Sunday, March 9, 2025

POLG mutation

Prince Frederik of Luxembourg, the son of Prince Robert of Luxembourg and Princess Julie of Nassau, has died at the age of 22.

Prince Robert shared the news in a statement on the website for the POLG Foundation, an organization started by Frederik to help with treatments and a cure for the illness.

Frederik was born with PolG mitochondrial disease, a rare genetic condition.

"It is with a very heavy heart that my wife and I would like to inform you of the passing of our son," Prince Robert wrote in the statement, sharing that Frederik had died on March 1.

The day before on "Rare Disease Day," Prince Robert shared that Frederik spoke with his family, including his brother Alexander and sister Charlotte, as well as cousins and other extended family, "one last time."

"After gifting each of us with our farewells – some kind, some wise, some instructive – in true Frederik fashion, he left us collectively with a final long-standing family joke. Even in his last moments, his humor, and his boundless compassion, compelled him to leave us with one last laugh… to cheer us all up."

He also wrote that Frederik asked, "Papa, are you proud of me?"

"He had barely been able to speak for several days, so the clarity of these words was as surprising as the weight of the moment was profound. The answer was very easy, and he had heard it oh so many times, but at this time, he needed reassurance that he had contributed all that he possibly could in his short and beautiful existence and that he could now finally move on," his father wrote.

The statement continued, "Frederik knows that he is my Superhero, as he is to all of our family, and to so very many good friends and now in great part thanks to his POLG Foundation, to so very many people the world over. Part of his superpower was his ability to inspire and to lead by example."

Prince Robert explained that Frederik was born with PolG mitochondrial disease.

Frederik wasn’t diagnosed until he was 14, "when his symptoms were showing more clearly and when the progression of his disease had become more acute."

The disease causes "such a wide range of symptoms and affects so many different organ systems, it is very difficult to diagnose and has no treatments much less a cure. POLG disease is a genetic mitochondrial disorder that robs the body’s cells of energy, in turn causing progressive multiple organ (brain, nerves, liver, intestines, muscles, swallowing and ocular function, etc.) dysfunction and failure. One might compare it to having a faulty battery that never fully recharges, is in a constant state of depletion and eventually loses power."

Prince Robert said Frederik "jumped" at the opportunity to create a foundation to find a cure.

"Though he always made it very clear that he did not want this dreadful disease to define him, he nonetheless immediately identified with and helped define the mission of The POLG Foundation."

According to his father’s statement, Frederik created the look for the charity in the United States, and launched a MITO clothing line, encouraged by Donna Karan.

He also "actively and literally gave of himself to develop multiple mouse models and cell lines in Switzerland, the United States, and Europe and to make these available to further facilitate research into POLG."

Prince Robert concluded, "On behalf of Frederik, Julie, Charlotte, Alexander, Mansour and the entire global POLG community, we thank you for helping this worthy cause that will honor our son. We will be resolutely focused on alleviating suffering for the POLG community and other diseases and conditions far beyond, associated with mitochondrial diseases."

https://www.foxnews.com/entertainment/prince-frederik-luxembourg-dead-22-from-rare-genetic-condition


VATER syndrome (VACTERL association)

Despite being born with rare life-threatening VATER syndrome (VACTERL association) and undergoing 16 surgeries before turning 16 and continued struggles with severe dyslexia, author JT Mestdagh is swimming in philanthropic endeavors and strives every day to approach life with a glass-half-full attitude.

Recently, Mestdagh, a Michigan native, penned a book titled "No Bad Days," featuring anecdotes shared with him by others. He hopes these stories will inspire young readers aged 13 to 19 to leverage the motivation to overcome life’s unexpected adversities.

"Through storytelling, I’ve been able to cope with my challenges," Mestdagh told Fox News Digital. "Being able to share with other peers of mine what I’m going through allows them to really open up and understand me. Also, for them to express what’s going on in their lives."

Mestdagh recounted how his challenges began at birth and continued well beyond his youth. In middle school, he underwent spinal cord surgery and experienced profound discomfort, limping and loss of bladder control.

His parents tirelessly researched to secure the best possible care for him, leading the Mestdagh family to travel from Detroit to Cincinnati and Denver for sometimes recurring procedures.

"It's been a little bit of a project in my life, but it’s been an amazing journey that I've learned so much from," Mestdagh said. "I don't know anything different, and I've just had a positive outlook on life."

