Evoked potentials for the prediction of vegetative state in the acute stage of coma

For comatose patients in intensive care units, it is important to anticipate their functional outcome as soon and as reliably as possible. Among clinical variables the Glasgow Coma Score (GCS) and the patient's pupil reactivity are the strongest predictive variables. Evoked potentials help to assess objectively brain function. Over the past 20 years, numerous studies have assessed their prognostic utility in terms of awakening from coma. Fewer studies, however, have focused upon the utility of evoked potentials in predicting progression to the vegetative state. In this area evoked potentials appear to have a highly predictive value. In anoxic coma the abolition of somatosensory evoked potentials (SEPs) is related to a poor outcome, defined as death or survival in a vegetative state, with a 100% specificity. Following traumatic brain injury, the predictive value for unfavourable outcome is 98.5% when there are no focal injuries likely to abolish SEP cortical components. In contrast, the presence of event-related evoked potentials, and particularly mismatched negativity (MMN), is a strong predictor of awakening and precludes comatose patients from moving to a permanent vegetative state (PVS).     

Predicting outcome in hypoxic-ischemic coma. A prospective clinical and electrophysiologic study.

A prospective analysis of 40 patients with hypoxic-ischemic coma lasting at least 6 h following sudden cardiac arrest was undertaken. The patients, all of whom had preserved brain-stem function, were studied electrophysiologically with electroencephalography (EEG), and median nerve somatosensory evoked potentials (SEPs) within 48 h to establish prognostic indices. Our results indicate that preserved brain-stem function does not necessarily predict favorable outcome following cardiac arrest as 26 of 40 (65%) patients died without awakening. The bilateral absence of cortical evoked potentials predicted death without awakening in 19 of 26 patients (73%) while malignant EEG change was similarly predictive in 11 patients (42%). Bilateral absence of cortical evoked potentials and/or malignant EEG change reliably predicted unfavorable outcome in 21/26 patients (81%). Patients with normal or delayed central conduction time (CCT) as well as 'benign' or 'uncertain' EEG findings had an uncertain prognosis as some entered a persistent vegetative state (PVS) or died without awakening. Fourteen patients (35%) awakened of whom 5 (13%) recovered completely while another 9 (23%) had varying degrees of motor or cognitive impairment. SEP and EEG findings did not distinguish between these outcomes.     

The prognostic value of evoked responses from primary somatosensory and auditory cortex in comatose patients.

OBJECTIVE: To evaluate somatosensory and auditory primary cortices using somatosensory evoked potentials (SEPs) and middle latency auditory evoked potentials (MLAEPs) in the prognosis of return to consciousness in comatose patients. METHODS: SEPs and MLAEPs were recorded in 131 severe comatose patients. Latencies and amplitudes were measured. Coma had been caused by transient cardiac arrest (n=49), traumatic brain injury (n=22), stroke (n=45), complications of neurosurgery (n=12) and encephalitis (n=3). One month after the onset of coma patients were classified as awake, still comatose or dead. Three months after (M3), they were classified into one of the 5 categories of the Glasgow outcome scale (GOS). RESULTS: At M3, 41.2% were dead, 47.3% were conscious (GOS 3-5) and 11.5% had not recovered consciousness. None of the patients in whom somatosensory N20 and auditory Pa were absent did return to consciousness and in the post-anoxic group, reduced cortical amplitude too was always associated with bad outcome. Conversely, N20 and Pa were present, respectively, in 33/69 and 34/69 patients who did not recover. CONCLUSIONS: The prognostic value of SEPs and MLAEPs in comatose patients depends on the cause of coma. Measurement of response amplitudes is informative. Abolition of cortical SEPs and/or cortical MLAEPs precludes post-anoxic comatose patients from returning to consciousness (100% specificity). In any case, the presence of short latency cortical somatosensory or auditory components is not a guarantee for return to consciousness. Late components should then be recorded.     

