Annals of the Child Neurology Society最新文献

{"title":"Access to novel therapies for Duchenne muscular dystrophy—Insights from expert treating physicians","authors":"Aravindhan Veerapandiyan, Anne M. Connolly, Katherine D. Mathews, Stanley Nelson, Craig McDonald, Richard S. Finkel, Vettaikorumakankav Vedanarayanan, Cuixia Tian, Susan Apkon, Julie A. Parsons, Jonathan H. Soslow, William Bryan Burnette, Kaitlin Y. Batley, Susan T. Iannaccone, Carolina Tesi Rocha, Kevin M. Flanigan, Diana Bharucha-Goebel, Sarah Wright, Migvis Monduy, Simona Treidler, Ashutosh Kumar, Nancy L. Kuntz, Vamshi K. Rao, Rachel Schrader, Saunder M. Bernes, Vikki Ann Stefans, Jena M. Krueger, Marcia V. Felker, Omer Abdul Hamid, Arpita Lakhotia, Susan Matesanz, Partha S. Ghosh, Natalie Katz, Hoda Abdel-Hamid, Chamindra G. Laverty, Bo Hoon Lee, Amy Harper, Leigh Ramos-Platt, Diana Castro, Russell J. Butterfield, Crystal M. Proud, Craig M. Zaidman, Emma Ciafaloni","doi":"10.1002/cns3.20076","DOIUrl":"10.1002/cns3.20076","url":null,"abstract":"<p>Duchenne muscular dystrophy (DMD) is a rare, X-linked, progressive, degenerative muscle disease due to pathogenic variants in the <i>DMD</i> gene resulting in absence of functional dystrophin protein.<span><sup>1</sup></span> Patients with DMD have irreversible muscle damage that begins at birth, and there is histologic evidence of disease progression with progressive inflammation and fibrosis within the first years of life.<span><sup>2</sup></span> Proactive interdisciplinary care, corticosteroids, and advances in disease-modifying treatments have changed the trajectory of the disease, leading to slower progression and improving life expectancy. This statement from clinicians who care for patients with DMD aims to provide insights into the current therapeutic landscape and access to novel therapies for DMD.</p><p>Recent years have seen a remarkable number of clinical trials to evaluate the disease-modifying ability of novel therapies for DMD. In addition to corticosteroids (deflazacort and vamorolone), several gene-targeted therapies were approved by the U.S. Food and Drug Administration (FDA). These include exon-skipping agents (eteplirsen, golodirsen, viltolarsen, and casimersen) that restore the reading frame of <i>DMD</i> transcripts and delandistrogene moxeparvovec-rokl, an adeno-associated virus–based microdystrophin gene transfer therapy. Further, there is a robust pipeline of targeted gene-based therapies and treatments targeting downstream pathways such as regulating muscle fiber degeneration and regeneration.<span><sup>3-5</sup></span> While existing treatments offer benefits by delaying or slowing disease progression, none provide a cure. The emergence of treatments that target the disease through multiple mechanisms underscores the importance of assessing combination therapies for DMD, akin to approaches used in treating oncological disorders. Given the progressive and irreversible nature of muscle degeneration in DMD, timely initiation of treatments is crucial. Delaying treatment initiation could result in permanent loss of motor function, underscoring the urgency of prompt intervention.</p><p>DMD is a severe and progressive rare disorder with significant gaps in available treatments. The low incidence and heterogeneity in genotypes and phenotypes pose challenges in conducting traditional large-scale placebo-controlled trials in a reasonable amount of time. The restoration of shortened functional forms of dystrophin serve as biomarkers representing appropriate endpoints in the FDA's accelerated approval pathway. This pathway allows FDA approval of drugs that treat serious conditions with unmet medical need based on a surrogate endpoint that is reasonably likely to predict clinical benefit.<span><sup>6</sup></span> It is important to note that therapies approved under accelerated approval are still required to undergo robust phase 3 confirmatory trials, providing data for traditional approval. There are currently 27 drugs approved","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 3","pages":"184-188"},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141357504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecularly targeted immunotherapy used to treat a novel overlap syndrome of pediatric N-methyl-\u0000d-aspartate receptor encephalitis (NMDARE) and possible neurosarcoidosis","authors":"Elizabeth Pickup,&nbsp;Christopher Redmond,&nbsp;Matthew A. Sherman,&nbsp;Lakshmi Ramachandran Nair,&nbsp;Sangeeta Sule,&nbsp;Elizabeth