Despite setbacks, Mestdagh maintains a strong work ethic and, through his organization, the JT Mestdagh Foundation, which he founded during his senior year in college, provides sick children diagnosed with colorectal issues and disabilities with drip bags, syringes, and solutions to irrigate their systems.

"The insurance companies don’t see a need to cover it," Mestdagh told Fox News Digital.

Recently, Mestdagh raised over $500k for children's charities.

To provide peace and stability for families already facing the heartache of their children’s conditions and sometimes financial challenges, Mestdagh works with doctors to find the patients in need and offers financial support for the families’ hospital stays.

His foundation also works with the Ronald McDonald House to provide Tattum Reading Program assistance for children with learning disabilities.

"The Tattum program really inspired me to read," he said. "I’ve struggled with reading the word ‘men’s’ for men’s bathroom. I could read it one day and the next I couldn’t. For someone with colorectal issues, that’s a real issue."


With the support of his parents and his community of people, whom he calls his "wolf pack," Mestdagh also credits his faith for helping to always create a new path forward.

"I grew up in a family of great faith in the Lord," he said. "My journey with faith has been very important to me. First and foremost comes my relationship with the Lord. He allows me to see that when one door closes, another opens."

"The foundation, we look at it with two main pillars, but with faith in all," Mestagh concluded.

"No Bad Days" will be released on April 1, 2025.

https://www.foxnews.com/media/author-rare-condition-raises-over-500k-childrens-charities-prioritizes-relationship-god

JT Jester, from Grosse Point, Michigan, was born with VATER/VACTERL syndrome, a serious, life-threatening disorder that affects many of the body’s systems. He also suffered from extreme dyslexia and short-term memory loss. Even when he was told he would never learn to read or write, Jester refused to be limited by these challenges. A graduate of High Point University, Jester is now an inspirational speaker, podcaster, philanthropist, as well as an experienced mountaineer, extreme skier, and adventurer. He established the JT Mestdagh Foundation to bring encouragement, joy, and laughter to people with physical and learning disabilities and their families.

His new book, No Bad Days: How to Find Joy in Any Circumstance, tells his inspirational true story and encourages people to move past their limitations and live full, passionate lives. He talked with Guideposts.org about his story, his new book, and what it truly means to have no bad days.

GP: In your life you have dealt with many challenges. What were they? How does your story begin?  

My journey started at birth. My parents thought they had a healthy pregnancy. But when I was born, I went right to the NICU. I spent the first 10 days of my life there. I was born with something called VACTERL syndrome, which is a birth defect that can affect many parts of your body. For me, it affected my gastrointestinal system and my spinal cord.

My medical journey began with multiple surgeries to correct my gastrointestinal system. As I continued to grow, other parts of VACTERL syndrome, which we were warned about, started to pop up. I had more surgeries in middle school and high school to repair my spinal cord. I was dealing with different symptoms, like a limp, loss of bladder control and things along those lines.

So the medical journey was obviously a priority in my family’s life, but then I had an education piece that was a challenge too. I was born with severe dyslexia and short-term memory loss. I had difficulty learning to read and write, but that’s all I wanted to do.

GP: In your book, you talk about how your parents relied on their faith during this time. Can you tell me about that?  

They were not expecting to have this hiccup in the road. Their faith played a big role in their life but it became even stronger. I think when we’re going through hard times, sometimes we become stronger in our faith. That’s when we rely on the good Lord more.

My dad told me a story about the day I was born. That evening, when he went home, he was worried about the [difficult] times to come. He picked up his Bible and it fell open to a very important passage. It was Mark 10: 13-16, which is about how God takes care of all his children. It was the first thing he saw, and it was a powerful message.

They also relied on each other during that time. There were other people in their life of course, like family and friends. But when you don’t experience [having a sick child] yourself, sometimes you don’t know how to react to it. So, they stayed strong in their faith together.

GP: How did your experience of growing and living with physical and learning challenges affect your own faith?  

One important thing I learned on my journey was finding my tribe. To be able to do that, I needed to put the right people into my life. Early on, it was my doctors, my educators, my parents and family. Nowadays, I’ve been blessed to be a part of a church that has been very influential in my faith journey. I’ve had amazing people along the way that have given me that ability to continue to grow. I build my tribes from the top down and created a stronger relationship with God.

