A cohort study on acute ocular motility disorders in pediatric emergency department

A cohort study on acute ocular motility disorders in pediatric emergency department Background: Acute ocular motility disorders (OMDs) in children admitted to Emergency Department (ED) represents a not so rare condition with a wide spectrum of different etiologies. The emergency physician must be skilled in rapidly identifying patients with potentially life threatening (LT) forms, requiring further diagnostic procedures. The aim of the study was to assess characteristics of children with acute Ocular Motility Disorders (OMDs), and to identify “red flags” for recognition of underlying life-threatening (LT) conditions. Methods: A retrospective cohort study evaluated children (2 months-17 years) admitted to a tertiary Emergency Department in 2009–2014. A subgroup analysis was performed comparing children with and without LT conditions. Results: Of 192 visits for OMDs, the isolated strabismus occurred most frequently (55.6%), followed by pupil disorders (31.8%), ptosis (5.2%) and combined OMDs (11.5%). The majority of acute OMDs involved no underlying LT conditions (n = 136) and most of them were infants or toddlers (50%). In a multivariable analysis, LT conditions included especially children over 6 years of age, increasing the odds ratio by 2% for each months of age (p = 0.009). LT etiologies were 16 times more likely in combined OMDs (p = 0.018), were over 13 times more likely to report associated extra-ocular signs/symptoms (p = 0.017) and over 50 times more likely to report co-morbidity (p = 0.017). Conclusion: OMDs are not an uncommon presentation at ED. Although most of them involve non-LT conditions, the ED physician should consider potential “red flags” for appropriate management of children such as age > 6 years, combined OMDs, extra-ocular symptoms and co-morbidity. Keywords: Child, Emergency department, Acute strabismus, Ptosis, Pupillar disorder, Red flags, Emergency department Background and acquired (head injury, infectious diseases, neurological Acute ocular motility disorders (OMDs) are a frequent and neoplastic diseases, toxic substances (systemically ad- reason for admission to an outpatient general hospital or ministered or topically instilled), vascular and auto- to a pediatric Emergency Department (ED). The clinical immune diseases), with different incidence rates manifestations of such disorders are represented by stra- compared to adults [1, 2]. So, the emergency physician bismus, ptosis, mydriasis (unilateral or bilateral) and must be skilled in rapidly identifying those patients requir- miosis, with isolated or associated presentations. In fact, ing further diagnostic procedures such as neuroradiologi- these disorders present with a wide variety of clinical pic- cal investigations, which could be superfluous and tures and underlie different etiologies, both congenital potentially dangerous in the developmental age. To our knowledge, data on presentation and manage- ment of OMDs in the pediatric population, especially in * Correspondence: umberto.raucci@opbg.net ED, are lacking. Previous literature studies report limited Umberto Raucci and Pasquale Parisi contributed equally to this work. knowledge, being mainly represented by case reports or Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, Rome, Italy reviews focusing only on specific ocular deficit. Our Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 2 of 9 study analyzed by medical charts review 6 years of ex- we compared children with a LT disease with the other perience in the ED of a tertiary pediatric hospital, with children (NLT). the aim to investigate etiology and management of OMDs. Specifically, the study planned to describe gen- Statistical analysis eral characteristics, etiology and health care resources We described the clinical and demographic features of utilization, trying to identify “red flags” significantly cor- all the patients enrolled, providing details of the overall related with potential life threatening (LT) conditions sample as well as of each of the two subgroups (patients and to address future research. with and without LT conditions). The two groups were compared by means of the Chi-square test for categor- Methods ical variables, and Student’s t test for continuous vari- After obtaining approval from the institutional ethics ables, after reviewing for appropriateness. We applied a committee, we conducted a retrospective cohort study logistic regression analysis model to assess the predictive of patients, aged between 2 months and 17 years, pre- variables associated with a diagnosis of LT conditions. senting with a primary complaint of acute OMDs to the Adjusted odds ratios (OR) and 95% confidence intervals ED of the Bambino Gesù Children’s Hospital in Rome, (CI) were used as measures of effect. The statistical sig- between January 2009 and December 2014. There is an nificance was set at p < 0.05 and SPSS software (version ongoing scientific collaboration and an agreement be- 22.0) was used to perform all the statistical analysis. tween the ED of the Bambino Gesù Children’s Hospital and the Post-Graduate Schools in Pediatrics of both Tor Vergata University of Rome and the Chair of Pediatrics, Results Faculty of Medicine and Psychology of Sapienza, Univer- Descriptive analysis of the overall study population sity of Rome. Exclusion criteria were represented by neo- During the 6-year study, among a total of 304,224 chil- natal age and patients in whom the diagnosis of OMDs dren admitted to our ED, 192 subjects presented with was already known. acute OMDs, at a rate of 0.6 visits per 1000 children. The following data were extracted from each medical Isolated strabismus occurred most frequently (n = 99; record: age, gender, triage code, time of onset, medical 51.6%) followed by isolated pupillary disorders (n = 61; history, ocular and extra-ocular signs/symptoms (sys- 31.8%), ptosis (n = 10; 5.2%) and combined OMDs (n = temic and/or neurological), physical examination find- 22; 11.5%) (Table 1). ings, specialist consultations, imaging techniques such as Our population comprised of 87 females (45.3%) and computed tomography (CT) scan and magnetic reson- 105 males (54.7%), (M/F ratio 1.2). Males prevailed in all ance imaging (MRI), final diagnosis, hospital admission OMDs group except among patients with combined and length of stay, where applicable. OMDs (Table 1). We decided to stratify our sample according to age in Children were aged from 2 to 214 months (mean age three groups: 2–36 months (infant/toddler), 37–72 months 63.34 ± 52.06 months, median 45.5) (Table 1). Most chil- (pre-schooler children) and 73–214 months (schooler- dren were aged between 2 and 36 months (n = 78; 40.6%), teenager). (Table 1). In this age group included pupil disorders and The following codes were used to describe the patient strabismus prevailed, whereas children aged over 6 years condition at the time of triage: red or immediate (need to old presented more frequently with ptosis and combined be seen immediately), yellow or very urgent, with high pri- OMDs (Table 1). ority (need to be seen in less than 15 min), green or urgent The OMD onset occurred more frequently within 24 h (need to be seen in 60–120 min), white or non-urgent before ED visit, with pupil disorders showing an onset in (need to be seen after previous triage codes). OMDs were less than 24 h in over two thirds of the cases, and the divided into four subgroups: isolated pupillar disorders, other disorders appearing more frequently after 72 h isolated strabismus, isolated ptosis and combined ocular (Table 1). On admission, the triage code was mainly yel- disorders. low and green (Table 1). Ninety-two children complained According to ED discharge diagnosis, patients were clas- of extra-ocular symptoms, involving mostly children with sified in two groups basing on the condition causing the ptosis followed by strabismus (Table 1). Twenty-seven pa- OMD: potentially life threatening (LT) diseases (metabolic tients reported co-morbidities (14.1%). diseases, cerebrovascular diseases, brain tumors, cerebral Children on current medical treatment accounted for infections, pseudotumor cerebri, demyelinating diseases, 7.3% of the cohort, more frequently among patients with brain injuries, myasthenia gravis, Bernard-Horner syn- isolated pupillary disorders (18% in this group); the acci- drome) and non-LT (NLT) diseases (transient condition, dental exposure to substances or medications was found pharmacologic/toxic causes, seizure, ocular disease, cra- only in children with pupillary disorders, accounting for nial nerve deficit, migraine, movement disorder). Then, 6,8% (13 patients). Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 3 of 9 Table 1 Characteristics of the overall population study and of four considered ocular motility disorders Characteristics Total Isolated Pupillar Disorders Isolated Strabismus Isolated Combined Ocular Disorders n = 192 (%) n = 61 (31.8%) n = 99 (51.6%) Ptosis n = 22 (11.5%) n = 10 (5.2%) Sex Female 87 (45.3%) 28 (45.9%) 43 (43.4%) 4 (40%) 12 (54.5%) Male 105 (54.7%) 33 (54.1%) 56 (56.6%) 6 (60%) 10 (45.5%) Age (months) (mean ± SD) 63.84 ± 52.02 60.51 ± 60 60.34 ± 44.7 102.4 ± 54.32 71.32 ± 54.8 Age group Infant –Toddler (2–36 months) 78 (40.6%) 31 (50.8%) 40 (40.4%) 2 (20%) 5 (22.7%) Preschooler (37–72 months) 45 (23.4%) 10 (16.4%) 26 (26.3%) 1 (10%) 9 (36.4%) Schooler-Teenager (73–214 months) 69 (35.9%) 20 (32.8%) 33 (33.3%) 7 (70%) 9 (40.9%) Triage White 6 (3.1%) 2 (3.3%) 2 (2%) 1 (10%) 1 (4.5%) Green 88 (45.8%) 23 (37.7%) 51 (51.5%) 4 (40%) 10 (45.5%) Yellow 93 (48.4%) 31 (50.8%) 46 (46.5%) 5 (50%) 11 (50%) Red 5 (2.6%) 5 (8.2%) 0 0 0 Clinical Onset Within 24 h 92 (47.9%) 41 (67.2%) 39 (39.4%) 3 (30%) 9 (40.9%) Within 72 h 28 (14.6%) 8 (13.1%) 16 (16.2%) 2 (20%) 2 (9.1%) Over 72 h 72 (37.5%) 12 (19.7%) 44 (44.4%) 5 (50%) 11 (50%) Systemic Symptoms 92 (47.9%) 27 (44.3%) 47 (47.5%) 9 (90%) 9 (40.9%) Specialist Consultation at ED 167 (87%) 45 (73.8%) 94 (94.9%) 8 (80%) 20 (90.9%) NeuroImaging 118 (61.5%) 22 (36.1%) 69 (69.7%) 9 (90%) 18 (81.8%) CT Scan 92 (47.9%) 21 (34.4%) 50 (50.5%) 7 (70%) 14 (63.6%) MRI 83 (43.2%) 10 (16.4%) 50 (50.5%) 8 (80%) 15 (68.2%) Outcome Discharged 71 (37%) 30 (49.2%) 36 (36.4%) 2 (20%) 3 (13.6%) Hospitalized 121 (63%) 31 (50.8%) 63 (63.6%) 8 (80%) 19 (86.4%) Lenght of Hospital Stay (mean ± SD) 10.42 ± 12.8 9.21 ± 14 9.19 ± 10.3 13 ± 6.1 16.8 ± 18.41 Life-Threatening Conditions 56 (29.2%) 10 (16.4%) 27 (27.3%) 6 (60%) 13 (59.1%) SD Standard Deviation, ED Emergency Department, CT Computed Tomography, MRI Magnetic Resonance Imaging In many cases, a specialist consultation was needed 70 and 80%), followed by children with combined OMDs (n = 167; 87%) (Table 1) with neurological and oph- (63.6 and 68.2%, respectively, Table 1). Among children thalmological consultations required most frequently admitted for OMDs, 63% were hospitalized, with an (respectively in 51.6 and 69.8% of the patients). Less average length of stay of 10.42 days. Patients with ptosis frequently, consultations by neurosurgeon (n = 11; and combined OMDs were more frequently hospitalized 5.7%), intensive care physician (n = 11; 5.7%) or max- (80 and 86.5%, respectively), with a longer hospital stay illofacial surgeon (n = 3; 1.6%) were requested. Neur- compared to the other OMDs (Table 1). ologist referral was performed mostly in children with ptosis (n = 7; 70%), while ophthalmologist consultation LT etiologies: Clinical characteristics and diagnostic was required mainly for children with ptosis (n =5; findings 50%) and pupillary disorders (n = 29; 47.5%). OMDs underlied a LT conditions in 56 children (29.2% Neuroimaging was performed in 118 children (61.5%), of the entire sample), more frequently among children mainly in patients with pupillary disorders (90%) and with ptosis and combined OMDs (Table 1). combined OMDs (81.8%) (Table 1), CT and MRI having The distribution of the various etiologies for acute been performed in 47.9 and 43.2% of the patients, re- OMDs is reported in Fig. 1. There was a significant dif- spectively (Table 1). Both CT and MRI were more fre- ference in the frequency of LT conditions in the different quently performed in patients with ptosis (respectively age groups (Table 2). On triage, a yellow code was more Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 4 of 9 Fig. 1 Distribution of the various etiologies for acute ocular motility disorders; OMDs: Ocular Motility Disorders frequently assigned to children with LT conditions (p = Children with LT conditions were over 13 times more 0.008) (Table 2). In the LT group, symptoms onset was likely to report associated extra-ocular signs or symp- more frequently as far as 72 h before the time of the toms (OR: 13.13; CI 95%: 1.585–108.811; p = 0.017) examination. In the other group, the onset was more com- (Table 3). monly within the 24 h preceding the ED visit (p =0.003) Regarding clinical history, children of the LT group was (Table 2). Extra-ocular manifestations were significantly 50 times more likely to report co-morbidities (OR:50.66; more common in the LT group (p = 0.001) and LT condi- CI 95%:2.006–1278,85; p = 0.017) (Table 3). For hospital- tions were significantly associated with combined OMDs ized LT children, the length of stay was increased by 18% (p =0.002) (Table 2). The co-morbidities were more fre- for each day (OR: 1.18; CI 95%: 1.053–1.331; p =0.005). In quently seen in children with LT etiologies (p =0.002) relation to diagnostic investigations, children with LT (Table 2). conditions were over 7 times more likely to undergo to a With regards to pharmacological aspects, children on CT (OR: 7.78; CI 95%: 1.457–41.575) (p =0.016) (Tables 3 current treatment appeared mainly in the NLT group and 4). (p = 0.048) (Table 2). Among specialist consultations, only neurosurgeon Discussion evaluation was more frequently requested in the LT OMDs are a not rare condition in ED, with a wide group (p = 0.001) (Table 2). All children with LT condi- spectrum of different underlying causes. One of the tions underwent neuroimaging (n = 56; 100%), versus strength-points in our study is the large sample of enrolled 45.6% (62 patients) in the other group (p = 0.001). children, thus providing reliable epidemiological data from All patients with LT conditions and 65 patients the ED of a Tertiary Pediatric Hospital, showing a rate of (47.8%) with NLT conditions were hospitalized. The 0.6 visits per 1000 visits. hospital stay was significantly longer in the LT group ED physicians must be skilled in rapidly identifying (p = 0.001) (Table 2). the few patients with potentially LT conditions of OMDs, requiring further diagnostic investigations such Logistic regression as neuro-radiologic investigations, that should be per- Regarding the children’s age, the odds that an older child formed only if needed. However, differential diagnosis is had LT conditions increased by 2% for each month of age challenging, and this may lead to excessive healthcare (OR = 1.02; CI 95%: 1.005–1. 036; p =0.009) (Table 3). spending and unnecessary testing and treatment even Considering the clinical subgroups, we reported that for not severe conditions [3]. LT conditions were 16 times more frequent in combined OMDs (OR:16.07; CI 95%:1.622–159,25; p = 0.018) In our sample, most of the included patients were (Table 3). infants and toddlers and most of the admissions Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 5 of 9 Table 2 Clinical and demographic characteristics of the two subgroups (Non-Life Threatening and Life Threatening conditions) Characteristics Non-Life Threatening n = 136 Life Threatening n = 56 p value Sex NS Female 59 (43.4%) 28 (50%) Male 77 (56.6%) 28 (50%) Age group 0.001 Infant -Toddler 68 (50%) 10 (17.9%) Preschooler 28 (20.6%) 17 (30.4%) Schooler-Teenager 40 (29.4%) 29 (51.8%) Age (months)(mean ± SD) 52.8 ± 47 90.66 ± 54.2 0.001 Triage 0.008 White 6 (4.4%) 0 Green 71 (52.2%) 17 (30.4%) Yellow 56 (41.2%) 37 (66.1%) Red 3 (2.2%) 2 (3.6%) Clinical Onset 0.003 Within 24 h 76 (55.9%) 16 (28.6%) Within 72 h 17 (12.5%) 11 (19.6%) Over72 hours 43 (31.6%) 29 (51.8%) SystemicSymptoms 0.001 No 92 (67.6%) 8 (14.3%) Yes 44 (32.4%) 48 (85.7%) Ocular Disorder 0.002 One disorder 127 (93.4%) 43 (76.8%) More one disorder 9 (6.6%) 13 (23.2%) Concomitant Disease 0.002 No 124 (91.2%) 41 (73.2%) Yes 12 (8.8%) 15 (26.8%) During Medical Treatment 0.048 No 123 (90.