George R. Hanna

Cerebral complications of angiography for transient ischemia and stroke Prediction of risk

We examined the records of 147 consecutive patients studied by femoral catheterization to identify factors contributing to angiographic risk in cerebrovascular disease. Cerebral complications occurred in 12.2 percent and were permanent in 5.2 percent. Computer-assisted multivariate analysis of 21 possible risk factors was done. Two of these risk factors correlated strongly with increased risk: number of previous transient ischemic attacks (TIAs) (p < 0.001), and the presence of arterial stenosis of greater than 90 percent (p < 0.03). Risk factors of marginal significance were: diabetes, female sex, and number of selective injections. A discriminant function for estimation of risk was derived: D = [8 × number of TIAs] + [6 × number of arteries catheterized] + [14 if diabetic, 0 if not] + [11 if female, 0 if male]. When D was > 55, 77 percent of patients had a complication. When D was < 55, 98 percent of patients had no complication. Unfortunately, patients in whom the study is most indicated tend to be those at greatest risk.

Evaluating Driving Performance of Outpatients with Alzheimer Disease

Background: Alzheimer disease (AD) is a progressive disease, with multiple physiologic, psychologic, and social implications. A critical issue in its management is when to recommend restrictions on autonomous functioning, such as driving an automobile. This study evaluates driving performance of patients with AD and its relation to patient scores on the Mini-Mental State Exam (MMSE). Methods: This study compared 29 outpatients with probable AD with 21 age-matched control participants on an interactive driving simulator to determine how the two groups differed and how such differences related to mental status. Results: Patients with AD (1) were less likely to comprehend and operate the simulator cognitively, (2) drove off the road more often, (3) spent more time driving considerably slower than the posted speed limit, (4) spent less time driving faster than the speed limit, (5) applied less brake pressure in stop zones, (6) spent more time negotiating left turns, and (7) drove more poorly overall. There were no observed differences between AD patients and the control group in terms of crossing the midline and driving speed variability. Among the AD patients, those who could not drive the simulator because of confusion and disorientation (n = 10) had lower MMSE scores and drove fewer miles annually. Those AD patients who had stopped driving also scored lower on their MMSE but did not perform more poorly on the driving simulator. Factor analysis revealed five driving factors associated with AD, explaining 93 percent of the variance. These five factors correctly classified 27 (85 percent) of 32 AD patients compared with the control group. Of the 15 percent who were improperly classified, there were three false positives (control participants misclassified as AD patients) and two false negatives (AD patients misclassified as control participants). The computed total driving score correlated significantly with MMSE scores (r = -.403, P = 0.011). Conclusion: Driving simulators can provide an objective means of assessing driving safety.

Cortical alterations in zones of secondary epileptogenesis: A neurophysiologic, morphologic and microchemical correlation study in the albino rat

Abstract Microchemical techniques combined with histological and electroencephalographic observations were used to study a cortical zone of secondary epileptogenesis, produced in rats by the contralateral topical application of powdered cobalt. The results were compared with similar but non-epileptic cortical specimens from animals subjected to contralateral thermocoagulative lesions, and with normal controls. At 21 days, all animals showed a ‘mirror focus’ of persistent spike activity contralateral to the site of cobalt application. No epileptic activity was seen contralateral to the coagulative lesions. A suppression of cortical electrical activity was found over both cobalt and coagulative lesions, which showed, histologically, neuronal loss, glial proliferation, and neovascularization. Silver impregnation studies showed similar patterns of axonal degeneration resulting from both types of lesions. There was abundant degeneration surrounding the site of injury and degeneration of transcallosal projections to the contralateral cortical area. Contralateral and homotopic to both lesions, DNA, an index of cellularity, increased significantly only in layers V and VI, suggesting a possible glial proliferation in association with the axonal degeneration. Two biochemical abnormalities were found peculiar to the mirror focus, and possibly causally related to the epileptic process. RNA, an index of protein synthesizing ribosomal organelles, was reduced in all cortical layers. Ganglioside sialic acid, a neuronal membrane component, was strikingly increased in layers III through V, with a maximum elevation in layer IV. In non-epileptic cortex contralateral to coagulative lesions, the intralaminar profiles of these two biochemical components were similar to normal controls. These results suggest that a pathologic decrease of neuronal ribosomes, associated with either an elaboration of synaptic contacts or a functional disturbance of ganglioside-related ion transport may be causally related to the epileptic process.

Effects of valproate and ethosuximide on thalamocortical excitability.

Sodium valproate and ethosuximide are anticonvulsants employed in the treatment of petit mal epilepsy; both drugs are considered to be thalamically active. Valproate and ethosuximide both decreased the average evoked response following the second of two stimuli delivered to the ventrolateral thalamus at stimulus frequencies in the region of 3 Hz. Ethosuximide, but not valproate, enhanced the average evoked response at high stimulus frequencies an action shared with several convulsant treatments having different modes of action. The clinical effects of valproate and ethosuximide can be related to this differential modulation of thalamocortical excitability.

