Test-Retest Reliability of Outpatient Telemetric Intracranial Pressure Measurements in Shunt-Dependent Patients with Hydrocephalus and Idiopathic Intracranial Hypertension.

BACKGROUND: Some patients with hydrocephalus and idiopathic intracranial hypertension treated for elevated intracranial pressure (ICP) with a cerebrospinal fluid shunt may continue to experience symptoms or develop new symptoms despite valve adjustments. Use of telemetric ICP measurements may help confirm clinical suspicion of cerebrospinal fluid underdrainage or overdrainage in these patients. However, point in time, duration, and activity during the measurements have never been standardized. We devised a simple, repeatable maneuver for outpatient telemetric ICP recording and evaluated its test-retest reliability. METHODS: Data of patients who underwent ventriculoperitoneal or ventriculoatrial shunt placement and subsequent telemetric ICP sensor implantation were retrospectively reviewed. Telemetric ICP recordings in patients were conducted in a standardized manner: The standing-supine-sitting paradigm requires postural changes in 10-minute intervals over 30 minutes. First, the patient is requested to walk; second, to lay down; third, to sit down with a headrest elevation of 60°. ICP data (in mmHg) were reported as mean ± SD values. Test-retest validity was assessed using Pearson correlation analysis. RESULTS: We evaluated 66 ICP datasets obtained repeatedly with a time difference of at least 24 hours. Overall test-retest reliability was excellent (Pearson correlation coefficient 0.99, P < 0.001), as were the scores for individual postures: standing (correlation 0.98, P < 0.001), supine (correlation 0.98, P < 0.001), and sitting (correlation 0.99, P < 0.001). The sum of square differences of the test-retest measures reflected a comparable validity of all tested positions. CONCLUSIONS: We confirmed high test-retest reliability of the standing-supine-sitting paradigm for telemetric ICP measurements in the outpatient setting. High test-retest reliability should be considered as prerequisite for clinical decision making.

EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia.

OBJECTIVE: Cerebral edema caused by the disruption of the blood-brain barrier is a major complication after stroke. Therefore, strategies to accelerate and enhance neurovascular recovery after stroke are of prime interest. Our main aim was to study the role of ephrinB2/EphB4 signaling in mediating the vascular repair and in blood-brain barrier restoration after mild cerebral ischemia occlusion/reperfusion. APPROACH AND RESULTS: Here, we show that the guidance molecule ephrinB2 plays a key role in neurovascular protection and blood-brain barrier restoration after stroke. In a focal stroke model, we characterize the stroke-induced damage to cerebral blood vessels and their subsequent endogenous repair on a cellular, molecular, and functional level. EphrinB2 and its tyrosine kinase receptor EphB4 are upregulated early after stroke by endothelial cells and perivascular support cells, in parallel to their reassembly during neurovascular recovery. Using both retroviral and pharmacological approaches, we show that the inhibition of ephrinB2/EphB4 signaling suppresses post-middle cerebral artery occlusion neurovascular repair mechanisms resulting in an aggravation of brain swelling. In contrast, the activation of ephrinB2 after brain ischemia leads to an increased pericyte recruitment and increased endothelial-pericyte interaction, resulting in an accelerated neurovascular repair after ischemia. CONCLUSIONS: We show that reducing swelling could result in improved outcome because of reduction in damaged brain tissue. We also identify a novel role for ephrinB2/EphB4 signaling in the maintenance of the neurovascular homeostasis and provide a novel therapeutic approach in reducing brain swelling after stroke.

Evaluation of long-term upregulation of Calbindin D28K as a preventive approach for ischaemic stroke.

Buffering of intracellular calcium peaks following an acute ischaemic stroke protects neurons from necrotic and apoptotic cell death. However, the need for on-demand delivery of protective agents due to the short therapeutic window in stroke therapy makes it difficult to apply a calcium-buffering strategy in patients. We investigated the effects of a preventive upregulation of the calcium-binding protein Calbindin D28K as a potential approach for patients at a high risk of ischaemic stroke. We overexpressed Calbindin D28K in the striatal and cortical region in mice using an adeno-associated viral vector (AAV) for 12 weeks, and then assessed neuroprotective effects after MCAO. In contrast to studies showing a neuroprotective effect of shortly induced Calbindin D28K overexpression, we found no increased survival of neurons overexpressing Calbindin D28K for 12 weeks.We suggest that neuronal calcium metabolism adapts to higher Calbindin D28K levels after long-term overexpression. This potentially preventive approach to protect from ischaemic stroke does not have clinical applicability.