Pub Date : 2024-07-08DOI: 10.1016/j.pediatrneurol.2024.06.015
Jacqueline Jeon-Chapman BS , Tais Estrela MD , Gena Heidary MD, PhD , Ryan Gise MD
Background
Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children.
Methods
Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded.
Results
A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss.
Conclusions
Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.
{"title":"Efficacy and Side Effects of Topiramate in Treatment of Children With Pseudotumor Cerebri Syndrome","authors":"Jacqueline Jeon-Chapman BS , Tais Estrela MD , Gena Heidary MD, PhD , Ryan Gise MD","doi":"10.1016/j.pediatrneurol.2024.06.015","DOIUrl":"10.1016/j.pediatrneurol.2024.06.015","url":null,"abstract":"<div><h3>Background</h3><p>Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children.</p></div><div><h3>Methods</h3><p>Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded.</p></div><div><h3>Results</h3><p>A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss.</p></div><div><h3>Conclusions</h3><p>Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 32-37"},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1016/j.pediatrneurol.2024.07.001
Anna K. Fiedler BS , Kai Zhang PhD , Tia S. Lal BS , Xiaoqian Jiang PhD , Stuart M. Fraser MD
Background
Pediatric stroke is an important cause of morbidity in children. Although research can be challenging, large amounts of data have been captured through collaborative efforts in the International Pediatric Stroke Study (IPSS). This study explores the use of an advanced artificial intelligence program, the Generative Pre-trained Transformer (GPT), to enter pediatric stroke data into the IPSS.
Methods
The most recent 50 clinical notes of patients with ischemic stroke or cerebral venous sinus thrombosis at the UTHealth Pediatric Stroke Clinic were deidentified. Domain-specific prompts were engineered for an offline artificial intelligence program (GPT) to answer IPSS questions. Responses from GPT were compared with the human rater. Percent agreement was assessed across 50 patients for each of the 114 queries developed from the IPSS database outcome questionnaire.
Results
GPT demonstrated strong performance on several questions but showed variability overall. In its early iterations it was able to match human judgment occasionally with an accuracy score of 1.00 (n = 20, 17.5%), but it scored as low as 0.26 in some patients. Prompts were adjusted in four subsequent iterations to increase accuracy. In its fourth iteration, agreement was 93.6%, with a maximum agreement of 100% and minimum of 62%. Of 2400 individual items assessed, our model entered 2247 (93.6%) correctly and 153 (6.4%) incorrectly.
Conclusions
Although our tailored generative model with domain-specific prompt engineering and ontological guidance shows promise for research applications, further refinement is needed to enhance its accuracy. It cannot enter data entirely independently, but it can be employed in tandem with human oversight contributing to a collaborative approach that reduces overall effort.
{"title":"Generative Pre-trained Transformer for Pediatric Stroke Research: A Pilot Study","authors":"Anna K. Fiedler BS , Kai Zhang PhD , Tia S. Lal BS , Xiaoqian Jiang PhD , Stuart M. Fraser MD","doi":"10.1016/j.pediatrneurol.2024.07.001","DOIUrl":"10.1016/j.pediatrneurol.2024.07.001","url":null,"abstract":"<div><h3>Background</h3><p>Pediatric stroke is an important cause of morbidity in children. Although research can be challenging, large amounts of data have been captured through collaborative efforts in the International Pediatric Stroke Study (IPSS). This study explores the use of an advanced artificial intelligence program, the Generative Pre-trained Transformer (GPT), to enter pediatric stroke data into the IPSS.