Recommendations for the use of electroencephalography and evoked potentials in comatose patients.

Predicting the outcome of a comatose or poorly responsive patient is a major issue for intensive care unit teams, in order to give the most accurate information to the family and to choose the best therapeutic option. However, determining the level of cortical activity in patients with disorders of consciousness is a real challenge. Reliable criteria are required to help clinicians in the decision-making process, especially in the acute phase of coma. In this paper, we propose recommendations for recording and interpreting electroencephalography and evoked potentials in comatose patients based on the literature and the clinical experience of a group of neurophysiologists trained in the management of comatose patients. We propose methodological guidelines and discuss prognostic value of each test as well as the limitations concerning recording and interpretation. Recommendations for the strategy and timing of neurophysiological assessments are also proposed according to various clinical situations.

Neurophysiological assessment of brain dysfunction in critically ill patients: an update.

The aim of this review was to provide up-to-date information about the usefulness of clinical neurophysiology testing in the management of critically ill patients. Evoked potentials (EPs) and electroencephalogram (EEG) are non-invasive clinical neurophysiology tools that allow an objective assessment of the central nervous system's function at the bedside in intensive care unit (ICU). These tests are quite useful in diagnosing cerebral complications, and establishing the vital and functional prognosis in ICU. EEG keeps a particularly privileged importance in detecting seizures phenomena such as subclinical seizures and non-convulsive status epilepticus. Quantitative EEG (QEEG) analysis techniques commonly called EEG Brain mapping can provide obvious topographic displays of digital EEG signals characteristics, showing the potential distribution over the entire scalp including filtering, frequency, and amplitude analysis and color mapping. Evidences of usefulness of QEEG for seizures detection in ICU are provided by several recent studies. Furthermore, beyond detection of epileptic phenomena, changes of some QEEG panels are early warning indicators of sedation level as well as brain damage or dysfunction in ICU. EPs offer the opportunity for assessing brainstem's functional integrity, as well as subcortical and cortical brain areas. A multimodal use, combining EEG and various modalities of EPs is recommended since this allows a more accurate functional exploration of the brain and helps caregivers to tailor therapeutic measures according to neurological worsening trends and to anticipate the prognosis in ICU.

Neurophysiological testing in neurocritical care.

PURPOSE OF REVIEW: To summarize a consensus of European authorities about the applications of clinical neurophysiology in the ICU and, particularly, for a clinically useful management of individual patients. RECENT FINDINGS: Clinical neurophysiology is useful for diagnosis (epilepsy, brain death, and neuromuscular disorders), prognosis (anoxic ischemic encephalopathy, head trauma, and neurological disturbances of metabolic and toxic origin), and follow-up. The prognostic significance of each test varies as a function of coma etiology. A distinction should be made between tests whose abnormalities are indicative of a poor prognosis (bilateral absence of N20 in anoxic coma, abnormalities suggesting pontine involvement in head trauma) and those whose relative normalcy constitutes an argument for a good prognosis (integrity of brainstem conductions in head trauma, presence of cognitive evoked potentials - mismatch negativity, P300 - irrespective of coma etiology).The highlights of the recent literature mainly concern continuous neuromonitoring for early detection of nonconvulsive seizures, both in adult and neonatal ICU, brain entry into the ischemic penumbra zone, and neuronal functional consequences of intracranial hypertension. SUMMARY: The domain of clinical neurophysiology is similar to that of clinical examination and complementary to that of imaging techniques. It substantially improves the individual management of ICU patients.

Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines.

