MRI brain lesion patterns in patients in anoxia-induced vegetative state

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Abstract

The object of this study was to analyze magnetic resonance imaging data from patients with disorders of consciousness who were suffering from non-traumatically induced brain lesions with respect to the pattern of vulnerability and to examine the associations between the sizes of these lesions and the clinical outcome of the patients. To this end, T1- and T2-weighted brain images were examined in twelve patients in the post-anoxic vegetative state after a median of 21 days after the causative event. Predominant in the characteristic lesion patterns were regions of pathological white matter signals within the frontal and occipital lobes and in the periventricular regions. The total volumes of the lesions were found to be associated with the severity of the patients' clinical outcomes as measured by the Ranchos Los Amigos Cognitive Scale after a median of 25 months. These lesion patterns demonstrated damage to cerebral networks critical to higher cognitive processes (“consciousness”) in both white and gray matter. The relevance of these findings for patients in anoxia-induced decreased levels of consciousness is discussed.

Introduction

The cerebral correlates to human consciousness remain topics of intense discussion and controversy [1], [2]. Survivors of severe traumatic or hypoxic brain damage who are initially comatose usually pass through a spectrum of clinical conditions before partially or fully recovering consciousness. If, after having been in a coma, the patient opens her or his eyes but remains unable to initiate voluntary motor activity, this marks the transition to the vegetative state (VS); the further transition to minimally conscious state (MCS) is marked by reproducible evidence of (simple) voluntary behaviour, whereas emergence from MCS is signaled by the return of functional communication or object use. Further developments lead to outcomes ranging from severe disability to a good recovery [3]. If, however, the patient remains in the VS for more than one month after the occurrence of brain damage, this condition is called the “persistent VS” (PVS). This state is not necessarily irreversible. Reversibility is much less likely in patients in the “permanent VS”, i.e. in a VS lasting more than 3 months after non-traumatic or 12 months after traumatic brain injury [4], [5]. The prognosis of patients in the VS/PVS due to cerebral anoxia has generally been considered to be particularly grave, but has been shown to be reversible in rare cases [4], [5], [6], [7], [8].

Over the past years, multiple investigations using electrophysiological, nuclear medical, and functional magnetic resonance imaging (fMRI) techniques have shown that, contrary to earlier expectations, patients with severe disorders of consciousness (PVS, MCS) respond to a variety of stimuli with cerebral cortical activity ([9], [10], [11], [12], [13], [14]]; cf. [15] for a review). It can, however, be argued that all these activation paradigms map neural activity reflecting automatic processing rather than demonstrating conscious awareness [16]. The use of paradigms during which subjects are instructed to remember or imagine well-defined mental actions, as suggested by Owen and co-workers [17], might reflect volitional neural activation only in cases that yield particularly robust specific findings in individual subjects. Certainly negative findings in such a paradigm do not exclude awareness. The application of the advanced imaging techniques necessary to employ this paradigm (the employment of which is further complicated by idiosyncracies of this difficult-to-investigate patient population) has generally been limited to specialized centers and thus most patients, world-wide, who are in the VS or PVS remain untested by these criteria.

The contribution of structural conventional MRI to this discussion has been minor up to now. The few MRI studies which describe lesions caused by global cerebral damage of a non-traumatic origin present heterogeneous findings and do not consider the PVS as a separate outcome group [18], [19]. After early autopsy studies which have been summarized by Kinney and Samuels [20], post-mortem aspects of the brain lesions of patients who had suffered from non-traumatic PVS have been investigated by Adams and co-workers [21]. They reported that brains of these patients exhibit massive damage of the gray matter both diffusely and focally, particularly in the neocortex and the thalamus, and widespread damage of the white matter, with consecutive atrophy and ventricular enlargement. In the present retrospective study, MRI findings from a group of patients who were in the VS/PVS after non-traumatic brain injury (cerebral anoxia) and belonged to different outcome classes were scrutinized, in order to investigate the MRI lesion pattern and size in vivo, in correlation with the clinical outcome after a follow-up period of a median of 25 months.

Section snippets

Patients and methods

Twelve patients were examined (8 males, 4 females; age range 37–73 years, median 52 years) who suffered from global cerebral anoxic damage caused by primary respiratory or cardiac arrest (for clinical features, cf. Table 1). Patients in whom cardiac/respiratory arrest was due to states directly involving the central nervous system (subarachnoid haemorrhage, encephalitis, and intoxication) and patients with previous brain lesions or a previous history of drug or alcohol abuse were not included.

Results

The distribution of the MRI findings is summarized in Table 2. All findings with respect to lesions were, to a large extent, symmetrical, so that the results are reported for both hemispheres together. All patients (except from patient 3) exhibited cortical lesions of some degree, generally most pronounced in the frontal and occipital lobes. The patients with the worst outcomes (outcome class 3) showed a more widespread lesion pattern of cortical lesions, whereas the patients with better

Discussion

This study of patients with severe disorders of consciousness after an event of prolonged cerebral hypoxia (VS/PVS) identified a characteristic pattern of brain lesions in MRI. All patients demonstrated extensive white matter lesions, with the largest lesions observed in the frontal and occipital lobe. Lesion magnitude showed an association with the severity of the outcome as quantitatively assessed by RLACS.

Previous MRI-based in vivo studies of patients who were in a long-term state of

Acknowledgement

This work was supported by the Fortüne Program of the Medical Faculty of the University of Tübingen (grant # 874).

References (29)

  • L. Sazbon et al.

    Course and outcome of patients in vegetative state of nontraumatic aetiology

    J Neurol Neurosurg Psychiatry

    (1993)
  • T. Bekinschtein et al.

    Emotion processing in the minimally conscious state

    J Neurol Neurosurg Psychiatry

    (2004)
  • S. Laureys et al.

    Auditory processing in the vegetative state

    Brain

    (2000)
  • N.D. Schiff et al.

    Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain

    Brain

    (2002)
  • Cited by (0)

    1

    Both authors contributed equally.

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