{"title":"Letter to the Editor: Alice in Wonderland Syndrome in Children With Severe Acute Respiratory Syndrome SARS-CoV-2 Infection: A Case Series of Two Patients in an Italian Hospital","authors":"Alexis Demas MD (Doctor, Neurologist), Michèle Demas MD (Doctor, Retired Paediatrician)","doi":"10.1016/j.pediatrneurol.2025.11.024","DOIUrl":"10.1016/j.pediatrneurol.2025.11.024","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Page 229"},"PeriodicalIF":2.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786862","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 : 2025-12-01DOI: 10.1016/j.pediatrneurol.2025.11.023
Abdelrahim A. Sadek MD, PhD , Amr A. Othman MD, PhD , Esraa A. Ahmed MD, MSc , Elsayed Abdelkreem MD, PhD
{"title":"Evidence From the Ket-Mid Study for Early Polytherapy in Children With Stage 1 Plus Status Epilepticus: Authors’ Response","authors":"Abdelrahim A. Sadek MD, PhD , Amr A. Othman MD, PhD , Esraa A. Ahmed MD, MSc , Elsayed Abdelkreem MD, PhD","doi":"10.1016/j.pediatrneurol.2025.11.023","DOIUrl":"10.1016/j.pediatrneurol.2025.11.023","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 208-209"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774853","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}
Electrophysiological subtypes of Guillain-Barré Syndrome (GBS) vary in pathophysiology and clinical presentation, but comparative data on their intensive care needs in critically ill children remain limited.
Methods
In this retrospective cohort study, we analyzed 224 children (1 month to 12 years) diagnosed with GBS and admitted to the Pediatric Intensive Care Unit of a tertiary care hospital in North India from January 2010 to December 2022. GBS was subtyped based on nerve conduction studies into acute motor axonal neuropathy (AMAN), acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor-sensory axonal neuropathy (AMSAN), inexcitable, or equivocal patterns. Clinical features, intensive care interventions, and outcomes were compared across subtypes.
Results
AMAN was the most common subtype (61.6%), followed by AIDP (20.1%) and AMSAN (8%). A prodromal illness was reported in 47.3% of cases. Mechanical ventilation was required in 54.9%, and tracheostomy in 24.2% of children. AMSAN was associated with a significantly longer duration of symptoms at presentation (P = 0.006). Autonomic instability, particularly hypertension (P = 0.04), was significantly more frequent in the AIDP group. However, Hughes disability scores, respiratory and cranial nerve involvement, and intensive care needs were similar across subtypes.
Conclusions
AMAN was the predominant GBS subtype in critically ill children. While AMSAN was associated with delayed presentation and AIDP with greater autonomic dysfunction, overall intensive care needs and short-term outcomes were comparable across subtypes.
{"title":"Axonal Versus Demyelinating Guillain-Barré Syndrome Subtypes in Critically Ill Children: Clinical and Autonomic Profiles","authors":"Deepankar Bansal DM, Manjinder Singh Randhawa DM, Rajalakshmi Iyer DM, Shivan Kesavan DM, Suresh Kumar Angurana DM, Karthi Nallasamy DM, Renu Suthar DM, Naveen Sankhyan DM, Jayashree Muralidharan MD, Arun Bansal MD","doi":"10.1016/j.pediatrneurol.2025.11.016","DOIUrl":"10.1016/j.pediatrneurol.2025.11.016","url":null,"abstract":"<div><h3>Background</h3><div>Electrophysiological subtypes of Guillain-Barré Syndrome (GBS) vary in pathophysiology and clinical presentation, but comparative data on their intensive care needs in critically ill children remain limited.