Sunday, March 31, 2024

Amniotic band syndrome

No, My Baby Isn't an 'Alien' — She's a Fighter Who Deserves a Chance

I always wanted to be a mother. When I found out I was pregnant, I was the happiest woman in the whole world. I couldn’t stop thinking about that little person that would join our family and would be so loved by my husband and me. The first three months of gestation were full of joy, curiosities, and a lot of wondering: If it was a boy or a girl, what his or her name would be, etc.

We used to talk to our baby every day, telling her that daddy and mommy were waiting for her. We were very excited to go to consultations every month and see the ultrasounds of her development. That changed when I reached the fourth month of pregnancy.

During that appointment the OB-GYN observed something abnormal, but he didn’t give us more specifics.

He only asked me to perform a 3D ultrasound where he could observe more details of the baby’s anatomy. We scheduled an appointment in a clinic where they had the equipment necessary to fully analyze organs and physiognomy of a fetus. When the day came to go to the consultation, we went in full of nerves and worries.

That day was devastating … we received the news that Helianny had many deformations of her hands, feet, eyes, lips, nose, skull, and brain. Only her other organs and [spinal] column were OK. Her condition was the result of amniotic band syndrome. She became entangled in string-like amniotic bands in the womb. That restricted her blood flow and affected her development.

While I cried inconsolably, the doctor suggested donating her organs. It seemed so cruel on her part to ask that at such a tragic moment in our lives. We left that office with our hearts broken and our dreams shattered. My husband and I felt an inexplicable pain like nothing we’ve ever felt before.

After crying for a long time, we stared into each other’s eyes; we hugged, and my husband said in my ear, "Let’s keep going. Do you want to?

I immediately told him yes of course I wanted to. And that’s how we decided to keep the pregnancy — we decided to give Helianny a chance. We immediately started seeking other medical opinions but the news just kept getting worse. Almost all the doctors suggested the same thing, to end the pregnancy, because it was in vain to continue since they predicted that Helianny would die in my womb or if we were lucky enough, she would be born alive but die shortly after delivery.

I have always believed in God and I clung to my unconditional faith. I went back to my OB-GYN and told him with an unwavering stance, "I will continue this pregnancy. Please manage it like any other," and so he did as I asked.

Against all odds, Helianny was born alive on August 21, 2015, at 39 weeks via C-section, weighing 10 lbs and measuring 18 inches.Against all odds, Helianny was born alive on August 21, 2015, at 39 weeks via C-section, weighing 10 lbs and measuring 18 inches.

The first days were very difficult. Due to my condition, I was only able to see her after 24 hours. The nurses started whispering that I didn’t want to see my own daughter, that I was rejecting her. After hearing those comments, I decided to try to get up even with the extreme pain I was feeling. When I first saw Helianny, I touched her face, caressed her hands and feet. I told her "Your mom is here."

I admit her appearance might seem shocking to most people. She had three protrusions on her head where her skull was not properly formed. Helianny had no eyebrows and had very pronounced veins on her forehead that seemed about to burst. Her eyes and nose were nonexistent; she had only two nasal holes, but she couldn’t breathe through them.

However, to me, she was beautiful in her own way.

Helianny was able to come home with her father and me after 13 days in observation. I felt at a crossroads without knowing where to go from there and without any guidance. To make matters worse, I live in Venezuela, and even three years ago, conditions were not good and have only gotten worse.

We struggled to get medical help and the financial resources needed to perform her first round of surgeries.

Because of her breathing issues, for the first months of her life we had to monitor her sleep every night.

My husband, mother-in-law, and I took three-hour shifts in case Helianny needed help. After some months, the time for her first intervention arrived (the installation of the valve in her head to control fluid in her brain). The same story repeated itself. The anesthesiologist said she didn’t believe that Helianny could survive this operation. But I was confident that my daughter would come out alive and Helianny didn’t disappoint me — the surgery was a success.

I thank God because so far everything has worked out. She had two other operations to correct a clubfoot and to release her lip. Helianny needs other surgeries (craniofacial reconstruction, eye prosthesis, nasal pyramid among others) but due to lack of financial resources we’ve had to put a hold on those.

Helianny has taught us to be strong and to be better every day.

Sometimes it’s impossible to not be uncomfortable when people stare at us in the street and see her as an alien. That’s why I dream about those surgeries — so they can see her like I do, as a beautiful little girl.

Of course other surgeries and more therapy will help to improve her quality of life. I want people to know that she has her own personality. She likes the water and the sound it makes, dogs barking make her laugh, she loves listening to music, and she finds her own way to show us that she loves us like when she touches our face when we speak to her.

She turned 3 years old in August, something that no one thought possible. She keeps defying all odds. Many times we complain about nonsense and I believe that Helianny teaches us that life is beautiful but short, and it’s up to us to make the best of it.

Nowadays, Helianny is attending therapies and I’ve seen a lot of improvement.

She recently was able to control her head a little more. I know that the remaining path is long, but we are willing to be by her side and do whatever is necessary for her well-being. We all have the right to an opportunity in life, and my little one also has that right. Sometimes I wonder what would happen to her when we are not here, and I always have to remind myself that the future is uncertain.

Sadly, many people attack her (and me) online but I reply that things can change in a second and suddenly you can be in a situation where you depend on others for everything.

I ask them, "Do you not deserve to live any more then?" Society wants to preach that we are equal but rarely apply it to real life if you are not "normal." In spite of all this, we try to live a normal life and include Helianny in all of our activities. We take her to birthdays parties and different social events. After all the ups and down and despite this long, difficult road, we feel blessed to be Helianny’s parents.

This post was written by Soleannys Carolina Lugo Estrada and reprinted with permission.


Thursday, March 28, 2024

Givinostat for Duchenne and Becker muscular dystrophy

Duvyzat (givinostat; Italfarmaco SpA, Milan, Italy), a histone deacetylase (HDAC) inhibitor, was approved by the Food and Drug Administration (FDA) to treat Duchenne muscular dystrophy (DMD) in individuals aged >6 years. This is the first nonsteroidal drug approved to treat DMD.

FDA approval was based upon results from the EPIDYS clinical trial (NCT02851797), a phase 3, randomized, double-blind, placebo-controlled trial, which evaluated the safety and efficacy of Duvyzat in ambulant boys with DMD. The study included 179 boys aged ≥6 years with genetically confirmed DMD, who were stratified based on their baseline vastus lateralis fat fraction (VLFF) into group A (VLFF >5% to ≤30%) and group B (VLFF ≤5% or >30%). Participants were randomized 2:1 to receive oral Duvyzat or placebo twice daily for 72 weeks, with dose adjustments based on weight and tolerability.

The study met the primary endpoint, which compared the mean change between baseline and 72 weeks in the ability to climb 4 stairs in the intention-to-treat, group A population. Additionally, secondary endpoints assessing muscle function and strength showed favorable results.

Duvyzat-treated individuals showed a slower decline in performing the four-stair climb assessment compared to placebo-treated individuals (difference vs placebo of 1.78 seconds, P=.037).
Duvyzat treatment was associated with 40% less decline in the North Star Ambulatory Assessment (NSAA) total score and item loss.
Duvyzat-treated individuals had a 30% reduction in vastus lateralis fat fraction (VLFF), a predictor of loss of ambulation, compared to the placebo-treated cohort.

The most common adverse events associated with givinostat treatment were diarrhea (36% vs 18% with placebo) and vomiting (29% vs 13% with placebo). No treatment-related deaths occurred.

According to prescribing information provided for Duvyzat, health care providers need to evaluate patient’s platelet counts and triglycerides prior to prescribing Dyvyzat and on an ongoing basis following treatment. Duvyzat also may cause QTc prolongation, and patients taking medications associated with QTc prolongation or who have certain heart disease types should avoid taking Duvyzat.

Comi GP, Niks EH, Vandenborne K, Cinnante CM, Kan HE, Willcocks RJ, Velardo D, Magri F, Ripolone M, van Benthem JJ, van de Velde NM, Nava S, Ambrosoli L, Cazzaniga S, Bettica PU. Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study. Front Neurol. 2023 Jan 30;14:1095121. doi: 10.3389/fneur.2023.1095121. PMID: 36793492; PMCID: PMC9923355.


Objective: No treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD.

Methods: Males aged 18-65 years with a diagnosis of BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment with givinostat or placebo. The primary objective was to demonstrate statistical superiority of givinostat over placebo for mean change from baseline in total fibrosis after 12 months. Secondary efficacy endpoints included other histological parameters, magnetic resonance imaging and spectroscopy (MRI and MRS) measures, and functional evaluations.

Results: Of 51 patients enrolled, 44 completed treatment. At baseline, there was greater disease involvement in the placebo group than givinostat, based on total fibrosis (mean 30.8 vs. 22.8%) and functional endpoints. Mean total fibrosis did not change from baseline in either group, and the two groups did not differ at Month 12 (least squares mean [LSM] difference 1.04%; p = 0.8282). Secondary histology parameters, MRS, and functional evaluations were consistent with the primary. MRI fat fraction in whole thigh and quadriceps did not change from baseline in the givinostat group, but values increased with placebo, with LSM givinostat-placebo differences at Month 12 of -1.35% (p = 0.0149) and -1.96% (p = 0.0022), respectively. Adverse events, most mild or moderate, were reported by 88.2% and 52.9% patients receiving givinostat and placebo.