Wells,&nbsp;Alexandra B. Kornbluh","doi":"10.1002/cns3.20074","DOIUrl":"10.1002/cns3.20074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Overlap syndromes have been described between <i>N</i>-methyl-\u0000<span>d</span>-aspartate receptor encephalitis (NMDARE) and other neuroinflammatory conditions, although rarely involving neurosarcoidosis. Molecularly targeted immunotherapy may be helpful in the empiric treatment of these conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We describe a 9-year-old boy with new-onset seizures and worsening encephalopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Initial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin-converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high-acuity pediatric neuroinflammatory disease with limited diagnostic clarity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"168-175"},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal prospective study of Sturge–Weber syndrome urine angiogenic factors and neurological outcome","authors":"Brooke Kimbrell,&nbsp;Kieran D. McKenney,&nbsp;SangEun Yeom,&nbsp;Isabelle Iannotti,&nbsp;Alyssa Day,&nbsp;Kelly Harmon,&nbsp;Alison Sebold,&nbsp;Lindsay Smegal,&nbsp;Katherine Kaplan,&nbsp;Cassie Daisy,&nbsp;Rama Aldakhlallah,&nbsp;Michael Taylor,&nbsp;Anna Pinto,&nbsp;Adrienne Hammill,&nbsp;Marsha A. Moses,&nbsp;Anne Comi","doi":"10.1002/cns3.20071","DOIUrl":"10.1002/cns3.20071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study identified biomarkers of neurological outcome in Sturge-Weber syndrome (SWS) via urine angiogenic factors and captured longitudinally derived natural history data within an SWS cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This longitudinal, prospective, multicentered study of 61 people with SWS aged 0.4–55 years reports port-wine birthmark score, Neuroscore, Neuro-Quality of Life, and urine angiogenic factors over a two-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cognitive Neuroscore worsened over time for children aged 0–2 years. Male sex was associated with worsening Cognitive Function Neuroscore during the study. Age of seizure onset before 2 years was strongly associated with worse Neuroscore. Children with SWS had low Neuro-Quality of Life related to cognitive function. Seizure severity, male sex, and earlier age of seizure onset were associated with worse Neuro-Quality of Life in school-aged children. Children with SWS have elevated basic fibroblast growth factor in their urine compared with controls, whereas higher vascular endothelial growth factor was associated with better Neuroscore.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study is the first multicenter, prospective, and longitudinal study of people with SWS. It identifies significant clinical prognostic factors such as age of seizure onset and male sex, informs symptom progression over time by age group, and suggests that further study of angiogenic mechanisms and potential biomarkers are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"120-134"},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141269533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute treatment of migraine in children aged 6−11: Real-world analysis of remote electrical neuromodulation (REN)","authors":"Klaus Werner,&nbsp;Trevor Gerson,&nbsp;Alit Stark-Inbar,&nbsp;Sharon Shmuely,&nbsp;Alon Ironi,&nbsp;Christina L. Szperka,&nbsp;Andrew D. Hershey","doi":"10.1002/cns3.20073","DOIUrl":"10.1002/cns3.20073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Migraine is a prevalent neurological disorder severely impacting children and adolescents, yet only one pharmacological treatment is approved for ages 6−12 years. Remote electrical neuromodulation (REN) is a nonpharmacological, prescribed, wearable device cleared by the Food and Drug Administration for acute and/or preventive treatment of migraine with or without aura in patients 12 years and older. This study evaluates REN's safety and efficacy in ages 6−11 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective acute treatment of migraine data were collected through the REN device (Nerivio) smartphone application. Endpoints were device safety (primary); consistent treatment efficacy (headache pain, functional disability, associated migraine symptoms), and REN-medication combinations 2 h post-treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Children (<i>n</i> = 293), median age 11 years (interquartile range = 9−11), 73.7% girls, conducted 5493 REN treatments. No adverse