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study, we analyzed 224 children (1 month to 12 years) diagnosed with GBS and admitted to the Pediatric Intensive Care Unit of a tertiary care hospital in North India from January 2010 to December 2022. GBS was subtyped based on nerve conduction studies into acute motor axonal neuropathy (AMAN), acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor-sensory axonal neuropathy (AMSAN), inexcitable, or equivocal patterns. Clinical features, intensive care interventions, and outcomes were compared across subtypes.</div></div><div><h3>Results</h3><div>AMAN was the most common subtype (61.6%), followed by AIDP (20.1%) and AMSAN (8%). A prodromal illness was reported in 47.3% of cases. Mechanical ventilation was required in 54.9%, and tracheostomy in 24.2% of children. AMSAN was associated with a significantly longer duration of symptoms at presentation (<em>P</em> = 0.006). Autonomic instability, particularly hypertension (<em>P</em> = 0.04), was significantly more frequent in the AIDP group. However, Hughes disability scores, respiratory and cranial nerve involvement, and intensive care needs were similar across subtypes.</div></div><div><h3>Conclusions</h3><div>AMAN was the predominant GBS subtype in critically ill children. While AMSAN was associated with delayed presentation and AIDP with greater autonomic dysfunction, overall intensive care needs and short-term outcomes were comparable across subtypes.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 168-173"},"PeriodicalIF":2.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736661","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 : 2025-11-29DOI: 10.1016/j.pediatrneurol.2025.11.017
Nicholas Joy BS , Jonathan Soslow MD, MSCI , W. Bryan Burnette MD , Andrew Liu PhD , Christine C. Guo PhD , Rakesh Pilkar PhD , James C. Slaughter DrPH , Meng Xu MS , Kimberly Crum RN , Karry Su BS , Christopher Spurney MD , Nazia Husain MBBS, MPH , Katheryn Gambetta MD , Brian D. Soriano MD , Frank J. Raucci Jr. MD, PhD , Kan Hor MD , Larry W. Markham MD , Jaclyn Tamaroff MD, MSCI
Background
The six-minute walk test and quantitative muscle testing (QMT) are commonly used skeletal muscle assessments in Duchenne muscular dystrophy; however, they present challenges in nonambulatory patients. Our objective was to evaluate whether 6-min activity-95th centile, a novel accelerometry metric capturing a participant's greatest amount of movement in six consecutive minutes, distinguished between ambulatory and nonambulatory individuals and correlated with QMT data.
Methods
Participants (N = 139) in an observational, longitudinal natural history study with median age of 12.0 years [interquartile range 10.0, 15.0] completed muscle testing and were instructed to wear an accelerometer on dominant wrist for 7 days and nights (a “wear”) at each of three annual study visits. One hundred two male participants were analyzed with a total of 184 valid wear periods.
Results
Six-minute activity centiles declined over 2 years (n = 28, P < 0.001). No significant declines in centiles were detected immediately following loss of ambulation (n = 11). Significant correlations were observed between 6-min activity centiles and indexed QMT, with strongest at 95th centile (rs = 0.647, P < 0.001). There was a relationship between 6-min centiles and time since loss of ambulation.
Conclusions
Ambulatory and nonambulatory patients with Duchenne muscular dystrophy were differentiated by 6-min activity and declined over time, modeling progression of skeletal myopathy. Six-minute activity-95th centile has potential for future use as an effort-independent outcome of skeletal muscle progression and functional decline for both ambulatory and nonambulatory individuals.