Conclusion: The study failed to achieve the primary endpoint. However, there was a potential signal from the MRI assessments suggesting givinostat could prevent (or slow down) BMD disease progression.

Giovarelli M, Zecchini S, Catarinella G, Moscheni C, Sartori P, Barbieri C, Roux-Biejat P, Napoli A, Vantaggiato C, Cervia D, Perrotta C, Clementi E, Latella L, De Palma C. Givinostat as metabolic enhancer reverting mitochondrial biogenesis deficit in Duchenne Muscular Dystrophy. Pharmacol Res. 2021 Aug;170:105751. doi: 10.1016/j.phrs.2021.105751. Epub 2021 Jun 29. PMID: 34197911.


Duchenne Muscular Dystrophy (DMD) is a rare disorder characterized by progressive muscle wasting, weakness, and premature death. Remarkable progress has been made in genetic approaches, restoring dystrophin, or its function. However, the targeting of secondary pathological mechanisms, such as increasing muscle blood flow or stopping fibrosis, remains important to improve the therapeutic benefits, that depend on tackling both the genetic disease and the downstream consequences. Mitochondrial dysfunctions are one of the earliest deficits in DMD, arise from multiple cellular stressors and result in less than 50% of ATP content in dystrophic muscles. Here we establish that there are two temporally distinct phases of mitochondrial damage with depletion of mitochondrial mass at early stages and an accumulation of dysfunctional mitochondria at later stages, leading to a different oxidative fibers pattern, in young and adult mdx mice. We also observe a progressive mitochondrial biogenesis impairment associated with increased deacetylation of peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) promoter. Such histone deacetylation is inhibited by givinostat that positively modifies the epigenetic profile of PGC-1α promoter, sustaining mitochondrial biogenesis and oxidative fiber type switch. We, therefore, demonstrate that givinostat exerts relevant effects at mitochondrial level, acting as a metabolic remodeling agent capable of efficiently promoting mitochondrial biogenesis in dystrophic muscle.

Tuesday, March 26, 2024

Krabbe disease

Many years ago I saw a 10 months infant male due to concerns regarding developmental regression. On examination it was evident that something dreadful was happening. A workup was initiated. For cerebral imaging a preoperative examination was necessary. The mother told me the pediatrician said, "Why, he looks pretty normal to me." (On another occasion the same pediatrician called me about a baby in the normal newborn nursery. The neonate had  lost interest in feeding. A variety of laboratory studies were obtained. The pediatrician mentioned that an ammonia was 400-500, He said, "I was planning on rechecking it tomorrow." I said, recheck it right now and I'll be over. The recheck value was greater than 1,000. Within hours the newborn was transferred to the University of Minnesota to be treated with peritoneal dialysis. The diagnosis was propionic acidemia. But I digress.) Lysosomal hydrolases were requested. I then had a call from David Wenger. "Guess the diagnosis," he said. Krabbe was my correct guess. The infant had an asymptomatic 2 year old brother. He was then tested, leading to a second phone call from David Wenger. Since the 2 year old was asymptomatic, he was deemed eligible for bone marrow transplantation. This was the first unrelated cord blood transplant done at the University of Minnesota. The transplantation was successful. I followed the older brother to adulthood. He had some attention difficulties and some tightness of the heel cords. See:

A somewhat similar story. See:

Newborn screening:


Thursday, March 21, 2024

Atidarsagene autotemcel for metachromatic leukodystrophy

The Food and Drug Administration (FDA) granted approval for Lenmeldy (atidarsagene autotemcel, Orchard Therapeutics, London, UK), the first gene therapy for children with pre-symptomatic late infantile, pre-symptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy (MLD). MLD is a rare genetic disorder affecting the brain and nervous system caused by a deficiency of the enzyme arylsulfatase A (ARSA), leading to sulfatide accumulation and severe neurological damage. The therapy involves a one-time infusion of genetically modified hematopoietic stem cells (HSCs) containing functional ARSA genes, aiming to halt disease progression.

Lenmeldy's approval was based on data from clinical trials showing improved motor function and survival rates in treated children compared to untreated individuals. Notably, treated children exhibited enhanced motor skills, cognitive function, and survival rates, highlighting the therapy's potential to alter disease outcomes positively.

According to a statement from Nicole Verdun, MD, Director of the Office of Therapeutic Products at the FDA’s Center for Biologics Evaluation and Research (CBER), “MLD is a devastating disease that profoundly affects the quality of life of patients and their families. “This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.”

Treatment with Lenmeldy requires preconditioning. The safety profile of Lenmeldy includes common side effects like fever and infections, necessitating close monitoring post-treatment for potential complications such as blood clots or encephalitis. Patients are advised to undergo lifelong monitoring for blood-related issues due to a potential risk of blood cancer associated with the therapy.

Horgan C, Watts K, Ram D, Rust S, Hutton R, Jones S, Wynn R. A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie ahead. JIMD Rep. 2023 Jun 22;64(5):346-352. doi: 10.1002/jmd2.12378. PMID: 37701322; PMCID: PMC10494509.


Metachromatic leukodystrophy (MLD) results from ARSA gene mutations. Affected individuals meet early milestones before neurological deterioration and early death. Atidarsagene autotemcel (arsa-cel), an autologous haematopoietic stem cell gene therapy (HSC-GT) product, has demonstrated sustained clinical benefits in MLD. Arsa-cel was approved for NHS treatment in February 2022 for asymptomatic late infantile or early juvenile disease, or early symptomatic early juvenile MLD. We evaluate the impact of this approval in the largest real-world dataset of MLD HSC-GT. Hospital records were reviewed for all patients referred for NHS treatment following arsa-cel approval. Information was gathered about disease phenotype, presentation, eligibility, and affected siblings. In the year following NHS approval, 17 UK MLD patients were referred for treatment. Four patients met eligibility criteria and have been treated, including 1 infant who weighed 5 kg at leukapheresis. Eleven patients failed screening: 10 symptomatic patients with late infantile disease and 1 with early juvenile disease and cognitive decline. Two further patients with later onset subtypes did not meet the approval criteria. Three out of four treated patients were diagnosed by screening after MLD was diagnosed in a symptomatic older sibling. The success of HSC-GT for MLD has heralded a new era of hope for families affected by this devastating disease, yet currently, most patients are ineligible for treatment at diagnosis. The feasibility of apheresis in infants and the availability of a licenced, effective HSC-GT product highlights the urgent need for newborn screening to ensure that patients can be diagnosed and treated before symptom onset.

Messina M, Gissen P. Atidarsagene autotemcel for metachromatic leukodystrophy. Drugs Today (Barc). 2023 Feb;59(2):63-70. doi: 10.1358/dot.2023.59.2.3461911. PMID: 36811406.


Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder of sphingolipid metabolism, due to a deficiency of the enzyme arylsulfatase A (ARSA). The main clinical signs of the disease are secondary to central and peripheral nervous system demyelination. MLD is subdivided into early- and late-onset subtypes based upon the onset of neurological disease. The early-onset subtype is associated with a more rapid progression of the disease that leads to death within the first decade of life. Until recently, no effective treatment was available for MLD. The blood-brain barrier (BBB) prevents systemically administered enzyme replacement therapy from reaching target cells in MLD. The evidence for the efficacy of hematopoietic stem cell transplantation is limited to the late-onset MLD subtype. Here, we review the preclinical and clinical studies that facilitated the approval of the ex vivo gene therapy atidarsagene autotemcel for early-onset MLD by the European Medicines Agency (EMA) in December 2020. This approach was studied in an animal model first and then in a clinical trial, eventually proving its efficacy in preventing disease manifestations in presymptomatic patients and stabilizing its progression in paucisymptomatic subjects. This new therapeutic consists of patients' CD34+ hematopoietic stem/progenitor cells (HSPCs) transduced with a lentiviral vector encoding functional ARSA cDNA. The gene-corrected cells get reinfused into the patients after a cycle of chemotherapy conditioning.

Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet. 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785; PMCID: PMC8795071.


Background: Effective treatment for metachromatic leukodystrophy (MLD) remains a substantial unmet medical need. In this study we investigated the safety and efficacy of atidarsagene autotemcel (arsa-cel) in patients with MLD.

Methods: This study is an integrated analysis of results from a prospective, non-randomised, phase 1/2 clinical study and expanded-access frameworks. 29 paediatric patients with pre-symptomatic or early-symptomatic early-onset MLD with biochemical and molecular confirmation of diagnosis were treated with arsa-cel, a gene therapy containing an autologous haematopoietic stem and progenitor cell (HSPC) population transduced ex vivo with a lentiviral vector encoding human arylsulfatase A (ARSA) cDNA, and compared with an untreated natural history (NHx) cohort of 31 patients with early-onset MLD, matched by age and disease subtype. Patients were treated and followed up at Ospedale San Raffaele, Milan, Italy. The coprimary efficacy endpoints were an improvement of more than 10% in total gross motor function measure score at 2 years after treatment in treated patients compared with controls, and change from baseline of total peripheral blood mononuclear cell (PBMC) ARSA activity at 2 years after treatment compared with values before treatment. This phase 1/2 study is registered with, NCT01560182.

