Reexamination of 123I-IMP-SPECT at interictal stages in adult partial epilepsy

123I-IMP-SPECT scans at the interictal stages in 13 epileptic patients with normal X-ray CT findings were reexamined at intervals of 1.9 +/- 0.8 years. Interictal scalp EEGs were recorded a few hours after each SPECT scan. All of the SPECT abnormalities indicated focal hypofixation images of 123I-IMP, i.e. zones of a decreased rCBF reflecting a functional inactivation. Among 11 patients with the SPECT abnormalities in the first SPECTs, eight cases had the complete or partial regional reproduction of the abnormalities in the second SPECTs. As changes in the SPECT findings, an alteration from the abnormal SPECT images to normal images (normalization), the reverse change, the enlargement and reduction of hypofixation sites were seen. Also the EEG foci had various changes (right and left regional changes, etc.). Because of these SPECT and EEG changes, the regional relationship between the SPECT abnormalities and EEG foci altered in 7 patients (a change from disagreement to agreement, etc.). The high reproduction rate of SPECT abnormalities appears to increase the reliability or utility of SPECT scans for a regional diagnosis of epileptic foci. The present SPECT changes, especially the normalization or the severse change, suggest that the interictal epileptic focus may have a functional fluctuation. In addition, the causes of regional disagreement between the SPECT abnormalities and EEG foci were discussed on the basis of the present SPECT and EEG changes.     

Sequential 123I-IMP-SPECT in acute infantile hemiplegia

Sequential 123I-N-isopropyl-p-iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) was performed in 2 patients with acute infantile hemiplegia. In both patients, low uptake of IMP was detected in the targeted abnormal hemisphere. The 123I-IMP-SPECT findings indicative of a pathologic condition persisted even when the clinical findings and electroencephalographic abnormalities improved. Because of its sensitivity, noninvasiveness, and accurate reflection of the cerebral blood flow distribution, 123I-IMP-SPECT is useful in the examination of acute infantile hemiplegia and in the evaluation of prognosis.     

Clinical Utility of Interictal High-Frequency Oscillations Recorded with Subdural Macroelectrodes in Partial Epilepsy

Background and Purpose

There is growing interest in high-frequency oscillations (HFO) as electrophysiological biomarkers of the epileptic brain. We evaluated the clinical utility of interictal HFO events, especially their occurrence rates, by comparing the spatial distribution with a clinically determined epileptogenic zone by using subdural macroelectrodes.

Methods

We obtained intracranial electroencephalogram data with a high temporal resolution (2000 Hz sampling rate, 0.05-500 Hz band-pass filter) from seven patients with medically refractory epilepsy. Three epochs of 5-minute, artifact-free data were selected randomly from the interictal period. HFO candidates were first detected by an automated algorithm and subsequently screened to discard false detections. Validated events were further categorized as fast ripple (FR) and ripple (R) according to their spectral profiles. The occurrence rate of HFOs was calculated for each electrode contact. An HFO events distribution map (EDM) was constructed for each patient to allow visualization of the spatial distribution of their HFO events.

Results

The subdural macroelectrodes were capable of detecting both R and FR events from the epileptic neocortex. The occurrence rate of HFO events, both FR and R, was significantly higher in the seizure onset zone (SOZ) than in other brain regions. Patient-specific HFO EDMs can facilitate the identification of the location of HFO-generating tissue, and comparison with findings from ictal recordings can provide additional useful information regarding the epileptogenic zone.

Conclusions

The distribution of interictal HFOs was reasonably consistent with the SOZ. The detection of HFO events and construction of spatial distribution maps appears to be useful for the presurgical mapping of the epileptogenic zone.     

Interictal Behavioral Changes in Epilepsy

Summary: Common behavioral alterations associated with epilepsy include increased interest in philosophical and religious concerns, increased and extensive writing of a cosmic or philosophical nature, changes in sexual behavior, and aggressiveness. Psychological stress, the effects of anticonvulsant therapy, and the actual occurrence of seizures or convulsions can be ruled out as possible causes of the syndrome. It is speculated that these behavioral alterations are the result of an intermittent spike focus in the temporal lobe that leads to an alteration in the responsiveness of the limbic system. Thus, there is a heightened emotional response to many stimuli as well as a decrease in sexual responsiveness. In an effort to discover the cause of the high incidence of sexual alterations, abnormalities in response to luteinizing hormone-releasing hormone (LHRH) were found in a group of patients with partial complex seizures, some of whom had no overt sexual dysfunction and had never received anticonvulsant therapy.     

