Lacrimal Obstruction in Craniosynostosis: Anatomical and Genetic Risk Factors.

PURPOSE: To investigate whether patients with craniosynostosis exhibit higher rates of nasolacrimal duct obstruction (NLDO) and to explore potential risk factors. METHODS: Retrospective review including all craniosynostosis patients treated at both the Divisions of Ophthalmology and Plastic, Reconstructive, and Oral Surgery at The Children's Hospital of Philadelphia between 2009 and 2020 was conducted. Synostosis characteristics, lacrimal disorders, and genetic data were collected. Main outcome measures were the rate of NLDO and associations with anatomical and syndromic/genetic risk factors. RESULTS: The total of 767 participants had a mean age of 2.8 ± 3.8 years, 465 (60.6%) were males, 485 (63.2%) had no syndromic association; 631 (82.3%) had one major suture involved, 128 (17%) had involvement of 2 to 4 major sutures, and 429 (55.9%) underwent craniofacial surgery. Forty-eight (6.2%) patients had NLDO, which more prevalent in the genetic/syndromic group (11.0% vs. 3.5%, respectively, p < 0.001), with the highest prevalence observed in patients with Apert syndrome (n = 4, 30.8%). The genetic variants most associated with NLDO were EFNB1 (n = 1, 100%) and FGFR2 (n = 6, 19.4%). There was no association between NLDO and the number or types of sutures involved or a history of craniofacial surgery. CONCLUSIONS: Nasolacrimal duct obstruction is more common in patients with craniosynostosis compared to the general population. Having a putative syndrome or a putative genetic variant and female sex were risk factors for NLDO. Ophthalmic evaluations for all craniosynostosis patients and careful assessments of any symptoms of tearing are recommended.

P-Score: A Reference-Image-Based Clinical Grading Scale for Vascular Change in Retinopathy of Prematurity.

PURPOSE: The International Classification of Retinopathy of Prematurity Third Edition (ICROP3) acknowledged that plus-like ROP vascular changes occur along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photo reference-image set for grading plus-like changes and compared intergrader agreement of the set to standard grading with no-plus/pre-plus/plus. DESIGN: Retinal photographic grading and expert consensus opinion PARTICIPANTS: Development: 34 international ICROP3 committee members. VALIDATION: 30 ophthalmologists with ROP expertise (15 ICROP3 committee members, 15 non-ICROP3 members) METHODS: Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on ICROP3-committee's 34 members' gradings and consensus image review, were used to establish standard photographs for the "Plus (P) Score." Study participants graded 150 fundus photographs two ways, separated by a 1-week washout period: (1) no-plus/pre-plus/plus disease, (2) choosing the closest P-Score image. MAIN OUTCOME MEASURES: Intergrader agreement measured by intraclass correlation coefficient (ICC) RESULTS: Intergrader agreement was higher using P-Score (ICC 0.75, 95% CI 0.71-0.79) than no-plus/pre-plus/plus (ICC 0.67, 95% CI 0.62-0.72). Mean P-Scores for images whose mode gradings were no-plus, pre-plus, and plus, were 2.5 (SD 0.7), 4.8 (SD 0.8), and 7.4 (SD 0.8), respectively. CONCLUSIONS: Intergrader agreement of plus-like vascular change in ROP using the P-Score is high. We recommend incorporation of this 9-image reference set into ICROP3 and clinician daily practice alongside zone/stage/plus. P-score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P-score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of ICROP.

INCIDENCE AND RISK FACTORS FOR EXUDATIVE RETINAL DETACHMENT FOLLOWING LASER PHOTOCOAGULATION FOR RETINOPATHY OF PREMATURITY.

PURPOSE: Exudative retinal detachment (ERD) may result from laser photocoagulation for retinopathy of prematurity. Although risk factors have been hypothesized from case reports, comparative studies have not been reported. We sought to evaluate risk factors for ERD following laser, comparing affected and unaffected infants. METHODS: Retrospective cohort study of infants undergoing retinopathy of prematurity laser at the Children's Hospital of Philadelphia over 6 years. All received near-confluent laser of avascular retina. Demographic, medical, and procedural risk factors for ERD were evaluated in univariate analysis because of the rarity of ERD. RESULTS: Among 149 lasered infants, 6 infants (4%, 95% confidence interval [CI] 1.5%-8.6%) developed ERD. Race was a significant risk factor ( P = 0.01). Among 71 African American or Hispanic infants, 6 (8.5%, 95% CI 3.2%-17.5%) developed ERD. Among 78 non-African American or Hispanic infants, 0 (0%, 95% CI 0%-4.6%) developed ERD. There were no significant differences in the other studied factors. CONCLUSION: Exudative retinal detachment was uncommon (4%) following retinopathy of prematurity laser. Despite so few cases, darker pigmented race with likely increased pigmented fundi was significantly associated with an increased ERD risk. Further study may reveal whether increased choroidal pigment causes greater laser tissue damage or makes it difficult to discern the ora, resulting in inadvertent lasering of the ciliary body, leading to ERD.

