Spreading Depolarisations After TBI: A Clinical Context

Abstract & Commentary

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.

Synopsis: Spreading depolarisations following severe traumatic brain injury are associated with a poor outcome. They serve to cause secondary injury and energy imbalance. This mechanism might provide a target for therapeutic intervention.

Source: Hartings JA, et al. Spreading depolarisations and outcome after traumatic brain injury: A prospective observational study. Lancet Neurol 2011;10:1058-1064.

This study reveals the association of two types of spreading depolarisations — cortical spreading (CSD) and isoelectric spreading (ISD) — with poor clinical outcome in patients with traumatic brain injury (TBI).1 The former occur in the background of baseline cortical electrical activity and the latter in isoelectric cortex, which is thought to be penumbral tissue.

The study included 109 patients with acute TBI who required surgical intervention. A majority of the patients suffered subdural hematomas and parenchymal contusions. Traumatic subarachnoid hemorrhage (tSAH) was frequently associated with these injuries. Patients were managed according to TBI guidelines. After the surgical evacuation of the lesion, an electrode strip was placed over the cortical surface on viable but frequently edematous or contused cortex with minimal tSAH. The electrocorticography was continued for a maximum of 7 days.

The study recorded 1328 depolarisations in 58 (56%) patients. Of these 38 had CSD only and 20 had at least one ISD, with or without CSD. Nineteen percent of patients who had no depolarisations had an unfavorable outcome by eGOS. However, 53% with CSD and 85% with ISD had unfavorable outcome. Eleven patients with depolarisations also had seizures. No individual covariate of outcome was associated with depolarisations.

Commentary

Spreading depolarisations are a spectrum of electrophysiological phenomena, which involve waves of depolarizing activity over injured and penumbral neurons, and were first described by Leao in 1944.2 These waves have since been better characterized, and the COSBID group has also reported their presence in other neurological illnesses.3 This is the first study demonstrating the clinical impact of spreading depolarisations on patient outcome.

There are numerous mechanisms of neuronal injury associated with spreading depolarisations such as calcium influx, loss of ionic gradients, and neuronal swelling. These are also 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).4 When the inverse response propagates with the depolarization wave, it is called cortical spreading ischemia. While in healthy cortex the depolarisations cause limited vascular disturbances lasting 10 minutes, in injured cortex they may be self-perpetuating and long-lasting (up to 100 mins). An inverse hemodynamic response causes further ischemia, which may then generate more depolarisations, causing a vicious cycle. In SAH, CSD result in cellular hypoxia, probably by both reducing supply and increasing consumption.5 In addition to local hemodynamic disturbances, CSD also causes glucose depletion even in the presence of a hyperemic response.6

These cellular phenomenon result in further metabolic insult to the neuronal cells likely affecting recovery in the penumbral region and causing further necrosis in vulnerable areas.

In the present study, every effort was made to avoid any confounding factors. The electrodes used are similar to the ones used in epilepsy localization and are not thought to cause cortical irritation. They can capture electrical activity within a distance of 5 cm.

Spreading depolarisations are a novel pathophysiological mechanism associated with secondary insults and poor outcome after TBI. However, causation, as the authors state, can only be proven if therapeutic interventions to modify the depolarisations result in improved outcome. Also, a non-invasive method of monitoring for and identifying depolarisations will make it easier to study its effects. Surely, this will be an area of active research in the coming years.

References

1. 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.

2. Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944;7:359-390.

3. Lauritzen M, et al. Clinical relevance of cortical spreading depression in neurological disorders: Migraine, malignant stroke, subarachnoid hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab 2011;31:17-35.

4. Dreier JP, et al. for the COSBID group. Cortical spreading depression is a novel process involved in ischemic damage in patients with aneurysmal subarachnoid hemorrhage. Brain 2009;132:1866-1881.

5. Boshe B, et al, for the COSBID group. Recurrent spreading depolarisations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann Neurol 2010;67: 607-617.

6. 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.