</p></div><div><h3>Methods</h3><p>The most recent 50 clinical notes of patients with ischemic stroke or cerebral venous sinus thrombosis at the UTHealth Pediatric Stroke Clinic were deidentified. Domain-specific prompts were engineered for an offline artificial intelligence program (GPT) to answer IPSS questions. Responses from GPT were compared with the human rater. Percent agreement was assessed across 50 patients for each of the 114 queries developed from the IPSS database outcome questionnaire.</p></div><div><h3>Results</h3><p>GPT demonstrated strong performance on several questions but showed variability overall. In its early iterations it was able to match human judgment occasionally with an accuracy score of 1.00 (n = 20, 17.5%), but it scored as low as 0.26 in some patients. Prompts were adjusted in four subsequent iterations to increase accuracy. In its fourth iteration, agreement was 93.6%, with a maximum agreement of 100% and minimum of 62%. Of 2400 individual items assessed, our model entered 2247 (93.6%) correctly and 153 (6.4%) incorrectly.</p></div><div><h3>Conclusions</h3><p>Although our tailored generative model with domain-specific prompt engineering and ontological guidance shows promise for research applications, further refinement is needed to enhance its accuracy. It cannot enter data entirely independently, but it can be employed in tandem with human oversight contributing to a collaborative approach that reduces overall effort.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 54-59"},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1016/j.pediatrneurol.2024.06.012
Laura S. Farach MD , Melissa A. Richard PhD , Aynara C. Wulsin MD, PhD , Elizabeth M. Bebin MD , Darcy A. Krueger MD, PhD , Mustafa Sahin MD, PhD , Brenda E. Porter MD, PhD , Tarrant O. McPherson PhD , Jurriaan M. Peters MD, PhD , Sarah O'Kelley PhD , Katherine S. Taub MD , Rajsekar Rajaraman MD , Stephanie C. Randle MD , William M. McClintock MD , Mary Kay Koenig MD , Michael D. Frost MD , Klaus Werner MD, PhD , Danielle A. Nolan MD , Michael Wong MD, PhD , Gary Cutter PhD , Elida Salazar
Background
Children with tuberous sclerosis complex (TSC) are at high risk for drug-resistant epilepsy (DRE). The ability to stratify those at highest risk for DRE is important for counseling and prompt, aggressive management, necessary to optimize neurocognitive outcomes. Using the extensively phenotyped PREVeNT cohort, we aimed to characterize whether the TSC genotype was associated with DRE.
Methods
The study group (N = 70) comprised participants with TSC enrolled at age less than or equal to six months with detailed epilepsy and other phenotypic and genotypic data, prospectively collected as part of the PREVeNT trial. Genotype-phenotype correlations of DRE, time to first abnormal electroencephalography, and time to epilepsy onset were compared using Fisher exact test and regression models.
Results
Presence of a TSC2 pathogenic variant was significantly associated with DRE, compared with TSC1 and participants with no pathogenic mutation identified. In fact, all participants with DRE had a TSC2 pathogenic variant. Furthermore, TSC2 variants expected to result in no protein product were associated with higher risk for DRE. Finally, TSC1 pathogenic variants were associated with later-onset epilepsy, on average 21.2 months later than those with other genotypes.
Conclusions
Using a comprehensively phenotyped cohort followed from infancy, this study is the first to delineate genotype-phenotype correlations for epilepsy severity and onset in children with TSC. Patients with TSC2 pathogenic variants, especially TSC2 pathogenic variants predicted to result in lack of TSC2 protein, are at highest risk for DRE, and are likely to have earlier epilepsy onset than those with TSC1. Clinically, these insights can inform counseling, surveillance, and management.