Deep Learning Approach for Differentiating Etiologies of Pediatric Retinal Hemorrhages: A Multicenter Study.

Retinal hemorrhages in pediatric patients can be a diagnostic challenge for ophthalmologists. These hemorrhages can occur due to various underlying etiologies, including abusive head trauma, accidental trauma, and medical conditions. Accurate identification of the etiology is crucial for appropriate management and legal considerations. In recent years, deep learning techniques have shown promise in assisting healthcare professionals in making more accurate and timely diagnosis of a variety of disorders. We explore the potential of deep learning approaches for differentiating etiologies of pediatric retinal hemorrhages. Our study, which spanned multiple centers, analyzed 898 images, resulting in a final dataset of 597 retinal hemorrhage fundus photos categorized into medical (49.9%) and trauma (50.1%) etiologies. Deep learning models, specifically those based on ResNet and transformer architectures, were applied; FastViT-SA12, a hybrid transformer model, achieved the highest accuracy (90.55%) and area under the receiver operating characteristic curve (AUC) of 90.55%, while ResNet18 secured the highest sensitivity value (96.77%) on an independent test dataset. The study highlighted areas for optimization in artificial intelligence (AI) models specifically for pediatric retinal hemorrhages. While AI proves valuable in diagnosing these hemorrhages, the expertise of medical professionals remains irreplaceable. Collaborative efforts between AI specialists and pediatric ophthalmologists are crucial to fully harness AI's potential in diagnosing etiologies of pediatric retinal hemorrhages.

Genetic testing for infantile nystagmus syndrome with or without associated findings.

PURPOSE: To review the published literature assessing the clinical utility of genetic testing in individuals with infantile nystagmus syndrome (INS), defined as binocular conjugate nystagmus and onset prior to 6 months of age, with or without associated findings. METHODS: A literature search was last conducted in October 2022. The results were limited to articles published in English. The search yielded 517 abstracts, of which 72 papers were reviewed in full text. Of these papers, 4 met the criteria for inclusion and were graded by a study methodologist. RESULTS: The 4 studies that met inclusion criteria used next-generation sequencing with gene panels ranging from 31 to 336 genes. The overall molecular diagnostic rate ranged from 35% to 60% in the included studies, although the yield was higher when genetic testing was guided by clinical phenotyping (approximately 80%) and in the subsets of patients with a family history (up to 88%). As many as 30% of patients tested had a reclassification of the diagnosis based on the genetic testing results. CONCLUSIONS: Genetic testing has the potential to provide a definitive diagnosis and identify treatable conditions in patients presenting with INS, especially when considered in conjunction with clinical phenotyping and family history.

Levodopa/Carbidopa to Augment the Treatment of Amblyopia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of levodopa/carbidopa to augment the treatment of amblyopia. METHODS: Literature searches for English language studies were last conducted in October 2022 in the PubMed database with no date restrictions. The combined searches yielded 55 articles, of which 23 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Nine studies were rated level I, and 3 studies were rated level II; there were no level III studies. RESULTS: The duration of treatment was limited to 3 to 16 weeks because of concern about long-term adverse effects such as tardive dyskinesia. This complication was not reported in any of the study participants. The dose of levodopa ranged from 1.5 to 8.3 mg/kg/day, generally divided into 3 daily doses. The carbidopa dose was approximately 25% of the levodopa dose in all treatments. Evidence from these studies indicates that augmenting traditional patch occlusion therapy with the oral administration of levodopa/carbidopa can improve the vision of amblyopic children, but the effect was small (0.17-0.3 logarithm of the minimum angle of resolution [logMAR] units) and only statistically significant when compared with patching alone in 2 of the 12 studies cited. Regression of vision was reported in the majority of studies (9 of 12 reported; range, 0-0.17 logMAR unit regression) after discontinuation of therapy. Short-term side effects of the medications were not consistently reported but were most frequently mild and included headache and nausea. CONCLUSIONS: The best available evidence is currently insufficient to show that augmenting amblyopia therapy using up to 16 weeks of levodopa/carbidopa will result in meaningful improvement in visual acuity. Given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Microbial patterns and culture utility in orbital cellulitis.