events were reported. Efficacy in at least 50% of REN treatments was calculated from all patients who voluntarily reported pain levels, symptoms, and/or disability at treatment onset and at 2 h post-treatment, with 72.2% (13/18) of patients reporting pain relief, 36.0% (9/25) pain freedom, 83.3% (15/18) functional disability relief, and 38.9% (7/18) functional disability freedom. Migraine-associated symptoms disappeared in at least 50% of REN treatments in 70.0% (7/10) of patients for nausea/vomiting, 50.0% (4/8) phonophobia, and 22.2% (2/9) photophobia; 63.6% (7/11) reported freedom from at least one associated symptom. REN was used as a standalone treatment, with over-the-counter medications, and with prescribed headache medications in 45.4%, 34.4%, and 20.9% of treatments, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>REN may serve as a safe and efficacious acute treatment of migraine for children. Providers and families seeking a safe, effective, pill- and needle-free treatment option for children suffering from migraine may consider REN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"135-145"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141117394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of anxiety in children during the COVID-19 pandemic","authors":"Carlos Lastra,&nbsp;Robert Abrahams,&nbsp;Gregory Anash,&nbsp;Kyle Prisby,&nbsp;Luz Goyco-Ortiz,&nbsp;Andrea Melean,&nbsp;Rosanne Moreno,&nbsp;Alexander Schramm","doi":"10.1002/cns3.20072","DOIUrl":"10.1002/cns3.20072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study assessed anxiety levels in children during the COVID-19 pandemic and explored how factors related to COVID-19 may have affected the prevalence of anxiety disorders among the pediatric population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Childhood anxiety symptoms were assessed at various pediatric practices in Central New Jersey between July 2021 and September 2022. The sample comprised 476 children and adolescents aged 8–17 who participated in the Screen for Child Anxiety Related Disorders (SCARED) questionnaire, administered at their annual well-child visits. Participants included both the child and the caregiver. The anxiety prevalence was compared with prepandemic standards published by the Centers for Disease Control (CDC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of anxiety for children aged 8–17 years (28.3%) was greater than prepandemic levels (7.1%; <i>p</i> &lt; 0.0001). Among children aged 8–11, anxiety increased from 6.6% to 38.1% (<i>p</i> &lt; 0.0001), while for children aged 11–17, anxiety increased from 10.5% to 22.2% (<i>p</i> &lt; 0.0001). Previously diagnosed anxiety was a strong predictor of a high anxiety score on the questionnaire (mean = 28.95) compared with children without a history of anxiety (mean = 17.65; <i>p</i> &lt; 0.001). Furthermore, a disparity was identified in the responses between the child and the caregiver questionnaires (<i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows that children's anxiety levels increased during the COVID-19 pandemic. Moreover, an inconsistency was found between children self-reporting anxiety and caregivers underreporting their child's anxiety. These findings underscore the need for targeted support for those affected, especially children with a history of anxiety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"153-161"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventative treatment of tuberous sclerosis complex with sirolimus: Phase I safety and efficacy results","authors":"Jamie K. Capal,&nbsp;David M. Ritter,&nbsp;David Neal Franz,&nbsp;Molly Griffith,&nbsp;Kristn Currans,&nbsp;Bridget Kent,&nbsp;E. Martina Bebin,&nbsp;Hope Northrup,&nbsp;Mary Kay Koenig,&nbsp;Tomoyuki Mizuno,&nbsp;Alexander A. Vinks,&nbsp;Stephanie L. Galandi,&nbsp;Wujuan Zhang,&nbsp;Kenneth D.R. Setchell,&nbsp;Kelly M. Kremer,&nbsp;Carlos M. Prada,&nbsp;Hansel M. Greiner,&nbsp;Katherine Holland-Bouley,&nbsp;Paul S. Horn,&nbsp;Darcy A. Krueger","doi":"10.1002/cns3.20070","DOIUrl":"10.1002/cns3.20070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a phase 1 clinical trial of sirolimus, treating five patients until 12 months of age. Enrolled infants had to be younger than 6 months of age with no history of seizures and no clinical indication for sirolimus treatment. Adverse events (AEs), tolerability, and blood concentrations of sirolimus measured by tandem mass spectrometry were tracked through 12 months of age, and clinical