Clinical neurophysiologic monitoring and brain injury from cardiac arrest

Electrophysiologic testing continues to play an important role in injury stratification and prognostication in patients who are comatose after cardiac arrest. As discussed previously, however, the adage about treating whole patients, not just the numbers, is relevant in this situation. EEG and SSEP can offer high specificity for discerning poor prognosis as long as they are applied to appropriate patient populations. As discussed previously, EEG and SSEP patterns change during the first hours to days after cardiac arrest and negative prognostic information should not be based solely on studies performed during the first 24 hours. Both electrophysiologic techniques also are susceptible to artifacts that may worsen the electrical patterns artificially and suggest a falsely poor prognosis. EEG is suppressed by anesthetic agents and hypothermia, both of which may produce ECS and burst suppression. Patients who experience respiratory arrest from a toxic ingestion of narcotics or barbiturates, in particular, may present with high-grade EEG patterns initially. Many patients also receive anesthetic medications at the time of tracheal intubation, which may linger beyond their normal half-life in patients who have hepatic or renal insufficiency or concurrent use of interacting medications. SSEP is much less susceptible to sedative anesthetic agents, but hypothermia is demonstrated to prolong evoked potential latencies. As therapeutic hypothermia becomes more common after cardiac arrest, the effect of temperature on electrophysiologic testing needs to be taken into account. The publications discussed previously also emphasize the need to adjust the prognostic value of electro-physiologic tests to the pretest probability of meaningful neurologic recovery in individual patients. Clearly, grade I EEG patterns and normal N20 potentials indicate a much better prognosis in patients who have a short du-ration of cardiac arrest, short duration of coma after resuscitation, and when the studies are performed within the first few days. In patients who remain in coma days after resuscitation and lack appropriate brainstem reflexes, however, even the most normal appearing electrophysiologic patterns do little to change the overall prognosis. Aside from prognostication, electrophysiologic testing holds great promise in defining the basic anatomy and physiology of coma emergence after cardiac arrest. In addition, quantitative EEG and automated evoked potentials have the potential to render these tools less subjective and arcane and more applicable for monitoring patients in the period during and immediately after resuscitation. Quantitative EEG also has great potential asa tool to define the time window for neuroprotective intervention and the means to track the response to such therapies in real time.     

Clinical correlates and prognosis in early spindle coma.

OBJECTIVE: To determine the prognostic significance of spindle coma (SC) according to etiology and EEG reactivity.METHODS: We reviewed 15 patients with SC due to various causes within 8 days of coma to determine the prognostic significance of this EEG pattern.RESULTS: The outcome among survivors was favorable: among 13 survivors, 9 were independent in all activities of daily living (ADLs) at 6 months; 3 were dependent in all ADLs; and one remained in coma. EEG reactivity to noxious stimuli best predicted outcome: All patients (whatever the coma etiology) with EEG reactivity survived; conversely, not all patients without EEG reactivity died.CONCLUSION: In our patients, EEG reactivity independent of etiology predicted survival, neurological examination did not predict outcome. Most SC survivors had a meaningful recovery achieving all ADLs. From the literature, the cause of SC was predictive of outcome: encephalopathy, seizures and trauma had the best prognosis while hypoxia, CRA and structural lesions carried the worst. Literature review revealed that 23% of patients [56/242] died or remained in a persistent vegetative state (PVS). Best outcomes occurred when SC was due to drugs, encephalopathy or seizures: (0/14 died or were in a PVS). With trauma 15% [25/169] died or were in a PVS). Intermediate outcomes occurred with hypoxia and cardio-respiratory arrest (CRA): 33% [7/21] died or were in a PVS. The gravest outcomes occurred with brain-stem and cerebral infarctions, and tumors: 73% [22/30] died or were in a PVS.     

