Quick, Effective Screening Tasks Identify Children With Medical Conditions or Disabilities Needing Physical Literacy Support.

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

Role of EEG as a monitoring tool in patients with glucose transporter type I deficiency syndrome (GLUT1-DS) on ketogenic diet.

RATIONALE: Glucose transporter type I deficiency syndrome (GLUT1-DS) is the fourth most frequent single-gene epilepsy refractory to standard antiepileptic drugs. Multiple seizure types and variable electrographic findings are reported. Ketogenic diet is expected to result in the complete resolution of the epileptiform activity. METHODS: A retrospective chart review of patients with GLUT1-DS on ketogenic diet between December 2012 and February 2022 was done. Analysis of the EEGs prior to and during the ketogenic diet was done. RESULTS: 34 patients on ketogenic diet were reviewed. Ten had clinical diagnosis of GLUT1-DS, and seven of them had genetic confirmation. 71% were female. The average age at seizure onset was 13.85 m.o. (range: 3-60, SD ±20.52), at diagnosis was 44.57 m.o (range: 19-79), and at the onset of ketogenic diet was 46.43 m.o. (range: 20-83). 29 months (range: 13-38) delay between symptoms onset until diagnosis was noticed. At the diagnosis 100% reported seizures: 71% myoclonic, 57% generalized motor, 57% absence, 28% atonic, and 14% focal motor. Also, 71% abnormal eye movements, 57% ataxia, and 28% intolerance to fasting. 86% had normal brain MRI. 71% had abnormal EEG. All were on ketogenic diet, and four on classical (1.75:1-2.25:1 ratio). Six were clinically seizure-free after the ketogenic diet. EEG features included notch delta, focal spike and wave, and generalized spike/polyspike and wave. One patient had bilateral independent centrotemporal spikes. Spikes showed high and very high amplitude in all of them (>200 µV). The variation of the spike index decreased in three patients but increased in two. CONCLUSION: Ketogenic diet is the choice treatment for patients with GLUT1-DS. Electrographic features could show worsening after initiation of the ketogenic diet even with seizure control. EEG did not prove to be a reliable tool for adjusting KD in our cohort. Centrotemporal spikes have not been reported in patients with GLUT-1 DS.

Potential Benefit of Add-on Δ9-Tetrahydrocannabinol in Pediatric Drug-Resistant Epilepsy: A Case Series.

We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.

A De Novo Missense Variant in TUBG2 in a Child with Global Developmental Delay, Microcephaly, Refractory Epilepsy and Perisylvian Polymicrogyria.

Polymicrogyria is a brain malformation characterized by excessive folding of the cortex. To date, numerous causes of polymicrogyria have been identified, including variants in the genes associated with tubulinopathies. Herein, we present a child with severe intellectual disability, refractory to treatment seizures, microcephaly and MRI findings consistent with polymicrogyria, closed-lip schizencephaly, periventricular heterotopia and a dysplastic corpus callosum. Exome sequencing identified a de novo missense variant in TUBG2, a gene not associated with human disease. The variant, NM_016437.3 c.747G>A p.(Met249Ile), is absent from available control databases and is predicated to be deleterious by in silico prediction programs. Laboratory studies show that cultured lymphoblasts derived from the patient grew significantly faster than controls. Recombinant protein was expressed (recombinant wild type and mutant TUBG2-FLAG) in 293T cells and lower levels of TUBG2 mutant compared with controls were observed. Furthermore, co-immuno-precipitation in cells transfected demonstrated that the TUBG2−GCP2 interaction is increased due to the MUT recombinant protein versus WT recombinant protein. In closing, this work provides preliminary evidence that TUBG2 may represent a novel disease gene responsible for polymicrogyria.

Characterization of physical literacy in children with chronic medical conditions compared with healthy controls: a cross-sectional study.

