Persistent vegetative state and minimally conscious state: a systematic review and meta-analysis of diagnostic procedures

Abstract

Background: Acute brain damage can cause major disturbances of consciousness, ranging all the way to the persistent vegetative state (PVS), which is also known as "unresponsive wakefulness syndrome". PVS can be hard to distinguish from a state of minimal preserved consciousness ("minimally conscious state," MCS); the rate of misdiagnosis is high and has been estimated at 37-43%. In contrast, PVS is easily distinguished from brain death. We discuss the various diagnostic techniques that can be used to determine whether a patient is minimally conscious or in a persistent vegetative state.

Methods: This article is based on a systematic review of pertinent literature and on a quantitative meta-analysis of the sensitivity and specificity of new diagnostic methods for the minimally conscious state.

Results: We identified and evaluated 20 clinical studies involving a total of 906 patients with either PVS or MCS. The reported sensitivities and specificities of the various techniques used to diagnose MCS vary widely. The sensitivity and specificity of functional MRI-based techniques are 44% and 67%, respectively (with corresponding 95% confidence intervals of 19%-72% and 55%-77%); those of quantitative EEG are 90% and 80%, respectively (95% CI, 69%-97% and 66%-90%). EEG, event-related potentials, and imaging studies can also aid in prognostication. Contrary to prior assumptions, 10% to 24% of patients in PVS can regain consciousness, sometimes years after the event, but only with marked functional impairment.

Conclusion: The basic diagnostic evaluation for differentiating PVS from MCS consists of a standardized clinical examination. In the future, modern diagnostic techniques may help identify patients who are in a subclinical minimally conscious state.

Figure 1

The diagnostic categorization of severely impaired consciousness. Two different aspects must be assessed: alertness (wakefulness) and awareness. The persistent vegetative state (PVS) is characterized by a lack of reproducible responses to the environment. As soon as simple responses to the environment are seen, the patient is said to be in a minimally conscious state (MCS). Functional communication (whether verbal or nonverbal) or functional use of objects indicates that the patient has emerged from the minimally conscious state. Patients will then often manifest a confusional or amnestic syndrome before regaining normal consciousness.

Figure 2

Results of the meta-analysis: sensitivities, specificities, and 95% confidence intervals (95% CI). Pooled sensitivities and specificities are additionally given for each of the techniques that are represented here by at least three different studies (pooled figures indicated by gray shading). Sensitivity is defined as the fraction of technically correctly classified MCS patients in reference to clinical evaluation with CRS-R as the gold standard. fMRI = functional magnetic resonance imaging; ERP = event-related cognitive potentials; qEEG = quantitative electroencephalography; TMS/EEG = combined transcranial magnetic stimulation and EEG; EMG = electromyography; FDG-PET = fluorodeoxyglucose positron emission tomography.

Figure 3

Methods for the diagnostic evaluation of consciousness. Fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain of a normal subject (left), a patient in a minimally conscious state (MCS, center), and a patient in a persistent vegetative state (PVS, right). Marked differences in cortical glucose metabolism are seen. Yellow and red correspond to high values for glucose metabolism, which is absolutely quantified in µmol of glucose per 100 g of brain tissue per minute. Reprinted with the kind permission of PD Dr. S. Förster, Department of Nuclear Medicine, Klinikum rechts der Isar, TU München (Munich).

eFigure

PRISMA flowchart of the literature search PVS = persistent vegetative state; MCS = minimally conscious state