Periodic epileptiform discharges in hypoxic encephalopathy: BiPLEDs and GPEDs as a poor prognosis for survival.

INTRODUCTION: Electrophysiologic tests in hypoxic encephalopathy consist of EEG and evoked/event-related potential studies. In most studies the generalized periodic epileptiform complexes have been reported combined with other EEG patterns and were indicators of a poor outcome in different etiologies of hypoxic encephalopathy (HE), but these have rarely been examined independently. METHODOLOGY: We analyzed from 2000 to 2007 the outcome of patients with HE and generalized periodic epileptiform complexes. We abstracted and tabulated clinical information, imaging findings, and outcome from the medical records. RESULTS: We found 52 patients in our database. Fourteen patients (eight BiPLEDs and six GPEDs) were associated with HE. Patients with BIPLEDs were 68+/-19.4 years old, 5 female (62%) and 3 (38%) men. GPEDs patients were 52.5+/-19.1 years old, 2 women (20%) and 4 (80%) men. Myocardial infarction and ventricular tachycardia were responsible of 57% of the HE cases. Neuroimaging studies in both groups showed cortical structural lesions in 84%. All patients were comatose and died. Two GPEDs patients developed status epilepticus. CONCLUSION: GPEDs and BIPLEDs after an anoxic insult carried a poor prognosis for survival. Aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology.

A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods.

Hemodynamic changes in simple partial epilepsy: a functional MRI study.

We performed functional MRI (fMRI) on a patient with a mass lesion while she happened to experience a simple partial seizure. We used regional T2* signal changes to localize seizure-related hemodynamic changes. Seizure activity was associated with changes in MR signal in different regions that showed sequential activation and deactivation. Our study has shown that epileptic activity leads to changes in cerebral hemodynamics. In selected patients, therefore, it might be possible to use fMRI as a noninvasive tool to detect and investigate cortical patterns of activation associated with seizure activity.

Photosensitive epilepsy studied by functional magnetic resonance imaging and magnetic resonance spectroscopy.

PURPOSE: To study metabolic and hemodynamic correlates of photic stimulation-triggered discharges. METHODS: Simultaneous EEG, functional MRI (tMRI) and magnetic resonance spectroscopy (MRS) were performed in nine patients with photosensitive epilepsy and in 12 normal subjects. RESULTS: Prominent visual cortex activation was seen in all normal subjects and patients, and no tMRI-registered hemodynamic abnormalities were correlated with the brief photoparoxysmal spike-wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike-wave response to the photic stimulation, the photosensitive patients showed four findings not seen in the normal subjects: (a) slightly, but significantly, elevated lactate levels in the occipital cortex in the resting state; (b) an increased area of visual cortical activation with photic stimulation; (c) simultaneous with the occipital cortex stimulus-induced increased fMRI signal, there were noncontiguous areas of signal attenuation most prominent in perirolandic regions; and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyrus. CONCLUSIONS: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients.

Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease.

OBJECTIVE: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease. BACKGROUND: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful. METHODS: TMS and clinical assessment in 121 patients with motor neuron disease. RESULTS: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11+/-6 months, TMS showed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period. CONCLUSIONS: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease.

Hemodynamic and metabolic aspects of photosensitive epilepsy revealed by functional magnetic resonance imaging and magnetic resonance spectroscopy.

PURPOSE: To study in humans the hemodynamic and metabolic consequences of both photic stimulation-triggered and spontaneous generalized epileptiform discharges. METHODS: Simultaneous EEG, functional magnetic resonance imaging (fMRI) and MR spectroscopy were performed in a 1.5-T scanner in 16 patients with generalized epilepsy, including nine with photosensitive epilepsy, and 12 normal subjects. RESULTS: With a flash stimulation duration of 2 s, prominent visual cortex activation was seen in all normals and patients. There were no fMRI-registered hemodynamic abnormalities found in relation to the brief photoparoxysmal spike-wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike-wave response to the photic stimulation, the photosensitive patients showed four unique findings compared with normals: (a) slightly, but significantly, increased lactate levels in the occipital cortex in the resting state, (b) an increased area of visual cortical activation with photic stimulation, (c) simultaneous with the occipital cortex stimulus-induced increased fMRI signal there were noncontiguous areas of signal attenuation most prominent in perirolandic regions, and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyrus. CONCLUSIONS: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients.

Accuracy of EEG dipole source localization using implanted sources in the human brain.

