issue of O, The Oprah Magazine, Robert went into detail regarding the rare disorder.

"The disease didn't hit me until I was about 43. I used to have a strong voice," he revealed. While it doesn't hurt, it certainly makes life a bit more complicated.

In the beginning, his symptoms were slight and came in the form of a "mild tremble for a couple of years." Evidently, they shouldn't worsen, but Robert believes his did.

How does one treat spasmodic dysphonia?

"There's a treatment for it: Botox shots. They put a needle into your voice box every four months," shared Robert.

The National Institute on Deafness and Other Communication Disorders also lists behavioral therapy (voice therapy) as a way to treat spasmodic dysphonia. However, this should be done in conjunction with Botox injections.

While there are surgical options available, the results are usually temporary. Dr. Robert Bastian, a former spokesman for Dysphonia International, told ABC News that "If you do anything surgical, the dystonia tries to win. It tries to figure out a way around its obstruction." Unfortunately, the cause is unknown which might explain why treatment is difficult to pin down.

For now, the "best guess spasmodic dysphonia experts have ... is that root of the neurological disorder lies in the basal ganglia," which is often referred to as the "processing area" of the brain.

Thankfully, organizations like Dysphonia International are "dedicated to improving the lives of people affected by spasmodic dysphonia and related voice conditions through research, education, awareness, and support," per its website.

https://www.distractify.com/p/robert-f-kennedy-jr-voice

Transparency update 4

CNN and two of its biggest stars are reportedly embroiled in a libel lawsuit involving a Florida heart surgeon.

The lawsuit involves alleged false reporting on infant mortality relating to the hospital’s open-heart surgery process. 

According to Puck, the suit brought by Dr. Michael Black dates to 2016. At the time, CNN reported that St. Mary’s Medical Center open-heart surgery on infants led to a mortality rate of “three times the national average.” 

Hospitals officials claim the reporting used cherry-picked data that was “flawed and deeply dishonest.” The network’s reporting prompted the hospital’s former chief executive, David Carbone, to resign and the hospital to shutter its pediatric cardiac surgery program. 

At the center of the lawsuit is star anchor Anderson Cooper who was deposed for the case. Cooper reportedly told attorneys that he never attended editorial meetings where the story was brought up and did not have any involvement in disseminating information on social media about the case.

He reportedly would not answer whether financial bonuses were tied to his show’s ratings—however, the questionable reports aired during his performance and online.

CNN’s fact-checking process is being scrutinized in the lawsuit. The so-called “Triad Process” was the subject of a 2017 New York Times article that referred to the system as a “three-pronged internal system designed to ensure that sensitive reporting by the network’s journalists is unimpeachable before it runs.” 

According to the report, Dr. Black is represented by the same attorneys prosecuting Dominion’s defamation case against Fox News, Tom Clare, and Libby Locke.

CNN could face a multi-million-dollar settlement if it is liable for any damages. 

https://barrettsportsmedia.com/2022/09/08/cnn-faces-libel-lawsuit-from-florida-heart-surgeon/

See: https://childnervoussystem.blogspot.com/2021/03/transparency-update-2.html

https://childnervoussystem.blogspot.com/2018/12/transparency-update-2.html

https://childnervoussystem.blogspot.com/2017/03/transparency-update.html

https://childnervoussystem.blogspot.com/2015/06/transparency.html

KCNMA1 mutation (Liang-Wang syndrome)

Two-year-old Lillian Brott loves her moose.

“Ready? Give him a kiss! You got him!” Lillian’s mom Lindsey said.

This was her first time in clinic for a checkup since having a sleep study done. And her family was hopeful to find some answers. Mr. Moose included.

Lillian had an echocardiogram done after a sleep study came back showing that she needed some help at home for sleeping–one symptom of KCNMA1 mutation, a newly discovered and very rare syndrome.

She also was in for an ultrasound, EKG, oxygen reading and blood pressure check at a recent doctor’s visit.

“She has so many specialists working with her,” Lindsey said. “She goes to PT, OT and speech therapy twice a week. She also has in-home and primary care as needed.”

She was first diagnosed with Liang-Wang syndrome in the NICU at Corewell Health’s Helen DeVos Children’s Hospital at just one month old. Doctors said there were only about 50 cases worldwide, and Lillian is the only child in Michigan with the condition.

A series of genetic tests brought about the diagnosis, and initially answered a few questions for the family. Doctors told her family they had not seen any other child in their many years of practice with this diagnosis.

“We had to get genetic testing done very early,” Lindsey said. “And I’m glad we did.”

