RARE DISEASE
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Synonyms: Benign intracranial hypertension, IIH, Pseudotumor cerebri
Synonyms: Benign intracranial hypertension, IIH, Pseudotumor cerebri
Synonyms: Benign intracranial hypertension, IIH, Pseudotumor cerebri
Drug discovery
4
drugs
With orphan designations
Overview
Idiopathic intracranial hypertension (IIH) is a neurological disorder marked by elevated intracranial pressure of unknown etiology, primarily affecting young, obese women. Symptoms include headaches, vision changes (e.g., transient obscurations, papilledema), pulsatile tinnitus, and potential vision loss. Diagnosis requires exclusion of secondary causes via neuroimaging and confirmed by lumbar puncture with elevated opening pressure (>25 cm CSF). Management focuses on weight loss, pharmacotherapy (e.g., acetazolamide), and surgical interventions (e.g., CSF shunting) for refractory cases [1][5][6][16].
Therapies
First-line: Weight loss (≥5–10% body weight) and sodium restriction [3][18].
Medical: Acetazolamide (reduces CSF production), topiramate (adjunct for headache/weight), or furosemide [8][13][16].
Surgical: CSF diversion (shunts), optic nerve sheath fenestration, or venous sinus stenting in refractory cases [3][8][16].
Categories: rare neurological diseases
Research Papers
1,582 drug discovery papers about Idiopathic intracranial hypertension, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,582 drug discovery papers about Idiopathic intracranial hypertension, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
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 < 0.001). Both migraine groups scored higher than controls (p <0.001) and lower than IIH (p <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 <0.001) and highest in IIH (p <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 <0.001 versus controls) and 77.8% of IIH patients (p <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 <0.001 versus all). Other radiological markers were similarly more prevalent in IIH (all p<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.
2026-06-27 | Endovascular treatment of tumor-related dural sinus stenosis, venous outflow obstruction, and secondary intracranial hypertension: a systematic review of the literature.
Tumors involving dural venous sinuses can lead to venous outflow obstruction and secondary intracranial hypertension. While surgical resection can decompress the sinus, such procedures carry significant risks. With the success of endovascular interventions for idiopathic intracranial hypertension (IIH), venous sinus stenting (VSS) and angioplasty have emerged as potential treatments for tumor-related sinus stenosis. However, evidence remains limited and dispersed. This systematic review aimed to synthesize the available literature on the safety and efficacy of endovascular treatment for tumor-related venous sinus obstruction. A systematic search of PubMed, Embase, and Web of Science was conducted from database inception to November 2025. Eligible studies included any report describing endovascular treatment (VSS and/or angioplasty) for tumor-related venous sinus obstruction, whether due to tumor invasion or compression, or even stenosis following surgery or radiotherapy. Data on patient demographics, tumor characteristics, procedural details, and outcomes were extracted and summarized descriptively. Twenty studies comprising 57 patients were included. Most patients were female (65%) with a mean age of 48 years. Meningioma represented the most common underlying tumor (75%). The majority of obstructions resulted from tumor compression or invasion (86%), and most patients underwent VSS alone (74%), while the rest underwent VSS and angioplasty (23%). No periprocedural complications were reported. Mean trans-stenotic pressure gradient decreased by 10 ± 9 mmHg post-treatment and mean lumbar opening pressure decreased by 11 ± 12 cmH2O. Clinical improvement was reported in 63% of patients, including resolution or improvement of papilledema in 94% and vision changes in 94%. Repeat intervention was required in 28% of cases, and only about half of patients achieved further improvement after reintervention. Endovascular therapy for tumor-related venous sinus stenosis appears safe and effective, leading to meaningful pressure reduction and symptomatic improvement in two-thirds of patients. These findings support VSS as a viable adjunct or alternative to surgery in selected patients. Nonetheless, the certainty of evidence remains very low, and current data cannot establish definitive conclusions.
2026-06-26 | Acetazolamide-induced metabolic acidosis in pediatric idiopathic intracranial hypertension: associations with bone mineral density, growth, and kidney function.
Although acetazolamide is the main medical treatment for idiopathic intracranial hypertension (IIH), data on acetazolamide-induced metabolic acidosis and its long-term outcomes are limited. This study aimed to investigate the severity of acetazolamide-related metabolic acidosis, associated risk factors, and its effects on bone mineral density (BMD), growth, and kidney function. This retrospective cohort study included pediatric patients with IIH treated with acetazolamide between 2018 and 2025. Demographic and clinical characteristics, anthropometric and laboratory findings at diagnosis and during follow-up, BMD measurements, and ultrasonography findings were collected. Metabolic acidosis was categorized by severity. Minimum and mean serum bicarbonate levels during follow-up were recorded. Forty-one patients (65.9% female; mean age 11.2 ± 3.1 years) were included. Metabolic acidosis was observed in all patients (39.0% mild, 53.7% moderate, 7.3% severe). Patients with moderate-to-severe acidosis had significantly lower BMI Z-scores and younger ages at diagnosis compared with those with mild acidosis. In multivariable analysis, cumulative acetazolamide dose remained independently associated with moderate/severe metabolic acidosis (OR 1.30, 95% CI 1.00-1.69; p = 0.049). BMD was assessed in 35 patients after a median acetazolamide exposure of 14 months and mildly reduced/low BMD was detected in 22.9%. Higher cumulative acetazolamide exposure and lower minimum bicarbonate levels were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. Although estimated glomerular filtration rate declined modestly from baseline to the last visit, this change was not associated with acidosis severity, treatment duration, or cumulative acetazolamide dose. Metabolic acidosis is highly prevalent among children receiving acetazolamide for IIH, and greater cumulative acetazolamide exposure appears to be associated with more severe acidosis. Lower bicarbonate levels and higher cumulative acetazolamide exposure were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. The limited number of patients undergoing BMD assessment, the relatively short exposure duration in some patients, and the absence of baseline BMD measurements limit definitive conclusions regarding the skeletal effects of acetazolamide.
