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.

Idiopathic intracranial hypertension associated with SARS-CoV-2 infection in an adult male patient: a case report and review of the literature.

BACKGROUND: Headache is a frequent symptom in coronavirus disease 2019 (COVID-19) patients, and idiopathic intracranial hypertension (pseudotumor cerebri) has been reported among patients who underwent lumbar puncture for persistent headaches. CASE PRESENTATION: A 45-year-old black man presented with dyspnea, cough, fever and headache for 05 days followed by blurring of vision associated with worsening of the headache. Physical examination was significant for tachypnea and oxygen desaturation and there were no abnormal neurologic findings. He tested positive for SARS-CoV-2 with nasopharyngeal swab PCR. His CSF opening pressure appeared high with normal CSF analysis and brain magnetic resonance imaging (MRI) revealed prominent subarachnoid space around the optic nerves and bilateral papilledema. He had significant improvement with medical therapy alone. CONCLUSION: Idiopathic intracranial hypertension (IIH) may occur in association with SARS-CoV-2 infection and should be considered when making a differential diagnosis for headache and blurring of vision. COVID-19 may play a role in the development of intracranial hypertension, even in the absence of known risk factors. Early diagnosis and treatment of IIH has paramount importance to prevent vision loss and other morbidities.

Are the ICHD-3 criteria for headache attributed to idiopathic intracranial hypertension valid? Headache phenotyping and field-testing in newly diagnosed idiopathic intracranial hypertension.

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.

Foundations of the Diagnosis and Management of Idiopathic Intracranial Hypertension and Pulsatile Tinnitus.

Venous sinus stenosis has garnered increasing academic attention as a potential etiology of idiopathic intracranial hypertension (IIH) and pulsatile tinnitus (PT). The complex anatomy of the cerebral venous sinuses and veins plays a crucial role in the pathophysiology of these conditions. Venous sinus stenosis, often found in the superior sagittal or transverse sinus, can lead to elevated intracranial pressure (ICP) and characteristic IIH symptoms. Stenosis, variations in dural venous anatomy, and flow dominance patterns contribute to aberrant flow and subsequent PT. Accurate imaging plays a vital role in diagnosis, and magnetic resonance (MR) venography is particularly useful for detecting stenosis. Management strategies for IIH and PT focus on treating the underlying disease, weight management, medical interventions, and, in severe cases, surgical or endovascular procedures. Recently, venous sinus stenting has gained interest as a minimally invasive treatment option for IIH and PT. Stenting addresses venous sinus stenosis, breaking the feedback loop between elevated ICP and stenosis, thus reducing ICP and promoting cerebrospinal fluid outflow. The correction and resolution of flow aberrances can also mitigate or resolve PT symptoms. While venous sinus stenting remains an emerging field, initial results are promising. Further research is needed to refine patient selection criteria and evaluate the long-term efficacy of stenting as compared to traditional treatments.

Challenges in the use of Venous Sinus Stenting in the Treatment of Idiopathic Intracranial Hypertension and Pulsatile Tinnitus.

Although numerous case series and meta-analyses have shown the efficacy of venous sinus stenting (VSS) in the treatment of idiopathic intracranial hypertension and idiopathic intracranial hypertension-associated pulsatile tinnitus, there remain numerous challenges to be resolved. There is no widespread agreement on candidacy; pressure gradient and failed medical treatment are common indications, but not all clinicians require medical refractoriness as a criterion. Venous manometry, venography, and cerebral angiography are essential tools for patient assessment, but again disagreements exist regarding the best, or most appropriate, diagnostic imaging choice. Challenges with the VSS technique also exist, such as stent choice and deployment. There are considerations regarding postprocedural balloon angioplasty and pharmacologic treatment, but there is insufficient evidence to formalize postoperative decision making. Although complications of VSS are relatively rare, they include in-stent stenosis, hemorrhage, and subdural hematoma, and the learning curve for VSS presents specific challenges in navigating venous anatomy, emphasizing the need for wider availability of high-quality training. Recurrence of symptoms, particularly stent-adjacent stenosis, poses challenges, and although restenting and cerebrospinal fluid-diverting procedures are options, there is a need for clearer criteria for retreatment strategies. Despite these challenges, when comparing VSS with traditional cerebrospinal fluid-diverting procedures, VSS emerges as a favorable option, with strong clinical outcomes, lower complication rates, and cost-effectiveness. Further research is necessary to refine techniques and indications and address specific aspects of VSS to overcome these challenges.