PURPOSE: To determine the prevalence and types of pathogens found in children with orbital cellulitis and to evaluate the utility of nonoperative cultures. METHODS: This was a retrospective cohort study of children with imaging-confirmed orbital cellulitis over a period of 8 years. Outcomes included prevalence and types of organisms, polymicrobial infection, mixed aerobic-anaerobic infection, effect of age, and culture utility. RESULTS: Of 220 children with orbital cellulitis, 112 (51%) had cultures taken; 69 (31%) had surgical intervention. Culture sources for the 112 children with cultures included blood (57 patients [51%]), sinus (53 [47%]), orbit (42 [38%]), brain (6 [5%]), and skin/conjunctiva/lacrimal sac (6 [5%]). Streptococcus anginosus group strains grew in cultures from 19 children (17%); methicillin-sensitive Staphylococcus aureus (MSSA), in 15 (13%); Streptococcus pyogenes, in 12 (11%); methicillin-resistant Staphylococcus aureus (MRSA), in 6 (5%); anaerobic/facultative gram negative rods, in 8 (7%); anaerobic Gram-positive cocci, other Viridans group streptococci, and Streptococci pneumoniae, in 3 (3%) each; and normal respiratory/skin flora, in 23 (21%). Polymicrobial infection (P = 0.08) and anaerobic organisms (P = 0.58) did not differ by age (range, 0.1-16.8 years). In all 220 (100%) children, nonoperative cultures were either not obtained (108 [49%]), not helpful in avoiding surgery (69 [31%]), showed no growth (39 [18%]), or grew an organism that did not change management from empiric therapy (4 [2%]). CONCLUSIONS: While many organisms may be cultured from children with orbital cellulitis, Streptococcus and MSSA were the most common in our study cohort. MRSA is uncommon, so initial empiric coverage is not necessary. Rates of polymicrobial and anaerobic infection were similar across ages. Our results indicate that nonoperative cultures are not indicated in the initial medical management of orbital cellulitis; in our cohort, they neither resulted in treatment changes nor helped avoid surgery.

Uveitis in pediatric inflammatory bowel disease.

There are currently no official uveitis screening guidelines for children with inflammatory bowel disease (IBD). In this retrospective cohort study of children with IBD with at least 1 ophthalmologist examination over 12 years, we investigated the prevalence and characteristics of uveitis in pediatric IBD. Outcomes included prevalence of uveitis, age at onset, and clinical characteristics of uveitis. A total of 315 children with IBD (mean age, 11.7 ± 4.3) had 974 eye examinations. Five children (1.6%; 95% CI, 0.7%-3.7%) had uveitis, with mean age at onset of 14.3 ± 5.6 years. Three of 209 children with Crohn's disease (1.4%; 95% CI, 0.5%-4.1%), 2 of 55 with IBD-unclassified (3.6%; 95% CI, 1.0%-12.3%) and 0 of 51 with ulcerative colitis (95% CI, 0.0%-7.0%) had uveitis. All uveitis was symptomatic. In our study cohort, uveitis was rare and symptomatic in pediatric IBD.

Outcome of Primary Monocanalicular Stent Placement in Pediatric Down Syndrome Patients with Congenital Nasolacrimal Obstruction.

PURPOSE: Congenital Nasolacrimal duct obstruction (CNLDO) is a relatively common problem in children with Down syndrome (DS). Probing and irrigation (PI) with monocanalicular stent intubation may be less successful than in non-DS patients, thus raising some concerns regarding the preferred treatment in this population. We aimed to analyze the surgical outcome of PI along with monocanalicular stent intubation in children with DS compared with non-DS patients. METHODS: Retrospective cohort study. Thirty-five eyes of 19 children with DS and 1,472 eyes of 1,001 children without DS underwent PI-monocanalicular stent intubation as a primary treatment for CNLDO. All patients were operated on by a single surgeon at the Children's Hospital of Philadelphia between 2009 and 2020. The main outcome measure was a surgical success, defined as the resolution of symptoms after surgery. RESULTS: A total of 1,020 patients were included, 48% females; mean age of 1.9 ± 1.4 years. The mean follow-up time was 35.0 months. The DS patients group consisted of 19 patients. Higher rates of right nasolacrimal duct obstruction and bilateral obstructions were observed in the DS group (100% vs. 73.2%; p = 0.006, and 84.2% vs. 46.8%; p = 0.001, respectively). Patients with DS had a lower success rate (57.1% vs. 92.4%; p < 0 .0001). The median time to failure was 3.1 months in the DS group, and 5.2 months in the group of patients without DS. The hazard ratio comparing DS to the no-DS outcome was 6.6 (95% CI: 3.2-13.7; p < 0.001). CONCLUSIONS: CNLDO in DS is more likely to be bilateral and less likely to resolve after primary monocanalicular stent placement.

