HIPDM-SPECT in patients with medically intractable complex partial seizures. Ictal study

Both interictal and ictal N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3,propanediamine -single photon emission computed tomography (HIPDM-SPECT) were performed in 16 patients with medically intractable complex partial seizures. Ictal HIPDM-SPECT localized epileptic foci in 13 of 14 patients with unilateral temporal focus and provided confirmative evidence of epileptic focus in 11 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci that had shown decreased rCP in a previous interictal study. Ictal HIPDM-SPECT in two patients with bitemporal foci showed more complicated patterns consisting of slightly increased rCP in bilateral multifocal regions. Ictal HIPDM-SPECT was particularly useful for investigating epileptic foci, and correlation with simultaneously recorded ictal electroencephalograms provided further insight for localizing epileptic foci.     

Ictal SPECT findings in typical absence seizures

Single photon emission computed tomography (SPECT) is known to reveal localized hyperperfusion during partial seizures, but is rarely performed in idiopathic generalized epilepsies. We report the ictal SPECT findings in a typical absence seizure. This 35-year-old woman with childhood absence epilepsy underwent prolonged electroencephalogram (EEG)-video monitoring, during which many stereotyped typical absence seizures were recorded. These consisted of brief staring spells with arrest of activity, associated with generalized 3 Hz spike-wave complexes on EEG. Following intravenous (i.v.) injection of 17.6 millicuries of Tc-99m Bicisate, SPECT was performed. The injection was performed during hyperventilation that induced a typical absence. Compared to the baseline SPECT scan that was normal, the ictal scan showed a generalized reduction in cortical activity. These findings do not support the “cortical” theory of typical absence seizures and the genesis of the 3 Hz spike-wave complexes. They may indeed support the subcortical or “centrencephalic” hypothesis.     

Ictal SPECT in supplementary motor area seizures

OBJECTIVES: We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure. METHODS: In four patients (four males, age range, 18-27 years) with SMA seizures, SPECT studies by radioisotope 99mTc-ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001). RESULTS: Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area. DISCUSSION: In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities.     

Ictal SPECT in supplementary motor area seizures

Abstract

Objectives: We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure.

Methods: In four patients (four males, age range, 18–27 years) with SMA seizures, SPECT studies by radioisotope 99mTc-ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001).

Results: Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area.

Discussion: In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities.     

Ictal brain imaging in presurgical evaluation of patients with medically intractable complex partial seizures

At the Indiana University Medical Center, 99 patients with medically intractable complex partial seizures (MI-CPS) had presurgical evaluation with subsequent anterior temporal lobectomy. The majority of the patients had single photon emission tomography (SPECT) performed interictally as well as during an actual epileptic seizure (ictal scan). Decreased regional cerebral perfusion (rCP) was seen in 54/94 (57%) of the interictal scans corresponding to the eventual site of the surgery. However, ictal scans provided a higher yield; increased rCP in the temporal lobe during an actual seizure was observed in 60/82 (73%) concordant to the side of surgery. SPECT is a useful, noninvasive method of localizing the epilepti-form focus in patients with MI-CPS considered for resective surgery. Both interictal and ictal SPECT need to be performed; combined interictal hypo-perfusion and ictal hyperperfusion in the same focal area are unique to epileptogenic lesions. Ictal SPECT studies can be performed in the majority of patients during the period of continuous video/EEG monitoring with only a little additional effort. Combining the results of functional brain imaging (interictal and ictal SPECT, PET) with clinical semiology of seizures, surface and sphenoidal EEG, magnetic resonance imaging and other non-invasive tests, anterior temporal lobectomy can be recommended in approximately two-thirds of the patients without resorting to potentially dangerous intracranial EEG monitoring.     