outcomes (seizure characteristics and developmental profiles) were tracked through 24 months of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 92 AEs, with 34 possibly, probably, or definitely related to treatment. Of those, only two were grade 3 (both elevated lipids) and all AEs were resolved by the age of 24 months. During the trial, 94% of blood sirolimus trough levels were in the target range (5–15 ng/mL). Treatment was well tolerated, with less than 8% of doses held because of an AE (241 of 2941). Of the five patients, three developed seizures (but were well controlled on medications) at 24 months of age. Of the five patients, four had normal cognitive development for age. One was diagnosed with possible autism spectrum disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These results suggest that sirolimus is both safe and well tolerated by infants with TSC in the first year of life. Additionally, the preliminary work suggests a favorable efficacy profile compared with previous TSC cohorts not exposed to early sirolimus treatment. Results support sirolimus being studied as preventive treatment in TSC, which is now underway in a prospective phase 2 clinical trial (TSC-STEPS).</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"106-119"},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140672304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Headache with migrainous features caused by delayed onset secondary angle closure glaucoma following laser treatment for retinopathy of prematurity","authors":"Christina J. Su,&nbsp;Carley Gilman,&nbsp;Andrew R. Lee,&nbsp;Shannon C. Agner","doi":"10.1002/cns3.20063","DOIUrl":"10.1002/cns3.20063","url":null,"abstract":"<p>As survival among preterm infants has increased over time, the number of children at risk of complications of prematurity has increased as well. Retinopathy of prematurity (ROP) is a disease of abnormal retinal blood vessel development and is one of the leading causes of preventable blindness in preterm babies.<span>^{1, 2}</span></p><p>We present a former 24-week premature infant who received left laser retinal photocoagulation at 2 months of age for ROP. At 9 years of age, he began experiencing new intermittent headaches behind the left eye that were described as achy and dull. The headaches were associated with light sensitivity, nausea, and vomiting, and they worsened when he moved his head forward. He denied vision changes, waking up from sleep due to headaches, numbness, tingling, or weakness. He had no prior headache history or family history of chronic headaches. His exam was notable for the oblong appearance of the left pupil, but his neurological exam was otherwise nonfocal. His symptoms and exam were thought to be most consistent with migraine headaches.</p><p>Due to the positional component of his headaches, further evaluation was pursued, including imaging and consultation with ophthalmology. Brain magnetic resonance imaging revealed no structural explanation for his headaches. Eye exams during this period revealed normal intraocular pressure (IOP) bilaterally and no optic disc edema. There were notable iris abnormalities and iridocorneal adhesions in his left eye consistent with prior history of retinal laser treatment. A lumbar puncture was not pursued due to no other signs or symptoms of increased intracranial pressure aside from the positional features.</p><p>Over the next month, several migraine treatments were trialed with inconsistent symptom relief, including acetaminophen in combination with prochlorperazine, diphenhydramine, valproate, and propranolol. Nonsteroidal anti-inflammatory drugs were avoided due to his history of chronic kidney disease. Approximately one month later, his headaches rapidly worsened to throbbing in the left frontal and temporal region. His neurological examination remained stable. However, his left eye pressure was elevated at 34 mmHg (normal ≤ 21 mmHg) during ophthalmologic evaluation. He developed further worsening headaches, blurred vision, nausea, and vomiting one week later. IOP of his left eye had increased to 46 mmHg and did not respond to pharmacologic IOP-lowering therapies. The patient was admitted for urgent Ahmed glaucoma drainage device implantation (New World Medical) in the left eye and experienced immediate headache relief after surgery.</p><p>Angle-closure glaucoma can present as early as two weeks after treatment of ROP. However, presentations have been reported anywhere from 12 to 45 years of age.