Doctors sent out a series of genetic testing, and it came back with a KCNMA1 mutation which causes Liang-Wang syndrome.

“We knew nothing about this disorder. But shockingly enough, Netflix had a series called Diagnosis. And on the fourth episode another little girl has the same diagnosis,” Lindsey said.

“We watched the series, and it was bittersweet. Every kid is so different. Some can be very serious and some very mild.”

‘An ultra-rare condition’

Caleb Bupp, MD, division chief for genetics at Corewell Health, had never heard about this condition. So he did his research.

“This is an ultra-rare condition,” he said. “When we have kids who are born with rare things, we do our best to figure out what it is.”

“Everybody’s issues seem so different with this condition,” Lindsey said. “So it’s helpful to have the support groups online, but it doesn’t always tell you what your child is going to do or not do.”

Dr. Bupp said that the evolution in rapid, broad, genetic testing really has helped a lot, especially in difficult diagnoses like this one.

Lillian underwent rapid whole-exome sequencing.

“You can only know so much without testing,” he said. “These tests find things that you would never have expected.”

Team Lillian

With Lillian’s genomic variant, heart issues can also be a problem.

She suffers from mild aortic root dilation and a moderately dilated ascending aorta and sees the pediatric cardiology team at Corewell Health’s Helen DeVos Children’s Hospital.

She also required surgery on her ear tubes and adenoids. A team of physicians at Corewell Health repeated several hearing tests and completed a tonsillectomy and adenoidectomy.

“This is not just about Lillian, it’s about every kid,” Lindsey said. “Any family who must go through something rare like this. I believe there are a lot more children out there with it.”

She said it’s a matter of access to genetic testing and that many kids might be living with it and have no idea.

Lilian also sees pediatric ophthalmology, speech, occupational therapy, physical therapy, ENT, audiology, pulmonology, palliative care, neurodevelopment, gastroenterology and urology.

A speech therapist works with her on eating solid foods and she will likely see orthopedics at some point too.

“She has quite the team here,” Lindsey said.

Another thing the family gathered from the support groups was seizures are common.

“She hasn’t had any yet to my knowledge,” Lindsey said. “We had an EEG done and it didn’t show any either. When we first got the diagnosis, we heard fifty percent of cases have seizures or fifty percent have uncontrolled body movements.”

Her family is plugged into the syndrome community and is talking with other families who have children with the same syndrome.

“I have been researching some of these issues and it gets very scary to read about life expectancy,” Lindsey said. “I’m always prepared for the worst.

“I’m just trying to make sense of it all.”

https://healthbeat.corewellhealth.org/one-in-a-million/?fbclid=IwAR2XKXbNBrAHf5B5EgIGINGf4rWmGMnwgucNOXKd3UV_JnHjHf--WyJLsZs

COVID vaccine issue redux

An Ohio mother is speaking out about her 12-year-old daughter suffering extreme reactions and nearly dying after volunteering for the Pfizer coronavirus vaccine trial.

Stephanie De Garay told "Tucker Carlson Tonight" Thursday that after reaching out to multiple physicians they claimed her daughter, Maddie De Garay, couldn’t have become gravely ill from the vaccine.

"The only diagnosis we've gotten for her is that it's conversion disorder or functional neurologic symptom disorder, and they are blaming it on anxiety," De Garay told Tucker Carlson. "Ironically, she did not have anxiety before the vaccine."

De Garay explained that after receiving the second coronavirus vaccine dose, her daughter started developing severe abdominal and chest pains. Maddie described the severity of the pain to her mother as "it feels like my heart is being ripped out through my neck."ideo

The Ohio mother added her daughter experienced additional symptoms that included gastroparesis, nausea, vomiting, erratic blood pressure, heart rate, and memory loss.

"She still cannot digest food. She has a…tube to get her nutrition," De Garay said to Carlson. "She also couldn't walk at one point, then she could…I don't understand why and [physicians] are not looking into why...now she's back in a wheelchair and she can't hold her neck up. Her neck pulls back."

Carlson asked whether any officials from the Biden administration or representatives from Pfizer company have reached out to the family.

"No, they have not," she answered.

"The response with the person that's leading the vaccine trial has been atrocious," she said. "We wanted to know what symptoms were reported and we couldn't even get an answer on that. It was just that ‘we report to Pfizer and they report to the FDA.’ That's all we got."

After her heartbreaking experience, the Ohio mother said she’s still "pro-vaccine, but also pro-informed consent." De Garay mentioned she’s speaking out because she feels like everyone should be fully aware of this tragic incident and added the situation is being "pushed down and hidden."

