Paediatric Idiopathic Intracranial Hypertension: Presenting Features, Management, and Visual Outcomes in a Single Centre Cohort.

Paediatric Idiopathic Intracranial Hypertension: Presenting Features, Management, and Visual Outcomes in a Single Centre Cohort. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Paediatric Idiopathic Intracranial Hypertension: Presenting Features, Management, and Visual Outcomes in a Single Centre Cohort. Robert Thomas Brady, Audrey Pang, Fiona Pearce, Pooja Harijan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6421572/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Idiopathic Intracranial Hypertension (IIH) is an important cause of papilloedema in children that can lead to visual loss. This study examined patient demographics combined with presenting signs and symptoms in paediatric patients with IIH. We also investigated the visual outcomes of these patients over the course of their treatment. Methods This retrospective study examines the presenting features and visual outcomes of children with IIH attending a tertiary multi-disciplinary-focused (paediatric neurology and neuro-ophthalmology) centre. Results 70% of our study population was female, and 60% of all children were overweight, although there was a significant difference in BMI ranges in younger (<10 years) and older children. Headache and papilloedema were the predominant presenting features in the study. Following treatment, most (96%) had visual acuity of better than 6/9 in both eyes. Visual field testing revealed half had enlargement of the blind spot on Humphrey visual field testing as expected with papilloedema. Most defects recovered with treatment, although residual visual field defects persisted in others. Our cases were treated successfully with medical therapy, and only one patient required acute surgical intervention with VP shunting on presentation. Conclusions With the increasing prevalence of obesity in the UK, the incidence of paediatric IIH may potentially increase. Our cohort had a favourable outcome following treatment, which emphasizes the importance of early diagnosis and management of this condition to prevent visual morbidity. We recommend a multidisciplinary approach to managing IIH patients to allow a comprehensive assessment of their visual function in response to treatment. Biological sciences/Neuroscience/Visual system Health sciences/Health care Figures Figure 1 Figure 2 Figure 3 Introduction Idiopathic intracranial hypertension (IIH) in children is an uncommon but serious condition that can lead to life-long visual morbidity. It is characterised by raised intracranial pressure (ICP), an absence of space-occupying lesions or venous thrombosis on neuro-imaging, and normal cerebrospinal fluid (CSF) composition in children presenting with signs and symptoms of raised ICP such as papilloedema and headaches ( 1 ). Since the 1980s, IIH cases have been diagnosed according to the Modified Dandy Criteria ( 2 ). More recently, Friedman et al. published revised diagnostic criteria that proposed subdividing cases into primary versus secondary ( 3 ). IIH is less common in children than adults, with a recent British survey reporting a national annual incidence of IIH in children aged 1–16 years of 0.8 per 100,000 ( 4 ). The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) has provided a wealth of information on the condition in adults ( 5 ). In the absence of comparable studies in children, their results have been extrapolated to the paediatric population. It is unclear, however, if differences between these groups exist. For example, female gender and obesity are strongly associated with adult IIH patients but not necessarily in younger paediatric patients. Studies have shown that the typical adolescent, post-pubertal IIH patient is obese and female, but obese males or pre-pubertal girls and boys who are not overweight may also have the condition ( 6 , 7 ). Despite our limited understanding of the pathophysiology of IIH, there remains great interest in studies looking at the epidemiology, diagnostic criteria, and treatment of IIH in both adults and children. In contrast, few studies detail the visual outcomes of this potentially sight-threatening condition. Our study aimed to determine patient demographics combined with presenting signs and symptoms in paediatric patients with IIH. We then wished to examine the visual outcomes of a British cohort of paediatric patients with confirmed IIH in a single tertiary referral centre. Materials and Methods A retrospective case notes review of paediatric IIH cases seen at was conducted. This tertiary medical centre has expertise in paediatric neurology, paediatric neuro-ophthalmology and paediatric neurosurgery. Institutional review board and ethics committee approval was obtained at this hospital. Case notes of all paediatric patients with IIH under 16 years at diagnosis, treated at the paediatric neurology department and paediatric ophthalmology clinics between 2007 and 2021, were reviewed. Inclusion criteria were patients who met the modified Dandy Criteria of ( 1 ) papilloedema, ( 2 ) normal neurological examination apart from signs related to raised ICP, ( 3 ) raised ICP exceeding 25cm H2O on lumbar puncture (LP) or CSF infusion study (CSFIS), ( 4 ) normal CSF analysis, ( 5 ) normal neuroimaging on Magnetic Resonance Imaging (MRI). Patients also needed to have a recorded ophthalmology review at the time of diagnosis and follow-up visual outcome data. 50 patients with complete investigations, assessments, and ophthalmological data were included in the analysis. Significantly, patients were excluded if they did not meet the Modified Dandy Criteria, if the diagnosis of IIH was in question or if complete ophthalmological data was unavailable. Data collected included the age at presentation, gender, height, weight, Body Mass Index (BMI), symptoms and signs and clinical findings of these patients at presentation. According to the SIGN guidelines for obesity in childhood and adolescence, we recorded the BMI. We expressed the degree of overweight/obesity in terms of UK BMI centile charts based on the 1990 reference population ( 8 ). In clinical practice, overweight children are those with a BMI > 91stcentile of the UK 1990 reference chart for age and sex, and obese children are those with a BMI > 98thcentile. Severe obesity is defined as a BMI > 99.6th centile. We documented reported symptoms of headache, vomiting, transient visual obscurations (TVOs) and pulsatile tinnitus. The headache history was carefully taken as we recognize that migraine can co-exist in patients with IIH. The ICHD-3 criteria were used in the headache evaluation tool ( 9 ). CSFIS was performed in cases where the LP results were borderline or in the absence of papilledema. This investigation is completed under general or local anaesthesia in the lateral decubitus position. It allows CSF's opening and steady-state pressures to be assessed, and the resistance to CSF outflow is measured (the difference between plateau and baseline pressures, divided by the infusion rate). A steady state above 20mmHg (equivalent to 27cm of H20) is regarded as high, and resistance to CSF outflow of > 13mmHg/ml/min is above the normal range ( 10 ). The initial and final best corrected visual acuity (BCVA), colour vision (using Ishihara plates) and visual field results (using the Humphrey Field Analyzer, Carl Zeiss, Meditech Inc, Dublin, CA, USA) of each eye were documented. Where available, we recorded the Optical Coherence Tomography (Cirrus HD-OCT, Carl Zeiss Meditech Inc, Dublin, CA, USA) scans of the retinal nerve fibre layer thickness (OCT RNFL). OCT RNFL was used to consolidate the diagnosis of papilloedema and monitor disease progress. Patients were excluded if they