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.

Pattern shift visual evoked responses. Two hundred patients with optic neuritis and/or multiple sclerosis.

Fifty-one patients with clinically pure optic neuritis (ON) and 149 with possible, probable, or definite multiple sclerosis (MS) were tested with pattern shift visual evoked responses (PSVER) and compared with a group of 43 normal subjects. Attention was paid to response latency, intereye latency difference, as well as differences in amplitude or duration of the major positive peak (P100). Abnormal PSVER cannot be recorded from everyone with confirmed ON. Abnormal responses were recorded from 91% of all patients (including those with MS) who had a history of ON, 57% of all MS patients, and 36% of patients without a history of ON or an abnormal eye examination. Measurements of amplitude and duration proved to be of little value in this setting. Though abnormalities of PSVER are not "specific" for ON or MS, because they also result from other disease processes, they afford more reliable, quantitative documentation of abnormal conduction in visual pathways than any other clinical test.

Brain stem auditory evoked responses: studies of waveform variations in 50 normal human subjects.

Brain stem auditory evoked responses (BAERs) were recorded in 50 normal adult subjects at various click rates. Attention was paid to absolute latencies, interwave latencies, interear interwave latencies, absolute amplitudes, and various amplitude ratios. The variability of waves VI and VII suggests that the clinical utility of these waves is restricted-their absence is not necessarily due to a CNS lesion. The wave IV-V complex appears with six different patterns. These variations must therefore be considered normal; none should be misconstrued as indicative of disease of the CNS. Repeated studies over a period of two to nine months showed no statistically significant changes in amplitude or latency measurements with the passage of time. Knowledge of these normal values and their variations, as a precondition for establishing criteria for abnormality, is essential to the interpretation of BAERs in clinical situations.

Electroencephalographic findings in phencyclidine intoxication.

The first report of electroencephalographic findings in clinically encountered phencyclidine intoxication is presented. When first seen, the patient was in a coma, initially distinguished only by nystagmus, waxy rigidity of the extremities, and an EEG with a widespread, sinusoidal theta rhythm interrupted every few seconds by periodic slow-wave complexes. The similarity of the EEG to that of deep ketamine anesthesia suggested intoxication with a ketamine-related (phenylcyclohexylamine) drug. Phencyclidine, the prototype of the phenylcyclohexylamine compounds and a widely abused hallucinogen, was subsequently identified in the urine and blood.

Retinocalcarine function in Alzheimer's disease. A clinical and electrophysiological study.

Impaired visual function in Alzheimer's disease (AD) could result from either precortical or cortical lesions, or both. In a parallel psychophysical study of visual function in AD, we found that contrast sensitivity function, color vision, stereoacuity, and backward masking were impaired relative to the performance of age-matched control subjects, whereas performance on a critical flicker fusion test was normal. The intent of the present study was to determine whether abnormalities of the retinocalcarine pathway contribute to visual dysfunction. We performed neuro-ophthalmological examinations on 38 patients with AD; from this group, 25 received additional psychophysical testing and 13 underwent electrophysiological testing. Clinical neuro-ophthalmological examinations, full-field electroretinograms, focal electroretinograms, and pattern visual evoked potentials were normal in all patients tested. There was no evidence of retinocalcarine abnormality specific to AD. We conclude that the visual impairment experienced by some patients with AD primarily results from involvement of the visual association cortices rather than from precortical damage, at least before the end stage of the disease.

Pattern shift visual, brainstem auditory, and short-latency somatosensory evoked potentials in multiple sclerosis.

Pattern shift visual (PSVER), brainstem auditory (BAER), and short-latency somatosensory (SER) evoked potentials are practical and reliable clinical tests that provide objective measures of impulse conduction in the respective central nervous system (CNS) white matter tracts. In large groups of patients with multiple sclerosis (MS), the abnormality rates were 56, 32, and 60% (PSVER, BAER, and SER, respectively). Evidence of clinically unsuspected lesions was found in 42, 21, and 51%, respectively. Abnormality rates for a definite MS group alone were higher. The tests provide confirmatory and additional evidence for multiple lesions in CNS white matter. They may also provide an objective assessment of the efficacy of therapeutic regimens.