By studying neuronal activity through neuronal electrogenesis, neurophysiological investigations provide a functional assessment of the nervous system and, therefore, has been used for quantitative assessment and follow-up of hepatic encephalopathy (HE). The different clinical neurophysiological approaches can be classified depending on the function to explore and their sensitivity to HE. The reliable techniques are those that reflect cortical function, i.e., cognitive-evoked potentials (EPs) (P300 paradigm), electroencephalogram (EEG), visual EPs (latency>100 ms) and somatosensory EPs (SEPs) (latency between 25 and 100 ms). Short-latency EPs (brainstem acoustic EPs, SEPs of a latency<25 ms) are in principle insensitive to HE, but can disclose brainstem conduction deficits due to oedema. SEPs and motor EPs can disclose myelopathies. Because of its parallelism to the clinical examination, clinical neurophysiology can complement the neurological examination: (i) to provide evidence of HE in patients who have normal consciousness; (ii) to rule out, at least under some conditions, disturbances of consciousness due to other causes (e.g. drug-induced disturbances, non-convulsive status epilepticus) with the reservation that the mildest degrees of encephalopathy might be associated with an EEG pattern similar to that induced by drugs; and (iii) to demonstrate the worsening or, conversely improvement, of HE in the follow-up period.

Bilateral carotid-cavernous fistula following head trauma: Possible worsening of brain injury following balloon catheter occlusion?

A 68-year-old woman developed right pulsatile exophtalmos in the early course of facial and head trauma. Investigations by visual evoked potentials suggested the presence of a bilateral prechiasmatic lesion. Intraocular pressure rapidly increased and a high-flow carotid-cavernous fistula was evident at carotid angiography. Immediately after the treatment of the right fistula by balloon embolisation, a systolic bruit was noted over the left eyeball and angiography disclosed the presence of a left carotid-cavernous fistula that was treated by the same approach. The patient developed brain oedema leading to death and we postulated that reestablishment of normal cerebral perfusion after abrupt closure of the fistulas may have played a deleterious role.

Neurophysiological patterns of vegetative and minimally conscious states.

This paper reviews the possible usefulness of electroencephalogram (EEG) and evoked potential (EP) recording in vegetative and poorly-responsive patients. There is a marked inter-individual EEG and EP variability, which reflects the state heterogeneity. Four clinical applications are described: (1) the identification of primary midbrain dysfunction--and, therefore, a possible reversibility--in post-traumatic states; (2) the identification of the permeability of sensory channels; (3) quantitative follow-up; and (4) individual assessment of cognitive functions and/or consciousness. Regarding this last issue, the loss of primary cortical EPs, although rarely observed, constitutes one major argument against consciousness. Conversely, cognitive EPs definitely proved the persistence of cognitive functions in several vegetative patients. Whether these cognitive functions are conscious or not remains a matter of debate.

Evoked potentials in severe brain injury.

Three-modality evoked potentials (EPs) have been used for several years in association with the electroencephalogram (EEG) as a diagnostic and prognostic tool in acute traumatic or nontraumatic coma. In 1993 we proposed to combine these in two indices: the index of global cortical function (IGCF) and the index of brain-stem conduction (IBSC). Four EP patterns based on both indices emerge at the acute stage of severe head trauma. These are easily explainable by pathophysiology. Pattern 1 corresponds to alterations in the index of global cortical function without changes in the index of brain-stem conduction. Its prognosis is good (80 to 90% of these patients recover). Pattern 2 is characterized by alterations of somatosensory EPs that are suggestive of midbrain dysfunction. The prognosis depends both on the reversibility of the midbrain dysfunction and on the extent of associated diffuse axonal lesions, whose evaluation requires MRI. Patients who recovered from Pattern 2 sometimes did so after a long interval during which they remained vegetative. Pattern 3 is characterized by alterations of brain-stem auditory EPs that are suggestive of pontine involvement. It usually follows uncontrolled intracranial hypertension and corresponds to evolving transtentorial herniation. All patients with that transient pattern eventually died. Pattern 4 is categorized by the disappearance of all activities of intracranial origin, contrasting with the preservation of all activities of retinal, spinal-cord, and peripheral-nerve origin. This pattern corresponds to brain death. In our experience, three-modality EPs are currently the best bedside brain-death confirmatory tool.