"Theta pattern coma" occurring in younger adults

Since our previous report, where "theta pattern coma" was described in 2 elderly patients as an EEG pattern with a grave prognosis, we have had the opportunity to see another 9 affected patients. In this article, 3 men with a mean age of 36 years who died after cardiorespiratory arrest presented a "theta coma pattern." The EEG activity was initially reactive to and attenuated by external stimulation in 2, but prior to death the pattern became arreactive. This article shows that "theta pattern coma" is not an age related phenomenon as previously considered. So far, 11 patients with this type of EEG abnormality have been seen in our department; all have died, and all were over 30 years of age. An expanded definition of "theta pattern coma" is given in the discussion. The pathophysiological mechanisms involved in generation of this abnormality are not known. This abnormality, when seen in the unconscious patient, should be classified as a grade 4 abnormality on the EEG coma scale and should be differentiated from rather diffuse theta activity in coma. The prognostic significance of "theta pattern coma" appears to be similar to that of "alpha pattern coma."     

Coexistence of ectopic rhythms and periodic EEG pattern in anoxic encephalopathy

In this paper, we reported unique EEG patterns in two patients with anoxic encephalopathy. In the patient with a longer survival, the early EEG showed: suppression-burst pattern and theta pattern coma during quiet states; and quasi-periodic, generalized, epileptiform discharges associated with alpha-theta pattern coma during periods of arousal. A second EEG showed a disappearance of suppression-burst pattern and alpha coma. A third EEG demonstrated a disappearance of quasi-periodic epileptiform discharges. Such distinct evolution of the electroencephalogram was associated clinically with increased responsiveness despite a fatal course of illness. The second patient who had a more dramatic course, had an EEG immediately preceding death, which showed a combination of periodic pattern and theta pattern coma.     

Physiologic and prognostic significance of "alpha coma".

A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest.     

Electroencephalographic assessment of coma.

SUMMARY: Altered mental status ranging from confusion to deep unresponsiveness can be described as coma. Electroencephalography is an important tool in assessing comatose patients. Some EEG patterns are seen with lighter stages of coma and have a good prognosis, whereas others are seen in deep, often irreversible coma. These EEG patterns carry a much more grave prognosis. This paper discusses the various EEG features seen in coma, ranging from intermittent rhythmic delta activity to electrocerebral inactivity. A discussion regarding etiology and prognosis is presented after the EEG pattern is described in detail. Special EEG features, such as alpha coma, beta coma, spindle coma, etc., are discussed toward the end.     

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 EEG in coma.

The EEG allows insight into thalamocortical function in comatose patients when this is inaccessible clinically. A single EEG can help with broad diagnostic categorization whereas continuous or serial EEG provides monitoring for unstable and potentially treatable conditions and for monitoring the effects of therapy. The EEG plays a supplemental role in establishing the prognosis in disease states that are capable of causing neuronal death. The most prevalent and problematic of these conditions involves survivors of cardiac arrest who are initially in coma with intact brainstem reflexes. In such patients single EEGs are of 100% specificity for no possibility of recovery of consciousness only for essentially complete generalized suppression (<10 microV) after the first day of the arrest. Several other generalized patterns, including less marked suppression, burst-suppression, epileptiform activity, periodic complexes, and alpha-theta coma patterns, usually but not invariably indicate a poor outcome. Serial EEGs, continuous raw and automated "trending," testing of reactivity, and the inclusion of multiple variables hold promise for an improved role in the prognostic determination in these patients.     

EEG and long-term outcome of term infants with neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: The prognostic value of a burst suppression pattern (BSP) on the electroencephalograph (EEG) in the prediction of long-term outcome for full term newborns with hypoxic-ischemic encephalopathy (HIE) is well established. The purpose of our study was to compare the patterns of burst suppression on EEG with long-term neurological outcome in term infants with HIE. METHODS: We retrospectively analyzed all records of all full-term newborn infants born at the University of Alberta Hospital between January 1, 1991 and December 31, 1992, who had clinical evidence of HIE and had at least one EEG during the first week of life. The EEGs were reviewed and blindly subclassified into a BSP, or if the pattern was not continuous or was incomplete, a modified burst suppression pattern (MBSP), based on specified electrophysiological criteria. The long-term neurological outcome was then correlated with the EEG pattern. RESULTS: Twenty-three full-term infants were studied. Fifteen had a BSP on EEG and 8 had a MBSP. Six of 15 infants with a BSP died. Of the 9 survivors with a BSP, 7 are disabled and two are normal. Of the 8 infants in the MBSP group, one infant died, two are disabled and 5 are normal. In the BSP group, 6/7 disabled infants developed cerebral palsy while in the MBSP group, only one developed cerebral palsy. CONCLUSION: The results are suggestive of a better outcome for infants with neonatal HIE and MBSP on EEG compared with those with a BSP. Subclassification of the EEG changes of neonatal HIE into BSP and MBSP may give a more accurate prediction of outcome in perinatal asphyxia and assist in discussion with parents about prognosis.     

