Association between sun exposure and risk of relapse in pediatric-onset multiple sclerosis

Chang G, Sebastian P, Virupakshaiah A, Schoeps VA, Cherbuin N, Casper TC, Gorman MP, Benson LA, Chitnis T, Rensel M, Abrams AW, Lotze T, Mar SS, Schreiner TL, Wheeler YS, Rose JW, Graves J, Krupp LB, Waldman AT, Lucas R, Waubant E; as the US Network of Pediatric Multiple Sclerosis Centers. Association Between Sun Exposure and Risk of Relapse in Pediatric-Onset Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2025 Mar;12(2):e200375. doi: 10.1212/NXI.0000000000200375. Epub 2025 Feb 12. PMID: 39938013; PMCID: PMC11820808.

Abstract

Background and Objectives

Low sun and ultraviolet radiation (UVR) exposures have been associated with increased risk of developing pediatric-onset multiple sclerosis (MS); however, their effect on disease course has not been well characterized. We primarily investigated whether there was an association between time spent in the sun in early childhood and risk of relapse in pediatric MS. We secondarily investigated the effect of sun exposure during more recent periods on risk of relapse.

Methods

We conducted a multicenter cohort study of participants with pediatric-onset MS recruited from 18 pediatric MS clinics across the United States between November 1, 2011, and July 1, 2017. Relapses were identified prospectively after study enrollment; relapses preceding study enrollment were entered retrospectively. Time spent in the sun at various periods of life was measured using a detailed environmental questionnaire, and ambient UVR exposure was determined using zip codes. Multivariable Cox regression models were used to assess the association between time spent in the sun and UVR dose at specific periods of life and the risk of relapse. Models were adjusted for demographic, clinical, and sun exposure–related characteristics.

Results

In our cohort of 334 children with MS, 206 (62%) experienced at least one relapse from disease onset to the end of the follow-up period. After adjustment, ≥30 minutes of daily sun exposure during the first summer of life was associated with a lower risk of relapse compared with <30 minutes (adjusted hazard ratio [aHR] 0.67, CI 0.48–0.92, p = 0.01). Greater time spent in the sun during the second trimester of pregnancy was also associated with reduced risk of relapse (aHR 0.68, CI 0.48–0.97, p = 0.04). UVR dose and time spent in the sun later in life were not significantly associated with relapse risk.

Discussion

In this large cohort study of children with MS, greater early childhood and prenatal sun exposure time was associated with lower risk of relapse. Further investigation of sun exposure at other periods is needed to better characterize its impact on disease course and guide potential future interventions.

CHD8 mutations in autism and brain development

Hoffmann A, Spengler D. Chromatin Remodeler CHD8 in Autism and Brain Development. J Clin Med. 2021 Jan 19;10(2):366. doi: 10.3390/jcm10020366. PMID: 33477995; PMCID: PMC7835889.

Abstract

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including 'humanized' mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans.

Weissberg O, Elliott E. The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders. Genes (Basel). 2021 Jul 26;12(8):1133. doi: 10.3390/genes12081133. PMID: 34440307; PMCID: PMC8393912.

Abstract

Chromodomain-helicase-DNA-binding protein 8 (CHD8) has been identified as one of the genes with the strongest association with autism. The CHD8 protein is a transcriptional regulator that is expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis. Considering the central role of CHD8 in the genetics of autism, a deeper understanding of the physiological functions of CHD8 is important to understand the development of the autism phenotype and potential therapeutic targets. Different CHD8 mutant mouse models were developed to determine autism-like phenotypes and to fully understand their mechanisms. Here, we review the current knowledge on CHD8, with an emphasis on mechanistic lessons gained from animal models that have been studied.

Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP, Penn O, Witherspoon K, Gerdts J, Baker C, Vulto-van Silfhout AT, Schuurs-Hoeijmakers JH, Fichera M, Bosco P, Buono S, Alberti A, Failla P, Peeters H, Steyaert J, Vissers LELM, Francescatto L, Mefford HC, Rosenfeld JA, Bakken T, O'Roak BJ, Pawlus M, Moon R, Shendure J, Amaral DG, Lein E, Rankin J, Romano C, de Vries BBA, Katsanis N, Eichler EE. Disruptive CHD8 mutations define a subtype of autism early in development. Cell. 2014 Jul 17;158(2):263-276. doi: 10.1016/j.cell.2014.06.017. Epub 2014 Jul 3. PMID: 24998929; PMCID: PMC4136921.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous disease in which efforts to define subtypes behaviorally have met with limited success. Hypothesizing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 mutations, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints. chd8 disruption in zebrafish recapitulates features of the human phenotype, including increased head size as a result of expansion of the forebrain/midbrain and impairment of gastrointestinal motility due to a reduction in postmitotic enteric neurons. Our findings indicate that CHD8 disruptions define a distinct ASD subtype and reveal unexpected comorbidities between brain development and enteric innervation.

Multiple sulfatase deficiency 2

Finglas A. View from inside: When multiple sulfatase deficiency changes everything about how you live and becomes your life. J Inherit Metab Dis. 2020 Nov;43(6):1143-1153. doi: 10.1002/jimd.12305. Epub 2020 Sep 24. PMID: 32845037.

Full article available through PubMed and Wiley. 

https://onlinelibrary.wiley.com/doi/10.1002/jimd.12305

10 CONCLUSION

I started this wave of support for MSD research hoping that Dylan could benefit in his lifetime from our efforts, and this hope remains. I also knew that many MSD patients and their families across the world could benefit if we can ensure science delivers a treatment. I will endeavor to do my best to assist the other MSD foundations that might wish to lean on my experience. Especially with regard to identifying research gaps and funding research in the future. I expect that together we can make life-changing differences for patients. I anticipate that funding from the various MSD charities can complement research initiatives that are underway and that show the most potential.

I wish that one day there will be treatment options available to MSD patients and that their families can appreciate it and enjoy a better life with their children. Without knowing the struggle and huge sacrifices by many, that it took to get treatments is something I wish my family could have had! There are many difficulties with trying to develop potential therapies for ultra-rare diseases that I realized in time due to my journey with MSD. There could be an element of bliss in not knowing these difficulties. If I ever get a call, one day, from a parent of a child affected by MSD to thank me for my efforts when there is a treatment… I would simply say that it was the many people who believed and supported our cause are the ones that really made it happen.

Family July 2019


I have invested so much of myself in MSD research I cannot ever see myself being able to walk away. I want to witness the first child being treated, with the efforts that have gone in this would be a very emotional experience! Many research initiatives have moved on and real progress has been made and for this I am so grateful. However, when you have a child that is affected by something as relentless as MSD, research is never fast enough. You have no option but to witness a decline in your child, which is soul destroying, while you try to do your best for them due to love. Having a child affected by MSD, and no treatment, is like starting with a piece of rock, every day a little bit gets chipped away, you cannot necessarily see it, but one day it will be gone.

SORD neuropathy 2

Pons N, Fernández-Eulate G, Pegat A, Théaudin M, Guieu R, Ripellino P, Devedjian M, Mace P, Masingue M, Léonard-Louis S, Petiot P, Roche P, Bernard E, Bouhour F, Good JM, Verschueren A, Grapperon AM, Salort E, Grosset A, Chanson JB, Nadaj-Pakleza A, Bédat-Millet AL, Choumert A, Barnier A, Hamdi G, Lesca G, Prieur F, Bruneel A, Latour P, Stojkovic T, Attarian S, Bonello-Palot N. SORD-related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages. Eur J Neurol. 2023 Jul;30(7):2001-2011. doi: 10.1111/ene.15793. Epub 2023 Apr 4. PMID: 36943151.

Abstract

Background and purpose: Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD-related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.