did not meet the Modified Dandy Criteria. The presence of optic nerve head drusen (ONHD) was assessed on B-Scan or Autofluorescence imaging. If IIH was confirmed, patients were started on treatment with either oral acetazolamide or oral topiramate. Some patients received a combination of both drugs during their treatment. If papilloedema was the primary feature, acetazolamide was the drug of choice, but if the papilledema was mild and headaches were the predominant feature, topiramate was used. Propranolol was used as an adjunct therapy in two patients who had co-existing migraine. Patients were also given dietary advice, and the need for weight loss was emphasized where appropriate. The paediatric neurosurgical team was involved when surgical intervention was required. Statistical analyses were performed using GraphPad Prism (Version 10.2) (GraphPad Software, CA, USA) software and Excel (Microsoft Corporation, WA, USA). All data are expressed as means ± standard error. One-way analysis of variance (ANOVA) was used with a Bonferroni test to compare between groups. A probability value of 95% (p < 0.05) was used to determine significance. Results Demographics of population – Patients predominantly made up of Caucasian children. Of the first 50 paediatric patients with confirmed IIH identified, the mean follow-up duration was 41 months with a standard deviation of 31 months. The mean age of the patients at presentation was 12.6 years with a standard deviation of 2.7 years (range 5–16 years). Of the 50 cases, 35 were female and 15 were male (Fig. 1A). Forty patients were > 10 years old at presentation, and ten were < 10. Ethnicity data was available for 88% of children, and white British made up 89%. The remaining ethnicities identified were South Asian (2.2%), White / Black Caribbean (2.2%), White / Asian (2.2%), and Other White (2.2%) (Fig. 1B). BMI measurements were available in 100% of selected patients at presentation. The mean BMI of these cases was 26.9 kg/m2 +/-6.3 kg/m2. In those younger patients less than 10, the average BMI was 21.0 kg/m2 +/-6.3 kg/m2 (n = 10), and in older patients > 10 years, the average BMI was 28.2 kg/m2+/-5.7 kg/m2 (n = 40). This difference was statistically significant (**, p < 0.001). According to the National Institute of Health and Care Excellence (NICE) guidelines on obesity updated Jul 2023, 40% ( 20 ) Children had a healthy BMI, 28% ( 14 ) were overweight, and 20% ( 10 ) were in the obesity 1 range. Significantly, 8% ( 4 ) were in the obesity 2 and 2% ( 1 ) were in obesity 3 ranges respectively. Notably, 50% of children under ten years were in the healthy range, and 40% were overweight. Presenting Signs and Symptoms – Most patients had headaches and optic disc swelling. Regarding symptoms, all but three cases presented with headache (94%), and 14 patients had nausea or vomiting (28%). Paediatric neurology recorded symptoms of migraine overlay in two patients at presentation. 22% of patients experienced transient visual obscurations (TVO), and 12% described diplopia. A single patient described symptoms of paraesthesia in the legs, facial weakness, and oscillopsia. Pulsatile tinnitus was only reported in 16% of cases (Fig. 2). Papilloedema was the most common sign present in 96% of all patients. Of those, a grade at presentation was made for 81% of patients. 4.1% ( 1 ) demonstrated Frisén grade 5 swelling, 20.8% ( 10 ) had grade 4, 22.9% ( 11 ) had grade 3, 31.2% ( 15 ) grade 2, 14.5% ( 7 ) had grade 1. No patients were identified to have co-existing ONHD (Fig. 3). Regarding imaging, all children underwent MR venograms, with 28% (14/50) demonstrating sinus narrowing or reported reduced flow. One of these children was found to have Chiari malformation, while no children had craniosynostosis. All patients had their CSF pressures measured. 30 (60%) patients had lumbar punctures (LP) performed, and 14 patients had elevated opening CSF pressures of > 25cmH20 (range 26–60 cmH20). In 20 (40%) cases, a CSFIS was performed. The mean baseline opening pressures of these cases was 26.0mmHg. Visual Function and Outcomes – Most patients had good visual function on presentation. The presenting best corrected visual acuity (BCVA) was better than or equal to 6/9 in both eyes in 86% of children (Fig. 3). Of those with BCVA worse than 6/9 at presentation, visual acuity tended to be asymmetric between the eyes. One child had underlying unilateral amblyopia, and one child had a BCVA of counting fingers' vision in both eyes. With treatment, almost all cases regained a visual acuity better than 6/9 in both eyes. Only one child had a VA of 6/12 bilaterally afterwards. The case with bilateral count fingers acuity regained 6/6 vision in the right eye and had residual visual loss of 6/15 in the left eye due to optic atrophy. At the last follow-up, 100% of cases had improved visual acuity, excluding the amblyopic eye, which had remained stable. 96% of cases had BCVA of better than 6/9 in both eyes. Colour vision on Ishihara testing was reduced in 22.4% (11 out of 49) cases, with one child excluded for having previously known colour blindness. With treatment, 73% ( 8 ) cases recovered colour perception, whilst one case deteriorated. Visual field testing on Humphrey Visual Field (HVF) analyser data was completed on 94% (47 cases). HVF testing was not done in the children aged < 7 years old as they were deemed too young to perform the test reliably while acutely unwell. Testing provided reliable field results in 41 of these patients. Of those, 51% ( 21 ) were revealed to have abnormalities. The most common visual field defect was enlarged blind spots 52% ( 11 ) and generalised restrictions. With treatment, 11 of these patients regained complete visual fields, and the other ten patients had residual defects at the last follow-up. In terms of neurological deficits, 14% ( 7 ) patients presented with sixth nerve palsy, three of which were bilateral. After treatment, all patients recovered from their cranial nerve palsies with a resolution of diplopia and no need for strabismus surgery. Diagnosis and Treatment – Medical treatment was sufficient to manage most patients In our study group, one child had a history of previous meningitis a few years prior to her IIH diagnosis, and another child had IIH secondary to levothyroxine medication. Reliable optical coherence tomography data and Frisén grade of papilloedema at presentation and last follow-up were available in 49 patients (98 eyes). The mean average RNFL thickness was 194 +/- 107 microns. Clinical grading appeared to correlate with average RNFL; eyes with resolved/no papilloedema had an average RNFL thickness of 105.9 +/- 25.5 microns. Those with grade I had an average RNFL of 122.4 +/- 18.7 microns, grade II's average RNFL was 155.6 +/- 30.1 microns, grade III 277.3 +/- 100.8 microns, and grade IV 292.0 +/- 99.2 microns. The mean improvement in average RNFL thickness was 81.3 microns throughout follow-up. All but two patients received medical treatment as first-line therapy. One patient required an emergency shunt, and a second responded well to analgesics and weight loss efforts alone post-LP. 50% (25) of cases received oral acetazolamide alone, and 22% ( 11 ) of cases received oral topiramate during their course of treatment. 