Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.

BACKGROUND: Cerebral infarction in patients with atrial fibrillation may vary from being clinically silent to catastrophic. The prevalence of silent cerebral infarction and its effect as a risk factor for symptomatic stroke are important considerations for the evaluation of patients with atrial fibrillation. METHODS AND RESULTS: This Veterans Affairs cooperative study was a double-blind controlled trial designed primarily to determine the efficacy of warfarin for the prevention of stroke in neurologically normal patients with nonrheumatic atrial fibrillation. It also was designed to evaluate patients with silent cerebral infarction. Computed tomography scans of the head were performed at entry, at the time of any subsequent stroke, and at termination of follow-up on all patients who completed the study without a neurological event. Of 516 evaluable scans performed at entry, 76 (14.7%) had evidence of one or more silent cerebral infarcts. Age (P = .011), a history of hypertension (P = .003), active angina (P = .012), and elevated mean systolic blood pressure (P < .001) were associated with the presence of this finding. Silent cerebral infarction occurred during the study at rates of 1.01% and 1.57% per year for the placebo and warfarin treatment groups, respectively (NS). Silent cerebral infarction at entry was not an independent predictor of later symptomatic stroke, but active angina was a significant predictor; 15% of the placebo-assigned patients with angina developed a stroke compared with 5% of the placebo-assigned patients without angina. CONCLUSIONS: Silent cerebral infarction is frequently seen in asymptomatic patients with atrial fibrillation. Age, history of hypertension, active angina, and elevated mean systolic blood pressure were associated with silent infarction at entry. The sample size was too small to determine whether warfarin had an effect on the incidence of silent infarction during the trial. Active angina at baseline was the only significant independent predictor for the later development of symptomatic stroke.

Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.

BACKGROUND: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects.

The potential of transcranial magnetic stimulation (TMS) to cause undesired or unexpected effects on cognition and other cerebral functions has received only limited study, although extensive clinical use has suggested that obvious problems are unlikely. Evidence so far accumulated suggests that exposure to TMS in the expected clinical situations will have no persistent effects on the electroencephalogram (EEG) or on cognitive function, although transient effects may occur. The absence of increases in either prolactin or adrenocorticotropic hormone (ACTH) in subjects undergoing TMS indicates that seizure-like events do not routinely occur, although recent evidence suggests that TMS may cause seizures or enhance the occurrence of epileptiform abnormalities in circumstances of heightened susceptibility. Despite these observations, treated seizure patients are unlikely to experience seizures with TMS. The technique is generally safe, but not entirely free from unwanted effects, and further study to define those effects is warranted.

Estimating the importance of epileptiform abnormalities discovered on cassette electroencephalographic monitoring.

Assessment of the importance of interictal epileptiform abnormalities discovered with cassette electroencephalographic (EEG) monitoring requires some appreciation of the frequency with which such abnormalities may be encountered in individuals without epilepsy. From a clinical experience involving more than 2500 patients, we have defined a group of 184 patients referred because of headache, with no additional referral information to suggest seizures. Only one (0.5%) of these patients had epileptiform abnormalities on cassette EEG, yielding 95% and 99% confidence limits for the incidence of epileptiform abnormalities in the unselected nonepileptic headache population of 1.5% and 1.8%. Presuming that the incidence of cassette EEG epileptiform abnormalities in the healthy population would be no higher than in this patient group, we suggest that epileptiform abnormalities are no more likely to be incidental findings on cassette EEG monitoring than on routine EEG. Consequently, the detection of such abnormalities seems a worthwhile aspect of cassette EEG interpretation when the goal of monitoring is the detection of evidence to support a diagnosis of epilepsy.

Clinical correlates of Doppler/ultrasound errors in the detection of internal carotid artery occlusion.

One recognized limitation of carotid Doppler/ultrasound is its accuracy in differentiating occlusion from near-total occlusion of the internal carotid artery, which is a crucial issue in management decisions. Clinical histories were reviewed in 58 patients with apparent occlusion of an internal carotid artery diagnosed by Doppler/ultrasound who also underwent angiography. False-positive results were detected in eight patients, for an overall accuracy of 86%. Among a group of 25 patients with acute cerebral or ocular events ipsilateral to an apparently occluded artery, false-positive results occurred in seven (accuracy of 72%). Among a group of 33 patients with asymptomatic or remotely symptomatic apparent occlusions, only one false-positive occurred, for an accuracy of 97%. This difference in accuracy between groups was significant. Thus, a Doppler/ultrasound diagnosis of occlusion was most inexact in those patients for whom the detection of continued patency was most likely to influence management.

Transcranial magnetic stimulation: an assessment of cognitive and other cerebral effects.

To assess possible persistent cerebral effects, we acquired EEG, measured serum prolactin, and administered cognitive and motor tests before and after transcranial magnetic stimulation of 30 healthy adults. We found no detrimental effects on EEG or test performance. A slight but statistically significant decline in serum prolactin lacked correlation with the extent of stimulation.