The assessment of severe head injury by short-latency somatosensory and brain-stem auditory evoked potentials

The relative prognostic value of short-latency somatosensory evoked potentials (SEPs) and brain-stem auditory evoked potentials (BAEPs) was assessed in 35 patients with post-traumatic coma. Analysis of the evoked potentials was restricted to those recorded within the first 4 days following head injury. Abnormal SEPs were defined as an increase in central somatosensory conduction time or an absence of the initial cortical potential following stimulation of either median nerve. Abnormal BAEPs were classified as an increase in the wave I-V interval or the loss of any or all of its 3 most stable components (waves I, III and V) following stimulation of either ear. SEPs reliably predicted both good and bad outcomes. All 17 patients in whom SEPs were graded as normal had a favourable outcome and 15 of 18 patients in whom SEPs were abnormal had an unfavourable outcome. Although abnormal BAEPs were associated with an unfavourable outcome in almost all patients (6 of 7), only 19 of 28 patients with normal BAEPs had a favourable outcome. The finding of normal BAEPs was therefore of little prognostic significance. These results confirm the superiority and greater sensitivity of the SEP in detecting abnormalities of brain function shortly after severe head trauma.     

Comparison of the prognostic utility of VEPs and SEPs in comatose children

Visual evoked potentials and somatosensory evoked potentials were recorded in 37 children in coma soon after admission and then repeatedly during coma and emergence from coma. Evoked potentials were graded in 4 categories, ranging from normal to absent, and then related to patient outcome. Somatosensory evoked potentials were reliable predictors of outcome, particularly if both the initial and early repeated somatosensory evoked potentials were considered. Visual evoked potentials were not as reliable predictors as somatosensory evoked potentials; however, the presence or absence of both was significantly related to outcome. These data are generally consistent with the adult literature. We suggest that somatosensory evoked potentials be the evoked potential of choice in evaluating the prognosis of comatose children.     

Neurological outcome in comatose children with bilateral loss of cortical somatosensory evoked potentials.

Bilateral loss of median nerve cortical somatosensory evoked potentials (SEP) in comatose patients is reported to be one of the most discriminating predictors of poor outcome.We reviewed 53 children with bilateral absent cortical SEP with respect to their outcome and their follow-up SEP. Brain injury was caused by global cerebral ischaemia in 18 children, severe head trauma (SHT) in 13, nervous system infections in 10, and other aetiologies in 12 children.Thirty of 53 children died within the first 4 weeks and another 8 children within 4 years after the event. Two children (both ischaemia) survived in a persistent vegetative state, 9 children (1 ischaemia, 2 SHT, 3 nervous system infections, 3 other aetiologies) survived with severe deficits and 4 children (all SHT) with mild or moderate deficits. In 30 children SEP were repeated and in 8 children (5 SHT, 2 nervous system infection, 1 other aetiology) unilateral or bilateral cortical responses reappeared.Although bilateral loss of cortical SEP predicted an unfavourable outcome in most patients, a few comatose children with SHT showed an outcome with mild or moderate neurological deficits.     

Electrophysiological prognostication and brain injury from cardiac arrest

Anoxic coma after cardiorespiratory arrest warrants precocious investigation to establish probable outcome. Electroencephalogram (EEG) may uncover subclinical seizures; EEG grades have provided accurate prognosis of poor and favorable outcomes, but are weakest in those patients in between. Somatosensory evoked potentials now have proven benefit in accurately establishing a poor outcome (death or persistent vegetative state) when cortical responses (N20) are absent. These studies are particularly helpful when clinical examination of coma, early on, might yield uncertain prognosis (i.e., when brain stem reflexes are present). Combining clinical examination with electrophysiology has increasingly yielded multimodality approaches to early prognostication of coma after cardiorespiratory arrest, with more recent studies using event-related and middle-latency potentials showing promise for distinguishing good outcome (to consciousness), from awake but vegetative states. Further studies are warranted for this multimodality approach which, hopefully, may yield more widespread practical use of these testing modalities.     