%) 55 (98.2%) Yes 13 (9.6%) 1 (1.8%) Specialist Consultation at ED NS. No 18 (13.2%) 7 (12.6%) Yes 118 (86.8%) 49 (87.6%) Neurologic Consultation NS No 68 (50%) 25 (44.6%) Yes 68 (50%) 31 (55.4%) Ophthalmologic Consultation 0.058 No 36 (26.5%) 22 (39.3%) Yes 100 (73.5%) 34 (60.7%) Neurosurgical Consultation 0.001 No 135 (99.3%) 46 (82.1%) Yes 1 (0.7%) 10 (17.9%) Anesthesiologic Consultation NS No 129 (94.9%) 52 (92.9%) Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 6 of 9 Table 2 Clinical and demographic characteristics of the two subgroups (Non-Life Threatening and Life Threatening conditions) (Continued) Characteristics Non-Life Threatening n = 136 Life Threatening n = 56 p value Yes 7 (5.1%) 4 (7.1%) Maxillo-Facial Surgery Consultation NS No 134 (98.5%) 55 (98.2%) Yes 2 (1.5%) 1 (1.8%) Outcome 0.001 Discharged 71 (52.2%) 0 Hospitalized 65 (47.8%) 56 (100%) Lenght of Hospital Stay(mean ± SD) 4.45 ± 4.7 17.59 ± 15.32 0.001 Neuro Imaging 0.001 No 74 (54.4%) 0 Yes 62 (45.6%) 56 (100%) CT Scan 0.001 No 90 (66.2%) 10 (17.9%) Yes 46 (33.8%) 46 (82.1%) MRI 0.001 No 99 (72.8%) 10 (17.9%) Yes 37 (27.2%) 46 (82.1%) SD Standard Deviation, ED Emergency Department, CT Computed Tomography, MRI Magnetic Resonance Imaging involved children who did not have underlying LT neuritis represented a common condition (15.2%), not diseases (Table 1). reported in previous literature case series [4, 5]. The leading cause of admission to our ED was isolated The second cause of presentation was isolated pupillar strabismus (55.6%) and the principal underlying cause were disorders, accounting for 31.8% of the cohort. The foremost ocular disorders (38.4%), as described in the literature cause was toxic effects (37.7%) of drugs or other substances, [4, 5]. Nevertheless, in our study, ocular nerve given orally or topically (belladona, scopolamina, datura Table 3 A regression logistic model of risk of Life Threatening conditions in children with Ocular Motility Disorders Variable B SE Wald DF Sig. OR Cl 95% Lower Upper Age (months) 0.020 0.008 6.744 1 0.009 1.02 1.005 1.036 Triage Code (yellow vs others) 0.410 0.707 0.336 1 0.562 1.51 0.377 6.019 Clinical Onset within 24 h 4.731 2 0.094 1.00 Clinical Onset within 72 h 2.395 1.378 3.020 1 0.082 11.00 0.736 163.414 Clinical Onset over 72 h 1.486 0.796 3.486 1 0.062 4.42 0.929 21.011 Ocular Disorder (combined vs isolated) 0.777 1.170 5.632 1 0.018 16.07 1.622 159.252 Systemic Symptoms 2.575 1.079 5.697 1 0.017 13.13 1.585 108.811 Concomitant Disease 3.925 1.647 5.677 1 0.017 50.66 2.006 1278.854 Children on Medical Treatment −2.585 2.213 1.364 1 0.243 0.08 0.001 5.769 Ophthalmologic Consultation −0.470 0.773 0.369 1 0.54 0.625 0.137 Neurosurgical Consultation 2.568 1.445 3.156 1 0.076 13.04 0.767 221.643 Lenght of Hospital Staying (days) 0.169 0.060 8.009 1 0.005 1.18 1.053 1.331 CT Scan 2.052 0.855 5.760 1 0.016 7.78 1.457 41.575 MRI 0.465 0.830 0.314 1 0.575 1.60 0.313 8.093 Constant −8.473 1.858 20.795 1 0.000 B: Coefficient (T-Statistics); SE Standard Error, Wald Test of Wald, DF Degree of Freedom, Sig Significance, OR Odds Ratio, CI 95% Confidential Interval 95%, CT Computed Tomography, MRI Magnetic Resonance Imaging Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 7 of 9 Table 4 Red Flags for Ocular Motility Disorders in Emergency disorders are more frequently older than 6 years of age. Department According to the logistic regression model, the odds that - Combined Ocular Motility Disorders an older child had a LT conditions increased by 2% for - Extraocular manifestation (i.e papilledema, headache, nausea or each month of age. These data might be correlated to a vomiting, weight loss) higher frequency of acquired OMDs causes, occurring - Associated neurological signs and symptoms - Presence of co-morbidities mostly over 6 years of age, respect to congenital causes, - Ptosis predominantly occurring in younger children. Our find- - Age > 6 years ings differ from previous studies in which a younger age - Strabismus also if isolated in subject with larger esodeviation at distance, recurrence of at diagnosis was described [15–18], probably due to a acute acquired concomitant esotropia higher frequency of congenital ptosis in these series compared to our study, where acquired conditions pre- species and direct exposure to nebulized anticholinergic dominate. Similarly, the combined OMDs are more agents such as ipratropium). In case of topical exposure to commonly associated with LT conditions (59.1%), involv- anticholinergic agents, the pupil changes usually resolve in ing especially the schooler-adolescent age group (40.9%). 24–48 h. Pilocarpine 1% test would confirm the pharmaco- Nevertheless, we should consider that the label “con- logic effect [6]. For this reason, pediatricians should inquire genital” does not always mean benign, as in about possible drug and toxic exposures and consider this neuroblastoma-related Bernard-Horner syndrome [19]. diagnosis, especially in well-appearing patients, to avoid un- Secondly, in our study, the LT conditions were signifi- necessary and potentially dangerous diagnostic investiga- cantly associated with combined OMDs; in fact, the lo- tions [6]. gistic regression reported that patients with LT Migraine diagnosis was estimated in 66.7% of pupillary etiologies were 16 times more likely to present more disorders (Fig. 1), particularly in mydriasis (70.7%). The than a single OMD. role of pupillary disorders in migraine patients is not Nevertheless, ED physicians should consider that an completely understood [7, 8]. The association between isolated acute OMDs might be insidious as well. In fact, migraine and monolateral or bilateral “tonic pupil” [9, even if in our study isolated strabismus was associated 10] might be caused by hyperactivity of the sympathetic with LT etiologies in a minority of cases, it should be nervous system or hypoactivity of the parasympathetic kept in mind that the acute onset of esotropia can be system [8]. due to a wide range of severe intracranial diseases [20]. Combined OMDs occurred in 11.5% of patients, In some cases, strabismus may represent the initial sign followed by isolated ptosis in 5.2% of children. In our of a neurologic dysfunction [21]. With this regard, the study, the leading diagnosis of combined OMDs were “red flags” suggesting intracranial pathology are: larger LT conditions (59.1%), mainly neoplastic (22.7%) and in- esodeviation at distance, recurrence of acute acquired fectious (22%) diseases. Combined OMDs such as ptosis concomitant esotropia, neurological signs and older age with anisocoria in a child may be suggestive of at onset (> 6 years) [22]. In particular, in childhood, dif- Bernard-Horner syndrome, whose etiologies can include ferently from adults, the acute onset of an esotropia is birth trauma, tumors such as neuroblastoma or benign frequently associated with an underlying central nervous neck masses [11]. In the case of third nerve palsy, com- system disorder [23]. bined OMDs are more easily recognized [4, 12]. Except In the case of benign episodic mydriasis, with no other for the first cause of third nerve palsy that is congenital accompanying symptoms, with short-term episodes and (33–38%), the other causes are all acquired LT condi- in absence of abnormalities on neurological examination, tions: trauma (28–32%), tumors (22–11%), vascular imaging tests are not recommended. In our study the (11%), meningitis (6%) [4]. Myasthenia Gravis, infre- isolated pupillary disorders were associated with LT eti- quently encountered in pediatric clinical practice, oc- ologies in only 16.4%. Accordingly, it is mandatory to curred in 4.5% of our children with combined OMDs in search for red