Predictors of success for drug discontinuation following neonatal seizures.

Guidelines for the discontinuation of antiepileptic drugs in neonatal seizures are not well defined. Some studies suggested possible criteria for antiepileptic drug discontinuation but no precise criteria have emerged. We performed a retrospective analysis of 58 infants with neonatal seizures during a 3 year period. Antiepileptic drugs were discontinued when patients were seizure-free for 3 months, had normal electroencephalography initially or at subsequent examination, and had a nonfocal examination. Normal initial electroencephalography was demonstrated to be a reliable predictor for discontinuing antiepileptic drugs successfully in 18 of 22 term infants; normal subsequent electroencephalography was a reliable predictor of successful discontinuation of antiepileptic drugs in 9 of 10 premature infants.

EEG outside the hairline: detection of epileptiform abnormalities.

We have assessed the reliability in 25 epileptic patients of EEG recording using disposable self-adhesive electrodes and a seven-channel extra-hairline montage, through comparison to simultaneous standard cable telemetry. Epileptiform abnormalities were detected in all patients on blind interpretation of data acquired using the novel technique. On comparison of specific epileptiform abnormalities identified blindly, a false positive rate of 10% and a false negative rate of 8% were encountered. Posterior temporal complexes accounted for most false negatives, and most false positives did not represent failings of the recording technique. We conclude that EEG recording outside the hairline with disposable electrodes represents a reliable means to acquire, quickly and simply, EEG evidence of epilepsy. As such, it may prove useful in the acute evaluation of patients presenting with apparent seizures.

Ambulatory cassette electroencephalography of psychiatric patients.

Indications and results of ambulatory cassette electroencephalography obtained on 133 hospitalized psychiatric patients were reviewed. Interictal epileptiform abnormalities were detected in 15 patients (11%), of whom six had an established diagnosis of epilepsy. Actual seizures were recorded in two patients, of whom one had an established diagnosis of epilepsy. Subclinical seizure activity was detected in only one patient, who also experienced overt seizures. Routine screening of psychiatric patients with ambulatory cassette electroencephalography does not seem to be justified, although the test can provide useful adjunctive evidence to support the diagnosis of epilepsy and clarify the nature of suspicious clinical episodes in selected patients.

Epileptiform abnormalities discovered on electroencephalographic screening of psychiatric inpatients.

The results of electroencephalographic screening of 3225 inpatients from a community general hospital psychiatric service were reviewed. When patients with a prior diagnosis of epilepsy were excluded, epileptiform abnormalities were discovered in 2.6% of patients. Patients younger than age 25 years and patients with a diagnostic impression of anorexia nervosa, recent barbiturate abuse, or nonpsychotic explosive behavior were significantly more likely to have epileptiform abnormalities. The use of certain therapeutic agents was associated with a significant excess of epileptiform abnormalities in patients aged 25 years and older. The most frequently encountered epileptiform abnormalities were photoconvulsive responses. Focal temporal epileptiform abnormalities were detected in only four patients without a prior diagnosis of epilepsy. The diagnosis of epilepsy on the basis of a primarily psychiatric presentation and the discovery of epileptiform abnormalities on electroencephalographic screening should be approached with caution.

Supervision of ambulatory cassette EEG screening: a strategy based on the temporal distribution of epileptiform abnormalities.

The interposition of screening personnel in the analysis of extended cassette EEG recordings requires a method for supervision by the responsible electroencephalographer. To this end, analysis was undertaken of the temporal distribution of epileptiform abnormalities and seizures on cassette EEG in 40 epilepsy unit inpatients for whom these abnormalities were confirmed by simultaneous cable telemetry. Epileptiform abnormalities were noted in the hour following sleep onset in 38 patients (92%). Seizures occurred primarily in wakefulness. One hundred cassette EEG tapes obtained for clinical purposes and previously found to contain evidence of epilepsy were then subjected to an abbreviated review. Eighty-seven contained epileptiform abnormalities in the first hour of sleep, and 7 additional tapes contained only EEG seizure activity coincident with reported clinical events. Considering that fewer than 20% of cassette recordings obtained in unrestricted clinical use are likely to harbor epileptiform abnormalities or seizures, correct identification of about 99% of tapes as normal or abnormal can be anticipated with an abbreviated review consisting of analysis of the first hour of sleep; and analysis of reported clinical events if no abnormalities are noted in the first hour of sleep. Such a review is sufficiently accurate to serve as a supervisory analysis of cassette EEG tapes that have been previously screened and reported to lack evidence of epilepsy.

Demonstration of superior sagittal sinus thrombosis by indium-111 platelet scintigraphy.

Superior sagittal sinus thrombosis, documented by cerebral angiography, was demonstrated by indium-111 platelet scintigraphy in a 40-year-old man presenting with seizures and intracerebral hematoma. Early scintigraphy demonstrated focal increased indium-111 activity at the two ends of the thrombus, while later scintigraphy showed diffuse increased activity in the area of the sinus. This initial experience suggests that platelet scintigraphy may provide unique information regarding the natural history of intracranial venous thrombosis.