{"title":"Drug-Resistant Epilepsy in Tuberous Sclerosis Complex Is Associated With TSC2 Genotype: More Findings From the Preventing Epilepsy Using Vigatrin (PREVeNT) Trial","authors":"Laura S. Farach MD , Melissa A. Richard PhD , Aynara C. Wulsin MD, PhD , Elizabeth M. Bebin MD , Darcy A. Krueger MD, PhD , Mustafa Sahin MD, PhD , Brenda E. Porter MD, PhD , Tarrant O. McPherson PhD , Jurriaan M. Peters MD, PhD , Sarah O'Kelley PhD , Katherine S. Taub MD , Rajsekar Rajaraman MD , Stephanie C. Randle MD , William M. McClintock MD , Mary Kay Koenig MD , Michael D. Frost MD , Klaus Werner MD, PhD , Danielle A. Nolan MD , Michael Wong MD, PhD , Gary Cutter PhD , Elida Salazar","doi":"10.1016/j.pediatrneurol.2024.06.012","DOIUrl":"10.1016/j.pediatrneurol.2024.06.012","url":null,"abstract":"<div><h3>Background</h3><p>Children with tuberous sclerosis complex (TSC) are at high risk for drug-resistant epilepsy (DRE). The ability to stratify those at highest risk for DRE is important for counseling and prompt, aggressive management, necessary to optimize neurocognitive outcomes. Using the extensively phenotyped PREVeNT cohort, we aimed to characterize whether the TSC genotype was associated with DRE.</p></div><div><h3>Methods</h3><p>The study group (N = 70) comprised participants with TSC enrolled at age less than or equal to six months with detailed epilepsy and other phenotypic and genotypic data, prospectively collected as part of the PREVeNT trial. Genotype-phenotype correlations of DRE, time to first abnormal electroencephalography, and time to epilepsy onset were compared using Fisher exact test and regression models.</p></div><div><h3>Results</h3><p>Presence of a <em>TSC2</em> pathogenic variant was significantly associated with DRE, compared with <em>TSC1</em> and participants with no pathogenic mutation identified. In fact, all participants with DRE had a <em>TSC2</em> pathogenic variant. Furthermore, <em>TSC2</em> variants expected to result in no protein product were associated with higher risk for DRE. Finally, <em>TSC1</em> pathogenic variants were associated with later-onset epilepsy, on average 21.2 months later than those with other genotypes.</p></div><div><h3>Conclusions</h3><p>Using a comprehensively phenotyped cohort followed from infancy, this study is the first to delineate genotype-phenotype correlations for epilepsy severity and onset in children with TSC. Patients with <em>TSC2</em> pathogenic variants, especially <em>TSC2</em> pathogenic variants predicted to result in lack of TSC2 protein, are at highest risk for DRE, and are likely to have earlier epilepsy onset than those with <em>TSC1</em>. Clinically, these insights can inform counseling, surveillance, and management.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 62-71"},"PeriodicalIF":3.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1016/j.pediatrneurol.2024.06.014
Maha Z. Mohammed MD , Iman Elagouza MD , Maha El Gaafary MD , Rana El-Garhy MSc , Omnia El-Rashidy MD
Background
Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER).
Methods
A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes.
Results
In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups.
Conclusions
Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.
{"title":"Intranasal Versus Buccal Versus Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Patients: A Randomized Controlled Trial","authors":"Maha Z. Mohammed MD , Iman Elagouza MD , Maha El Gaafary MD , Rana El-Garhy MSc , Omnia El-Rashidy MD","doi":"10.1016/j.pediatrneurol.2024.06.014","DOIUrl":"10.1016/j.pediatrneurol.2024.06.014","url":null,"abstract":"<div><h3>Background</h3><p>Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER).</p></div><div><h3>Methods</h3><p>A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes.</p></div><div><h3>Results</h3><p>In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (<em>P</em> = 0.763 and <em>P</em> = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups.</p></div><div><h3>Conclusions</h3><p>Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"158 ","pages":"Pages 135-143"},"PeriodicalIF":3.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141707266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-29DOI: 10.1016/j.pediatrneurol.2024.06.013
Mongkol Chanvanichtrakool MD , John M. Schreiber MD , Wei-Liang Chen MD , John Barber MS , Anqing Zhang PhD , Nicholas Ah Mew MD , Andreas Schulze MD, PhD , Greta Wilkening PsyD , Sandesh C.S. Nagamani MBBS, MD , Andrea Gropman MD , The Urea Cycle Disease Consortium
Background
This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.
Methods
Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.
Results
Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 μmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 μmol/L increase in glutamine.
Conclusions
This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.
