Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.

Optimal evaluation of digital electroencephalograms.

Currently available digital EEG equipment provides considerably greater opportunities for clinical data analysis than is generally appreciated especially when appropriate software is used. Data from 7 different laboratories that had been obtained for routine diagnostic evaluations on 7 different EEG instruments and stored on compact disks were investigated. Since the instruments do not filter the data at input, ultra slow activity down to 0.01 Hz is currently being recorded but the attenuation factor is instrument dependent. Nevertheless, relevant clinical information is potentially available in these data and needs to be explored. Several examples in regard to epilepsy are presented. Determination of seizure onset may depend on the frequencies that are examined. The use of appropriate filter settings and viewing windows for the clinical question to be answered is stressed. Differentiation between simple and complex spike wave discharges, as well as spread of spikes, can readily be achieved by expanding the time base to 1 or 2 seconds and placing a cursor on the peak of the negative spike. Latencies in the millisecond range can then become apparent. EEGs co-registered with MEG should be evaluated with the same software in order to allow an adequate assessment of the similarities and differences between electrical and magnetic activity. An example of a comparison of EEG, planar gradiometers and magnetometers for an averaged spike is shown.

Body part asymmetry in partial seizure.

Clinically differentiating between localisation related and generalised epilepsy is important because it carries significant implications for planning diagnostic management strategy. Asymmetry of body parts such as toes, popliteal crease levels, thumbs, cubital crease levels, and forehead and facial structures, are common in patients with localisation related epilepsy syndromes. We retrospectively studied 337 patients with seizure disorders. Body part asymmetry was routinely documented. Fifty-six were excluded because of non-epileptic seizures, pure psychiatric disorders, non-epileptic neurological disorders, brain tumours and strokes. The relationship between clinically detectable body asymmetry (BA) and the electro-anatomic characteristics of their epilepsy was explored. Body asymmetry was found in 88 out of 282 cases, in which 64 (73.5%) suffered from localisation related epilepsy. Among localisation related epilepsy, BA were found in 41.5% (n=64/154) of patients. In contrast, only 18.75% (n=24/128) of patients with generalised seizure disorders showed similar findings (P<0.0001). Among patients with partial onset seizures, lateralisation of BA was concordant with their seizure origin in 75.9% (n=41/54) and discordant in 24.1% (n=13/54). Investigation results of 10 partial epilepsy cases were non-lateralising at the time of study. Peak age of onset of concordant case was 0-5 years old while discordant group was 6-15 years old. We conclude that BA in patients with seizure disorder is a useful clue to diagnosis of localisation related seizure and may provide clues for lateralising seizure origin in partial onset seizures.

The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in human cortex in normal controls and subjects with focal epilepsy.

Alpha-2 noradrenergic agonists may have wide applicability in the treatment of pre-frontal cortex deficits in primates and behavioral dysfunction in man. We have undertaken this study to determine the effect of an alpha-2 agonist, guanfacine, on regional cerebral blood flow (rCBF) in humans. Three subject groups were evaluated: normal controls, subjects with frontal lobe epilepsy (FLE), and subjects with temporal lobe epilepsy (TLE). All underwent a number of PET scans using 15O-water, with half before and half after a single dose of guanfacine. A wide area of increased rCBF was seen in the frontal lobe, maximal at the central region, following guanfacine in controls and subjects with TLE. Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal cortex on the epileptogenic side with only small increases seen in the mid- to anterior temporal perisylvian areas. The ability of alpha-2 agonists to enhance performance of tasks reliant on prefrontal cortex, without improving tasks believed to rely on intact temporal-hippocampal function, may be explained by these results. Epileptogenic zones appear to create both direct and indirect changes in patterns of drug response. Further studies on the cognitive properties of these agents in humans should be encouraged.

Electropalatographic and spectrographic descriptions of allophonic variants of /1/.

Prevocalic and postvocalic /1/ were investigated in three adult subjects utilizing a combination of electropalatographic and acoustic techniques. Results indicated that prevocalic /1/ was characterized by both alveolar and lateral lingua-palatal contact, while postvocalic /1/ was primarily alveolar contact only. Acoustically, prevocalic /1/ had a lower first formant and higher second formant than postvocalic /1/. In addition, the second and third formants were often weak or absent for prevocalic but not postvocalic /1/. Vowel context had a greater effect on the electropalatographic and acoustic characteristics of prevocalic than postvocalic /1/. Models that relate physiological and acoustical aspects of speech were utilized to account for the observed results.

Positron emission tomography: the contribution of cognitive activation paradigms to the understanding of the epilepsies.

Cognitive activation paradigms coupled with positron emission tomographic techniques may aid in the identification of functional and epileptogenic zones for presurgical evaluation. More work is needed to determine the most clinically efficacious paradigms for different seizure types. The real strength of activation positron emission tomography lies in the ability to study shifts in cognitive circuitry that accompany a fixed neuropathologic entity for both groups of similar subjects and individuals. These techniques are enhancing our understanding of the fundamentals of brain plasticity and may be used in the future to predict precise surgical risks.

