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Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity., Methods: This is a prospective case-control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry., Results: Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate-severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = -0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH., Interpretation: We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595-607., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy., Objective: To provide evidence-based, accurate MRI signs for IIH diagnosis., Design, Setting, and Participants: This prospective cohort study was conducted from January 2018 to May 2021 with 3 validation cohorts at 2 Danish headache centers and with 3 independent international cohorts. Consecutive patients with suspected IIH were enrolled. Eligibility required the clinical suspicion of IIH, age 18 years or older, and written informed consent. The validation cohorts comprised patients with confirmed IIH from Austria and the US, and patients without IIH from the US. Data analysis was performed from December 2021 to August 2023., Exposure: Standardized diagnostic workup was performed to classify cases according to current criteria, and blinded evaluation of cerebral radiological diagnostics and papilledema was performed., Main Outcomes and Measures: The primary outcomes were MRI signs associated with IIH as assessed by univariate analyses. An MRI score estimating papilledema was calculated using machine learning. Internal validation of associations with lumbar puncture opening pressure and outcome and external validation of accuracy were performed in 3 cohorts., Results: Of 192 eligible patients (185 women [96.4%]; median [IQR] age, 28.0 [23.0-35.0] years), 110 were classified as having IIH, 4 as having probable IIH, and 1 as having suspected IIH without papilledema; 77 did not have IIH and served as controls, with corresponding age, sex, and weight. Papilledema at diagnosis was associated with perioptic subarachnoid space distension (56 patients [68.3%] vs 21 patients [41.2%]), posterior globe flattening (53 patients [66.3%] vs 10 patients [21.3%]), optic nerve disc protrusion (35 patients [30.4%] vs 2 patients [2.3%]), and transverse sinus venous stenosis (75 patients [79.8%] vs 29 patients [46.8%]). The papilledema-estimating MRI score showed optimal balance between sensitivity (49%) and specificity (87%) when 2 of the 3 latter signs were present and was associated with the lumbar puncture opening pressure and ophthalmological outcome. The score showed strong diagnostic accuracy in the external validation cohorts (587 patients; area under the receiver operating characteristic curve, 0.86) and outperformed the current (2013) diagnostic MRI criteria., Conclusions and Relevance: The findings of this cohort study of patients with IIH and controls suggest that an evidence-based MRI score including posterior globe flattening, optic nerve disc protrusion, and transverse sinus stenosis can estimate the presence of papilledema more accurately than the current diagnostic criteria.

Background: Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension., Methods: Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure., Results: We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aβ-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aβ-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001)., Conclusions: cNfL, pNfL and total-tau/Aβ-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KS: No conflicts of interest. JJK: Received funding from the Lundbeck Foundation, Rigshospitalet-Glostrup and Odense University Hospital. RHJ: Paid lectures for Pfizer, Eli-Lilly, Merck, TEVA, Novartis, Lundbeck and Allergan. Investigator in clinical trials with Eli-Lilly, Novartis and Lundbeck; Director of Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen. Recived research funding from University of Copenhagen, Rigshospitalet, Lundbeck Foundation, The Medical Society in Copenhagen, NovoNordisk Foundation and Tryg Foundation. TP: No conflicts of interest. CSK: No conflicts of interest. SGH: No conflicts of interest. SMH: No conflicts of interest. EAW: Medical Advisory Board for StatuManu ICP ApS. Received research funding from Øjenforeningen (Fight for Sight, Denmark) and the Synoptik Foundation. LDM: No conflicts of interest. DB: Presentations (TEVA, Novartis, Pfizer), Travel Support (Allergan, TEVA, Pfizer, Abbvie), Advisory Boards (Novartis, Lilly, Teva, Lundbeck, Pfizer, Abbvie) and Participations in clinical trials (TEVA, Lundbeck, Novartis, Lilly, Novo Nordic Foundation) outside the submitted work (other headache disorders), receiving grants from Odense University Hospital and Rigshospitalet, University of Copenhagen during the conduction of the work.

Background: Headache burden is substantial in idiopathic intracranial hypertension. The classification of idiopathic intracranial hypertension headache by the International Classification of Headache Disorders (ICHD) is an important tool for research and clinical purposes., Methods: We phenotyped headaches and tested sensitivity and specificity of the ICHD-3 criteria for idiopathic intracranial hypertension headache in a prospective cohort of patients suspected of idiopathic intracranial hypertension at two tertiary headache centers., Results: Sensitivity was 93% and specificity was 100% of ICHD-3 criteria for idiopathic intracranial hypertension-related headache validated in idiopathic intracranial hypertension ( n  = 140) and patients in whom idiopathic intracranial hypertension was suspected but disproven ( n =  103). The phenotype of new/worsened headaches related to idiopathic intracranial hypertension suspicion was equally migraine-like (p = 0.76) and tension-type-like (p = 0.08). Lumbar puncture opening pressure was higher ( p  < 0.0001) and pulsatile tinnitus more frequent ( p  < 0.0001) in idiopathic intracranial hypertension patients, but neither improved the applicability of the headache criteria, nor did papilledema., Conclusion: Headache phenotype is not distinct in idiopathic intracranial hypertension. ICHD-3 criteria for idiopathic intracranial hypertension headache are sensitive and specific, but simplicity can be improved without compromising accuracy. We propose that a new or worsened headache temporally related to active idiopathic intracranial hypertension is a sufficient criterion for idiopathic intracranial hypertension headache regardless of headache phenotype or accompanying symptoms, and that elements of idiopathic intracranial hypertension diagnostics (papilledema and opening pressure) be segregated from headache criteria. Trial Registration: ClinicalTrials.gov Identifier: NCT04032379., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NSH received funding from the Novo Nordic Foundation during the conduction of the work and gave lectures for Pfizer, University of Southern Denmark, and University of Copenhagen. JJK received funding from the Lundbeck Foundation, Rigshospitalet-Glostrup, and Odense University hospital for the duration of the study. HMY received support from Abbvie for participation in non-related courses. RHJ gave lectures for Pfizer, Eli-Lilly, Merck, TEVA, Novartis, Lundbeck and Allergan; was investigator in clinical trials with Eli-Lilly, Novartis and Lundbeck. She is the Director of Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen and received research funding from University of Copenhagen, Rigshospitalet, Lundbeck Foundation, The Medical Society in Copenhagen, NovoNordisk Foundation and Tryg Foundation. DB gave lectures for TEVA, Novartis, Pfizer. Received travel support from Allergan, TEVA, Pfizer, Abbvie; was in advisory boards for Novartis, Lilly, Teva, Lundbeck, Pfizer, Abbvie and participated in clinical trials for TEVA, Lundbeck, Novartis, Lilly, Novo Nordic Foundation outside the submitted work. Received grants from Odense University Hospital and Rigshospitalet, University of Copenhagen during the conduction of the work.

Background: Idiopathic intracranial hypertension (IIH) occurs more frequently in obese females of childbearing age. A link between eating disorders and poor outcome has been suggested but remains unproven., Methods: This prospective field study at two tertiary headache centers included patients with clinically suspected IIH after standardized diagnostic work-up. Eating disorders were evaluated using validated questionnaires (EDQs). Primary outcome was the impact of eating disorders on IIH severity and outcome, secondary outcome was the prevalence and type of eating disorders in IIH compared to controls., Results: We screened 326 patients; 143 patients replied to the EDQs and were classified as 'IIH' or 'non-IIH' patients. The demographic profile of EDQ-respondents and non-respondents was similar. Presence of an eating disorder did not impact IIH severity (lumbar puncture opening pressure (p = 0.63), perimetric mean deviation (p = 0.18), papilledema (Frisén grad 1-3; p = 0.53)) nor IIH outcome (optic nerve atrophy (p = 0.6), impaired visual fields (p = 0.18)). Moreover, we found no differences in the prevalence and type of eating disorders when comparing IIH with non-IIH patients (p = 0.09)., Conclusion: Eating disorders did not affect IIH severity or outcome. We found the same prevalence and distribution pattern of eating disorders in IIH and non-IIH patients advocating against a direct link between IIH and eating disorders., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.W.: No conflicts of interest. J.L.: No conflicts of interest. M.B.L.: No conflicts of interest. N.S.H.: Received funding from the Novo Nordic Foundation (NNF20OC0065926) during the conduction of the work and gave lectures for Pfizer, University of Southern Denmark, and University of Copenhagen. J.J.K.: Received funding from the Lundbeck Foundation, Odense University Hospital and Rigshospitalet during the study. L.H.: No conflicts of interest. S.M.H.: Received grants from Fight for Sight, Denmark and the Synoptik Foundation. L.D.M.: No conflicts of interest. R.H.J.: Gave lectures for Pfizer, Eli-Lilly, ATI, Merck, TEVA, Novartis, Lundbeck and Allergan. Investigator in clinical trials with ATI, Eli-Lilly, Novartis and Lundbeck. Director of Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen. Recived research funding from University of Copenhagen, Rigshospitalet, ATI, Lundbeck Foundation, The Medical Society in Copenhagen, NovoNordisk Foundation and Tryg Foundation. D.B.: Participated in clinical trials and served with lectures as well as on advisory or speaker boards for Novartis, Eli Lilly, Lundbeck, Pfizer, Abbvie and Teva outside the submitted work (migraine). Received grants from Odense University Hospital and Rigshospitalet, University of Copenhagen during the conduct of the study.

