The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema.

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes.

Complications in Aneurysmal Subarachnoid Hemorrhage Patients With and Without Subdural Electrode Strip for Electrocorticography.

Purpose: Patients with aneurysmal subarachnoid hemorrhage (aSAH) frequently develop secondary noninfectious and infectious complications with an important impact on clinical course and outcome. In this study, we report on the rate of typical extracranial and intracranial complications in 30 prospectively enrolled patients with severe aSAH who received a linear subdural recording strip for continuous electrocorticography to detect ictal epileptiform events and spreading depolarizations.

Methods: The group was compared with 30 retrospectively included patients with aSAH who had not received a subdural recording strip, but were treated during the same period.

Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons.

Objective: To characterize pathogenic effects of antibodies to dipeptidyl-peptidase-like protein 6 (DPPX), a subunit of Kv4.2 potassium channels, on gut and brain neurons.

Methods: We identified a new patient with anti-DPPX encephalitis and analyzed the effects of the patient's serum and purified immunoglobulin G (IgG), and of serum of a previous patient with anti-DPPX encephalitis, on the activity of enteric neurons by voltage-sensitive dye imaging in guinea pig myenteric and human submucous plexus preparations.

A validation study of the use of near-infrared spectroscopy imaging in primary and secondary motor areas of the human brain.

The electroencephalographically measured Bereitschafts (readiness)-potential in the supplementary motor area (SMA) serves as a signature of the preparation of motor activity. Using a multichannel, noninvasive near-infrared spectroscopy (NIRS) imager, we studied the vascular correlate of the readiness potential. Sixteen healthy subjects performed a self-paced or externally triggered motor task in a single or repetitive pattern, while NIRS simultaneously recorded the task-related responses of deoxygenated hemoglobin (HbR) in the primary motor area (M1) and the SMA.

How spreading depolarization can be the pathophysiological correlate of both migraine aura and stroke.

The term spreading depolarization describes a mechanism of abrupt, massive ion translocation between neurons and the interstitial space, which leads to a cytotoxic edema in the gray matter of the brain. In energy-compromised tissue, spreading depolarization is preceded by a nonspreading silencing (depression of spontaneous activity) because of a neuronal hyperpolarization. By contrast, in tissue that is not energy compromised, spreading depolarization is accompanied by a spreading silencing (spreading depression) of spontaneous activity caused by a depolarization block.

Excitotoxicity and metabolic changes in association with infarct progression.

Background And Purpose: We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression.

Methods: In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging.

Criteria for the diagnosis of noninfectious and infectious complications after aneurysmal subarachnoid hemorrhage in DISCHARGE-1.

Patients with aneurysmal subarachnoid hemorrhage (aSAH) frequently develop secondary noninfectious and infectious complications that have an important impact on clinical course and outcome. We here report on criteria for the diagnosis of the most important complications after aSAH based on clinical status, neuroimaging, and laboratory tests, including cerebrospinal fluid parameters. These criteria will be used for a retrospective analysis of aSAH patients who were recruited at the Charité Berlin for the CoOperative Study on Brain Injury Depolarisations (COSBID) before the Depolarisations in Ischaemia after Subarachnoid Haemorrhage-1 (DISCHARGE-1) trial started.

Spreading ischemia after aneurysmal subarachnoid hemorrhage.

Spreading depolarization (SD) is a wave of mass neuronal and glial depolarization associated with net influx of cations and water. Prolonged SDs facilitate neuronal death. SD induces tone alterations in cerebral resistance arterioles, leading to either transient hyperperfusion (physiological neurovascular coupling) in healthy tissue or hypoperfusion (inverse neurovascular coupling = spreading ischemia) in tissue at risk for progressive damage.

Correlates of spreading depolarization in human scalp electroencephalography.

It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear.

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.

Background: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.

Increased extracellular K+ concentration reduces the efficacy of N-methyl-D-aspartate receptor antagonists to block spreading depression-like depolarizations and spreading ischemia.

Background And Purpose: Spreading depression (SD)-like depolarizations may augment neuronal damage in neurovascular disorders such as stroke and traumatic brain injury. Spreading ischemia (SI), a particularly malignant variant of SD-like depolarization, is characterized by inverse coupling between the spreading depolarization wave and cerebral blood flow. SI has been implicated in particular in the pathophysiology of subarachnoid hemorrhage.