Involuntary orientation of attention to unattended deviant nociceptive stimuli is modulated by concomitant visual task difficulty. Evidence from laser evoked potentials.

OBJECTIVE: Recent laser evoked potential (LEP) studies showed that unattended rare intensity-deviant nociceptive stimuli enhance the LEP vertex positivity P2 ('P400 effect'). It was hypothesized to reflect an involuntary switch of attention to nociceptive events. If true the P400 effect (1) should be produced when attention is focused on a task in another sensory modality (primary task), and (2) should be modulated by the primary task difficulty. METHODS: Subjects had to count the number of visual symbols presented on a screen. In a difficult condition, symbols were digits 1-4 (interference between amount and meaning). In an easy condition, symbols were letters X (no interference). Nociceptive CO2 laser stimuli were simultaneously delivered on the left hand. Occasional stronger deviant stimuli (16%) were presented at random. In additional sessions, the strong stimuli were presented alone in homogenous series (100%). RESULTS: LEP amplitude at about 400 ms was larger for rare deviant than for homogenous stimuli. Visual task difficulty decreased LEP amplitude at this latency. Deviant stimuli seemed also to interfere with performance in the visual task. CONCLUSIONS: The results give evidence for considering the P400 effect as reflecting an involuntary attentional shift to nociceptive events. SIGNIFICANCE: The study provides electrophysiological evidences for an intrusive capacity of pain to attract attention and to decrease behavioural performance in concurrent processes. In turn, such an attentional shift is tampered if attention is very engaged in a concomitant task.

Propofol infusion syndrome associated with short-term large-dose infusion during surgical anesthesia in an adult.

In this case report we describe a case of propofol infusion syndrome in an adult after a short-term infusion of large-dose propofol during a neurosurgical procedure. Large-dose propofol (9 mg.kg(-1).h(-1)) was given for only 3 h during surgery and was followed by a small-dose infusion (2.3 mg.kg(-1).h(-1)) for 20 h postoperatively. The patient had also received large doses of methylprednisolone. He developed a marked lactic acidosis with mild biological signs of renal impairment and rhabdomyolysis but no cardiocirculatory failure. There were no other evident causes of lactic acidosis as documented by laboratory data. We believe this is the first report of reversible lactic acidosis associated with a short duration of large-dose propofol anesthesia.

Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma.

Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 micromol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes.

Electroencephalography (EEG) and somatosensory evoked potentials (SEP) to prevent cerebral ischaemia in the operating room.

We review the principal aspects of EEG and SEP to detect and prevent cerebral ischaemia in the operating room during interventions at risk. EEG and SEP are variables that indirectly reflect cerebral blood flow (CBF) provided that anaesthetic regimen, body temperature, and arterial blood pressure of the patient are stable. When CBF decreases and reaches the functional threshold, slowing and/or attenuation of EEG occurs while the amplitude and the latency of cortical SEP are, respectively decreased and lengthened. Based on these changes, numerous criteria corresponding to critical thresholds have been defined. A decrease in EEG amplitude greater than 30% or EEG changes lasting more than 30 s have been considered as significant by clinicians. The main criteria resulting from computerized EEG analysis were a reduction in total power and/or in spectral edge frequency. Regarding SEP, a more than 50% decrease in N20 amplitude and/or a more than 1 ms increase in central conduction time were the most frequently used criteria. According to the bulk of literature, it may be concluded that processed EEG analysis is more sensitive than visual EEG analysis to detect cerebral ischaemia, and that SEP are not less sensitive than conventional EEG. Moreover, literature shows that SEP are as specific as computerized EEG analysis to disclose ischaemia during carotid endarterectomy.

Exogenous and endogenous components of ultralate (C-fibre) evoked potentials following CO2 laser stimuli to tiny skin surface areas in healthy subjects.