Impact of Ramadan fasting on vision and headache-related quality of life in women with idiopathic intracranial hypertension: A prospective observational study.

BACKGROUND: Ramadan fasting is an obligatory religious practice for Muslims. However, research data on the effect of Ramadan on idiopathic intracranial hypertension (IIH) symptoms are lacking. This study aimed to study the effect of Ramadan fasting on the severity of headache and visual symptoms and related quality-of-life activities. METHODS: This prospective cohort study targeted females diagnosed with IIH (n = 102) who were eligible to fast for Ramadan in 2023. The patients were recruited from the Neurology Clinic in Beni-Suef University Hospital, Egypt. Body mass index (BMI), monthly headache days and intensity of headache attacks, six-item Headache Impact Test (HIT-6), and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores during Ramadan were compared to those during the (non-fasting) month of Shaaban, the preceding month to Ramadan. RESULTS: There was a significant increase in the BMI of patients with IIH in Ramadan compared to the (non-fasting) month of Shaaban, at a median (interquartile range [IQR]) of 30.5 (26.6-35.8) kg/m2 and 30.1 (26.6-35.2) kg/m2, respectively (p = 0.002). The median (IQR) value of monthly headache days was significantly increased during Ramadan in comparison to the (non-fasting) month of Shaaban, at 20 (11.5-30) vs. 15 (10-25) (p < 0.001). There was a statistically significant worsening in the visual analog scale (VAS) scores (median [IQR] 7 [5-8] vs. 6.5 [5-8]), HIT-6 scores (median [IQR] 61 [58-67] vs. 59 [53-61.5]), and NEI-VFQ-25 total scores (median [IQR] 1312.5 [1238.8-1435] vs 1290 [1165-1417.5]) during Ramadan in comparison to the (non-fasting) month of Shaaban (p < 0.001 for all comparisons). The change in BMI in Ramadan was positively correlated with the change in monthly headache days (r = 0.24, p = 0.014), VAS (r = 0.20, p = 0.043), HIT-6 (r = 0.25, p = 0.010) and NEI-VFQ-25 scores (r = 0.24, p = 0.016). CONCLUSION: Ramadan fasting had an aggravating effect on headache, visual symptoms, and related quality-of-life activities, which might be attributed to weight gain during this month. Whether proper nutritional management to prevent weight gain during Ramadan may help mitigate this worsening effect is a mission of future studies.

Effectiveness and Safety of Ventriculoperitoneal Shunt Versus Lumboperitoneal Shunt for Idiopathic Intracranial Hypertension: A Systematic Review and Comparative Meta-Analysis.

INTRODUCTION: Idiopathic Intracranial Hypertension (IIH) is a condition characterized by elevated intracranial pressure. Although several mechanisms have been proposed as underlying causes of IIH, no identifiable causative factor has been determined for this condition. Initial treatments focus on weight or CSF reduction, but severe cases may require surgery. This study compares outcomes in IIH patients treated with lumboperitoneal shunts (LPSs) versus ventriculoperitoneal shunts (VPSs). METHODS: This systematic-review and meta-analysis follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and includes studies about VPS and LPS patients, reporting one of the outcomes of interest. We conducted searches on PubMed, Embase, Web of Science, and Cochrane Library. RESULTS: Our analysis involved twelve studies, comprising 5990 patients. The estimated odds ratio (OR) for visual improvement was 0.97 (95% CI 0.26-3.62; I2 = 0%) and for headache improvement was 0.40 (95% CI 0.20-0.81; I2 = 0%), favoring LPS over VPS. Shunt revision analysis revealed an OR of 1.53 (95% CI 0.97-2.41; I2 = 77%). The shunt complications showed an OR of 0.91 (95% CI 0.68-1.22; I2 = 0%). The sub-analyses for shunt failure uncovered an OR of 1.41 (95% CI 0.92-2.18; I2 = 25%) and for shunt infection events an OR of 0.94 (95% CI 0.50-1.75; I2 = 0%). CONCLUSIONS: The interventions showed general equivalence in complications, shunt failure, and other outcomes, but LPS seems to hold an advantage in improving headaches. Substantial heterogeneity highlights the need for more conclusive evidence, emphasizing the crucial role for further studies. The findings underscore the importance of considering a tailored decision between VPS and LPS for the management of IIH patients.