flags such as neurological signs or symp- which ptosis was accompanied by strabismus. toms. In particular, the mydriasis associated with head- In our study, isolated ptosis was determined mainly by aches should always alert the clinician to possibilities of LT conditions, such as brain infections. Of note, ophthal- serious potential LT conditions [24]. moplegic migraine diagnosis was made in two children Similarly, acute-onset ptosis, that in our study is asso- with ptosis; its recognition may save patients from un- ciated with life-threatening causes in 60% of the patients, necessary tests and interventions [13, 14] In these cases, may underlie serious etiologies, such as neuroblastoma, it can be crucial to investigate on the presence of posi- myasthenia gravis or muscular dystrophy, even present- tive family history of idiopathic headache. ing as an isolated finding [25, 26]. With the aim to identify clinical features predictive of Our study demonstrates that the extra-ocular manifes- LT conditions, we firstly highlight that children with LT tations, such as papilledema, headache or nausea, weight Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 8 of 9 loss and vomiting, were significantly associated with LT Availability of data and materials The datasets used and/or analyzed during the current study are available conditions; in addition, patients with LT conditions were from the corresponding author on reasonable request. 50 times more likely to report a comorbidity. Given the broad spectrum of OMDs causes, if a cer- Authors’ contributions UR and PP conceptualized and designed the study, drafted the initial tain benign diagnosis (i.e. ipratropium local exposure) manuscript, interpreted data, reviewed and revised the manuscript and cannot be made, in absence of red flags for a severe equally contributed to the work; NV and VF participated in the design of the underlying etiology, ophthalmologic and neurologic con- study, performed statistical analysis, interpreted data, GG, FS, RR participated in the design of the study, collected and interpreted data, reviewed and sultations should be warranted before proceeding to fur- revised the manuscript; SP and SP, interpreted data, participated in critically ther investigation, In fact, growing CT utilization at ED revising the intellectual contents of manuscript; AR and NP coordinated the has been reported also in pediatric age; probably reflect- study, interpreted data, critically revised and approved the final version of the manuscript as submitted; All authors read and approved the final ing the increased availability of CT, the improvements in manuscript as submitted. CT diagnostic capabilities, and an increased need of phy- sicians and patients for diagnostic certainty [27]. Parallelly, Ethics approval and consent to participate a rise in CT use is associated with increased health care The study was approved by the Ethics Committee of the Bambino Gesù Children’s Hospital according to the Declaration of Helsinki (as revised in expenditures, increased hospitalization length, and in- Seoul, Korea, October 2008). creased exposure to ionizing radiation [28]. Conclusions of our work can be limited by the expos- Competing interests The authors declare that they have no competing interests. No financial or ure to some confounding factors, as tends to be inevit- non-financial benefits have been received or will be received from any party able in any retrospective study design. In fact, some related directly or indirectly to the subject of this article. No honorarium, important and relevant details may not have been docu- grant, or other form of payment was given to anyone to produce the manuscript. mented in clinical records. In addition, this is a single-center study performed at an academic tertiary Hospital and the frequency of some conditions could be Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in overestimated at this care level. published maps and institutional affiliations. Author details Conclusion Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, Rome, Italy. Chair of Pediatrics, NESMOS Department, We can state that acute OMDs in children admitted to Faculty of Medicine and Psychology, Sapienza University, c/o Sant’Andrea ED represents a not so rare condition with a wide Hospital, Rome, Italy. National Centre for Epidemiology, Surveillance, and spectrum of different etiologies. The leading clinical pre- Health Promotion, National Institute of Health, Rome, Italy. University Hospital Pediatric Department, Bambino Gesù Children’s Hospital, IRCCS Tor sentations in our sample was isolated strabismus, Vergata University, Rome, Italy. Pediatric Division, SS Giovanni and Paolo followed by isolated pupil disorders, ptosis and com- Hospital, Venice, Italy. Ophthalmology Department, Bambino Gesù bined OMDs. Most of the admissions to ED for OMDs Children’s Hospital, IRCCS, Rome, Italy. Neurology Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. involved children who did not have underlying LT condi- tions and most of them were infants or toddlers who Received: 22 March 2018 Accepted: 21 May 2018 could be referred directly as outpatients to a pediatric ophthalmologist. Conversely, we would like to stress that References children with LT conditions included especially children 1. Prentiss KA, Dorfman DH. Pediatric ophthalmology in the emergency over 6 years of age. The risk of LT events was signifi- department. Emerg Med Clin North Am. 2008;26:181–98. vii. https://doi.org/ cantly higher in children with combined OMDs and/or 10.1016/j.emc.2007.11.001. 2. Fleisher GR, Ludwing S. The textbook of pediatric emergency medicine. associated extra-ocular signs/symptoms, with comorbid- Philadelphia, PA: Lippincott Williams & Wilkins; 2010. ity in their clinical history. Obviously, further prospect- 3. Uscher-Pines L, Pines J, Kellermann A, Gillen E, Mehrotra A. Emergency ive studies are needed to improve OMDs management department visits for nonurgent conditions: systematic literature review. Am J Manag Care. 2013;19:47–59. in pediatric ED. 4. Ng Ys LCJ. Oculomotor nerve palsy in childhood. Can J Ophthalmol. 2005; 40:645–53. 5. Schumacher-Feero LA, Yoo KW, Solari FM, Biglan AW. Third cranial nerve Abbreviations palsy in children. Am J Ophthalmol. 1999;128:216–21. CI: Confidence Interval; CT: Computed Tomography; ED: Emergency 6. Osorio MJ, Zuckerbraun NS, Painter M. Acute pupil asymmetry in a 6- Department; LT: Life Threatening; MRI: Magnetic Resonance Imaging; month-old boy. Diagnosis: pharmacologic anisocoria. Pediatr Ann. 2009;38: NLT: Non-Life Threatening; OMDs: Ocular Motility Disorders; OR: Odd Ratio; 622–4. 627. https://doi.org/10.3928/00904481-20091016-07. SD: Standard Deviation 7. Maggioni F, Mainardi F, Malvindi ML, Zanchin G. The borderland of migraine with aura: episodic unilateral mydriasis. J Headache Pain. 2011;12:105–7. Acknowledgements https://doi.org/10.1007/s10194-010-0255-7. We would like to thank sincerely Frank Di Chiappari, Ed.D, M.Ed, Adjunct 8. Martin-Santana I, Gonzàlez-Hernàndez A, Tandòu-Càrdenes L, López-Méndez Professor of English as a Second Language at Harvard and Southern New P. Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology Hampshire University, USA, for his precious collaboration to edit the English clinic of a tertiary hospital. Neurologia. 2015;30:290–4. https://doi.org/10.1016/j. in this manuscript without profit. nrl.2014.01.003. Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 9 of 9 9. Patel R, Davis C, Sivaswamy L. Anisocoria – not always cause for alarm. J Pediatr. 2014;164:1497. https://doi.org/10.1016/j.jpeds.2014.02.004. 10. Millar E, Habib M, Gnanaraj L. Bilateral tonic pupil secondary to migraine in a child. J Pediatr Ophthalmol Strabismus. 2010;47:e1–2. https://doi.org/10. 3928/01913913-20100920-08. 11. Cahill JA, Ross J. Eye on children: acute work-up for pediatric Horner's syndrome. Case presentation and review of the literature. J Emerg Med. 2015;48:58–62. https://doi.org/10.1016/j.jemermed.2014.07.041. 12. Mudgil AV, Repka MX. Ophthalmologic out come after third cranial nerve palsy or paresis in childhood. J AAPOS. 1999;3:2–8. 13. Gulkilik G, Cagatay HH, Oba EM, Uslu C. Ophthalmoplegic migraine associated with recurrent isolated ptosis. Ann Ophthalmol (Skokie). 2009;41:206–7. 14. Stidham DB, Butler IJ. Recurrent isolated ptosis in presumed ophthalmoplegic migraine of childhood. Ophthalmology. 2000;107:1476–8. 15. Nemet AY, Segal O, Mimouni M, Vinker S. Associated morbidity of pediatric ptosis — a large, community based case–control study. Graefes Arch Clin Exp Ophthalmol. 2014;252:1509–14. https://doi.org/10.1007/s00417-014-2759-3. 16. Essawy RE, Elsada MA. Clinical and demographic characteristics of ptosis in children: a national tertiary hospital study. Eur J Ophthalmol. 2013;(3):356–60. https://doi.org/10.5301/ejo.5000239. 17. Griepentrog GJ, Diehl N, Mohney BG. Incidence and demographics of childhood ptosis. Ophthalmology. 2011;118:1180–3. https://doi.org/10.1016/ j.ophtha.2010.10.026. 18. Berry-Brincat A, Willshaw H. Paediatric blepharoptosis: a 10-year review. Eye (Lond). 2009;23:1554–9. https://doi.org/10.1038/eye.2008.311. 19. Olitsky SE, Nelson LB. Common ophthalmologic concerns in infants and children. Pediatr Clin N Am. 1998;45:993–1012. 20. Kemmanu V, Hegde K, Seetharam R, Shetty BK. Varied aetiology of acute acquired comitant esotropia: a case series. Oman J Ophthalmol. 2012;5:103–5. 21. Gunton KB, Wasserman BN, De Benedictis C. Strabismus. Prim Care. 2015;42: 393–407. 22. Buch H, Vinding T. Acute acquired comitant esotropia of childhood: a classification based on 48 children. Acta Ophthalmol. 2015;93:568–74. https://doi.org/10.1016/j.pop.2015.05.006. 23. Herlihy EP, Phillips JO, Weiss AH. Esotropia greater at distance: children vs adults. JAMA Ophthalmol. 2013;131:370–5. https://doi.org/10.1001/ jamaophthalmol.2013.1878. 24. Ault J. Teaching case: migraine and pupil dilation. Headache. 2011;51:324–6. 25. Olitsky SE, Nelson LB. Common ophthalmologic concerns in infant and children. Ped Clin North Am. 1998;45:993–1012. https://doi.org/10.1111/j. 1526-4610.2010.01837.x. 26. Clarke WN. Paediatric ophthalmology: things that do not require referral. Paediatr Child Health. 2005;10:395–6. 27. Broder J, Fordham LA, Warshauer DM. Increasing utilization of computed tomography in the pediatric emergency department, 2000-2006. Emerg Radiol. 2007;14:227–32. 28. Korley FK, Pham JC, Kirsch TD. Use of advanced radiology during visits to US emergency departments for injury-related conditions, 1998-2007. JAMA. 2010;304:1465–71. https://doi.org/10.1001/jama.2010.1408. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Italian Journal of Pediatrics Springer Journals
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Abstract

Background: Acute ocular motility disorders (OMDs) in children admitted to Emergency Department (ED) represents a not so rare condition with a wide spectrum of different etiologies. The emergency physician must be skilled in rapidly identifying patients with potentially life threatening (LT) forms, requiring further diagnostic procedures. The aim of the study was to assess characteristics of children with acute Ocular Motility Disorders (OMDs), and to identify “red flags” for recognition of underlying life-threatening (LT) conditions. Methods: A retrospective cohort study evaluated children (2 months-17 years) admitted to a tertiary Emergency Department in 2009–2014. A subgroup analysis was performed comparing children with and without LT conditions. Results: Of 192 visits for OMDs, the isolated strabismus occurred most frequently (55.6%), followed by pupil disorders (31.8%), ptosis (5.2%) and combined OMDs (11.5%). The majority of acute OMDs involved no underlying LT conditions (n = 136) and most of them were infants or toddlers (50%). In a multivariable analysis, LT conditions included especially children over 6 years of age, increasing the odds ratio by 2% for each months of age (p = 0.009). LT etiologies were 16 times more likely in combined OMDs (p = 0.018), were over 13 times more likely to report associated extra-ocular signs/symptoms (p = 0.017) and over 50 times more likely to report co-morbidity (p = 0.017). Conclusion: OMDs are not an uncommon presentation at ED. Although most of them involve non-LT conditions, the ED physician should consider potential “red flags” for appropriate management of children such as age > 6 years, combined OMDs, extra-ocular symptoms and co-morbidity. Keywords: Child, Emergency department, Acute strabismus, Ptosis, Pupillar disorder, Red flags, Emergency department Background and acquired (head injury, infectious diseases, neurological Acute ocular motility disorders (OMDs) are a frequent and neoplastic diseases, toxic substances (systemically ad- reason for admission to an outpatient general hospital or ministered or topically instilled), vascular and auto- to a pediatric Emergency Department (ED). The clinical immune diseases), with different incidence rates manifestations of such disorders are represented by stra- compared to adults [1, 2]. So, the emergency physician bismus, ptosis, mydriasis (unilateral or bilateral) and must be skilled in rapidly identifying those patients requir- miosis, with isolated or associated presentations. In fact, ing further diagnostic procedures such as neuroradiologi- these disorders present with a wide variety of clinical pic- cal investigations, which could be superfluous and tures and underlie different etiologies, both congenital potentially dangerous in the developmental age. To our knowledge, data on presentation and manage- ment of OMDs in the pediatric population, especially in * Correspondence: umberto.raucci@opbg.net ED, are lacking. Previous literature studies report limited Umberto Raucci and Pasquale Parisi contributed equally to this work. knowledge, being mainly represented by case reports or Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, Rome, Italy reviews focusing only on specific ocular deficit. Our Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 2 of 9 study analyzed by medical charts review 6 years of ex- we compared children with a LT disease with the other perience in the ED of a tertiary pediatric hospital, with children (NLT). the aim to investigate etiology and management of OMDs. Specifically, the study planned to describe gen- Statistical analysis eral characteristics, etiology and health care resources We described the clinical and demographic features of utilization, trying to identify “red flags” significantly cor- all the patients enrolled, providing details of the overall related with potential life threatening (LT) conditions sample as well as of each of the two subgroups (patients and to address future research. with and without LT conditions). The two groups were compared by means of the Chi-square test for categor- Methods ical variables, and Student’s t test for continuous vari- After obtaining approval from the institutional ethics ables, after reviewing for appropriateness. We applied a committee, we conducted a retrospective cohort study logistic regression analysis model to assess the predictive of patients, aged between 2 months and 17 years, pre- variables associated with a diagnosis of LT conditions. senting with a primary complaint of acute OMDs to the Adjusted odds ratios (OR) and 95% confidence intervals ED of the Bambino Gesù Children’s Hospital in Rome, (CI) were used as measures of effect. The statistical sig- between January 2009 and December 2014. There is an nificance was set at p < 0.05 and SPSS software (version ongoing scientific collaboration and an agreement be- 22.0) was used to perform all the statistical analysis. tween the ED of the Bambino Gesù Children’s Hospital and the Post-Graduate Schools in Pediatrics of both Tor Vergata University of Rome and the Chair of Pediatrics, Results Faculty of Medicine and Psychology of Sapienza, Univer- Descriptive analysis of the overall study population sity of Rome. Exclusion criteria were represented by neo- During the 6-year study, among a total of 304,224 chil- natal age and patients in