Mismatch negativity predicts recovery from the vegetative state
Introduction
Severe brain injury results in high morbidity and mortality rates. The majority of patients experience long-term or lifelong disabilities, bringing along major costs for family and society. So far there has been limited research concerning the group of young adults, who have the highest risks (Jennett, 1996, Finfer and Cohen, 2001).
Many individuals who sustain severe acquired brain injury experience prolonged or permanent disorders of consciousness. Acute severe brain injury inevitably results in coma, a state of loss of consciousness with the eyes closed, with no sleep–wake cycle (Multi-Society Task Force on Persistent Vegetative State, 1994a). If not resulting in death within a period of 3 to 4 weeks, this coma will develop into a vegetative state (VS, Jennett and Plum, 1972), where the patient seems awake but not aware: uncommunicative and unresponsive to the environment. VS is defined as persistent (PVS) as presence for longer than a month (Bernat, 2006). If recovery continues, patients regain minimal responsiveness to external stimuli (minimally conscious state, MCS) (Giacino et al., 2002), that eventually may result in full recovery of consciousness and responsiveness. Otherwise, patients may remain for a long time, or even the rest of their life span, in a vegetative or minimally conscious state. In a later stage it may be considered permanent although on clinical rather than temporal considerations (Working Party of the Royal College of Physicians, 2003). Once this diagnosis has been made, ethical and legal issues around withdrawal of treatment may arise (Jennett, 2005). The current study focuses on patients who were in VS for at least a month.
In general, 1–14 percent of the traumatic, and 12 percent of the non-traumatic prolonged comatose patients shift into VS (Multi-Society Task Force on Persistent Vegetative State, 1994a, Multi-Society Task Force on Persistent Vegetative State, 1994b). Fifty-two percent of the traumatic and 15 percent of the non-traumatic vegetative patients do recover to consciousness (Multi-Society Task Force on Persistent Vegetative State, 1994b). Since recovery from VS to consciousness does occur and depends on residual brain capacities, longitudinal research in the post-acute phase within this group is of great importance to understand what underlies.
The diagnosis of VS and MCS is based on clinical observation of behavioural criteria mostly. Several uncertainties stick to this method. First, observational methods depend on the subjective interpretation of behavioural responses, while conscious experience often occurs without behavioural signs. Second, no initial behavioural differences exist between the patients who may recover to consciousness and those who remain permanently vegetative.
To obtain complementary objective information about the level of consciousness in non-responsive patients, the present study focuses on neurophysiological responses during the recovery from VS to consciousness. A longitudinal study was performed in which the Mismatch Negativity (MMN) (Näätänen et al., 1978) was examined.
MMN is generated by the brain’s automatic response to physical stimulus deviation from the preceding stimulus in repetitive auditory input, revealing that physical features of auditory stimuli are fully processed regardless whether they are attended to or not (Näätänen et al., 2004). Mismatch negativity has repeatedly shown to predict outcome after coma (Fischer et al., 1999, Fischer et al., 2004, Kane et al., 1993, Kane et al., 1996, Luauté et al., 2005, Morlet et al., 2000). Fischer et al., 1999, Fischer et al., 2004 demonstrated that in the acute phase the presence of MMN predicted the exclusion of shifting into PVS. Additionally, Luauté et al. (2005) showed that when MMN was present in comatose patients no patient turned to permanent VS 1 year after the brain insult. MMN responses have been found in VS and MCS patients, especially when complex tones or musical notes were used (Jones et al., 1994, Kotchoubey et al., 2003, Kotchoubey et al., 2005). Additionally, in the study of Kotchoubey et al. (2005) 6 months after the brain insult clinical improvement was observed more frequently in VS and MCS patients with a significant MMN than in those without the MMN. Up to now researchers have not longitudinally investigated MMN responses during the recovery from VS. The present study reports on longitudinal changes in MMN responses during recovery to consciousness, and on its prognostic value in VS patients.
Section snippets
Participants
Ten severely brain-injured patients (7 were male; age M = 17.3, SD = 4.4, 8–25 years), who were admitted to an Early Intensive Neurorehabilitation Programme (Eilander et al., 2005), took part in the study between November 2002 and January 2004. The duration of the patients’ participation in the programme ranged from 1.5 to 5.2 months (M = 3.5 months; SD = 1.03) (Table 1). Time since injury at admission ranged from 6.2 to 19.4 weeks (M = 11.6 weeks; SD = 3.6). All but two patients suffered from a traumatic
Behavioural indices of recovery
At admission, the patients’ averaged LoC score was 3.6 (±0.52). At the end of the programme the average LoC score had increased to 5.9 (±1.9). Five patients reached a conscious level (exit MCS: LoC 7 or 8), 2 patients were still in MCS (LoC 5 or 6), and 3 patients were still in VS (LoC 2–4) at the end of the programme (see Table 1 for LoCdischarge).
The long-term outcome scores on the DRS and GOSE could be obtained for 9 patients, and are shown in Table 1. Two to 3 years after the injury the
Discussion
MMN-amplitude predicted the level of consciousness, and functional outcome 2 years after the injury. All patients who ultimately recovered to consciousness already showed higher amplitudes and shorter latencies in VS (first measurement) in comparison to the patients who remained in VS or MCS. A less strong prognostic value was found for the long-term functional outcome. The DRS and GOSE scores reveal that most of the conscious patients were still severely disabled about 2 years after their
Acknowledgements
This study was financially supported by: Stichting Centraal Fonds RVVZ, Johanna Kinderfonds, CZ groep Zorgverzekeringen, Zorgverzekeraar VGZ, Zorg en Zekerheid, Stichting Bio Kinderrevalidatie, and Hersenstichting Nederland. We gratefully acknowledge the cooperation of the patients and their families on this study. We are grateful to all members (H. van Dall, P.L. Hoenderdaal, J.C.M. Lavrijsen, A.I.R. Maas, A.J.H. Prevo, H. Stroink, A.J.J.M. Vingerhoets and H. van der Vlugt) of the scientific
References (39)
Chronic disorders of consciousness
Lancet
(2006)- et al.
Severe traumatic brain injury
Resuscitation
(2001) - et al.
Mismatch negativity and late auditory evoked potentials in comatose patients
Clin Neurophysiol
(1999) - et al.
A new method for off-line removal of ocular artifact
Electroencephalogr Clin Neurophysiol
(1983) - et al.
Persistent vegetative state after brain damage. A syndrome in search of a name
Lancet
(1972) - et al.
Auditory stimulation effect on a comatose survivor of traumatic brain injury
Arch Phys Med Rehabil
(1994) - et al.
Electrophysiological indicator of awakening from coma
Lancet
(1993) - et al.
Brain potentials in human patients with extremely severe diffuse brain damage
Neurosci Lett
(2001) - et al.
Stimulus complexity enhances auditory discrimination in patients with extremely severe brain injuries
Neurosci Lett
(2003) - et al.
Information processing in severe disorders of consciousness: vegetative state and minimally conscious state
Clin Neurophysiol
(2005)