Delayed-Onset Idiopathic Intracranial Hypertension After Liposuction: A Case Report and Review.

ABSTRACT: Although systemic complications following liposuction are rare, visual impairment has been reported in a few cases and may occur for a variety of reasons. Here we present the case of a 31-year-old woman who underwent 360° liposuction and subsequently developed headaches and delayed partial visual disturbance 10 days after the procedure. She had symptoms suggestive of idiopathic intracranial hypertension, which was confirmed by lumbar puncture. A literature search revealed other case reports of visual changes or headaches following high-volume liposuction. Our case provides further evidence of a rare association between liposuction and idiopathic intracranial hypertension, emphasizing the need for thorough preoperative evaluations and the consideration of possible risks.

Venous sinus stenting for idiopathic intracranial hypertension: An updated Meta-analysis.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure and primarily affects obese women of reproductive age. Venous sinus stenting (VSS) is a surgical procedure used to treat IIH, but its safety and efficacy are still controversial. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Multiple databases were searched for studies evaluating the safety and efficacy of VSS in IIH patients and meta-analysis was performed to pool the data. RESULTS: A total of 36 studies involving 1066 patients who underwent VSS were included. After VSS, a significant reduction in trans-stenotic gradient pressure was observed. Patients also showed significantly lower cerebrospinal fluid (CSF) opening pressure. Clinical outcomes demonstrated improvement in tinnitus (95%), papilledema (89%), visual disturbances (88%), and headache (79%). However, 13.7% of patients experienced treatment failure or complications. The treatment failure rate was 8.35%, characterized by worsening symptoms and recurrence of IIH. The complications rate was 5.35%, including subdural hemorrhage, urinary tract infection, stent thrombus formation, and others. CONCLUSION: VSS appears to be a safe and effective treatment option for IIH patients who are unresponsive to medical therapy or have significant visual symptoms. However, long-term outcomes and safety of the procedure require further investigation.

Endovascular stenting for cerebral venous sinus stenosis secondary to meningioma invasion.

INTRODUCTION: Symptomatic intracranial hypertension (IH) due to venous outflow obstruction secondary to dural venous sinus (DVS) tumoral invasion affects up to 3% of intracranial meningioma patients. The literature regarding endovascular therapies of such patients is limited to a few case reports and a recent single-centre case series. PURPOSE: We describe our single-centre experience of endovascular therapy in patients with clinically symptomatic IH secondary to DVS meningioma invasion. METHODS: We performed a retrospective review of clinical and radiological data of all patients with refractory IH and meningiomas invading the DVS who were referred for possible DVS venoplasty and stenting. Seven endovascular procedures in six female patients were done. Presumed secondarily induced lateral transverse sinus stenosis was also stented in four patients as part of the primary intervention. RESULTS: All patients experienced complete symptomatic resolution at 6-month follow-up. Five patients had no symptom recurrence over a mean follow-up period of 3.5 years. One patient with multiple meningiomas developed recurrent IH 2 years following stenting secondary to in-stent tumour re-invasion. This was re-stented with consequent 6 months post-retreatment symptomatic relief at the time of writing. No procedure-related complications occurred. CONCLUSION: In the setting of DVS stenosis secondary to meningioma invasion, endovascular therapy is a safe and successful therapeutic option with promising mid-term results. The procedure should be considered in cases where complete surgical tumour resection is unlikely or carries a significant risk. If present, secondarily induced stenoses at the lateral ends of the transverse sinuses should also be considered for treatment.

The impact of eating disorders on idiopathic intracranial hypertension.

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.

Undiagnosed sagittal synostosis as cause of "idiopathic" intracranial hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a rare condition in children, but if diagnosed needs to be promptly treated to avoid clinical sequalae. The main purpose of this paper was to test our clinical experience with a cohort of normocephalic children with craniosynostosis who do not present in the routine way to craniofacial services, due to the normal head shape and age, diagnosed with IIH. METHODS: We retrospectively reviewed all children who were referred to neurosurgery from 2012 to 2022 for management of IIH on our prospectively kept database. We determined what treatments were offered and if there was an associated craniosynostosis. RESULTS: In total, 19 children were identified with an average age at referral of 11.5 years (st dev 4.0 years) with 11 male and 8 female. The most common presenting symptoms and signs were papilloedema (18/19), headaches (15/19), visual deterioration (9/19), nausea and vomiting (7/19) and diplopia (4/19). Five out of 19 children (26.3%) had a sagittal suture fused that was not identified at the time of treatment and all children were normocephalic. CONCLUSION: There is a cohort of children with IIH who will have concomitant craniosynostosis and ideally would benefit from cranial vault expansion as primary surgery rather than cerebrospinal fluid (CSF) diversion. We suggest all children with IIH requiring neurosurgical intervention have cross-sectional imaging to look for occult craniosynostosis prior to intervention.

