Arzu Bilgin-Freiert

Cerebral Hemodynamic and Metabolic Effects of Remote Ischemic Preconditioning in Patients with Subarachnoid Hemorrhage

BACKGROUND Remote ischemic preconditioning (RIPC) is a form of endogenous neuroprotection induced by transient, subcritical ischemia in a distant tissue. RIPC effects on cerebral hemodynamics and metabolism have not been explored in humans. This study evaluates hemodynamic and metabolic changes induced by RIPC in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS Patients underwent three or four RIPC sessions 2-12 days following SAH. Continuous vitals, intracranial pressure (ICP), and transcranial Doppler (TCD) data were collected. Brain microdialysis metabolic changes were monitored. ICP and TCD morphological clustering and analysis of intracranial pulse (MOCAIP) metrics were compared to positive and negative control groups for cerebral vasodilation. RESULTS Seven ICP and six TCD recordings from four patients demonstrated an increase in mean ICP (8-14.57 mmHg, p < 0.05). There was a reduction in middle cerebral artery (MCA) mean velocities (111-87 cm/s, p = 0.039). ICP and TCD MOCAIP metrics demonstrated variances consistent with vasodilation that returned to baseline following the RIPC. Over the duration of the RIPC, microdialysis showed reduction in the lactate/pyruvate (L/P) ratio (42.37-33.77, p = 0.005) and glycerol (174.04-126 μg/l, p < 0.005), which persisted for 25-54 h after the last RIPC. CONCLUSIONS This study demonstrated cerebrovascular effects induced by RIPC consistent with transient vasodilation. Cerebral metabolic effects suggest protection from ischemia and cell membrane preservation lasting up to 2 days following RIPC.

Peripheral vascular disease as remote ischemic preconditioning, for acute stroke

OBJECTIVES Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke. METHODS Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patients demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge. RESULTS The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20-93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS≤4: PVD 47.1%, control 4.35%, p<0.003), significantly more favorable outcomes at discharge (mRS≤2: PVD 30.8%, control 3.84%, p<0.012), and a significantly lower mortality rate (PVD 26.9%, control 57.7%, p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (admission: PVD 39.6 mL, control 148.3 mL, p<0.005 and discharge: PVD 111.7 mL, control 275 mL, p<0.001). CONCLUSION Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models.

Effects of Remote Ischemic Preconditioning on the Coagulation Profile of Patients With Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study

BACKGROUND Animal studies suggest that ischemic preconditioning prolongs coagulation times. OBJECTIVE Because coagulation changes could hinder the translation of preconditioning into clinical settings where hemorrhage may be an issue, such as ischemic or hemorrhagic stroke, we evaluated the effects of remote ischemic preconditioning (RIPC) on coagulation in patients undergoing RIPC after aneurysmal subarachnoid hemorrhage (SAH). METHODS Twenty-one patients with SAH (mean age, 56.3 years) underwent 137 RIPC sessions 2 to 12 days after SAH, each consisting of 3 to 4 cycles of 5 to 10 minutes of lower limb ischemia followed by reperfusion. Partial thromboplastin time (PTT), prothrombin time (PT), and international normalized ratio (INR) were analyzed before and after sessions. Patients were followed for hemorrhagic complications. RESULTS No immediate effect was identified on PTT (mean pre-RIPC, 27.62 s; post-RIPC, 27.54 s; P = .82), PT (pre-RIPC, 10.77 s; post-RIPC, 10.81 s; P = .59), or INR (pre-RIPC, 1.030; post-RIPC, 1.034; P = .57) after each session. However, statistically significant increases in PT and INR were identified after exposure to at least 4 sessions (mean PT pre-RIPC, 11.33 s; post-RIPC, 12.1 s; P = .01; INR pre-RIPC, 1.02; post-RIPC, 1.09; P = .014, PTT pre-RIPC, 27.4 s; post-RIPC, 27.85 s; P = .092) with a direct correlation between the number of sessions and the degree of increase in PT (Pearson correlation coefficient = 0.59, P = .007) and INR (Pearson correlation coefficient = 0.57, P = .010). Prolonged coagulation times were not observed in controls. No hemorrhagic complications were associated with the procedure. CONCLUSION RIPC by limb ischemia appears to prolong the PT and INR in human subjects with SAH after at least 4 sessions, correlating with the number of sessions. However, values remained within normal range and there were no hemorrhagic complications.

An evidence-based approach to the efficient use of computed tomography imaging in the neurosurgical patient.

BACKGROUND Computed tomography (CT) is the current standard for rapidly diagnosing some of the more common structural pathologies that affect the neurosurgical patient perioperatively. With this convenience comes the potential for its overuse. OBJECTIVE To investigate the utility of head CT scans ordered for various clinical indications. METHODS All head CT studies ordered by the UCLA Neurosurgery Department from August 15, 2011 through December 15, 2011, were prospectively studied. Variables collected included demographic information, diagnosis, surgical procedures, indication for CT, CT findings, and whether the study led to a documentable change in management. RESULTS There were 801 head CT studies ordered for the 462 patients who were admitted to the neurosurgical service. The authors identified 14 indications for ordering a head CT with the following probabilities of a positive finding: examination change (17/56, 30.3%), follow-up (4-6 hours after intracerebral hemorrhage; 16/126, 12.7%), CT angiography (11/30, 36.7%), routine postoperative imaging (6/126, 4.7%), postventriculostomy placement (4/62, 6.5%), immediately before (4/31, 12.9%) or after removal of (2/42, 4.8%) a ventriculostomy, surveillance (>24 hours after intracerebral hemorrhage or external ventricular drain placement) (3/66, 4.5%), headaches (2/8, 25%), ground level fall (1/8, 12.5%), intracranial pressure spikes (2/6, 33.3%), and delayed (6-24 hours after intracerebral hemorrhage; 1/25, 4%). CONCLUSION The probability of discovering a clinically significant finding varies widely for each of the listed study indications. This prospective analysis of all CT scans ordered at a single institution suggests that imaging studies obtained without a change in neurological status were unlikely to produce a positive finding, and even when there was a positive finding, it was extremely unlikely to result in any intervention.

Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury.

Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of cerebral spinal fluid provides a quick, non-invasive modality for evaluating the metabolic activity of brain-injured patients. In a prospective study, we compared the CSF of 44 TBI patients and 13 non-injured control subjects. CSF was screened for ten parameters: β-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace). Using mixed effects measures, we discovered statistically significant differences between control and trauma concentrations (mM). TBI patients had significantly higher concentrations of PG, while statistical trends existed for lactate, glutamine, and creatine. TBI patients had a significantly decreased concentration of total creatinine. There were no significant differences between TBI patients and non-injured controls regarding β- or α-glucose, alanine, pyruvate or acetate. Correlational analysis between metabolites revealed that the strongest significant correlations in non-injured subjects were between β- and α-glucose (r = 0.74), creatinine and pyruvate (r = 0.74), alanine and creatine (r = 0.62), and glutamine and α-glucose (r = 0.60). For TBI patients, the strongest significant correlations were between lactate and α-glucose (r = 0.54), lactate and alanine (r = 0.53), and α-glucose and alanine (r = 0.48). The GLM and multimodel inference indicated that the combined metabolites of PG, glutamine, α-glucose, and creatinine were the strongest predictors for CMRO2, ICP, and GOSe. By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury.