Michel Johannes Antonius Maria van Putten

Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: A prospective cohort study*

Objective: To evaluate the value of continuous electroencephalography in early prognostication in patients treated with hypothermia after cardiac arrest. Design: Prospective cohort study. Setting: Medical intensive care unit. Patients: Sixty patients admitted to the intensive care unit for therapeutic hypothermia after cardiac arrest. Intervention: None. Measurements and Main Results: In all patients, continuous electroencephalogram and daily somatosensory evoked potentials were recorded during the first 5 days of admission or until intensive care unit discharge. Neurological outcomes were based on each patient’s best achieved Cerebral Performance Category score within 6 months. Twenty-seven of 56 patients (48%) achieved good neurological outcome (Cerebral Performance Category score 1–2). At 12 hrs after resuscitation, 43% of the patients with good neurological outcome showed continuous, diffuse slow electroencephalogram rhythms, whereas this was never observed in patients with poor outcome. The sensitivity for predicting poor neurological outcome of low-voltage and isoelectric electroencephalogram patterns 24 hrs after resuscitation was 40% (95% confidence interval 19%–64%) with a 100% specificity (confidence interval 86%–100%), whereas the sensitivity and specificity of absent somatosensory evoked potential responses during the first 24 hrs were 24% (confidence interval 10%–44%) and 100% (confidence interval: 87%–100%), respectively. The negative predictive value for poor outcome of low-voltage and isoelectric electroencephalogram patterns was 68% (confidence interval 50%–81%) compared to 55% (confidence interval 40%–60%) for bilateral somatosensory evoked potential absence, both with a positive predictive value of 100% (confidence interval 63%–100% and 59%–100% respectively). Burst-suppression patterns after 24 hrs were also associated with poor neurological outcome, but not inevitably so. Conclusions: In patients treated with hypothermia, electroencephalogram monitoring during the first 24 hrs after resuscitation can contribute to the prediction of both good and poor neurological outcome. Continuous patterns within 12 hrs predicted good outcome. Isoelectric or low-voltage electroencephalograms after 24 hrs predicted poor outcome with a sensitivity almost two times larger than bilateral absent somatosensory evoked potential responses.

Continuous Quantitative EEG Monitoring in Hemispheric Stroke Patients Using the Brain Symmetry Index

Background and Purpose— There is increased awareness that continuous brain monitoring might benefit neurological patients, because it may allow detection of derangement of brain function in a possible reversible state, allowing early intervention. Here, we explore if quantitative continuous electroencephalography (cEEG) monitoring is technically feasible and possibly clinically relevant in patients with acute ischemic hemispheric stroke. Materials— Twenty-one consecutive patients with an acute hemispheric stroke were monitored in our stroke unit, using cEEG for 12 to 24 hours on the day of admission. EEGs were quantified using a particular measure for symmetry, the brain symmetry index (BSI). This measure was subsequently correlated with the clinical condition of the patient using the National Institute of Health Stroke Scale (NIHSS). Results— cEEG was technically feasible. We found a most satisfying positive correlation between the BSI and the NIHSS, with &rgr;≈0.86 (P<0.01). Conclusions— Technically, cEEG monitoring posed no major problems. It was found that the BSI correlates satisfactorily with the clinical neurological condition of our stroke patients. This suggests that the BSI can be used as a measure to monitor possible changes of brain function in this patient category.

Ischemic Cerebral Damage An Appraisal of Synaptic Failure

In the human brain, ≈30% of the energy is spent on synaptic transmission. Disappearance of synaptic activity is the earliest consequence of cerebral ischemia. The changes of synaptic function are generally assumed to be reversible and persistent damage is associated with membrane failure and neuronal death. However, there is overwhelming experimental evidence of isolated, but persistent, synaptic failure resulting from mild or moderate cerebral ischemia. Early failure results from presynaptic damage with impaired transmitter release. Proposed mechanisms include dysfunction of adenosine triphosphate-dependent calcium channels and a disturbed docking of glutamate-containing vesicles resulting from impaired phosphorylation. We review energy distribution among neuronal functions, focusing on energy usage of synaptic transmission. We summarize the effect of ischemia on neurotransmission and the evidence of long-lasting synaptic failure as a cause of persistent symptoms in patients with cerebral ischemia. Finally, we discuss the implications of synaptic failure in the diagnosis of cerebral ischemia, including the limited sensitivity of diffusion-weighted MRI in those cases in which damage is presumably limited to the synapses.

Early EEG contributes to multimodal outcome prediction of postanoxic coma.