whom the diagnosis of OMDs dren admitted to our ED, 192 subjects presented with was already known. acute OMDs, at a rate of 0.6 visits per 1000 children. The following data were extracted from each medical Isolated strabismus occurred most frequently (n = 99; record: age, gender, triage code, time of onset, medical 51.6%) followed by isolated pupillary disorders (n = 61; history, ocular and extra-ocular signs/symptoms (sys- 31.8%), ptosis (n = 10; 5.2%) and combined OMDs (n = temic and/or neurological), physical examination find- 22; 11.5%) (Table 1). ings, specialist consultations, imaging techniques such as Our population comprised of 87 females (45.3%) and computed tomography (CT) scan and magnetic reson- 105 males (54.7%), (M/F ratio 1.2). Males prevailed in all ance imaging (MRI), final diagnosis, hospital admission OMDs group except among patients with combined and length of stay, where applicable. OMDs (Table 1). We decided to stratify our sample according to age in Children were aged from 2 to 214 months (mean age three groups: 2–36 months (infant/toddler), 37–72 months 63.34 ± 52.06 months, median 45.5) (Table 1). Most chil- (pre-schooler children) and 73–214 months (schooler- dren were aged between 2 and 36 months (n = 78; 40.6%), teenager). (Table 1). In this age group included pupil disorders and The following codes were used to describe the patient strabismus prevailed, whereas children aged over 6 years condition at the time of triage: red or immediate (need to old presented more frequently with ptosis and combined be seen immediately), yellow or very urgent, with high pri- OMDs (Table 1). ority (need to be seen in less than 15 min), green or urgent The OMD onset occurred more frequently within 24 h (need to be seen in 60–120 min), white or non-urgent before ED visit, with pupil disorders showing an onset in (need to be seen after previous triage codes). OMDs were less than 24 h in over two thirds of the cases, and the divided into four subgroups: isolated pupillar disorders, other disorders appearing more frequently after 72 h isolated strabismus, isolated ptosis and combined ocular (Table 1). On admission, the triage code was mainly yel- disorders. low and green (Table 1). Ninety-two children complained According to ED discharge diagnosis, patients were clas- of extra-ocular symptoms, involving mostly children with sified in two groups basing on the condition causing the ptosis followed by strabismus (Table 1). Twenty-seven pa- OMD: potentially life threatening (LT) diseases (metabolic tients reported co-morbidities (14.1%). diseases, cerebrovascular diseases, brain tumors, cerebral Children on current medical treatment accounted for infections, pseudotumor cerebri, demyelinating diseases, 7.3% of the cohort, more frequently among patients with brain injuries, myasthenia gravis, Bernard-Horner syn- isolated pupillary disorders (18% in this group); the acci- drome) and non-LT (NLT) diseases (transient condition, dental exposure to substances or medications was found pharmacologic/toxic causes, seizure, ocular disease, cra- only in children with pupillary disorders, accounting for nial nerve deficit, migraine, movement disorder). Then, 6,8% (13 patients). Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 3 of 9 Table 1 Characteristics of the overall population study and of four considered ocular motility disorders Characteristics Total Isolated Pupillar Disorders Isolated Strabismus Isolated Combined Ocular Disorders n = 192 (%) n = 61 (31.8%) n = 99 (51.6%) Ptosis n = 22 (11.5%) n = 10 (5.2%) Sex Female 87 (45.3%) 28 (45.9%) 43 (43.4%) 4 (40%) 12 (54.5%) Male 105 (54.7%) 33 (54.1%) 56 (56.6%) 6 (60%) 10 (45.5%) Age (months) (mean ± SD) 63.84 ± 52.02 60.51 ± 60 60.34 ± 44.7 102.4 ± 54.32 71.32 ± 54.8 Age group Infant –Toddler (2–36 months) 78 (40.6%) 31 (50.8%) 40 (40.4%) 2 (20%) 5 (22.7%) Preschooler (37–72 months) 45 (23.4%) 10 (16.4%) 26 (26.3%) 1 (10%) 9 (36.4%) Schooler-Teenager (73–214 months) 69 (35.9%) 20 (32.8%) 33 (33.3%) 7 (70%) 9 (40.9%) Triage White 6 (3.1%) 2 (3.3%) 2 (2%) 1 (10%) 1 (4.5%) Green 88 (45.8%) 23 (37.7%) 51 (51.5%) 4 (40%) 10 (45.5%) Yellow 93 (48.4%) 31 (50.8%) 46 (46.5%) 5 (50%) 11 (50%) Red 5 (2.6%) 5 (8.2%) 0 0 0 Clinical Onset Within 24 h 92 (47.9%) 41 (67.2%) 39 (39.4%) 3 (30%) 9 (40.9%) Within 72 h 28 (14.6%) 8 (13.1%) 16 (16.2%) 2 (20%) 2 (9.1%) Over 72 h 72 (37.5%) 12 (19.7%) 44 (44.4%) 5 (50%) 11 (50%) Systemic Symptoms 92 (47.9%) 27 (44.3%) 47 (47.5%) 9 (90%) 9 (40.9%) Specialist Consultation at ED 167 (87%) 45 (73.8%) 94 (94.9%) 8 (80%) 20 (90.9%) NeuroImaging 118 (61.5%) 22 (36.1%) 69 (69.7%) 9 (90%) 18 (81.8%) CT Scan 92 (47.9%) 21 (34.4%) 50 (50.5%) 7 (70%) 14 (63.6%) MRI 83 (43.2%) 10 (16.4%) 50 (50.5%) 8 (80%) 15 (68.2%) Outcome Discharged 71 (37%) 30 (49.2%) 36 (36.4%) 2 (20%) 3 (13.6%) Hospitalized 121 (63%) 31 (50.8%) 63 (63.6%) 8 (80%) 19 (86.4%) Lenght of Hospital Stay (mean ± SD) 10.42 ± 12.8 9.21 ± 14 9.19 ± 10.3 13 ± 6.1 16.8 ± 18.41 Life-Threatening Conditions 56 (29.2%) 10 (16.4%) 27 (27.3%) 6 (60%) 13 (59.1%) SD Standard Deviation, ED Emergency Department, CT Computed Tomography, MRI Magnetic Resonance Imaging In many cases, a specialist consultation was needed 70 and 80%), followed by children with combined OMDs (n = 167; 87%) (Table 1) with neurological and oph- (63.6 and 68.2%, respectively, Table 1). Among children thalmological consultations required most frequently admitted for OMDs, 63% were hospitalized, with an (respectively in 51.6 and 69.8% of the patients). Less average length of stay of 10.42 days. Patients with ptosis frequently, consultations by neurosurgeon (n = 11; and combined OMDs were more frequently hospitalized 5.7%), intensive care physician (n = 11; 5.7%) or max- (80 and 86.5%, respectively), with a longer hospital stay illofacial surgeon (n = 3; 1.6%) were requested. Neur- compared to the other OMDs (Table 1). ologist referral was performed mostly in children with ptosis (n = 7; 70%), while ophthalmologist consultation LT etiologies: Clinical characteristics and diagnostic was required mainly for children with ptosis (n =5; findings 50%) and pupillary disorders (n = 29; 47.5%). OMDs underlied a LT conditions in 56 children (29.2% Neuroimaging was performed in 118 children (61.5%), of the entire sample), more frequently among children mainly in patients with pupillary disorders (90%) and with ptosis and combined OMDs (Table 1). combined OMDs (81.8%) (Table 1), CT and MRI having The distribution of the various etiologies for acute been performed in 47.9 and 43.2% of the patients, re- OMDs is reported in Fig. 1. There was a significant dif- spectively (Table 1). Both CT and MRI were more fre- ference in the frequency of LT conditions in the different quently performed in patients with ptosis (respectively age groups (Table 2). On triage, a yellow code was more Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 4 of 9 Fig. 1 Distribution of the various etiologies for acute ocular motility disorders; OMDs: Ocular Motility Disorders frequently assigned to children with LT conditions (p = Children with LT conditions were over 13 times more 0.008) (Table 2). In the LT group, symptoms onset was likely to report associated extra-ocular signs or symp- more frequently as far as 72 h before the time of the toms (OR: 13.13; CI 95%: 1.585–108.811; p = 0.017) examination. In the other group, the onset was more com- (Table 3). monly within the 24 h preceding the ED visit (p =0.003) Regarding clinical history, children of the LT group was (Table 2). Extra-ocular manifestations were significantly 50 times more likely to report co-morbidities (OR:50.66; more common in the LT group (p = 0.001) and LT condi- CI 95%:2.006–1278,85; p = 0.017) (Table 3). For hospital- tions were significantly associated with combined OMDs ized LT children, the length of stay was increased by 18% (p =0.002) (Table 2). The co-morbidities were more fre- for each day (OR: 1.18; CI 95%: 1.053–1.331; p =0.005). In quently seen in children with LT etiologies (p =0.002) relation to diagnostic investigations, children