To determine the physical literacy, defined as the capability for a physically active lifestyle, of children with medical conditions compared with healthy peers, this multicenter cross-sectional study recruited children with medical conditions from cardiology, neurology (including concussion), rheumatology, mental health, respirology, oncology, hematology, and rehabilitation (including cerebral palsy) clinics. Participants aged 8-12 years (N = 130; mean age: 10.0 ± 1.44 years; 44% female) were randomly matched to 3 healthy peers from a normative database, based on age, gender, and month of testing. Total physical literacy was assessed by the Canadian Assessment of Physical Literacy, a validated assessment of physical literacy measuring physical competence, daily behaviour, knowledge/understanding, and motivation/confidence. Total physical literacy mean scores (/100) did not differ (t(498) = -0.67; p = 0.44) between participants (61.0 ± 14.2) and matched healthy peers (62.0 ± 10.7). Children with medical conditions had lower mean physical competence scores (/30; -6.5 [-7.44 to -5.51]; p < 0.001) but higher mean motivation/confidence scores (/30; 2.6 [1.67 to 3.63]; p < 0.001). Mean daily behaviour and knowledge/understanding scores did not differ from matches (/30; 1.8 [0.26 to 3.33]; p = 0.02;/10; -0.04 [-0.38 to 0.30]; p = 0.81; respectively). Children with medical conditions are motivated to be physically active but demonstrate impaired movement skills and fitness, suggesting the need for targeted interventions to improve their physical competence. Novelty: Physical literacy in children with diverse chronic medical conditions is similar to healthy peers. Children with medical conditions have lower physical competence than healthy peers, but higher motivation and confidence. Physical competence (motor skill, fitness) interventions, rather than motivation or education, are needed for these youth.

Cannabis Use for Therapeutic Purposes by Children and Youth at a Tertiary Teaching Hospital in Canada: A Retrospective Chart Review.

BACKGROUND: The study of the use of cannabis for therapeutic purposes in the pediatric population is increasing, yet data on efficacy and safety are limited. Characterization of pediatric cannabis use for therapeutic purposes will improve understanding of the circumstances under which it occurs and the associated outcomes. OBJECTIVE: To describe the use of cannabis for therapeutic purposes, regardless of authorization, in a pediatric tertiary teaching hospital. METHODS: A retrospective chart review was completed for patients 18 years of age or younger who used cannabis for therapeutic purposes, regardless of authorization, between May 1, 2014, and May 1, 2017. Patients whose cannabis use was documented as recreational were excluded. RESULTS: In total, 300 patients were identified, of whom 37 met the inclusion criteria. Of these, 30 patients had documentation of medically supervised cannabis use. Most were using cannabis for seizures (n = 28), and many of these (n = 23) were patients with seizures described as intractable or refractory. Of the 27 patients who were experiencing seizures at initiation of medical cannabis, 21 had documentation of a decrease in seizure frequency. This decrease was transient for 16 patients, with a mean duration of 130.4 days (standard deviation 99.1 days). Seven patients self-medicated with cannabis. They obtained cannabis without authorization and used it for chronic pain (n = 5) and/or anxiety (n = 5). CONCLUSIONS: Medically supervised cannabis use occurred most often in patients with intractable or refractory seizures. According to these data, seizure response is variable, and initial decreases may be transient for pediatric patients using cannabis. To ensure greater consistency and rigour in the conduct of prospective research and thus to generate better-quality research on the therapeutic effects of medical cannabis, development of a standardized care record is needed.

CONTEXTE: Les études portant sur l'utilisation du cannabis à des fins thérapeutiques par les enfants augmentent, mais les données concernant l'efficacité et la sécurité de cette drogue sont limitées. La caractérisation de l'usage du cannabis à des fins thérapeutiques permettra de mieux comprendre les circonstances de l'utilisation de cette drogue ainsi que les effets qui lui sont associés. OBJECTIF: Décrire l'utilisation du cannabis à des fins thérapeutiques, qu'elle soit autorisée ou non, dans un hôpital d'enseignement de soins pédiatriques tertiaires. MÉTHODES: Un examen rétrospectif des dossiers a été mené auprès de patients d'âge égal ou inférieur à 18 ans, qui ont fait un usage autorisé ou non de cannabis à des fins thérapeutiques entre le 1er mai 2014 et le 1er mai 2017. Les patients qui utilisaient du cannabis à des fins récréatives ont été exclus de l'étude. RÉSULTATS: Au total 300 patients ont été identifiés et 37 d'entre eux répondaient au critère d'inclusion. La prise de cannabis sous supervision médicale de 30 d'entre eux était documentée. La plupart utilisaient le cannabis en cas de crise (n = 28) et bon nombre d'entre eux (n = 23) étaient des patients dont les crises étaient décrites comme insolubles ou réfractaires. Des 27 patients qui avaient des crises au début de la prise de cannabis médical, 21 ont enregistré une diminution de la fréquence des crises. Seize patients ont obtenu une diminution éphémère, qui a duré en moyenne 130,4 jours (écart type : 99,1 jours). Sept patients se soignaient eux-mêmes à l'aide de cannabis. Ils obtenaient du cannabis sans autorisation et l'utilisaient pour soulager des douleurs chroniques (n = 5) ou leur anxiété (n = 5). CONCLUSIONS: Les patients qui subissaient des crises incurables ou réfractaires utilisaient le plus souvent du cannabis sous supervision médicale. Selon ces données, la réponse aux crises est variable et les baisses initiales du nombre de crises pourraient être éphémères chez les enfants utilisant du cannabis. Il convient de préparer un dossier de soins normalisé pour mener des recherches prospectives plus cohérentes et rigoureuses et donc générer des recherches de meilleure qualité sur les effets thérapeutiques du cannabis médical.