Findings: At the time of analyses, 26 patients treated with arsa-cel were alive with median follow-up of 3·16 years (range 0·64-7·51). Two patients died due to disease progression and one due to a sudden event deemed unlikely to be related to treatment. After busulfan conditioning, all arsa-cel treated patients showed sustained multilineage engraftment of genetically modified HSPCs. ARSA activity in PBMCs was significantly increased above baseline 2 years after treatment by a mean 18·7-fold (95% CI 8·3-42·2; p<0·0001) in patients with the late-infantile variant and 5·7-fold (2·6-12·4; p<0·0001) in patients with the early-juvenile variant. Mean differences in total scores for gross motor function measure between treated patients and age-matched and disease subtype-matched NHx patients 2 years after treatment were significant for both patients with late-infantile MLD (66% [95% CI 48·9-82·3]) and early-juvenile MLD (42% [12·3-71·8]). Most treated patients progressively acquired motor skills within the predicted range of healthy children or had stabilised motor performance (maintaining the ability to walk). Further, most displayed normal cognitive development and prevention or delay of central and peripheral demyelination and brain atrophy throughout follow-up; treatment benefits were particularly apparent in patients treated before symptom onset. The infusion was well tolerated and there was no evidence of abnormal clonal proliferation or replication-competent lentivirus. All patients had at least one grade 3 or higher adverse event; most were related to conditioning or to background disease. The only adverse event related to arsa-cel was the transient development of anti-ARSA antibodies in four patients, which did not affect clinical outcomes.

Interpretation: Treatment with arsa-cel resulted in sustained, clinically relevant benefits in children with early-onset MLD by preserving cognitive function and motor development in most patients, and slowing demyelination and brain atrophy.

Faccioli S, Sassi S, Pandarese D, Borghi C, Montemaggiori V, Sarzana M, Scarparo S, Butera C, Calbi V, Aiuti A, Fumagalli F. Preserving Ambulation in a Gene Therapy-Treated Girl Affected by Metachromatic Leukodystrophy: A Case Report. J Pers Med. 2023 Apr 6;13(4):637. doi: 10.3390/jpm13040637. PMID: 37109023; PMCID: PMC10144348.


(1) Background: Atidarsagene autotemcel is a hematopoietic stem and progenitor cell gene therapy (HSPC-GT) approved to treat early-onset metachromatic leukodystrophy (MLD). The purpose of this case report is to describe the long-term management of residual gait impairment of a child with late infantile MLD treated with HSPC-GT. (2) Methods: Assessment included Gross Motor Function Measure-88, nerve conduction study, body mass index (BMI), Modified Tardieu Scale, passive range of motion, modified Medical Research Council scale, and gait analysis. Interventions included orthoses, a walker, orthopedic surgery, physiotherapy, and botulinum. (3) Results: Orthoses and a walker were fundamental to maintaining ambulation. Orthopedic surgery positively influenced gait by reducing equinovarus. Nonetheless, unilateral recurrence of varo-supination was observed, attributable to spasticity and muscle imbalance. Botulinum improved foot alignment but induced transient overall weakness. A significant increase in BMI occurred. Finally, a shift to bilateral valgopronation was observed, more easily managed with orthoses. (4) Conclusions: HSPC-GT preserved survival and locomotor abilities. Rehabilitation was then considered fundamental as a complementary treatment. Muscle imbalance and increased BMI contributed to gait deterioration in the growing phase. Caution is recommended when considering botulinum in similar subjects, as the risk of inducing overall weakness can outweigh the benefits of spasticity reduction.

Wednesday, March 20, 2024

Efgartigimod in generalized myasthenia gravis

Frangiamore R, Rinaldi E, Vanoli F, Andreetta F, Ciusani E, Bonanno S, Maggi L, Gallone A, Colasuonno A, Tramacere I, Cheli M, Pinna A, Mantegazza R, Antozzi C. Efgartigimod in generalized myasthenia gravis: A real-life experience at a national reference center. Eur J Neurol. 2024 Apr;31(4):e16189. doi: 10.1111/ene.16189. Epub 2024 Jan 2. PMID: 38164996.


Background and purpose: Inhibition of the neonatal Fc receptor (FcRn) for IgG is a promising new therapeutic strategy for antibody-mediated disorders. We report our real-life experience with efgartigimod (EFG) in 19 patients with generalized myasthenia gravis (gMG) along a clinical follow-up of 14 months.

Methods: EFG was administered according to the GENERATIVE protocol (consisting of a Fixed period of two treatment cycles [given 1 month apart] of four infusions at weekly intervals, followed by a Flexible period of re-cycling in case of worsening). Eight patients were positive for acetylcholine receptor antibody, four for muscle-specific tyrosine kinase antibody, and two for lipoprotein-related protein 4 antibody, and five were classified as triple negative. Efficacy of EFG was assessed by the Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Composite, and Quantitative Myasthenia Gravis scales.

Results: Fifty-three percent of patients needed three treatment cycles, 26% needed four, and 21% needed five along the 14-month clinical follow-up. Meaningful improvement was observed at the end of each cycle with the clinical scores adopted. EFG had a dramatic effect on disease course, as during the year before treatment eight of 19 patients (42%) were hospitalized, and 15 of 19 (79%) needed treatment with plasma exchange or immunoglobulins; three of 19 (16%) were admitted to the intensive care unit. During EFG, none of the patients was hospitalized and only one patient required plasma exchange and intravenous immunoglobulins. No major side effects or infusion-related reactions occurred.

Conclusions: We observed that EFG was safe and modified significantly the course of the disease along a 14-month follow-up. Our experience strengthens the role of FcRn inhibition as an effective new tool for long-term treatment of gMG.

Howard JF Jr, Bril V, Vu T, Karam C, Peric S, De Bleecker JL, Murai H, Meisel A, Beydoun SR, Pasnoor M, Guglietta A, Van Hoorick B, Steeland S, T'joen C, Utsugisawa K, Verschuuren J, Mantegazza R; ADAPT+ Study Group. Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis. Front Neurol. 2024 Jan 17;14:1284444. doi: 10.3389/fneur.2023.1284444. PMID: 38318236; PMCID: PMC10842202.


Objective: ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).

Methods: ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.

Results: As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab-. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab- participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5-7.6]).

Conclusion: Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.

Howard JF Jr, Bril V, Burns TM, Mantegazza R, Bilinska M, Szczudlik A, Beydoun S, Garrido FJRR, Piehl F, Rottoli M, Van Damme P, Vu T, Evoli A, Freimer M, Mozaffar T, Ward ES, Dreier T, Ulrichts P, Verschueren K, Guglietta A, de Haard H, Leupin N, Verschuuren JJGM; Efgartigimod MG Study Group. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology. 2019 Jun 4;92(23):e2661-e2673. doi: 10.1212/WNL.0000000000007600. Epub 2019 May 22. PMID: 31118245; PMCID: PMC6556100.


Objective: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.

Methods: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.

Results: Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.

Conclusions: Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.

Classification of evidence: This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

Tuesday, March 19, 2024

First child to an 88 year old father

The incredible news that Rosh HaYeshivah HaGaon HaRav Tzvi Kushelevsky welcomed his first child, a ben bechor, at the age of 88 on Sunday morning spread quickly on Israeli media and was even widely reported on secular sites.

After the Rosh HaYeshivah left the hospital, the first place he went to was the home of HaGaon HaRav Moshe Shternbuch to thank him for the bracha he gave him nine months ago that he’ll be zocheh to a ben zachar.

According to a B’Chadrei Chareidim report, HaRav Kushelevsky, who got married to his second wife six years ago, consulted with HaRav Shternbuch on the shidduch and after it was finalized, asked him to be the mesadeir kiddushin. According to HaRav Kushelevsky’s talmidim, immediately after the siddur kiddushin, HaRav Shternbuch told the Rosh Yeshivah: “You’ll be zocheh to have zera shel kayama from this zivug.”

But in the past year, HaRav Shternbuch added another bracha: “You’ll be zocheh to a ben zachar.” Nine months months later, the baby was born.

When HaRav Kushelevsky arrived at HaRav Shternbuch’s home to thank him for his bracha, the Rav answered: “I don’t know if the bracha helped, the ikar is to thank Hashem. We were zochech that Hakadosh Baruch separated us from the goyim and we acknowledge when He does chasadim for us. By us, the goal is not the nissim in itself but the recognition of chasdei Hashem.”

HaRav Kushelevesky then asked for a bracha that his son be a big talmid chacham. HaRav Shternbuch responded that “that already depends only on you.”

A ben bechor was born to Rosh Yeshivas Heichal HaTorah HaGaon HaRav Tzvi Kushelevsky, 88, on Sunday morning.

