Patient delay, lead times and adherence to diagnostic guidelines in children and adolescents with idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is a challenging neurologic disorder affecting children and adolescents, although most frequently found in adulthood. One of the feared complications irreversible visual loss, but chronic headache, cognitive problems lowered quality life contribute to burden disease [1Yri H.M. et al.The course headache idiopathic hypertension: 12-month prospective follow-up study.Eur J Neurol. 2014; 21: 1458-1464Crossref PubMed Scopus (52) Google Scholar, 2Stiebel-Kalish H. al.Childhood overweight or obesity increases risk IIH recurrence fivefold.Int Obes (Lond). 38: 1475-1477Crossref (10) 3Mulla Y. al.Headache determines hypertension.J Headache Pain. 2015; 16: 521Crossref (59) Scholar]. The pathophysiologic mechanisms remain elusive [4Mollan S. al.What are research priorities for hypertension? A priority setting partnership between patients healthcare professionals.BMJ Open. 2019; 9e026573Crossref (36) Scholar], disturbance venous outflow from brain proposed as one mechanisms. two prominent factors obesity/overweight female gender [2Stiebel-Kalish 5Matthews Y.Y. al.Pseudotumor cerebri syndrome childhood: incidence, clinical profile national population-based cohort study.Arch Dis Child. 2017; 102: 715-721Crossref (54) Clinical presentation, long-term outcome related well-described [5Matthews 6Hilely A. al.Long-Term Follow-up Pseudotumor Cerebri Syndrome Prepubertal Children, Adolescents, Adults.Pediatr 101: 57-63Abstract Full Text PDF 7Mahajnah M. Syndrome: From Childhood Adulthood Risk Factors Presentation.J Child 2020; 35: 311-316Crossref Scholar] care guidelines relating diagnosis management have been published [8Babiker, M.O., al., Fifteen-minute consultation: child with hypertension. Arch Educ Pract Ed, 2014. 99(5): p. 166–172.Google 9Jensen R.H. Radojicic Yri associated headache.Ther Adv Neurol Disord. 2016; 9: 317-326Crossref 10Mollan S.P. al.Evaluation adult hypertension.Pract 2018; 18: 485-488Crossref (32) However, data regarding diagnostic intervals healthcare´s ability adhere these not before. Although incidence expected increase rapidly due close relationship 11Brara S.M. al.Pediatric extreme childhood obesity.J Pediatr. 2012; 161: 602-607Abstract (69) 12Tibussek D. adolescence – results Germany-wide ESPED-survey.Klin Padiatr. 2013; 225: 81-85Crossref (38) it still relatively rare an adolescents ranging 0.5−0.9 per 100 000 13Gordon K. Pediatric pseudotumor cerebri: descriptive epidemiology.Can Sci. 1997; 24: 219-221Crossref Thus, individual doctor, there unfamiliarity current lack experience condition. For instance, misdiagnosis quite common; inadequate initial assessment failure meet criteria, missed differential just inaccurate use ICD-codes common causes contributing this [14Krishnakumar al.Idiopathic pitfalls diagnosis.Dev Med 56: 749-755Crossref (12) 15Fisayo al.Overdiagnosis hypertension.Neurology. 86: 341-350Crossref (96) Understanding provided important might improve both short outcome. In 45 diagnosed IIH, our aims were investigate: 1) findings presenting symptoms; 2) patient delay, lead time final possible associations 3) adherence process according Friedman criteria evaluation ophthalmologic work-up; 4) Healthcare region Mid Sweden. This population-based, retrospective, single-center study was performed at Uppsala University Childrenʼs Hospital, Sweden, tertiary referral center and/or complicated disease. serves seven counties Sweden population 2.1 million people. Patient retrieved local registries all county hospitals, including filling following criteria: age (0−17.99 yr), period (2000−2020), International Classification Diseases (ICD) code G93.2 H47.1 (papilledema) I67.4 (hypertensive encephalopathy). diagnoses included rule out coding. Medical records pediatric, neuropediatric, ophthalmology, neurosurgery departments scrutinized. All met Friedman´s (Box 1): papilledema, normal examination (except 6th cranial nerve abnormality), neuroimaging features suggestive IIH) cerebrospinal fluid (CSF) constituents lumbar puncture (LP) opening pressure (OP) ≥ 250 mm H2O (≥280 if obese sedated) [16Friedman D.I. Liu G.T. Digre K.B. Revised adults children.Neurology. 81: 1159-1165Crossref (818) degree papilledema noted severe, moderate, mild specified more detailed grading like Frisén scale [17Frisén L. Swelling optic head: staging scheme.J Neurosurg Psychiatry. 