Value of a revised EEG coma scale for prognosis after cerebral anoxia and diffuse head injury

The prognostic validity for survival of a recently devised EEG grading scale was tested in anoxic and post-traumatic coma. This scale divides EEG in coma into five major grades and ten subdivisions with emphasis on the presence of dominant activities, their amplitude, persistence, distribution and reactivity. In this scale, patterns previously not allocated, such as "spindle pattern coma," "alpha pattern coma," and "theta pattern coma" are also included. The prognostic power of the revised scale was tested retrospectively without knowledge of clinical data in a group of patients with cerebral anoxia after cardiac arrest lasting more than seven minutes and in a group of diffuse head injuries. The validity of the scale was found to be higher than those used in previously published studies, reaching 98.4% prognostic accuracy in anoxic encephalopathies and was very high in head injuries.     

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 usefulness of EEG, exogenous evoked potentials, and cognitive evoked potentials in the acute stage of post-anoxic and post-traumatic coma

Three-modality evoked potentials (TMEPs) have been used for several years in association with the EEG as a diagnostic and prognostic tool in acute anoxic or traumatic coma. Cognitive EPs have been recently introduced. EEG and cognitive EPs provide functional assessment of the cerebral cortex. TMEP parameters can be described by two indices: the index of global cortical function (IGCF) and the index of brainstem conduction (IBSC). Although it remains a unique tool for epilepsy assessment, the value of EEG is largely limited by its high sensitivity to the electrical environmental noise, its dependence on sedative drugs, and its inability to test the brainstem. Major TMEP alterations (absence of cortical activities more than 24 hours after the onset of post-anoxic coma, major pontine involvement in head trauma) are associated in all cases with an ominous prognosis (death or vegetative state). However, even if mild TMEP changes are associated with a good prognosis in 65% (post-anoxic coma) to 90% (head trauma) of cases, some patients never recover despite exogenous TMEPs that are only mildly altered in the acute stage. Thus, cognitive EPs can usefully complement exogenous EPs as a prognostic tool in coma. Indeed, even if the absence of cognitive EPs in comatose patients does not have any prognostic value, their presence implies a very high (more than 90%) probability of consciousness recovery. The major technical challenge for the future will be the development of reliable tools for continuous EEG and TMEP monitoring.     

Sleep organization pattern as a prognostic marker at the subacute stage of post-traumatic coma.

OBJECTIVES: The aim of this study is to identify the predictive indexes for post-traumatic coma prognosis, which is important to better direct acute and subacute treatments and rehabilitation efforts. The pattern of sleep organization is a potential prognostic marker, but its role has not been established yet in the context of modern critical care. In the present study, we used a new protocol to evaluate the prognostic value of the different levels of sleep-wake organization recorded at the subacute stage of post-traumatic coma. METHODS: Twenty-four head-injured comatose patients were monitored with 24h polysomnographic recordings. The predictivity of the different levels of sleep-wake organization on polysomnography was compared with other possible prognostic indexes (i.e. neuroradiological findings, age and Glasgow Coma Scores (GCS)). Main outcome measures were survival and the degree of disability after recovery from coma. RESULTS: The presence of organized sleep patterns, but not GCS, was highly predictive of better outcome (odds ratio=10.78, P=0.01), even after correction for potentially confounding variables with multivariate analysis. CONCLUSIONS: Our study demonstrates that the sleep-wake organization pattern based on 24h polysomnographic recordings at the subacute stages of post-traumatic coma is a reliable prognostic marker, both for survival and for functional recovery.     