Persistent Elevation of Opening Pressure Despite Treatment and Symptom Resolution in Pediatric Intracranial Hypertension.

BACKGROUND: Currently no guidelines for repeating a lumbar puncture to guide management in primary intracranial hypertension (PIH) exist. METHODS: An institutional database of patients 18 years and younger followed in the institution's pediatric intracranial hypertension clinic was examined for opening pressure changes in PIH at diagnosis, before medication wean, and following medication wean, as well as to examine whether measurements at the time of diagnosis differed between those with and without disease recurrence. RESULTS: Forty-two patients were included in this study; 36% were male and the mean age at diagnosis was 11.01 years. Treatment duration averaged 9.68 months in those without recurrence and 8.5 months in those with recurrence. Average body mass index percentile of patients with disease recurrence was 83.7 and 72.1 in those without recurrence (P = 0.16). Average opening pressure values of all patients at diagnosis, prewean, and postwean was 36.53 cm H2O, 30.7 cm H2O, and 31.1 cm H2O, respectively. There was no statistically significant difference in opening pressures across these time points (P = 0.14). The change in opening pressure from diagnosis to postwean was statistically significant with a reduction of 5.18 cm H2O (P = 0.04). There was no statistical difference between change in opening pressure at diagnosis versus postwean between those with and without recurrence (P = 0.17). CONCLUSIONS: This clinical observational study suggests that mean opening pressure measurements in patients with PIH remain elevated both before and after medication wean despite papilledema resolution and patient-reported PIH symptoms. Clinically, this suggests that other features such as signs of optic disc edema and symptoms should be used to inform a clinical determination of disease recurrence and treatment course.

Spontaneous rhinorrhea and idiopathic intracranial hypertension: a complex and challenging association.

INTRODUCTION: Spontaneous CSF leak is a known complication of idiopathic intracranial hypertension (IIH). Patients with CSF rhinorrhea present a unique challenge within the IIH population, as the occurrence of a leak can mask the typical IIH symptoms and signs, complicating the diagnosis. Treatment of leaks in this population can also be challenging, with the risk of rhinorrhea recurrence if intracranial hypertension is not adequately treated. OBJECTIVE: The aim of this narrative review was to examine current literature on the association between spontaneous CSF rhinorrhea leaks and IIH, focusing on key clinical features, diagnostic approaches, management strategies, and outcomes. MATERIAL AND METHODS: A literature search was executed using the PubMed and Scopus databases. The search was confined to articles published between January 1985 and August 2023; extracted data was then analysed to form the foundation of the narrative review. RESULTS: This search yielded 26 articles, comprising 943 patients. Average age was 46.8 ± 6.5 years, and average body mass index was 35.8 ± 4.8. Most of the patients were female (74.33%). Presenting symptoms were rhinorrhea, headaches and meningitis. The most common imaging findings were empty sella and encephalocele. The standard treatment approach was endoscopic endonasal approach for correction of CSF rhinorrhea leak, and shunt placement was also performed in 128 (13%) patients. Recurrences were observed in 10% of cases. CONCLUSIONS: The complex relationship between spontaneous CSF leaks and IIH is a challenge that benefits from multidisciplinary evaluation and management for successful treatment. Treatments such as endoscopic repair, acetazolamide, and VP/ /LP shunts reduce complications and recurrence. Personalised plans addressing elevated intracranial pressure are crucial for successful outcomes.