Multiwavelength output from a Nd:YAG /Cr:LiSAF hybrid laser.

A prototype solid-state, multispectral hybrid laser has been designed and tested. The laser provides simultaneous outputs at several wavelengths. The hybrid-laser concept is based on the efficient use of flash-lamp-pump energy distributed between two complementary lasing materials, Nd:YAG and Cr:LiSAF, that share the same pump cavity. The prototype Q-switched hybrid laser provides dual-fundamental-wavelength output at 850 and 1064 nm as well as frequency-doubled output at 532 nm. The laser achieved 3.6% slope efficiency (combined) in free-running operation and 2.4% when Q switched. Higher efficiencies can be obtained with improvements in laser crystal quality and pump cavity configuration.

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.

Dynamic [18F]fluorodeoxyglucose positron emission tomography and hypometabolic zones in seizures: reduced capillary influx.

We performed dynamic [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomographic (PET) analyses in 8 patients. Rate constants of influx (K1*), efflux (k2*), phosphorylation (k3*), and dephosphorylation (k4*) were derived for the regions of interest (ROIs), which included (1) the hypometabolic epileptogenic regions and (2) the homologous regions in the contralateral hemispheres. In addition, the four constants were determined from at least one clearly defined (control) ROI from the same plane and its homologous contralateral ROI. Influx (K1*) in the epileptogenic region was reduced in comparison with the contralateral ROI. Reductions in influx (K1*), which averaged 18 +/- 13% (mean +/- SD), [18F]FDG phosphorylation (k3*) (25 +/- 20%), and brain glucose utilization rates (26 +/- 10%) were observed in the epileptogenic region. Reductions in efflux were not statistically significant (k2* = 13 +/- 28%) but were comparable in magnitude to the average reduction in K1*. No ipsilateral versus contralateral differences were seen for any rate constants measured outside the epileptogenic region. Influx correlated highly with phosphorylation in the epileptogenic region. Our data suggest that the hypometabolic epileptogenic focus seen in [18F]FDG-PET studies is also a region of reduced blood-brain barrier glucose transporter activity and that reductions in phosphorylation are proportional to reductions in [18]FDG influx.

Surgical outcomes in pure frontal lobe epilepsy and foci that mimic them.

In this study we examined 37 subjects with a diagnosis of intractable frontal lobe epilepsy (FLE) based on non-invasive pre-surgical evaluation. Twenty-six underwent chronic intracranial ictal recordings (CIR) with video monitoring; 20 of these went on to surgical resection. Eleven underwent surgery without CIR. Retrospectively, we determined that 19 had pure FLE, 12 had frontal plus extrafrontal epileptogenic zones, and six others did not have FLE. We analysed the whole group and individual categories to evaluate the determinants of surgical outcome. Sixty percent of the pure frontal group is seizure free with all having > or = 75% reduction. The frontal-plus group had only 10% seizure free with 70% having > or = 75% reduction. Being in the pure frontal group was associated with better outcomes than the 'frontal-plus' group (P < 0.05; chi-square). Subjects with FSIQ > or = 85, focal pathologies and 18FDG-PET scans which were normal or had focal abnormalities (P < or = 0.05, all, chi-square) were more likely to have excellent outcomes. MRI abnormalities, surface EEG, and location and size of resection were not predictive of surgical outcomes. Rasmussen's encephalitis, incomplete surgical strategies and bilateral foci were apparent in those with poor outcomes, and surgical size predicted post-operative deficits (chi-square; P < 0.001). We conclude that careful, hypothesis-driven implants and operating procedures can result in good surgical outcomes for frontal lobe epilepsy subjects even when lesions are not apparent on routine neuroimaging.

Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction: preliminary study.

OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. DESIGN AND METHODS: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Visual working memory in primary generalized epilepsy: an 18FDG-PET study.

It is generally believed that patients with primary generalized epilepsy have normal cognition and neuroimaging studies. We have previously shown that patients with juvenile myoclonic epilepsy (JME) have impaired visual working memory. In this study we examined relative regional changes in 18FDG uptake during a visual working memory paradigm in patients with JME. At rest, there were regional decreases in relative glucose uptake compared to controls. Unlike control subjects, increased activity in the dorsolateral prefrontal cortex was not found during the working memory task. Other regions with increased uptake in controls, such as premotor cortex and basal frontal cortex, also showed no increases, whereas medical temporal structures appeared to play a role in JME but not in control subjects' task performance. The data suggest that JME, a type of primary generalized epilepsy, may suffer from cortical disorganization that affects both the epileptogenic potential and frontal lobe cognitive functioning.

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.

Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones.

