2026-08-04 | Cerebrospinal fluid shunting or dural venous sinus stenting to preserve vision in idiopathic intracranial hypertension (IIH Intervention): protocol for an open-label, multicentre, randomised controlled phase IIb trial.

Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and typically affects young women with obesity. Patients are at risk of permanent visual loss due to papilloedema. Some require emergency intervention to rapidly reduce papilloedema and preserve vision. The international standard of care for patients with sight-threatening IIH is cerebrospinal fluid (CSF) shunting. However, dural venous sinus stenting (DVSS) is an emerging procedure that is offered at many neuroscience centres internationally as the primary intervention. Currently, there are no randomised controlled trial data supporting the efficacy of any interventional approach for preserving vision in sight-threatening IIH. IIH Intervention is a UK-based two-arm, open-label, multicentre, randomised controlled phase IIb clinical trial with integrated health economic evaluation to compare CSF shunting with DVSS in patients who have confirmed IIH and are at risk of permanent visual loss due to severe papilloedema. The primary outcome is the global thickness of the peripapillary retinal nerve fibre layer (RNFL), an indicator of papilloedema, measured by optical coherence tomography (OCT) over a 6-month period. Secondary outcomes are global thickness of the RNFL over 12 and 24 months, as well as macular ganglion cell layer volume, perimetric mean deviation, headache outcomes, intervention reporting measures (including complications and revisions) and patient-reported outcomes over 6, 12 and 24 months. The protocol was approved initially on 12 December 2022 by West Midlands-South Birmingham Research Ethics Committee (ref: 22/WM/0230). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. ISRCTN57142415.

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2026-08-02 | Developmental transition in pathophysiological mechanisms of pediatric idiopathic intracranial hypertension and growth plate disorders: A multi-level structural equational modeling systematic review and meta-analysis.

Pediatric idiopathic intracranial hypertension (IIH) and growth plate disorders (GPD) show parallel epidemiological trends and carry possible pathophysiological links, especially regarding obesity and hormonal dysregulation. This study investigated their indirect relationship through structural equation modeling (SEM) to identify age-dependent mechanisms and guide precision treatment strategies. Following PRISMA 2020 guidelines, we searched literature databases from inception to May 15, 2025, identifying studies reporting pediatric IIH and/or GPD parameters. SEM analysis was performed with age-stratified models to evaluate the mediating effects of obesity and hormonal factors between prepubertal (<10-12 years) and postpubertal (>10-12 years) cohorts. We included 22 eligible studies with total of 2293 individuals. SEM revealed peculiar age-dependent mechanisms. In prepubertal children, venous pressure (β = 0.68, P-value<0.001) and vitamin D/hormonal pathways (β = 0.56, P-value<0.001) dominated, with obesity showing minimal effect (β = 0.28, P-value = 0.001). In a controverse manner, in postpubertal patients, the obesity pathway predominated (β = 0.76, P-value<0.001) with reduced venous (β = 0.29, P-value = 0.003) and hormonal (β = 0.16, P-value = 0.038) contributions. Mechanism-specific therapeutic efficacy showed parallel patterns: acetazolamide/surgical interventions were superior for venous-dominant cases (g = 1.86/1.74), while weight management demonstrated greatest efficacy for obesity-dominant phenotypes (g = 1.75). Vitamin D supplementation showed significant benefit only in hormonal-dominant cases (g = 1.64). Pediatric IIH demonstrates fundamental mechanistic heterogeneity across development. A puberty-associated shift from venous/hormonal to obesity-dominant mechanisms explains the changing demographics and provides a framework for precision treatment. Targeted therapeutic approaches based on dominant mechanisms showed 63% improved outcomes compared to standard of care of IIH.

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2026-07-23 | Carbonic anhydrases I and II.

Carbonic anhydrase (CA, EC 4.2.1.1) isoforms I (CA I) and II (CA II) are widespread cytosolic proteins in most vertebrates. They are abundant in the red blood cells and many other tissues, being involved in physiological processes such as pH regulation, CO₂/bicarbonate homeostasis, respiration, and secretion of electrolytes rich in acid or bicarbonate in the stomach, kidneys, cerebrospinal fluid, eyes, and bones. The genetics, biochemistry, expression, localization in tissues and organs, kinetic properties, and catalytic mechanisms of these enzymes are well understood at the molecular level. At least five different inhibition mechanisms were described with more than 50 chemotypes acting as inhibitors. The activation with amine/amino acid activators was also well studied. The physiological role of CA I is poorly understood, whereas CA II is a physiologically dominant isoform, playing crucial functions in a host of tissues/organs. Interfering with its activity by means of inhibitors has been and is currently exploited in therapy for the management of edema, glaucoma, epilepsy, obesity, acute mountain sickness, and idiopathic intracranial hypertension. Promising preclinical data pointed to the potential use of CA II inhibitors for the management of other conditions, such as neuropathic pain, cerebral ischemia, rheumatoid arthritis, Alzheimer's disease, osteoporosis, and obstructive sleep apnea. Many CA inhibitors are in clinical use for the management of such conditions, among which are acetazolamide, thiazides and high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, and antiepileptics such as sulthiame, topiramate and zonisamide, whereas SLC-0111 is in clinical development as an antitumor agent. CA activators are not yet used clinically, but they might have pharmacological applications in the management of neurodegeneration, emotional memory disorders, obsessive-compulsive disorders, phobias, generalized anxiety, and post-traumatic stress. Finding novel modulators of activity for these enzymes may lead to innovative therapeutic applications and deepen our understanding of enzymes, their inhibitors, and their activators.

