Progress and recognition of idiopathic intracranial hypertension: A narrative review.

BACKGROUND: Idiopathic intracranial hypertension (IIH) mainly affects obese young women, causing elevated intracranial pressure, headaches, and papilledema, risking vision loss and severe headaches. Despite weight loss as the primary treatment, the underlying mechanisms remain unclear. Recent research explores novel therapeutic targets. AIMS: This review aimed to provide a comprehensive understanding of IIH's pathophysiology and clinical features to inform pathogenesis and improve treatment strategies. METHODS: Recent publications on IIH were searched and summarized using PubMed, Web of Science, and MEDLINE. RESULTS: The review highlights potential pathomechanisms and therapeutic advances in IIH. CONCLUSION: IIH incidence is rising, with growing evidence linking it to metabolic and hormonal disturbances. Early diagnosis and treatment remain challenging.

The relationship between body mass index and cerebrospinal fluid pressure in children with pseudotumor cerebri.

BACKGROUND: Childhood obesity has become a major global health problem. Obesity is associated with major health problems, such as diabetes, hypertension, dyslipidemia, cardiovascular disease. Obesity is also considered a risk factor for Pseudotumor cerebri (PTC). The present study aimed to investigate the relationship between body mass index (BMI), and cerebrospinal fluid (CSF) pressure in patients with pseudotumor cerebri. METHODS: A total of 48 children diagnosed with PTC, who were aged < 18 years and followed up in the pediatric clinic were included in the retrospective study. National BMI percentile curves were used for reference. We investigated statistically the relationship between BMI, clinical and laboratory results, and CSF pressure in patients. RESULTS: Of total patients 27 were female (56.25%) and 21 were male (43.75%). With regard to the BMI percentile, 20 (41.67%) were overweight or obese. CSF pressure was higher in overweight and obese patients compared to children with BMI in normal ranges (p < 0.05). A statistically significant positive correlation was also observed between BMI and CSF pressure values and between monocyte and CSF values (p < 0.05). CONCLUSIONS: The results of the present study indicate a direct relationship between CSF pressure and BMI in children with PTC. Appropriate diet, exercise, and medical treatment in overweight and obese children can make a significant contribution to the treatment of PTC. Additionally, a significant correlation was observed between CSF pressure and monocyte levels.

Radiological signs supporting idiopathic intracranial hypertension in symptomatic patients with lumbar puncture opening pressure < 250 mm.

Lumbar puncture opening pressure (LPOP) exceeding 250mmH2O is key in diagnosing idiopathic intracranial hypertension (IIH), per revised Friedman's criteria. Some patients do not meet LPOP criteria (with or without papilledema), despite having IIH-related symptoms and neuroimaging findings. This study aimed to investigate the radiological findings and clinical symptoms in patients suspected of having IIH without meeting the LPOP criteria. We retrospectively evaluated cerebral venous sinus stenosis using the conduit Farb score (CFS) and other radiological findings suggestive of IIH by computed tomography venography and magnetic resonance venography in females ≥ 18 years-old with chronic headaches, suspected IIH, and LPOP < 250 mm. Eighty-eight women (56 with LPOP < 200 mm H2O and 32 with LPOP ranging between 200 and 250mmH2O) were included. Among patients with LPOP 200-250mmH2O, 40% (12) exhibited three or more radiological findings supporting IIH, compared to 17% (8) in the LPOP < 200 mmH2O group (p = 0.048). Cerebral venous stenosis (CFS ≤ 5) was observed in 80% (24) of those with LPOP 200-250 mmH2O, contrasting with 40% (19) of those with LPOP < 200 mmH2O (p < 0.001). Cerebral venous stenosis was significantly more common in patients with LPOP 200-250 mmH2O than < 200 mmH2O, suggesting that they may benefit from IIH treatment.

Arachnoid granulations in idiopathic intracranial hypertension: Do they have an influence?