背景：这项在一家临床中心进行的回顾性临床研究旨在确定伴有或不伴有高氨血症（HA）危象的尿素循环障碍（UCD）患者中癫痫发作的发生率。此外，我们还试图找出生化指标和脑电图（EEG）在检测 HA 期间亚临床癫痫发作方面的作用：方法： 对2006年至2022年期间在国立儿童医院参加尿素循环障碍联合会纵向研究（UCDC-LS）（NCT00237315）的UCD患者的病历进行回顾性分析，以寻找HA危机期间临床和亚临床癫痫发作的证据，并同时检测初始生化水平：共有 85 名 UCD 患者纳入分析。85 名患者中有 56 人（66%）经历了 HA 危机，共发生了 163 次 HA 事件。在13%的HA事件中观察到癫痫发作。在所有伴有脑电图的 HA 事件中，27% 没有临床癫痫发作的脑病危象和 53% 有临床癫痫发作的危象中发现了亚临床癫痫发作。氨每增加 100 μmol/L，癫痫发作的几率增加 2.65 倍（95% 置信区间 [CI]，1.51 至 4.66）；谷氨酰胺每增加 100 μmol/L，癫痫发作的几率增加 1.14 倍（95% 置信区间 [CI]，1.04 至 1.25）：本研究强调了在临床癫痫发作或脑病合并 HA 的患者危机期间进行脑电图监测的实用性。在 HA 事件期间，测量初始氨和谷氨酰胺有助于确定癫痫发作风险并指导脑电图监测决策。
{"title":"Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises","authors":"Mongkol Chanvanichtrakool MD , John M. Schreiber MD , Wei-Liang Chen MD , John Barber MS , Anqing Zhang PhD , Nicholas Ah Mew MD , Andreas Schulze MD, PhD , Greta Wilkening PsyD , Sandesh C.S. Nagamani MBBS, MD , Andrea Gropman MD , The Urea Cycle Disease Consortium","doi":"10.1016/j.pediatrneurol.2024.06.013","DOIUrl":"10.1016/j.pediatrneurol.2024.06.013","url":null,"abstract":"<div><h3>Background</h3><p>This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.</p></div><div><h3>Methods</h3><p>Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.</p></div><div><h3>Results</h3><p>Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 μmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 μmol/L increase in glutamine.</p></div><div><h3>Conclusions</h3><p>This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 48-55"},"PeriodicalIF":3.2,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1016/j.pediatrneurol.2024.06.010
Meagan Watson MPH, MBAc , Jason Kreuzman OTR/L , Karen Zeribi MHS , Jeannette M. Iskander PhD , Amanda Hopper MLIS , Laura Simon MD , Gayle Chesley PhD , Aaron Fobian PhD
Background
Pediatric functional neurological disorders (FNDs) are common but grossly under-researched. This survey study aims to define the current landscape of pediatric FND treatment in the United States, identifying treatment programs, care team composition, treatment approaches, and aftercare management.
Methods
The Functional Neurological Disorder Society (FNDS) Pediatric Special Interest Group (SIG), a diverse set of clinician and caregiver stakeholders, collected information on available treatment programs in the United States via survey. Current programs were identified through the FNDS Pediatric SIG and FND Hope's provider registry.
Results
Thirty-nine care team members from 24 health care centers yielded 31 unique FND treatment settings. Centers existed in 16 states, concentrated in the Midwest and Southern regions. Outpatient settings (62%) were more prevalent than inpatient. A psychologist (PhD/PsyD) was the most common clinician (52%) with dedicated time to treat FNDs. Most settings accepted ages six to 21 (55%) and treated all FND symptoms (77%). A spectrum of treatment approaches was endorsed with the most common being cognitive behavioral therapy (77%) and personalized approaches (58%). A biopsychosocial approach was evident, with most settings reporting active involvement with school (97%) and caregivers (94%). Most settings (74%) encouraged treatment re-engagement when needed with no strict time limits. All respondents provided aftercare recommendations or referrals.
Conclusions
Pediatric FND treatment is available across the United States, but there is high variability in care team membership, treatment approach, and aftercare management. Future research is necessary to develop effective and sustainable treatment to improve access for this population.
