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.

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.

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.

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.

Attentional modulation of the nociceptive processing into the human brain: selective spatial attention, probability of stimulus occurrence, and target detection effects on laser evoked potentials.

Laser evoked potentials (LEPs) are brain responses to activation of skin nociceptors by laser heat stimuli. LEPs consist of three components: N1, N2, and P2. Previous reports have suggested that in contrast to earlier activities (N1), LEPs responses after 230-250 ms (N2-P2) are modulated by attention to painful laser stimuli. However, the experimental paradigms used were not designed to specify the attentional processes involved in these LEP modulations. We investigated the effects of selective spatial attention and oddball tasks on LEPs. CO(2) laser stimuli of two different intensities were delivered on the dorsum of both hands of ten subjects. One intensity was frequently presented, and the other rarely. Subjects were asked to pay attention to stimuli delivered on one hand and to count rare stimuli, while ignoring stimuli on the other hand. Frequent and rare attended stimuli evoked enhanced N160 (N1) and N230 (N2) components in comparison to LEPs from unattended stimuli. Both components showed scalp distribution contralateral to the stimulus location. The vertex P400 (P2) was unaffected by spatial attention and stimulus location, but its amplitude increased after rare stimuli, whether attended or unattended. An additional parietal P600 component was induced by the attended rare stimuli. It is suggested that several attentional processes can modify nociceptive processing in the brain at different stages. LEP activities in the time-range of N1 and N2 (120-270 ms) showed evidence of processes modulated by the direction of spatial attention. Conversely, processes underlying P2 (400 ms) were not affected by spatial attention, but by the probability of the stimulus. This probability effect was not due to P3b-related processes that were observed at a later latency (600 ms). Indeed, P600 could be seen as a P3b evoked by conscious detection of rare targets.

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.

State-of-the-art of neuromonitoring for prevention of immediate and delayed paraplegia in thoracic and thoracoabdominal aorta surgery.

BACKGROUND: The prevention of immediate and delayed paraplegia after thoracoabdominal aorta surgery relies on hemodynamic maneuvers (aimed at restoration of an adequate spinal cord perfusion pressure) and cytoprotective measures (hypothermia, drugs). METHODS: The indications for implementing these measures can be provided by motor-evoked potential (MEP) or somatosensory-evoked potential (SEP) monitoring. RESULTS: Intraoperative interactions between the surgeon and the neurophysiologist can be described by algorithms to be applied in the presence or absence of intraoperative MEP or SEP changes. CONCLUSIONS: It should be noted that normal SEPs or MEPs at the end of surgery do not systematically guarantee the nonoccurrence of delayed paraplegia, especially when segmental arteries have been ligated, in which case postoperative SEP monitoring is indicated.

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.

Fomepizole therapy for reversal of visual impairment after methanol poisoning: a case documented by visual evoked potentials investigation.

PURPOSE: To illustrate the safety and efficacy of fomepizole in a case of methanol poisoning with initial visual impairment. DESIGN: Interventional case report. METHODS: A 60-year-old man was admitted with blurred vision and changes in color perception 18 hours after ingesting 100 ml methanol. Fomepizole was chosen for antidotal therapy in combination with hemodialysis. Flash electroretinogram (fERG) and flash visual evoked potentials (fVEPs) examinations were obtained at the bedside 2 hours after admission and on days 1 and 8. The monocular pattern-reversal visual evoked potentials (pVEPs) were investigated on days 1 and 8. RESULTS: A complete reversal of visual impairment was achieved within 20 hours. An abnormal b-wave amplitude and an increased peak III latency at VEPs were present on admission and recovered within 24 hours. CONCLUSIONS: Fomepizole appeared safe and effective for a patient who had severe methanol poisoning presenting with visual impairment.

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).

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.