title: Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension.
abstract: The syndrome idiopathic intracranial hypertension (IIH) includes symptoms and signs of raised intracranial pressure (ICP) and impaired vision, usually in overweight persons. The pathogenesis is unknown. In the present prospective observational study, we characterized the histopathological changes in biopsies from the frontal brain cortical parenchyma obtained from 18 IIH patients. Reference specimens were sampled from 13 patients who underwent brain surgery for epilepsy, tumors or acute vascular diseases. Overnight ICP monitoring revealed abnormal intracranial pressure wave amplitudes in 14/18 IIH patients, who underwent shunt surgery and all responded favorably. A remarkable histopathological observation in IIH patients was patchy astrogliosis defined as clusters of hypertrophic astrocytes enclosing a nest of nerve cells. Distinct astrocyte domains (i.e. no overlap between astrocyte processes) were lacking in most IIH biopsy specimens, in contrast to their prevalence in reference specimens. Evidence of astrogliosis in IIH was accompanied with significantly increased aquaporin-4 (AQP4) immunoreactivity over perivascular astrocytic endfeet, compared to the reference specimens, measured with densitometry. Scattered CD68 immunoreactive cells (activated microglia and macrophages) were recognized, indicative of some inflammation. No apoptotic cells were demonstrable. We conclude that the patchy astrogliosis is a major finding in patients with IIH. We propose that the astrogliosis impairs intracranial pressure-volume reserve capacity, i.e. intracranial compliance, and contributes to the IIH by restricting the outflow of fluid from the cranium. The increased perivascular AQP4 in IIH may represent a compensatory mechanism to enhance brain fluid drainage.
authors.affiliation: Department of Neurosurgery, Oslo University Hospital - Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: p.k.eide@medisin.uio.no.
authors.forename: Per Kristian
authors.initials: PK
authors.lastname: Eide
authors.affiliation: Department of Neurosurgery, Oslo University Hospital - Rikshospitalet, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Vigdis Andersen
authors.initials: VA
authors.lastname: Eidsvaag
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
authors.affiliation: Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Hans-Arne
authors.initials: HA
authors.lastname: Hansson
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005911:Gliosis / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D011559:Pseudotumor Cerebri / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4
keywords: Aquaporin-4; Astrogliosis; Benign intracranial hypertension; Interstitial fluid disturbance; Pseudotumor cerebri; Pulsatile intracranial pressure