背景：6分钟步行试验和定量肌肉试验（QMT）是常用的骨骼肌评估杜氏肌营养不良；然而，它们在非门诊患者中提出了挑战。我们的目的是评估6分钟活动-95百分位（一种新颖的加速度测量指标，捕捉参与者在连续6分钟内的最大运动量）是否能区分动态和非动态个体，并与QMT数据相关。方法：在一项观察性、纵向自然历史研究中，参与者（N = 139）的中位年龄为12.0岁[四分位数间距10.0,15.0]，完成了肌肉测试，并被指示在三次年度研究访问中每次在主手腕上佩戴加速度计7天7夜（“佩戴”）。对102名男性参与者进行了184个有效磨损期的分析。结果：6分钟活动百分位数在2年内下降（n = 28, P < 0.001）。在丧失行走能力后未立即检测到明显的百分位下降（n = 11）。6分钟活动百分位与指标QMT之间存在显著相关性，其中第95百分位相关性最强（rs = 0.647, P < 0.001）。6分位与丧失活动能力的时间之间存在相关性。结论：杜氏肌营养不良症患者可通过6分钟活动来区分，并随着时间的推移而下降，模拟骨骼肌病的进展。6分钟活动-95百分位有潜力在未来作为一个不依赖于运动和非运动个体的骨骼肌进展和功能衰退的结果。
{"title":"Six-Minute Activity-95th Centile, a Novel Wearable-Derived Clinical Outcome Assessment for Duchenne Muscular Dystrophy","authors":"Nicholas Joy BS , Jonathan Soslow MD, MSCI , W. Bryan Burnette MD , Andrew Liu PhD , Christine C. Guo PhD , Rakesh Pilkar PhD , James C. Slaughter DrPH , Meng Xu MS , Kimberly Crum RN , Karry Su BS , Christopher Spurney MD , Nazia Husain MBBS, MPH , Katheryn Gambetta MD , Brian D. Soriano MD , Frank J. Raucci Jr. MD, PhD , Kan Hor MD , Larry W. Markham MD , Jaclyn Tamaroff MD, MSCI","doi":"10.1016/j.pediatrneurol.2025.11.017","DOIUrl":"10.1016/j.pediatrneurol.2025.11.017","url":null,"abstract":"<div><h3>Background</h3><div>The six-minute walk test and quantitative muscle testing (QMT) are commonly used skeletal muscle assessments in Duchenne muscular dystrophy; however, they present challenges in nonambulatory patients. Our objective was to evaluate whether 6-min activity-95<sup>th</sup> centile, a novel accelerometry metric capturing a participant's greatest amount of movement in six consecutive minutes, distinguished between ambulatory and nonambulatory individuals and correlated with QMT data.</div></div><div><h3>Methods</h3><div>Participants (N = 139) in an observational, longitudinal natural history study with median age of 12.0 years [interquartile range 10.0, 15.0] completed muscle testing and were instructed to wear an accelerometer on dominant wrist for 7 days and nights (a “wear”) at each of three annual study visits. One hundred two male participants were analyzed with a total of 184 valid wear periods.</div></div><div><h3>Results</h3><div>Six-minute activity centiles declined over 2 years (n = 28, <em>P</em> < 0.001). No significant declines in centiles were detected immediately following loss of ambulation (n = 11). Significant correlations were observed between 6-min activity centiles and indexed QMT, with strongest at 95<sup>th</sup> centile (r<sub>s</sub> = 0.647, <em>P</em> < 0.001). There was a relationship between 6-min centiles and time since loss of ambulation.</div></div><div><h3>Conclusions</h3><div>Ambulatory and nonambulatory patients with Duchenne muscular dystrophy were differentiated by 6-min activity and declined over time, modeling progression of skeletal myopathy. Six-minute activity-95<sup>th</sup> centile has potential for future use as an effort-independent outcome of skeletal muscle progression and functional decline for both ambulatory and nonambulatory individuals.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 187-195"},"PeriodicalIF":2.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768778","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 : 2025-11-28DOI: 10.1016/j.pediatrneurol.2025.11.018
Margaret Kasbarian, Harrison Cheng, Jada Phan, Troy Zeier MS, Jessica Bee PharmD, BCPPS, Jacklyn L. Wright PharmD, BCPPS, Jenna A. Chiang PsyD, ABPP-CN, Asri Yuliati MD
Background
Cenobamate is an antiseizure medication (ASM) for the treatment of focal-onset seizures in adults aged 18 years and older—while currently used off-label in children and adolescents, its pediatric potential is significant. Studies demonstrated a promising median seizure reduction of up to 65% in patients with treatment-resistant focal epilepsy.
Methods
This study aimed to investigate the effectiveness and safety of cenobamate as an adjunctive ASM in epilepsy patients under 18 years. The primary objective was to assess the effectiveness of cenobamate by examining seizure reduction. Secondary end points included adverse drug reactions (ADRs) and the median dose. Data were summarized using descriptive statistics, including mean, standard deviation, median, interquartile range, and percentages.