with LT (Table 2). conditions were over 7 times more likely to undergo to a With regards to pharmacological aspects, children on CT (OR: 7.78; CI 95%: 1.457–41.575) (p =0.016) (Tables 3 current treatment appeared mainly in the NLT group and 4). (p = 0.048) (Table 2). Among specialist consultations, only neurosurgeon Discussion evaluation was more frequently requested in the LT OMDs are a not rare condition in ED, with a wide group (p = 0.001) (Table 2). All children with LT condi- spectrum of different underlying causes. One of the tions underwent neuroimaging (n = 56; 100%), versus strength-points in our study is the large sample of enrolled 45.6% (62 patients) in the other group (p = 0.001). children, thus providing reliable epidemiological data from All patients with LT conditions and 65 patients the ED of a Tertiary Pediatric Hospital, showing a rate of (47.8%) with NLT conditions were hospitalized. The 0.6 visits per 1000 visits. hospital stay was significantly longer in the LT group ED physicians must be skilled in rapidly identifying (p = 0.001) (Table 2). the few patients with potentially LT conditions of OMDs, requiring further diagnostic investigations such Logistic regression as neuro-radiologic investigations, that should be per- Regarding the children’s age, the odds that an older child formed only if needed. However, differential diagnosis is had LT conditions increased by 2% for each month of age challenging, and this may lead to excessive healthcare (OR = 1.02; CI 95%: 1.005–1. 036; p =0.009) (Table 3). spending and unnecessary testing and treatment even Considering the clinical subgroups, we reported that for not severe conditions [3]. LT conditions were 16 times more frequent in combined OMDs (OR:16.07; CI 95%:1.622–159,25; p = 0.018) In our sample, most of the included patients were (Table 3). infants and toddlers and most of the admissions Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 5 of 9 Table 2 Clinical and demographic characteristics of the two subgroups (Non-Life Threatening and Life Threatening conditions) Characteristics Non-Life Threatening n = 136 Life Threatening n = 56 p value Sex NS Female 59 (43.4%) 28 (50%) Male 77 (56.6%) 28 (50%) Age group 0.001 Infant -Toddler 68 (50%) 10 (17.9%) Preschooler 28 (20.6%) 17 (30.4%) Schooler-Teenager 40 (29.4%) 29 (51.8%) Age (months)(mean ± SD) 52.8 ± 47 90.66 ± 54.2 0.001 Triage 0.008 White 6 (4.4%) 0 Green 71 (52.2%) 17 (30.4%) Yellow 56 (41.2%) 37 (66.1%) Red 3 (2.2%) 2 (3.6%) Clinical Onset 0.003 Within 24 h 76 (55.9%) 16 (28.6%) Within 72 h 17 (12.5%) 11 (19.6%) Over72 hours 43 (31.6%) 29 (51.8%) SystemicSymptoms 0.001 No 92 (67.6%) 8 (14.3%) Yes 44 (32.4%) 48 (85.7%) Ocular Disorder 0.002 One disorder 127 (93.4%) 43 (76.8%) More one disorder 9 (6.6%) 13 (23.2%) Concomitant Disease 0.002 No 124 (91.2%) 41 (73.2%) Yes 12 (8.8%) 15 (26.8%) During Medical Treatment 0.048 No 123 (90.%) 55 (98.2%) Yes 13 (9.6%) 1 (1.8%) Specialist Consultation at ED NS. No 18 (13.2%) 7 (12.6%) Yes 118 (86.8%) 49 (87.6%) Neurologic Consultation NS No 68 (50%) 25 (44.6%) Yes 68 (50%) 31 (55.4%) Ophthalmologic Consultation 0.058 No 36 (26.5%) 22 (39.3%) Yes 100 (73.5%) 34 (60.7%) Neurosurgical Consultation 0.001 No 135 (99.3%) 46 (82.1%) Yes 1 (0.7%) 10 (17.9%) Anesthesiologic Consultation NS No 129 (94.9%) 52 (92.9%) Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 6 of 9 Table 2 Clinical and demographic characteristics of the two subgroups (Non-Life Threatening and Life Threatening conditions) (Continued) Characteristics Non-Life Threatening n = 136 Life Threatening n = 56 p value Yes 7 (5.1%) 4 (7.1%) Maxillo-Facial Surgery Consultation NS No 134 (98.5%) 55 (98.2%) Yes 2 (1.5%) 1 (1.8%) Outcome 0.001 Discharged 71 (52.2%) 0 Hospitalized 65 (47.8%) 56 (100%) Lenght of Hospital Stay(mean ± SD) 4.45 ± 4.7 17.59 ± 15.32 0.001 Neuro Imaging 0.001 No 74 (54.4%) 0 Yes 62 (45.6%) 56 (100%) CT Scan 0.001 No 90 (66.2%) 10 (17.9%) Yes 46 (33.8%) 46 (82.1%) MRI 0.001 No 99 (72.8%) 10 (17.9%) Yes 37 (27.2%) 46 (82.1%) SD Standard Deviation, ED Emergency Department, CT Computed Tomography, MRI Magnetic Resonance Imaging involved children who did not have underlying LT neuritis represented a common condition (15.2%), not diseases (Table 1). reported in previous literature case series [4, 5]. The leading cause of admission to our ED was isolated The second cause of presentation was isolated pupillar strabismus (55.6%) and the principal underlying cause were disorders, accounting for 31.8% of the cohort. The foremost ocular disorders (38.4%), as described in the literature cause was toxic effects (37.7%) of drugs or other substances, [4, 5]. Nevertheless, in our study, ocular nerve given orally or topically (belladona, scopolamina, datura Table 3 A regression logistic model of risk of Life Threatening conditions in children with Ocular Motility Disorders Variable B SE Wald DF Sig. OR Cl 95% Lower Upper Age (months) 0.020 0.008 6.744 1 0.009 1.02 1.005 1.036 Triage Code (yellow vs others) 0.410 0.707 0.336 1 0.562 1.51 0.377 6.019 Clinical Onset within 24 h 4.731 2 0.094 1.00 Clinical Onset within 72 h 2.395 1.378 3.020 1 0.082 11.00 0.736 163.414 Clinical Onset over 72 h 1.486 0.796 3.486 1 0.062 4.42 0.929 21.011 Ocular Disorder (combined vs isolated) 0.777 1.170 5.632 1 0.018 16.07 1.622 159.252 Systemic Symptoms 2.575 1.079 5.697 1 0.017 13.13 1.585 108.811 Concomitant Disease 3.925 1.647 5.677 1 0.017 50.66 2.006 1278.854 Children on Medical Treatment −2.585 2.213 1.364 1 0.243 0.08 0.001 5.769 Ophthalmologic Consultation −0.470 0.773 0.369 1 0.54 0.625 0.137 Neurosurgical Consultation 2.568 1.445 3.156 1 0.076 13.04 0.767 221.643 Lenght of Hospital Staying (days) 0.169 0.060 8.009 1 0.005 1.18 1.053 1.331 CT Scan 2.052 0.855 5.760 1 0.016 7.78 1.457 41.575 MRI 0.465 0.830 0.314 1 0.575 1.60 0.313 8.093 Constant −8.473 1.858 20.795 1 0.000 B: Coefficient (T-Statistics); SE Standard Error, Wald Test of Wald, DF Degree of Freedom, Sig Significance, OR Odds Ratio, CI 95% Confidential Interval 95%, CT Computed Tomography, MRI Magnetic Resonance Imaging Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 7 of 9 Table 4 Red Flags for Ocular Motility Disorders in Emergency disorders are more frequently older than 6 years of age. Department According to the logistic regression model, the odds that - Combined Ocular Motility Disorders an older child had a LT conditions increased by 2% for - Extraocular manifestation (i.e papilledema, headache, nausea or each month of age. These data might be correlated to a vomiting, weight loss) higher frequency of acquired OMDs causes, occurring - Associated neurological signs and symptoms - Presence of co-morbidities mostly over 6 years of age, respect to congenital causes, - Ptosis predominantly occurring in younger children. Our find- - Age > 6 years ings differ from previous studies in which a younger age - Strabismus also if isolated in subject with larger esodeviation at distance, recurrence of at diagnosis was described [15–18], probably due to a acute acquired concomitant esotropia higher frequency of congenital ptosis in these series compared to our study, where acquired conditions pre- species and direct exposure to nebulized anticholinergic dominate. Similarly, the combined OMDs are more agents such as ipratropium). In case of topical exposure to commonly associated with LT conditions (59.1%), involv- anticholinergic agents, the pupil changes usually resolve in ing especially the schooler-adolescent age group (40.9%). 