INTRODUCTION: We previously demonstrated that patients with frontal lobe epilepsy show deficits on a visual working memory paradigm and that this paradigm produces increased 18FDG uptake in the dorsolateral prefrontal cortex (DPFC), premotor cortex, angular and supramarginal gyri, basal forebrain, and ventral frontal poles of normal subjects when compared with a control task. We hypothesized that subjects with frontal lobe epilepsy would have impaired frontal activation during this task. METHODS: One resting and two activated images were obtained with 18FDG-PET in 15 subjects and 14 controls. One was a delayed (DMS) and one an immediate (IMS) match to sample paradigm. Discriminant and factor analyses were used to analyze the data, supplemented by selected t tests. RESULTS: No differences in glucose uptake were found between the DMS and IMS in the epilepsy subjects, in distinct contrast to controls. A comparison between controls and epilepsy subjects showed differences both ipsilateral and contralateral to the epileptic focus in the frontal regions involved in the task, with small changes in nonfrontal, task-related regions as well. The task itself brought out or highly exaggerated differences seen at rest. There was weak evidence that other frontal and temporal regions were attempting to compensate for the DPFC deficit. CONCLUSION: A unilateral epileptic focus is capable of suppressing function along a large task-related circuit ipsilateral and contralateral to the focus. Peripheral cortical regions compensate poorly for the area of dysfunction.

Marginal bone levels around maxillary implants supporting overdentures or fixed prostheses: a comparative study using detailed narrow-beam radiographs.

The issue of changes in marginal bone levels around maxillary implants supporting overdentures has been studied very little because of radiographic difficulties when using conventional intraoral techniques. The present study used detailed narrow-beam radiography, which offers excellent opportunities to depict implants and the surrounding bone in severely resorbed maxillae. Marginal bone levels around implants in patients with overdentures were compared to corresponding bone levels in a group of matched control patients with fixed prostheses supported by osseointegrated implants. No statistically significant difference in marginal bone height was noted between the groups. This finding is not in accordance with an earlier report on continuous loss of marginal bone around many maxillary implants supporting overdentures.

Long-term changes in marginal and periapical periodontal conditions in patients with fixed prostheses: a radiographic study.

Patients treated at a prosthodontic department during the years 1968-73 with fixed restorations (at least five units) were followed up in 1991-92. The aim of the present study was to compare marginal and periapical periodontal conditions on radiographs from 1968-73 and 1991-92 and relate the changes to the results of the prosthodontic treatment. In the group in which the restorations remained unchanged, 90% of the abutments that were not root filled and showed no periapical radiolucency when the restorations were placed, were still not root filled and showed no periapical radiolucency at the follow-up examination. The corresponding figure for the group in which the restorations had been replaced was only 69%. The changes in marginal bone levels also differed between the groups. In the group with remaining restorations, 66% of the surfaces were given the same score on a five-point scale both in 1968-73 and in 1991-92. In the other group, only 54% were scored the same on both occasions. Thus, unfavourable changes in both periapical and marginal periodontal conditions were associated with poorer results for the fixed restorations.

Studies of working memory using 18FDG-positron emission tomography in normal controls and subjects with epilepsy.

We have studied three groups of subjects with a working memory paradigm, using 18FDG-PET. Controls show the greatest increase on uptake in dorsolateral prefrontal cortex, basal forebrain and angular gyrus. A group of subjects with focal frontal epilepsy did not show increases compared to a control task of attention. Primary generalized epilepsy subjects show the greatest changes in angular gyrus, dorsal temporal, medial frontal and parietal regions. Factor and regression analyses extend these observations and show reliance of both patient groups on the medial and inferior temporal lobe. We propose that the normal network of working memory is disrupted by these two forms of epilepsy and different networks are accessed. Declarative memory may be used as a compensatory system, which results in decreased performance.

Unusual seizure types.

There is no consensus as to what constitutes a diagnostic complex partial seizure type for any given focus. Nevertheless, some forms are seen infrequently, such as in the patient just described who had parietal seizures, whereas others, such as the bland onset followed by oral-alimentary automatisms of temporal lobe epilepsy, are more common. It helps to be aware of the possible origins of these unusual forms when differentiating electrical seizures from pseudoseizures, planning for use of specific pharmacologic treatments, or planning a surgical resection. Although one cannot recommend a surgical resection based on semiology alone, one can place intracranial electrodes more strategically when the hypothesis regarding the seizure focus includes the clinical characteristics of the patient's seizures.

Cortical metabolic activation in humans during a visual memory task.

A delayed match-to-sample (DMS) task of abstract, visual memory was performed during the uptake period of 18F-fluorodeoxyglucose. The increase in glucose uptake of cortical and subcortical regions ("activation") during the DMS task was compared with that during a control, immediate match-to-sample task using positron emission tomography. Both discriminant analysis and paired t tests supported the observation that the dorsolateral prefrontal area underwent the greatest activation, while a factor analysis revealed the functional correlation matrices of the tasks. Activations in the ventral premotor cortex and supramarginal and angular gyri were highly correlated with the change in the dorsolateral prefrontal cortex. The basal forebrain/ventral pole region showed a smaller but independently significant change. The findings support the role of the dorsal prefrontal region in the nonspatial working memory of humans.