OBJECTIVES: The location of electrical sources in the brain can be estimated by calculating inverse solutions in which the location, amplitude and orientation of the electrical sources are fitted to the scalp EEG. To assess localization accuracy of the moving dipole inverse solution algorithm (ISA), we studied two patients who had depth electrodes implanted for presurgical planning of epilepsy surgery. METHODS: Artificial dipoles were created by connecting a single sine wave pulse generator to different pairs of electrodes in multiple orientations and depths. Surface EEG recordings of the resulting pulses were evaluated with the ISA using a 4-shell spherical head model and plotted on the subjects' MRI. Dipole localization errors were evaluated with respect to the number of averaged pulses, different electrode montages and different dipole locations and orientations. RESULTS: Dipoles located at 40-57 mm from the scalp surface had localization errors that were greater than those located at 62-85 mm. Localization accuracy improved with increasing numbers of pulses and recording electrodes. Results with a standard 10-20 array of 21 electrodes showed an average localization error of 17 mm, whereas 41 electrodes improved this to 13 mm. Mean angular errors were 31 and 30 degrees, respectively. CONCLUSIONS: The ISA was able to differentiate between tangential and radial dipoles. We conclude that our implementation of the ISA is a useful and sound method for localizing electrical activity in the brain.

Evaluation and prognostication in coma.

Electroencephalography (EEG) and evoked potential (EP) studies are neurophysiologic techniques which provide information on physiological state and response to therapy, and may aid diagnosis and prognosis. Serial studies or continuous monitoring may enable changes to be detected prior to irreversible deterioration in the patient's condition. Current computer technology allows simultaneous display and correlation of electrophysiologic parameters, cardiovascular state and ICP. Continuous EEG monitoring in the ICU has been shown to have a decisive or contributing impact on medical decision making in more than three-quarters of patients. In addition, continuous EEG monitoring has revealed previously unsuspected non-convulsive seizures in two-thirds of patients. Somatosensory and auditory EPs can provide useful prognostic information in coma patients, however, these tests are etiologically non-specific and must be carefully integrated into the clinical situation. Motor EPs offer a potentially useful tool for evaluating motor system abnormalities in the ICU. Thus, neurophysiologic tests are established monitoring tools in the neurological intensive care unit.

Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions.

We evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of diverse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptogenic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three-dimensional data not available from conventional analysis.

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation.

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.

Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) represent different approaches to mapping the motor cortex. fMRI identifies areas of hemodynamic changes during task performance while TMS provides electrophysiologic data concerning the localization and density of cortical motoneurons. Here we define the spatial correlation between fMRI and TMS maps and compared them with direct electrical cortical stimulation (ECS). We performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar pulse sequence during the performance of a motor task. We also performed focal TMS with surface EMG recordings from the muscles primarily involved in the fMRI task. We coregistered the stimulation sites in real time with the fMRI maps using a frameless stereotactic system. In both patients we also performed ECS of the cortex during surgery under local anesthesia. fMRI maps were validated by the electrophysiologic data both pre- and intraoperatively. Our results suggest that regions of fMRI activation correspond spatially to areas of highest motoneuron density as demonstrated by electrophysiologic techniques.

Periodic lateralized epileptiform discharges--a critical review.

It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity, the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence, particularly from functional neuroimaging studies, strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum, with the nature of the underlying neuronal injury, the patient's preexisting propensity to have seizures, and the co-existence of any acute metabolic derangements all contributing to whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence, dynamics, and relevance of this pattern.

Assessment of cortical motor output: compound muscle action potential versus twitch force recording.

To determine whether motor evoked potential (MEP) amplitude and area are accurate measurements of the magnitude of response to magnetic cortical stimulation, we simultaneously recorded the twitch and MEP in the first dorsal interosseous muscle of 8 normal subjects. Consecutive stimuli were delivered at increasing stimulus intensities (SI) or with increasing levels of background voluntary muscle contraction (BVC). There was stimulus to stimulus variability in MEP amplitude, area and twitch force. At low SI and at low levels of background contraction, there was a good correlation between twitch amplitude and MEP amplitude and area (r = 0.6-0.96, P < 0.005). Increasing either variable caused the correlation to decrease significantly (r = 0.02-0.31, P > 0.01). With increasing SI, MEP amplitude and area plateaued but twitch force continued to increase. A similar pattern was observed with higher levels of background muscle contraction although in some subjects a second increase in MEP amplitude and area was seen. Collision experiments demonstrated that the amplitude of the EMG activity resulting from repetitive motoneuron firing increased as SI was increased. This is due to multiple descending volleys which result in repetitive firing of some spinal motoneurons. Rapid, repetitive firing of some motor units is likely to result in phase cancellation and, therefore, the MEP amplitude, and to a lesser extent area, do not accurately reflect the net motor output.