The Rosh Yeshivah and his first wife, Rebbetzin Sora Leah, a’h, (the daughter of the Rosh Yeshiva of Gateshead, HaRav Aryeh Zev Gurwitz, z’tl) weren’t zohech to children. After the Rebbetzin passed away six years ago, HaRav Tzvi remarried to his second wife, a US native who was 50 at the time and had two children.

This morning, after five years of marriage, a baby boy was born to the Rosh Yeshivah and his wife at Hadassah Ein Kerem Hospital in Jerusalem.

The woman in a bowl has died


A Nigerian girl with no limbs who lived her life in a plastic bowl has died.

Rahma Haruna, 19, became well known when photos of her appeared online earlier this year (2016). She suffered from a mysterious condition that stopped her arms and legs developing properly and was in constant pain.

She died on Dec 25 (2016).

News of her death was shared by local journalist Sani Maikatanga, whose photos were responsible for the wider world becoming aware of Rahma's plight, said a report in Britain's Telegraph.

Ms Maikatanga said in a social media post: "Rahma Haruna a 19 years old girl has pass away on Sunday 25th of December 2016... may Almighty grant her Jannatul Firdausi (paradise)."

Rahma, whose arms and legs stopped developing when she was six months old, lived with her family in the village of Lahadin Makole, close to Kano in Nigeria, the Telegraph reported.

Practically immobile and in chronic pain, for many years she spent most of her waking hours in a plastic bowl, which her family transported her around in.

Her younger brother Fahad would take her into Kano each day to beg for handouts.

However, last year a journalist, Ibrahim Jirgi, gave the family a wheelchair.

Earlier this year, Rahma's mother Fadi told reporters: "From six months when she learnt how to sit that was when it began. She didn't learn how to crawl.

"She started with a fever and that was it. Then stomach pains. Then her body parts like hands and legs. She cannot use any if the ache strikes."

Fahad revealed he dedicated much of his life to helping his sister: "I help her in many ways," he said.

"Bathing her is another thing I do, and taking her out every day.

"I feel happy whenever I see people helping her. I like taking to our relatives. She feels happy when we visit them."

The Haruna family experienced an upturn in their fortunes when Ms Maikatanga's images of Rahma went viral on social media, prompting an inundation of requests from strangers who wanted to help in any way they could, the Telegraph said.

Despite her severe disability, Rahma held entrepreneurial ambitions, telling journalists she dreamt of starting a business.

"A grocery store and anything people buy, that is what I want," she said.


Friday, March 15, 2024

Elective MRI full-body scan

As some doctors say, "If you look, you will find."

In August 2023, Mary Ann Waldron, a healthy Arizona woman, decided to undergo an elective MRI full-body scan at a SimonMed Imaging facility, never expecting to find anything serious.

She was shocked when the scan detected a large aneurysm in her pancreas area, ultimately saving her life.

Today, a strong proponent of full-body scans as a preventative measure, Waldron is eager to share her story as a cautionary tale for others.

"I believe we each need to take responsibility for our health," she told Fox News Digital. "I’m more than 70 years old, and despite being asymptomatic, I wanted to learn if I had any early-stage cancers."

Dr. Brett Osborn, a Florida neurologist and longevity expert, also recognizes the benefits of full-body MRI scans.

"Full-body scanning, mainly through MRI, presents a significant advancement in modern medicine's diagnostic capabilities," he told Fox News Digital. (He was not involved in Waldron's care.)

"MRI technology allows for a comprehensive, noninvasive examination of the body to detect a wide range of conditions, including cancer and vascular malformations like aneurysms, without the need for potentially harmful X-rays, as is the case with CT scans."

The results of Waldron’s scan indicated that there "may be an aneurysm." A follow-up CT scan of her abdomen and pancreas was then recommended.

"If in fact I had an aneurysm, then this was life-threatening, as death is imminent when an aneurysm bursts, unless the person is already in an operating suite," said Waldron.

Dr. Barry Sadegi, SimonMed's chief medical officer in Scottsdale, Arizona, emphasized the danger of Waldron’s condition.

"Pancreaticoduodenal artery aneurysms are extremely rare, representing only 2% of all splanchnic (abdominal organ) aneurysms," he told Fox News Digital.

"The majority (64%) of patients who seek treatment present after the aneurysm has ruptured."

Aneurysm rupture can be life-threatening, Sadegi confirmed, as it results in abdominal bleeding.

In many cases, there are no symptoms of an aneurysm, which was the case for Waldron.

"And because I had no prior imaging studies of this area for comparison, there was no way to know how long this aneurysm had been present or for how much longer it would exist before bursting," she added.

Once doctors confirmed that Waldron had an aneurysm, she was referred to a vascular surgeon, who determined that she would need immediate surgery.

"We scheduled the procedure and were advised to drive from Sedona to Chicago, as the risk of flying with changes in pressure was dangerous," she said. "The size and location of my aneurysm was unusually large and uncommon."

Waldron underwent an angiogram of the mesenteric artery (a major artery of the abdomen). The surgeon performed an embolization of the aneurysm, placing several titanium wires to block the artery and close off the sac of the aneurysm, preventing further blood flow and bursting.

Today, Waldron is feeling healthy and is back to her regular routines.

"It is now necessary for me to take daily blood thinners, which make me susceptible to bruising, but other than that I am feeling well," she told Fox News Digital.

"I have resumed my usual activities of golf, swimming and walking."

Waldron will continue to see her doctor every six months for the next couple of years for ultrasounds of the stented area.

"This was a truly life-saving surgery," she said.

"Generally, early detection enables early intervention, which provides the best opportunity for successful resolution. In my case, the detection was not early in the formation of the aneurysm, but was early enough to correct it."

She added, "I believe these scans can detect abnormalities at an early stage, helping us prolong our lives — and certainly the quality of our lives."

The majority of the U.S. health care system is reactive rather than proactive, Sadegi stated — "more focused on treating illness after it develops rather than preventing it."

The scan, he said, is a means of empowering patients who want to take an active role in their disease prevention.

"Although the American College of Radiology does not currently recommend MRI whole-body screening for the general population, many SimonONE patients have similar stories in which the scan resulted in very positive health outcomes," he said.

Some of the conditions that SimonMed’s scans have discovered have included other aneurysms, severe arterial stenoses in the neck and head, and masses in the brain, pituitary gland, neck, thyroid, mediastinum, lungs, liver, pancreas, kidneys, lymph nodes, bladder, endometrium and prostate gland, said Sadegi.

Because the MRI scans don’t use ionizing radiation, Sadegi said the test itself is low-risk.

There is the risk of overdiagnosis, however, as Osborn noted.

"This is where benign conditions are detected and treated unnecessarily, leading to undue stress, further testing, and potentially unnecessary interventions and their inevitable complications," he told Fox News Digital.

"These studies are imperfect," he told Fox News Digital. "Is the patient ready to deal with a positive finding? Often, it’s unclear whether a lesion is benign or malignant. And then what? Are these studies worth the ‘risk’ at this point?"

He added, "I defer to my patients and allow them to make an informed decision. To me, however, the benefits far outweigh the risks."

In Waldron’s case, she was OK with the risks.

"Because there can be false positives, one may argue that there is unnecessary expense in the whole-body scan and unnecessary radiation in the follow-up studies that confirm there are no issues," she said.

"I defer to my patients and allow them to make an informed decision. To me, however, the benefits far outweigh the risks."

"But this, in my opinion, is a minor trade-off for the peace of mind one achieves either knowing all is well or knowing what needs to be addressed."

This type of scan also has some limitations.

It does not screen for blood-borne tumors, such as leukemia, or for skin tumors, such as melanoma or basal cell carcinoma, according to Sadegi. It also might not detect smaller nodules in the lungs.

The scan is also not ideal for detecting musculoskeletal conditions involving bones or joints.

Sadegi said it cannot replace colonoscopies for colon or rectal screenings; and mammography and MRI of the breasts are more sensitive for breast cancer.

Right now, given the associated costs, most insurance carriers do not cover a full-body MRI, Osborn pointed out.

"The numbers don’t make sense to them," he said. "It’s simply a matter of dollars and cents. Many scans, at significant cost, would have to be performed to save one life … This is the ‘business’ of medicine and one of the main reasons why, historically speaking, insurance companies have not embraced preventive care."

That could change in the future, he said.

"As consumer interest in preventive care soars — and people want to live longer, healthier lives — it may be the driver of change."


A man suffering from severe migraines, obesity and complicated type-2 diabetes was found to have parasitic tapeworm larvae in his brain, which was the result of eating partially cooked bacon, according to a report published by the American Journal of Case Reports last week.

The 52-year-old man had a medical history of chronic migraines, type-2 diabetes mellitus which was complicated by peripheral neuropathy, hyperlipidemia and obesity.

The study noted that the man told doctors his migraines occurred almost weekly and were not responsive to medication. He also said he did not travel to high-risk areas, lived at home with his wife and cat, and preferred lightly cooked, non-crispy bacon, which he admitted having eaten most of his life.

The man underwent numerous tests, including a CT scan, which uncovered multiple cysts in his brain. But there was no evidence of hydrocephalus, or buildup of fluid.

Doctors also conducted an MRI which demonstrated the same findings as the CT, but also noted there was concern about neurocysticercosis.