{"title":"The Current State of Pediatric Functional Neurological Disorder Treatment in the United States","authors":"Meagan Watson MPH, MBAc , Jason Kreuzman OTR/L , Karen Zeribi MHS , Jeannette M. Iskander PhD , Amanda Hopper MLIS , Laura Simon MD , Gayle Chesley PhD , Aaron Fobian PhD","doi":"10.1016/j.pediatrneurol.2024.06.010","DOIUrl":"10.1016/j.pediatrneurol.2024.06.010","url":null,"abstract":"<div><h3>Background</h3><p>Pediatric functional neurological disorders (FNDs) are common but grossly under-researched. This survey study aims to define the current landscape of pediatric FND treatment in the United States, identifying treatment programs, care team composition, treatment approaches, and aftercare management.</p></div><div><h3>Methods</h3><p>The Functional Neurological Disorder Society (FNDS) Pediatric Special Interest Group (SIG), a diverse set of clinician and caregiver stakeholders, collected information on available treatment programs in the United States via survey. Current programs were identified through the FNDS Pediatric SIG and FND Hope's provider registry.</p></div><div><h3>Results</h3><p>Thirty-nine care team members from 24 health care centers yielded 31 unique FND treatment settings. Centers existed in 16 states, concentrated in the Midwest and Southern regions. Outpatient settings (62%) were more prevalent than inpatient. A psychologist (PhD/PsyD) was the most common clinician (52%) with dedicated time to treat FNDs. Most settings accepted ages six to 21 (55%) and treated all FND symptoms (77%). A spectrum of treatment approaches was endorsed with the most common being cognitive behavioral therapy (77%) and personalized approaches (58%). A biopsychosocial approach was evident, with most settings reporting active involvement with school (97%) and caregivers (94%). Most settings (74%) encouraged treatment re-engagement when needed with no strict time limits. All respondents provided aftercare recommendations or referrals.</p></div><div><h3>Conclusions</h3><p>Pediatric FND treatment is available across the United States, but there is high variability in care team membership, treatment approach, and aftercare management. Future research is necessary to develop effective and sustainable treatment to improve access for this population.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"158 ","pages":"Pages 144-155"},"PeriodicalIF":3.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1016/j.pediatrneurol.2024.06.007
Sandra Jimenez Giraldo MD , Michael Michaelis BS , Lauren Kerr BA , Christopher Cortina MS , Bo Zhang PhD , Mark P. Gorman MD
Background
Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neuroimmune disease with peak onset at 18 months, associated with neural crest tumors in 50% of patients. In part due to its rarity, misdiagnosis at onset is common, can delay treatment, and may contribute to adverse outcomes. Patient-reported registries may overcome some of these challenges in rare disease research. In this context, the OMSLife Foundation collaborated with the National Organization of Rare Diseases to create a patient-reported registry in OMAS.
Methods
Retrospective analysis was performed of data entered by parents of patients with OMAS into nine online surveys assessing demographics, symptoms at onset, triggers, time of diagnosis, treatment, and additional therapies.
Results
A total of 194 patients were enrolled. There was a female predominance (54%) and high rate of parental autoimmunity (31%). Age at onset peaked between 12 and 18 months overall. The age of onset was older in female patients (median [interquartile range]: females 22 [15 to 31] vs males 18 [14 to 23], P = 0.0223, P = 0.0223). Symptoms at onset most commonly included ataxia (84%) and were typically severe. Initial misdiagnosis occurred in nearly 50% and tumor discovery was delayed in 18 patients, but overall median time to correct diagnosis was 25 days. Most patients (56%) received combination immunomodulatory therapies, and nearly all underwent supportive therapies.
Conclusions
Patient- and parent-powered research is feasible in OMAS and created the second largest published cohort of pediatric patients with OMAS. Results were similar to other large cohorts and also validated findings from prior case reports and smaller case series.