Tuberous sclerosis complex associated intracranial lesion found by antenatal ultrasound.

Tuberous sclerosis complex (TSC) is characterized by the growth of benign tumors in the skin, brain, kidneys, lung and heart [1]. Prognosis is mostly determined by the extent of brain involvement as tumors in the brain lead to seizures, cognitive impairment and behavioral problems. Current evidence suggests anti-epileptic treatment before the onset of seizures reduces epilepsy severity and risk of cognitive impairment in TSC however identifying these children prior to the onset of seizures is challenging. Our case shows retrospectively reviewed antenatal ultrasounds of a male child diagnosed postnatally at 12 days of life with TSC. Analysis found a soft tissue mass in the right ventricle on antenatal ultrasound which was not captured in the initial ultrasound report. Though there are no reports of sensitivity of neurosonography for the antenatal detection of intracranial abnormalities associated with TSC, our case suggests that antenatal ultrasound could be used as a screening modality for antenatal diagnosis of TSC.

No improvement in quality of life in children with epilepsy treated with the low glycemic index diet.

BACKGROUND: Up to 30% of children with epilepsy show a poor therapeutic response to pharmacologic treatment. Ketogenic diets, including the less strict low glycemic index treatment (LGIT), may improve seizure control in pharmacoresistant epilepsy. However, little is known about the quality of life (QoL) in children on LGIT. To explore psychosocial implications of the LGIT on pediatric patients and their caregivers, we have conducted a pilot study to explore the QoL of children and adolescents on the diet. METHODS: Pediatric patients on LGIT and their parents completed standardized, validated QoL questionnaires (Pediatric Quality of Life Epilepsy Module), one retrospectively and one while being on LGIT. An additional questionnaire included two open-ended questions in order to gain a better understanding of personal experiences of families. RESULTS: We enrolled six patients with epilepsy on LGIT between the age of 3 and 13 years. Self-reported QoL decreased in all adolescents, regardless of improvement in seizure control. Parent-reported QoL improved in three of six participants, remained stable in one, and decreased in two patients (both displayed no seizure improvement). Parents and adolescents reported positive experiences of trying new foods and being more health conscious, as well as negative themes such as social isolation and meal preparation difficulties. CONCLUSIONS: The lack of improvement in patient-reported QoL points towards an overall negative impact of the LGIT on patient well-being, despite positive effects on seizure control. Our preliminary results indicate that the benefits of seizure control may subjectively be outweighed by adverse social effects of the LGIT. Families should be made aware of psychosocial risks of the diet. Whenever possible, children should be part of the therapeutic decision-making process. Larger prospective studies are required to fully assess the overall impact of the LGIT.

Continuous Electroencephalography Monitoring for Critically Ill Neonates: A Canadian Perspective.