OBJECTIVE: The aim of this study was to investigate whether the relative narrowing of the dural venous sinuses by arachnoid granulations (AGs) is more pronounced in patients with idiopathic intracranial hypertension (IIH) compared to healthy controls. BACKGROUND: IIH is characterized by increased intracranial pressure, which is associated with symptoms such as headache and visual disturbances. The role of cerebral venous drainage obstruction in IIH is the subject of ongoing research. MATERIALS AND METHODS: In this retrospective case-control study, 3D contrast-enhanced magnetic resonance images of a cohort of 43 patients with IIH were evaluated for (1) the number of AGs per venous sinus and (2) the diameters of the dural venous sinuses at the site of an AG and at standardized measurement points. In addition, the minimum width of the transverse/sigmoid sinus was measured. All data were compared to the same data from a cohort of 43 control participants. RESULTS: Patients with IIH showed less relative sinus narrowing by AG compared to controls (median: 7%, interquartile range [IQR] 10% vs. 11%, IQR 9% in controls; p = 0.009). In patients with IIH, sinus diameter was larger at the site of an AG (70 ± 25 mm2) compared to its diameter at the standardized measurement point (48 ± 23 mm2; p = 0.010). In the superior sagittal sinus (SSS), patients with IIH had smaller AGs (median: 3 mm2, IQR 2 mm2 vs. 5 mm2, IQR 3 mm2 in controls; p = 0.023) while the respective sinus segment was larger (median: 69 mm2; IQR 21 mm2 vs. 52 mm2, IQR 26 mm2 in controls; p = 0.002). The right transverse sinus was narrower in patients with IIH (41 ± 21 mm vs. 57 ± 20 mm in controls; p < 0.001). CONCLUSIONS: In contrast to our hypothesis, patients with IIH showed less pronounced relative sinus narrowing by AG compared to controls, especially within the SSS, where AGs were smaller and the corresponding sinus segment wider. Smaller AGs could result in lower cerebrospinal fluid resorption, favoring the development of IIH. Conversely, the smaller AGs could also be a consequence of IIH due to backpressure in the SSS because of the narrower transverse/sigmoid sinus, which widens the SSS and compresses the AG.

Association of Extent of Transverse Sinus Stenosis With Cerebral Glymphatic Clearance in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a neurologic disorder characterized by symptoms of elevated intracranial pressure in the absence of a clear cause. There is a developing theory that IIH may, in part, be related to abnormal cerebral glymphatic clearance. In addition, transverse sinus stenosis (TSS) is a common finding in IIH of unclear pathophysiologic significance. Similarly, whether or not TSS is associated with glymphatic outflow in IIH is unknown. The aim of this investigation was to explore the possible association between glymphatic outflow and extent of TSS in patients with IIH. METHODS: The study cohort consisted of patients with IIH and healthy controls who were retrospectively identified from our tertiary care institution located in upstate New York from 2016 to 2023. Patients with IIH were included if they had brain MRIs completed with sufficient sequences for analysis. Brain MRIs were computationally analyzed using diffusion tensor imaging analysis along the perivascular space technique to quantify the glymphatic function in patients with IIH. Glymphatic clearance, the primary outcome, was then correlated with the degree of TSS on MR venography using 2 different scoring systems, the 'Farb score' and 'Carvalho score.' RESULTS: Overall, 81 patients with IIH (70 [86%] female, mean age 29.8 years [SD: 8.2 years], mean BMI 41 [SD: 8.4]) and 10 normal controls were identified with sufficient imaging. Based on the Carvalho TSS score, IIH patients without TSS had significantly lower glymphatic clearance than healthy controls (mean ALPS index: 1.196 [SD: 0.05] vs 1.238 [SD: 0.04], respectively; p = 0.018). Furthermore, IIH patients with TSS had significantly lower glymphatic outflow than healthy controls (1.129 [SD: 0.07] vs 1.238 [SD: 0.04], respectively; p < 0.0001) and IIH patients without TSS (1.129 [SD: 0.07] vs 1.196 [SD: 0.05], respectively; p < 0.0001). In addition, there was a significant association between increasing extent of TSS and declining glymphatic clearance (p < 0.0001, R = 0.62). Finally, IIH patients with severe TSS had significantly lower glymphatic flow than IIH patients with mild stenosis (1.121 [SD: 0.07] vs 1.178 [SD: 0.05], respectively; p < 0.0001). These findings were similarly recapitulated using the Farb TSS scoring system. DISCUSSION: These preliminary findings suggest that the extent of TSS is associated with the degree of glymphatic clearance in IIH, providing novel insights into IIH pathophysiology. Further research is required to clarify the possible causal relationship between TSS and impaired glymphatic clearance in IIH.

Managing idiopathic intracranial hypertension in the eye clinic.

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.

Can optic disc vessel density help in cases of residual disc elevation after shunt surgery in cases of idiopathic intracranial hypertension?