背景：肌阵挛-肌阵挛-共济失调综合征（OMAS）是一种罕见的神经免疫性疾病，发病高峰期为18个月，50%的患者与神经嵴肿瘤有关。由于该病罕见，发病时的误诊很常见，可能会延误治疗，并导致不良后果。患者报告登记可克服罕见病研究中的部分挑战。在此背景下，OMSLife 基金会与美国国家罕见病组织（National Organization of Rare Diseases）合作，在 OMAS 中建立了一个患者报告登记处：方法：对OMAS患者父母在九项在线调查中输入的数据进行回顾性分析，调查内容包括人口统计学、发病时的症状、诱因、诊断时间、治疗和额外疗法：共有 194 名患者参与了调查。其中女性患者占多数（54%），父母自身免疫的比例较高（31%）。发病年龄在12至18个月之间达到高峰。女性患者的发病年龄更大（中位数[四分位数间距]：女性 22 [15 至 31] vs 男性 18 [14 至 23]，P = 0.0223，P = 0.0223）。发病时最常见的症状包括共济失调（84%），而且通常很严重。近50%的患者最初被误诊，18名患者的肿瘤被延迟发现，但总的正确诊断中位时间为25天。大多数患者（56%）接受了联合免疫调节疗法，几乎所有患者都接受了支持疗法：结论：由患者和家长推动的OMAS研究是可行的，并建立了第二大已发表的OMAS儿科患者队列。研究结果与其他大型队列相似，同时也验证了之前病例报告和小型病例系列研究的结果。
{"title":"Inaugural Patient-Reported Registry of Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome: Presentation, Diagnosis, and Treatment of 194 Patients","authors":"Sandra Jimenez Giraldo MD , Michael Michaelis BS , Lauren Kerr BA , Christopher Cortina MS , Bo Zhang PhD , Mark P. Gorman MD","doi":"10.1016/j.pediatrneurol.2024.06.007","DOIUrl":"10.1016/j.pediatrneurol.2024.06.007","url":null,"abstract":"<div><h3>Background</h3><p>Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neuroimmune disease with peak onset at 18 months, associated with neural crest tumors in 50% of patients. In part due to its rarity, misdiagnosis at onset is common, can delay treatment, and may contribute to adverse outcomes. Patient-reported registries may overcome some of these challenges in rare disease research. In this context, the OMSLife Foundation collaborated with the National Organization of Rare Diseases to create a patient-reported registry in OMAS.</p></div><div><h3>Methods</h3><p>Retrospective analysis was performed of data entered by parents of patients with OMAS into nine online surveys assessing demographics, symptoms at onset, triggers, time of diagnosis, treatment, and additional therapies.</p></div><div><h3>Results</h3><p>A total of 194 patients were enrolled. There was a female predominance (54%) and high rate of parental autoimmunity (31%). Age at onset peaked between 12 and 18 months overall. The age of onset was older in female patients (median [interquartile range]: females 22 [15 to 31] vs males 18 [14 to 23], <em>P</em> = 0.0223, <em>P</em> = 0.0223). Symptoms at onset most commonly included ataxia (84%) and were typically severe. Initial misdiagnosis occurred in nearly 50% and tumor discovery was delayed in 18 patients, but overall median time to correct diagnosis was 25 days. Most patients (56%) received combination immunomodulatory therapies, and nearly all underwent supportive therapies.</p></div><div><h3>Conclusions</h3><p>Patient- and parent-powered research is feasible in OMAS and created the second largest published cohort of pediatric patients with OMAS. Results were similar to other large cohorts and also validated findings from prior case reports and smaller case series.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"158 ","pages":"Pages 128-134"},"PeriodicalIF":3.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1016/j.pediatrneurol.2024.06.011
Qunying Zhang MS , Yi Du ME , Xingjian Liu MS , Zhengyan Xu MS , Yu Wang BS , Lili Ren MD , Ziming Wu MD
Background
To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments.
Methods
Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0.
Results
Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies.
Conclusions
This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.