Effects of antiepileptic drugs on thalamocortical excitability

Comparative effects of anticonvulsant drugs on the thalamocortical system were analyzed quantitatively. Paired stimuli were delivered to the ventrolateral thalamus with evoked responses recorded from the ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were developed with an on-line computer. Effects of phenytoin and diazepam were generally similar, with depression of excitability and slight elevation of thresholds. Ethosuximide produced a pronounced pair-interval dependent effect of unchanged or increased excitability and lowered threshold at shorter intervals, with depressed excitability and raised threshold at longer intervals. These data demonstrate a marked difference in effect of the petit mal and grand mal agents tested and suggest a basis for the effectiveness of ethosuximide in controlling 3-per-second repetitive activity.

Behcet's Disease: Presentation With Sagittal Sinus Thrombosis Diagnosed Noninvasively

The standard evaluation of patients with intracranial hypertension frequently does not reveal a discrete pathophysiologic process, leading in these cases to classification of the syndrome as “benign.” We present a 35‐year‐old woman with a recent diagnosis of pseudotumor cerebri who presented with headache, emesis, and blurring of vision. Her symptoms were progressive despite two lumbar punctures that revealed normal cerebrospinal fluid under high pressure. Contrast and noncontrast CT scans were normal; both the cerebrospinal fluid and CT neuroimaging were thus consistent with benign intracranial hypertension. An MRI, however, supported the presence of sagittal sinus thrombosis, a finding which was confirmed by MR venography. Further workup for an underlying cause of sinus thrombosis disclosed symptoms and signs fulfilling the diagnostic criteria for Behcets disease. Cerebral venous (or sinus) thrombosis should be considered in the differential diagnosis of intracranial hypertension. Behcets disease, while extremely rare, should be considered as a potential cause of cerebral venous thrombosis. Magnetic resonance venography can serve as a useful diagnostic study in situations where confirmation or exclusion of sinus thrombosis is required.

Epileptic Phenomena of Cortical Freezing in the Cat: Persistent Multifocal Effects of Discrete Superficial Lesions

Although often considered a transient phenomenon, the epilepsy induced by cortical freezing offers a number of experimental advantages over other methods. It avoids chemical contamination of the tissues under study. It avoids localized and systemic toxic effects which may be produced by the application of foreign substances. The epileptic effect is prompt and reliable, and the lesion is complete from the time of its inception. By timed extradural application of a metallic freezing probe of a known temperature, the “dose” can be precisely regulated, and lesions of any desired size and configuration can be relibaly reproduced in a series of animals or in a variety of locations.

The thalamocortical system as a neuronal machine: The interaction of ventrolateral nucleus with sensorimotor cortex in the cat

Summary The concept that the ventrolateral (VL) thalamic projections to sensorimotor cortex form a ‘self-modifying’ machine— i.e. , a machine whose response is due to both incoming information and information from its past history of use — has been substantiated by: (1) Developing a quantitative measure (specific output) of the cortical response evoked from pulse pairs delivered to VL. (2) Utilizing this measure to illustrate the differences which occur when nonsequential versus sequential testing is used. The dependence of specific output on both parameter changes put in by the experimenter and the existing conditions within the neuronal machine at the time of testing — i.e. , conditions set by past history — are illustrated. The adoption of a specific trajectory due to a selected sequence of stimuli further illustrates the adaptive nature of this system. Cerebellar influences have been investigated, in part, by ablating contralateral brachium conjunctivum and observing the changes which occur in machine performance. The principal influence of the cerebellum appears to be to impose stricter bounds on the modifying factors, on specific output amplitudes over sequential trajectories and on the dynamic cortical activity occurring during the first 10–25 msec after the delivery of a stimulus to VL.

Temporal Relationship of EEG Abnormalities in Migraine to Headache and Medication

SYNOPSIS

Development of the Thalamocortical Augmenting Response in the Kitten

Summary: Study of the developing central nervous system can lead to better understanding of the mature central nervous system. The thalamocortical augmenting response is a complex neurophysiological response considered to be related to the occurrence of some forms of epileptic activity. Using a paradigm previously developed in adult cats, we assessed the development of the thalamocortical augmenting response in kittens and found that the relative proportion of thalamocortical activity occurring at high frequencies of thalamic stimulation increased with increasing age. Anticonvulsants effective against petit mal seizures also increase the relative proportion of thalamocortical activity following high frequencies of thalamic stimulation. Developmental changes in the thalamocortical augmenting response can be related to the age‐dependent decreases in the prevalence of petit mal seizures.