Racial Differences in Retinopathy of Prematurity.

PURPOSE: To delineate racial differences in the incidence and time course of ROP in a large cohort of premature infants. METHODS: The secondary analysis of data from the two Postnatal Growth and ROP Studies (G-ROP-1 and G-ROP-2) that were collected in 41 hospitals in North America from 2006 to 2017. According to self-reported maternal race, premature infants were classified into 3 groups: White (N = 5580), Black (N = 3252), and Asian (N = 353). Incidence, severity, and time course of ROP; plus disease; and postnatal weight gain rate were compared among racial groups. RESULTS: Black infants had significantly smaller BW (mean 1035 vs. 1131 vs.1144 grams, P < .001) and lower GA (28.2 vs. 28.6, vs. 29.1 weeks, P < .001) than White and Asian infants. However, Black infants had lower incidences of severe ROP (11.1% vs. 12.4% vs. 11.9%), ROP (42.1% vs. 43.2% vs. 30.6%), and plus disease (3.6% vs. 6.3%, vs. 5.9%) than White and Asian infants (BW and GA adjusted risk ratio for Black vs. White 0.69 for severe ROP, 0.83 for ROP, 0.44 for plus disease, all P < .0001). Mean daily-weight-gain on days of life 11-20 and 21-30 were similar across groups (P > .05), but lower in Black and Asian infants on days 31-40 (P < .001). There were no differences in the timing of severe ROP and ROP across racial groups. CONCLUSIONS: Despite relatively lower GA, BW, and daily-weight-gain, Black preterm infants had lower incidences of ROP and plus disease than White preterm infants. The mechanisms for these differences require further investigation.

Surgical Treatments to Improve Visual Acuity in Infantile Nystagmus Syndrome: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the efficacy of surgical procedures to improve visual acuity (VA) in patients with infantile nystagmus syndrome (INS). METHODS: Literature searches were last conducted in January 2022 in the PubMed database for English-language studies with no date restrictions. The combined searches yielded 354 abstracts, of which 46 were reviewed in full text. Twenty-three of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: One included study was a randomized trial; the remaining 22 were case series. The 23 studies included children and adults with INS and a variable proportion with anomalous head position (AHP), strabismus, and sensory diagnoses. The surgical interventions evaluated included large recessions, tenotomy and reattachment (TAR), myectomy with or without pulley fixation, and anterior extirpation of the 4 horizontal rectus muscles, as well as various procedures to correct an AHP in which VA was reported as a secondary outcome. The data were mixed, with improvements in binocular best-corrected visual acuity (BCVA) ranging from no improvement to 0.3 logarithm of the minimum angle of resolution (logMAR), or 3 lines. (Most studies were in the range of 0.05-0.2 logMAR.) Statistically significant improvement in VA was noted in 12 of 16 studies (75%) that performed statistical analyses, with no clear advantage of any single procedure. Complications and reoperations were lowest in patients who underwent TAR and highest in those who underwent myectomy or anterior extirpation. CONCLUSIONS: The best available evidence suggests that eye muscle surgery in patients with INS results in a modest improvement in VA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association of Cardiovascular Disease with Retinopathy of Prematurity.

PURPOSE: To determine the associations of presence and types of cardiovascular diseases (CVDs) with development of retinopathy of prematurity (ROP) in premature infants undergoing ROP examinations. STUDY DESIGN: We performed secondary analyses of data from the multi-center Postnatal Growth and ROP Validation Study (GROP-2). CVD was categorized based on pulmonary blood flow (PBF), systemic blood flow (SBF), pulmonary hypertension (PPHN), or dysrhythmia. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated from multivariable logistic regression models that included any ROP or severe ROP as outcome variable and any CVD or type of CVD as independent variable, with adjustment of covariates including birth weight (BW), gestational age (GA), and days on supplemental oxygen in the first month of postnatal life. RESULT: Among 3980 infants, 528 (13.3%) had CVD (304 had increased PBF, 101 had decreased PBF, and 49 had PPHN), 1643 (40.4%) developed ROP, and 503 (12.6%) developed severe ROP. In multivariable analyses, presence of CVD was not significantly associated with increased risk of any ROP (aOR = 1.15, 95% CI: 0.90-1.46, p = .26) or severe ROP (aOR = 0.98, 95% CI: 0.72-1.34, p = .92). However, there were trends associating CVD resulting in increased PBF with a higher risk of ROP (aOR = 1.32, 95% CI: 0.97-1.80, p = .08) and PPHN with a higher risk of severe ROP (aOR = 2.04, 95% CI: 0.96-4.35, p = .07). When adjusting only for BW and GA, these associations were significant (aOR = 1.47, 95% CI: 1.09-1.99, and aOR = 2.35, 95% CI: 1.19-4.65, respectively). CONCLUSION: CVD with increased PBF likely increases the risk of ROP. PPHN likely increases the risk of severe ROP.