Ictal MEG in two children with partial seizures

We report on the successful identification of epileptic foci in two children with partial epilepsy using ictal magnetoencephalography (MEG). Case 1 is a 12-year-old male suffering with simple partial seizures with leftwards nystagmus. Ictal SPECT revealed a hyperperfusion area in the right lateral occipital area, and MRI revealed cortical dysplasia in the same area. Interictal EEG dipoles were concentrated in the right mesial occipital lobe. Both interictal and ictal MEG dipoles were concentrated in the right mesial occipital lobe, which corresponded well with neuroimaging data and his clinical features. Case 2 is a 5-year-old female suffering with simple partial seizures with left-side facial twitching. Interictal EEG dipoles were located in her left motor area, the pre-sylvian fissure, close to the location of the interictal MEG-estimated dipoles. Ictal EEGs showed no remarkable changes associated with her clinical manifestations. However, ictal MEG showed high-voltage slow waves over her left hemisphere, and ictal MEG iso-contour maps revealed a clear dipolar pattern, which suggested that the MEG dipole was located in the area of the sylvian fissure. Ictal SPECT revealed hyperperfusion areas around the left sylvian fissure. Conclusion: Ictal MEG is useful for determining the precise location of epileptic focus in patients with motionless seizures, including children.     

Interictal and postictal language testing accurately lateralizes language dominant temporal lobe complex partial seizures

PURPOSE: Noninvasive tests that accurately localize seizure onset provide great value in the presurgical evaluation of patients with intractable epilepsy. This study examined the diagnostic utility of three expressive language disturbances in lateralizing language-dominant (DOM) temporal lobe complex partial seizures: (1) the postictal language delay (PILD; time taken to correctly read a test phrase out loud immediately following seizures); (2) the production of postictal phonemic paraphasic errors (PostPE); and (3) interictal phonemic paraphasic errors (InterPE). METHODS: All 60 subjects underwent inpatient video/EEG monitoring and had surgically confirmed temporal lobe epilepsy (TLE). We determined the presence and number of PostPE and, PILD times (in s) for 212 seizures, and InterPE on the Boston Naming Test (BNT). Each technique's diagnostic usefulness was evaluated via logistic regression and ROC curve analysis. Sensitivity, specificity, positive predictive value and negative predictive values were computed. RESULTS: PILD, PostPE and InterPE production were equally effective and accurate in lateralizing DOM seizure onset. Patients with DOM TLE had a longer PILD and committed more PostPE and InterPE than those with nondominant (NDOM) TLE. Respective sensitivity and specificity values were as follows: PILD (84%, 86%), PostPE (94%, 64%), and InterPE (97%, 86%). No single predictor was significantly better but a combination model yielded enough incremental utility to collectively outperform each separate predictor model. CONCLUSIONS: Interictal language testing is as accurate as postictal language testing in predicting DOM lateralization of TLE. Clinicians should also attend to the quality of errors produced during interictal and postictal language testing.     

Ictal vomiting in partial seizures of temporal lobe origin

We report 3 cases presenting ictal vomiting during partial seizures of temporal lobe origin. Two patients had complex partial seizures accompanying vomiting characteristics. Ictal vomiting occurred early in the course of the seizure when rhythmic discharges involved predominantly the left hemisphere, the language dominance hemisphere. The other patient had ictal vomiting in simple partial seizures which originated from the right temporal lobe or the language nondominant side. All 3 patients underwent anterior temporal lobectomy with promising outcomes. Pathologic diagnosis included hippocampal sclerosis in 2 patients and astrocytoma in 1 patient. In our patients, ictal vomiting does not lateralize temporal lobe epilepsy and is not specific to pathology.     