AIM: To detect if we can use the reduction in the optic disc vessel density as an indicator to the reduction in intracranial tension in patients with residual optic disc elevation after shunt surgery as fundus examination in those cases is not conclusive. PATIENTS AND METHOD: 21 patients with papilledema due to idiopathic intracranial hypertension underwent shunt surgery. Full neurological and ophthalmological assessments were done. The optic disc vessel density was measured before and 3 months after surgery. Patients were then divided according to the resolution of papilledema into 2 groups: 1) Residual disc elevation group. 2) Completely resolved disc edema group. CSF pressure was measured via lumber puncture preoperative for all patients and 3 months post-operative only for patients with residual disc edema. A comparison between both groups was done. RESULTS: There was a highly statistically significant difference between the two groups as regard the papilledema grade (the residual disc elevation group had a higher grade of papilledema) with P-value=0.000. As regard the difference in the preoperative optic disc vessel density between the two groups, there were statistically significant differences (optic disc vessel density was more in the residual disc elevation group). As regard the postoperative optic disc vessel density, there were non-significant differences between the two groups in whole image, inside disc and peripapillary vessel density (either in macro or microvasculature). CONCLUSION: The optic disc vessel density decreased with normal postoperative CSF opening pressure in cases with residual disc elevation postoperatively. Thus, in cases of residual optic disc swelling after shunt surgery, we can detect the reduction of intracranial pressure by the reduction in the optic disc vessel density which is a safe non-invasive technique. That may help in cases of residual disc elevation.

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.

Rebound Intracranial Hypertension.

PURPOSE OF REVIEW: Rebound intracranial hypertension (RIH) is a post-procedural treatment complication in patients with spontaneous intracranial hypotension (SIH) characterized by transient high-pressure headache symptoms. This article reviews the epidemiology, clinical features, risk factors, and treatment options for RIH. RECENT FINDINGS: This article discusses how changes in underlying venous pressure and craniospinal elastance can explain symptoms of RIH, idiopathic intracranial hypertension (IIH), and SIH. The pathophysiology of RIH provides a clue for how high and low intracranial pressure disorders, such as IIH and SIH, are connected on a shared spectrum.

Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension.

BACKGROUND: Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH. METHODS: This was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks. RESULTS: Cognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315). CONCLUSIONS: In patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

Interrelation Between Cerebrospinal Fluid Pressure, Intracranial Morphology and Venous Hemodynamics Studied by 4D Flow MRI.

PURPOSE: To quantify the effects of CSF pressure alterations on intracranial venous morphology and hemodynamics in idiopathic intracranial hypertension (IIH) and spontaneous intracranial hypotension (SIH) and assess reversibility when the underlying cause is resolved. METHODS: We prospectively examined venous volume, intracranial venous blood flow and velocity, including optic nerve sheath diameter (ONSD) as a noninvasive surrogate of CSF pressure changes in 11 patients with IIH, 11 age-matched and sex-matched healthy controls and 9 SIH patients, before and after neurosurgical closure of spinal dural leaks. We applied multiparametric MRI including 4D flow MRI, time-of-flight (TOF) and T2-weighted half-Fourier acquisition single-shot turbo-spin echo (HASTE). RESULTS: Sinus volume overlapped between groups at baseline but decreased after treatment of intracranial hypotension (p = 0.067) along with a significant increase of ONSD (p = 0.003). Blood flow in the middle and dorsal superior sagittal sinus was remarkably lower in patients with higher CSF pressure (i.e., IIH versus controls and SIH after CSF leak closure) but blood flow velocity was comparable cross-sectionally between groups and longitudinally in SIH. CONCLUSION: We were able to demonstrate the interaction of CSF pressure, venous volumetry, venous hemodynamics and ONSD using multiparametric brain MRI. Closure of CSF leaks in SIH patients resulted in symptoms suggestive of increased intracranial pressure and caused a subsequent decrease of intracranial venous volume and of blood flow within the superior sagittal sinus while ONSD increased. In contrast, blood flow parameters from 4D flow MRI did not discriminate IIH, SIH and controls as hemodynamics at baseline overlapped at most vessel cross-sections.

Lumbar Puncture for Diagnosis of Idiopathic Intracranial Hypertension in Typical Patients.