24% ( 12 ) cases received both acetazolamide and topiramate as treatment. Children were on medication for an average of 399 +/-232 days. During the treatment course, seven patients had to stop acetazolamide. Four ceased treatments for a period of observation, three due to side effects, and one patient became pregnant. Three were changed to topiramate: one for needle phobia (inability to monitor electrolytes), one due to lack of treatment response and another due to side effects. Five patients (10%) had a recurrence of symptoms and signs once weaned off acetazolamide, requiring re-treatment. Two cases required surgical treatment with ventriculoperitoneal (VP) shunt surgery, both of these children were very unwell when they presented. Both were female and had grade four optic disc swelling. One 6-year-old was obese with bilateral count fingers visual acuity whilst the other was ten years of age with vomiting and a left 6th nerve palsy. One other child required an additional therapeutic lumbar puncture. One patient who received VP shunt surgery had IIH secondary to meningitis. Discussion Few studies have characterised the visual outcomes of paediatric IIH. This study postulated, and found that, the majority of paediatric patients presenting with IIH, who undergo medical management, have excellent visual outcomes. We also found that children with normal BMI ranges can suffer from the condition which contrasts with the typical association of raised BMI in adult cases although the underpinning aetiology remains unknown. As a tertiary centre with paediatric neurology and paediatric neuro-ophthalmology services in the United Kingdom, we receive increasing numbers of referrals for paediatric IIH. We sought to evaluate the presenting characteristics and visual function pre- and post-treatment as we feel this cohort may have a different disease profile from those reported in other adult IIH studies. Regarding ICP, Avery et al. ( 8 ) have suggested that the upper limit for the paediatric population can be as high as 28 cm H2O. However, most of our patients develop papilloedema below this pressure level. As with previous studies, the majority (70%) of our study population was female, and most of them were overweight, with more than half in the obese category. We found that raised BMI was comparable to older (pubertal) children which has been reported although this was not understood to impact final visual outcomes ( 9 ). Headache is the predominant presenting symptom in this study (94%), consistent with most other reports ( 10 ). Sixth nerve palsy was the most common cranial nerve palsy at presentation in our patients. The reported incidence of sixth nerve (VI) palsy in paediatric patients with IIH range from 9–59% ( 11 ). The incidence of sixth nerve palsy in our study falls in the middle of this range. Although it is traditionally accepted that sixth nerve palsy can often occur in IIH, unusual presentations of other cranial nerve palsies, such as the facial (VII) nerve palsy, oculomotor (III) or trochlear (IV) nerve palsies, are recognised ( 12 ). All cases had MRI neuroimaging, and the majority had further MRV imaging performed to assess for vascular abnormalities, particularly the narrowing of the venous sinus associated with IIH or venous sinus thrombosis ( 13 ). CSF infusion studies in paediatric patients are performed at our institute, as measuring the baseline, and steady-state CSF pressures during the infusion study and the resistance to CSF outflow provides more information on ICP. This detailed assessment allows for a more accurate diagnosis of intracranial hypertension ( 14 ). The majority (96%) of our patients presented with papilloedema. In a recent update by Cleves-Bayon et al. ( 15 ), papilloedema is regarded as the single most important predictor of visual loss in IIH patients. However, it is interesting to note that visual function, measured by acuity and colour vision, was well preserved at presentation in 86% and 77.6%, respectively. The most common visual field defect was enlarged blind spots, with only two patients recording more significant defects on presentation. Following treatment, the majority (96%) had good visual acuity of better than 6/9 in both eyes. Despite severe papilloedema and Frisén grading of > 3 in 23 of 49 patients, their final visual acuity outcome was still better than 6/9. We used 6/9 acuity as a baseline, as this level of vision is needed to obtain a driver's license in future. Only one case suffered significant visual loss due to optic atrophy, primarily due to the late presentation and the delay in diagnosis. Our cases were treated with acetazolamide, which is widely accepted as the first-line treatment for IIH since the findings of the idiopathic intracranial hypertension treatment trial (IIHTT) results were published ( 16 ). Our study population responded well to medical treatment, and only two patients required acute surgical intervention with VP shunting on presentation. Compared to a recent study by Gospe et al. ( 17 ), where they reported that 19% of the study eyes developed permanent visual acuity or visual field loss, the incidence in our study is lower. They observed that papilloedema Frisén grade > 3 was associated with poor visual outcomes. Our study is too small to conclude any relationship between the grade of optic disc swelling and visual outcome. However, despite the papilloedema of Frisén grade > 3 noted in 46% of our patients, their visual outcome was good. Another notable contribution by Inger et al 2019, reported excellent final visual acuities achieved in children who were medically managed alone ( 18 ). The weakness of this study is its retrospective nature. The follow-up duration for our patients is variable as they often prefer to return to their local hospital for subsequent reviews. We do not have an accurate staging of the pubertal status of our patients; therefore, this data has not been included. Due to our small study population, we cannot conclude if primary or secondary IIH impacts visual outcomes. This study also reiterates the importance of recognizing patients with secondary causes of papilloedema that may be indistinguishable from those with IIH ( 3 ). The strengths of our study are that a multidisciplinary team reviews the patients in a single unit setting to aid in the diagnosis and monitoring of their signs and symptoms. We can perform CSF infusion studies on borderline cases to confirm their diagnosis. They undergo a comprehensive eye review by a paediatric ophthalmology team, supported by a paediatric neuro-ophthalmologist, where we confirm the presence of papilloedema and rule out other confounding conditions, such as isolated ONHD. Subsequent reviews are conducted to monitor their visual function before and after treatment. Imaging technologies such as autofluorescence and optical coherence tomography imaging of the retinal nerve fibre layer (OCT RNFL) are helpful in the diagnosis and monitoring of patients with IIH ( 19 , 20 ). The challenge remains in performing investigations and obtaining reliable results on a paediatric population ( 21 ). We realise the need for further prospective, targeted data collection in the subsequent paediatric patients who present with IIH. There is also a need for more extensive, dedicated paediatric studies to have a more evidence-based approach to treating paediatric IIH, as the current therapies merely extrapolate on the limited evidence available in adult literature. Conclusion Paediatric IIH is an essential cause of papilloedema in children that can lead to visual loss. With the increasing prevalence of obesity in the UK, the incidence of paediatric IIH may potentially increase. Our cohort had a favourable outcome following treatment, which emphasises the importance of early diagnosis and management of this condition to prevent visual morbidity. We recommend a multidisciplinary approach to managing IIH patients to allow a comprehensive assessment of their visual function in response to treatment. Declarations Acknowledgements We would like to acknowledge all of the clinical and support staff at the department of neurology and paediatric neuro-ophthalmology at Addenbrooke’s Hospital, Cambridge, UK for all of their support and assistance. The authors have no declarations of interest. References Barkatullah AF, Leishangthem L, Moss HE. MRI findings as markers of idiopathic intracranial hypertension. Curr Opin Neurol. 