Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies

Abstract

Substantial progress has been made over the past two decades in detecting, predicting and promoting recovery of consciousness in patients with disorders of consciousness (DoC) caused by severe brain injuries. Advanced neuroimaging and electrophysiological techniques have revealed new insights into the biological mechanisms underlying recovery of consciousness and have enabled the identification of preserved brain networks in patients who seem unresponsive, thus raising hope for more accurate diagnosis and prognosis. Emerging evidence suggests that covert consciousness, or cognitive motor dissociation (CMD), is present in up to 15–20% of patients with DoC and that detection of CMD in the intensive care unit can predict functional recovery at 1 year post injury. Although fundamental questions remain about which patients with DoC have the potential for recovery, novel pharmacological and electrophysiological therapies have shown the potential to reactivate injured neural networks and promote re-emergence of consciousness. In this Review, we focus on mechanisms of recovery from DoC in the acute and subacute-to-chronic stages, and we discuss recent progress in detecting and predicting recovery of consciousness. We also describe the developments in pharmacological and electrophysiological therapies that are creating new opportunities to improve the lives of patients with DoC.

Abstract

In this Review, the authors discuss recent progress in the detection and prediction of recovery of consciousness in patients with disorders of consciousness caused by severe brain injuries. They describe the ongoing development of pharmacological and electrophysiological therapies designed to enhance recovery.

Key points

• A common pathophysiological mechanism underlying disorders of consciousness (DoC) is the withdrawal of excitatory synaptic activity across the cerebrum produced by deafferentation or disfacilitation of neocortical, thalamic and striatal neurons.

• Recovery from coma involves various mechanisms, culminating in the restoration of excitatory neurotransmission across long-range corticocortical, thalamocortical and thalamostriatal connections.

• The re-emergence of consciousness is associated with a shift in patterns of neuronal activity across the corticothalamic system that can be measured with EEG, PET or resting-state functional MRI.

• Task-based functional MRI and EEG can reveal cognitive motor dissociation in up to 15–20% of patients who seem unresponsive on behavioural examination, and emerging evidence suggests that early detection of cognitive motor dissociation in the intensive care unit predicts 1-year functional outcomes.

• Amantadine is the only therapy that has been associated with the acceleration of recovery of consciousness in a randomized controlled trial of patients with subacute traumatic DoC, but multiple pharmacological and neuromodulatory therapies are now being tested.

• Emerging advances in diagnostic and prognostic techniques provide new opportunities to detect consciousness, monitor its recovery, elucidate its neuronal substrate and identify the therapeutic potential of promoting re-emergence of consciousness in a subset of patients with DoC.