De Garay said she had joined a Facebook support group to help people cope with the unexpected events happening from the coronavirus vaccine trial, and she said it was shut down.

"It's just not right," she said.

"They need to do research and figure out why this happened, especially to people in the trial. I thought that was the point of it," De Garay concluded. "They need to come up with something that's going to treat these people early because all they're going to do is keep getting worse."

Sen. Ron Johnson, R-Wis., has sent letters to the CEOs of Pfizer and Moderna seeking answers about adverse reactions to the COVID-19 vaccine following a June 28 press conference with affected individuals. The conference in Milwaukee included stories from five people, including De Garay.

The Wisconsin senator noted that some adverse reactions were detailed in Pfizer's and Moderna's Food and Drug Administration (FDA) emergency use authorization (EUA) memorandums following early clinical trials.

Those reactions included nervous system disorders and musculoskeletal and connective tissue disorders for the Pfizer EUA memo. The Moderna EUA memo included reactions such as nervous system disorders, vascular disorders and musculoskeletal and connective tissue disorders, according to Johnson's letter.

https://www.foxnews.com/media/ohio-woman-daughter-covid-vaccine-reaction-wheelchair

See: https://childnervoussystem.blogspot.com/2023/01/covid-vaccine-issue.html

Transverse myelitis after COVID vaccination

One orthopedic surgeon had his career ripped away from him by developing a career-ending condition just seven days after receiving the COVID-19 vaccine.

During an appearance on "Fox & Friends Weekend," Dr. Joel Wallskog shared the chilling details of how he contracted Transverse Myelitis, going from a "completely healthy 50-year-old" to a crippled, unemployed orthopedic surgeon, in a matter of a week.

"I was a completely healthy 50-year-old person with really no medical problems until about seven days after my first – or I should say one and only Moderna shot – that I received from December 30th of 2020. So, I was completely otherwise healthy until seven days after the shot," Dr. Wallskog shared with co-host Rachel Campos-Duffy.

Campos-Duffy shared her sympathies with Dr. Wallskog, asking the surgeon, "what happens next? Who takes responsibility for this?"

Dr. Wallskog replied, "what happens is you're abandoned."

"You get your shot, you do what you think is the right thing, and you kind of do your part, and then all of a sudden you're abandoned. And what I say is a lot of these people that are injured are really abandoned from the standpoint of physically, financially and emotionally," Dr. Wallskog continued.

Campos-Duffy bolstered Dr. Wallskog's claim, arguing that Big Pharma has not only evaded the "brunt" of alleged vaccine injuries, but made "billions of dollars." Recognizing that victims are provided no financial support, Dr. Wallskog founded an advocacy organization in an effort to spark change.

"That's who I fight for. I'm fine. And fortunately, I'm financially stable, but I fight for all the people that aren't. And that's why I started an advocacy organization to try to help us support them," he said, Sunday.

"You know, there's no pharma fund and there's a fund called – through the government – called the CICP or the Countermeasures Injury Compensation Program. But to date, the program has only paid out three claims totaling less than $5,000. And unfortunately, their denial rate for these people that are injured is 96.5%," the surgeon said.

While those numbers are attributed to Dr. Wallskog, this isn't the first time the claims process has been questioned. Reuters reported that by the end of the 2022 calendar year, over 7,500 vaccine jury injury claims - though not specific to the Moderna jab -had remained in limbo, with a reported 68 having been denied.

The orthopedic surgeon went on to argue that online censorship of the vaccine victim community has "devastated" the cause.

"It's devastated us. I mean, as you know, through kind of the Twitter files or data dump from Twitter, they even acknowledged in the files that true stories of vaccine-injured people; they were instructed to censor them. And it's devastating to us, because part of it is acknowledgment. I mean, with acknowledgment, we can hopefully then get diagnostics and treatments," he concluded.

According to a recent statement on their website, "Moderna’s vaccines have protected the lives of hundreds of millions of people around the world from COVID-19 and have dramatically lessened the burden of the pandemic to society."

https://www.foxnews.com/media/orthopedic-surgeon-covid-vaccine-developing-career-ending-condition-been-abandoned

Catecholaminergic polymorphic ventricular tachycardia

Sammy Berko, a teenage boy from Missouri City, Texas, went to a rock climbing gym where he suffered cardiac arrest and died. Two hours later he was alive.

"He climbed to the top of the wall, rang the bell, as we were told, and then his body went limp, and it looked like he was either playing around or passed out. They weren't quite sure and when they realized he was unresponsive, they lowered him slowly," Jennifer Berko, Sammy's mother, told Houston's Fox 26.

