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

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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.


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).


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).


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.

ABBREVIATIONS ABP = arterial blood pressure; CBF = cerebral blood flow; CPP = cerebral perfusion pressure; ETV = endoscopic third ventriculostomy; fAMP = fundamental amplitude of ICP; ICP = intracranial pressure; MAP = mean ABP; NPH = normal pressure hydrocephalus; PRx = pressure reactivity index; RAP = cerebrospinal compensatory reserve index; Rout = resistance to CSF outflow.

Article Information

Correspondence Afroditi Despina Lalou: Newnham College, University of Cambridge, United Kingdom. adl43@cam.ac.uk.

INCLUDE WHEN CITING Published online March 16, 2018; DOI: 10.3171/2017.7.JNS17216.

Disclosures Prof. M. Czosnyka receives a licensing fee from Cambridge Enterprise, Ltd., for the ICM+ software. The patient data are derived from our ICM+ data archive and could possibly partially overlap with those of previous studies on NPH.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Graphs showing the difference in the trend between the original ICP and PRx (icpreal and prxnd, respectively) and the detrended signal (ICP and prxdma, respectively). Selected calculation periods of PRx at baseline and during infusion tests are shown. The values on the y-axes of the graphs are expressed as mm Hg (upper) and index score (lower). The numbers on the x-axis of the lower panel represent the date and time. ICP = detrended ICP; icpreal = original ICP signal; prxdma = PRx detrended with moving average filter; prxnd = PRx nondetrended.

  • View in gallery

    Scatterplots showing Rout versus PRx values derived from lumbar infusion studies, in all investigated patients versus those who were selected for CSF diversion. Left: Relationship between PRx and Rout in our cohort of 131 patients with NPH without shunts who were undergoing lumbar infusion studies. Right: Relationship between PRx and Rout in 82 patients as derived from lumbar infusion prior to treatment but who were selected for neurosurgical treatment.

  • View in gallery

    Scatterplots showing Rout versus Prx values derived from the lumbar infusion study, according to outcomes. Left: Relationship between PRx and Rout in patients who improved sustainably after surgery. Right: Relationship between PRx and Rout in patients who did not improve after surgery.



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