A reappraisal of rhythmic coma patterns in children

OBJECTIVE: This study was designed to determine the prevalence of rhythmic coma patterns in comatose children and to ascertain the prognostic significance of reactive rhythmic coma patterns. METHODS: We retrospectively analyzed and classified electroencephalogram (EEGs) in comatose children between two months and 18 years of age during the period 1996 - 2003 according to modified Young's classification. Outcome at one-year was scored according to the Paediatric Cerebral and Overall Performance Category Scale. Outcomes were compared using Fisher's exact test and Mann-Whitney test. RESULTS: Analysis of 63 electroencephalogram (EEG) records in 38 patients showed rhythmic patterns in 19 records (30.2%; 9 alpha, 4 spindle, 4 theta and 2 beta coma patterns, total number of children = 14). Aetiology and outcome of alpha coma patterns and other rhythmic coma patterns were similar. In five children, one type of rhythmic pattern changed to another. Records with reactive rhythmic coma 66.7% (6/9), were associated with favourable outcome. Sixty percent of the records (6/10 records in seven children) with non-reactive pattern were associated with unfavourable outcome. This clinically significant difference did not reach statistical significance (lower Paediatric Cerebral and Overall Performance Category Scale score p= 0.14; favourable outcome p=0. 19). CONCLUSION: Rhythmic coma patterns in comatose children are not uncommon. Aetiology, reactivity and outcome of individual patterns are similar and thus make the rhythmic coma patterns distinct EEG signatures in comatose children. There was a clinically significant better outcome with reactive rhythmic coma patterns.     

The electroencephalographic substratum of the awakening

The aim of the present study was to characterize the regional electroencephalographic substratum of the awakening process by means of a Hz-by-Hz EEG spectral power analysis. For this purpose, we recorded a group of 25 female subjects who slept for at least two consecutive nights in the laboratory. The post-sleep waking EEG was compared to the one recorded during the presleep wakefulness from four midline derivations (Fz-A1, Cz-A1, Pz-A1, Oz-A1). Results indicated that the first 10 min after awakening are characterized by an increase of EEG power in the low-frequency range (1-9 Hz) compared to the corresponding presleep waking period, and by a significant decrease of EEG power in the beta range (18-24 Hz). As regards topographic differences, the increase of EEG power upon awakening in the delta-theta range showed a parieto-occipital prevalence. Moreover, the occipital derivation showed a larger decrease of power in the beta range as compared to the other derivations. In conclusion, the EEG substratum of the sleep offset period is characterized by a pattern of increased EEG power in the delta-theta and low-alpha bands, and of decreased power in the beta range. This pattern could be considered as the spectral EEG signature of the sleep inertia phenomenon. The state of post-sleep EEG hypo-arousal does not subside in the first 10-min period after awakening considered in the present analysis. Finally, according to our results, the more posterior scalp locations show stronger EEG signs of sleep inertia, and could be the last ones to properly wake up.     

EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in adults

The EEG has long been established as an important laboratory test when assessing cerebral function in comatose states. During the last three decades, several grading scales regarding severity of the EEG abnormality in coma have been suggested to increase the prognostic power of the EEG for survival. Their main limitation was, that the majority of EEG abnormalities in coma fell in the middle of the five point scaling systems, i.e. Grade 3 abnormality on the five grade abnormality scales. In addition, it was considered that non-reactivity of EEG pattern in coma is confined only to the most advanced grades. The purpose of the present article is to define precisely the main five abnormality grades and their subdivisions, and to allocate them in five principal categories regarding their significance for survival. The five categories are: 1 = optimal, 2 = benign if persistent, 3 = uncertain, 4 = malignant if persistent, and 5 = fatal unless caused by drug effect or hypothermia. After the inclusion of more recently described coma patterns, it was possible to outline prognostic significance for survival in eleven types of abnormalities with assurance. Only four remain of uncertain prognostic significance. The EEG abnormalities as discussed in this article are generally applicable only to coma after diffuse brain trauma and cerebral hypoxia. However, they may also be found in some other diffuse encephalopathies associated with coma.     