<span>^{3, 4}</span> Angle-closure glaucoma symptoms can first present with intermittent headaches due to periodic elevation of IOP followed by spontaneous normalizatio","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"176-177"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mononeuritis multiplex as clinical presentation of systemic lupus erythematosus","authors":"Natalie Weston,&nbsp;Audrey Cortesi,&nbsp;Vettaikorumakankav Vedanarayanan,&nbsp;Jamie Shanahan,&nbsp;Rosemary G. Peterson","doi":"10.1002/cns3.20068","DOIUrl":"10.1002/cns3.20068","url":null,"abstract":"<p>Systemic lupus erythematosus (SLE) is a heterogeneously presenting, chronic, multisystem autoimmune disease. Neurological manifestations of SLE can affect both central and peripheral nervous systems and are associated with reduced health-related quality of life and increased mortality.<span>^1-3</span> While most neurological manifestations occur around the time of SLE diagnosis, they may precede diagnosis, creating diagnostic and therapeutic challenges. Mononeuritis multiplex (MNM) is a rare SLE manifestation, usually occuring years after diagnosis.<span>⁴</span> We present an 11-year-old girl who presented with severe, rapidly progressive MNM due to SLE. This is the first report of MNM as the initial SLE manifestation in a pediatric patient, and only the second report of MNM at time of SLE diagnosis.<span>⁵</span></p><p>This previously healthy 11-year-old girl presented with progressively worsening distal right leg pain, antalgic gait, and intermittent fever, preceded by recent influenza A infection. Her evaluation was significant for normocytic anemia, elevated inflammatory markers, and magnetic resonance imaging (MRI) suggestive of an inflammatory myopathy (Figure 1). The differential diagnosis included postinfectious reactive myositis versus new-onset chronic immune-mediated inflammatory disease. She was discharged on a prednisone taper with further evaluation pending.</p><p>Over the next month, her examination became progressively more abnormal, with increasingly severe distal upper and lower extremity weakness, pain, paresthesias, muscle atrophy, and gait instability. She developed bilateral claw hand deformity and foot drop, absent toe flexion and extension, and absent Achilles reflexes. Brain MRI demonstrated abnormal small T2 hyperintensity in the right lateral pons. Spine MRI and lumbar puncture were normal. Figure 1 shows bilateral lower extremity MRI, with abnormalities interpreted as myositis versus neurogenic atrophy.</p><p>Nerve conduction and electromyography demonstrated severe axonal sensory and motor neuropathy with asymmetric involvement, consistent with mononeuritis multiplex. The presence of this neuropathy and patchy myopathic changes supported clinical diagnosis of vasculitic neuropathy. Muscle biopsy of left vastus lateralis demonstrated neurogenic atrophy without perivascular or endomysial inflammation (Figure 2). However, as the biopsy was completed after an initial steroid course, potential inflammatory muscular findings may have been masked.</p><p>With a likely diagnosis of rapidly progressive MNM from vasculitic neuropathy, extensive multidisciplinary diagnostic evaluation for potential etiologies continued. Prior rheumatologic evaluation had been pertinent for positive antinuclear antibody, and despite any specific clinical manifestations for SLE outside of neurological disease, a full evaluation revealed high-titer positive SS-A antibody (&gt;8.0 ai), positive dsDNA antibody, RNP","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"178-180"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sudden unexpected death in epilepsy in a patient with a brain-responsive neurostimulation device","authors":"Richard Wang,&nbsp;Patricia E. McGoldrick,&nbsp;Galadu Subah,&nbsp;Carrie R. Muh,&nbsp;Steven M. Wolf","doi":"10.1002/cns3.20062","DOIUrl":"10.1002/cns3.20062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. Although most witnessed SUDEPs follow seizures, mechanisms are uncertain. Investigations into the pathophysiology of SUDEP have relied on models and rare recordings of brain function at the time of the event. The brain-responsive neurostimulation (RNS) device from Neuropace offers a therapeutic option for drug-refractory epilepsy (DRE), enabling the recording of brain activity and the preemptive termination of seizures. Therefore, patients who experience SUDEP while being treated with an RNS device can provide insights into neural activity at the moment of this