BACKGROUND: Patients with typical features of pseudotumor cerebri syndrome (PTCS) must undergo lumbar puncture (LP) to demonstrate elevated opening pressure and cerebrospinal fluid (CSF) analysis to rule out alternative diagnoses. As LP may be associated with significant morbidity, this study aims to determine its necessity in diagnosing typical PTCS. METHODS: Retrospective chart review at 3 university-based neuro-ophthalmology practices included women aged 18-45 years with body mass index >25, papilledema, negative neuroimaging, and who met criteria for PTCS or probable PTCS. RESULTS: One hundred fifty-six patients were enrolled. Seven (4.5%) had clinically insignificant CSF abnormalities. No diagnoses or management changed based on LP/CSF results. CONCLUSION: LP may not be routinely required in the initial evaluation of typical patients with PTCS evaluated by experienced clinicians We caution, however, that further prospective study is required to determine potential risks and benefits of LP as a tool in the diagnosis of IIH before recommending general practice changes.

Systemic and adipocyte transcriptional and metabolic dysregulation in idiopathic intracranial hypertension.

BACKGROUNDIdiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess, and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH phenotype.METHODSIn fasted, matched IIH (n = 97) and control (n = 43) patients, we assessed glucose and insulin homeostasis and leptin levels. Body composition was assessed along with an interrogation of adipose tissue function via nuclear magnetic resonance metabolomics and RNA sequencing in paired omental and subcutaneous biopsies in a case-control study.RESULTSWe demonstrate an insulin- and leptin-resistant phenotype in IIH in excess of that driven by obesity. Adiposity in IIH is preferentially centripetal and is associated with increased disease activity and insulin resistance. IIH adipocytes appear transcriptionally and metabolically primed toward depot-specific lipogenesis.CONCLUSIONThese data show that IIH is a metabolic disorder in which adipose tissue dysfunction is a feature of the disease. Managing IIH as a metabolic disease could reduce disease morbidity and improve cardiovascular outcomes.FUNDINGThis study was supported by the UK NIHR (NIHR-CS-011-028), the UK Medical Research Council (MR/K015184/1), Diabetes UK, Wellcome Trust (104612/Z/14/Z), the Sir Jules Thorn Award, and the Midlands Neuroscience Teaching and Research Fund.

Analysis of the Peripapillary Choroidal Vascular Characteristics in Papilledema Associated with Pseudotumor Cerebri.

SIGNIFICANCE: Choroidal vascularity index measured by image binarization method from peripapillary optical coherence tomography sections has been found significantly lower in papilledema patients than healthy controls. PURPOSE: The purpose of this study was to compare peripapillary choroidal parameters in papilledema patients with control subjects. METHODS: Peripapillary spectral domain optical coherence tomography scans of 34 patients with papilledema and 34 healthy controls are acquired for the study. Images are binarized with the ImageJ software (National Institutes of Health, Bethesda, MD) to calculate total choroidal area, stromal area, luminal area, and choroidal vascularity index. RESULTS: Total choroidal area, luminal area, and choroidal vascularity were significantly lower in papilledema patients compared with healthy controls on right (1.343 ± 0.286 vs. 1.694 ± 0.344, P < .001; 0.880 ± 0.209 vs. 1.167 ± 0.255, P < .001; 65.28 ± 2.99% vs. 68.68 ± 2.81%, P < .001, respectively) and left eyes (1.376 ± 0.308 vs. 1.647 ± 0.339, P < .001; 0.899 ± 0.231 vs. 1.134 ± 0.237, P < .001; 64.92 ± 3.44 vs. 68.84 ± 3.23, P < .001, respectively). No difference was found between active and remitted stages of papilledema in terms of choroidal parameters. CONCLUSIONS: Peripapillary total choroidal area, luminal area, and choroidal vascularity index are significantly reduced in patients with papilledema. These parameters might be beneficial tools for evaluating choroidal vascularity in papilledema quantitatively and differential diagnosis for optic disc edema.

The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?

BACKGROUND: It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system. METHODS: 10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses. RESULTS: A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH. CONCLUSIONS: The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.

Telemetric monitoring in idiopathic intracranial hypertension demonstrates intracranial pressure in a case with sight-threatening disease.

The understanding of raised intracranial pressure (ICP) is increasing with the directed use of intracranial telemetric ICP monitors. This case uniquely observed ICP changes by telemetric monitoring in a patient with idiopathic intracranial hypertension (IIH), who developed rapid sight-threatening disease. A lumbar drain was inserted, as a temporising measure, and was clamped prior to surgery. This resulted in a rapid rise in ICP, which normalised after insertion of a ventriculoperitoneal shunt. This case highlighted the utility of the ICP monitor and the lumbar drain as a temporising measure to control ICP prior to a definitive procedure as recommended by the IIH consensus guidelines.