Novel advances in monitoring and therapeutic approaches in idiopathic intracranial hypertension

Abstract

Purpose of review: The current article appraises the recent developments in idiopathic intracranial hypertension (IIH), with particular attention to novel therapeutic avenues and advanced clinical assessment and monitoring with optical coherence tomography and telemetric intracranial pressure devices.

Recent findings: The incidence of IIH is increasing. The first consensus guidelines for IIH have been published detailing investigation and management algorithms for adult IIH. Improved understanding, clinical assessment and monitoring are emerging with the use of optical coherence tomography. Intracranial pressure telemetry is providing unique insights into the physiology of raised intracranial pressure in IIH. There are now an increasing number of ongoing clinical trials evaluating weight loss methods and novel targeted therapies, such as 11ß-HSD1 inhibition and Glucagon-like peptide 1 (GLP-1) receptor agonists.

Summary: Several studies are evaluating new therapies for IIH. Monitoring techniques are advancing, aiding diagnosis and allowing the clinician to accurately evaluate changes in papilloedema and intracranial pressure.

Box 1

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FIGURE 1

(a) Fundus photograph of the right optic disc in a patient referred for papilloedema. The optic nerve shape is irregular. Note there is no loss of view of any of the retinal vessels as they run over the border of the optic nerve. (b) Fundus photograph of the left optic disc in a patient referred for papilloedema. (c) Red-free fundus photograph of the right optic disc highlights hyper reflectivity at the optic nerve head. (d) Red-free fundus photograph of the left optic disc highlights hyper reflectivity at the optic nerve head. (e) Blue autoflurorescence (BAF) imaging using the Heidelberg Spectralis optic coherence tomography (OCT) imaging. This clearly highlights buried optic disc drusen as a cause of the pseudopapilloedema. (f) BAF OCT imaging clearly highlights buried optic disc drusen in the left eye as a cause of the pseudopapilloedema. (g) BAF and an OCT disc volume imaging cross-section showing one of the drusen (white arrow) in the right eye and the depth of the drusen with obvious elevation of the over laying optic nerve tissue. (h) BAF and an OCT disc volume imaging cross-section showing one of the drusen in the left eye (white arrow) and the depth of the drusen with obvious elevation of the over laying optic nerve tissue.

FIGURE 2

(a) Optical coherence tomography infra-red image, in same patient as other figures, shows the cross-sectional cut for (b) with the arrowed line. (b) OCT cross-sectional volume image shows a typical peripapilliary hyperreflective ovoid mass-like structures (PHOMS) (arrow). (c) OCT infra-red image, in same patient as other figures, shows the cross-sectional cut for (S) with the arrowed line. Note the reduction in optic nerve head swelling. (d) OCT cross-sectional volume image shows the reduction in the size of the PHOMS (arrow). (e and f) Fundus photographs of the right (e) and left (f) eye at baseline showing Frisen grade 4 papilloedema. (g and h) Resolution of papilloedema following bariatric surgery seen on fundus photographs. (i and j) Resolution of papilloedema seen on OCT as reduction of total retinal thickness at the optic nerve head in right (i) and left (j) eyes. OCT, optical coherence tomography.

FIGURE 3

(a) Intracranial pressure telemetry, 1 h baseline recording of patient with intracranial hypertension. Mean 23.8 mmHg (32.3 cm CSF), range 11.8–46.5 mmHg. (b) Above patient during presentation with fulminant IIH. Mean 48.6 mmHg (66.1 cm CSF) range 23.6–85.0 mmHg. Note peak values of 85 mmHg (115.6 cm CSF). (c) Histogram of pressure recordings from (a) and (b) – arrow demonstrates right shift with increasing pressure and waveform variability. CSF, cerebrospinal fluid.

FIGURE 4

The major ion channels responsible for CSF secretion in the choroid plexus are shown with sites of action of acetazolamide, AZD4017 and exenatide. Cortisone is converted to the active cortisol by 11ß-HSD1, cortisol binds to the GR and MR receptors, which upregulate Na⁺ K⁺ ATPase activity; AZD4017 inhibits 11ß-HSD1 reducing local availability of cortisol. Exenatide binds and activates GLP-1R stimulating the conversion of ATP to cAMP by AC. cAMP activates PKA, which inhibits the Na⁺ H⁺ exchanger reducing Na⁺ re-absorption and also inhibits the Na⁺ K⁺ ATPase reducing Na⁺ excretion. Carbonic anhydrase catalyzes the conversion of H₂O and CO₂ to H⁺ and HCO₃⁻, which is important in the establishment of the osmotic gradient. Both acetazolamide and topiramate inhibit carbonic anhydrase function. AC, adenylate cyclase; AE2, anion exchange protein 2; cAMP, cyclic adenosine monophosphate; CSF, cerebrospinal fluid; CTFR, cystic fibrosis transmembrane conductance regulator; GLP-1: glucagon-like peptide 1; GLP-1R: glucagon-like peptide 1 receptor; 11ß-HSD, 11ß-hydroxysteroid dehydrogenase type 1; GR/MR, glucocorticoid and mineralocorticoid receptors; KCC1, K-Cl cotransporter 1; NHE1, Na-H antiporter; NKA, N-K ATPase; NKCC1, Na-K-Cl cotransporter; PKA, protein kinase A.