Calcitonin gene-related peptide (CGRP) levels in peripheral blood in patients with idiopathic intracranial hypertension and migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a dominant role in migraine. This prospective study was designed to investigate CGRP levels in patients with idiopathic intracranial hypertension (IIH) and compare the results of migraine patients and healthy controls (HC). As a second objective, CGRP levels obtained from IIH patients defining sustained headache after the resolution of papilledema were compared with those not defining post-IIH headache. METHODS: Thirty-six patients with IIH, 36 with episodic migraine (EM), 18 with chronic migraine (CM), and 36 HC were included in the study. CGRP levels were studied from blood samples obtained from the antecubital vein by using a commercial ELISA kit. RESULTS: Serum CGRP levels of the patient groups were significantly higher than the HC (p < 0.001). As compared with controls, both CM (p Adj<0.001) and IIH (p Adj=0.039) had significantly increased levels of CGRP. Levels recorded from EM patients did not differ from the HC (p Adj=0.661). In 16 IIH patients, persistent headache was reported after the normalization of intracranial pressure (ICP). Twenty patients did not report post-IIH headaches. Comparison of serum CGRP levels of these two groups revealed significantly higher CGRP levels in patients with sustained headaches obtained from blood samples both at the initial and control visit (p Adj <0.001). CONCLUSIONS: CGRP levels of the patient groups were higher than the HC. High levels recorded in patients with IIH indicates the role of CGRP in IIH related headache and even higher levels in patients with sustained headache after normalization of ICP strengthens this finding.

Myelin oligodendrocyte glycoprotein (MOG) associated optic neuritis in a patient with idiopathic intracranial hypertension (IIH) and compressive optic neuropathy case report.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) has a wide phenotypic expression and should be considered in a differential diagnosis of patients with optic disc edema and increased intracranial pressure because MOGAD can mimic IIH and compressive optic neuropathy. CASE PRESENTATION: A 53-year-old woman with a history of presumed idiopathic intracranial hypertension ("IIH") presented with new headache and visual loss. She had a BMI of 35.44 kg/m2 and a past medical history significant for depression, hepatitis C, hyperlipidemia, and uterine cancer post-hysterectomy. She had undergone multiple lumboperitoneal shunts for presumed IIH and had a prior pituitary adenoma resection. Her visual acuity was no light perception OD and counting fingers OS. After neuro-ophthalmic consultation, a repeat cranial MRI showed symmetric thin peripheral optic nerve sheath enhancement of the intra-orbital optic nerves OU. Serum MOG antibody was positive at 1:100 and she was treated with intravenous steroids followed by plasma exchange and rituximab. CONCLUSIONS: This case highlights the importance of considering MOGAD in the differential diagnosis of optic neuropathy. Although likely multifactorial, we believe that the lack of improvement in our case from presumed IIH and despite adequate neurosurgical decompression of a pituitary adenoma with compression of the optic apparatus reflected underlying unrecognized MOGAD. Clinicians should consider repeat imaging of the orbit (in addition to the head) in cases of atypical IIH or compressive optic neuropathy especially when the clinical course or response to therapy is poor or progressive.

Diffusion-Weighted Imaging Reveals Impaired Glymphatic Clearance in Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: The pathophysiology underlying idiopathic intracranial hypertension (IIH) remains incompletely understood. While one theory postulates impaired cerebral glymphatic clearance in IIH, there is a paucity of methods to quantify glymphatic activity in human brains. The purpose of this study was to use advanced diffusion-weighed imaging to evaluate the glymphatic clearance of IIH patients and how it may relate to clinical severity. MATERIALS AND METHODS: DWI was used to separately evaluate the diffusivity along the cerebral perivascular spaces and lateral association and projection fibers, with the degree of diffusivity used as a surrogate for glymphatic function (diffusion tensor image analysis along the perivascular space. Patients with IIH were compared with normal controls. Glymphatic clearance was correlated with several clinical metrics, including lumbar puncture opening pressure and Frisen papilledema grade (low grade: 0-2; high grade: 3-5). RESULTS: In total, 99 patients with IIH were identified and compared with 6 healthy controls. Overall, patients with IIH had significantly lower glymphatic clearance based on DWI-derived diffusivity compared with controls (P = .005). Additionally, in patients with IIH, there was a significant association between declining glymphatic clearance and increasing Frisen papilledema grade (P = .046) but no correlation between opening pressure and glymphatic clearance (P = .27). Furthermore, healthy controls had significantly higher glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .015) and high-grade papilledema (P = .002). Lastly, patients with IIH and high-grade papilledema had lower glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .005). CONCLUSIONS: Patients with IIH possess impaired glymphatic clearance, which is directly related to the extent of clinical severity. The DWI-derived parameters can be used for clinical diagnosis or to assess response to treatment.