Methods: Patients followed at neuromuscular reference centres in France and Switzerland were ascertained. Sanger sequencing and next generation sequencing were performed to sequence SORD, and mass spectrometry was used to measure patients' serum sorbitol.

Results: Thirty patients had SORD peripheral neuropathy associating LL weakness with muscular atrophy, foot deformities (87%), and sometimes proximal LL weakness (20%) or distal upper limb weakness (50%). Eighteen had dHMN, nine had CMT2, and three had intermediate CMT. Most of them had a mild or moderate disease severity. Sixteen carried a homozygous c.757delG (p.Ala253Glnfs*27) variant, and 11 carried compound heterozygous variants, among which four variants were not yet reported: c.403C > G, c.379G > A, c.68_100 + 1dup, and c.850dup. Two unrelated patients with different origins carried a homozygous c.458C > A variant, and one patient carried a new homozygous c.786 + 5G > A variant. Mean serum sorbitol levels were 17.01 mg/L ± 8.9 SD for patients carrying SORD variants.

Conclusions: This SORD-inherited peripheral neuropathy cohort of 30 patients showed homogeneous clinical presentation and systematically elevated sorbitol levels (22-fold) compared to controls, with both diagnostic and potential therapeutic implications.

Laššuthová P, Mazanec R, Staněk D, Sedláčková L, Plevová B, Haberlová J, Seeman P. Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients. Sci Rep. 2021 Apr 19;11(1):8443. doi: 10.1038/s41598-021-86857-0. PMID: 33875678; PMCID: PMC8055917.

Abstract

Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained the spectrum and frequency of SORD variants among a large cohort of Czech patients with unknown cause of HN. Exome sequencing data were analysed for SORD (58 patients). The prevalent c.757del variant was tested with fragment analysis (931 patients). Sanger sequencing in additional 70 patients was done. PCR primers were designed to amplify the SORD gene with the exclusion of the pseudogene SORD2P. Sequence differences between gene and pseudogene were identified and frequencies of SNPs were calculated. Eighteen patients from 16 unrelated families with biallelic variants in the SORD gene were found and the c.757del was present in all patients on at least one allele. Three novel, probably pathogenic, variants were detected, always in a heterozygous state in combination with the c.757del on the second allele. Patients presented with a slowly progressive axonal HN. Almost all patients had moderate pes cavus deformity. SORD neuropathy is frequent in Czech patients and the third most common cause of autosomal recessive HN. The c.757del is highly prevalent. Specific amplification of the SORD gene with the exclusion of the pseudogene is essential for a precise molecular diagnostics.

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

Rahman S, Copeland WC. POLG-related disorders and their neurological manifestations. Nat Rev Neurol. 2019 Jan;15(1):40-52. doi: 10.1038/s41582-018-0101-0. PMID: 30451971; PMCID: PMC8796686.

Abstract

The POLG gene encodes the mitochondrial DNA polymerase that is responsible for replication of the mitochondrial genome. Mutations in POLG can cause early childhood mitochondrial DNA (mtDNA) depletion syndromes or later-onset syndromes arising from mtDNA deletions. POLG mutations are the most common cause of inherited mitochondrial disorders, with as many as 2% of the population carrying these mutations. POLG-related disorders comprise a continuum of overlapping phenotypes with onset from infancy to late adulthood. The six leading disorders caused by POLG mutations are Alpers-Huttenlocher syndrome, which is one of the most severe phenotypes; childhood myocerebrohepatopathy spectrum, which presents within the first 3 years of life; myoclonic epilepsy myopathy sensory ataxia; ataxia neuropathy spectrum; autosomal recessive progressive external ophthalmoplegia; and autosomal dominant progressive external ophthalmoplegia. This Review describes the clinical features, pathophysiology, natural history and treatment of POLG-related disorders, focusing particularly on the neurological manifestations of these conditions.

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/

Solomon BD. VACTERL/VATER Association. Orphanet J Rare Dis. 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383; PMCID: PMC3169446.

Abstract

VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.

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