Background and Objectives: Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure without an identifiable cause that mostly affects obese persons of childbearing age. In this prospective case series, we have evaluated the overall outcome of pregnancy and birth in participants with IIH and their newborn children. We also provide a proposal for the management of pregnant persons with IIH., Methods: In this observational study, neuro-ophthalmological findings, the course of IIH-related symptoms, disease management, and pregnancy outcomes were evaluated. The participants were divided into 3 groups according to the course of the disease during pregnancy: stable, worsened, and new diagnosed. Furthermore, the type of delivery and outcome of newborn children such as gestational age, weight at birth, and the presence of asphyxia were compared between the groups., Results: We observed 47 pregnancies in 42 participants; 2 had spontaneous abortions. There were 19 (47%) participants in the stable, 18 (45%) in the worsened, and 3 (8%) in the new diagnosed groups, respectively. A relapse of IIH occurred in 2 (5%). Worsening of IIH-related symptoms was experienced by 18/37 (49%) participants: headache by 17/18 (94%), tinnitus by 11/18 (61%), and vision by 7/18 (39%) (mostly in the first and second trimester). In 8/18 (44%), the symptoms were transient or alleviated in the second and third trimester. Body mass index before and after pregnancy did not significantly differ among the groups. A total of 8 participants were treated with acetazolamide. The frequency of cesarean section was 17/40 (43%). Preterm delivery occurred in 22%. No increased risk of asphyxia was observed, and all infants, but one, were healthy., Discussion: Worsening of headache, tinnitus, and/or vision were experienced by half of pregnant participants with IIH, mostly transient in the first and second trimester, rarely required specific treatment, and were not identified as a relapse of IIH. There was no difference in gestational age and weight at birth in children among the groups, and no perinatal asphyxia was noted. Weight gain in the participants was not identified as a risk factor for relapse of IIH in pregnancy. The rate of cesarean and preterm delivery was higher than in the non-IIH population. A proposal for the management of IIH in pregnancy is provided., Competing Interests: V. Vukovic-Cvetkovic: lectures for Novartis, Merck, and MSD and investigator in clinical trials with Lundbeck and Allergan. D. Beier: advisory board of Pfizer, Lundbeck, AbbVie, Novartis, Eli Lilly and Company, and Teva and participation in clinical trials of Teva, Lundbeck, and Novartis. L. Buchgreitz: lecture for AbbVie/Allergan. J.J. Korsbæk: funding from Lundbeck of Candy Foundation. R. Jensen: lectures for Pfizer, Eli Lilly and Company, Merck, TEVA, Novartis, Lundbeck, and Allergan; investigator in clinical trials with Eli Lilly and Company, Novartis, and Lundbeck; director of Danish Headache Center and Lifting The Global Burden of Headache; founder of Master of Headache Disorders at the University of Copenhagen; and received research funding from the University of Copenhagen, Rigshospitalet, Lundbeck Foundation, The Medical Society in Copenhagen, The Capital Region, Novo Nordisk Foundation, and Tryg Foundation. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Background and Purpose: There is a need to improve the diagnostic process of patients suspected of papilledema. In patients with known or suspected idiopathic intracranial hypertension a fundus imaging and perimetric visual field assessment system (COMPASS) performed at a headache center was validated in comparison to an assessment (Topcon plus OCTOPUS) at a neuroophthalmological clinic., Methods: For intermethod assessment, blinded fundus images and perimetry from COMPASS versus Topcon plus OCTOPUS were assessed by a neuroophthalmologist. For interrater assessment, fundus images and perimetry obtained by the COMPASS system were assessed by an untrained medical doctor, a trained neurologist and a trained medical student and compared to the neuroophthalmologist's assessments., Results: For the intermethod variation of the presence of papilledema on fundus images, a kappa value of 0.60, sensitivity of 87% and specificity of 73% were found. The interrater variation of the presence of papilledema on fundus images showed kappa values ranging from 0.43 to 0.74, sensitivity values ranging from 70% to 96% and specificity values ranging from 46% to 93% when comparing the assessments made by the headache center staff with neuroophthalmologist's assessments. The COMPASS showed a 59% sensitivity and moderate agreement in detecting visual field defects compared with OCTOPUS. The visual field assessment showed only slight to fair agreement from 0.19 to 0.31 between assessments made by the headache center staff and the neuroophthalmologist., Conclusion: The COMPASS system can be used with reasonable sensitivity in the assessment of papilledema in patients suspected of idiopathic intracranial hypertension at a tertiary headache center., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension., Methods: Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure., Results: Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with ( n  = 17) and without ( n  = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p  = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate -0.0043 (95% CI -0.0073 to -0.0023), p  = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H 2 O) (slope regression estimate -0.0080 (95% CI -0.0123 to -0.0039), p  < 0.001). Estimated cerebrospinal fluid pressure predicted increased lumbar opening pressure >20 mm Hg (27 cm H 2 O) with 78% sensitivity and 92% specificity (AUC 0.81, p  = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H 2 O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p =  0.002)., Conclusion: Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.