BACKGROUND: Continuous EEG monitoring, in the form of amplitude-integrated (aEEG) or conventional EEG (cEEG), is used in the neonatal intensive care unit (NICU) to detect subclinical central nervous system pathologies, inform management, and prognosticate neurodevelopmental outcomes. To learn more about provider attitudes and current practices in Canada, we evaluated neurologist and neonatologist opinions regarding NICU EEG monitoring. METHODS: A 15-item electronic questionnaire was distributed to 114 pediatric neurologists and 176 neonatologists working across 25 sites. RESULTS: The survey was completed by 87 of 290 physicians. Continuous EEG monitoring is utilized by 97% of pediatric neurologists and 92% of neonatologists. Neurologists and neonatologists differ in their EEG monitoring preferences. For seizure detection and diagnosis of encephalopathy, significantly more neonatologists favor aEEG alone or in combination with cEEG, whereas most neurologists prefer cEEG (p = 0.047, 0.001). There is a significant difference in the perceived gaps in monitoring patients with cEEG between neonatologists (13% would monitor more) and neurologists (41% would monitor more) (p = 0.007). Half of all respondents (53%) reported that they would be interested in attending an education session on neonatal EEG monitoring. CONCLUSIONS: Canadian neurologists and neonatologists do not agree on the best monitoring approach for critically ill neonates. Furthermore, neonatologists perceive a smaller cEEG monitoring gap as compared with neurologists. However, many participants from both specialties would like to increase long-term EEG monitoring in the NICU setting. Facilitating access to EEG monitoring and enhancing education may help to address these needs.

La surveillance continue par électroencéphalographie dans le cas de nouveau-nés gravement malades : une perspective canadienne. Contexte: La surveillance continue par électroencéphalographie (EEG), que ce soit à amplitude intégrée (EEGai) ou conventionnelle (EEGc), est utilisée dans les unités de soins intensifs néonatals (USIN) afin de détecter des pathologies sous-cliniques du système nerveux central, de fournir des indications en matière de prise en charge et d'établir des pronostics quant à l'évolution neuro-développementale de ces nouveau-nés. Afin d'en savoir plus au sujet des attitudes des prestataires de soins et des pratiques actuelles dans ce domaine au Canada, nous avons cherché à évaluer les points de vue de neurologues et de néonatologistes en ce qui regarde la surveillance continue par EEG dans les USIN. Méthodes: Un questionnaire en ligne abordant 15 aspects a été envoyé à 114 neuro-pédiatres et à 176 néonatologistes travaillant dans 25 établissements différents. Résultats: Ce sondage a été complété par 87 médecins sur 290. Il en ressort que la surveillance continue par EEG est utilisée par 97 % des neuro-pédiatres et par 92 % des néonatologistes. Cela dit, les neuro-pédiatres et les néonatologistes n'ont pas les mêmes préférences quant à l'utilisation de cet examen. Quand il s'agit de détecter des crises convulsives et de diagnostiquer des cas d'encéphalopathie, on remarque qu'un nombre nettement plus élevé de néonatologistes favorisent la seule EEGai ou la combinent avec la EEGc tandis que davantage de neurologues ont dit préférer la seule EEGc (p = 0,047 ; p = 0,001). Qui plus est, on peut dénoter une différence notable entre les néonatologistes et les neurologues en ce qui a trait aux écarts perçus de surveillance des patients au moyen de la EEGc, 13 % des premiers assurant une surveillance supérieure alors qu'ils sont 41 % parmi les deuxièmes à assurer une surveillance supérieure (p = 0,007). Enfin, plus de la moitié des répondants (53 %) ont affirmé être intéressés à assister à des séances de formation portant sur la surveillance continue par EEG destinée aux nouveau-nés. Conclusions: Les neurologues et les néonatologistes canadiens divergent quant à la meilleure approche de surveillance dans le cas de nouveau-nés gravement malades. En outre, les néonatologistes ont tendance à percevoir un écart de surveillance moins important si on les compare aux neurologues. Néanmoins, nombreux sont les répondants formés dans ces deux spécialités qui souhaiteraient augmenter à long terme la surveillance par EEG dans les USIN. Le fait de faciliter l'accès à ces examens et d'améliorer l'enseignement pourrait ainsi permettre de répondre aux besoins.

Combined Conventional and Amplitude-Integrated EEG Monitoring in Neonates: A Prospective Study.