My trials taught me a lot too. We are all going to fall and we’re all going to have those challenges in life. It’s those experiences that build our relationship with the Lord.

GP: What role has the power of prayer played in your life?   

I’ve been blessed to have so many people in my life praying for me, so prayer is one of the biggest things in my life. I think that prayers are truly answered.

Prayer has also been important for myself, to build and grow my relationship with God. I think that is why I love the outdoors so much. Prayer goes everywhere with us, but for me it’s [strongest] in nature.  Whenever I’m in nature, I call it God’s country. I’m able to connect with Him in the beauty of what He has created. I can escape from the challenges I face, or those naysayers in life that didn’t believe I could do different things.

GP: One of your many accomplishments was climbing to the peak of Mt. Kilimanjaro. What did you learn from that experience? 

It came with its challenges, but when I made it to the top, it was such an amazing spiritual moment. Reaching that [summit] was a great joy and a huge success. Because of my medical [history], this was something no one thought I’d be able to do. It was something I never thought I’d be able to do.

It made me realize that if you put your mind to it, you can accomplish anything. In my book, I talk about how we all have our mountain to climb in life, and how getting up to the summit and then continuing is so important.

GP: Speaking of your book, I’m very struck by the title, “No Bad Days.” Where does that title come from and what does it mean to you?

The phrase “no bad days” came from when I was seven- years-old, in the hospital having one of my spinal cord surgeries. My dad came into the room and said, “JT, I’m so sorry for what you’re going through.” He told me that I looked at him and said, “Dad, it’s okay. There are no bad days. There are only hard days. And we get through those.” I know that was the good Lord speaking through me. It became a life slogan for my whole family.

When people see the book, they ask me, “How do you not have any bad days?” For me, every day is a blessing. We can wake up, breathe the air around us, see the people in our lives and see the way God’s working throughout our world. We are going to have our discomforts, our pains, our challenges in life. There are going to be hard days, but we get through those with the people in our life.

GP: What do you hope people will get out of your book? 

The book talks about my life journey, but it also brings in other people’s journeys. Whether that’s the loss of a loved one, living with learning challenges like dyslexia, or medical challenges. The book encapsulates all these different people’s stories and their tactics of how they have overcome hardship.

The book also talks about storytelling and how important it is. We all have challenges in life and being able to express them to others is so crucial. It allows you to be open to people that you trust, and then in return, they trust you and express what’s going on in their life. You can support them and help them, and they will be there to support and help you.

And it’s not just having someone there for you in challenging times, but someone there to motivate you and push you and to make you grow even more. My book is about how we all have to share our stories and continue in helping each other. We all have a story that God is writing for us.

GP: What advice would you have for people who are looking to find more joy in their lives? 

Find your passions in life. For me, being in nature is where I find a lot of joy. And find the people to do those passions with. Having good, strong, faithful relationships are so important to finding joy.

My second tip is to just get outside and get moving. Be active in some way. Some days that can be very hard to do, but it will help get your mind motivated.

GP: What about those days when someone just is not able to do this? What advice would you give to people who are having very hard days? 

In the hardest of days, having your tribe is important. That’s something that you can rely on and lean on. When I have a hard day, I will sometimes call one of my very close friends who has been a great teacher to me.

This is also why your relationship with God is so important. Knowing that you’re not alone because He’s there to support and love you. We are all going to have those very hard days, so being able to rely on our relationship with the Lord is the most important.

This interview has been lightly edited for clarity and length. 

https://guideposts.org/inspiring-stories/there-are-no-bad-days-the-inspiring-true-story-of-jt-jester/


Thursday, March 6, 2025

Eculizumab to treat children with generalized myasthenia gravis

The Food and Drug Administration (FDA) has approved the expansion of the indication of Soliris (eculizumab; Alexion Pharmaceuticals, Boston, MA) to now include treatment for pediatric patients aged ≥6 years with anti-acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG). Soliris, a monoclonal antibody that targets the complement cascade, was previously approved for adults with AChR positive gMG in 2017 and adults with neuromyelitis optica spectrum disorder (NMOSD) in 2019, in addition to its initial approval for paroxysmal nocturnal hemoglobinuria (PNH) and a subsequent approval for atypical hemolytic uremic syndrome (aHUS).

