Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs.

BACKGROUND: Circumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence. METHODS: Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. RESULTS: In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. CONCLUSIONS: Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. TRIAL REGISTRATION: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.

Fulminant and fatal onset of pan-aquaporinopathy.

Early administration of high-dose steroids and plasma exchange (PE) offers the best chance of treating neuromyelitis optica spectrum disease (NMOSD) attacks, but up to 20% of patients fail to respond. We report the case of a first devastating NMOSD attack leading to death despite optimal treatment. While receiving steroids during a bilateral blinding optic neuritis, this female patient suffered a severe attack involving the spinal cord and circumventricular organs (CVOs), including the pineal gland. Early adjunctive daily PE failed to prevent sudden death. AQP4-antibodies were strongly positive. To our knowledge, this is the first case of exceptionally severe monophasic NMOSD leading to full-blown lesions in all AQP4-expressing sites. Lesions of the periventricular ependyma and CVOs are highly exceptional and the involvement of the pineal gland, which is also a CVO, is novel. Moreover, the patient's condition continued to worsen until death, without any sign of recovery. We term this unexpected outcome the 'anti-Lazarus effect'. Although the mechanisms of resistance to treatment remain elusive, very early initiation of immunosuppressive drugs or adjunctive salvage therapies could be envisioned to manage these devastating attacks.

Circumventricular organs of human brain visualized on post-contrast 3D fluid-attenuated inversion recovery imaging.

PURPOSE: Although contrast-enhanced three-dimensional T2 fluid-attenuated inversion recovery (3D T2-FLAIR) images are useful for assessing various neuronal diseases, physiological enhancement of the circumventricular organs on the images have not been investigated. We aimed to assess the physiological appearance of the circumventricular organs on contrast-enhanced 3D T2-FLAIR images. METHODS: We studied 3-T MR images of the brain of 30 individuals with no apparent brain abnormalities. In ten areas of the brain, the degree of contrast enhancement on 3D T2-FLAIR and magnetization-prepared rapid gradient-echo (MPRAGE) images was evaluated using a 4-point grading system. The pre- and post-contrast mean contrast ratios (CRs) of the anterior pituitary gland, median eminence, and pineal gland were compared. RESULTS: On post-contrast 3D T2-FLAIR images, marked enhancement was most frequently scored in the median eminence, followed by the choroid plexus, posterior pituitary gland, and pineal gland. In 10 of the 30 cases, the vascular organ of the lamina terminalis and the area postrema were enhanced but the subcommissural organ was not. The difference in the mean pre- and post-contrast CRs of the median eminence and pineal gland was statistically significant, while that of the anterior pituitary gland was not. CONCLUSION: On contrast-enhanced 3D T2-FLAIR images, the circumventricular organs show variable enhancement. Our findings help to recognize physiological and abnormal enhancement of brain structures on contrast-enhanced 3D T2-FLAIR images.