2021;34(1):75–83. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002;59(10):1492–5. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159–65. Matthews YY, Dean F, Matyka K, McLachlan K, Solanki G, Lim MJ, et al. UK surveillance of childhood idiopathic intracranial hypertension (IIH). Archives of Disease in Childhood. 2012;97(Suppl 1):A6. Wall M, Kupersmith MJ, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. The idiopathic intracranial hypertension treatment trial: clinical profile at baseline. JAMA Neurol. 2014;71(6):693–701. Sheldon CA, Paley GL, Xiao R, Kesler A, Eyal O, Ko MW, et al. Paediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort. Ophthalmology. 2016;123(11):2424–31. Malem A, Sheth T, Muthusamy B. Paediatric Idiopathic Intracranial Hypertension (IIH)-A Review. Life (Basel). 2021;11(7). Avery RA, Shah SS, Licht DJ, Seiden JA, Huh JW, Boswinkel J, et al. Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med. 2010;363(9):891–3. Nitzan–Luques A, Bulkowstein Y, Barnoy N, Aran A, Reif S, Gilboa T. Improving paediatric idiopathic intracranial hypertension care: a retrospective cohort study. Scientific Reports. 2022;12(1):19218. Albakr A, Hamad MH, Alwadei AH, Bashiri FA, Hassan HH, Idris H, et al. Idiopathic intracranial hypertension in children: Diagnostic and management approach. Sudan J Paediatr. 2016;16(2):67–76. Reid JE, Reem RE, Aylward SC, Rogers DL. Sixth Nerve Palsy in Paediatric Intracranial Hypertension. Neuroophthalmology. 2016;40(1):23–7. Friedman DI, Forman S, Levi L, Lavin PJ, Donahue S. Unusual ocular motility disturbances with increased intracranial pressure. Neurology. 1998;50(6):1893–6. Dwyer CM, Prelog K, Owler BK. The role of venous sinus outflow obstruction in paediatric idiopathic intracranial hypertension. J Neurosurg Pediatr. 2013;11(2):144–9. Lalou AD, McTaggart JS, Czosnyka ZH, Garnett MR, Krishnakumar D, Czosnyka M. Cerebrospinal fluid dynamics in paediatric pseudotumor cerebri syndrome. Childs Nerv Syst. 2020;36(1):73–86. Cleves-Bayon C. Idiopathic Intracranial Hypertension in Children and Adolescents: An Update. Headache. 2018;58(3):485–93. Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. Jama. 2014;311(16):1641–51. Gospe SM, 3rd, Bhatti MT, El-Dairi MA. Anatomic and visual function outcomes in paediatric idiopathic intracranial hypertension. Br J Ophthalmol. 2016;100(4):505–9. Inger HE, McGregor ML, Jordan CO, Reem RE, Aylward SC, Scoville NM, et al. Surgical intervention in paediatric intracranial hypertension: incidence, risk factors, and visual outcomes. J aapos. 2019;23(2):96 .e1-.e7 . Lee YA, Tomsak RL, Sadikovic Z, Bahl R, Sivaswamy L. Use of Ocular Coherence Tomography in Children With Idiopathic Intracranial Hypertension-A Single-Centre Experience. Pediatr Neurol. 2016;58:101-6.e1. El-Dairi MA, Holgado S, O'Donnell T, Buckley EG, Asrani S, Freedman SF. Optical coherence tomography as a tool for monitoring paediatric pseudotumor cerebri. J aapos. 2007;11(6):564–70. Kumar A, Hekmatjah N, Yu Y, Han Y, Ying G-S, Oatts JT. Factors Associated With Visual Field Testing Reliability in Children With Glaucoma or Suspected Glaucoma. American Journal of Ophthalmology. 2024;264:187–93. Additional Declarations There is no conflict of interest Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6421572","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":441622756,"identity":"0b5b6dca-6442-4d16-9c7a-3f79975d7a27","order_by":0,"name":"Robert Thomas Brady","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYFACHjCZACYZG4DEAeYDzIS1JBgga2FLgGhhI14LjwFeLebtvQcfV/74k8cvdvjxB8Yd9+T5buR8e1zwhyGPX74BqxaZM+eSDc8kGBRLzk4zk2A8U2w480buduOZbQzFkm3YbZGQyDGTbEgwSNxwO8GMgbEtgXHDjdxt0rwNDIkbjuHUYv4ToiX98wegFvsNN3KeSfP8YUjcj1uLGSNES46BBFBLIlALmzQPG9AWHN6X4DmXLNmQZpw4c3ZOmUTimYTkmWeemUnztkkkzjiWgF0Le+/Bjw02con90umbP3zckWDbdzwZ5DCbxP7mA9itQQFgYwXApAQRyuGAnxjDR8EoGAWjYCQBAFhOYhRX8a9XAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5839-8566","institution":"Addenbrooke's Hospital, Cambridge, UK","correspondingAuthor":true,"prefix":"","firstName":"Robert","middleName":"Thomas","lastName":"Brady","suffix":""},{"id":441622757,"identity":"d4ff82ca-b9fa-47df-81f8-05c20e040ff7","order_by":1,"name":"Audrey Pang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Audrey","middleName":"","lastName":"Pang","suffix":""},{"id":441622758,"identity":"50ea6934-b13a-41de-b8e9-e8111774ad07","order_by":2,"name":"Fiona Pearce","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fiona","middleName":"","lastName":"Pearce","suffix":""},{"id":441622759,"identity":"c8baeab1-6741-4443-9b16-675048df7113","order_by":3,"name":"Pooja Harijan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Pooja","middleName":"","lastName":"Harijan","suffix":""},{"id":441622760,"identity":"47c8c71c-7693-4c02-bafd-21808b2d9743","order_by":4,"name":"Deepa Krishnakumar","email":"","orcid":"","institution":"Cambridge","correspondingAuthor":false,"prefix":"","firstName":"Deepa","middleName":"","lastName":"Krishnakumar","suffix":""},{"id":441622761,"identity":"53a2e3e8-a14a-4821-b2a6-c2d42c635b6f","order_by":5,"name":"Brinda Muthusamy","email":"","orcid":"","institution":"Addenbrooke's hospital","correspondingAuthor":false,"prefix":"","firstName":"Brinda","middleName":"","lastName":"Muthusamy","suffix":""}],"badges":[],"createdAt":"2025-04-10 15:31:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6421572/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6421572/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80584866,"identity":"2938e819-717b-427e-94a9-f7651d3ea732","added_by":"auto","created_at":"2025-04-15 00:26:58","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36116,"visible":true,"origin":"","legend":"\u003cp\u003eDemographics of paediatric patients with IIH. A – Gender distribution, B – Ethnic distribution\u003c/p\u003e","description":"","filename":"Figure11200DPI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6421572/v1/88cbd69baf1dec734a7b8aec.jpg"},{"id":80585663,"identity":"43d201e1-017a-470b-a927-8c146b12c983","added_by":"auto","created_at":"2025-04-15 00:42:58","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53774,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of symptoms of IIH in paediatric patients at presentation\u003c/p\u003e","description":"","filename":"Figure21200DPI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6421572/v1/b05860f7d76c63a7000f740c.jpg"},{"id":80585376,"identity":"c9c095df-8aa7-4c14-8ce7-4ebca4b6bd89","added_by":"auto","created_at":"2025-04-15 00:34:58","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57613,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of signs of IIH in paediatric patients at presentation\u003c/p\u003e","description":"","filename":"Figure31200DPI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6421572/v1/a03e29e57a9e2d4bb8e1b036.jpg"},{"id":93018711,"identity":"6aedaab0-8872-415e-a9a3-f01c19af7bdd","added_by":"auto","created_at":"2025-10-08 08:24:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":493275,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6421572/v1/01c19cfd-3977-4ecb-bcad-b4fab4e65702.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Paediatric Idiopathic Intracranial Hypertension: Presenting Features, Management, and Visual Outcomes in a Single Centre Cohort.