Cerebral autoregulation, cerebrospinal fluid outflow resistance, and outcome following cerebrospinal fluid diversion in normal pressure hydrocephalus

Abstract

OBJECTIVE Normal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery. METHODS The authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients' outcome 6 months after surgery (improvement, temporary improvement, and no improvement). RESULTS The PRx was negatively correlated with resistance to CSF outflow (R = -0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = -0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = -0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = -0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013). CONCLUSIONS Autoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.

Cerebrospinal fluid dynamics in non-acute post-traumatic ventriculomegaly

“…Unlike "pure" iNPH and PTH shunt responders with high Rout, cerebral autoregulation and blood flow could vary in patients after TBI, especially severe TBI [3,27,30]. An inverse relationship between disturbed autoregulation and Rout has previously been reported in a mixed aetiology NPH cohort [30]. Our patients did not have the required parameters monitored in order to test this.…”

“…Finally, since vascular bed reactivity can be altered following TBI, and some of our current findings are suggesting cerebral blood volume disturbance in PTH, it would be of interest to explore the cerebral blood flow autoregulation of these patients and how it relates to CSF circulation. Unlike "pure" iNPH and PTH shunt responders with high Rout, cerebral autoregulation and blood flow could vary in patients after TBI, especially severe TBI [3,27,30]. An inverse relationship between disturbed autoregulation and Rout has previously been reported in a mixed aetiology NPH cohort [30].…”

“…Finally, we used a comparison group of consecutive, gender-matched idiopathic Normal Pressure Hydrocephalus (iNPH) patients with ventriculomegaly and clinical symptoms suggestive of NPH, that had a lumbar infusion test as part of their routine investigations and a positive response to shunt surgery with clinical documentation of improved symptoms at 6-month follow-up. The iNPH group had undergone infusion studies between 2003 and 2018 and the results previously reported [29][30][31]. Normal controls were not available, as all studies in our centre are performed on clinical indication.…”

Non-canonical, potassium-driven cerebrospinal fluid clearance

“…Intracranial compliance (C i ) and CSF resistance (R CSF ) describe the ability of the entire intracranial space (including brain, meninges, and outflow routes) to accommodate an increasing CSF volume that would otherwise increase intracranial pressure (ICP). In humans, these parameters are measured by a CSF constant rate infusion test (Aquilina et al, 2012, Eide, 2018, Lalou et al, 2018 and can aid in diagnosis and evaluation of conditions like hydrocephalus, which has decreased C i (Kahle et al, 2016). We developed a miniaturized version of this test to determine the C i and R CSF in mice.…”

Cerebrospinal fluid dynamics in pediatric pseudotumor cerebri syndrome

“…This is because it is the production, circulation or reabsorption of CSF that makes ICP dynamic and is likely to be deranged in PTCS. Historically, only around 30% of these disturbances have been shown to be reflected on steady-state ICP values [7,[15][16][17][18][19][20]. For these reasons, monitoring of ICP in conjunction with CSF dynamics has long been established in the field [9,11,[21][22][23].…”