Rutu M. Dave, Janetta Arellano, Charles Grose, Rachel Pearson
{"title":"Recurrent encephalitis and stroke following cessation of acyclovir prophylaxis in a patient with neonatal herpes simplex virus with RNF213 mutation","authors":"Rutu M. Dave, Janetta Arellano, Charles Grose, Rachel Pearson","doi":"10.1002/cns3.20079","DOIUrl":"https://doi.org/10.1002/cns3.20079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Herpes simplex virus (HSV) encephalitis can be associated with many secondary neurological complications, but having multiple episodes of recurrent neurological complications is rare in an individual. Understanding the course of each complication can reduce time to diagnosis and adequate treatment. Additionally, we postulate the role of <i>RNF213</i> mutation in HSV susceptibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We describe a unique presentation of HSV-1 encephalitis in an infant with a pathogenic <i>RNF213</i> mutation who went on to develop multiple rare neurological complications over the course of her illness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our patient was first diagnosed with neonatal HSV-1 encephalitis at age 2 weeks. She had recurrence of HSV encephalitis (HSE) with associated vasculopathy that led to right middle cerebral artery and posterior cerebral artery infarctions at 13 months, and then later developed post-HSE anti-<i>N</i>-methyl-\u0000<span>d</span>-aspartate receptor encephalitis. All of this occurred concomitant with <i>RNF213</i> mutation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This patient demonstrates that, though rare, multiple neurological complications can occur in a single person, thus highlighting the importance of close surveillance of patients with a history of neonatal HSE and pursuing a broad differential in patients with subtle or recurrent symptoms. Furthermore, we propose a potential role of <i>RNF213</i> mutation in the pathogenesis of our patient's multiple medical conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 3","pages":"235-241"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320713","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}
Alexandra Santana Almansa, Stephen M. Chrzanowski, Farrah Rajabi, Megan Day-Lewis, Pui Y. Lee, Hart G. W. Lidov, Laura L. Lehman, Leslie H. Hayes
{"title":"LMNA-related muscular dystrophy presenting as an inflammatory myopathy","authors":"Alexandra Santana Almansa, Stephen M. Chrzanowski, Farrah Rajabi, Megan Day-Lewis, Pui Y. Lee, Hart G. W. Lidov, Laura L. Lehman, Leslie H. Hayes","doi":"10.1002/cns3.20075","DOIUrl":"https://doi.org/10.1002/cns3.20075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>There are overlapping features between inflammatory myopathies and muscular dystrophies, particularly laminopathies. Key features that characterize laminopathies include axial and proximal weakness, contractures, and cardiac abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods/Results</h3>\u0000 \u0000 <p>A 12-year-old girl diagnosed with juvenile dermatomyositis as a child presented with cardiac failure and was found to have an <i>LMNA</i> likely pathogenic variant, with a phenotype most consistent with Emery–Dreifuss muscular dystrophy type 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The spectrum of clinical features of <i>LMNA</i>-related muscular dystrophies can mimic or present with inflammatory myopathy-like features. Early identification of <i>LMNA</i>-related muscular dystrophies is crucial to ensure appropriate cardiac screening and prevent devastating cardiac complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 3","pages":"242-247"},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320648","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}
Shermila Pia, Elizabeth Stackhouse, Shehanaz Ellika
{"title":"A rare and devastating etiology of febrile seizure","authors":"Shermila Pia, Elizabeth Stackhouse, Shehanaz Ellika","doi":"10.1002/cns3.20080","DOIUrl":"https://doi.org/10.1002/cns3.20080","url":null,"abstract":"<p>This 21-month-old boy with a history of multiple febrile seizures presented in refractory febrile status epilepticus. He had rhinorrhea and cough and tested positive for influenza type A. Cerebrospinal fluid analysis showed an elevated protein of 49 mg/dL (reference 10–32 mg/dL) with normal cells, glucose, lactate, meningitis/encephalitis, and autoimmune encephalitis panels. Magnetic resonance imaging revealed T2 hyperintensity, diffusion restriction, and susceptibility signal loss involving the bilateral cerebral cortices, cerebral white matter, thalami, basal ganglia, cerebellum, and brainstem (Figure 1). Metabolic screening and rapid whole-genome sequencing including <i>RANBP2</i> were unrevealing.</p><p>He was diagnosed with acute necrotizing encephalopathy (ANE) due to influenza A. He was treated with intravenous immunoglobulin (IVIG) and high-dose methylprednisolone. His course was complicated by severe paroxysmal sympathetic hyperactivity and prolonged hypoxic respiratory failure. Two months after the initial presentation, he had cortical blindness, diffuse spasticity, and dystonia without purposeful movements.</p><p>ANE is a rare but severe parainfectious disorder predominantly occuring in the pediatric age group and is associated with significant neurological morbidity and mortality.<span><sup>1, 2</sup></span> First described in 1997,<span><sup>3</sup></span> ANE typically presents with seizure and encephalopathy concomitant with viral illness. Influenza type A is the most commonly identified pathogen,<span><sup>1</sup></span> but many others have been implicated. More recently, familial/genetic ANE has been reported in association with pathogenic variants in <i>RANBP2</i>, and genetic testing is now recommended in the evaluation of these patients.<span><sup>1, 2</sup></span> Radiographically, ANE is characterized by symmetric T2 hyperintensity, diffusion restriction, and susceptibility signal loss in bilateral cerebral cortices, thalami, basal ganglia, cerebral white matter, brainstem, and cerebellar hemispheres.<span><sup>4, 5</sup></span> A characteristic trilaminar pattern of diffusion restriction on the apparent diffusion coefficient map in the thalami is specific for ANE,<span><sup>4, 5</sup></span> with the core demonstrating high signal intensity, pericore showing low signal intensity, and peripheral zone of high signal intensity, corresponding with pathologic findings of hemorrhagic necrosis in the core, pericore cytotoxic edema, and perilesional vasogenic edema.<span><sup>5</sup></span> The prognosis is poor, with less than 10% full recovery, nearly 30% mortality, and significant neurological morbidity in survivors.<span><sup>1, 2</sup></span> Early treatment with high-dose steroids is associated with improved outcomes.</p><p><b>Shermila Pia</b>: Conceptualization; writing—original draft; writing—review & editing. <b>Elizabeth Stackhouse</b>: Writing—review & editing. <b>Shehanaz Ellika</b>: Data curation; supervisi","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"2 3","pages":"251-252"},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.20080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320844","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}
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
{"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}
Elizabeth Pickup, Christopher Redmond, Matthew A. Sherman, Lakshmi Ramachandran Nair, Sangeeta Sule, Elizabeth Wells, Alexandra B. Kornbluh
{"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, Christopher Redmond, Matthew A. Sherman, Lakshmi Ramachandran Nair, Sangeeta Sule, Elizabeth Wells, 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}