event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We report the history and electrocorticographic (ECoG) recordings of a patient with DRE who experienced SUDEP years after RNS placement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patient History</h3>\u0000 \u0000 <p>A girl with Phelan–McDermid syndrome and Lennox–Gastaut syndrome had an RNS device implanted at the age of 14 to treat DRE. Initially, electrodes were positioned in the right orbitofrontal (OF) and right premotor frontal regions, with the OF lead later changed to the centromedian thalamic nucleus. At age 19, the patient was found unconscious and in cardiac arrest by her parents. Although spontaneous circulation returned en route to the hospital, the patient did not regain consciousness and died. Subsequent analysis of ECoGs from RNS recordings at the time of death indicated seizure onset in the right premotor frontal cortex, which persisted despite seizure termination attempts by the RNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We present a patient with SUDEP associated with the onset of RNS-refractory seizures. The significance of this report is highlighted by the rarity of literature on neuronal function at the time of SUDEP. Moreover, it underscores the potential for devices capable of monitoring ECoG activity to shed light on the mechanisms underlying SUDEP and to inform interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"162-167"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140721154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG band power and phase-amplitude coupling in patients with Dravet syndrome","authors":"Joanne C. Hall,&nbsp;Shahid Bashir,&nbsp;Melissa Tsuboyama,&nbsp;Raidah Al-Bradie,&nbsp;Ali Mir,&nbsp;Mona Ali,&nbsp;Annapurna Poduri,&nbsp;Alexander Rotenberg","doi":"10.1002/cns3.20061","DOIUrl":"10.1002/cns3.20061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dravet syndrome (DS) is an epileptic encephalopathy caused by haploinsufficiency of the <i>SCN1A</i> gene. <i>SCN1A</i> gene deficiency limits the firing rates of fast-spiking inhibitory interneurons, which should reflect in abnormal aggregate network oscillatory electroencephalography (EEG) activity that can be measured by spectral power and phase-amplitude coupling (PAC) analysis. In this retrospective pilot study, we tested whether spectral EEG frequency band power and PAC metrics distinguish children with DS from age-matched controls, an early step toward establishing EEG markers of target engagement by gene or drug therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>EEG data were collected from patients with DS (<i>N</i> = 6) and age-matched control pediatric participants (<i>N</i> = 11) and analyzed for cumulative spectral power and PAC and classification capacity of these metrics, by logistic regression analysis. For this initial spectral and PAC analysis, we focused on sleep EEG, where myogenic artifact is minimal and where <i>δ</i>–<i>γ</i> and <i>θ</i>–<i>γ</i> coupling is otherwise expected to be robust.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cumulative <i>δ</i> (1– &lt;4 Hz) and <i>θ</i> (4–7 Hz) power was significantly reduced in the DS group, compared with age-matched controls (<i>p</i> = 0.001 and <i>p</i> = 0.02, respectively). The <i>δ</i> power was a stronger classifier of separating DS from controls than <i>θ</i> power, with 87% and 83% accuracy, respectively. The <i>γ</i> power trended toward significant reduction (<i>p</i> = 0.08) in the DS group. We found significantly lower PAC between 1–2 Hz phase and 63–80 Hz amplitude in patients with DS compared with the age-matched controls (<i>p</i> = 0.003), with 78% classification accuracy between groups for PAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In this pilot study assessing EEG patterns during sleep, we found lower <i>δ</i>–<i>θ</i> power and PAC in patients with DS versus controls, which may reflect abnormal aggregate macroscale network communication patterns resulting from <i>SCN1A</i> deficiency. These measures may be useful metrics of therapeutic target engagement, particularly if the therapy restores the underlying DS pathophysiology. The sorting capacity of these metrics distinguished patients with DS from patients without DS and may in turn facilitate near-future development of disease and therapy target engagement biomarkers in this syndrome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 2","pages":"92-105"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}