{"title":"Vestibular Migraine and Recurrent Vertigo in Children: A Diagnostic Focus From a Tertiary Hospital Study","authors":"Qunying Zhang MS , Yi Du ME , Xingjian Liu MS , Zhengyan Xu MS , Yu Wang BS , Lili Ren MD , Ziming Wu MD","doi":"10.1016/j.pediatrneurol.2024.06.011","DOIUrl":"10.1016/j.pediatrneurol.2024.06.011","url":null,"abstract":"<div><h3>Background</h3><p>To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments.</p></div><div><h3>Methods</h3><p>Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0.</p></div><div><h3>Results</h3><p>Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies.</p></div><div><h3>Conclusions</h3><p>This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"158 ","pages":"Pages 86-93"},"PeriodicalIF":3.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gold standard for evaluation of the severity of moyamoya vasculopathy is the Suzuki grade determined with cerebral catheter angiography (CA). With greater use of magnetic resonance angiography (MRA) it is important to understand if MRA is truly comparable to CA.
Methods
Children with moyamoya were evaluated using the Suzuki score for CA and the modified MRA six-stage Suzuki score to describe the angiographic findings in moyamoya from initial narrowing of the distal internal carotid artery to the “puff of smoke” appearance of the lenticulostriate collaterals and finally to the disappearance of this network of collaterals. Using Cohen kappa we compared Suzuki grade based on CA with MRA in the same patients.
Results
A total of 27 children with moyamoya were reviewed. We calculated a weighted Cohen kappa of 0.49 (P < 0.0001), which is a moderate correlation.
Conclusions
We suggest caution in the reliance on MRA for the diagnosis and evaluation of severity of moyamoya in children.
评估莫亚莫亚血管病严重程度的金标准是通过脑导管血管造影（CA）确定的铃木分级。随着磁共振血管造影术（MRA）的应用越来越广泛，了解 MRA 是否能真正与 CA 相媲美显得尤为重要。我们使用 CA 的铃木评分和改良的 MRA 六阶段铃木评分对患有 moyamoya 的儿童进行了评估，以描述 moyamoya 的血管造影结果，从最初的远端颈内动脉狭窄到出现 "烟雾状 "的皮质袢，最后到袢网消失。我们使用科恩卡帕（Cohen kappa）比较了同一患者中基于 CA 和 MRA 的铃木分级。共对 27 名患有 moyamoya 的儿童进行了复查。我们计算出的加权科恩卡帕值为 0.49（< 0.0001），属于中度相关。我们建议在依赖 MRA 诊断和评估儿童莫亚莫亚症的严重程度时要谨慎。
{"title":"Magnetic Resonance Angiography Alone Is Insufficient for Diagnosis and Surgical Planning in Children With Moyamoya","authors":"Laura L. Lehman MD, MPH , Clara Wu BS , Matsanga-Leyila Kaseka MD, MSc , Prakash Muthusami MD , Derek Armstrong MD , Peter Dirks MD, PhD , Manohar Shroff MD, DABR , Mahendranath Moharir MD, MSc , Daune Macgregor MD , Gabrielle deVeber MD, MSc , Nomazulu Dlamini MD, MSc, PhD","doi":"10.1016/j.pediatrneurol.2024.06.008","DOIUrl":"10.1016/j.pediatrneurol.2024.06.008","url":null,"abstract":"<div><h3>Background</h3><p>The gold standard for evaluation of the severity of moyamoya vasculopathy is the Suzuki grade determined with cerebral catheter angiography (CA). With greater use of magnetic resonance angiography (MRA) it is important to understand if MRA is truly comparable to CA.</p></div><div><h3>Methods</h3><p>Children with moyamoya were evaluated using the Suzuki score for CA and the modified MRA six-stage Suzuki score to describe the angiographic findings in moyamoya from initial narrowing of the distal internal carotid artery to the “puff of smoke” appearance of the lenticulostriate collaterals and finally to the disappearance of this network of collaterals. Using Cohen kappa we compared Suzuki grade based on CA with MRA in the same patients.</p></div><div><h3>Results</h3><p>A total of 27 children with moyamoya were reviewed. We calculated a weighted Cohen kappa of 0.49 (<em>P</em> < 0.0001), which is a moderate correlation.</p></div><div><h3>Conclusions</h3><p>We suggest caution in the reliance on MRA for the diagnosis and evaluation of severity of moyamoya in children.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 1-3"},"PeriodicalIF":3.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1016/j.pediatrneurol.2024.06.009
Sydney Peters BS , Kristen Sportiello BS , Shreya Mandalapu BA , Ashlie Nguyen PsyD , Ryan Carrier MD , Carolyn Dickinson NP , Alex Paciorkowski MD , David Bearden MD
Background
ZC4H2-associated rare disorder (ZARD) is caused by pathogenic variations in the ZC4H2 gene on the X chromosome. This gene codes for a zinc finger protein involved in neural development. ZARD is characterized by highly variable symptoms, potentially influenced by the sex of the individual.