Objectives: Early identification of potential recovery of postanoxic coma is a major challenge. We studied the additional predictive value of EEG. Methods: Two hundred seventy-seven consecutive comatose patients after cardiac arrest were included in a prospective cohort study on 2 intensive care units. Continuous EEG was measured during the first 3 days. EEGs were classified as unfavorable (isoelectric, low-voltage, burst-suppression with identical bursts), intermediate, or favorable (continuous patterns), at 12, 24, 48, and 72 hours. Outcome was dichotomized as good or poor. Resuscitation, demographic, clinical, somatosensory evoked potential, and EEG measures were related to outcome at 6 months using logistic regression analysis. Analyses of diagnostic accuracy included receiver operating characteristics and calculation of predictive values. Results: Poor outcome occurred in 149 patients (54%). Single measures unequivocally predicting poor outcome were an unfavorable EEG pattern at 24 hours, absent pupillary light responses at 48 hours, and absent somatosensory evoked potentials at 72 hours. Together, these had a specificity of 100% and a sensitivity of 50%. For the remaining 203 patients, who were still in the “gray zone” at 72 hours, a predictive model including unfavorable EEG patterns at 12 hours, absent or extensor motor response to pain at 72 hours, and higher age had an area under the curve of 0.90 (95% confidence interval 0.84–0.96). Favorable EEG patterns at 12 hours were strongly associated with good outcome. EEG beyond 24 hours had no additional predictive value. Conclusions: EEG within 24 hours is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest.

EEG in ischaemic stroke: Quantitative EEG can uniquely inform (sub-)acute prognoses and clinical management

Investigations of (sub-)acute ischaemic stroke (IS) employing quantitative electroencephalographic (QEEG) methods, in concert with other assessments, are reviewed. Numerous outcomes from hundreds of patients collectively indicate that (sub-)acute QEEG indices from standard systems can uniquely inform clinical management, particularly prognostication of outcomes from IS. Two classes of QEEG indices have proven particularly informative. The first quantifies the power of abnormal, slow activity relative to that of faster activity and the second, interhemispheric voltage asymmetry (broadband). Both have been identified as statistically significant predictors of outcomes assessed (via routine clinical scales) in the weeks and months following IS. Furthermore both have demonstrated higher predictive value than concomitant neurological assessments and scales, and to improve upon outcome prediction afforded by neuroimaging alone. These indices also may continuously provide unique, real-time insights into the efficacy of thrombolytic therapy, prior to clinical changes. Two key applications of QEEG which should prove valuable for future clinical management of IS are: (1) continuous, acute monitoring to inform about the efficacy of thrombolysis and decisions about potential additional interventions, and; (2) brief, subacute recording to inform outcome prognostication and clinical decisions about, for example, rehabilitation strategies. Ongoing research and technological developments will continue to facilitate clinical translation of QEEG investigations reviewed herein.

Detecting temporal lobe seizures from scalp EEG recordings: a comparison of various features

OBJECTIVE Sixteen different features are evaluated in their potential ability to detect seizures from scalp EEG recordings containing temporal lobe (TL) seizures. Features include spectral measures, non-linear methods (e.g. zero-crossings), phase synchronization and the recently introduced Brain Symmetry Index (BSI). Besides an individual comparison, several combinations of features are evaluated as well in their potential ability to detect TL seizures. METHODS Sixteen long-term scalp EEG recordings, containing TL seizures from patients suffering from temporal lobe epilepsy (TLE), were analyzed. For each EEG, all 16 features were determined for successive 10s epochs of the recording. All epochs were labeled by experts for the presence or absence of seizure activity. In addition, triplet combinations of various features were evaluated using pattern recognition tools. Final performance was evaluated by the sensitivity and specificity (False Alarm Rate (FAR)), using ROC curves. RESULTS In those TL seizures characterized by unilateral epileptiform discharges, the BSI was the best single feature. Except for one low-voltage EEG with many artifacts, the sensitivity found ranged from 0.55 to 0.90 at a FAR of approximately 1/h. Using three features increased the sensitivity to 0.77-0.97. In patients with bilateral electroencephalographic changes, the single best feature most often found was a measure for the number of minima and maxima (mmax) in the recording, yielding sensitivities of approximately 0.30-0.96 at FAR approximately 1/h. Using three features increased the sensitivity to 0.38-0.99, at the same FAR. In various recordings, it was even possible to obtain sensitivities of 0.70-0.95 at a FAR = 0. CONCLUSIONS The Brain Symmetry Index is the most relevant individual feature to detect electroencephalographic seizure activity in TLE with unilateral epileptiform discharges. In patients with bilateral discharges, mmax performs best. Using a triplet of features significantly improves the performance of the detector. SIGNIFICANCE Improved seizure detection can improve patient care in both the epilepsy monitoring unit and the intensive care unit.

The revised brain symmetry index

Objective: recently, the extended brain symmetry index (BSI) was introduced to assist the visual interpretation of the EEG, in particular to quantify both the spatial (left-right) and the temporal spectral characteristics. The BSI has found application in monitoring during carotid endarterectomy, acute stroke and focal seizure detection. Here, we present additional relevant characteristics and a slightly modified version of this index, simulating its behavior as may occur in various clinical conditions, with an emphasis on the detection of cerebral ischaemia. - Methods: The behavior of the revised and standard sBSI and tBSI is illustrated using random noise signals to simulate various changes in the EEG. The indices are evaluated as a function of spatial and temporal changes, and as a function of the number of channels. - Results: The r-sBSI and the r-tBSI are normalized in the range [0–1] with sensitivities of about 0.05 for a 10% difference in signal amplitude, either spatial or temporal. The baseline value of the sBSI shows a modest dependence on the number of channels used. - Conclusions: The revised BSI has an improved sensitivity (about two times) to detect interhemispheric asymmetry and diffuse changes. The modified expression of the tBSI is more compact and allows a more intuitive understanding than previously proposed. - Significance: qEEG assists in a more objective interpretation of the EEG, and is relevant in neuromonitoring.