Benign Partial Epilepsy with Affective Symptoms: Hyperkinetic Behavior During Interictal Periods

Summary: We report a 4-year-old boy with benign partial epilepsy (BPE) with affective symptoms associated with hyperkinetic behavior during interictal periods. He had had hypermobility and restlessness since about age 3. At 4 years, 6 months, he developed episodes consisting of an expression of terror without complete loss of consciousness. Although we first suspected an acute psychic problem, the ictal EEG was abnormal. After carbamazepine (CBZ) therapy, the frequency of the attacks decreased dramatically and the hyperkinetic behavior gradually diminished.     

Clinical Usefulness of the Dipole Tracing Method for Localizing Interictal Spikes in Partial Epilepsy

Summary: Purpose: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy.
Methods : Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictayictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG).
Results : In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe.
Conclusions : The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.     

Interictal EEG and the Diagnosis of Epilepsy

Summary:  The interictal EEG provides information that aids in diagnosis and management of epilepsy. One must remember that the EEG is merely a tool, and its usefulness depends largely upon the skill of the individual who wields it. Like all diagnostic tests, it has significant limitations and cannot substitute for a careful history and exercise of good judgment. Nonetheless, in skilled hands, it provides unique and vital information in many patients, and enhances our understanding of their condition.     

Interictal Behavioral Features of Patients With Epilepsy

Summary: Three questions are dealt with in this paper. (1) Do patients with epilepsy differ behaviorally from normal control groups and from persons with other medical and neurological conditions with respect to emotional adjustment, and if so, in what ways? (2) Are patients with temporal lobe epilepsy different emotionally or behaviorally from patients with other types of epilepsy? (3) To what degree does underlying brain dysfunction create a substrate for abnormal and maladaptive behavior? A review of the literature reveals the following. (1) Persons with epilepsy demonstrate more emotional and psychiatric problems than normal individuals and more difficulties than other patient groups having nonneurological disorders, but have about the same incidence of these problems as persons with other neurological disorders. (2) Increased emotional and psychiatric problems are not found among patients with temporal lobe epilepsy in comparison to patients with other types of epilepsy, although there are some behavioral peculiarities which appear in a small proportion of these patients. (3) There is a mild tendency for impairment on neuropsychological tests to be associated with emotional and psychiatric problems in epilepsy.     

Interictal Cardiovascular Autonomic Responses in Patients with Epilepsy

Summary: Purpose: To evaluate the interictal autonomic nervous system function in 84 patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy, and 47 patients receiving long-term carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure disorder. Methods: We assessed autonomic control of the cardiovascular regulatory system, by standardized cardiovascular reflex tests measuring changes in heart rate (HR) and blood pressure (BP) at rest and after certain stimuli. Results: The HR and BP responses were similar to those of control subjects in patients with newly diagnosed epilepsy. However, HR variation during normal breathing and maximum systolic BP increase in isometric work were diminished in patients, who had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time. Diminished HR responses to the Valsalva maneuver were noted in patients receiving CBZ as monotherapy and during deep breathing in patients receiving CBZ combined with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses in isometric work. When analyzed in relation to epilepsy type, suppressed HR responses in normal breathing were associated with primary generalized epilepsy (PGE), whereas diminished BP responses in isometric work were associated with partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1 patient receiving long-term CBZ monotherapy for partial epilepsy had two abnormal cardiovascular response test results. Conclusions: Our results show that cardiovascular responses mediated by both the parasympathetic and sympathetic nervous system are diminished in patients with epilepsy. However, the changes appear to be clinically significant in only a few of them and appear to be associated with CBZ medication. Further studies are needed to detect the underlying complex interactions and clinical significance of autonomic nervous system dysfunction in patients with epilepsy.     

Two cases of adult Down's syndrome presenting parietal low uptake in 123I-IMP-SPECT]

We performed 123I-IMP-SPECT to patients with Down's syndrome who were supposed to have neuropathological findings of dementia of the Alzheimer's type. In case 1, a 52-year-old man with dementia, bilateral posterior parietal low uptake and right temporal low uptake were noted. Uptake was markedly lower in the right hemisphere. Case 2, a 38-year-old man not exhibiting clinical features of dementia, presented slightly decreased uptake in bilateral posterior parietal areas. We conclude that the patterns of abnormally decreased uptake in these cases of Down's syndrome are similar to those in dementia of Alzheimer's type, and that there is a possibility to detect the predemented stage of Down's syndrome by 123I-IMP-SPECT.     