Background: Based on expert opinion, abducens nerve palsy and a neuroimaging criterion (≥3 neuroimaging signs suggestive of elevated intracranial pressure) were added to the diagnostic criteria for idiopathic intracranial hypertension. Our objective was to validate this., Methods: This prospective study included patients with new-onset idiopathic intracranial hypertension for a standardized work-up: interview, neuro-ophthalmological exam, lumbar puncture, neuroimaging. Neuroimaging was evaluated by a blinded neuroradiologist., Results: We included 157 patients classified as idiopathic intracranial hypertension (56.7%), probable idiopathic intracranial hypertension (1.9%), idiopathic intracranial hypertension without papilledema (idiopathic intracranial hypertension-without papill edema; 0%), suggested idiopathic intracranial hypertension-without papill edema (4.5%), or non-idiopathic intracranial hypertension (36.9%). Moderate suprasellar herniation was more common in idiopathic intracranial hypertension than non-idiopathic intracranial hypertension (71.4% versus 47.4%, p < 0.01), as was perioptic nerve sheath distension (69.8% versus 29.3%, p < 0.001), flattening of the globe (67.1% versus 11.1%, p < 0.001) and transverse sinus stenosis (60.2% versus 18.9%, p < 0.001). Abducens nerve palsy was of no diagnostic significance. Sensitivity of ≥3 neuroimaging signs was 59.5% and specificity was 93.5%., Conclusion: Moderate suprasellar herniation, distension of the perioptic nerve sheath, flattening of the globe and transverse sinus stenosis were associated with idiopathic intracranial hypertension. We propose that idiopathic intracranial hypertension can be defined by two out of three objective findings (papilledema, opening pressure ≥25 cm cerebrospinal fluid and ≥3 neuroimaging signs).

Objective: To identify the most frequent causes of secondary pseudotumor cerebri syndrome and compare phenotype, clinical presentation, and symptoms of secondary pseudotumor cerebri syndrome to the primary form of pseudotumor cerebri syndrome, idiopathic intracranial hypertension., Methods: The study was a prospective cohort study including patients with new-onset pseudotumor cerebri syndrome. Diagnostic work up was standardized. Patients were diagnosed with secondary pseudotumor cerebri syndrome or idiopathic intracranial hypertension according to the revised Friedman criteria. Secondary pseudotumor cerebri syndrome patients were categorized into five causes: medication, systemic causes, sleep apnea, cerebrovascular causes, and several competing causes. Phenotype, clinical presentation, symptoms and neuroimaging were compared between groups., Results: Out of 278 cases, 28 secondary pseudotumor cerebri syndrome and 120 idiopathic intracranial hypertension patients were included. The most frequent causes of secondary pseudotumor cerebri syndrome were medication (n  =  8, 28.6%) and systemic causes (n = 8, 28.6%), followed by sleep apnea (n = 5, 17.9%), cerebrovascular causes (n = 4, 14.3%) and several competing causes (n = 3, 10.7%). Secondary pseudotumor cerebri syndrome and idiopathic intracranial hypertension patients were phenotypically alike and predominately female, premenopausal, and obese. Symptoms and objective findings at disease onset were similar between groups., Conclusion: Secondary pseudotumor cerebri syndrome should be considered in all patients with suspected pseudotumor cerebri syndrome as secondary pseudotumor cerebri syndrome and idiopathic intracranial hypertension patients are phenotypically and clinically alike. A thorough diagnostic workup is needed as treatment of idiopathic intracranial hypertension and secondary pseudotumor cerebri syndrome is markedly different.