"Cysticercosis is a condition caused by infection with the larval form of Taenia Solium, a pork tapeworm that uses pigs as an intermediate host," the study read. "Humans become infected when they ingest water or food contaminated with tapeworm cysts."

The man underwent more tests to find out more on a correlation between the migraines and Cysticercosis, involving blood and urine cultures and HIV antibodies, though all came back nonreactive.

But when the Cysticercosis lgG Cysts antibody came back with a positive result, doctors were able to confirm the suspicion of neurocysticercosis.

Researchers said the man’s "preference for soft bacon" could have led to him developing an intestinal tapeworm.

They then put him under a regime of medications, and after 14 days, he was determined to be successfully treated.

Researchers said the man’s "lifelong preference for soft bacon" could have led to him developing an intestinal tapeworm and not cysticercosis.

"Taeniasis occurs when consuming undercooked pork and the larval cysts embedded within, while cysticercosis is contracted when humans ingest eggs found in the feces of other humans with taeniasis," researchers wrote.

"It can only be speculated, but given our patient’s predilection for undercooked pork and benign exposure history, we favor that his cysticercosis was transmitted via autoinfection after improper handwashing after he had contracted taeniasis himself from his eating habits."

The Centers for Disease Control and Prevention warns that if a person consumes undercooked and infected pork, then gets tapeworm infection in the intestines, that person will pass the eggs in their feces.

Cysticercosis typically occurs in low-income countries, the CDC noted, though people who have never traveled outside the U.S. could still contract it.

"A person infected with a tapeworm who does not wash his or her hands might accidentally contaminate food with tapeworm eggs while preparing it for others," the CDC said.

After entering the body, the eggs hatch and the larvae sometimes attach to the brain.

Symptoms of cysticercosis include headache, epilepsy, dizziness and stroke.

Byrnes E, Shaw B, Shaw R, Madruga M, Carlan SJ. Neurocysticercosis Presenting as Migraine in the United States. Am J Case Rep. 2024 Mar 7;25:e943133. doi: 10.12659/AJCR.943133. PMID: 38449298; PMCID: PMC10932825.


BACKGROUND Cysticercosis is a condition caused by infection with the larval form of Taenia solium, a pork tapeworm that uses pigs as an intermediate host. Humans become infected when they ingest water or food contaminated with tapeworm cysts. Cysticercosis is increasing in frequency in developed countries due to increased access to travel. Neurocysticercosis occurs when Taenia solium cysts embed within the nervous system. The clinical presentation of neurocysticercosis ranges from asymptomatic to life-threatening, largely depending on the brain parenchymal involvement. The diagnosis is typically made with a combination of clinical evaluation, serology, and neuroimaging. Treatment for parenchymal neurocysticercosis may involve anthelmintic agents, symptomatic agents, surgery, or a combination of methods. CASE REPORT A 52-year-old man with a medical history of migraine headaches, complicated type 2 diabetes mellitus, and obesity presented with a 4-month change in his migraines becoming severe, worse over his occiput bilaterally, and unresponsive to abortive therapy. His exposure history was unremarkable except for a habit of eating undercooked bacon, by which he would have developed neurocysticercosis via autoinfection. Neuroimaging and serology confirmed a diagnosis of neurocysticercosis and he was treated accordingly with antiparasitic and anti-inflammatory medications. CONCLUSIONS This presentation is nonspecific and can easily be overlooked, especially if there is an underlying known neurological condition such as migraine. This case illustrates that neurocysticercosis should be considered when an existing neuropathological condition displays a change in presentation or requires a change in therapeutic management, even without obvious risk factors.


Thursday, March 14, 2024

ADGRG1 mutations

Inspired by a patient

Note: ADGRG1 and GPR56 are interchangeable. See:

Kuo CY, Tsai MH, Lin HH, Wang YC, Singh AK, Chang CC, Lin JJ, Hung PC, Lin KL. Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings. Epilepsia Open. 2023 Mar;8(1):154-164. doi: 10.1002/epi4.12685. Epub 2023 Jan 11. PMID: 36524291; PMCID: PMC9977754.


Objective: Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic-related migration disorder. It has been attributed to loss-of-function of the ADGRG1 gene, which encodes an adhesion G protein-coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro).

Methods: We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole-exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting.

Results: The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole-exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High-amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre-school age. Partial callosotomy provided short-term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3.

Significance: Sleep EEG findings of high-amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.

Izzo G, Toto V, Faiola S, Cattaneo E, Cavallari U, Passarini A, Gladin CR, Scelsa B, Parazzini C, Righini A. Cobblestone-like brain malformation with a new bi-allelic ADGRG1 (GPR-56) mutation: Fetal imaging-pathology correlation. J Neuroimaging. 2023 Jul-Aug;33(4):527-533. doi: 10.1111/jon.13130. Epub 2023 May 31. PMID: 37259271.


Background and purpose: Autosomal recessive cobblestone-like cortical malformation of the brain, with no eye or muscle involvement, has been reported in patients with biallelic mutations in ADGRG1 (formerly GPR56) and in other brain surface defects (eg, variants in COL3A1). We reported the intra-uterine brain MRI (iu-MRI), post-mortem MRI (pm-MRI), and neuropathology findings of a new ADGRG1 mutation in a fetus at early gestation. Imaging findings were compared with those of the sibling harboring the same mutation, to provide insights about the evolving morphology of such malformation.

Methods: A 21-week fetus underwent iu-MRI for a suspected cortical anomaly on ultrasound. After the MRI results, the termination of the pregnancy was carried out. A pm-MRI scan and autopsy were performed. A neuropathology-imaging correlation was achieved. The 5-year old sibling affected by developmental impairment also underwent a brain MRI. Both subjects underwent a genetic investigation.

Results: Two patterns of abnormality of the cerebral surface were identified on both fetal MRI: one at the vertex resembling a cobblestone-cortex due to neuronal overmigration into the subarchnoid space and the other in the occipital areas resembling polymicrogyria. These details closely matched the neuropathology findings. MRI findings of the sibling consisted of typical ADGRG1/GPR56-related brain findings showing a polymicrogyric-like cortex, also reported as bilateral frontal-parietal polymicrogyria. A flattened pons and small cerebellar vermis were present in both cases. Genetic testing demonstrated a novel homozygous variant c.1484T>C in the c gene in both cases.

Conclusion: Our findings provide further evidence of the overlap of ADGRG1/GPR56-related brain dysgenesis with cobblestone-like cortical malformation of the brain.

Jha R, Kovilapu UB, Devgan A, Sondhi V. Two Novel Compound Heterozygous ADGRG1/GPR56 Mutations Associated with Diffuse Cerebral Polymicrogyria. J Pediatr Genet. 2020 Jul 29;11(1):74-80. doi: 10.1055/s-0040-1714716. PMID: 35186395; PMCID: PMC8847064.


Background Polymicrogyria (PMG) has environmental or genetic etiologies. We report a 8-year-old boy with diffuse PMG and two novel adhesion G protein-coupled receptor G1 ( ADGRG1 ) / G protein-coupled receptor 56 ( GPR56 ) mutations. Case Report The proband has intellectual disability, spastic quadriparesis, and intractable epilepsy without antenatal or perinatal insults. Brain magnetic resonance imaging revealed PMG involving fronto-polar, parietal and occipital lobes with decreasing antero-posterior gradient, and a thinned-out brain stem. Targeted exome sequencing identified two novel compound heterozygote ADGRG1/GPR56 mutations (c.C209T and c.1010dupT), and each parent carries one of these mutations. Subsequent pregnancy was terminated because the fetus had the same mutations. Conclusion The detected mutations expanded the genetic etiology of PMG and helped the family to avoid another child with this devastating condition.

Laser functional hemispherectomy surgery

For only the second time in the world, doctors at the University of Chicago Medicine Comer Children’s Hospital and the Department of Neurosurgery used a minimally invasive surgery to disconnect the right and left sides of the brain and the left epilepsy-generating zones in a boy with epilepsy, stopping his seizures.

Neurosurgeon Peter Warnke, MD, performed the 8-hour laser functional hemispherectomy surgery in February 2021. The patient, Zachary Kurek from northwest Indiana, who was 11 at the time, suffered a stroke at birth, causing him to lose most of the function of the left side of his brain.

His epilepsy was getting worse as he got older, causing dozens of seizures a day that medication couldn’t control. Anything startling, such as a loud noise or a barking dog, could trigger a seizure, causing his body to lock up and fall. Zachary suffered countless bad bruises, a few broken bones and teeth, embarrassment, stress and the inability to do many normal activities. His mother said he was becoming depressed, angry and unable to sleep.

With Zachary facing a lifetime of these seizures and with very limited function in his left cerebral hemisphere as a result of the stroke, Warnke and his team studied the boy’s case. They determined that they could completely disconnect the right and left sides of his brain, and separate any epileptogenic tissue in the left hemisphere, without worsening his verbal or physical functioning.