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.

Evoked potentials in Guillain-Barré syndrome.

We studied evoked potentials (EPs) in 27 patients with typical acute Guillain-Barré syndrome and 3 with Fisher's syndrome. Three of 21 had BAEP abnormalities: 1 with bilateral I-III, 1 with unilateral I-III, and another with unilateral III-V interwave latency prolongations. Three with Fisher's syndrome had normal BAEPs (one had a poorly formed wave V unilaterally with one click polarity only). Ten of 21 median nerve EPs and 9 of 12 peroneal or tibial nerve somatosensory EPs were abnormal. Seven patients with normal somatosensory EPs had abnormal F waves from the same nerve; none had normal late responses and abnormal somatosensory EPs. These observations differ from previous reports on the frequency and interpretation of EP abnormalities in Guillain-Barré syndrome.

Computerized EEG frequency analysis: sensitivity and specificity in patients with focal lesions.

We performed computerized EEG frequency analysis (C-EEGFA) in 69 controls and 20 patients with focal brain lesions and focally abnormal conventional EEGs. Individual channel EEG frequency analysis variables that were helpful in differentiating the 2 groups were absolute delta and theta band power, relative delta, theta, and alpha band powers, and median-power frequency. High-frequency beta band power (20 to 32 Hz) was not useful. Changes in EEG with age were seen only after age 50 and generally consisted of an increase in anterior alpha power, with no significant increase in slowing. Correlations of C-EEGFA variables with posterior alpha power were more significant than correlations with age. Calculating normative C-EEGFA data for 5 subsets of controls, each with a different amount of posterior alpha power, increased the sensitivity of the EEG frequency analysis test without altering the specificity. Even with this correction 2 of 20 patients with focal lesions and focally abnormal conventional EEGs had normal C-EEGFA studies. If these obvious focal lesions produced normal results, more subtle diseases might not be detected. A significant clinical utility of C-EEGFA remains to be proven.

Absence of evoked potential abnormalities in acute transverse myelopathy.

We studied 12 consecutive patients with inflammatory acute transverse myelopathy (ATM) and no prior history of neurologic disease. All had normal pattern shift visual and brainstem auditory evoked potentials. All of nine patients tested also had normal median nerve short-latency somatosensory evoked potentials. None developed new neurologic signs in 18 months' mean follow-up. In contrast, 72% of 50 patients with definite, probable, or possible multiple sclerosis (MS) had abnormalities in at least one evoked potential test. When defined as a virtually or completely transverse inflammatory lesion, acute transverse myelopathy differs from MS.

Ifosfamide causes a diazepam-sensitive encephalopathy.

An encephalopathy characterized by confusion, stupor, and mutism frequently occurs during administration of the chemotherapeutic drug ifosfamide (IFX). We investigated two patients who developed encephalopathy during IFX infusion. Both exhibited a rapid and near-complete restoration of baseline mental status functioning concurrent with EEG improvement after administration of intravenous diazepam. We recommend an EEG and trial of benzodiazepines in patients with IFX encephalopathy.

Evoked potentials in motor system diseases.

We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis.

Facilitation of magnetic motor evoked potentials during the cortical stimulation silent period.

We investigated the relationship between stimulus intensity and magnetic motor evoked potentials (MEPs) elicited 100 msec after a conditioning stimulus that was 25% of stimulator output above resting motor threshold (RMT) during tonic contraction of abductor pollicis brevis. In five subjects, MEPs elicited with stimuli less than 25% above RMT were inhibited during the EMG cortical stimulation silent period (CSSP) produced by the conditioning stimulus, relative to MEPs elicited with the test stimulus given at rest. However, increasing the intensity of the test stimulus increased the amplitude of MEPs elicited during the CSSP relative to MEPs elicited at rest, such that MEPs elicited with stimuli 30 to 45% above RMT were facilitated during the CSSP. Increasing the intensity of the test stimulus also increased the amplitude of MEPs elicited with paired stimulation at rest, and caused facilitation in one subject. Since facilitation of MEPs was never accompanied by shortening of MEP latency, our observations point to supraspinal facilitory mechanisms. We suggest that facilitation of MEPs during the CSSP reflects temporal and spatial summation of conditioning and test stimuli.