Time–frequency analysis of single pulse electrical stimulation to assist delineation of epileptogenic cortex

Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic tissue. The current gold standard is the seizure onset zone in ictal, i.e. chronic, electrocorticography recordings. Single pulse electrical stimulation can evoke epileptic, spike-like responses in areas of seizure onset also recorded by electrocorticography. Recently, spontaneous pathological high-frequency oscillations (80-520 Hz) have been observed in the electrocorticogram that are related to epileptic spikes, but seem more specific for epileptogenic cortex. We wanted to see whether a quantitative electroencephalography analysis using time-frequency information including the higher frequency range could be applied to evoked responses by single pulse electrical stimulation, to enhance its specificity and clinical use. Electrocorticography data were recorded at a 2048-Hz sampling rate from 13 patients. Single pulse electrical stimulation (10 stimuli, 1 ms, 8 mA, 0.2 Hz) was performed stimulating pairs of adjacent electrodes. A time-frequency analysis based on Morlet wavelet transformation was performed in a [-1 s : 1 s] time interval around the stimulus and a frequency range of 10-520 Hz. Significant (P = 0.05) changes in power spectra averaged for 10 epochs were computed, resulting in event-related spectral perturbation images. In these images, time-frequency analysis of single pulse-evoked responses, in the range of 10-80 Hz for spikes, 80-250 Hz for ripples and 250-520 Hz for fast ripples, were scored by two observers independently. Sensitivity, specificity and predictive value of time-frequency single pulse-evoked responses in the three frequency ranges were compared with seizure onset zone and post-surgical outcome. In all patients, evoked responses included spikes, ripples and fast ripples. For the seizure onset zone, the median sensitivity of time-frequency single pulse-evoked responses decreased from 100% for spikes to 67% for fast ripples and the median specificity increased from 17% for spikes to 79% for fast ripples. A median positive predictive value for the evoked responses in the seizure onset zone of 17% was found for spikes, 26% for ripples and 37% for fast ripples. Five out of seven patients with <50% of fast ripples removed by resection had a poor outcome. A wavelet transform-based time-frequency analysis of single pulse electrical stimulation reveals evoked responses in the frequency range of spikes, ripples and fast ripples. We demonstrate that time-frequency analysis of single pulse electrical stimulation can assist in delineation of the epileptogenic cortex using time-frequency single pulse-evoked fast ripples as a potential new marker.

Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients.

OBJECTIVE To evaluate how the motor unit number index (MUNIX) is related to high-density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS). METHODS Both MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS). RESULTS There was a significant positive correlation between MUNE and MUNIX values in ALS patients (r=0.49 at baseline; r=0.56 at 4 months; r=0.56 at 8 months, all p<0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p<0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values. CONCLUSIONS In ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE. SIGNIFICANCE MUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS.

Electroencephalogram Predicts Outcome in Patients With Postanoxic Coma During Mild Therapeutic Hypothermia

Objective:To assess the value of electroencephalogram for prediction of outcome of comatose patients after cardiac arrest treated with mild therapeutic hypothermia. Design:Prospective cohort study. Setting:Medical ICU. Patients:One hundred forty-two patients with postanoxic encephalopathy after cardiac arrest, who were treated with mild therapeutic hypothermia. Measurements and Main Results:Continuous electroencephalogram was recorded during the first 5 days of ICU admission. Visual classification of electroencephalogram patterns was performed in 5-minute epochs at 12 and 24 hours after cardiac arrest by two independent observers, blinded for patients’ conditions and outcomes. Patterns were classified as isoelectric, low voltage, epileptiform, burst-suppression, diffusely slowed, or normal. Burst-suppression was subdivided into patterns with and without identical bursts. Primary outcome measure was the neurologic outcome based on each patient’s best achieved Cerebral Performance Category score within 6 months after inclusion. 67 patients (47%) had favorable outcome (Cerebral Performance Category, 1–2). In patients with favorable outcome, electroencephalogram patterns improved within 24 hours after cardiac arrest, mostly toward diffusely slowed or normal. At 24 hours after cardiac arrest, the combined group of isoelectric, low voltage, and “burst-suppression with identical bursts” was associated with poor outcome with a sensitivity of 48% (95% CI, 35–61) and a specificity of 100% (95% CI, 94–100). At 12 hours, normal or diffusely slowed electroencephalogram patterns were associated with good outcome with a sensitivity of 56% (95% CI, 41–70) and a specificity of 96% (95% CI, 86–100). Conclusions:Electroencephalogram allows reliable prediction of both good and poor neurologic outcome of patients with postanoxic encephalopathy treated with mild therapeutic hypothermia within 24 hours after cardiac arrest.