Physiological alterations of pineal recess crowding in symptomatic non-hydrocephalic pineal cysts

Pineal cysts are prevalent in the population. Due to more widespread use of magnetic resonance imaging, an increasing number of symptomatic patients with non-hydrocephalic pineal cysts are referred to neurologists and neurosurgeons. Currently, there is no generally accepted theoretical framework for linking symptoms to a pineal cyst. We have previously suggested that cyst-induced crowding of the pineal recess may affect venous runoff from the deep cerebral veins crossing the cyst. However, evidence underpinning this hypothesis is sparse. In the present study, we asked whether crowding of the pineal recess without imaging signs of hydrocephalus may be accompanied with alterations in blood flow of the internal cerebral veins, cerebrospinal fluid flow in the Sylvian aqueduct and cerebrospinal fluid-mediated tracer clearance from the brain along extravascular pathways (referred to as glymphatic function). This prospective, observational study included symptomatic individuals with non-hydrocephalic pineal cysts who underwent a standardized magnetic resonance imaging protocol (n = 25): Eleven patients were treated surgically with craniotomy and cyst extirpation and 14 individuals were managed conservatively without surgery. Our findings suggest that cyst-induced crowding of the pineal recess may have brain-wide effects: (i) There was a significant negative correlation between degree of crowding within the pineal recess and change in maximum venous flow velocity at the cyst, and a significant positive correlation between maximum venous flow velocity change at the cyst and net cerebrospinal fluid flow in the Sylvian aqueduct; (ii) increased degree of crowding in the pineal recess was accompanied by significantly impaired glymphatic enrichment in the cerebral cortex and subcortical white matter, indicative of a brain-wide effect in this cohort who also reported markedly impaired subjective sleep quality; (iii) there was a significant negative correlation between the apparent diffusion coefficient (suggestive of interstitial water content) within the thalamus and glymphatic enrichment of tracer and (iv) pineal recess crowding associated with symptoms. Comparison of the surgical cases [in whom 10/11 (91%) reported marked clinical improvement at follow-up] and the conservatively managed cases [in whom 1/14 (7%) reported marked clinical improvement at follow-up] showed differences in pre-treatment glymphatic tracer enrichment as well as differences in tracer enrichment in subarachnoid cerebrospinal fluid spaces. Taken together, we interpret these observations to support the hypothesis that cyst-induced crowding of the pineal recess without hydrocephalus may alter blood flow of the internal cerebral veins and cerebrospinal fluid flow and even cause brain-wide impairment of glymphatic transport with possible implications for cerebrospinal fluid transport of trophic factors such as melatonin.