1982; 45: 13-18Crossref medical records. statistical purposes grade dichotomized severe/moderate mild. Patients without (IIHWOP) excluded study, will be presented another paper. flowchart details Figure 1. Information other conditions (including any medication), symptoms, sex, age, dependent body mass index (BMI) Obesity Task Force diagnosis, well investigations, retrieved. Data also dates symptom onset, first by pediatrician/pediatric neurologist/ophthalmologist/general practitioner, neuroimaging, LP measurement OP. Two route debut defined: delay (time onset assessment) i.e. OP performed). Time purposes. defined 0−4 weeks long > 4 weeks. 0−2 2 complete basic laboratory investigation blood count (CBC), creatinine+electrolytes, B-glucose, thyroid functions tests (TFTs). Non-parametric used small sample sizes non-normal distribution data. Fisherʼs exact test assess association categorical variables (sex, vs. long, long). continuous variables, debut, BMI, OP, Mann Whitney U group comparisons. Associations BMI investigated Spearmanʼs rho. rates calculated dividing number patient-years during 2011−2020 when we had hospitals. two-tailed level significance set p < 0.05. Because exploratory nature p-values adjusted multiple comparisons should interpreted caution. analysis program, SPSS, version 27 (IBM Corporation, Illinois, USA). approved Swedish Ethical Review Authority (registration 2020/06417). There clear dominance 7 years (80%, 32/40). overall female-male (F:M) ratio 3:1. Mean 13.3 (median 14.1; min. 4.3, max. 17.9) majority 13 older (64%, 29/45). Sixty-four percent (27/42) either diagnosis. 83% (5/6) aged 10−12 overweight, increasing frequency seen higher 2a 2b. Headache, nausea, affected vision (encompassing decreased acuity, blurry obscurations) diplopia symptoms. (4%) asymptomatic incidentally after being referred ophthalmologist; because pronounced heredity refractive errors second question iridocyclitis discrete joint pain, which resolved spontaneously. major symptoms Table 1 3, respectively.Table 1Clinical study. Some than disease/disorder. Three (2 epilepsy low seizure severity, Arnold Chiari type radiologic signs hydrocephalus). psychiatric (1 depression, depression anxiety bipolar disorder). neuropsychiatric autism, attention deficit hyperactivity combined Asperger syndrome) neurodevelopmental (mild intellectual disability). 3 diseases Stargardt disease, irritable bowel syndrome, reaching specific * missing diagnosis.Clinical dataN (%)Sex Female34 (76) Male11 (24)Other No (healthy)26 (58) Yes19 (42)Migraine4 (9)Asthma/allergy4 (9)Neurologic disease3 (7)Psychiatric disorder3 (7)Neuropsychiatric disorder2 (4)Neurodevelopmental disorder1 (2)Other3 (7)Age 0−6 yr5 (11) 7−12 yr11 (24.5) 13−18 yr29 (64.5)Age Normal15 Overweight13 (31) Obesitas14 (33) Open table new tab Figure. 3Percent (n=45) symptom. frequent present 89% (40/45). More each patient.View Large Image ViewerDownload Hi-res image Download (PPT) Detailed information where available 80% (36/45). Thirty-nine (14/36) their visit through ophthalmology department, while 36% (13/36) 25% (9/36) within primary pediatric respectively. span neurologist/ophthalomologist/general practitioner varied; 51% (22/43) sought advice month 23% (10/43) 1−3 months, 26% (11/43) months. asymptomatic. work-up co-ordinated department regardless location neurologist made IIH. Neuroimaging immediately (within 48 hours) 73% (33/45) 91% (41/45) cases. corresponding numbers 60% (27/45) (36/45), Details about rate investigations (i.e. OP) illustrated 4. reached hours patients, 5. statistically significant, 79% (11/14) compared 54% (7/13) 33% (3/9) department. no delay.Figure 5Cumulative percentage assessment. Eighty-nine weeks, weeks.View shorter (p=0.01) strabismus (p=0.01), nausea tended (p=0.06 p=0.12, respectively). We did find (age, BMI). Regarding time, age) nor observe tendency rapid (p=0.07). Furthermore, age. analyses except analysis. Further 2.Table 2* high (** almost diplopia) *** photophobia Body (BMI).Clinical symptomsAssociation delayAssociation timeAssociation OPp-valuep-valuep-valueClinical Sex1.001.000.09 Age0.520.860.88 OP0.01*0.57 Age BMI0.730.830.17Symptoms Headache1.001.000.78 Nausea0.120.750.57 Affected vision0.350.530.66 Strabismus0.01*0.760.01*** Vertigo0.701.000.72 Diplopia0.06**0.750.11 Photophobia1.001.000.03*** Upon assessment, bilateral papilledema. 65% (29/45) whom 29% (13/45) 7% (3/45) moderate remaining 35% (16/45), specified. ages, neither bearing on care; 50% (8/16) 46% (6/13) Examination fields, color 100% (42/42), 62% (26/42), 47% (20/43) cases, Of those examined, acuity 57% (24/42), fields 69% (18/26), (10/20). ages who lacked field were; >12 (12/16), 6−8 (1/16) 5−6 (3/16), deemed able co-operate. Nineteen (8/43) impairment 0.3) unilaterally/bilaterally half them bilaterally. vision, (6/6) (4/14) impairment. significantly having (p=0.01). 