Paramedics and doctors proceeded to administer CPR for two hours before informing Jennifer that, "He's, gone." She and her husband, Craig, sat with their son for a few minutes to say their goodbyes.

"I started talking to him, just telling him how much I love him and sorry that we didn't know how to save him. Suddenly, as I started praying, my husband said, 'Oh my gosh, he's moving,'" said Jennifer to the local news station.

The couple shouted for the medical team who raced back in and began administering aid.

Due to how long Sammy went without oxygen there was fear he suffered a major brain injury. However, aside from some physical injury, he has so far only experienced short term memory loss. "I don't remember anything about the day it happened. The last thing I remember is the night before we had to sign waivers online (for the rock climbing gym), and then I woke up, not even in the pediatric ICU," Sammy told Fox 26. "I woke up in the transitional ICU and that's the first thing I remember. Then I remember my dad telling me, this is what happened and you better remember this time, because he said it so many times."

Despite how lucky Sammy was, that does not mean the road to recovery has been easy. Sammy has been working to recover strength in his legs after a month in the hospital and is undergoing physical therapy for the ischemic spine injury.

"I was very struck by his story. It's very gripping and very unusual. That only young man you know, who had this Catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a super rare genetic disorder that affects his heart," Dr. Stacey Hall, Medical Director of the Pediatric Rehabilitation Program at TIRR Memorial Hermann told Fox 26. "We do see kids all the time here who have had CPR, but with very prolonged CPR, we typically see very severe global anoxic brain injury, so to me, he is a literal miracle."

The Berkos are currently preparing their home to accommodate Sammy's wheelchair.

"I knew it would be a weird, crazy experience learning to walk again and working on strength without using my legs to be able to balance me. It has just been an amazing experience here actually, like I've noticed that I'm better every day! I'm doing something new every single day," Sammy told the local station.

This tragedy also shed some light on a past tragedy as, three years prior, the Berkos lost their son Frankie to what they now know is the same genetic mutation that almost killed Sammy. He and his mother underwent testing and are currently taking medication to help prevent any future issues.

https://www.foxnews.com/us/texas-teen-dies-rock-climbing-two-hours-later-he-revives-literal-miracle

Przybylski R, Abrams DJ. Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor. Curr Opin Cardiol. 2023 Mar 28. doi: 10.1097/HCO.0000000000001051. Epub ahead of print. PMID: 37016946.

Abstract

Purpose of review: Gain-of-function variants in the gene encoding the cardiac ryanodine receptor (RYR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). The exercise stress test (EST) has long been fundamental in diagnosis and management, but recent work has further explored its role. A new entity termed calcium release deficiency syndrome (CRDS) has been associated with loss-of-function RYR2 variants and a different arrhythmic phenotype.

Recent findings: Standard EST is not perfectly reproducible with regards to provocation of arrhythmia in CPVT. A newly described burst EST protocol may be more sensitive in this regard. Nadolol is the most effective beta blocker in CPVT, though arrhythmic events remain frequent and dual therapy with flecainide and/or left cardiac sympathetic denervation may add protection. A recent report renews debate regarding the use of implantable defibrillator therapy in CPVT. CRDS is characterized by later age of presentation, normal/near normal EST, and ventricular arrhythmia induced by a novel ventricular stimulation protocol.
Summary: Burst EST may aid in the diagnosis and management of CPVT. Nadolol is the preferred beta blocker in CPVT, and consideration should be given to early dual therapy. CRDS should be suspected in patients with arrhythmic events, rare RYR2 variants, and a phenotype inconsistent with CPVT.

Pérez PR, Hylind RJ, Roston TM, Bezzerides VJ, Abrams DJ. Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia. Heart Lung Circ. 2023 Apr 7:S1443-9506(23)00110-5. doi: 10.1016/j.hlc.2023.01.018. Epub ahead of print. PMID: 37032191.

Abstract

Over the last three decades, the genetic basis of various inherited arrhythmia syndromes has been elucidated, providing key insights into cardiomyocyte biology and various regulatory pathways associated with cellular excitation, contraction, and repolarisation. As varying techniques to manipulate genetic sequence, gene expression, and different cellular pathways have become increasingly defined and understood, the potential to apply various gene-based therapies to inherited arrhythmia has been explored. The promise of gene therapy has generated significant interest in the medical and lay press, providing hope for sufferers of seemingly incurable disorders to imagine a future without repeated medical intervention, and, in the case of various cardiac disorders, without the risk of sudden death. In this review, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT), discussing the clinical manifestations, genetic basis, and molecular biology, together with current avenues of research related to gene therapy.