Background: Our objective was to assess optic nerve sheath diameter (a marker of elevated intracranial pressure) and optic disc elevation (a marker of papilledema) in pseudotumor cerebri syndrome using transorbital sonography., Methods: The study was a prospective case-control study. We included patients with new-onset pseudotumor cerebri syndrome and matched healthy controls. All had fundoscopy, lumbar puncture with opening pressure and transorbital sonography. Sonography was assessed by a blinded observer., Results: We evaluated 45 patients and included 23 cases. We recruited 35 controls. Optic nerve sheath diameter was larger in pseudotumor cerebri syndrome compared to controls (6.3 ± 0.9 mm versus 5.0 ± 0.5 mm, p < 0.001) and so was optic disc elevation (0.9 ± 0.4 mm versus 0.4 ± 0.1 mm, p < 0.001). The optimal cut-off point for optic nerve sheath diameter was 6 mm with a sensitivity of 74% for prediction of pseudotumor cerebri syndrome and 68% for prediction of elevated opening pressure. Specificity was 94%. The optimal cut-off point for optic disc elevation was 0.6 mm. Sensitivity was 100% and specificity 83% for prediction of pseudotumor cerebri syndrome., Conclusion: Optic disc elevation and optic nerve sheath diameter are increased in new-onset pseudotumor cerebri syndrome. Optic disc elevation achieved high specificity and excellent sensitivity for diagnosis of pseudotumor cerebri syndrome. Transorbital sonography (TOS) is a potential, non-invasive screening tool for pseudotumor cerebri syndrome in headache clinics.

Background and Objectives: Psychiatric disease is a frequent comorbidity in idiopathic intracranial hypertension (IIH) and has been associated with a poor subjective outcome. No prospective studies have investigated psychiatric comorbidities in new-onset IIH. Our primary aim was to investigate disease severity in IIH depending on comorbid psychiatric disease. Important secondary outcomes were disease severity after 6 months and prevalence of psychiatric diseases in IIH., Methods: This prospective, observational cohort study consecutively included patients with clinically suspected, new-onset IIH from 2 headache centers. A standardized diagnostic workup was completed to confirm or exclude IIH according to the revised Friedman criteria: semi-structured interview, neurologic and neuro-ophthalmologic examination, lumbar puncture with opening pressure (OP), and neuroimaging. Exclusion criteria were known IIH, secondary intracranial hypertension, missing data, and pregnancy. Disease severity was evaluated based on papilledema, visual fields, OP, and headache in patients with IIH without psychiatric disease (IIH-P) compared with patients with IIH with psychiatric disease (IIH+P). A blinded neuro-ophthalmologist assessed visual outcomes. Age- and sex-matched prevalence rates of psychiatric diseases in the general population were found in national reports., Results: A total of 258 patients were screened; 69 were excluded. A total of 189 patients with clinically suspected IIH were then evaluated with the diagnostic workup and IIH was confirmed in 111 patients (58.7%). A total of 45% of patients with IIH had a psychiatric comorbidity. Visual fields were worse in patients with IIH+P at baseline (-8.0 vs -6.0 dB; p = 0.04) and after 6 months (-5.5 vs -4.0 dB; p < 0.01) compared with IIH-P. Highly prevalent psychiatric disorders were major depressive disorder (24.3%; n = 27), anxiety or stress-related disorders (24.3%; n = 27), and emotionally unstable personality disorder (6.3%; n = 7). Substance abuse (1.8%), schizophrenia (0.9%), and bipolar disorder (0.9%) were rare. In the general population, prevalence estimates of major depressive disorder and emotionally unstable personality disorder were 1.8%-3.3% and 2%, respectively., Discussion: Visual fields were significantly worse at baseline and 6 months in IIH+P compared with IIH-P. Psychiatric comorbidities, particularly depression and emotionally unstable personality disorder, were highly prevalent in IIH. Increased awareness of psychiatric disease as a marker for worse visual status may improve patient care., (© 2022 American Academy of Neurology.)