10 6 severe progressive analyses. Adequate cases magnetic resonance imaging (MRI) venography (47%, 21/45) computer tomography (CT) followed MRI (53%, 24/45). neuroradiology (21/45) patients. enlarged sheath 52% (11/21), empty/partial empty sella 38% (8/21), herniation suprasellar cisterna (7/21), flattened posterior globe/sclera transverse sinus stenosis 19% (4/21) tortuosity 9% (2/21). mean 400 370; 260, 500 threshold level) 44% Routine CSF white cells, glucose, albumin, IgG, IgG-index). undertaken 59% (23/39) cases; CBC 97% (38/39), creatinine+electrolytes 95% (37/39), B-glucose 85% (33/39), TFTs 67% (26/39). Antinuclear antibodies (ANA) 25-OH D vitamin levels analyzed (10/39) 15% (6/39) annual 0.7 000. females males, 1.2 0.3 000, condition potential loss morbidity. An early correct may reduce minimize total delay. Moreover, difficulties today evaluation, stating that baseline least together urgent [18Mollan consensus management.J 89: 1088-1100Crossref (215) 19Hoffmann J. al.European federation guideline 19: 93Crossref (87) 20Cleves-Bayon C. Intracranial Hypertension Children Adolescents: Update.Headache. 58: 485-493Crossref viewpoint remember presentation range acute fulminant insidious even headache. certain exist, seem affect strabismus, indicating age). studies [21Wang F. al.Population-Based Evaluation Lumbar Puncture Opening Pressures.Front 10: 899Crossref (9) 22Avery R.A. Reference children: historical overview data.Neuropediatrics. 206-211Crossref 91%. Deciding best/optimal point decision based factors. considering secondary increased (ICP) papilledema) accompanying reasonable argue delayed space-occupying lesions thrombosis need handling ruled out. seemed further Under ideal circumstances, direct connection proximity radiology once contraindication has hydrocephalus lesion herniation). identify prolonged time. hospitals same resources diagnosing Unfamiliarity probably reasons Also, explicit regional available. reflect fact ophthalmologists better equipped pediatricians general practitioners make ICP. According routines, (most often daycare units). subjects expedite workup. Overall, quickly, hours, can improved. awareness education achieve this. Initial very stage. Fundoscopy always performed, examinations missing. reason why lacking clear, reflection poor co-operation, presentation. Lack occurred bit counties. explanation ophthalmologist´s omission Considering tested, finding supported [20Cleves-Bayon 23Wall treatment trial: baseline.JAMA 71: 693-701Crossref (261) seems relevant perform formal perimetry Most above 6−7 recommended guidelines. seldomly reported [6Hilely demonstrates case, believe central become compromised progresses. considered examination. adequately method choice, some CT initially. Ancillary testing exclude etiologies extent sampling CBC, 97%, 95%, 85%, 67%, Analysis ANA 25-OH-D infrequent. uncertainty different recommendations reviews 18Mollan 24Barmherzig R. Szperka C.L. Children.Curr Pain Rep. 23: 58Crossref (15) Evaluating solely careful history difficult, hands experienced proposing bare minimum beyond CBCs Adherence focus would merit investigations. coherent previous findings. diplopia, less vertigo, photophobia, tinnitus, phonophobia observed, they accompanied especially only unlikely females, overweight/obesity Notably, 87% overweight. Whether random sign creeping down groups Western countries needs verified larger studies. atopy possibility autoimmune component recently put forward [25Agraz al.Clinical hypertension.Clin Ophthalmol. 13: 881-886Crossref (7) Our do support theory, (4/45) asthma/allergy, comparable [26Andersson expression asthma schoolchildren changed 1996 2006.Pediatr Allergy Immunol. 2010; 859-866Crossref (0) Similar studies, proportion (47%) fulfilling Misdiagnosis, ICD codes, fundoscopy papilledema), measure obtaining values contributed Surprisingly, identified meeting received prone errors, unnecessary tests, invasive procedures, follow-ups, safety. researchers performing retrospective epidemiological must aware fact. Only studying register data, scrutinizing records, generate misleading conflicting results. way overcome problem employ trials, given relative rarity condition, multicenter level. par United Kingdom little 0.5 Germany [12Tibussek 0.6 Canada [27Bursztyn L.L. al.Has rising children?.Can 49: 87-91Abstract strengths includes large included. tried lost I67.4. 2000−2010 could include region. thorough review hospital performed. General limitations relates design, varying amount estimate prompt knowledge personnel Over common, thus adapting stringency using term advisable.