Significance of spontaneous epileptiform abnormalities associated with a photoparoxysmal response.

Spontaneous epileptiform abnormalities (SEAs) are reported to occur in up to 65% of patients with a photoparoxysmal response (PPR). Although the PPR is usually assumed to indicate primary generalized epilepsy, the clinical significance of associated SEAs is not known. We conducted the first study designed to correlate seizure classification with type of SEA in photosensitive patients. We examined seizure classifications and SEAs in 115 consecutive patients who had a PPR. A PPR was the only epileptiform abnormality in 47 patients (41%). Twenty-seven patients (24%) had focal SEAs and 41 (36%) had only generalized SEAs. Seventeen patients (15%) had partial seizures and 40 (35%) had only generalized seizures. Seizure classification was strongly associated with type of SEA (p < 0.0001). Patients with focal SEAs tended to have partial seizures, while patients with generalized SEAs tended to have only generalized tonic-clonic or absence seizures. Also, the presence of SEAs was significantly associated with a history of seizures (p < 0.0001), compared with patients who had a PPR but no SEAs. Although the PPR is often presumed to signify primary generalized epilepsy, most patients with a PPR and focal SEAs have partial seizures.

Crossed inhibition in the human motor system.

We used transcranial magnetic stimulation in humans to investigate the effect of focal unilateral stimulation of the motor cortex on the function of the contralateral motor cortex. Surface-recorded, rectified, averaged electromyography (EMG) showed relative silent periods in small hand muscles at 35-64 and 123-158 ms following ipsilateral cortical stimulation over the hand area. The first inhibitory phase started 11 ms after the minimum corticospinal conduction time from the contralateral cortex, appropriate for transcallosal conduction. Foot muscles (with focal stimulation over the ipsilateral hand area) also showed silent periods at 61-104 ms, indicating a marked spread of the inhibitory effect throughout the opposite motor cortex. H-reflex studies in the upper limb showed that this inhibitory effect was not mediated at the level of the alpha motoneuron. Single motor unit peristimulus time histogram studies in upper limb muscles showed inhibition similar to that seen in the surface recordings and no evidence of excitation following ipsilateral motor cortex stimulation. Transcranial magnetic stimulation performed with large circular coils centered at the vertex activates both excitatory and inhibitory processes bilaterally so that focal unilateral stimulation is preferable in detailed studies of motor system physiology.

Electrophysiologic monitoring in the intensive care unit.

Electroencephalography (EEG) and evoked potential studies are established monitoring tools in the neurological intensive care unit (ICU). These neurophysiologic techniques provide information on physiological state and response to therapy, and may aid diagnosis and prognosis. Serial studies or continuous monitoring may enable changes to be detected prior to irreversible deterioration in the patient's condition. Current computer technology allows simultaneous display and correlation of electrophysiologic parameters, cardiovascular state and intracranial pressure (ICP). Continuous EEG monitoring in the ICU has been shown to have a decisive or contributing impact on medical decision making in more than three-quarters of patients. In addition, continuous EEG monitoring has revealed previously unsuspected non-convulsive seizures in one-third of patients. SEPs and BAEPs can provide useful prognostic information in coma-however, these tests are etiologically nonspecific and must be carefully integrated into the clinical situation. Motor evoked potentials offer a potentially useful tool for evaluating motor system abnormalities in the ICU.

Effects of routine hyperventilation on PCO2 and PO2 in normal subjects: implications for EEG interpretations.

There are few data in the EEG literature describing the time course of hyperventilation-(HV) induced changes in blood gases, despite this being a routine activating procedure. We studied changes in blood gases and EEG in nine normal adult subjects before, during, and after HV. The mean PCO2 fell 18 mm Hg from the baseline during HV and recovered in 7 min. The mean PO2 rose 7 mmHg during HV and fell to 25 mm Hg below baseline 5 min after HV. The PCO2 recovery period is longer than is usually assumed in clinical EEG. The PO2 fall to a nadir at 5 min after the end of HV suggests that close attention should be paid to this period, as is confirmed by the re-buildup seen in moyamoya disease. Despite uniform changes in blood gases, the EEG median power frequency change showed marked variability; on average, it dropped by 1 Hz during HV and returned to baseline within 2 min of resumption of normal respiration. The EEG root-mean-square power showed a 200% increase during HV and also had returned to normal within 2 min.