In an open-label, multicenter, phase 3 clinical study (NCT03759366; ECU-MG-303) 11 adolescent participants aged 12 to 17 years with AChR positive gMG received weekly treatment with Soliris. The primary endpoint was change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score.

At week 26:QMG total score showed a least-squares mean change of -5.8 (standard error [SE], 1.2; P=.0004).
Myasthenia Gravis–Activities of Daily Living (MG-ADL) total score, a key secondary endpoint, showed a least-squares mean change of -2.3 (SE, 0.6; P=.0017).
All other secondary endpoints were met with statistical significance, demonstrating the efficacy of Soliris for improving outcomes related to symptoms, muscle strength, ability to perform daily activities, and quality of life.
Pharmacokinetic, pharmacodynamic, and safety findings were consistent with results observed in adults treated with Soliris.
3 participants experienced serious adverse events, including myasthenia gravis (MG) worsening, MG crisis, or peritonsillar abscess, and pyrexia.

Soliris’s prescribing information includes a Boxed Warning for serious meningococcal infections caused by Neisseria meningitidis.

https://practicalneurology.com/news/soliris-now-approved-to-treat-children-with-generalized-myasthenia-gravis?c4src=news:feed

Wednesday, February 26, 2025

Divalent small interfering RNA to treat KCNT1 genetic epilepsy

Andreone BJ, Lin J, Tocci J, Rook M, Omer A, Carito LM, Yang C, Zhoba H, DeJesus C, Traore M, Haruehanroengra P, Prinzen A, Miglis G, Deninger M, Li M, Lynch T, Howat B, Rogers KA, Gallant-Behm CL, Kinberger GA, Yudowski G, Chen Q, Jackson AL, McDonough SI. Durable suppression of seizures in a preclinical model of KCNT1 genetic epilepsy with divalent small interfering RNA. Epilepsia. 2025 Jan 27. doi: 10.1111/epi.18278. Epub ahead of print. PMID: 39871703.

Abstract

Objective: Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system.

Methods: The ATL-201 molecule is two identical synthetic double-stranded siRNAs, covalently linked, with 100% nucleotide base pair match to sequence present in both human KCNT1 and mouse Kcnt1 that does not contain any known pathogenic variant. ATL-201 activity was tested in cortical neurons cultured from wild-type mice and in mice homozygous for Kcnt1-Y777H, the mouse ortholog to the human pathogenic KCNT1-Y796H missense variant. Seizures and nest-building behavior were measured in freely behaving Kcnt1-Y777H mice. The number and duration of seizures were measured by electrocorticography in mice dosed with ATL-201 or phosphate-buffered saline in a 6-month durability study and in a 2-month dose-efficacy study.

Results: In vitro, ATL-201 reduced KCNT1 transcript from whole-cell lysate and eliminated potassium currents from KCNT1 channels in heterologous expression. ATL-201 also eliminated sodium-activated potassium currents recorded from individual cortical neurons. In vivo, ATL-201 suppressed seizures in Kcnt1-Y777H homozygous mice in a dose-dependent manner with near-complete suppression from 2 weeks to at least 4 months. Kcnt1-Y777H mice had defects in nest building, whereas in ATL-201-treated mice nest building was equivalent to wild-type mice.

Significance: Patients with KCNT1-driven epilepsy experience up to hundreds of seizures per day and have severe impairment in cognitive, motor, and language development and high mortality. The dose-dependent efficacy and long durability of ATL-201 in mice show promise for ATL-201 as a disease-modifying treatment of KCNT1 epilepsy.

Thursday, February 20, 2025

Diagnosing rare diseases

Durmus H. Editorial: Diagnosis and identification of novel disorders and ultra-rare disorders in science and clinical routine. Front Genet. 2024 Nov 20;15:1522931. doi: 10.3389/fgene.2024.1522931. PMID: 39634273; PMCID: PMC11614831.

The application of rapid exome sequencing (rES) has emerged as a crucial advance in diagnostic landscape, especially for critically ill patients presenting with rare diseases. This editorial reflects findings from a comprehensive study involving 575 patients that highlighted the transformative impact of rES on clinical decision-making and patient outcomes .