Results
Among 31 patients, 52% experienced a 75-100% reduction in seizure frequency, 16% had a 50-75% reduction, 13% had a 25-50% reduction, and 19% had no reduction or an increase in seizure frequency upon initiating cenobamate. These outcomes correspond to a median seizure reduction rate of 80%. The most common ADR was sedation (32.3%), followed by aggression and other mood changes. The median maintenance dose was 150 mg; patients weighing <50 kg received a median dose of 137.5 mg/day (5.2 mg/kg/day). Notably, patients were on a median of five ASMs before starting cenobamate, which decreased to two with cenobamate, suggesting a potential role in simplifying treatment regimens.
Conclusions
Our study showed that initiating cenobamate as adjunctive therapy was effective and safe for pediatric patients with treatment-resistant epilepsy, reducing seizure frequency and establishing improved seizure control.
{"title":"Safety and Effectiveness of Cenobamate in Pediatric Patients With Treatment-Resistant Epilepsy","authors":"Margaret Kasbarian, Harrison Cheng, Jada Phan, Troy Zeier MS, Jessica Bee PharmD, BCPPS, Jacklyn L. Wright PharmD, BCPPS, Jenna A. Chiang PsyD, ABPP-CN, Asri Yuliati MD","doi":"10.1016/j.pediatrneurol.2025.11.018","DOIUrl":"10.1016/j.pediatrneurol.2025.11.018","url":null,"abstract":"<div><h3>Background</h3><div>Cenobamate is an antiseizure medication (ASM) for the treatment of focal-onset seizures in adults aged 18 years and older—while currently used off-label in children and adolescents, its pediatric potential is significant. Studies demonstrated a promising median seizure reduction of up to 65% in patients with treatment-resistant focal epilepsy.</div></div><div><h3>Methods</h3><div>This study aimed to investigate the effectiveness and safety of cenobamate as an adjunctive ASM in epilepsy patients under 18 years. The primary objective was to assess the effectiveness of cenobamate by examining seizure reduction. Secondary end points included adverse drug reactions (ADRs) and the median dose. Data were summarized using descriptive statistics, including mean, standard deviation, median, interquartile range, and percentages.</div></div><div><h3>Results</h3><div>Among 31 patients, 52% experienced a 75-100% reduction in seizure frequency, 16% had a 50-75% reduction, 13% had a 25-50% reduction, and 19% had no reduction or an increase in seizure frequency upon initiating cenobamate. These outcomes correspond to a median seizure reduction rate of 80%. The most common ADR was sedation (32.3%), followed by aggression and other mood changes. The median maintenance dose was 150 mg; patients weighing <50 kg received a median dose of 137.5 mg/day (5.2 mg/kg/day). Notably, patients were on a median of five ASMs before starting cenobamate, which decreased to two with cenobamate, suggesting a potential role in simplifying treatment regimens.</div></div><div><h3>Conclusions</h3><div>Our study showed that initiating cenobamate as adjunctive therapy was effective and safe for pediatric patients with treatment-resistant epilepsy, reducing seizure frequency and establishing improved seizure control.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 218-222"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782441","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 : 2025-11-28DOI: 10.1016/j.pediatrneurol.2025.11.021
Kuntal Sen MD, Aravindhan Veerapandiyan MD
{"title":"Survivorship in Child Neurology: A Transformative Era","authors":"Kuntal Sen MD, Aravindhan Veerapandiyan MD","doi":"10.1016/j.pediatrneurol.2025.11.021","DOIUrl":"10.1016/j.pediatrneurol.2025.11.021","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 196-197"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768780","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 : 2025-11-27DOI: 10.1016/j.pediatrneurol.2025.11.020
Natalie Kukulka MD , Paul Vermilion MD , Bo Lee MD
Duchenne Muscular Dystrophy (DMD) is a progressive and life-limiting neuromuscular disorder with profound implications for affected individuals and their families. Advances in genetic and molecular therapies, including exon skipping agents, gene therapy, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based approaches have ushered in a new era of disease-modifying treatments. However, these breakthroughs also introduce complex ethical and psychosocial challenges. As we continue to extend life expectancy and improve motor outcomes for individuals with DMD, there is also a need to ensure autonomy-supportive environments, particularly during the transition to adulthood. This review provides a comprehensive exploration of the evolving landscape of DMD management, the long-term and ethical considerations of experimental therapies, and the psychosocial impacts on patients and caregivers. In the context of recent major advancements in medical care, we reflect on the impact of the growing group of DMD “boys” navigating the transition to adulthood. Lastly, this review highlights the critical need for multidisciplinary care models that address not only the biological but also the evolving psychological and social dimensions of the disease. By synthesizing perspectives from treatment innovation and ethical discourse, this article equips readers with a holistic understanding of the transformative potential and challenges associated with DMD therapies. This review aims to support multidisciplinary neuromuscular clinics to more fully meet the needs of an increasingly diverse population of patients with an ever-expanding potential.
