Magnetic Resonance Imaging Signs of Idiopathic Intracranial Hypertension.

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.

Neurofilament light chain is elevated in patients with newly diagnosed idiopathic intracranial hypertension: A prospective study.

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 (Aß-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/Aß-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aß-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/Aß-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.

Diagnosis of idiopathic intracranial hypertension: A proposal for evidence-based diagnostic criteria.

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).

Psychiatric Comorbidities in Patients With Idiopathic Intracranial Hypertension: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Psychiatric disease is a frequent co-morbidity in idiopathic intracranial hypertension (IIH) and has been associated with a poor subjective outcome. No prospective studies have investigated psychiatric co-morbidities in new-onset IIH. Our primary aim was to investigate disease severity in IIH depending on co-morbid 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 two headache centers. A standardized diagnostic work-up was completed to confirm or exclude IIH according to the revised Friedman criteria: semi-structured interview, neurological and neuro-ophthalmological exam, lumbar puncture with opening pressure, neuroimaging. Exclusion criteria were known IIH, secondary intracranial hypertension, missing data, pregnancy. Disease severity was evaluated based on papilledema, visual fields, opening pressure and headache in IIH patients without psychiatric disease (IIH-P) compared to IIH patients 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: 258 patients were screened, 69 were excluded. 189 patients with clinically suspected IIH were then evaluated with the diagnostic work-up, and IIH was confirmed in 111 patients (58.7%). 45% of IIH patients had a psychiatric co-morbidity. Visual fields were worse in patients with IIH+P at baseline (-8.0 versus -6.0 dB, p = 0.04) and after 6 months (-5.5 versus -4.0 dB, p < 0.01) compared to 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 to IIH-P. Psychiatric co-morbidities, 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.

Endonasal Endoscopic Approach for Minimally Invasive Orbital Decompression in Nonthyroid Proptosis-A Scoping Review.

OBJECTIVE: The endoscopic endonasal approach (EEA) was originally performed to treat thyroid orbitopathy and proptosis. Since then, this approach also has been used to treat other causes of proptosis. This review systematically identifies surgical outcome and complication rates in patients without thyroid proptosis who underwent endoscopic endonasal orbital decompression. METHODS: Databases were searched using the following search terms: orbital disease, surgical decompression, and endoscopic endonasal approach. Two independent reviewers screened all abstracts and titles for relevance and all articles passing this screen were subjected to full-text review. To assess risk of bias, we used ROBINS-I (Risk Of Bias in Non-randomized Studies-of Interventions). RESULTS: Eight studies with a total of 74 patients with nonthyroid proptosis were included. Pre- and postoperative eye examination was performed in all studies, but the extent of examination was varying. With a mean age of 35.7 years, most patients were adolescent, and most pathologies induced unilateral proptosis Complications to EEA for orbital decompression were transient diplopia (5 patients/6.8%), transient facial dysesthesia (2 patients/2.7%), ptosis (1 patient/1.4%), infarction (1 patient/1.4%), sinus obstruction (1 patient/1.4%), and enophtalmos (1 patient/1.4%). The authors reported successful reduction of proptosis in all but 2 patients (97.2%), and only 2 authors reported a need for secondary decompression. CONCLUSIONS: Medial orbital decompression using EEA is a feasible approach for orbital decompression in patients with nonthyroid proptosis. While being comparable in primary outcome to transorbital approaches, the EEA seems superior in terms of complication rates.

[Orbital decompression in non-thyroid-associated diseases].

Hypoxia triggers hypoxia-inducible factor (HIF). Not only hypoxia triggers downstream HIF target genes for transcription, as intermittent hyperoxia also possesses similar capabilities, suggesting that fluctuations in oxygen availability may be equally important for inducing HIF transcription. This review describes some of the mechanisms, whereby intermittent hyperbaric hyperoxia may explain some of the observations during hyperbaric oxygen therapy such as enhanced wound healing, angiogenesis and tissue healing, and concludes that oxidative stress enhances certain antibiotics in infection control.

Neurofilament light chain as biomarker in idiopathic intracranial hypertension.

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.