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      Influence of sex and disease etiology on the development of papilledema and optic nerve sheath extension in the setting of intracranial pressure elevation in children

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          Abstract

          Introduction

          Dilatation of the optic nerve sheath diameter and swelling of the optic disc are known phenomena associated with intracranial pressure elevation.

          Research question

          Do sex and disease etiology have an impact on the development of optic disc elevation and optic nerve sheath extension in children in the setting of ICP elevation? Fundoscopic papilledema and point-of-care-ultrasound techniques-optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE) - were compared in this regard.

          Material and methods

          72 children were included in this prospective study; 50 with proven pathology (e.g. pseudotumor cerebri, tumor), 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array-transducer. This was compared with fundoscopic optic disc findings and in 28 patients with invasive ICP values, stratified for sex and etiology.

          Results

          In patients with proven disease, significant more girls (69%) had fundoscopic papilledema compared with boys (37%, p < 0.05). Girls had also larger US-ODE values (0.86 ± 0.36 mm vs. 0.65 ± 0.40 mm in boys). 80% of tumor patients had initial papilledema (100% girls, 79% boys), compared with 50% in pseudotumor cerebri (PTC) (83% girls, 30% boys). US-ONSD had no sex- and no etiology-specificity.

          Discussion and conclusion

          Presence of papilledema appears to be influenced by sex and etiology, whereas US-ONSD is not. Girls seem more likely to develop papilledema under similar conditions. Male sex and PTC appear as risk factors for being undetected by fundoscopic findings. US-ONSD and US-ODE seem useful tools to identify pathologies with potentially increased ICP requiring treatment in children regardless of sex and etiology.

          Highlights

          • •

            The reliability of US-ONSD to estimate ICP is independent of sex and etiology.

          • •

            Sex and etiology seem to influence papilledema/optic disc elevation in children.

          • •

            US-ODE is a quantifiable, sex independent option to detect ICP increase in children.

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          Most cited references39

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          Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children.

          Deborah Friedman, Grant Liu, Kathleen B. Digre (2013)
          The pseudotumor cerebri syndrome (PTCS) may be primary (idiopathic intracranial hypertension) or arise from an identifiable secondary cause. Characterization of typical neuroimaging abnormalities, clarification of normal opening pressure in children, and features distinguishing the syndrome of intracranial hypertension without papilledema from intracranial hypertension with papilledema have furthered our understanding of this disorder. We propose updated diagnostic criteria for PTCS to incorporate advances and insights into the disorder realized over the past 10 years.
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            Pathogenesis of optic disc edema in raised intracranial pressure.

            Sohan Hayreh (2016)
            Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure.
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              Swelling of the optic nerve head: a staging scheme

              L Frisén (1982)
              Article 0 comments Cited 60 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Susanne Regina Kerscher
                Journal
                Journal ID (nlm-ta): Brain Spine
                Journal ID (iso-abbrev): Brain Spine
                Title: Brain & Spine
                Publisher: Elsevier
                ISSN (Electronic): 2772-5294
                Publication date PMC-release: 12 December 2023
                Publication date Collection: 2024
                Publication date (Electronic): 12 December 2023
                Volume: 4
                Electronic Location Identifier: 102729
                Affiliations
                [a ]Department of Neurosurgery and Neurotechnology, Division of Pediatric Neurosurgery, University Hospital of Tuebingen, Germany
                [b ]Department of Diagnostic and Interventional Radiology, University Hospital Ulm, Germany
                [c ]Department of Pediatric Neurology and Developmental Medicine, University Children’ s Hospital of Tuebingen, Germany
                Author notes
                [∗ ]Corresponding author. Department of Neurosurgery and Neurotechnology, Division of Pediatric Neurosurgery, University Hospital of Tuebingen, Germany. susanne.kerscher@ 123456uniklinik-ulm.de
                Article
                Publisher Item ID: S2772-5294(23)01017-2 Publisher ID: 102729
                DOI: 10.1016/j.bas.2023.102729
                PMC ID: 10951694
                PubMed ID: 38510611
                SO-VID: 7b9946aa-03da-4e52-bd6f-4dc0d8ac3588
                Copyright © © 2023 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 8 June 2023
                Date revision received : 3 December 2023
                Date accepted : 8 December 2023
                Categories
                Subject: Article

                Keywords: optic nerve sheath diameter,onsd,fundoscopy,sex-specificity,etiology-specificity,icp
                Data availability:
                Keywords: optic nerve sheath diameter, onsd, fundoscopy, sex-specificity, etiology-specificity, icp

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