Comparative study of interictal PET and ictal SPECT in complex partial seizures

Objective – To compare the sensitivity of ictal ^99mTc-HMPAO single photon emission computed tomography (SPECT) with interictal ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in localization of the epileptogenic focus in patients with medically intractable complex partial seizures (MI-CPS). Material and methods – Retrospective analysis was performed on patients with MI-CPS who underwent anterior temporal lobectomy from January 1993 onwards when PET became available to us for clinical studies at the Indiana University Medical Center. There were 38 female and 29 male patients (total=67) with MI-CPS, 10 to 55.5 years of age (mean 31) and duration of their epilepsy from 1-46 years (mean 21). Interictal PET was evaluated for evidence of focal hypometabolism and ictal SPECT for focal perfusion abnormality (hyperperfusion or hypoperfusion) by visual analysis. Results – Both Ictal SPECT and interictal FDG-PET studies were obtained in 36 patients with MI-CPS. PET showed definite hypometabolism in 30 and questionable hypometabolism in an additional two patients. Ictal SPECT correctly localized the seizure focus in 27 patients by demonstrating ictal hyperperfusion whereas in one the hyperperfusion was falsely localized. In an additional seven patients the ictal SPECT provided probable localization by demonstrating ictal hypoperfusion in the appropriate temporal lobe. The sensitivity of ictal SPECT and interictal PET was 34/36 and 32/36, respectively, the difference was not statistically significant (χ²_y=0.18, DF=1, P=0.67). In six of the 36 patients the two tests were complementary to each other in providing localizing information. Conclusion – Ictal SPECT and interictal PET are equally sensitive and reliable techniques in localizing the epileptogenic focus in patients with MI-CPS. They play a critical role in providing localization in MRI negative patients allowing surgical resection to be undertaken in many without additional invasive electrographic monitoring.     

Self-injection ictal SPECT during partial seizures

The authors compared ictal SPECT injection performed by medical personnel with self-injection ictal SPECT in six patients with refractory temporal lobe epilepsy. Self-injection was safe and started faster. Self-injection subtraction ictal SPECT coregistered to MRI (SISCOM) was localizing in three patients who had a complex partial seizure, but only one of three patients who had a simple partial seizure, which may limit its usefulness in clinical practice. The localizing information of self-injection was better in three patients, and obviated the need for depth-EEG studies in one patient.     

Vigabatrin in the treatment of complex partial seizures.

We report the effect of vigabatrin on seizure frequency in 13 severely drug-resistant patients with intractable complex partial seizures (CPS) with or without secondary generalization. Patients were followed for a 3-month period before vigabatrin administration to establish a 'baseline'. Six patients became seizure free for 2-3 weeks immediately after starting vigabatrin. In seven patients a transient (4-6 weeks) increase in seizures above baseline occurred, which was attenuated by vigabatrin dose increments. After 3 months, the mean baseline CPS frequency was reduced from 7.75 +/- 1.18 (median 8, range 2.6-16) to 2.77 +/- 0.7 (median 1, range 0-7). At 6 months a > 50% improvement remained in seven patients. After 12 or more months CPS frequency returned to baseline in four patients, improved (by 25-62.5%) in four and deteriorated in three. One patient who was seizure free lost control at 16 months. Other effects were drowsiness (3), weight increase (3), diarrhoea (1), depression (2) and mood elevation (2). Four patients discontinued vigabatrin; one because of severe depression, three owing to lack of efficacy. Three patients have undergone and two are awaiting neurosurgery for their epilepsy. Thus, CPS frequency progressively deteriorated toward baseline in all patients, however, secondary generalizations were abolished in four and reduced in two.     

Pre- and postictal, not ictal, heart rate distinguishes complex partial and psychogenic nonepileptic seizures

Psychogenic nonepileptic seizures (PNES) remain poorly understood neurobiologically. Previously reported work suggests that adjunct ictal heart rates (HRs) may differentiate PNES from complex partial seizures (CPS). We retrospectively reviewed and compared preictal, ictal, and postictal HR differences in patients with PNES (n=42) and CPS controls (n=46) electively admitted for video/EEG monitoring to further characterize PNES autonomic patterns. Statistically significant preictal HR increases (P=0.006) and postictal (P=0.015) HR reductions normalized to baseline were identified in subjects with PNES compared with CPS controls. Ictal HRs were not found to differentiate between PNES and CPS events. This pattern of pre-event HR increases and postevent HR decreases in patients with PNES compared with those with CPS suggests frontolimbic neural circuit dysfunction and merits further exploration.     

Febrile seizures in patients with complex partial seizures

Febrile seizures occurred in 14 of 155 (9%) out-patients with complex partial seizures. Twelve patients had prolonged or recurrent febrile seizures, convulsive status epilepticus or a transient postictal neurological deficit. Febrile seizures were associated with perinatal abnormalities, an earlier onset of epilepsy and with a poor seizure control. Recurrent febrile seizures or those with complicating features are associated with an unfavourable therapeutic outcome in adult patients with complex partial seizures.     