{"title":"Duchenne Muscular Dystrophy: Clinical Innovations, Ethical Considerations, and Evolving the Path to Adulthood","authors":"Natalie Kukulka MD , Paul Vermilion MD , Bo Lee MD","doi":"10.1016/j.pediatrneurol.2025.11.020","DOIUrl":"10.1016/j.pediatrneurol.2025.11.020","url":null,"abstract":"<div><div>Duchenne Muscular Dystrophy (DMD) is a progressive and life-limiting neuromuscular disorder with profound implications for affected individuals and their families. Advances in genetic and molecular therapies, including exon skipping agents, gene therapy, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based approaches have ushered in a new era of disease-modifying treatments. However, these breakthroughs also introduce complex ethical and psychosocial challenges. As we continue to extend life expectancy and improve motor outcomes for individuals with DMD, there is also a need to ensure autonomy-supportive environments, particularly during the transition to adulthood. This review provides a comprehensive exploration of the evolving landscape of DMD management, the long-term and ethical considerations of experimental therapies, and the psychosocial impacts on patients and caregivers. In the context of recent major advancements in medical care, we reflect on the impact of the growing group of DMD “boys” navigating the transition to adulthood. Lastly, this review highlights the critical need for multidisciplinary care models that address not only the biological but also the evolving psychological and social dimensions of the disease. By synthesizing perspectives from treatment innovation and ethical discourse, this article equips readers with a holistic understanding of the transformative potential and challenges associated with DMD therapies. This review aims to support multidisciplinary neuromuscular clinics to more fully meet the needs of an increasingly diverse population of patients with an ever-expanding potential.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 210-217"},"PeriodicalIF":2.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774519","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 : 2025-11-27DOI: 10.1016/j.pediatrneurol.2025.11.019
Ibrahim Elsharkawi MD , Amy Goldstein MD , Rebecca D. Ganetzky MD , Eva Morava MD, PhD
Primary mitochondrial diseases comprise a clinically, genetically, and biochemically heterogenous group of disorders associated with multisystemic involvement and significant morbidity and mortality of various etiologies. To date, no disease modifying therapies have been FDA approved, and treatment is largely symptomatic and supportive. Because of the rarity of mitochondrial specialists, most patients with mitochondrial diseases are cared for by clinicians without mitochondrial-specific expertise. Therefore, these clinicians by necessity rely on existing literature or older prognostic approaches which may be discordant with modern clinical practice and evolving therapeutic strategies and outcomes. Furthermore, existing literature may be skewed to the more severe end of the spectrum as publications may disproportionately focus on the most severe or unusual cases. Prognostic, therapeutic, and palliative discussions should ideally take place in a multidisciplinary setting where shared decision making can take place between the patient, family, and clinician team. Prognosis is increasingly shaped by the unprecedented development of various therapeutic modalities and personalized medicine. We aim to highlight the multipronged challenges and considerations faced in counseling patients and caregivers and draw from our own patient cohorts and observations in contemporary mitochondrial medicine to offer additional insights and future considerations for approaching patient counseling and prognostication.
