Barbara E. Swartz

Neuroimaging in temporal lobe epilepsy : test sensitivity and relationships to pathology and postoperative outcome

Summary: We studied patients with documented temporal lobe seizures to evaluate the predictive value of computed tomography (CT), magnetic resonance imaging (MRI), and F‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) for surgical therapy and the relationships between these tests and the pathologic diagnoses. CT detected abnormalities in 32.5%, with an accuracy of 19% when accuracy was defined as congruence with electrophysiologic studies. MRI detected abnormalities in 81%, with an accuracy of 67%. FDG‐PET detected abnormalities in 85%, with an accuracy of 82%. Pathologic change was detected in 79% of the excised temporal neocortex, 65% of amygdalae, and 93% of hippocampi. After follow‐up periods of 20–71 months (mean 41 months), 67% of patients were free of seizures and 94% had at least a 90% reduction in seizure frequency. There was no relationship between the type of abnormality on MRI or the type of pathology and postoperative outcome. Better outcomes were associated with focal or regional ictal onsets as recorded by surface EEG. Worse out‐comes were associated with hypometabolism that extended outside the temporal lobe. Pathologic change in the temporal neocortex was associated with extension of hypometabolism outside the temporal lobe.

Neuroimaging in Patients with Seizures of Probable Frontal Lobe Origin

Twenty‐two patients whose electroclinical ictal characeristics suggested frontal lobe seizure foci were studied. Computed tomography (CT) scans showed abnormalities in only 32% of patients whereas magnetic resonance imaging was informative in 45%. 18FDG‐Positron emission tomography (PET) scanning revealed decreased metabolism in 64% of the group. The areas of hypometabolism were focal, regional, or hemispheric. Focal frontal hypometabolism was significantly correlated with the electroclinical (semiologic) ictal localization. Therefore, FDG‐PET scanning is a sensitive and specific technique for investigating patients with seizures of probable frontal lobe origins.

The Human Brain GLUT1 Glucose Transporter: Ultrastructural Localization to the Blood—Brain Barrier Endothelia

Immunogold electron microscopy was used to examine human brain resections to localize the GLUT1 glucose transporter. The tissue examined was obtained from a patient undergoing surgery for treatment of seizures, and the capillary profiles examined had characteristics identical to those described previously for active, epileptogenic sites (confirmed by EEG analyses). A rabbit polyclonal antiserum to the full-length human erythrocyte glucose transporter (GLUT1) was labeled with 10-nm gold particle-secondary antibody conjugates and localized immunoreactive GLUT1 molecules in human brain capillary endothelia, with <0.25% of the particles beyond the capillary profile. Erythrocyte membranes were also highly immunoreactive, whereas macrophage membranes were GLUT1-negative. The number of immunoreactive sites per capillary profile was observed to be 10-fold greater in humans than in previous studies of rat and rabbit brain capillaries. In addition, half of the total number of immunoreactive gold particles were localized to the luminal capillary membrane. We suggest that the blood–brain barrier GLUT1 glucose transporter is up-regulated in seizures, and this elevated transporter activity is characterized by increased GLUT1 transporters, particularly on the luminal capillary membranes. In addition, acute modulation of glucose transporter activity is presumed to involve translocation of GLUT1 from cytoplasmic to luminal membrane sites, demonstrable with quantitative immunogold electron microscopy.

Hippocampal cell loss in posttraumatic human epilepsy.

Summary:  Purpose: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables.

Controlled micro release of pharmacological agents: Measurements of volume ejected in vitro through fine tipped glass microelectrodes by pressure

Abstract The amounts of substances delivered by applying pressure to fine. Theta-type, fluid-filled glass microelectrodes were quantitated by in vitro measurement. Relationships between the volumes ejected, the duration of pressure application, and tip size were investigated. The tip sizes ranged between ⩽ 0.6 and 1.2 μm o.d. and were suitable for recording intracellularly from cortical neurons in awake cats. With electrodes of tip sizes ⩾ 0.6 μm, the volumes of fluid ejected increased linearly with time. Volumes were determined by measuring the activity of ejected radio isotopes or the size of droplets of an aqueous solution expressed into mineral oil. Measurements were obtained over periods of up to 180 sec of pressure application (80 psi). The volumes expressed ranged between 10 1 −10 5 μm 3 . The rate of ejection increased as the tip size increased. Tips of 0.6 μm passed up to 2 × 10 2 μm 3 ; 0.9 μm, up to 4 × 10 3 μm 3 and 1.2 μm up to 5 × 10 4 μm 3 volumes for 30 sec of pressure application. The output rate was greater for ejections of ethanolic solution than for aqueous solution. The repeatability of ejection from individual electrodes was also tested. Relatively consistent, reproducible delivery was found for electrodes with tips between 0.6 and 1.2 μm. The results suggest that the pressure microinjection method affords more predictable, quantitative delivery than the iontophoretic method. Femtomolar (10 −15 M) amounts of pharmacologically active substances can be administered by such means.