That way, if seizure activity occurred in the left side of his brain, it would be unable to send signals to the right side of the brain or to the fibers that transmit seizure activity, so Zachary’s body wouldn’t react. The neurosurgery team used sophisticated imaging of his brain’s fiber connections that would need to be disconnected by lasers.

A laser hemispherectomy is a highly complex, risky and challenging operation to help people with epilepsy. UChicago Medicine, which is a Level IV Pediatric Epilepsy Center, has performed more than 250 laser surgeries, Warnke estimated.

But to completely disconnect a whole hemisphere with implanted laser fibers was a new challenge. Rather than remove a portion of the skull to access the brain, as traditionally done in a procedure called a callosotomy, Warnke and his team drew on their previous research, which they were first to publish, suggesting that interstitial lasers could be used to disconnect the two hemispheres of the brain.

“If we could replace open surgery with this, that would be a major breakthrough,” said Warnke, UChicago Medicine’s Director of Stereotactic and Functional Neurosurgery. “We’ve entered uncharted territory, but added a new level of safety as the surgery is carried out in the MRI scanner. It provides continuous vision and real-time monitoring of the brain temperature and imaging of the cell damage produced.”

Not only have the seizures stopped, but his whole attitude has changed. He’s optimistic and happy now.

Warnke and his team have since done two more successful laser surgeries like this on other patients, he said.

It's been almost three years since Zachary's surgery and he hasn’t had a single seizure, his parents said. Warnke described his progress as “remarkable.”

“Where we’re at now is amazing,” said his mother Amanda Morey. “Not only have the seizures stopped, but his whole attitude has changed. He’s optimistic and happy now.”

Warnke performed the surgery using an MRI-guided Visualase laser ablation system. Five small holes about the size of coffee stirrers were drilled into Zachary’s head and catheters were inserted. Five laser fibers were inserted into those catheters and moved deep into Zachary’s brain. Constant guidance from an MRI, providing the exact location and temperature of the laser fibers every seven seconds, allowed Warnke to use the laser’s heated tip to ablate and seal off the connections between the two brain hemispheres.

In the future, laser epilepsy surgery at Comer Children’s will be done using a new state-of-the-art robot. The robot will be able to insert the laser fibers in the brain with greater speed and precision, shortening the surgery time.

Julia Henry, MD, Zachary’s neurologist and epileptologist, said UChicago Medicine treats more children for seizures than any other hospital in the Chicago area and has a team of epilepsy experts.

Zachary’s case was discussed by a team of doctors with a wealth of experience and knowledge. When medications weren’t working, Henry told Zachary’s mother about different surgical treatment options available to him. He then underwent additional EEG evaluation and specialized imaging, which concluded that he’d be a good candidate for a hemispherectomy. With the family’s consent, Henry brought Zachary’s case to the Epilepsy Surgery Conference for review. That’s where Warnke proposed doing the surgery with a new laser technique.

Henry encourages parents whose children are not having success with seizure medications to talk to their doctors about surgical options. While a laser hemispherectomy might not be appropriate for every patient with epilepsy, Henry said the risk of death is less than 1%, and between 73% and 83% of children have their seizures cured by surgery.

Knowing what I know now, I wouldn’t have hesitated, and I wouldn’t have waited this long. It worked out perfectly for him.

“This surgery is a big and scary procedure. Disconnecting half my child’s brain? That’s a lot for any parent to process. But the results can be so dramatic,” Henry said. “The kids come to us so impaired. They have bad, frequent seizures. Life is really a struggle. There are a lot of patients who might be good candidates for this, and this minimally invasive approach might open up the option for them.”

Zachary remains on anti-seizure medication because it’s still possible he could have a seizure. But his quality of life has improved dramatically. As of October 2023, Zachary was getting all As and Bs in school and playing basketball – things that wouldn't have been possible if he was still having seizures.

After his surgery in 2021, mother and son were getting out of the car when a wind gust suddenly slammed the car door shut. Instinctively, Zachary braced himself for a seizure but then realized nothing was happening. He looked at his mom and smiled, and said, “Oh yeah! I don’t have seizures anymore!”

“There was so much that he went through, and I was very hesitant to do this surgery at first. I kept thinking about all the ‘what ifs’,” Amanda said. “Knowing what I know now, I wouldn’t have hesitated, and I wouldn’t have waited this long. It worked out perfectly for him.”

Carotid dissection

The autopsy results for an Indiana mother of two who died in February on a flight home from her vacation in the Dominican Republic have reportedly been released.

A forensic pathologist told Stefanie Smith's family that the 41-year-old woman died of natural causes; specifically, a carotid artery dissection in her neck, her brother Chris Volz said in an interview with ABC News.

"It was truly a tragic medical event that happened," he told the outlet, adding that the autopsy did not suggest foul play.

Smith was on an American Airlines flight from Punta Cana headed to a connection in Charlotte, North Carolina, when she suddenly began convulsing soon after takeoff, forcing the plane to divert to Turks and Caicos, as her friend, Maria Yannotti, previously told Fox News Digital.

"Her boyfriend had told us that they were getting ready to … get altitude, or they hadn't been in the air very long. But he said that he looked over at her, and her head was tilted back in her seat. Her eyes were rolled in the back of her head, and he thought she was just making fun of them. They normally joke around … like that," said Yannotti, who was on the trip to Punta Cana with her fiancé, Smith and Smith's boyfriend.

"And he said, ‘Next thing you know, she was convulsing,’" Yannotti added.

Smith's boyfriend asked flight attendants for help, and they began performing CPR, to no avail.

The Turks and Caicos Island Police announced that day they received a call at 6:12 p.m. from "the Air Traffic Control Tower requesting medical assistance for a 41-year-old female, who at the time was receiving [CPR]." Authorities dispatched a medical team and police to the scene and transported Smith to the Cheshire Hall Medical Centre, where she was pronounced dead.

Just before her plane took off, Smith texted Yannotti at 4:55 p.m., asking Yannotti to remind her to call once she reached her connection in Charlotte because she had "a funny story" to tell.

Yannotti said Smith and her boyfriend went with them on the trip to celebrate Yannotti's fiancé's birthday.

"Everything she had, I had," Yannotti said. "We ate about the same meals. We drank about the same drinks. You know, it wasn't like [any]body was belligerent. [W]e just had our nice drinks by the pool and by the beach. I mean, most of the time, we watched them open the bottles right in front of us. We were having a great time. We played beach volleyball. We swam."

Yannotti, who said she has known Smith for nearly two years because their partners are friends, went on to describe her friend as a "ball of energy" and "the life of the party."

"She's definitely one of a kind. She was a ball of energy. She was always willing to help somebody, excited, always smiling. When I met her … I just knew we were going to click because she was a personality like myself. She was just full of life. I mean, she would give anybody a shirt off her back. Sometimes she would put … people before herself, and she loved to have a good time. Loved to laugh … sing karaoke. Just the life of the party."

Smith leaves behind an 18-year-old son and 16-year-old daughter. Her body is expected to be flown back to the United States next week, ABC reported.

Seizures as cause of pediatric sudden unexplained deaths

Gould L, Reid CA, Rodriguez AJ, Devinsky O; for SUDC Video Working Group. Video Analyses of Sudden Unexplained Deaths in Toddlers. Neurology. 2024 Feb 13;102(3):e208038. doi: 10.1212/WNL.0000000000208038. Epub 2024 Jan 4. PMID: 38175965.


Background and objectives: More than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly sleep-related and unwitnessed with unremarkable autopsies, limiting our understanding of death mechanisms. We sought to understand potential mechanisms of death by evaluating videos of sudden deaths in toddlers.

Methods: In our registry of 301 sudden unexplained child deaths, a series of 7 consecutively enrolled cases with home video recordings of the child's last sleep period were independently assessed by 8 physicians for video quality, movement, and sound.

Results: Four boys and 3 girls (13-27 months at death) with terminal videos shared similar demographic features to the 293 other registry cases without video recordings. Five video recordings were continuous and 2 were triggered by sound or motion. Two lacked audio. All continuous recordings included a terminal convulsive event lasting 8-50 seconds; 4 children survived for >2.5 minutes postconvulsion. Among discontinuous videos, time lapses limited review; 1 suggested a convulsive event. Six were prone with face down, and 1 had autopsy evidence of airway obstruction. Primary cardiac arrhythmias were not supported; all 7 children had normal cardiac pathology and whole-exome sequencing identified no known cardiac disease variants.

Discussion: Audio-visual recordings in 7 toddlers with unexplained sudden deaths strongly implicate that deaths were related to convulsive seizures, suggesting that many unexplained sleep-related deaths may result from seizures.

In a study designed to better understand sudden unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures accompanied by muscle convulsions as a potential cause.

Experts estimate in excess of 3,000 families each year in the United States lose a baby or young child unexpectedly and without explanation. Most are infants, in what is referred to as sudden infant death syndrome, or SIDS, but at least 400 cases involve children age 1 and older, in what is called sudden unexplained death in children (SUDC). Over half of these children are toddlers, between age 1 and 3.

The study findings come from a registry of more than 300 SUDC cases that was set up a decade ago by researchers at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers that were potentially attributable to seizures. These seizures lasted less than 60 seconds and occurred within 30 minutes immediately prior to each child’s death, say the study authors.