Somatosensory evoked potentials in patients with hypoxic coma--correlation with neurologic prognosis

Somatosensory evoked potentials to median nerve stimulations were recorded in 21 patients with hypoxic coma within 24 hours from the onset. According to the neurologic prognosis, the patients were classified into 4 groups, such as I, complete recovery (5 patients), II, partial recovery (3 patients), III, vegetable state (8 patients), IV, brain death (5 patients). Measurements performed include central conduction time (N13-N20 interpeak latency) and amplitude ratio between N20 and P25. As N20 and P25 disappeared in 3 of 8 vegetable patients and all of brain death patients, disappearance of these waves indicates poor neurologic prognosis. Central conduction time showed no significant difference. Amplitude ratio between N20 and P25 (P25/N20) revealed significant decrease in vegetative patients for normal control subjects, complete recovery and partial recovery patients (p less than 0.05). Measurement of this ratio in early phase is useful to predict neurologic outcome in patients with hypoxic coma.     

Functional recovery despite prolonged bilateral loss of somatosensory evoked potentials: report on two patients

A bilateral loss of short latency somatosensory evoked potentials (SSEPs) after head trauma or non-traumatic brain damage is normally associated with a deleterious neurological outcome. An adequate recovery in reported in two deeply comatose patients with head trauma or severe hypertensive encephalopathy despite prolonged bilateral loss of SSEPs over days, found in repeated recordings. Hence, a bilateral loss of SSEPs should not be considered alone for prediction of outcome in cerebral injury.     

Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest

Short-latency somatosensory evoked potentials (SEPs) were evaluated in patients after cardiorespiratory arrest to study their pattern of recovery in the acute stage of anoxic-ischaemic coma. Fifty consecutive comatose patients were investigated within 8 h after cardiorespiratory resuscitation. In 30 patients no cortical SEPs were recorded and none of the patients recovered cognition. In 20 patients cortical SEPs were recorded and 5 recovered. The different susceptibility of frontal and parietal cortical structures to anoxia was reflected by the dissociated loss of parietal or frontal potentials in 6 patients. Post-mortem pathology in 15 patients confirmed extensive anoxic-ischaemic damage of cerebral and cerebellar cortex and thalamus in patients without cortical SEPs whereas the histological lesions were restricted to Sommer's sector and Purkinje cells in those with preserved SEPs. SEPs thus reflect the extent of brain damage after cardiorespiratory resuscitation.     

Pyramidal tract function during onset of brain death.

In 51 patients with primary brain lesions, who fulfilled the criteria of brain death, sequential recording of transcranial magnetic evoked potentials (TMEPs) and somatosensory evoked potentials (SEPs) were performed. In all comatose patients with apnoeic cranial nerve areflexia the TMEP could not be elicited, while the response after cervical magnetic stimulation was always preserved. Similarly, no cortical SEPs were preserved in apnoeic cranial nerve areflexia; however, the cervical somatosensory response was preserved in 44%. In deteriorating patients with coma grade III TMEPs were preserved in 3 instances, while cortical SEPs were already absent. Current brain death criteria, however, were not challenged, as TMEPs were absent in all 51 patients, at the latest when apnoea was noted.     

Prognosis in prolonged coma patients with diffuse axonal injury assessed by somatosensory evoked potential

A total of 43 prolonged coma patients with diffuse axonal injury received the somatosensory evoked potential examination one month after injury in the First Affiliated Hospital, School of Medicine, Zhejiang University in China. Somatosensory evoked potentials were graded as normal, abnormal or absent (grades Ⅰ-Ⅲ) according to N20 amplitude and central conduction time. The outcome in patients with grade Ⅲ somatosensory evoked potential was in each case unfavorable. The prognostic accuracy of grade Ⅲ somatosensory evoked potential for unfavorable and non-awakening outcome was 100% and 80%, respectively. The prognostic accuracy of grade Ⅰ somatosensory evoked potential for favorable and wakening outcome was 86% and 100%, respectively. These results suggest that somatosensory evoked potential grade is closely correlated with coma severity and degree of recovery. Somatosensory evoked potential is a valuable diagnostic tool to assess prognosis in prolonged coma patients with diffuse axonal injury.     