BACKGROUND/OBJECTIVE: Seizure monitoring via amplitude-integrated EEG is standard of care in many neonatal intensive care units; however, conventional EEG is the gold standard for seizure detection. We compared the diagnostic yield of amplitude-integrated EEG interpreted at the bedside, amplitude-integrated EEG interpreted by an expert, and conventional EEG. METHODS: Neonates requiring seizure monitoring received amplitude-integrated EEG and conventional EEG in parallel. Clinical events and amplitude-integrated EEG were interpreted at bedside. Subsequently, amplitude-integrated EEG and conventional EEG were independently analyzed by experienced neonatology and neurology readers. Sensitivity and specificity of bedside amplitude-integrated EEG as compared to expert amplitude-integrated EEG interpretation and conventional EEG were evaluated. RESULTS: Thirteen neonates were monitored for an average duration of 33 hours (range 15-94, SD 25). Fourteen seizure-like events were detected by clinical observation, and 12 others by bedside amplitude-integrated EEG analysis. One of the clinical, and none of the bedside amplitude-integrated EEG events were confirmed as seizures on conventional EEG. Post hoc expert amplitude-integrated EEG interpretation revealed eight suspected seizures, all different from the ones detected by the bedside amplitude-integrated EEG team, of which one was confirmed via conventional EEG. Eight seizures were recorded on conventional EEG. Expert amplitude-integrated EEG interpretation had a sensitivity of 13% with 46% specificity for individual seizure detection, and a sensitivity of 50% with 46% specificity for detecting patients with seizures. CONCLUSION: Real-world bedside amplitude-integrated EEG monitoring failed to detect all seizures evidenced via conventional EEG, while misclassifying other events as seizures. Even post hoc expert amplitude-integrated EEG interpretation provided limited sensitivity and specificity. Considering the poor sensitivity and specificity of bedside amplitude-integrated EEG interpretation, combined monitoring may provide limited clinical benefit.

Valproic acid as a monotherapy in drug-resistant methyl-CpG-binding protein 2 gene (MECP2) duplication-related epilepsy.

Duplication of the methyl-CpG-binding protein 2 gene (MECP2) is a rare condition that results in epilepsy in half of the cases. Although this condition has been well characterized in the literature, there is a lack of research on MECP2 duplication-related epilepsy and its management. We present the case of an eleven-year old male with MECP2 duplication and epilepsy, who was resistant to polytherapy. The patient responded well to valproic acid (VPA) initially and upon re-challenge. This case report provides evidence for the use of VPA as an initial monotherapy for treatment of drug-resistant MECP2 duplication-related epilepsy.

The impact of electronic consultation on a Canadian tertiary care pediatric specialty referral system: A prospective single-center observational study.

BACKGROUND: Champlain BASE™ (Building Access to Specialists through eConsultation) is a web-based asynchronous electronic communication service that allows primary-care- practitioners (PCPs) to submit "elective" clinical questions to a specialist. For adults, PCPs have reported improved access and timeliness to specialist advice, averted face-to-face specialist referrals in up to 40% of cases and high provider satisfaction. OBJECTIVE: To determine whether the expansion of eConsult to a pediatric setting would result in similar measures of improved healthcare system process and high provider acceptance reported in adults. DESIGN: Prospective observational cohort study. SETTING: Single Canadian tertiary-care academic pediatric hospital (June 2014-16) servicing 1.2 million people. PARTICIPANTS: 1. PCPs already using eConsult. 2.Volunteer pediatric specialists provided services in addition to their regular workload. 3.Pediatric patients (< 18 years-old) referred for none-acute care conditions. MAIN OUTCOMES AND MEASURES: Specialty service utilization and access, impact on PCP course-of-action and referral-patterns and survey-based provider satisfaction data were collected. RESULTS: 1064 eConsult requests from 367 PCPs were answered by 23 pediatric specialists representing 14 specialty-services. The top three specialties represented were: General Pediatrics 393 cases (36.9%), Orthopedics 162 (15.2%) and Psychiatry 123 (11.6%). Median specialist response time was 0.9 days (range <1 hour-27 days), most consults (63.2%) required <10minutes to complete and 21/21(100%) specialist survey-respondents reported minimal workload burden. For 515/1064(48.4%) referrals, PCPs received advice for a new or additional course of action; 391/1064(36.7%) referrals resulted in an averted face-to-face specialist visit. In 9 specialties with complete data, the median wait-time was significantly less (p<0.001) for an eConsult (1 day, 95%CI:0.9-1.2) compared with a face-to-face referral (132 days; 95%CI:127-136). The majority (>93.3%) of PCPs rated eConsult as very good/excellent value for both patients and themselves. All specialist survey-respondents indicated eConsult should be a continued service. CONCLUSIONS AND RELEVANCE: Similar to adults, eConsult improves PCP access and timeliness to elective pediatric specialist advice and influences their care decisions, while reporting high end-user satisfaction. Further study is warranted to assess impact on resource utilization and clinical outcomes.

Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome.

White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.

Pointed rhythmic theta waves: a unique EEG pattern in KCNQ2-related neonatal epileptic encephalopathy.

We report the case of an infant with KCNQ2-related neonatal epileptic encephalopathy presenting with intractable seizures beginning on the second day of life, which were resistant to multiple antiepileptic drugs. Continuous EEG recordings starting on the sixth day of life demonstrated a unique pattern of inter-and postictal focal rhythmic pointed theta waves of lambdoid morphology in the immediate postictal period, localizing to the side of the antecedent seizure. Interictal EEG exhibited discontinuous background, including patterns of burst suppression and multifocal discharges, predominantly in the centrotemporal regions, which were aggravated during sleep. MRI demonstrated T1 signal abnormalities in the basal ganglia, bilaterally. Genetic testing revealed a de novo missense mutation in KCNQ2 at position c.545 T>G, encoding a previously unreported substitution (p.Val182Gly). Seizure control was achieved immediately after starting a lidocaine infusion at age 4 weeks. The patient remained largely seizure-free following add-on oral carbamazepine for maintenance therapy and weaning off lidocaine. This is the first report of a patient with KCNQ2-related neonatal epileptic encephalopathy and therapy-refractory seizures aborted by lidocaine, demonstrating a unique EEG pattern of inter- and postictal focal rhythmic pointed theta waves. Whether this pattern could be an early EEG marker for this disorder remains to be confirmed. [Published with video sequences on www.epilepticdisorders.com].

Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene.

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease-gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created "matching" platforms. We describe four individuals from three unrelated families "matched" by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease-causing gene and interprets the variants as "pathogenic." TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.

Lumbar puncture simulation in pediatric residency training: improving procedural competence and decreasing anxiety.

BACKGROUND: Pediatric residents must become proficient with performing a lumbar puncture (LP) during training. Residents have traditionally acquired LP skills by observing the procedure performed by a more senior resident or staff physician and then attempting the procedure themselves. This process can result in variable procedural skill acquisition and trainee discomfort. This study assessed changes in resident procedural skill and self-reported anxiety when residents were provided with an opportunity to participate in an interactive training session and practice LPs using a simulator. METHODS: All pediatric residents at our institution were invited to participate. Residents were asked to report their post-graduate year (PGY), prior LP attempts and self-reported anxiety scores as measured by the standardized State-Trait Anxiety Inventory - State Anxiety Scale (STAI-S) prior to completing an observed pre-test using an infant-sized LP simulator. Staff physicians observed and scored each resident's procedural skill using a previously published 21-point scoring system. Residents then participated in an interactive lecture on LP technique and were given an opportunity for staff-supervised, small group simulator-based practice within 1 month of the pre-test. Repeat post-test was performed within 4 months. RESULTS: Of the pediatric residents who completed the pre-test (N = 20), 16/20 (80 %) completed both the training session and post-test. Their PGY training level was: PGY1 (38 %), PGY2 (25 %), PGY3 (25 %) or PGY4 (12 %). Procedural skill improved in 15/16 residents (paired t-test; p < 0.001), driven by a significant improvement in skill for residents in PGY1 (P = 0.015) and PGY2 (p = 0.003) but not PGY3 or PGY4. Overall anxiety scores were higher at baseline than at post testing (mean ± SD; 44.8 ± 12.1 vs 39.7 ± 9.4; NS) however only PGY1 residents experienced a significant reduction in anxiety (paired t-test, p = 0.04). CONCLUSION: LP simulation training combined with an interactive training session may be a useful tool for improving procedural competence and decreasing anxiety levels, particularly among those at an earlier stage of residency training.