24–48 h. Pilocarpine 1% test would confirm the pharmaco- Nevertheless, we should consider that the label “con- logic effect [6]. For this reason, pediatricians should inquire genital” does not always mean benign, as in about possible drug and toxic exposures and consider this neuroblastoma-related Bernard-Horner syndrome [19]. diagnosis, especially in well-appearing patients, to avoid un- Secondly, in our study, the LT conditions were signifi- necessary and potentially dangerous diagnostic investiga- cantly associated with combined OMDs; in fact, the lo- tions [6]. gistic regression reported that patients with LT Migraine diagnosis was estimated in 66.7% of pupillary etiologies were 16 times more likely to present more disorders (Fig. 1), particularly in mydriasis (70.7%). The than a single OMD. role of pupillary disorders in migraine patients is not Nevertheless, ED physicians should consider that an completely understood [7, 8]. The association between isolated acute OMDs might be insidious as well. In fact, migraine and monolateral or bilateral “tonic pupil” [9, even if in our study isolated strabismus was associated 10] might be caused by hyperactivity of the sympathetic with LT etiologies in a minority of cases, it should be nervous system or hypoactivity of the parasympathetic kept in mind that the acute onset of esotropia can be system [8]. due to a wide range of severe intracranial diseases [20]. Combined OMDs occurred in 11.5% of patients, In some cases, strabismus may represent the initial sign followed by isolated ptosis in 5.2% of children. In our of a neurologic dysfunction [21]. With this regard, the study, the leading diagnosis of combined OMDs were “red flags” suggesting intracranial pathology are: larger LT conditions (59.1%), mainly neoplastic (22.7%) and in- esodeviation at distance, recurrence of acute acquired fectious (22%) diseases. Combined OMDs such as ptosis concomitant esotropia, neurological signs and older age with anisocoria in a child may be suggestive of at onset (> 6 years) [22]. In particular, in childhood, dif- Bernard-Horner syndrome, whose etiologies can include ferently from adults, the acute onset of an esotropia is birth trauma, tumors such as neuroblastoma or benign frequently associated with an underlying central nervous neck masses [11]. In the case of third nerve palsy, com- system disorder [23]. bined OMDs are more easily recognized [4, 12]. Except In the case of benign episodic mydriasis, with no other for the first cause of third nerve palsy that is congenital accompanying symptoms, with short-term episodes and (33–38%), the other causes are all acquired LT condi- in absence of abnormalities on neurological examination, tions: trauma (28–32%), tumors (22–11%), vascular imaging tests are not recommended. In our study the (11%), meningitis (6%) [4]. Myasthenia Gravis, infre- isolated pupillary disorders were associated with LT eti- quently encountered in pediatric clinical practice, oc- ologies in only 16.4%. Accordingly, it is mandatory to curred in 4.5% of our children with combined OMDs in search for red flags such as neurological signs or symp- which ptosis was accompanied by strabismus. toms. In particular, the mydriasis associated with head- In our study, isolated ptosis was determined mainly by aches should always alert the clinician to possibilities of LT conditions, such as brain infections. Of note, ophthal- serious potential LT conditions [24]. moplegic migraine diagnosis was made in two children Similarly, acute-onset ptosis, that in our study is asso- with ptosis; its recognition may save patients from un- ciated with life-threatening causes in 60% of the patients, necessary tests and interventions [13, 14] In these cases, may underlie serious etiologies, such as neuroblastoma, it can be crucial to investigate on the presence of posi- myasthenia gravis or muscular dystrophy, even present- tive family history of idiopathic headache. ing as an isolated finding [25, 26]. With the aim to identify clinical features predictive of Our study demonstrates that the extra-ocular manifes- LT conditions, we firstly highlight that children with LT tations, such as papilledema, headache or nausea, weight Raucci et al. Italian Journal of Pediatrics (2018) 44:62 Page 8 of 9 loss and vomiting, were significantly associated with LT Availability of data and materials The datasets used and/or analyzed during the current study are available conditions; in addition, patients with LT conditions were from the corresponding author on reasonable request. 50 times more likely to report a comorbidity. Given the broad spectrum of OMDs causes, if a cer- Authors’ contributions UR and PP conceptualized and designed the study, drafted the initial tain benign diagnosis (i.e. ipratropium local exposure) manuscript, interpreted data, reviewed and revised the manuscript and cannot be made, in absence of red flags for a severe equally contributed to the work; NV and VF participated in the design of the underlying etiology, ophthalmologic and neurologic con- study, performed statistical analysis, interpreted data, GG, FS, RR participated in the design of the study, collected and interpreted data, reviewed and sultations should be warranted before proceeding to fur- revised the manuscript; SP and SP, interpreted data, participated in critically ther investigation, In fact, growing CT utilization at ED revising the intellectual contents of manuscript; AR and NP coordinated the has been reported also in pediatric age; probably reflect- study, interpreted data, critically revised and approved the final version of the manuscript as submitted; All authors read and approved the final ing the increased availability of CT, the improvements in manuscript as submitted. CT diagnostic capabilities, and an increased need of phy- sicians and patients for diagnostic certainty [27]. Parallelly, Ethics approval and consent to participate a rise in CT use is associated with increased health care The study was approved by the Ethics Committee of the Bambino Gesù Children’s Hospital according to the Declaration of Helsinki (as revised in expenditures, increased hospitalization length, and in- Seoul, Korea, October 2008). creased exposure to ionizing radiation [28]. Conclusions of our work can be limited by the expos- Competing interests The authors declare that they have no competing interests. No financial or ure to some confounding factors, as tends to be inevit- non-financial benefits have been received or will be received from any party able in any retrospective study design. In fact, some related directly or indirectly to the subject of this article. No honorarium, important and relevant details may not have been docu- grant, or other form of payment was given to anyone to produce the manuscript. mented in clinical records. In addition, this is a single-center study performed at an academic tertiary Hospital and the frequency of some conditions could be Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in overestimated at this care level. published maps and institutional affiliations. Author details Conclusion Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, Rome, Italy. Chair of Pediatrics, NESMOS Department, We can state that acute OMDs in children admitted to Faculty of Medicine and Psychology, Sapienza University, c/o Sant’Andrea ED represents a not so rare condition with a wide Hospital, Rome, Italy. National Centre for Epidemiology, Surveillance, and spectrum of different etiologies. The leading clinical pre- Health Promotion, National Institute of Health, Rome, Italy. University Hospital Pediatric Department, Bambino Gesù Children’s Hospital, IRCCS Tor sentations in our sample was isolated strabismus, Vergata University, Rome, Italy. Pediatric Division, SS Giovanni and Paolo followed by isolated pupil disorders, ptosis and com- Hospital, Venice, Italy. Ophthalmology Department, Bambino Gesù bined OMDs. Most of the admissions to ED for OMDs Children’s Hospital, IRCCS, Rome, Italy. Neurology Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. involved children who did not have underlying LT condi- tions and most of them were infants or toddlers who Received: 22 March 2018 Accepted: 21 May 2018 could be referred directly as outpatients to a pediatric ophthalmologist. Conversely, we would like to stress that References children with LT conditions included especially children 1. Prentiss KA, Dorfman DH. 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Italian Journal of PediatricsSpringer Journals

Published: May 29, 2018

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