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 < 0.001). Both migraine groups scored higher than controls (p <0.001) and lower than IIH (p <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 <0.001) and highest in IIH (p <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 <0.001 versus controls) and 77.8% of IIH patients (p <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 <0.001 versus all). Other radiological markers were similarly more prevalent in IIH (all p<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.
2026-06-27 | Endovascular treatment of tumor-related dural sinus stenosis, venous outflow obstruction, and secondary intracranial hypertension: a systematic review of the literature.
Tumors involving dural venous sinuses can lead to venous outflow obstruction and secondary intracranial hypertension. While surgical resection can decompress the sinus, such procedures carry significant risks. With the success of endovascular interventions for idiopathic intracranial hypertension (IIH), venous sinus stenting (VSS) and angioplasty have emerged as potential treatments for tumor-related sinus stenosis. However, evidence remains limited and dispersed. This systematic review aimed to synthesize the available literature on the safety and efficacy of endovascular treatment for tumor-related venous sinus obstruction. A systematic search of PubMed, Embase, and Web of Science was conducted from database inception to November 2025. Eligible studies included any report describing endovascular treatment (VSS and/or angioplasty) for tumor-related venous sinus obstruction, whether due to tumor invasion or compression, or even stenosis following surgery or radiotherapy. Data on patient demographics, tumor characteristics, procedural details, and outcomes were extracted and summarized descriptively. Twenty studies comprising 57 patients were included. Most patients were female (65%) with a mean age of 48 years. Meningioma represented the most common underlying tumor (75%). The majority of obstructions resulted from tumor compression or invasion (86%), and most patients underwent VSS alone (74%), while the rest underwent VSS and angioplasty (23%). No periprocedural complications were reported. Mean trans-stenotic pressure gradient decreased by 10 ± 9 mmHg post-treatment and mean lumbar opening pressure decreased by 11 ± 12 cmH2O. Clinical improvement was reported in 63% of patients, including resolution or improvement of papilledema in 94% and vision changes in 94%. Repeat intervention was required in 28% of cases, and only about half of patients achieved further improvement after reintervention. Endovascular therapy for tumor-related venous sinus stenosis appears safe and effective, leading to meaningful pressure reduction and symptomatic improvement in two-thirds of patients. These findings support VSS as a viable adjunct or alternative to surgery in selected patients. Nonetheless, the certainty of evidence remains very low, and current data cannot establish definitive conclusions.
2026-06-26 | Acetazolamide-induced metabolic acidosis in pediatric idiopathic intracranial hypertension: associations with bone mineral density, growth, and kidney function.
Although acetazolamide is the main medical treatment for idiopathic intracranial hypertension (IIH), data on acetazolamide-induced metabolic acidosis and its long-term outcomes are limited. This study aimed to investigate the severity of acetazolamide-related metabolic acidosis, associated risk factors, and its effects on bone mineral density (BMD), growth, and kidney function. This retrospective cohort study included pediatric patients with IIH treated with acetazolamide between 2018 and 2025. Demographic and clinical characteristics, anthropometric and laboratory findings at diagnosis and during follow-up, BMD measurements, and ultrasonography findings were collected. Metabolic acidosis was categorized by severity. Minimum and mean serum bicarbonate levels during follow-up were recorded. Forty-one patients (65.9% female; mean age 11.2 ± 3.1 years) were included. Metabolic acidosis was observed in all patients (39.0% mild, 53.7% moderate, 7.3% severe). Patients with moderate-to-severe acidosis had significantly lower BMI Z-scores and younger ages at diagnosis compared with those with mild acidosis. In multivariable analysis, cumulative acetazolamide dose remained independently associated with moderate/severe metabolic acidosis (OR 1.30, 95% CI 1.00-1.69; p = 0.049). BMD was assessed in 35 patients after a median acetazolamide exposure of 14 months and mildly reduced/low BMD was detected in 22.9%. Higher cumulative acetazolamide exposure and lower minimum bicarbonate levels were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. Although estimated glomerular filtration rate declined modestly from baseline to the last visit, this change was not associated with acidosis severity, treatment duration, or cumulative acetazolamide dose. Metabolic acidosis is highly prevalent among children receiving acetazolamide for IIH, and greater cumulative acetazolamide exposure appears to be associated with more severe acidosis. Lower bicarbonate levels and higher cumulative acetazolamide exposure were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. The limited number of patients undergoing BMD assessment, the relatively short exposure duration in some patients, and the absence of baseline BMD measurements limit definitive conclusions regarding the skeletal effects of acetazolamide.
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Drug Discovery Landscape
4 orphan drug designations for Idiopathic intracranial hypertension.
4 orphan drug designations for Idiopathic intracranial hypertension.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Octreotide acetate | small molecules | EMA | 2021-12-10 | — | Granzer Regulatory Consulting & Services GmbH |
Octreotide Acetate | peptides | FDA | 2021-07-19 | — | NBO Pharma LLC |
exenatide | peptides | FDA | 2017-05-16 | — | Boyd Consultants Ltd |
Exenatide | peptides | EMA | 2016-03-21 | — | Boyd Consultants Limited |
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