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Ming-Yuan Tseng, Marek Czosnyka, Hugh Richards, John D. Pickard, and Peter J. Kirkpatrick

Object

The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow.

Methods

In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 ± 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0–5, 132 measurements in 32 patients).

There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation.

Conclusions

The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.

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Peter J. Kirkpatrick, Pietr Smielewski, Peter C. Whitfield, Marik Czosnyka, David Menon, and John D. Pickard

✓ Near-infrared spectroscopy was used to monitor changes in the cerebral oxygenation state in 13 patients during carotid endarterectomy. Variations in the levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb) were compared with changes in middle cerebral artery flow velocity measured using transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow velocity on application of the internal carotid artery cross-clamp, seven demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy, recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in three of these patients. Intraoperative shunts accelerated recovery of HbO2 and Hb signals in two of three individuals. Release of the internal carotid cross-clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those patients in whom spontaneous recovery had not occurred; in five instances, a hyperemia evolved with raised flow velocity and HbO2 to above baseline values. Cross-clamping and subsequent reperfusion of the external carotid artery had no effect on any parameter measured. The authors conclude that near-infrared spectroscopy can register changes in cerebral oxygenation during carotid endarterectomy without significant contamination from extracranial tissues.

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Peter J. Kirkpatrick, Piotr Smielewski, Marek Czosnyka, David K. Menon, and John D. Pickard

✓ A multimodality recording system was used in 14 ventilated patients with closed head injury to assess the potential use of near-infrared spectroscopy (NIRS) in the neurointensive care unit. Signals of intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, jugular venous saturation, and NIRS-derived changes in the chromophores of oxy- and deoxyhemoglobin were digitized and recorded. After a review of 886 hours of continuous monitoring, 376 hours were considered free from artifact and were entered for final analysis. In nine of the patients 38 events were recorded that demonstrated clear changes in cerebral perfusion pressure accompanied by hemodynamic changes in middle cerebral artery flow velocity (transcranial Doppler) and cortical perfusion (laser Doppler flowmetry). Near-infrared spectroscopy showed correlated changes in 37 events (97%) whereas jugular venous saturation monitoring registered only 20 (53%). There was associated peripheral oxygen desaturation in eight cases (21%), intracranial hypertension in 10 (26%), and cerebral hyperemia in eight (21%). The remaining 12 events (32%) appeared to be complex changes of uncertain origin. Iatrogenic factors were identified as causative in 14 cases (37%). The potential application of NIRS in adults and the importance of using multiple parameter recording systems in the interpretation of cerebral events are discussed.

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Afroditi Despina Lalou, Marek Czosnyka, Joseph Donnelly, John D. Pickard, FMedSci, Eva Nabbanja, Nicole C. Keong, Matthew Garnett, and Zofia H. Czosnyka

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.

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Nicole C. H. Keong, Alonso Pena, Stephen J. Price, Marek Czosnyka, Zofia Czosnyka, and John D. Pickard

The pathophysiology of NPH continues to provoke debate. Although guidelines and best-practice recommendations are well established, there remains a lack of consensus about the role of individual imaging modalities in characterizing specific features of the condition and predicting the success of CSF shunting. Variability of clinical presentation and imperfect responsiveness to shunting are obstacles to the application of novel imaging techniques. Few studies have sought to interpret imaging findings in the context of theories of NPH pathogenesis. In this paper, the authors discuss the major streams of thought for the evolution of NPH and the relevance of key imaging studies contributing to the understanding of the pathophysiology of this complex condition.