Role of I-123-Iomazenil SPECT imaging in drug resistant epilepsy with complex partial seizures

Fifteen patients with therapy resistant partial complex seizures with no structural lesions were examined interictally with 123-I-IOMAZENIL SPECT for measurement of benzodiazepine receptor distribution and with 99m-Tc-HMPAO SPECT for measurement of cerebral blood flow distribution. Regional abnormalities were correlated with the seizure onset patterns in EEG later recorded with implanted subdural strips. SPECT scans were made immediately after and at 1 and 2 h after intravenous injection of 123-I-Iomazenil. During that time there was a continuous change from an immediate flow-related distribution toward a more specific receptor distribution. The decay of radioactivity of I-123 in the brain was linear over time. Two patients on benzodiazepine treatment showed much faster elimination and showed no focal abnormalities. Eight patients with clear-cut unifocal seizure onset showed concordant focal benzodiazepine defects. These patients showed a progressive focus/homotopic non-focus enhancement over time much larger than the HMPAO scans in the same patients. Also the estimated focal area of abnormality was more restricted in the Iomazenil scans than in HMPAO scans. Five patients had more complex seizure onset patterns. In these patients a mismatch between the locations of abnormalities in Iomazenil and HMPAO scans were often found but benzodiazepine receptor abnormalities were more circumscribed also in these patients. The results suggest that 123-I-Iomazenil SPECT is more useful than 99m-Tc-HMPAO SPECT when applied interictally in patients with partial complex epilepsy, since in addition to demonstrate the hemispheric laterality of the epileptogenic zone, 123-I-Iomazenil appears to indicate its anatomical location with higher confidence, which could be of practical value for positioning of intracranial EEG electrodes.     

Ictal SPECT in children with partial epilepsy due to focal cortical dysplasia

We studied the usefulness of ictal single-photon emission computed tomography in the presurgical evaluation of children with partial epilepsy resulting from focal cortical dysplasia. Fifteen children, age 1-18 years, were identified with partial epilepsy caused by focal cortical dysplasia (confirmed by histology) who underwent subtraction ictal single-photon emission computed tomography during presurgical evaluation. All children later underwent surgery at the Cleveland Clinic Epilepsy Center between 1996 and 2000. The findings of ictal single-photon emission computed tomography and brain positron emission tomography were classified as localized when "localizing and concordant" with the surgical resection site, nonconcordant when "localizing but not concordant" with the surgical resection, or nonlocalized when "no well-localized region of ictal hyperperfusion was observed on the difference image". In 15 patients, age 1.5-18 years (median age 8 years), epilepsy was classified as frontal in 7, posterior temporal/occipital in 3, temporal in 2, multilobar in 2, and parietal in 1. Of 15 patients, preoperative magnetic resonance imaging revealed focal cortical dysplasia in 11, positron emission tomography was localized in 9, and ictal single-photon emission computed tomography was localized in 8 patients. In 4 patients with normal magnetic resonance imaging but scalp electroencephalographic findings of partial epilepsy, ictal single-photon emission computed tomography and positron emission tomography were localized in 3 each. Fourteen patients were monitored for 6-39 months (mean 20 months). Six of 7 patients (85%) with localized ictal single-photon emission computed tomography compared with 4 of 7 (57%) with nonconcordant/nonlocalized ictal single-photon emission computed tomography had no seizures at follow-up. In 4 patients with normal magnetic resonance imaging, 3 patients with localized ictal single-photon emission computed tomography were free of seizures compared with 1 with nonconcordant ictal single-photon emission computed tomography who continued to have seizures. Ictal single-photon emission computed tomography is a useful adjunctive test in presurgical evaluation of children with refractory partial epilepsy due to focal cortical dysplasia, especially when brain magnetic resonance imaging is normal.     