In recent years, rES has become the preferred genetic testing modality for critically ill patients, including neonates and young infants, in urgent clinical situations. Its ability to provide timely diagnoses can significantly guide management decisions and improve clinical care pathways. The study, conducted over 4 years (2016–2019) provides valuable insights into the operational effectiveness and clinical utility of rES. The study reported a notable increase in rES referrals, escalating from two in the first quarter of 2016 to ten per week by late 2019. This increase reflects growing recognition of rES as a critical tool in diagnosing complex genetic disorders. The median turnaround time for results improved from 17 days to 11 days, this highlighted advances in sequencing technology and laboratory efficiencies.

The overall diagnostic yield was 30.4%, with variations observed across different clinical entities. For instance, craniofacial anomalies showed a high diagnostic yield of 58.3%, whereas conditions like severe combined immune deficiency yielded no diagnoses at all. These findings suggest that rES, although not universally effective for all conditions, is vital for many patients and offers information that can change clinical management even in the absence of a definitive diagnosis.

The importance of rES extends beyond providing definitive genetic diagnoses. Even if genetic causes remain elusive, information gleaned from rES may influence clinical decisions such as direction of treatment or the need for further investigation. This dual effect in both making diagnoses and informing clinical strategies highlights the multifaceted role of rES in patient care.

Implementation of rES should be accompanied by careful ethical considerations, particularly regarding informed consent and genetic counselling. In high-stake situations, it is very important to ensure that patients and families understand the implications of genetic tests. Clinicians must navigate the complexity of informing uncertain or negative findings while remaining sensitive to the emotional impact on families.

As rES continues to evolve, its integration into routine clinical practice for older patients should be prioritized. The potential for RES to guide treatment decisions in cancer care and other adult-onset conditions is significant and requires further investigation. Ongoing research should focus on optimizing diagnostic strategies and understanding the broader implications of genetic findings in diverse cohorts.

Lessons learned from the use of rapid exome sequencing in critically ill patients underline its fundamental role in modern medicine era. The ability to quickly identify genetic causes of rare diseases not only increases diagnostic accuracy but also improves clinical outcomes. As these technologies continue to be developed and their applications expanded, the hope is to further close the gap between genetics and clinical practice, ultimately benefiting patients across the healthcare.

Wojcik MH, Lemire G, Berger E, Zaki MS, Wissmann M, Win W, White SM, Weisburd B, Wieczorek D, Waddell LB, Verboon JM, VanNoy GE, Töpf A, Tan TY, Syrbe S, Strehlow V, Straub V, Stenton SL, Snow H, Singer-Berk M, Silver J, Shril S, Seaby EG, Schneider R, Sankaran VG, Sanchis-Juan A, Russell KA, Reinson K, Ravenscroft G, Radtke M, Popp D, Polster T, Platzer K, Pierce EA, Place EM, Pajusalu S, Pais L, Õunap K, Osei-Owusu I, Opperman H, Okur V, Oja KT, O'Leary M, O'Heir E, Morel CF, Merkenschlager A, Marchant RG, Mangilog BE, Madden JA, MacArthur D, Lovgren A, Lerner-Ellis JP, Lin J, Laing N, Hildebrandt F, Hentschel J, Groopman E, Goodrich J, Gleeson JG, Ghaoui R, Genetti CA, Gburek-Augustat J, Gazda HT, Ganesh VS, Ganapathi M, Gallacher L, Fu JM, Evangelista E, England E, Donkervoort S, DiTroia S, Cooper ST, Chung WK, Christodoulou J, Chao KR, Cato LD, Bujakowska KM, Bryen SJ, Brand H, Bönnemann CG, Beggs AH, Baxter SM, Bartolomaeus T, Agrawal PB, Talkowski M, Austin-Tse C, Abou Jamra R, Rehm HL, O'Donnell-Luria A. Genome Sequencing for Diagnosing Rare Diseases. N Engl J Med. 2024 Jun 6;390(21):1985-1997. doi: 10.1056/NEJMoa2314761. PMID: 38838312; PMCID: PMC11350637.

Abstract

Background: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined.

Methods: We sequenced and analyzed the genomes of families with diverse phenotypes who were suspected to have a rare monogenic disease and for whom genetic testing had not revealed a diagnosis, as well as the genomes of a replication cohort at an independent clinical center.