Brainstem auditory and short-latency somatosensory evoked responses in brain death.

Thirty-five patients who met all clinical criteria for brain death and 53 patients who did not were tested with brainstem auditory (BAER) and short-latency somatosensory (SER) evoked responses. Of the brain-dead patients, 77% had no waves present in the BAER, including wave I, whereas 69% had medullary components present in the SER. These data suggest that the SER has greater clinical utility in the brain-death setting, because it is important to have a wave present that established that the input signal has reached the central nervous system. No brain-dead patients had subsequent waves in either test. These results are correlated with neuropathologic findings and contrasted with data obtained in the comatose but not brain-dead patients.

Hemispheric threshold differences for motor evoked potentials produced by magnetic coil stimulation.

A brief monophasic pulse through an electromagnetic coil preferentially activates motor pathways of each hemisphere, depending on the direction of coil current flow. Using the preferred direction for each hemisphere, the minimum stimulus intensity (threshold) that evoked compound muscle action potentials in the contralateral abductor digiti minimi (ADM) muscle was significantly less for the left hemisphere than the right. Threshold for biceps on each side was significantly higher than ADM, but there was no side-to-side difference. Assessing handedness using a standard handedness index, those who had less tendency to use the right hand for everyday tasks had greater differences between hemispheres for ADM thresholds. The lower threshold of the left-hemisphere projection to hand muscles is probably related to the asymmetry of corticomotoneuronal monosynaptic connections; a greater number project to the motor neuron pool of the right- than left-hand muscles.

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.

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.

Cervical magnetic stimulation.

We stimulated the cervical region with a 9-cm-diameter magnetic coil on centered on the spinous processes in 21 normal subjects. We obtained maximal amplitudes with clockwise coil current in right-sided upper extremity muscles and counterclockwise coil current in left-sided upper extremity muscles. Optimal stimulation sites for biceps, triceps, and abductor digiti minimi were C-3 or C-4, C-4 or C-5, and C-4, C-5, or C-6, respectively. The latencies of the muscle responses varied little in the same subject in spite of marked amplitude changes due to suboptimal position of the coil or submaximal stimulator output. In abductor digiti minimi, the amplitude of the muscle response on cervical magnetic stimulation was 9 to 100% of the supramaximal amplitude on wrist electrical stimulation. We established normal values for latency, amplitude, and interside differences for the above 3 upper extremity muscles. The findings were reproducible, and the latencies obtained with large coils from different manufacturers in the same subjects were comparable. We found no advantage in bipolar recording over tendon-belly montage. Comparison of magnetic and electrical needle root stimulation in the same subjects showed that the magnetic stimulus was more proximal in biceps and triceps, and that the site of excitation was approximately the same in abductor digiti minimi. Indirect assessment of the longitudinal site of excitation based on F-wave minimal latency indicated that excitation occurred within millimeters of the emergence of axon of the peripheral motor neuron.

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.

Physiological motor asymmetry in human handedness: evidence from transcranial magnetic stimulation.

We hypothesized that human handedness might be associated with measurable differences in the excitability of the motor system. We compared the thresholds for electromyographic activation of the left and right abductor pollicis brevis (APB) and biceps muscles in 30 left-handers and 30 right-handers, by varying the direction of a brief monophasic pulse in a circular electromagnetic coil centered over the vertex of the scalp. In right-handers, we found that the threshold for activation of muscles in the right arm was lower than the threshold for activation of corresponding muscles in the left arm. In left-handers, the reverse was true. Threshold asymmetry was influenced significantly by the consistency with which each subject used the writing hand to perform other motor tasks, and was not significant between non-consistent left-handers and right-handers. Our results indicate that human handedness, and in particular, consistency of hand preference, are associated with lateralized differences in the excitability of motor system projections activated by transcranial magnetic stimulation. Our findings might reflect physiological differences in corticospinal tract function or cortical motor representation.