For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health.

Published in the journal Neurology online January 4, the new study involved an analysis by a team of eight physicians of the rare SUDC cases for which there were home video recordings. The recordings, from either security systems or commercial crib cameras, were made while each child was sleeping on the night or afternoon of their death.

Five of the seven recordings were running nonstop at the time and showed direct sound and visible motion indicative of a seizure happening. The remaining two recordings were triggered by sound or motion, but only one suggested that a muscle convulsion, a sign of seizure, had occurred. As well, only one toddler had a documented previous history of febrile seizures. Autopsies, which had been previously performed on all the children in the study, revealed no definitive cause of death.

“Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep,” said study lead investigator Laura Gould, MSc, MA, PT, a research assistant professor at NYU Langone. Gould lost her own daughter, Maria, to SUDC at the age of 15 months in 1997, a tragedy that prompted her to successfully lobby to establish the SUDC Registry and Research Collaborative at NYU Langone. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure.

“These study findings show that seizures are much more common than patients’ medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults,” said study senior investigator and neurologist Orrin Devinsky, MD.

Dr. Devinsky, a professor in the Departments of Neurology, Neurosurgery, and Psychiatry, as well as director of NYU Langone’s Comprehensive Epilepsy Center, adds that “convulsive seizures may be the smoking gun that medical science has been looking for to understand why these children die.”

“Studying this phenomenon may also provide critical insight into many other deaths, including those from SIDS and epilepsy,” said Dr. Devinsky, who co-founded the SUDC Registry and Research Collaborative with Gould.

Further research, Dr. Devinsky notes, is also needed to determine precisely how seizures with or without fever may induce sudden death. Previous research in patients with epilepsy, he says, points to difficulty breathing that is known to occur immediately after a seizure and that can lead to death. This has been found to happen more frequently in those who have epilepsy, as it does in the children involved in the study, while they are sleeping face down on the stomach and without anyone witnessing the death.

Continuous monitoring of child deaths and improvements in health records to track how often these convulsive seizures precede death, he explains, will be needed for this to be confirmed. Seizure-related deaths are underreported in people both with and without epilepsy.

For the study, experts in forensic pathology, neurology, and sleep medicine analyzed each recording for video quality, sound, and motion. From this, they were able to determine which toddlers showed signs of muscle convulsions as a sign of seizures prior to their death and when. Access to the videos was and remains strictly limited to the researchers involved in the study.

Funding support for this study was provided by SUDC UK, NYU Langone’s Finding a Cure for Epilepsy and Seizures (FACES), and the SUDC Foundation. Additional funding support was provided by the National Center for Advancing Translational Sciences and National Institutes of Health grant UL1TR001445.

Besides Gould and Dr. Devinsky, other NYU Langone researchers involved in this study are Codi-Ann Reid, BS, and Alcibiades J. Rodriguez, MD. Co-investigators of the SUDC video study group are Alison Krywanczyk, MD, at the Cuyahoga County Medical Examiner’s Office in Cleveland; Kristen Landi, MD, at the New York City Office of the Chief Medical Examiner; Melissa Guzzetta, DO, at the Office of the County Medical Examiner in Middlesex, New Jersey; Heather Jarrell, MD, at the Office of the Medical Investigator, University of New Mexico, in Albuquerque; Kelly Lear, MD, at the Arapahoe County Coroner’s Office in Centennial, Colorado; Tara Mahar, MD, and Katherine Maloney, MD, at the Erie County Medical Examiner’s Office in Buffalo, New York; Declan McGuone, MBBCh, at Yale University in New Haven, Connecticut; Alex Williamson, MD, at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York; Katheryn Pinneri, MD, at the Montgomery County Forensic Service in Conroe, Texas; and Victoria Delavale, MPH, and Daniel Friedman, MD, at NYU Grossman School of Medicine.

Wednesday, March 13, 2024

Triumph over adversity 7

Paul Alexander, known as "the man in the iron lung," having spent most of his life living inside a metal chamber that helped him breathe, has died aged 78, a fundraiser for his health care confirmed Tuesday.

Alexander, of Dallas, Texas, contracted polio in the summer of 1952 when he was 6 years old, leaving him paralyzed from the neck down.

He was forced to live inside the chamber for the rest of his extraordinary life, yet was known for his positive and graceful attitude.

"In this time Paul went to college, became a lawyer, and a published author," wrote Christopher Ulmer, who created a GoFundMe page for Alexander to help finance his health care needs.

"His story traveled wide and far, positively influencing people around the world. Paul was an incredible role model that will continue to be remembered."

At 21, Alexander became the first person to graduate from a high school in Dallas without ever attending class in person, reports the Daily Mail.

He pursued his dreams of becoming a trial lawyer and represented clients in court in a three-piece suit and a modified wheelchair that held his paralyzed body upright.

He also staged a sit-in for disability rights and published a 155-page memoir, "Three Minutes for a Dog: My Life in an Iron Lung," which took five years to complete. Alexander wrote each word with a pen attached to a stick in his mouth, the Daily Mail reports.

Alexander has been recognized by Guinness World Records as the person who has spent the longest amount of time living in an iron lung.

In an interview with Reuters before his death, Alexander said: "My story is an example of why your past or even your disability does not have to define your future."

The ventilator, a large yellow metal chamber, required Alexander to lie his entire body down inside with just his head exposed outside.

Air pressure is continuously cycled up and down to stimulate breathing. People who have contracted polio typically need iron lungs, as do those who have become paralyzed due to poisons.

Ulmer wrote that the GoFundMe was set up after Alexander had been "taken advantage of by people who were supposed to care for his best interests." Although the page did not go into further detail.

"This theft, combined with the high cost of health care, has left Paul with little money to survive," Ulmer wrote.

"He struggles to maintain his iron lung, afford health care, and find housing that accommodates his needs," Ulmer wrote before Alexander’s death.

Ulmer said Paul had been living in a small one-room apartment that did not have a window.

Alexander’s brother, Philip, said the fundraiser, which raised more than $143,000, helped him live out his final years.

"I am so [grateful] to everybody who donated to my brother’s fundraiser. It allowed him to live his last few years stress-free," Paul was quoted as saying on the GoFundMe page.

"It will also pay for his funeral during this difficult time. It is absolutely incredible to read all the comments and know that so many people were inspired by Paul. I am just so grateful."

Paul Alexander still remembers the sound of the screen door slamming on that rainy July day in 1952.

The then-6-year-old had just run inside after playing in the field behind his Dallas home. He was feverish and his neck ached. He walked in barefoot, dragging mud onto the kitchen floor. The door sprang shut behind him. He knew his mom would be mad when she saw the mess, but he was taken aback by the fear in her voice.

“God, please, no,” she said. She knew then polio had come for her son.

1952 was riddled with fear for many parents. It was the worst year for polio in the U.S., with nearly 60,000 cases reported across the country. Some cities shut down popular gathering places—movie theaters, swimming pools, bars, bowling alleys. The virus most commonly affects children, entering the body through the mouth via tiny particles of contaminated feces or, more rarely, droplets from a sneeze or cough. It can lead to flu-like symptoms and has the potential to invade a person’s spinal cord or brain, causing paralysis and potentially death.

For Alexander, the infection started as body aches and a high fever, but not long after, he lost his ability to walk, swallow, and breathe. Doctors performed a tracheotomy and put him in an iron lung—a sealed tank used to treat polio patients who had trouble breathing on their own. During the epidemic, hospital wards were lined with these respirators. They stimulate breathing by varying air pressure to compress and depress the chest. Children typically spent a couple weeks in one while recovering from the disease, lying on their backs, unable to do much. But Alexander didn’t get out of his.

Eighteen months after he was admitted, doctors said he could go home, thinking he wouldn’t live much longer. His body was nearly completely paralyzed from the neck down, and he couldn’t breathe outside the iron lung. His family brought him—and the lung—home and had what they thought would be their last Christmas together.

But Alexander is still alive today. He’s 74 and resides in Dallas—and for the second time in his life, living through the outbreak of a virus that he is at a high risk of suffering from. Unlike the polio virus, the coronavirus hasn’t been disproportionately impacting children. Those most at risk of developing a severe case of COVID-19 are adults over 65 and those with underlying medical conditions. Alexander checks both boxes.

As the world awaits a vaccine, Alexander and his caretakers are limiting contact with others. He still relies on an iron lung to keep him alive. In fact, he’s one of the last people in the world still using the machine.

“It’s like a big tin can,” he tells me over Skype one morning in June. His head sticks out of the yellow tube, and I can hear the machinery expanding and compressing in the background. Between the noise and the fuzzy screen, it’s sometimes hard to make out what he’s saying. I find myself asking him to repeat himself. Alexander is patient with me and starts his sentences over. It’s not the most efficient way to conduct an interview, but we’re making do, given the circumstances.

Though more modern ventilators have been invented over the years, Alexander stuck with his iron lung. As a boy he learned how to breathe without it for extended periods of time—a skill that opened doors for him. When he was 8, a physical therapist taught him how to “frog breathe,” or use muscles in his mouth and throat to gulp air into his lungs.