Therapeutic Hypothermia and Reliability of Somatosensory Evoked Potentials in Predicting Outcome after Cardiopulmonary Arrest

The loss of the N20 component on testing median somatosensory evoked potentials (SSEP) has been established as the most reliable indicator of unfavorable prognosis in post-cardiopulmonary arrest patients. With the intervention of therapeutic hypothermia in the management of patients who remain comatose following cardiopulmonary arrest that association is now in dispute. Abandoning SSEP as a key prognostic indicator of neurologic outcome would be a serious loss and cannot be justified.     

EEG and evoked potentials in comatose patients with severe brain damage

EEGs and evoked potentials were recorded in 76 deeply comatose and unresponsive patients with traumatic or non-traumatic cerebral damage. Spontaneous EEG activity was absent in 37 of the patients on the initial examination. The cortical somatosensory evoked potentials were invariably absent in these patients as were the visual evoked potentials. Brain-stem evoked potentials were abnormal, either lacking all waves or with only wave I or II present. Cerebral angiography performed in 33 of the patients within minutes to a few hours after the neurophysiological examination verified an established brain death, showing full intracerebral circulatory arrest in all. Spontaneous EEG activity was initially present in 32 patients on the first examination, 20 of whom had bilaterally abolished cortical somatosensory potentials. Ten of the patients died a few hours after the initial examination, another 10 were followed for 2-3 days and subsequently developed electrocortical silence (ECS). Twelve of the patients with spontaneous EEG activity had preserved cortical somatosensory potentials, either uni- or bilaterally. The only two who survived were found in this group. In the patients followed with multiple recordings over a few days, the first parameter to indicate a grave prognosis was always disappearance of the cortical somatosensory potentials bilaterally, which generally occurred hours, and sometimes a day or two, before cessation of the spontaneous EEG activity. EEG records from 7 patients did not meet the technical criteria of ECS; all, however, had abolished cortical somatosensory potentials bilaterally, and none in this group survived.     

Multimodality evoked potentials in closed head trauma

Patients with closed head injuries who had Glasgow coma scale scores of 7 or less were studied with evoked potentials soon after trauma. Of the patients, 39 had brain-stem auditory evoked potentials (BAEPs); 12, stroboscopic visual evoked potentials (VEPs); and 23, short-latency somatosensory evoked potentials (SSEPs). Evoked potential results were graded from 1 (normal) to 4 (most abnormal). Outcomes were categorized by the Glasgow outcome scale, with good outcome and moderate disability further classified as "favorable" and severe disability, vegetative state, and death as "unfavorable." The BAEPs and VEPs were reliable predictors of an unfavorable but not a favorable outcome. The SSEPs reliably predicted both kinds of outcomes. No instances of "false pessimism" were encountered in any modality. Evoked potential results were more reliable than intracranial pressure, pupillary light reaction, or motor findings in predicting outcome. Frequent occurrence of peripheral auditory injuries was shown.     

Proving cortical death after vascular coma: Evoked potentials,EEG and neuroimaging

Objectives

Several studies have shown that bilateral abolition of somatosensory evoked potentials after a nontraumatic coma has 100% specificity for nonawakening with ethical consequences for active care withdrawal. We propose to evaluate the prognostic value of bilateral abolished cortical components of SEPs in severe vascular coma.

Predictive value of P300 event-related potentials compared with EEG and somatosensory evoked potentials in non-traumatic coma

Developments in ethical decision making are increasing demand for more accurate predictions of outcome in coma. New neurophysiologic tests are needed to improve the ability to predict awakening as well as poor outcome. We have recently reported that the P300 event-related potential (P300) correlates with awakening and depth of nontraumatic coma. In this companion study, the predictive value of the P300 was compared with median nerve somatosensory evoked potentials (SEP) and EEG in 20 patients in non-traumatic coma. We also evaluated the predictive value of a simplified grading scale for both the EEG and SEP (the USC SEP scale and USC EEG scale). The resence of a P300 was significantly associated with higher Glasgow coma scores (GCS) and awakening. Severe abnormalities of the somatosensory evoked potentials significantly correlated with the absence of awakening and a low GCS. Moderate abnormalities of the SEP were significantly associated with awakening and higher GCS scores. the EEG was significantly associated with GCS score and severe abnormalities of the EEG were predictive of the absence of awakening and very low GCS scores. The data indicates that the P300 and SEP are more effective than the EEG in predicting awakening, and that the SEP and EEG are more effective than the P300 in predicting poor outcome. We conclude that, in addition to EEG and SEP, the P300 should be considered in the prognostic evaluation of patients in nontraumatic coma. Further, simplified scales for the EEG and SEP are predictive of depth of coma and outcome.     