The value of early postictal EEG in children with complex febrile seizures

PURPOSE: To assess the usefulness of an early postictal EEG in neurologically normal children with complex febrile seizures. METHODS: We conducted a retrospective chart review of all neurologically normal children who were hospitalized over a period of 2.5 years after complex febrile seizures, and had an EEG up to 1 week after the seizure. RESULTS: Thirty-three patients (mean age, 17.8 months) qualified for inclusion into the study. Twenty-four patients were qualified as complex cases based on one factor (prolonged in 9, repetitive in 13, and focal in 2). Nine other patients had two complex factors: in six patients, the seizures were long and repetitive; in two patients, the seizures were focal and repetitive; and in one patient, the seizures were long, focal, and repetitive. Thirteen (39%) patients experienced prior febrile seizures. All 33 patients had a normal postictal sleep EEG. Our results indicate with a 95% probability that the true rate of abnormalities in an early postictal EEG performed on otherwise normal children with complex febrile seizures is 8.6% or less. CONCLUSIONS: The yield of abnormalities of an early postictal EEG in this population is low and similar to the reported rate of abnormalities in children with simple febrile seizures. The routine practice of obtaining an early EEG in neurologically normal children with complex febrile seizures is not justified.     

Influence of levetiracetame on ictal and postictal EEG in patients with partial seizures

To investigate the influence of levetiracetame (LEV) treatment on the interhemispheric seizure pattern propagation and postictal recovery of electroencephalography (EEG) background activity. Twenty-three adult patients (age > 16 years) with pharmacoresistant focal epilepsies presenting at the Epilepsy Center Erlangen for pre-surgical evaluation were enrolled in the study. Those eligible patients receiving only one antiepileptic drugs were recruited to the 48-h baseline phase and, after at least two seizures, were randomized to the 7-day treatment phase with either LEV ( n  = 11) or placebo ( n  = 12). All participants were submitted to continuous day-and-night video-EEG monitoring. The daily dose of LEV was 1000 mg (500 mg bid.) on the first treatment day and was increased to 2000 mg (1000 mg bid.) from the second day onward. The EEG changes relating to the time delay of the interhemispheric seizure pattern propagation and to the postictal recovery of the background activity were analysed by computerized video-EEG recording and compared using the non-parameter Mann–Whitney U -exact test ( α  = 0.05). A prolonged latency of the contralateral seizure pattern propagation was observed in the LEV group, whereas a more rapid propagation was observed in the placebo group ( P  = 0.009). Postictal generalized slowing of the background activity was recorded in 21 patients during the baseline phase. More rapid postictal recovery of the EEG background activity was observed in the LEV, but not in the placebo group ( P  = 0.03). This study demonstrated that LEV not only prevented the seizure pattern propagation but also helped the speedy recovery of the postictal background activity in the EEG.     

Self-abatement of complex partial seizures

Seven of 71 patients with complex partial seizures claimed they were able to abate their seizures, while none of 18 with simple partial seizures were able to do so. Self-abatement exercises included highly stereotyped cognitive and physical components unique to the individual. Those who could abate their seizures had attained higher educational status, better social and vocational adjustment, and better psychological adjustment than did the control group of patients with epilepsy. The self-abatement group was also more likely to have right hemispheric electroencephalographic abnormalities. Characterization of the self-abatement group may be relevant to the selection of candidates for behavioral therapy for epilepsy.     

Ictal clinical patterns and ictal EEG in a case of partial seizures of frontotemporal origin associated with complex symptomatology

The patient was a 35-year-old, unmarried male whose epileptic psychomotor fits persisted since the age of 13. The author has observed the case for about 12 years, so that incomplete information concerning epileptic symptoms was considered to be compensated considerably by longitudinal observation, including ictal seizure and ictal EEG's. In this patient seizure with impaired consciousness which correspond rhythmic slow waves of EEG tracing might be a nuclear sign; several kinds of automatism then might be considered as postictal phenomenon. The most important of all was tonic seizure of psychomotor epilepsy particularly in the face which was not seen in the petit mal epilepsy. With observation of ictal period as well as ictal EEG, differential identification of centrencephalic epilepsy and psychomotor epilepsy may not be totally impossible. The case also showed a typical productive psychotic episodes of Landolt, which could be treated favorably by 10 mg of intravenous Haloperidol. This method, named as "pathologization" of Helmchen, was found by the present author as a useful treatmental means of choice.