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Biomedical subjects

R P Lesser

Publications and source records attributed to R P Lesser.

At least 55 records · Page 3Linked to original sources

Driving and epilepsy. A review and reappraisal.

Driving and epilepsy is a problem that involves physicians as both care providers to patients and consultants to regulatory authorities. Driving restrictions for people with seizure disorders are intended to ensure the public's safety, but such restrictions may unduly harm the welfare of many people with seizures. In the United States, all states now permit some people with epilepsy to drive. In general, only people whose seizures are adequately controlled are licensed to drive. Adequate control has been judged principally by the seizure-free interval, but individual state standards widely vary. There is a trend toward greater liberalization of driving standards for people with seizure disorders, but the appropriateness and application of these standards continue to raise questions, as does the role physicians should have in the licensing process. Our responsibilities to persons with disabilities and advances in our understanding of seizures and the nature of driving risks warrant a reappraisal of the current medical, legal, and social implications of driving and epilepsy.

Accidents, Traffic

Dominant-side intracarotid amobarbital spares comprehension of word meaning.

Abolition of speech production after intracarotid amobarbital injection is generally considered evidence for language laterality. However, complex auditory comprehension may be preserved after injection of the dominant (left) side. The possibility that this sparing may be due to the intracarotid amobarbital injection not adequately deactivating some of the areas responsible for speech comprehension in the posterior part of the hemisphere was tested with a task known to be critically dependent on the left posterotemporal-inferoparietal region, one assessing visuo-verbal semantic relatedness. Even when the intracarotid injection of the left side produced marked deficits of speech production, comprehension of semantic relations was still intact in eight of 15 patients. Ten of these 15 patients also received right carotid injections, none of which affected comprehension of semantic relatedness. These data indicate that the intracarotid amobarbital injection cannot always specify the laterality of all language functions, an important concern when considering surgical procedures in the dominant posterotemporal-inferoparietal region.

Adolescent

Capillary prolactin measurement for diagnosis of seizures.

Measurement of serum prolactin levels can be useful in the diagnosis of epilepsy, since prolactin levels often rise after seizures, but not after most imitators of epilepsy. Utility of the test is limited by the need to obtain blood 10 to 20 minutes after the episode. The present study documents the validity of prolactin measurements using capillary blood, which was obtained by the finger-stick method after a possible seizure and then applied to filter paper. Venous and capillary prolactin levels were determined 10 to 20 minutes after seizure-like episodes in 20 patients who were studied in an epilepsy monitoring unit. Venous and capillary prolactin values correlated, with a Pearson coefficient of 0.90. Using a criteria of any elevation above the laboratory upper limit of normal, capillary prolactin values correctly identified seizure versus pseudoseizure in 9 (100%) of 9 patients with generalized tonic-clonic seizures, in 5 (71%) of 7 patients with complex partial seizures, and 4 (100%) of 4 patients with pseudoseizures. Prolactin values were unaffected by leaving filter paper samples at room temperature for up to 1 week. This study suggests the utility of diagnostic capillary blood collection kits to assist in the diagnosis of epilepsy in outpatients.

Adult

Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

Amygdala

Basal temporal language area.

Language interference was elicited by electrical stimulation of the dominant basal temporal region in 8 out of 22 cases and in none of 7 cases with subdural electrodes implanted over the nondominant temporal lobe. Language interference was elicited by stimulation of electrodes placed over the fusiform gyrus 3-7 cm from the tip of the temporal lobe. Electrical stimulation of the basal temporal language area produced a global receptive and expressive aphasia with speech arrest at high stimulus intensities. Other higher cortical function, for example copying complex designs or memory of nonverbal information was intact, in spite of the total inability to process verbal information. At lower stimulus intensities partial aphasias with a predominant receptive component occurred. Surgical resection of the basal temporal language area produces no lasting language deficit.

Adolescent

Mapping the distribution of amobarbital sodium in the intracarotid Wada test by use of Tc-99m HMPAO with SPECT.

The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures. The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium. Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient. SPECT revealed a statistically different distribution from that predicted with conventional angiography. The distribution also often differed from that of DSA, although the difference was not significant. SPECT revealed infrequent delivery to mesial temporal lobe structures. This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.

Adolescent

Multifocal independent epileptiform discharges in children: ictal correlates and surgical therapy.

We obtained continuous EEG/video recordings on four children who had the interictal EEG pattern of multifocal independent epileptiform discharges (MIED). The prominent feature of their evaluation was the evidence that their clinical seizures appeared to be of focal origin; 42/44 seizures were manifested by "fencing postures." Three patients subsequently underwent epilepsy surgery: one focal resection of superior frontal-parietal cortex and two hemidecorticectomies. Seizure control improved in all three patients, and one patient is now seizure-free. Our patients differ from those previously reported in that they had a predominance of tonic seizures and had no history of infantile spasms or Lennox-Gastaut syndrome. Some patients, such as ours, with MIED may have clinical seizures of more focal origin than might be expected from their interictal EEG and, therefore, may benefit from resective epilepsy surgery.

Adolescent

A continuing controversy: magnesium sulfate in the treatment of eclamptic seizures.

It would appear from the above that Pritchard agrees with the use of some agents other than magnesium sulfate that have known anticonvulsant properties. We believe that the subject at issue is whether magnesium sulfate should be used in treating the seizures of eclampsia. In our "Controversies" article, we do not address the issue of whether magnesium sulfate modifies pathophysiological factors leading to preeclampsia, but restrict ourselves to the treatment of the seizure per se, once seizures supervene, and the avoidance of their recurrence. The pathophysiological mechanisms and optimal treatment of preeclampsia and of eclampsia (excepting seizures) remain to be determined, as does the use of magnesium sulfate in this condition. Eclamptic seizures are clinically and electroencephalographically indistinguishable from generalized tonic-clonic seizures. Whether seizures arise in or out of the setting of preeclampsia, they should be treated as are other seizures, with known anticonvulsants. Controlled clinical trials are needed to address the effectiveness of alternative antiseizure regimens.