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2026-07-21 | Venous Sinus Stenting for Pulsatile Tinnitus: A Systematic Review and Meta-Analysis.

Pulsatile tinnitus (PT) is frequently caused by venous sinus stenosis and may be associated with idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) directly addresses venous outflow obstruction and has emerged as a therapeutic option; however, outcome data remain heterogeneous. We performed an updated systematic review and meta-analysis to evaluate the efficacy and durability of VSS for PT and to compare outcomes between IIH-associated and isolated PT. MEDLINE, Scopus, and Web of Science were searched from inception through December 2025 following PRISMA guidelines. Clinical studies reporting PT outcomes after VSS were included. Random-effects meta-analyses of proportions were conducted to estimate pooled rates of overall improvement, complete resolution, and recurrence. Prespecified subgroup analyses compared IIH versus isolated PT. Thirty-two studies comprising 850 patients were included (641 with IIH; 209 with isolated PT). Venous sinus stenosis accounted for 90.3% of treated etiologies. The pooled rate of overall PT improvement was 89.8% (95% CI, 85.5-92.9). Complete resolution occurred in 87.1% (95% CI, 82.5-90.6). Recurrence at last follow-up was 10.9% (95% CI, 8.3-14.2). Improvement and complete resolution rates did not differ significantly between IIH and isolated PT. Recurrence was higher in IIH (12.0%) than in isolated PT (5.7%), without reaching statistical significance. VSS is associated with high rates of PT improvement and complete resolution with low recurrence. Recurrence trends appear higher in IIH, suggesting underlying pathophysiology may influence durability.

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2026-07-06 | Papilledema is not the point: intracranial pressure dysregulation as a common pathway in migraine and idiopathic intracranial hypertension

Abstract Accumulating evidence challenges the traditional distinction between migraine and idiopathic intracranial hypertension (IIH). We tested whether impaired CSF volume/pressure regulation driven by dural venous sinus stenosis represents a shared substrate. Brain MRI and magnetic resonance venography scans from 161 consecutive patients - migraine without aura (MwoA, n=89), migraine with aura (MwA, n=36) and IIH (n=36) - were retrospectively analysed and compared with 37 prospectively recruited healthy controls. An Extended Combined Conduit Score – designed to quantify the degree and extent of venous-sinus narrowing, with higher values indicating greater outflow impairment, and also evaluating the superior sagittal sinus - quantified stenosis. Additional neuroradiological markers of raised intracranial pressure (empty sella, posterior globe flattening, optic nerve sheath diameter) were recorded. A receiver operating characteristic analysis defined the optimal stenosis degree threshold for distinguishing patients from controls, after which prevalence comparisons were performed. Median Extended Combined Conduit Score increased step wise from controls (2, interquartile range 1–3) to MwoA (3, 2–4), MwA (3, 3–4) and IIH (6, 5–6) (p &lt; 0.001). Both migraine groups scored higher than controls (p &lt;0.001) and lower than IIH (p &lt;0.001). The area under the receiver operating characteristic curve was 0.786 (95% confidence interval 0.716–0.856); a cut off ≥ 3 provided 74.5% sensitivity and 73.0% specificity. Using this threshold, venous stenosis was more frequent in MwoA and MwA than in controls (each p &lt;0.001) and highest in IIH (p &lt;0.001 versus all); MwA exceeded MwoA (p =0.007) and was comparable to IIH (p =0.187). Bilateral stenosis occurred in 0% of controls, nearly 25% of patients with migraine (p &lt;0.001 versus controls) and 77.8% of IIH patients (p &lt;0.001). Empty sella was more common in MwoA (p =0.004) and MwA (p =0.025) than in controls, and markedly enriched in IIH (p &lt;0.001 versus all). Other radiological markers were similarly more prevalent in IIH (all p&lt;0.001) showing no additional significant between-group differences. Findings support a pathogenetic continuum linking MwoA, MwA and IIH, challenging the diagnostic primacy of papilledema, the rarity of IIH without it, and the perceived irrelevance of unilateral sinus narrowing. As already observed in IIH, an impaired intracranial volume/pressure regulation appears a necessary though not sufficient condition for migraine development; a “primary” predisposition to migraine, likely multifactorial and widely variable among individuals and in the same individual over time, is required for typical migraine pain to develop, also modulating its frequency. Future studies should assess whether targeting intracranial pressure, thus potentially preventing calcitonin gene-related peptide release, may complement or substitute calcitonin gene-related peptide based therapies in migraine patients.

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