Complex Partial Seizures of Hippocampal and Amygdalar Origin

Summary: We studied the first clinical manifestations of 72 complex partial seizures (CPS) in 17 drug‐resistant patients. CPS were indicated to be of hippocampalamygdalar origin by scalp and depth EEG. We asked: (a) Do all CPS of hippocampal‐amygdalar origin start with an initial motionless stare and/or oroalimentary automatisms? (b) If not, what other clinical manifestations appear at onset of the CPS? Results showed that ˜39% of CPS begin with motionless staring, 25% with nonfocal discrete movements, 21% with oroalimentary automatisms, 10% with perseverative stereotyped automatisms, and 6% with vocalizations. Nonfocal discrete movements and oroalimentary automatisms were identified as the most common second and third clinical sequential manifestations during a CPS. We conclude that although ˜60% of CPS of hippocampal‐amygdalar origin start with motionless staring or oroalimentary automatisms, 40% do not.

The advantages of digital over analog recording techniques

In the past few years digital technology has brought EEG and evoked potentials into emergency rooms, intensive care units and operating rooms with a variety of automatic data trending. Networking of these systems makes access to clinical neurophysiologists nearly immediate. Digital EEG has made montage reformatting and quantitation of parameters readily available. Increased spatial and temporal resolution is available with routine EEG, and combined topographic and frequency mapping of a given potential, spike or seizure focus is possible. In the future, these and other features such as dipole mapping and cognitive EP analysis will be available on a routine basis.

The safety and efficacy of chronically implanted subdural electrodes: A prospective study

BACKGROUND The popularity of subdural electrodes for the presurgical evaluation of patients with intractable seizures is increasing. However, few reports have prospectively dealt with their efficacy and safety. METHODS We conducted a 5-year prospective study of patients evaluated by the California Comprehensive Epilepsy Program, who subsequently underwent subdural electrode implantation at one of two institutions. Efficacy was examined by ultimate outcome with regards to postsurgery resection seizure frequency. Fifty-five patients underwent 58 implant procedures and postresection outcomes were available in 47 patients. Safety was defined by the incidence of expected and unexpected complications, and neuropathologic examination of tissue specimens. RESULTS The most common expected adverse effects during implant were fever < or = 102 degrees (41%), cerebrospinal fluid leakage (19%), headache (15%), and nausea (4%). There were no infections. Unexpected adverse events included fever > 102 degrees F (5%), migraine (5%), iatrogenic electrode dysfunction (5%), and temporalis muscle fibrosis (5%). The incidence of pathologic findings suggestive of foreign body reaction was 10%. There were no permanent sequelae. Surgical outcomes were excellent in all (> or = 75% seizure reduction) with 50% seizure free regardless of the focus. CONCLUSIONS Subdural electrodes are a safe, easy, and efficacious tool for evaluating seizure foci prior to resective surgery. They should no longer be considered investigational devices.

Electrophysiology of bimanual-bipedal automatisms.

Summary: To determine the localizing value and electrophysiology of bimanual‐bipedal automatisms (BBAs), we studied these behaviors in 54 seizures of 8 patients with temporal or frontal lobe seizure onset. BBAs occurred with a frequency of 27% in frontal lobe epilepsy (FLE) and of 7% in temporal lobe epilepsy (TLE). The distribution of electrode sites showing ictal activity during these automatisms was significantly different in the two patient groups (0.0001 Chi‐square). Mesioand/or laterotemporal plus orbital frontal areas were involved areas when the behaviors appeared in patients with TLE; dorsolateral and mesiofrontal regions were the most commonly involved when the behaviors occurred during the course of frontal lobe seizures. We concluded that BBAs represent activation of frontal lobe circuitry but are not unique to seizures of frontal lobe origin. Eyelid flutter and repetitive body movements in either the axial or sagittal plane were significantly associated with the frontal lobe group whereas oral‐alimentary automatisms were associated with the temporal lobe group. Thus, these associated behaviors may help indicate whether a frontal or temporal lobe seizure onset has occurred when BBAs are observed. A new concept of ictal expression is proposed to conform with the results as well as with other apparently disparate ictal behaviors that may have localizing value.

An 18FDG-PET study of cortical activation during a short-term visual memory task in humans.

Studies of subhuman primates and man have shown that the prefrontal cortex is important for spatial working memory. We have used 18fluorodeoxyglucose positron emission tomography (18FDG-PET) to study a non-spatial, abstract visual memory task of in man. Using a regions-of-interest approach with discriminant analysis of the relative regional cerebral metabolic rate of glucose consumption (rCMRGlc), we found that changes in dorsal prefrontal, premotor/motor frontal and posterior cingulate areas differentiated the primary memory task from the control task. Less robust increases in glucose uptake were observed in lateral parietal cortex, while some subcortical and limbic regions showed decreases. This is the first activation study with a non-spatial, visual task. These results complement previous studies in that they substantiate the role of the prefrontal cortex in the mediation of cross-temporal contingencies of behavior, and point to a role of the premotor region in this mediation as well.