Eclampsia

Parameters for direct cortical electrical stimulation in the human: histopathologic confirmation.

Safe parameters for electrical cortical stimulation in humans are difficult to estimate from the animal experimental literature. We therefore examined the light microscopic histology at a total of 11 sites of direct subdural electrical stimulation, taken as part of anterior temporal lobectomies in 3 patients. Stimulations had been done through 3.175 mm diameter electrodes, with 0.3 msec square wave pulses of alternating polarity at 50 pulses/sec. In 2 patients, one site each had been used as a common reference for stimulation, receiving over 251 stimulation trials, most of 2-5 sec duration, at currents of 12.5-15.0 mA, 1 day prior to resection. The maximum charge per phase was 4.0-4.4 microC; the maximum charge density was 52-57 microC per geometric cm2 per pulse at the electrode surfaces. Comparison of hematoxylin and eosin, periodic acid-Schiff, and cresyl violet-stained material from the electrode sites with that from other regions did not show any histologic abnormalities attributable to the electrical stimulation. The relatively brief and intermittent periods utilized for human stimulation testing do not appear to cause structural damage at the light microscopic level at charge densities that exceed the threshold for damage established in animal studies with more continuous, chronic stimulation schedules.

Electric Stimulation

Dextromethorphan for treatment of complex partial seizures.

We performed a double-blind, crossover, add-on study of the antitussive agent dextromethorphan (DM 120 mg/d) as therapy for seizures on 9 patients suffering from severe complex partial seizures. DM had no significant influence on key laboratory values, nor on anticonvulsant drug levels. Side effects were negligible. Complex partial seizure frequency increased 25% during the DM arm of the study, although this increase was not clinically significant.

Adult

Characterization of the basal temporal language area in patients with left temporal lobe epilepsy.

We evaluated 5 consecutive patients with subdural grid electrodes (including placement over the left basal temporal region) for focal resections for control of intractable epilepsy. All 5 had language dysfunction when we performed cortical stimulation over the basal temporal region (the inferior temporal gyrus, the parahippocampal gyrus) using a systematic battery of language tests. The area in which language interference could be produced began from at least 11 to 35 mm posterior to the temporal tip and ended at least 39 to 74 mm posterior to the temporal tip. The most consistently impaired language tasks were spontaneous speech and passage reading, but there was impairment of all language functions tested in some patients. Language deficits after dominant temporal lobectomy may result from resection of this area.

Adult

The evaluation of patients with intractable complex partial seizures.

Conceptual advantages, together with advances in both technique and technology, have considerably altered the approach to intractable epilepsy over the past two decades. Appropriate utilization of these advances allows our evaluation of patients with intractable seizures to be much more precise and specific than was once the case and allows us to improve considerably our ability to treat patients with intractable epilepsy. We propose an algorithm for the evaluation and treatment of patients with intractable complex partial seizures. Other forms of intractable epilepsy may benefit from similar diagnostic and therapeutic approaches.

Decision Trees

Vertical and horizontal epileptic gaze deviation and nystagmus.

Periods of epileptic nystagmus consisting of rightward eye deviation and right-beating nystagmus, alternating with upward eye deviation and upbeating nystagmus, occurred in a comatose patient with a left hemisphere subdural hematoma and seizures. The periods of upbeating nystagmus were associated with symmetric, low-voltage 3 to 4 Hz bifrontal spikes. Rightward eye deviation and right-beating nystagmus occurred with diffuse, predominantly left hemispheric 4 to 6 Hz sharp waves. No eye movements occurred in the absence of spike and wave activity. These correlations agree with current concepts of the cortical control of saccadic eye movements in monkeys studied by electrical stimulation.

Aged

Subdural electrodes in the evaluation for epilepsy surgery in children and adults.

To evaluate the utility and safety of chronic extraoperative subdural EEG and functional localization studies in children compared to adults, we studied 61 patients each of whom had similar evaluations for epilepsy surgery, regardless of age. The 23 children and adolescents (3 to 18 years old) and the 38 adults (20 to 41 years old) each had several days and nights of extraoperative EEG from scalp and chronically-implanted subdural electrodes, and the same percentage of children and adults also had functional localization studies including cortical electrical stimulation. The methods and results of these studies and of the subsequent resections did not differ between the two groups, and they both had similar rate of complications and similar incidence of good outcome. The subdural technique was as effective and well-tolerated in children and adolescents as in adults. Other invasive EEG techniques have not yet been systematically compared between children and adults, but the subdural technique, at least, appears to be suitable for patients over a wide age range.

Adolescent

Failure of high-dose intravenous magnesium sulfate to control myoclonic status epilepticus.

An unsuccessful attempt to terminate myoclonic status epilepticus with elevation of serum magnesium levels is described. During 3 days, serum magnesium was increased from 1.5 mEq/L to 14.2 mEq/L by continuous i.v. infusion of 3-6 g/h of magnesium sulfate. Other anticonvulsants were maintained at nearly constant levels. Cerebrospinal fluid magnesium was 3.5 mEq/L during the infusion. Despite magnesium-related neuromuscular blockade and accompanying cessation of visible myoclonus, the electroencephalogram revealed ongoing blunted sharp-wave activity at the baseline frequency. Transient complications of the infusion included prolongation of the PR interval on the electrocardiogram, hypomotility of the gastrointestinal tract, and peripheral muscle flaccidity, all of which resolved within 24 h of return to normal serum magnesium levels. These results suggest that the therapeutic role of magnesium in myoclonic status epilepticus is limited.

Adult