Cerebrospinal fluid lactate dehydrogenase in neonatal intracranial hemorrhage.

Cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) was measured in 54 neonates with intracranial hemorrhage and compared with 82 control, 27 traumatic lumbar puncture, seven meningitis, and 30 asphyxiated newborns. Hospital data, neonatal outcomes, and long-term neurodevelopmental follow-up results were reviewed. CSF LDH was not significantly affected by traumatic lumbar puncture but was elevated in proportion to the severity of CNS hemorrhage as scored by computerized tomography. LDH was also significantly associated with subsequent seizures and hydrocephalus and abnormal long-term developmental outcome.

Cassette electroencephalography in the evaluation of neonatal seizures.

Three-channel cassette electroencephalographic (EEG) recording for up to 24 hours was obtained from 37 neonates with clinically diagnosed or suspected seizures but no seizure activity on routine EEG. EEG seizures were recorded in seven patients, five of whom had experienced clinical seizures in the 24 hours prior to cassette EEG recording. EEG seizures were detected in only one of nine neonates with recurring clinical episodes believed unlikely to be seizures and in only one of 18 without recent clinical events. Cassette EEG can enhance the detection and differentiation of seizures in neonates with persistent clinical episodes but is of low yield otherwise.

Neuropsychological signs of asymptomatic carotid stenosis.

Several investigators have reported cognitive deficits associated with symptomatic carotid artery disease. This paper reports the findings of a study investigating cognitive deficits associated with asymptomatic carotid stenosis. Experimental subjects consisted of six patients who, in the course of routine physical examinations, showed carotid bruits and, on carotid ultrasound studies, showed 70% or greater stenosis in one or both arteries. No clinical symptoms had been associated with that stenosis. Six control subjects who were group-matched in terms of age and years of education were drawn from a control group evaluated previously for comparison with a transient ischemic attack (TIA) sample. All patients received a battery of tests consisting of a Wechsler Adult Intelligence Scale-Revised, abbreviated Halstead-Reitan Neuropsychological Battery, Revised Wechsler Memory Scale, and a written word fluency measure. Findings were converted to Rating Equivalents according to standard guidelines and an average Impairment Index was computed for each subject. ANOVA revealed that the two groups were significantly different in terms of the average Impairment Index. The clinical significance of these findings is discussed and implications for future research are reviewed.

Ambulatory cassette EEG in clinical practice.

We reviewed ambulatory cassette EEG (A/EEG) records of 500 patients. Epileptiform abnormalities, seizures, or both were detected in 87 patients (17.4%), including 22 who were not taking anticonvulsant drugs. Epileptiform abnormalities were found in 1.5% of patients with syncope and in none without a clear history of episodic complaints. Abnormalities were found in 5.1% of patients referred by nonneurologic physicians. Some clinical seizures were not accompanied by A/EEG change and some episodes were not seizures, despite detection of epileptiform abnormalities.

Reliability and accuracy of localization by scalp ictal EEG.

One hundred forty-four scalp ictal EEGs from 54 patients were analyzed independently by three electroencephalographers for side and lobe of seizure onset. Observers did not know the patients' identities. Accuracy was determined by depth EEG. We found 58 to 60% agreement between observers for lobe, and 64 to 74% for side, of seizure onset; 21 to 38% agreement with depth EEG for lobe, and 46 to 49% agreement for side, of seizure onset; best accuracy for lateralization of seizure onset in temporal lobe seizures, but erroneous in 3 to 17%. More formal criteria are needed before scalp ictal records can be used reliably or accurately for localization.

Cassette electroencephalographic recording of neonates with apneic episodes.

To evaluate the practical importance of seizures as a cause of neonatal apnea, we obtained extended cassette electroencephalographic recording for periods as long as 24 hours from 50 neonates experiencing apneic episodes unassociated with clinical seizure activity. Electroencephalographic recording through definite apneic episodes was obtained in 37 neonates; a total of 153 episodes were detected. None was associated with electroencephalographic seizure activity, although one term neonate without documented apneic episodes had seizure activity detected by cassette electroencephalography and may have had apneic seizures. The episodic apnea and bradycardia commonly encountered in preterm neonates is unlikely to be a manifestation of seizure activity, and extended electroencephlographic monitoring of such patients is of low yield.

A cerebral effect of carotid sinus stimulation. Observation during intraoperative electroencephalographic monitoring.

Surgical manipulation in the region of the carotid sinus resulted in diffuse electroencephalographic slowing in two patients, despite the absence of bradycardia or hypotension. Direct observation confirmed the absence of carotid compression. The effect was abolished by infiltration of lidocaine hydrochloride into the carotid sinus area. Carotid clamping in one patient failed to produce similar electroencephalographic changes. We believe that this is the first observation of an influence of carotid sinus stimulation on human cerebral activity not attributable to reflex cardiovascular changes or complicated by the possibility of carotid compression.