CO2 laser stimulation of tiny skin surface areas on the hand dorsum generate ultralate laser evoked potentials (LEPs) with a major positivity maximal at the vertex at a latency of about 1 s. These potentials follow selective and direct activation of C-fibres in the superficial layers of the skin. To identify the endogenous P3 component in ultralate LEPs, we used a 2-stimulus oddball paradigm (20% probability of targets). Ultralate LEPs were recorded in eight healthy subjects with 19 channels EEG and EOG. Laser stimuli (n = 200/subject, < 0.5 mm diameter, 5 ms duration, 9.4 mJ/mm2 energy density) were applied in a pseudo-random order to the proximal phalanx of either middle finger (target) or index (non-target) of the left hand. Vigilance was maintained during recording sessions. Subject's task was to press a button to any kind of sensation perceived at the target zone. We observed a negative-positive (N965-P1139) complex maximal at Cz for all stimulus conditions. This complex was of significantly larger amplitude for rare events. For the target responses, a second distinct positive peak was observed with a mean latency of 1343 +/- 103.5 ms with maximum amplitude at Pz. This latest peak may represent an endogenous P3-like component as it is linked to the subject's detection of the target stimulus (rare events).

Nociceptive processing in the human brain of infrequent task-relevant and task-irrelevant noxious stimuli. A study with event-related potentials evoked by CO2 laser radiant heat stimuli.

Laser evoked potentials (LEPs) are nociceptive-related brain responses to activation of cutaneous nociceptors by laser radiant heat stimuli. We previously showed that LEP amplitude during the P2 period (approximately 400 ms) was increased by rare noxious stimuli, inside and outside the focus of spatial attention. It was postulated that this effect reflected a P3a response indexing an involuntary shift of attention. In the present study, LEPs were recorded in a three-stimulus oddball paradigm, commonly used to evoke P3a (or novelty-P3). CO(2) laser-induced noxious stimuli were delivered on one hand (80%, frequent). Two series of rare stronger-intensity deviant stimuli were randomly intermixed: target stimuli (10%) were delivered on the same hand while distractor stimuli (10%) were delivered on the other hand. Subjects were instructed to count targets. During an additional session, strong stimuli were delivered alone on one hand without instruction (100%, no-task stimuli). All stimulus types evoked a first positivity around 360 ms (P360). Targets and distractors elicited a late positive complex (LPC) around 465-500 ms. Topography of LPC to distractors was central and significantly more anterior than that of LPC to targets. Distractor LPC corresponds to P3a (or novelty-P3) indexing an involuntary orientation of attention toward an unexpected new/deviant event. It suggests that at least an early part of the LEP positivity (P360) is independent of P3-activities.

Electrophysiological correlates of attentional orientation in humans to strong intensity deviant nociceptive stimuli, inside and outside the focus of spatial attention.

Laser evoked potentials (LEPs) are electrical brain responses to nociceptive heat stimuli. In a recent study [Legrain, V., Guérit, J.M., Bruyer, R. and Plaghki, L., Pain, 99 (2002) 21-39.], we found that amplitude at approximately 400 ms was increased by rare intensity deviant nociceptive stimuli (P400 effect). In that study, laser stimuli were randomly delivered on both hands, and subjects were focusing attention on one hand in order to detect rare stimuli. As the P400 effect was found for rare stimuli when spatial attention was directed both towards and away from the stimulated hand, it was postulated to represent a P3a component reflecting an involuntary orientation of attention to unexpected deviant stimuli. However LEPs to strong and weak intensity stimuli were averaged together and some effects could have been underestimated. So, we present a new interpretation of the P400 effect based on separate analyses of strong and weak intensity deviant stimuli. Indeed, the P400 effect was only observed for strong stimuli, and again on both attended and unattended hands. Thus, if the P400 effect reflects P3a, only strong deviant stimuli provided enough signals to induce attentional switching even when they were delivered outside the focus of spatial attention. It is suggested that attentional switching could have been triggered by neural systems having detected sharp increase of intensity. Weak deviant stimuli were not salient enough to induce attentional switching.