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic intracranial hypertension (IIH) in children is an uncommon but serious condition that can lead to life-long visual morbidity. It is characterised by raised intracranial pressure (ICP), an absence of space-occupying lesions or venous thrombosis on neuro-imaging, and normal cerebrospinal fluid (CSF) composition in children presenting with signs and symptoms of raised ICP such as papilloedema and headaches (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Since the 1980s, IIH cases have been diagnosed according to the Modified Dandy Criteria (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). More recently, Friedman et al. published revised diagnostic criteria that proposed subdividing cases into primary versus secondary (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIIH is less common in children than adults, with a recent British survey reporting a national annual incidence of IIH in children aged 1\u0026ndash;16 years of 0.8 per 100,000 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) has provided a wealth of information on the condition in adults (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In the absence of comparable studies in children, their results have been extrapolated to the paediatric population. It is unclear, however, if differences between these groups exist. For example, female gender and obesity are strongly associated with adult IIH patients but not necessarily in younger paediatric patients. Studies have shown that the typical adolescent, post-pubertal IIH patient is obese and female, but obese males or pre-pubertal girls and boys who are not overweight may also have the condition (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite our limited understanding of the pathophysiology of IIH, there remains great interest in studies looking at the epidemiology, diagnostic criteria, and treatment of IIH in both adults and children. In contrast, few studies detail the visual outcomes of this potentially sight-threatening condition.\u003c/p\u003e \u003cp\u003eOur study aimed to determine patient demographics combined with presenting signs and symptoms in paediatric patients with IIH. We then wished to examine the visual outcomes of a British cohort of paediatric patients with confirmed IIH in a single tertiary referral centre.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eA retrospective case notes review of paediatric IIH cases seen at \u0026lt;\u0026thinsp;HOSPITAL REDACTED\u0026thinsp;\u0026gt;\u0026thinsp;was conducted. This tertiary medical centre has expertise in paediatric neurology, paediatric neuro-ophthalmology and paediatric neurosurgery. Institutional review board and ethics committee approval was obtained at this hospital.\u003c/p\u003e \u003cp\u003eCase notes of all paediatric patients with IIH under 16 years at diagnosis, treated at the paediatric neurology department and paediatric ophthalmology clinics between 2007 and 2021, were reviewed. Inclusion criteria were patients who met the modified Dandy Criteria of (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) papilloedema, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) normal neurological examination apart from signs related to raised ICP, (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) raised ICP exceeding 25cm H2O on lumbar puncture (LP) or CSF infusion study (CSFIS), (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) normal CSF analysis, (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) normal neuroimaging on Magnetic Resonance Imaging (MRI). Patients also needed to have a recorded ophthalmology review at the time of diagnosis and follow-up visual outcome data.\u003c/p\u003e \u003cp\u003e50 patients with complete investigations, assessments, and ophthalmological data were included in the analysis. Significantly, patients were excluded if they did not meet the Modified Dandy Criteria, if the diagnosis of IIH was in question or if complete ophthalmological data was unavailable.\u003c/p\u003e \u003cp\u003eData collected included the age at presentation, gender, height, weight, Body Mass Index (BMI), symptoms and signs and clinical findings of these patients at presentation. According to the SIGN guidelines for obesity in childhood and adolescence, we recorded the BMI. We expressed the degree of overweight/obesity in terms of UK BMI centile charts based on the 1990 reference population (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In clinical practice, overweight children are those with a BMI\u0026thinsp;\u0026gt;\u0026thinsp;91stcentile of the UK 1990 reference chart for age and sex, and obese children are those with a BMI\u0026thinsp;\u0026gt;\u0026thinsp;98thcentile. Severe obesity is defined as a BMI\u0026thinsp;\u0026gt;\u0026thinsp;99.6th centile. We documented reported symptoms of headache, vomiting, transient visual obscurations (TVOs) and pulsatile tinnitus. The headache history was carefully taken as we recognize that migraine can co-exist in patients with IIH. The ICHD-3 criteria were used in the headache evaluation tool (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCSFIS was performed in cases where the LP results were borderline or in the absence of papilledema. This investigation is completed under general or local anaesthesia in the lateral decubitus position. It allows CSF's opening and steady-state pressures to be assessed, and the resistance to CSF outflow is measured (the difference between plateau and baseline pressures, divided by the infusion rate). A steady state above 20mmHg (equivalent to 27cm of H20) is regarded as high, and resistance to CSF outflow of \u0026gt;\u0026thinsp;13mmHg/ml/min is above the normal range (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe initial and final best corrected visual acuity (BCVA), colour vision (using Ishihara plates) and visual field results (using the Humphrey Field Analyzer, Carl Zeiss, Meditech Inc, Dublin, CA, USA) of each eye were documented. Where available, we recorded the Optical Coherence Tomography (Cirrus HD-OCT, Carl Zeiss Meditech Inc, Dublin, CA, USA) scans of the retinal nerve fibre layer thickness (OCT RNFL). OCT RNFL was used to consolidate the diagnosis of papilloedema and monitor disease progress. Patients were excluded if they did not meet the Modified Dandy Criteria. The presence of optic nerve head drusen (ONHD) was assessed on B-Scan or Autofluorescence imaging.\u003c/p\u003e \u003cp\u003eIf IIH was confirmed, patients were started on treatment with either oral acetazolamide or oral topiramate. Some patients received a combination of both drugs during their treatment. If papilloedema was the primary feature, acetazolamide was the drug of choice, but if the papilledema was mild and headaches were the predominant feature, topiramate was used. Propranolol was used as an adjunct therapy in two patients who had co-existing migraine. Patients were also given dietary advice, and the need for weight loss was emphasized where appropriate. The paediatric neurosurgical team was involved when surgical intervention was required.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using GraphPad Prism (Version 10.2) (GraphPad Software, CA, USA) software and Excel (Microsoft Corporation, WA, USA). All data are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error. One-way analysis of variance (ANOVA) was used with a Bonferroni test to compare between groups. A probability value of 95% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was used to determine significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDemographics of population \u0026ndash; Patients predominantly made up of Caucasian children.\u003c/p\u003e \u003cp\u003eOf the first 50 paediatric patients with confirmed IIH identified, the mean follow-up duration was 41 months with a standard deviation of 31 months. The mean age of the patients at presentation was 12.6 years with a standard deviation of 2.7 years (range 5\u0026ndash;16 years). Of the 50 cases, 35 were female and 15 were male (Fig.