Prognosis of patients in coma after acute subdural hematoma due to ruptured intracranial aneurysm

Acute subdural hematomas (aSDH) secondary to intracranial aneurysm rupture are rare. Most patients present with coma and their functional prognosis has been classically considered to be very poor. Previous studies mixed good-grade and poor-grade patients and reported variable outcomes. We reviewed our experience by focusing on patients in coma only and hypothesized that aSDH might worsen initial mortality but not long-term functional outcome. Between 2005 and 2013, 440 subarachnoid hemorrhage (SAH) patients were admitted to our center. Nineteen (4.3%) were found to have an associated aSDH and 13 (2.9%) of these presented with coma. Their prospectively collected clinical and outcome data were reviewed and compared with that of 104 SAH patients without aSDH who presented with coma during the same period. Median aSDH thickness was 10 mm. Four patients presented with an associated aneurysmal cortical laceration and only one had good recovery. Overall, we observed good long-term outcomes in both SAH patients in coma with aSDH and those without aSDH (38.5% versus 26.4%). Associated aSDH does not appear to indicate a poorer long-term functional prognosis in SAH patients presenting with coma. Anisocoria and brain herniation are observed in patients with aSDH thicknesses that are smaller than those observed in trauma patients. Despite a high initial mortality, early surgery to remove the aSDH results in a good outcome in over 60% of survivors. Aneurysmal cortical laceration appears to be an independent entity which shows a poorer prognosis than other types of aneurysmal aSDH.     

The clinical significance of EEG cyclic alternating pattern during coma.

To define the clinical significance of EEG "cyclic alternating pattern" (ECAP). ECAP is the periodic presence of a high-voltage slow waves alternating with low voltage irregular faster activity. This term was first described in comatose patients in 1944. It has been less recognized and may be underreported since then. The clinical significance of ECAP in the state of coma remains unknown. We reviewed our prospective EEG database for consecutive patients studied over a period of 4 years (n = 4,819) looking for patterns consistent with ECAP. We reviewed the charts of the patients with the above EEG pattern to define the clinical setting and the eventual outcome. Eleven patients were identified. All patients identified were found to be in the coma state at the time of the EEG. The majority of patients (n = 10) survived the coma, and half returned to the community in good functional status. ECAP is seen rarely in comatose patients. Regardless of the cause of the coma, the presence of ECAP carries an overall good prognosis for both survival and recovery.     

The electroencephalogram in altered states of consciousness

The EEG can be very helpful in the evaluation of patients with altered states of consciousness. Diffuse slowing of background rhythms and the presence of triphasic waves suggests metabolic dysfunction, particularly hepatic. Generalized fast activity may be seen in patients with a drug intoxication. Abnormalities, such as PLEDs or focal continual PDA, support a diagnosis of supratentorial lesion, whereas a normal appearing EEG in a comatose patient suggests a brain-stem lesion. In addition, the EEG may reveal that the alteration in consciousness is due to continual epileptic activity without motor manifestations (nonconvulsive status) that had not been suspected. As indicated, certain patterns have prognostic implications. However, as these patterns are not specific for a single etiology, the EEG is of most help when the cause is known. For example, burst suppression or a diffuse alpha pattern coma can be seen in either hypoxia or a drug intoxication. With hypoxia, these patterns carry an extremely poor prognosis for useful recovery, whereas complete recovery is often seen in cases secondary to drug ingestion. As a more extreme example, a patient whose EEG shows ECS secondary to drug intoxication may recover but will not if the ECS is due to hypoxia or severe head trauma. If the etiology of the encephalopathy is unknown, then sequential records are needed for prognosis.     

Prognostic significance of alpha frequency EEG rhythm in coma after cardiac arrest.

Sixty-five patients who remained in coma for more than 24 hours after resuscitation from cardiac arrest were divided into two groups according to their EEGs. Thirteen patients were found to have rhythm of alpha frequency while 52 had the usual EEG findings after cerebral anoxia. Three patients from the group with alpha frequency EEG rhythms regained full consciousness but showed severe sequelae. Our results suggest that the prognosis of comatose patients with EEG rhythm of alpha frequency is no poorer than that of other individuals who are comatose after cardiac arrest.