Alexander was wary of health care professionals, scarred from the times in the hospital when they’d forced him to try to breathe outside the lung, causing him to pass out. But the therapist convinced him to keep trying by making a deal with him: if he could learn to breathe outside the lung for three minutes, she would give him one of her boxer puppies.

“It was difficult, but I worked at it,” Alexander says.

After working at it for a year, the puppy was his. Breathing on his own meant he could spend hours outside the iron lung. He adapted in other ways as well. His father fashioned a stick that he could put in his mouth to play with his toys. (Today, he uses a similar instrument to dial the phone and type on a keyboard.) He learned how to paint and write with a paintbrush or pencil in his mouth, too.

As he grew older, he realized that if he wanted to be successful at something, it would have to be something of the mind. “I had to go to school,” he says. “There was no other way.”

One of the first students to attend the homebound program in his school district, Alexander ended up graduating at the top of his class. He then attended Southern Methodist University before transferring to UT to study economics and finance. “I needed something bigger,” he says. For the first time in his life, he was away from home.

When he got to Austin, though, his hired caretaker never showed up. He refused to call his parents for help, fearing they’d take him home. “I was so determined to do this,” he says. “I thought, I’m going to die or I’m going to go to school.” 

His first month at UT, students in his residence hall took care of him. They fed him and took him to class in his wheelchair. He says a lot of his professors were “angels” and believed in him. It took him seven years, but he graduated in 1978. And he wasn’t done with school yet. He attended UT Law, but this time around, the professors weren’t as encouraging. Alexander remembers one who brought him into his office and told him, “You don’t look like a lawyer,” and, “You’re not going to pass my class.” But he did.

He graduated in 1984 and passed the bar two years later. He spent decades as a lawyer in Dallas, practicing family law and taking on bankruptcy cases, representing clients in court from his wheelchair. When new clients came into his office, they’d see the iron lung and often ask, “What is that?”

It’s a moment Kathy Gaines, his caretaker of over 30 years, knows well. At the start of his career, he put an ad in the newspaper for a caretaker and Gaines responded. Before she met him, she’d never seen an iron lung before. “I walked in, and there was this big, yellow, monster machine, and I was like, ‘Woah, what the hell is this?’” she says. “Paul likes that—it’s like, ‘Wow, that’s a cool car,’ you know?”

She started taking on tasks: cooking his meals, shaving his beard, brushing his teeth, tying his tie—“You have to know how to tie a tie to help a lawyer,” she says—and eventually began working for him full time. Over the years, she’s learned everything about him. She can tell if he’s not getting enough oxygen, or when he’s dehydrated. “I know his body language so well, better than him,” she says. “He gets mad at me. I say, ‘Paul, drink.’ He says, ‘I’m not thirsty.’ I say, ‘Paul, you are thirsty, drink.’”

As Alexander aged, it became more difficult to breathe on his own. Now, he’s completely confined to his iron lung. He stopped practicing law in the last few years and set a new goal: telling his life’s story. Lying on his back in the iron lung, he wrote using a pen attached to a plastic stick. A mirror above his head reflected his notes back to him. He self-published his memoir, Three Minutes for a Dog, in April. It took eight years to complete. Gaines calls it “his big victory.”

One of the reasons Alexander wants to share his story is so people understand the severity of polio. After American virologist Jonas Salk developed a successful polio vaccine in 1955, countries began spearheading immunization campaigns. Since 1979, no cases of polio have originated in the U.S., meaning many Americans don’t understand how prevalent polio once was. Children in the U.S. are vaccinated against the disease by the time they’re 6. But vaccine-preventable diseases, like polio or measles or mumps, haven’t disappeared. Though it’s close to being eliminated, polio is still endemic in three countries: Afghanistan, Pakistan, and Nigeria. And “if we let ourselves become vulnerable by not vaccinating,” the Centers for Disease Control and Prevention warns, “a case that could touch off an outbreak of some disease that is currently under control is just a plane ride away.”

“Polio could come back,” Alexander tells me. Now that we’re living through a pandemic, his words, and the CDC’s, don’t sound alarmist at all. As I talk with Alexander, a living reminder of how an invisible virus can alter one’s life forever, it’s easy to draw parallels between the polio outbreak and the coronavirus pandemic. The calls to avoid gatherings of people. The fears. The anticipation of a cure. I find myself reading the pages of his memoir, in which he implores the world not to forget about the destructive consequences of polio, with a new sense of urgency. “It is extremely important,” he writes, “that you know what this is and what I have had to live with.”

Tuesday, March 12, 2024

Batten disease and vision loss

Grayson Naff, 8, is preparing for life without vision.

The Ohio second-grader was diagnosed last year with Batten disease, a rare genetic disorder that causes vision loss, seizures, cognitive decline, impaired mobility and, ultimately, death.

As the disease progresses and his vision further declines, the child — with the support of his mother, Emily Blackburn, and a host of educators and experts — has started the necessary training to navigate the world without eyesight.

Naff’s current vision is around 20/200-20/300, which is considered legally blind.

He sees best about 5 to 10 inches in front of him, Blackburn said.

Recently, the boy began "white cane training."

A white cane is a critical mobility tool for the blind or visually impaired. It scrapes along the ground as the person walks, allowing the individual to gather important information about the surroundings.

"White cane training is important for certain individuals with vision loss to increase their independence while traveling throughout their environment," Rhianna Witt, an orientation and mobility specialist with Montgomery County Educational Service Center (MCESC) in Dayton, Ohio, told Fox News Digital.

"The white cane allows [the blind person] to detect changes in elevation, obstacles and changes in surface texture," she said. "It is a tool used for previewing the environment."

The white cane also signals to others that the person using it has low vision, Witt noted, which makes the person more visible in public places and street crossings.

"It’s important for students to learn to use their white cane with a certified orientation and mobility specialist," Witt said.

"Practicing using their cane in practical and age-appropriate environments will help them develop the skills needed as they get older and/or their vision changes."

Naff was introduced to the white cane in his elementary school gym, and then he walked the halls using it, his mother said.

"His favorite color is red, so he liked how the white cane had red [on it]," Blackburn told Fox News Digital. "He learned how wide to move it, how to hold it, how to use it to hear different materials on the ground and how to fold it up."

Witt praised the boy for working hard on his orientation and mobility training.

"The focus has been to ensure that he is navigating his school well and gaining the skills necessary to problem-solve when his vision may be affecting his ability to orient or navigate," she said.

While the white cane training was an important step for Naff — it was difficult for his mother.

"I was extremely anxious for him to be introduced to the white cane," she said.

"Losing vision can sometimes be an invisible disability, but when you have a white cane, it suddenly becomes real."

"No one prepares you for this — I wake up every day and have to remember that this is our life."

"Accepting that my son is legally blind — and that if he goes down the typical path of children with Batten disease, he will likely lose all of his vision — is heartbreaking."

An even more difficult realization, she said, is that loss of vision is only the beginning of the disease’s devastating effects.

"No one prepares you for this," Blackburn said. "I wake up every day and have to remember that this is our life."

Her son has also started training in Braille, which allows visually impaired people to read by feeling a system of raised dots.

Becca King, teacher of the visually impaired at MCESC in Dayton, Ohio, has been helping the boy with his Braille lessons.

"Learning to read Braille is a lot like learning to read print," she told Fox News Digital. "It’s important to have the fundamentals and to take it step by step."

"Grayson is a pleasure to work with," she told Fox News Digital. "He is enthusiastic about learning and is willing to do anything that I ask him to. He has an infectious personality, and he is truly the highlight of my day when I get to see him."

She added, "He is a bright light to all who know him."

Naff also has an aide at school who helps him scribe — meaning he writes down what the boy says.

The young student also has a portable desktop magnifying device that magnifies and changes contrast to help him see his papers at school.

Every six months, Naff and his family drive seven hours to see his ophthalmologist at the University of Iowa, who specializes in juvenile inherited eye disease.

During each visit, "Grayson goes through a whole day of eye exams to test if his vision has changed," Blackburn said.

Their next visit is scheduled for May.

"The only way we move forward is with hope and the love we have for Grayson."

"The anxiety and anticipation is challenging, because we want to accept Grayson's vision however it may be, but our hope is that he'll have his vision for as long as possible," his mother said.

Naff is also taking Miglustat, a medication that could help ease or slow down symptoms.

Cost is a concern, though. Since the drug is not yet FDA-approved for use with Batten disease, it has a hefty co-pay.

"If insurance doesn’t cover it, it’s about $100 per pill, or $9,000 each month," Blackburn said.

There is currently no cure for Batten disease, with life expectancy typically in the mid-teens to early 20s.

"The only way we move forward is with hope and the love we have for Grayson," said Blackburn.

"We take pictures, we make memories, we try to live life as normal as possible — but with a crack in our hearts and hope for the future."

There are resources available through private agencies, schools and government agencies to assist with the difficult transition that comes with vision loss, Witt pointed out.

"It is helpful to find a community of people who are going through a similar experience and can provide advice and stories of hope," she added.

Anyone wanting more information about Grayson Naff’s journey and Batten disease can visit