Interictal Aggression in Epilepsy: The Buss-Durkee Hostility Inventory

Summary: Adult patients with left, right, or bilateral temporal lobe epilepsy or absence epilepsy, and normal controls completed the Buss-Durkee Hostility Inventory (BDHI), a standardized questionnaire of aggressive tendencies. Patients with left temporal lobe seizure foci scores higher on the Suspición scale than did other patients or controls (p < 0.05). Factor analysis scale scores identified three factors: hostile feelings, covert aggression, and overt aggression. The groups differed on their pattern of factor scores (p < 0.01): patients with left temporal lobe epilepsy scored higher than other groups on hostile feelings, normal controls scored higher on Covert aggression, and bitemporal patients scores higher on Overt aggression. Patients with absence seizures did not differ from controls. Lateralization of the seizure focus in patients with temporal lobe epilepsy may alter expression of aggressive behavior.     

Correlation Between Interictal Regional Cerebral Blood Flow and Depth-Recorded Interictal Spiking in Temporal Lobe Epilepsy

Summary: Purpose: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60–70% of cases. Correlation with ictal EEG changes is observed in ～50–60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship. Methods: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [^99mTc]hexamethyl-propylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data. Results: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes. Conclusions: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.     

Interictal Autonomic Nervous System Function in Patients with Epilepsy

Summary: We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels.     

Treatment of Interictal Depression with Citalopram in Patients with Epilepsy

The purpose of this study is to assess the efficacy and safety of the selective serotonin-reuptake inhibitor (SSRI) citalopram in depressed epileptic patients. We evaluated 43 epileptic patients who suffered from depression and whose total score on the 21 items of the Hamilton Scale for Depression (HAMD 21) exceeded 15 points. These patients were examined by the psychiatrist and scaled before treatment and after 4 and 8 weeks of treatment with citalopram. The dose of citalopram was flexible, related to the actual condition of the patient. In each patient and in the whole group of patients we compared the monthly seizure frequency (total, partial seizures, generalized tonic–clonic seizures) recorded during treatment with citalopram with that recorded during the 2 months preceding the start of citalopram. During treatment we observed a decrease in the total score on the HAMD 21 from a mean initial value of 21.5 ± 2.9 (range, 17–26) prior to therapy 14.5 ± 2.9 (range, 10–19) (P < 0.001) after 4 weeks of treatment and to 9.9 ± 3.1 (range, 4–19) (P < 0.001) after 8 weeks of treatment. There were 9 (20.9%) responders after 4 weeks of treatment and 28 responders (65.1%) after 8 weeks, all of them with decrease on the HAMD 21 greater than 50%. Nausea was the most common adverse event in 7 patients (16.3%) during the first month of treatment and in 3 patients (6.9%) during the second month of treatment. Sexual dysfunction (decrease of libido) was reported in 2 (4.7%) male patients during the entire course of treatment. No seizure worsening was observed in our patients. Monthly seizure frequency did not change significantly: 2.24 (±0.76) seizures before treatment with citalopram, 2.29 (±0.81) seizures in the first month of treatment, 2.21 (±1.00) seizures in the second month of treatment. No occurrence of de novo generalized tonic–clonic seizures was recorded in individual patients. Citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients.     

Interictal Spiking Increases with Sleep Depth in Temporal Lobe Epilepsy

Summary: Purpose : To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy.
Methods: At the time of study, subjects were seizure-free for 224 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2).
Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal.
Conclusions: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.     

Interictal Spikes and Hippocampal Somatostatin Levels in Temporal Lobe Epilepsy

We investigated the relationship between somatostatin-like immunoreactivity (SSLI) and interictal spikes (IIS) in human temporal lobe epileptic tissue. IIS counted manually from depth electrode recordings obtained preoperatively were expressed as spike frequency in anterior, middle, and posterior portions of hippocampus. SSLI was determined by radioimmunoassay (RIA). An inverse relationship between SSLI in the entorhinal cortex (EC) and IIS frequency in hippocampus was present (r = -0.55, p = 0.06). No correlation between IIS and SSLI in CA4, CA3, CA1, or the dentate was evident. This finding suggests a role of the EC in generation, regulation, or expression of interictal paroxysmal electrical activity in temporal lobe epilepsy (TLE), for which somatostatin may be a marker.     

Usefulness of Ictal and Interictal 99mTC Ethyl Cysteinate Dimer Single Photon Emission Computed Tomography in Patients with Refractory Partial Epilepsy

Summary: Purpose: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in ～90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for ～6 h. facilitating the performance of ictal studies. Methods: In a prospective, open-label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of ^99mTc-ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal ^99mTc-ECD SPECT. Results: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases. Conclusions: ^99mTc-ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc-ECD are similar to those reported with ^99mTc-HMPA0. Because ^99mTc-ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.