Association of Surgical Necrotizing Enterocolitis and Its Timing with Retinopathy of Prematurity.

OBJECTIVE: The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP). STUDY DESIGN: This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8-28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia. RESULTS: Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9-3.7) and 2.5 (95% CI: 1.9-3.3), respectively; p < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1-4.8], and 3.3 [95% CI: 2.3-4.7] respectively, p < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3-3.4], and 1.9 [95% CI: 1.3-2.8] respectively, p < 0.001) compared with infants without surgical NEC. CONCLUSION: Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. KEY POINTS: · Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC.. · Increased ROP risk is seen in infants with both early- or later onset surgical NEC.. · Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC..

Daily Oxygen Supplementation and Risk of Retinopathy of Prematurity.

PURPOSE: Excessive oxygen supplementation increases risk of retinopathy of prematurity (ROP). While numerous oxygen parameters could be considered when predicting ROP (saturation targets, actual saturation, fraction of inspired oxygen, etc.), complicated measures are impractical as screening criteria. We sought to develop a simple, clinically useful measure of daily oxygen supplementation during ages 0-28 days to improve prediction of ROP. METHODS: Secondary analysis of two Postnatal Growth and ROP (G-ROP) Study cohorts (G-ROP-1 and G-ROP-2) at 45 hospitals. Infants with a known ROP outcome and complete oxygen data were included. Associations between severe ROP and days on supplemental oxygen (FiO2 > 21%), during ages 0-28 days (DSO28) were assessed, controlling for birth weight (BW) and gestational age (GA). New screening criteria incorporating DSO were developed and compared to current guidelines. RESULTS: Among 8,949 studied infants, 459 (5.1%) developed type 1 ROP. DSO28 was associated with severe ROP (adjusted-OR 1.05 per day supplemental oxygen, 95%CI 1.03-1.07, p < .0001). The following criteria had 100% sensitivity for type 1 ROP and higher specificity than current guidelines: new BW/GA criteria with DSO (BW<901 g, GA<26 weeks, or DSO >3), 23.4% fewer infants examined; modified G-ROP criteria including DSO, 29.0% fewer infants; original G-ROP criteria, 31.8% fewer infants. CONCLUSION: In high-level neonatal-care settings, incorporating DSO (a simple measure of oxygen supplementation) into screening criteria improves sensitivity and specificity for type 1 ROP over current BW-GA criteria, but does not perform as well as the validated G-ROP criteria.

Ocular Findings in Children with Headache.

PURPOSE: To determine the prevalence of ophthalmological findings suggesting an ocular cause for headache or occult neurological disease, among children with headache. METHODS: Retrospective cross-sectional study on children with headache at a tertiary outpatient ophthalmology clinic. All children underwent sensorimotor, anterior segment, and dilated fundoscopic examinations, with or without cycloplegic refraction. Prevalence of one or more new findings of ocular or occult neurological cause of headache, including glaucoma, uveitis, optic nerve elevation, or possible asthenopia from strabismus or refractive issues. Headache characteristics and associated symptoms were evaluated as risk factors for ocular findings. RESULTS: Among 1,878 children with headache (mean age 10 yrs, range 2-18), 492 (26.1%, 95% CI 24.3-28.2%) children had one or more new ocular findings that could cause headache or indicate intracranial disease: refractive issues (342, 18.2%), strabismus (83, 4.4%), optic nerve elevation (51, 2.7%; 26 with papilledema, 25 with pseudopapilledema), uveitis (6, 0.3%), and glaucoma (2, 0.1%). Shorter headache duration was associated with ocular findings (p = .047), but headache frequency, photophobia, nausea/vomiting, and visual changes were not. In univariable analysis, visual changes (p ≤ .001), nausea/vomiting (p ≤ .002), and morning headache (p = .02) were associated with optic nerve elevation. CONCLUSION: An ophthalmologic examination including cycloplegic refraction is indicated in children with headache, as one-quarter have a treatable ocular condition, which may be related to the headache, or sign of intracranial pathology. While nausea, visual changes, or morning headache should raise concern, coincident visual, ocular, or systemic symptoms are not reliable predictors of discovering ocular pathology in a child with headache.