\u0026nbsp;1A). Forty patients were \u0026gt;\u0026thinsp;10 years old at presentation, and ten were \u0026lt;\u0026thinsp;10. Ethnicity data was available for 88% of children, and white British made up 89%. The remaining ethnicities identified were South Asian (2.2%), White / Black Caribbean (2.2%), White / Asian (2.2%), and Other White (2.2%) (Fig.\u0026nbsp;1B).\u003c/p\u003e \u003cp\u003eBMI measurements were available in 100% of selected patients at presentation. The mean BMI of these cases was 26.9 kg/m2 +/-6.3 kg/m2. In those younger patients less than 10, the average BMI was 21.0 kg/m2 +/-6.3 kg/m2 (n\u0026thinsp;=\u0026thinsp;10), and in older patients\u0026thinsp;\u0026gt;\u0026thinsp;10 years, the average BMI was 28.2 kg/m2+/-5.7 kg/m2 (n\u0026thinsp;=\u0026thinsp;40). This difference was statistically significant (**, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAccording to the National Institute of Health and Care Excellence (NICE) guidelines on obesity updated Jul 2023, 40% (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Children had a healthy BMI, 28% (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) were overweight, and 20% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) were in the obesity 1 range. Significantly, 8% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) were in the obesity 2 and 2% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) were in obesity 3 ranges respectively. Notably, 50% of children under ten years were in the healthy range, and 40% were overweight.\u003c/p\u003e \u003cp\u003ePresenting Signs and Symptoms \u0026ndash; Most patients had headaches and optic disc swelling.\u003c/p\u003e \u003cp\u003eRegarding symptoms, all but three cases presented with headache (94%), and 14 patients had nausea or vomiting (28%). Paediatric neurology recorded symptoms of migraine overlay in two patients at presentation. 22% of patients experienced transient visual obscurations (TVO), and 12% described diplopia. A single patient described symptoms of paraesthesia in the legs, facial weakness, and oscillopsia. Pulsatile tinnitus was only reported in 16% of cases (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003ePapilloedema was the most common sign present in 96% of all patients. Of those, a grade at presentation was made for 81% of patients. 4.1% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) demonstrated Fris\u0026eacute;n grade 5 swelling, 20.8% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) had grade 4, 22.9% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) had grade 3, 31.2% (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) grade 2, 14.5% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) had grade 1. No patients were identified to have co-existing ONHD (Fig.\u0026nbsp;3). Regarding imaging, all children underwent MR venograms, with 28% (14/50) demonstrating sinus narrowing or reported reduced flow. One of these children was found to have Chiari malformation, while no children had craniosynostosis. All patients had their CSF pressures measured. 30 (60%) patients had lumbar punctures (LP) performed, and 14 patients had elevated opening CSF pressures of \u0026gt;\u0026thinsp;25cmH20 (range 26\u0026ndash;60 cmH20). In 20 (40%) cases, a CSFIS was performed. The mean baseline opening pressures of these cases was 26.0mmHg.\u003c/p\u003e \u003cp\u003eVisual Function and Outcomes \u0026ndash; Most patients had good visual function on presentation.\u003c/p\u003e \u003cp\u003eThe presenting best corrected visual acuity (BCVA) was better than or equal to 6/9 in both eyes in 86% of children (Fig.\u0026nbsp;3). Of those with BCVA worse than 6/9 at presentation, visual acuity tended to be asymmetric between the eyes. One child had underlying unilateral amblyopia, and one child had a BCVA of counting fingers' vision in both eyes. With treatment, almost all cases regained a visual acuity better than 6/9 in both eyes. Only one child had a VA of 6/12 bilaterally afterwards. The case with bilateral count fingers acuity regained 6/6 vision in the right eye and had residual visual loss of 6/15 in the left eye due to optic atrophy.\u003c/p\u003e \u003cp\u003eAt the last follow-up, 100% of cases had improved visual acuity, excluding the amblyopic eye, which had remained stable. 96% of cases had BCVA of better than 6/9 in both eyes. Colour vision on Ishihara testing was reduced in 22.4% (11 out of 49) cases, with one child excluded for having previously known colour blindness. With treatment, 73% (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) cases recovered colour perception, whilst one case deteriorated.\u003c/p\u003e \u003cp\u003eVisual field testing on Humphrey Visual Field (HVF) analyser data was completed on 94% (47 cases). HVF testing was not done in the children aged\u0026thinsp;\u0026lt;\u0026thinsp;7 years old as they were deemed too young to perform the test reliably while acutely unwell. Testing provided reliable field results in 41 of these patients. Of those, 51% (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) were revealed to have abnormalities. The most common visual field defect was enlarged blind spots 52% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and generalised restrictions. With treatment, 11 of these patients regained complete visual fields, and the other ten patients had residual defects at the last follow-up. In terms of neurological deficits, 14% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) patients presented with sixth nerve palsy, three of which were bilateral. After treatment, all patients recovered from their cranial nerve palsies with a resolution of diplopia and no need for strabismus surgery.\u003c/p\u003e \u003cp\u003eDiagnosis and Treatment \u0026ndash; Medical treatment was sufficient to manage most patients\u003c/p\u003e \u003cp\u003eIn our study group, one child had a history of previous meningitis a few years prior to her IIH diagnosis, and another child had IIH secondary to levothyroxine medication. Reliable optical coherence tomography data and Fris\u0026eacute;n grade of papilloedema at presentation and last follow-up were available in 49 patients (98 eyes). The mean average RNFL thickness was 194 +/- 107 microns. Clinical grading appeared to correlate with average RNFL; eyes with resolved/no papilloedema had an average RNFL thickness of 105.9 +/- 25.5 microns. Those with grade I had an average RNFL of 122.4 +/- 18.7 microns, grade II's average RNFL was 155.6 +/- 30.1 microns, grade III 277.3 +/- 100.8 microns, and grade IV 292.0 +/- 99.2 microns. The mean improvement in average RNFL thickness was 81.3 microns throughout follow-up.\u003c/p\u003e \u003cp\u003eAll but two patients received medical treatment as first-line therapy. One patient required an emergency shunt, and a second responded well to analgesics and weight loss efforts alone post-LP. 50% (25) of cases received oral acetazolamide alone, and 22% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) of cases received oral topiramate during their course of treatment. 24% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) cases received both acetazolamide and topiramate as treatment. Children were on medication for an average of 399 +/-232 days. During the treatment course, seven patients had to stop acetazolamide. Four ceased treatments for a period of observation, three due to side effects, and one patient became pregnant. Three were changed to topiramate: one for needle phobia (inability to monitor electrolytes), one due to lack of treatment response and another due to side effects. Five patients (10%) had a recurrence of symptoms and signs once weaned off acetazolamide, requiring re-treatment.