ABSTRACT & COMMENTARY
Hypoperfusion Response During Cortical Spreading Depolarizations
By Halinder S. Mangat, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Mangat reports no financial relationships relevant to this field of study.
Cortical spreading depolarizations (CSD) are common after severe brain trauma and are accompanied by alterations in cerebral blood flow physiology. In this study, the inverse neurovascular coupling is described, demonstrating cerebral hypoperfusion in response to CSD. This may be a novel mechanism of secondary brain injury.
Hinzman JM, et al. Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma. Brain 2014;137:2960-2972.
This study examines and describes the occurrence of an inverse neurovascular coupling response in peri-contusional brain tissue as a potential and novel mechanism for secondary brain injury.1 Electrocorticography recordings were coupled with peri-contusional cerebral blood flow, recorded using a thermal diffusion probe and a brain oximetry probe. A total of 876 recordings of cortical spreading depolarizations (CSD) were made in 17 of 24 patients with traumatic brain injury, with 106 days of data recording. Cerebral blood flow (CBF) data were limited to 39% of the study duration due to technical reasons. Both physiological neurovascular coupling (hyperemia) as well as inverse coupling (hypoperfusion) were seen in 42% of patients, while no CBF changes were seen in the remaining patients.
There appeared to be a relationship between the vascular response to CSD and cerebral autoregulation. Patients with a hyperemic response had intact autoregulation, whereas those with hypoperfusion had impairment in autoregulation. In one patient with a transformation from a hyperemic to hypoperfusion response, autoregulation had worsened. Although baseline CBF was comparable in both response types, if initial CBF was in the ischemic range, the majority of responses resulted in hypoperfusion, and CSD duration was longer in these episodes. Although patients with increased ischemic duration had worse outcomes, there was no difference in outcomes based on those with and without CSDs.
Commentary
CSDs have been described following several acute neurological injuries and are associated with poor outcome.2-4 CSD is an electrophysiological phenomenon resulting in complete and sustained depolarization of neurons and astrocytes, and it causes complete loss of ionic cell membrane gradients.5 CSD is accompanied by a vascular response, which may be of three possible types — none, transient hyperemia (physiological hyperdynamic response), or vasoconstriction causing hypoperfusion (inverse hemodynamic response).
Following CSD, energy-dependent ion pumps attempt to re-establish ionic gradients and cause depletion of metabolic substrates.6,7 These substrates are supplied by hyperemia associated with CSD. However, if there is hypoperfusion during CSD, there is cellular hypoxia and reduction in metabolic substrate provision while demand is increased, resulting in further neuronal injury. The hyperemic response after CSD has been demonstrated in humans. This study confirms the presence of an inverse neurovascular response in humans after brain injury. A transformation of hemodynamic response from hyperemic to hypoperfusion is also demonstrated in two patients.
In addition, the correlation with cerebral autoregulation has not been demonstrated previously. Whether the state of dynamic autoregulation entirely determines the type of hemodynamic response to CSD remains to be evaluated. These findings may provide insight into novel mechanisms of secondary neuronal injury after brain trauma. Poor autoregulation after severe traumatic brain injury is associated with worse outcome. It is likely that altered electrophysiological and hemodynamic responses are both a result of the primary injury and contribute to secondary injury and, therefore, are associated with neuronal injury and likely worse clinical outcomes.
References
- Hinzman JM, et al. Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma. Brain 2014;137:2960-2972.
- Hartings JA, et al., for the COSBID group. Spreading depolarisations and outcome after traumatic brain injury: A prospective observational study. Lancet Neurol 2011;10:1058-1064.
- Lauritzen M, et al. Clinical relevance of cortical spreading depression in neurological disorders: Migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab 2011;31:17-35.
- Dreier JP, et al., for the COSBID study group. Cortical spreading depression is a novel process involved in ischemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain 2009;132:1866-1881.
- Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944;7:359-390.
- Bosche B, et al., for the COSBID study group. Recurrent spreading depolarisations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann Neurol 2010;67:607-17.
- Hashemi P, et al. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperemia: Evidence for risk of an adverse effect of Leao’s spreading depression. J Cereb Blood Flow Metab 2009;29:166-175.