{"title":"Counseling and Prognostic Challenges in Survivorship and Mortality in Primary Mitochondrial Disease: Reshaping a Once Bleak Landscape","authors":"Ibrahim Elsharkawi MD , Amy Goldstein MD , Rebecca D. Ganetzky MD , Eva Morava MD, PhD","doi":"10.1016/j.pediatrneurol.2025.11.019","DOIUrl":"10.1016/j.pediatrneurol.2025.11.019","url":null,"abstract":"<div><div>Primary mitochondrial diseases comprise a clinically, genetically, and biochemically heterogenous group of disorders associated with multisystemic involvement and significant morbidity and mortality of various etiologies. To date, no disease modifying therapies have been FDA approved, and treatment is largely symptomatic and supportive. Because of the rarity of mitochondrial specialists, most patients with mitochondrial diseases are cared for by clinicians without mitochondrial-specific expertise. Therefore, these clinicians by necessity rely on existing literature or older prognostic approaches which may be discordant with modern clinical practice and evolving therapeutic strategies and outcomes. Furthermore, existing literature may be skewed to the more severe end of the spectrum as publications may disproportionately focus on the most severe or unusual cases. Prognostic, therapeutic, and palliative discussions should ideally take place in a multidisciplinary setting where shared decision making can take place between the patient, family, and clinician team. Prognosis is increasingly shaped by the unprecedented development of various therapeutic modalities and personalized medicine. We aim to highlight the multipronged challenges and considerations faced in counseling patients and caregivers and draw from our own patient cohorts and observations in contemporary mitochondrial medicine to offer additional insights and future considerations for approaching patient counseling and prognostication.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 223-228"},"PeriodicalIF":2.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782391","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 : 2025-11-26DOI: 10.1016/j.pediatrneurol.2025.11.015
Jacob Thorstensen PhD , Heather Godfrey FNP, MNNP, BN, BSc , Regan King MSc , Ephrem Zewdie MD, PhD , Adam Kirton MD, MSc , Keith Owen Yeates PhD , Frank MacMaster PhD , Karen Barlow PhD, MSc, MBChB, MRCPCH
Background
Although most children and adolescents with a mild traumatic brain injury recover quickly, a significant minority develop intractable headaches, cognitive difficulties, and/or mood disturbances known as persistent postconcussion symptoms (PPCS). Repetitive transcranial magnetic stimulation (rTMS) offers significant therapeutic potential in PPCS.
Methods
Fourteen adolescents (15.6 ± 1.5 years, 10 females) with PPCS ≥3 months postinjury (median: 4, 3-16 months) were recruited into an open label, single centre, safety/feasibility rTMS trial. Four weeks of once daily rTMS (20 visits, 10 Hz at 120% of resting motor threshold, 3000 stimulations per session) was applied to the left dorsolateral prefrontal cortex. Adverse events were monitored at every treatment. Additional outcomes included the Post-Concussion Symptom Inventory (PCSI) and Pediatric Quality of Life Inventory (PedsQL).
Results
No serious adverse events were observed. Headaches were the most frequent adverse event; but headaches tended to decrease in frequency over the treatment course. Twelve out of 14 participants attended 90% or more of the rTMS sessions. After 4 weeks of rTMS, PCSI total scores decreased from pre-rTMS values by 27.5 ± 20.9 points (Z = −3.3, P < 0.001) and PedsQL total scores increased by 12 ± 12.6 points (t13 = −3.5, P = 0.004). One-month post-rTMS, PedsQL scores were still increased but PCSI scores were not different from baseline.
Conclusions
High frequency rTMS to the left dorsolateral prefrontal cortex is safe/feasible for adolescents with PPCS. Results provide data to inform large randomized, sham-controlled trials to explore the efficacy of rTMS to treat pediatric PPCS.
背景：虽然大多数患有轻度创伤性脑损伤的儿童和青少年恢复迅速，但仍有少数人出现顽固性头痛、认知困难和/或情绪障碍，即持续性脑震荡后症状（PPCS）。重复经颅磁刺激（rTMS）在PPCS中具有显著的治疗潜力。方法：选取14例损伤后PPCS≥3个月（中位数：4,3 -16个月）的青少年（15.6±1.5岁，10例女性），进行开放标签、单中心、安全性/可行性rTMS试验。对左背外侧前额皮质施加为期四周的每日一次rTMS（20次，10hz，静息运动阈值的120%，每次3000次刺激）。每次治疗均监测不良事件。其他结果包括脑震荡后症状量表（PCSI）和儿科生活质量量表（PedsQL）。结果:未见严重不良事件。头痛是最常见的不良事件；但在治疗过程中，头痛的频率趋于降低。14名参与者中有12名参加了90%或更多的rTMS会议。rTMS 4周后，PCSI总分较rTMS前下降了27.5±20.9分（Z = -3.3, P < 0.001）， PedsQL总分上升了12±12.6分（t13 = -3.5, P = 0.004）。rtms后1个月PedsQL评分仍升高，但PCSI评分与基线无显著差异。结论：高频rTMS治疗青少年PPCS是安全可行的。结果为大型随机、假对照试验提供了数据，以探索rTMS治疗儿童PPCS的疗效。
{"title":"Repetitive Transcranial Magnetic Stimulation in Adolescents With Persistent Postconcussion Symptoms After Mild Traumatic Brain Injury: An Open Label Safety and Feasibility Study","authors":"Jacob Thorstensen PhD , Heather Godfrey FNP, MNNP, BN, BSc , Regan King MSc , Ephrem Zewdie MD, PhD , Adam Kirton MD, MSc , Keith Owen Yeates PhD , Frank MacMaster PhD , Karen Barlow PhD, MSc, MBChB, MRCPCH","doi":"10.1016/j.pediatrneurol.2025.11.015","DOIUrl":"10.1016/j.pediatrneurol.2025.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Although most children and adolescents with a mild traumatic brain injury recover quickly, a significant minority develop intractable headaches, cognitive difficulties, and/or mood disturbances known as persistent postconcussion symptoms (PPCS). Repetitive transcranial magnetic stimulation (rTMS) offers significant therapeutic potential in PPCS.</div></div><div><h3>Methods</h3><div>Fourteen adolescents (15.6 ± 1.5 years, 10 females) with PPCS ≥3 months postinjury (median: 4, 3-16 months) were recruited into an open label, single centre, safety/feasibility rTMS trial. Four weeks of once daily rTMS (20 visits, 10 Hz at 120% of resting motor threshold, 3000 stimulations per session) was applied to the left dorsolateral prefrontal cortex. Adverse events were monitored at every treatment. Additional outcomes included the Post-Concussion Symptom Inventory (PCSI) and Pediatric Quality of Life Inventory (PedsQL).</div></div><div><h3>Results</h3><div>No serious adverse events were observed. Headaches were the most frequent adverse event; but headaches tended to decrease in frequency over the treatment course. Twelve out of 14 participants attended 90% or more of the rTMS sessions. After 4 weeks of rTMS, PCSI total scores decreased from pre-rTMS values by 27.5 ± 20.9 points (<em>Z</em> = −3.3, <em>P</em> < 0.001) and PedsQL total scores increased by 12 ± 12.6 points (<em>t</em><sub>13</sub> = −3.5, <em>P</em> = 0.004). One-month post-rTMS, PedsQL scores were still increased but PCSI scores were not different from baseline.</div></div><div><h3>Conclusions</h3><div>High frequency rTMS to the left dorsolateral prefrontal cortex is safe/feasible for adolescents with PPCS. Results provide data to inform large randomized, sham-controlled trials to explore the efficacy of rTMS to treat pediatric PPCS.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"175 ","pages":"Pages 198-207"},"PeriodicalIF":2.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774810","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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