Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: Possible link to blood–brain barrier dysfunction

Abstract

SUMMARY Spreading depolarization describes a sustained neuronal and astroglial depolarization with abrupt ion translocation between intraneuronal and extracellular space leading to a cytotoxic edema and silencing of spontaneous activity. Spreading depolarizations occur abundantly in acutely injured human brain and are assumed to facilitate neuronal death through toxic effects, increased metabolic demand, and inverse neurovascular coupling. Inverse coupling describes severe hypoperfusion in response to spreading depolarization. Ictal epileptic events are less frequent than spreading depolarizations in acutely injured human brain but may also contribute to lesion progression through increased metabolic demand. Whether abnormal neurovascular coupling can occur with ictal epileptic events is unknown. Herein we describe a patient with aneurysmal subarachnoid hemorrhage in whom spreading depolarizations and ictal epileptic events were measured using subdural opto-electrodes for direct current electrocorticography and regional cerebral blood flow recordings with laser-Doppler flowmetry. Simultaneously, changes in tissue partial pressure of oxygen were recorded with an intraparenchymal oxygen sensor. Isolated spreading depolarizations and clusters of recurrent spreading depolarizations with persistent depression of spontaneous activity were recorded over several days followed by a status epilepticus. Both spreading depolarizations and ictal epileptic events where accompanied by hyperemic blood flow responses at one optode but mildly hypoemic blood flow responses at another. Of note, quantitative analysis of Gadolinium-diethylene-triamine-pentaacetic acid (DTPA)–enhanced magnetic resonance imaging detected impaired blood–brain barrier integrity in the region where the optode had recorded the mildly hypoemic flow responses. The data suggest that abnormal flow responses to spreading depolarizations and ictal epileptic events, respectively, may be associated with blood–brain barrier dysfunction.

Characterization of the Relationship Between Intracranial Pressure and Electroencephalographic Monitoring in Burst-Suppressed Patients

“…This is suggested by another study by Woitzik et al which found evidence of delayed cerebral ischemia in aSAH patients with no angiographic evidence of vasospasm, but did experience CSDs (Woitzik et al, 2012). This inverted neurovascular coupling after aSAH has also been observed using laser Doppler flowmetry (LDF) during ictal epileptic activity (Winkler et al, 2012). While these studies provide insight into pathological neurovascular coupling in the acute period following an injury, the reliance on additional and unconventional monitoring modalities has limited the studies on human patients.…”

Interplay between Cortical Spreading Depolarization and Seizures

“…It is believed that the blood-brain barrier is disrupted by this inciting insult, allowing for changes in extracellular concentrations of ions including a decrease in magnesium concentrations and elevation in potassium levels [7,8,9]. Such changes alter the local neuronal microenvironment and trigger a cascade of cellular events ultimately leading to glutamate-induced toxicity [10].…”

A laser Doppler system for monitoring cerebral microcirculation: implementation and evaluation during neurosurgery

“…Previous studies based on Monte Carlo simulations using similar optical probe tip designs have estimated the optical sampling depth to approximately 1 mm in brain tissue [16,9,18]. The probe design could also be compared with previous investigations where a subdural optode-strip was used on the brain surface [7,35]. As the LDPM system can be equipped with multiple detectors our configuration also allows for multipoint recordings, but with the added advantage of measurement possibilities inside the tissue.…”

“…Recently Dreier et al applied LDPM on the surface of the brain using an optode strip combined with electrodes to study spreading ischemia 2009 [7] and epileptic activity 2012 [35] in patients with subarachnoid haemorrhage. LDPM is, however, still not an established monitoring method in the neurosurgical and neurointensive care setting.…”