\u003c/p\u003e \u003cp\u003eTwo cases required surgical treatment with ventriculoperitoneal (VP) shunt surgery, both of these children were very unwell when they presented. Both were female and had grade four optic disc swelling. One 6-year-old was obese with bilateral count fingers visual acuity whilst the other was ten years of age with vomiting and a left 6th nerve palsy. One other child required an additional therapeutic lumbar puncture. One patient who received VP shunt surgery had IIH secondary to meningitis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFew studies have characterised the visual outcomes of paediatric IIH. This study postulated, and found that, the majority of paediatric patients presenting with IIH, who undergo medical management, have excellent visual outcomes. We also found that children with normal BMI ranges can suffer from the condition which contrasts with the typical association of raised BMI in adult cases although the underpinning aetiology remains unknown. As a tertiary centre with paediatric neurology and paediatric neuro-ophthalmology services in the United Kingdom, we receive increasing numbers of referrals for paediatric IIH. We sought to evaluate the presenting characteristics and visual function pre- and post-treatment as we feel this cohort may have a different disease profile from those reported in other adult IIH studies.\u003c/p\u003e \u003cp\u003eRegarding ICP, Avery et al. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) have suggested that the upper limit for the paediatric population can be as high as 28 cm H2O. However, most of our patients develop papilloedema below this pressure level. As with previous studies, the majority (70%) of our study population was female, and most of them were overweight, with more than half in the obese category. We found that raised BMI was comparable to older (pubertal) children which has been reported although this was not understood to impact final visual outcomes (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHeadache is the predominant presenting symptom in this study (94%), consistent with most other reports (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Sixth nerve palsy was the most common cranial nerve palsy at presentation in our patients. The reported incidence of sixth nerve (VI) palsy in paediatric patients with IIH range from 9\u0026ndash;59% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The incidence of sixth nerve palsy in our study falls in the middle of this range. Although it is traditionally accepted that sixth nerve palsy can often occur in IIH, unusual presentations of other cranial nerve palsies, such as the facial (VII) nerve palsy, oculomotor (III) or trochlear (IV) nerve palsies, are recognised (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll cases had MRI neuroimaging, and the majority had further MRV imaging performed to assess for vascular abnormalities, particularly the narrowing of the venous sinus associated with IIH or venous sinus thrombosis (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). CSF infusion studies in paediatric patients are performed at our institute, as measuring the baseline, and steady-state CSF pressures during the infusion study and the resistance to CSF outflow provides more information on ICP. This detailed assessment allows for a more accurate diagnosis of intracranial hypertension (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe majority (96%) of our patients presented with papilloedema. In a recent update by Cleves-Bayon et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), papilloedema is regarded as the single most important predictor of visual loss in IIH patients. However, it is interesting to note that visual function, measured by acuity and colour vision, was well preserved at presentation in 86% and 77.6%, respectively. The most common visual field defect was enlarged blind spots, with only two patients recording more significant defects on presentation. Following treatment, the majority (96%) had good visual acuity of better than 6/9 in both eyes. Despite severe papilloedema and Fris\u0026eacute;n grading of \u0026gt;\u0026thinsp;3 in 23 of 49 patients, their final visual acuity outcome was still better than 6/9. We used 6/9 acuity as a baseline, as this level of vision is needed to obtain a driver's license in future. Only one case suffered significant visual loss due to optic atrophy, primarily due to the late presentation and the delay in diagnosis.\u003c/p\u003e \u003cp\u003eOur cases were treated with acetazolamide, which is widely accepted as the first-line treatment for IIH since the findings of the idiopathic intracranial hypertension treatment trial (IIHTT) results were published (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Our study population responded well to medical treatment, and only two patients required acute surgical intervention with VP shunting on presentation. Compared to a recent study by Gospe et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), where they reported that 19% of the study eyes developed permanent visual acuity or visual field loss, the incidence in our study is lower. They observed that papilloedema Fris\u0026eacute;n grade\u0026thinsp;\u0026gt;\u0026thinsp;3 was associated with poor visual outcomes. Our study is too small to conclude any relationship between the grade of optic disc swelling and visual outcome. However, despite the papilloedema of Fris\u0026eacute;n grade\u0026thinsp;\u0026gt;\u0026thinsp;3 noted in 46% of our patients, their visual outcome was good. Another notable contribution by Inger et al 2019, reported excellent final visual acuities achieved in children who were medically managed alone (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe weakness of this study is its retrospective nature. The follow-up duration for our patients is variable as they often prefer to return to their local hospital for subsequent reviews. We do not have an accurate staging of the pubertal status of our patients; therefore, this data has not been included. Due to our small study population, we cannot conclude if primary or secondary IIH impacts visual outcomes. This study also reiterates the importance of recognizing patients with secondary causes of papilloedema that may be indistinguishable from those with IIH (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The strengths of our study are that a multidisciplinary team reviews the patients in a single unit setting to aid in the diagnosis and monitoring of their signs and symptoms. We can perform CSF infusion studies on borderline cases to confirm their diagnosis. They undergo a comprehensive eye review by a paediatric ophthalmology team, supported by a paediatric neuro-ophthalmologist, where we confirm the presence of papilloedema and rule out other confounding conditions, such as isolated ONHD. Subsequent reviews are conducted to monitor their visual function before and after treatment. Imaging technologies such as autofluorescence and optical coherence tomography imaging of the retinal nerve fibre layer (OCT RNFL) are helpful in the diagnosis and monitoring of patients with IIH (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The challenge remains in performing investigations and obtaining reliable results on a paediatric population (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe realise the need for further prospective, targeted data collection in the subsequent paediatric patients who present with IIH. There is also a need for more extensive, dedicated paediatric studies to have a more evidence-based approach to treating paediatric IIH, as the current therapies merely extrapolate on the limited evidence available in adult literature.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePaediatric IIH is an essential cause of papilloedema in children that can lead to visual loss. With the increasing prevalence of obesity in the UK, the incidence of paediatric IIH may potentially increase. Our cohort had a favourable outcome following treatment, which emphasises the importance of early diagnosis and management of this condition to prevent visual morbidity. We recommend a multidisciplinary approach to managing IIH patients to allow a comprehensive assessment of their visual function in response to treatment.\u003c/p\u003e "},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe would like to acknowledge all of the clinical and support staff at the department of neurology and paediatric neuro-ophthalmology at Addenbrooke\u0026rsquo;s Hospital, Cambridge, UK for all of their support and assistance.\u003c/p\u003e \u003cp\u003eThe authors have no declarations of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarkatullah AF, Leishangthem L, Moss HE. MRI findings as markers of idiopathic intracranial hypertension. Curr Opin Neurol. 2021;34(1):75\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002;59(10):1492\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthews YY, Dean F, Matyka K, McLachlan K, Solanki G, Lim MJ, et al. UK surveillance of childhood idiopathic intracranial hypertension (IIH). Archives of Disease in Childhood. 2012;97(Suppl 1):A6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWall M, Kupersmith MJ, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. The idiopathic intracranial hypertension treatment trial: clinical profile at baseline. JAMA Neurol. 2014;71(6):693\u0026ndash;701.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheldon CA, Paley GL, Xiao R, Kesler A, Eyal O, Ko MW, et al. Paediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort. Ophthalmology. 2016;123(11):2424\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalem A, Sheth T, Muthusamy B. Paediatric Idiopathic Intracranial Hypertension (IIH)-A Review. Life (Basel). 2021;11(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAvery RA, Shah SS, Licht DJ, Seiden JA, Huh JW, Boswinkel J, et al. Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med. 2010;363(9):891\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitzan\u0026ndash;Luques A, Bulkowstein Y, Barnoy N, Aran A, Reif S, Gilboa T. Improving paediatric idiopathic intracranial hypertension care: a retrospective cohort study. Scientific Reports. 2022;12(1):19218.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbakr A, Hamad MH, Alwadei AH, Bashiri FA, Hassan HH, Idris H, et al. Idiopathic intracranial hypertension in children: Diagnostic and management approach. Sudan J Paediatr. 2016;16(2):67\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReid JE, Reem RE, Aylward SC, Rogers DL. Sixth Nerve Palsy in Paediatric Intracranial Hypertension. Neuroophthalmology. 2016;40(1):23\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedman DI, Forman S, Levi L, Lavin PJ, Donahue S. Unusual ocular motility disturbances with increased intracranial pressure. Neurology. 1998;50(6):1893\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDwyer CM, Prelog K, Owler BK. The role of venous sinus outflow obstruction in paediatric idiopathic intracranial hypertension. J Neurosurg Pediatr. 2013;11(2):144\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLalou AD, McTaggart JS, Czosnyka ZH, Garnett MR, Krishnakumar D, Czosnyka M. Cerebrospinal fluid dynamics in paediatric pseudotumor cerebri syndrome. Childs Nerv Syst. 2020;36(1):73\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCleves-Bayon C. Idiopathic Intracranial Hypertension in Children and Adolescents: An Update. Headache. 2018;58(3):485\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. Jama. 2014;311(16):1641\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGospe SM, 3rd, Bhatti MT, El-Dairi MA. Anatomic and visual function outcomes in paediatric idiopathic intracranial hypertension. Br J Ophthalmol. 2016;100(4):505\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInger HE, McGregor ML, Jordan CO, Reem RE, Aylward SC, Scoville NM, et al. Surgical intervention in paediatric intracranial hypertension: incidence, risk factors, and visual outcomes. J aapos. 2019;23(2):96\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e.e1-.e7\u003c/span\u003e\u003cspan address=\"http://.e1-.e7\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee YA, Tomsak RL, Sadikovic Z, Bahl R, Sivaswamy L. Use of Ocular Coherence Tomography in Children With Idiopathic Intracranial Hypertension-A Single-Centre Experience. Pediatr Neurol. 2016;58:101-6.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Dairi MA, Holgado S, O'Donnell T, Buckley EG, Asrani S, Freedman SF. Optical coherence tomography as a tool for monitoring paediatric pseudotumor cerebri. J aapos. 2007;11(6):564\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar A, Hekmatjah N, Yu Y, Han Y, Ying G-S, Oatts JT. Factors Associated With Visual Field Testing Reliability in Children With Glaucoma or Suspected Glaucoma. American Journal of Ophthalmology. 2024;264:187\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6421572/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6421572/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Purpose\r\nIdiopathic Intracranial Hypertension (IIH) is an important cause of papilloedema in children that can lead to visual loss. This study examined patient demographics combined with presenting signs and symptoms in paediatric patients with IIH. We also investigated the visual outcomes of these patients over the course of their treatment.\r\n \r\nMethods\r\nThis retrospective study examines the presenting features and visual outcomes of children with IIH attending a tertiary multi-disciplinary-focused (paediatric neurology and neuro-ophthalmology) centre. \r\n\r\nResults \r\n70% of our study population was female, and 60% of all children were overweight, although there was a significant difference in BMI ranges in younger (\u003c10 years) and older children. Headache and papilloedema were the predominant presenting features in the study. Following treatment, most (96%) had visual acuity of better than 6/9 in both eyes. Visual field testing revealed half had enlargement of the blind spot on Humphrey visual field testing as expected with papilloedema. Most defects recovered with treatment, although residual visual field defects persisted in others. Our cases were treated successfully with medical therapy, and only one patient required acute surgical intervention with VP shunting on presentation. \r\n\r\nConclusions\r\nWith the increasing prevalence of obesity in the UK, the incidence of paediatric IIH may potentially increase. Our cohort had a favourable outcome following treatment, which emphasizes the importance of early diagnosis and management of this condition to prevent visual morbidity. We recommend a multidisciplinary approach to managing IIH patients to allow a comprehensive assessment of their visual function in response to treatment.","manuscriptTitle":"Paediatric Idiopathic Intracranial Hypertension: Presenting Features, Management, and Visual Outcomes in a Single Centre Cohort.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-15 00:26:54","doi":"10.21203/rs.3.rs-6421572/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cd3b73e9-d125-489f-9809-b2a41b20b465","owner":[],"postedDate":"April 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47024489,"name":"Biological sciences/Neuroscience/Visual system"},{"id":47024490,"name":"Health sciences/Health care"}],"tags":[],"updatedAt":"2025-10-08T08:16:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-15 00:26:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6421572","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6421572","identity":"rs-6421572","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}