The importance of brain stem evoked potentials in the diagnosis of neurosurgical patients]

The technique of Brainstem Electric Response Audiometry (BERA) is a non-invasive electrophysiologic method used in comatose patients for localization of areas of neuronal and synaptic dysfunction not evident in clinical evaluation. This test has a diagnostic and prognostic value in detection of abnormalities and evaluation of comatose head-injured patients at a reversible clinical stage. In contrast to most clinical signs, brainstem auditory evoked potentials are independent of levels of consciousness, analgesics, sedatives. This test is aetiologically non-specific and must be carefully integrated into the clinical situation. Generators of brainstem auditory evoked potentials are located in the auditory nerve (waves I and II) and brainstem (waves III-V). Patients in acute posttraumatic coma are assessed by means of Glasgow Coma Score (GCS), which is reliable in forecasting a favourable outcome. Patients with a score 8 points have an unfavourable outcome in 16%. Brainstem auditory evoked potentials are reliable predictors of unfavourable outcome. Subsequent brainstem auditory evoked potential testing provides relevant prognostic information, since improvement of graded brainstem auditory evoked potentials indicates a favourable outcome. Progressive deterioration of brainstem auditory evoked potentials indicates irreversible damage and is associated with unfavourable outcome, whereas singular abnormal evoked potentials may result from reversible neuronal dysfunction. The absence of waves III-V associated with the end EEG activity is the proof of brain death. Serial BERA monitoring has been used to evaluate progressive clinical syndromes, such as "uncal herniation" and evolving brain death. The use of serial BERA recordings appeared to improve the outcome predictions in comparison with single BERA tests. A combination of brainstem auditory evoked potentials, somatosensory and visual evoked potentials (multimodality evoked potentials-MEP) provides more information for management of a patient than a single evoked potential modality. The main goal to use BERA is early detection of secondary deterioration in comatose patients suffering from intracranial lesions. The results of brainstem auditory evoked potentials and clinical examination of patients obtained within the acute phase after head injury may indicate increased intracranial pressure (ICP) and incipient transtentorial herniation but do not always predict outcome (GOS). The outcome can be better evaluated later, 3-6 days after head injury. In summary, BERA is a non-invasive, safe and objective method of evaluating patients after severe head injury and adds valuable information for assessment of their outcome.     

Persistent vegetative state. Review and report of electrodiagnostic studies in eight cases

Of 81 comatose patients studied for two years, eight entered the persistent vegetative state (PVS), of whom four died and four survived. Clinically, all eight showed characteristic findings of wakefulness without cognitive function. Electrodiagnostic studies were characterized by (1) electroencephalograms that showed a range of patterns that were unchanged from the comatose through the vegetative state, (2) normal brainstem auditory evoked responses, (3) median somatosensory evoked responses that showed prolonged central conduction time, and (4) diminishing amplitude of the N20 response. These features may serve for identifying and monitoring patients in the PVS with a view to accurately predicting outcome.     

Central somatosensory conduction time in comatose patients.

Somatosensory conduction time between the dorsal column nuclei and the cerebral cortex may be measured following median nerve stimulation by recording evoked potentials from both scalp and neck. Central conduction times were significantly increased relative to normal (5.6 +/ 0.5 msec) in 11 of 24 comatose patients. Results within 10 and 35 days of onset of coma were correlated with the final clinical outcome. Conduction times were independent of serum phenobarbital (0 to 630 mumol per liter) and of central body temperature (35.0 to 38.5 degrees C). Serial studies in coma demonstrated (1) short-term increases during temporary metabolic disorders, and (2) sustained increases with gradual recovery over many months, particularly after head injury.