Results: We sequenced the genomes of 822 families (744 in the initial cohort and 78 in the replication cohort) and made a molecular diagnosis in 218 of 744 families (29.3%). Of the 218 families, 61 (28.0%) - 8.2% of families in the initial cohort - had variants that required genome sequencing for identification, including coding variants, intronic variants, small structural variants, copy-neutral inversions, complex rearrangements, and tandem repeat expansions. Most families in which a molecular diagnosis was made after previous nondiagnostic exome sequencing (63.5%) had variants that could be detected by reanalysis of the exome-sequence data (53.4%) or by additional analytic methods, such as copy-number variant calling, to exome-sequence data (10.8%). We obtained similar results in the replication cohort: in 33% of the families in which a molecular diagnosis was made, or 8% of the cohort, genome sequencing was required, which showed the applicability of these findings to both research and clinical environments.

Conclusions: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.).


Ketogenic diet treatment for super-refractory status epilepticus

Ren Y, Zhang M, Fu X, Zhang Y, Liu F, Wu C, Shi H, Tian F, Liu G, Lin Y, Su Y, Chen W. Ketogenic diet treatment for super-refractory status epilepticus in the intensive care unit: feasibility, safety and effectiveness. Front Neurol. 2025 Jan 13;15:1517850. doi: 10.3389/fneur.2024.1517850. PMID: 39871989; PMCID: PMC11769800.

Abstract

Background and aims: To investigate the feasibility, safety and effectiveness of the ketogenic diet (KD) for super-refractory status epilepticus (SRSE) in the intensive care unit (ICU).

Methods: We conducted a prospective investigation on patients with SRSE treated with the KD. The primary outcome measures were ketosis development as a biomarker of feasibility and resolution of SRSE as effectiveness. KD-related side effects were also investigated.

Results: Twelve patients (9 females and 3 males) with SRSE, with a median age of 34 years [range 16-69, interquartile range (IQR) 18-52], were treated with a KD. The median duration of SRSE prior to KD treatment was 21 days (range 4-46). SRSE resolved in 75% (9/12) of patients at a median of 3 days (range 1-18) after KD initiation. Among the nine KD responders, all were successfully weaned off anesthetic agents at a median of 16 days (range 4-32) after KD initiation, and all were also successfully weaned off ventilator. Side effects varied, and included gastrointestinal intolerances, malnutrition and metabolic abnormalities, electrolyte disturbance, and acute weight loss, although most of them could be corrected. No patient died due to KD, and neurofunctions continued to improve under KD therapy.

Conclusion: The KD may be feasible and effective for the treatment of SRSE in the ICU. Moreover, it is relatively safe. However, there are numerous adverse events that can be corrected under close monitoring.

Ketogenic diet for drug-resistant epilepsy caused by structural pathology

Zhang H, Su S, Zhang H, Sun L, Liu Y, Liu G. Effectiveness and safety analysis of ketogenic diet therapy for drug-resistant epilepsy caused by structural pathology. Front Neurol. 2024 Oct 30;15:1497969. doi: 10.3389/fneur.2024.1497969. PMID: 39539663; PMCID: PMC11557543.

Abstract

Objective: To explore the effectiveness and safety of the ketogenic diet (KD) in children with drug resistant epilepsy (DRE) caused by structural etiology.

Methods: The children were categorized into acquired brain injury group and malformations of cortical development (MCD) group based on the etiology. Follow-up assessments were performed at 1, 3, and 6 months after KD treatment to observe seizure reduction, behavioral and cognitive improvements, adverse reactions events, and reasons for discontinuation withdrawal. Statistical analysis was conducted on the results.

Results: We found the seizure-free rates at 1, 3, and 6 months were 4.8% (2/42), 19% (8/42), and 21.4% (9/42), respectively. The seizure control effective rates were 42.9% (18/42), 52.4% (22/42), and 54.8% (23/42) at the corresponding time points. Compared to the acquired brain injury group, the MCD group showed a higher seizure control effective rate. Further analysis within the MCD group revealed the highest efficacy in focal cortical dysplasia (FCD). At the 3-month follow-up, cognitive and behavioral improvements were observed in 69% (29/42) of children. The main reasons for discontinuation were lack of efficacy and poor compliance.

Significance: Finally, we get that KD is a safe and effective treatment for drug resistant epilepsy caused by structural etiology, with the added benefit of improving behavioral and cognitive abilities in children. The efficacy is higher in children with MCD, particularly in cases of FCD. Early intervention with KD is recommended for this population.