Background: Idiopathic intracranial hypertension is characterized by increased intracranial pressure without any pathological findings on neuroimaging, except for signs of high intracranial pressure. Before diagnosing idiopathic intracranial hypertension secondary causes of increased intracranial pressure should be excluded., Objective: to characterize the phenotype of patients with secondary intracranial hypertension and to identify possible risk factors for secondary intracranial hypertension., Methods: We have systematically searched the PubMed database. The publications were analyzed according to the patient phenotype, age, gender, comorbidities, body mass index/weight status, and additional medication. The results are summarized in four categories: medication, infection, hormonal induced intracranial hypertension and miscellaneous groups of diseases related to sIH., Results: We identified 105 eligible papers which included 272 cases. There were 49.6% pediatric cases. Among the adult group,70.9% were women. A total of 40.4% of all cases were obese or overweight, 27% among adults and 13.4% among pediatric cases. Increased BMI and recent weight gain, anemia, renal diseases and hypertension were the most frequent comorbidities related to sIH., Conclusion: Among sIH patients, 40.4% were obese or overweight; two thirds were women. We recommend that even patients with a typical IIH phenotype should be screened for secondary causes.

Idiopathic intracranial hypertension (IIH) is a challenging disease characterized by an increase in intracranial pressure which occurs without any known cause. The disease is mainly seen in obese females of child-bearing age. While originally described as rare, the incidence is increasing in parallel with pandemic obesity, and clinicians in all fields are increasingly likely to meet patients with IIH. The condition causes major morbidity due to chronic headache and visual loss if untreated. In the past ten years new diagnostic criteria and guidelines for management have been published.

The diagnosis and management of idiopathic intracranial hypertension (IIH) can be difficult and multiple medical subspecialities are often involved. Several national and international guidelines regarding the investigations and management of IIH have been published in recent years but still there is no consensus about the optimal organization of IIH-care. The objective of this review was to propose and describe a referral pathway and an organization scheme for diagnosis and management of IIH. An extensive search of existing literature was conducted and summarized. In total, 237 IIH-articles were identified and hereof 43 included. The clinical practice in our specialized IIH-clinic is characterized and described. We conclude that an educational campaign involving medical care providers and patients with chronic headaches is necessary. A detailed organizational proposal for a referral pathway and management of IIH patients based on the literature search and our clinical experience from a highly specialized IIH outpatient clinic is suggested and discussed.

Background: Damage of the optic nerve is the major complication of idiopathic intracranial hypertension. A biomarker indicative for optic nerve damage would help identifying high-risk patients requiring surgical procedures. Here, we studied the potential of cerebrospinal fluid neurofilament to predict idiopathic intracranial hypertension-induced optic nerve damage., Methods: In two centers, serum and cerebrospinal fluid of 61 patients with clinically suspected idiopathic intracranial hypertension were prospectively collected. Neurofilament concentrations were measured and related to ophthalmological assessment., Results: The average cerebrospinal fluid neurofilament concentration in patients with moderate and severe papilledema was increased compared to patients with minor and no papilledema (1755 ± 3507 pg/ml vs. 244 ± 102 pg/ml; p  < 0.001). Cerebrospinal fluid neurofilament concentrations correlated with the maximal lumbar puncture opening pressure (r = 0.67, p  < 0.001). In patients fulfilling the Friedman criteria for idiopathic intracranial hypertension with or without papilledema (n = 35), development of bilateral visual field defects and bilateral atrophy of the optic nerve were associated with increased average age-adjusted cerebrospinal fluid neurofilament concentrations. At last follow-up (n = 30), 8/13 of patients with increased, but only 3/17 with normal, cerebrospinal fluid neurofilament had developed bilateral visual field defects and/or bilateral optic nerve atrophy resulting in a sensitivity of 72.7% and a specificity of 73.7% of cerebrospinal fluid neurofilament to detect permanent optic nerve damage., Conclusions: Cerebrospinal fluid neurofilament is a putative biomarker for optical nerve damage in idiopathic intracranial hypertension.