Methods
The ZC4H2-Associated Rare Disorder Natural History Study is a prospective natural history study conducted among individuals with ZARD that consists of standardized interviews, developmental assessments, and neurological examinations conducted every six months for two years. In this article, we present data from baseline visits with 40 participants, the largest ZARD cohort studied thus far, focusing on genotype-phenotype correlations and sex differences. Fisher exact, maximum likelihood χ2, and Mann-Whitney tests were utilized.
Results
Males tended to have maternally inherited ZC4H2 pathogenic variations, whereas females tended to have de novo variations (P < 0.001). Female participants were more likely to have contractures at birth (P < 0.01), arthrogryposis multiplex congenita (P < 0.001), spasticity on examination (P < 0.1), and lower limb muscle atrophy (P < 0.05). Male participants were more likely to have seizures (P < 0.1), intermittent pain (P < 0.01), severe vision impairment (P < 0.05), dysphagia for solids (P < 0.01), and generalized muscle atrophy (P < 0.05).
Conclusions
Our study suggests there is significant overlap in severity and range of symptoms between males and females, although several symptoms are more common in one sex than the other. Further analysis is needed to better understand how pathogenic variation type affects phenotype.
{"title":"Genotype-Phenotype Correlations and Sex Differences in ZC4H2-Associated Rare Disorder","authors":"Sydney Peters BS , Kristen Sportiello BS , Shreya Mandalapu BA , Ashlie Nguyen PsyD , Ryan Carrier MD , Carolyn Dickinson NP , Alex Paciorkowski MD , David Bearden MD","doi":"10.1016/j.pediatrneurol.2024.06.009","DOIUrl":"10.1016/j.pediatrneurol.2024.06.009","url":null,"abstract":"<div><h3>Background</h3><p><em>ZC4H2</em>-associated rare disorder (ZARD) is caused by pathogenic variations in the <em>ZC4H2</em> gene on the X chromosome. This gene codes for a zinc finger protein involved in neural development. ZARD is characterized by highly variable symptoms, potentially influenced by the sex of the individual.</p></div><div><h3>Methods</h3><p>The <em>ZC4H2</em>-Associated Rare Disorder Natural History Study is a prospective natural history study conducted among individuals with ZARD that consists of standardized interviews, developmental assessments, and neurological examinations conducted every six months for two years. In this article, we present data from baseline visits with 40 participants, the largest ZARD cohort studied thus far, focusing on genotype-phenotype correlations and sex differences. Fisher exact, maximum likelihood <em>χ</em><sup>2</sup>, and Mann-Whitney tests were utilized.</p></div><div><h3>Results</h3><p>Males tended to have maternally inherited <em>ZC4H2</em> pathogenic variations, whereas females tended to have <em>de novo</em> variations (<em>P</em> < 0.001). Female participants were more likely to have contractures at birth (<em>P</em> < 0.01), arthrogryposis multiplex congenita (<em>P</em> < 0.001), spasticity on examination (<em>P</em> < 0.1), and lower limb muscle atrophy (<em>P</em> < 0.05). Male participants were more likely to have seizures (<em>P</em> < 0.1), intermittent pain (<em>P</em> < 0.01), severe vision impairment (<em>P</em> < 0.05), dysphagia for solids (<em>P</em> < 0.01), and generalized muscle atrophy (<em>P</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>Our study suggests there is significant overlap in severity and range of symptoms between males and females, although several symptoms are more common in one sex than the other. Further analysis is needed to better understand how pathogenic variation type affects phenotype.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"158 ","pages":"Pages 100-112"},"PeriodicalIF":3.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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