Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis

BACKGROUND: The pathophysiological role of the extensive interictal cerebral hypometabolism in complex partial seizures (CPS) in refractory mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is poorly understood. Our aim was to study ictal-interictal SPECT perfusion versus interictal fluorodeoxyglucose (FDG)-PET metabolic patterns. METHODS: Eleven adults with refractory unilateral mTLE-HS, who were rendered seizure free after epilepsy surgery, were included. All had an interictal FDG-PET and an interictal and ictal perfusion SPECT scan. FDG-PET data were reconstructed using an anatomy-based reconstruction algorithm, which corrected for partial volume effects, and analyzed semi-quantitatively after normalization to white matter activity. Using Statistical Parametric Mapping (SPM), we compared interictal metabolism of the patient group with a control group. We correlated metabolic with ictal perfusion changes in the patient group. RESULTS: Global cerebral grey matter glucose metabolism in patients was decreased 10-25% compared with control subjects. Interictal PET hypometabolism and ictal SPECT hypoperfusion were maximal in the ipsilateral frontal lobe. Ictal frontal lobe hypoperfusion was associated with crossed cerebellar diaschisis. The ipsilateral temporal lobe showed maximal ictal hyperperfusion and interictal hypometabolism, which was relatively mild compared with the degree of hypometabolism affecting the frontal lobes. CONCLUSION: Interictal hypometabolism in mTLE-HS was greatest in the ipsilateral frontal lobe and represented a seizure-related dynamic process in view of further ictal decreases. Crossed cerebellar diaschisis suggested that there is a strong ipsilateral frontal lobe inhibition during CPS. We speculate that surround inhibition in the frontal lobe is a dynamic defense mechanism against seizure propagation, and may be responsible for functional deficits observed in mTLE.     

The nurse's role in delivery of radioisotope for ictal SPECT scan.

The Medical College of Georgia Hospital and Clinics (MCG) was one of the first centers in the United States (US) to institute a video electroencephalography (EEG) epilepsy monitoring unit and epilepsy surgery program. In order to surgically remove the area in the brain giving rise to seizures, the epileptogenic zone must be identified and localized. One of the newer methods used to identify the epileptogenic seizure focus is the ictal Single Photon Emission Computed Tomography (SPECT) scan, which MCG began performing in 1993. The nurses staffing the six bed Epilepsy Monitoring Unit (EMU) are trained by the Nuclear Radiology Department and Radiation Safety Officer to bandle the radioisotope during mixing, calibration and injection. The bedside nursing protocol developed assures patient and staff radiation safety and efficacious injection. Over 300 patients have been injected by nurses with a high degree of safety to patients and staff. This has resulted in positive scans that aid diagnosis. The success of the ictal SPECT protocol can be attributed to the active collaboration of our multidisciplinary team.     

发作间期PET显像与发作期SPECT脑显像在小儿顽固性癫痫定位诊断中的价值

目的:探讨发作间期FDG PET与发作期SPECT脑显像在小儿顽固性癫痫定位诊断中的价值。方法:对30例小儿顽固性癫痫患者行发作间期FDG PET与发作期SPECT显像,并对结果进行对比分析。结果:16例发作间期PET表现为局限性单叶代谢减低,14例表现为多灶或弥漫性改变。发作期SPECT显像18例为单叶局限性高灌注,10例为多处高灌注灶。30例患者中26例(86.7%)两项检查结果相符合,12例PET发作间期呈多病灶或弥漫性改变者,6例于发作期转化为单叶局限性病灶。结论:发作期SPECT结合发作间期PET显像,两者联合应用优势互补,可提高癫痫定位的准确性,为进一步治疗提供更可靠的信息。     

Subtraction ictal SPECT coregistered to MRI for seizure focus localization in partial epilepsy

Peri-ictal single-photon emission computed tomography (SPECT) of the brain is increasingly used in localizing the seizure focus in presurgical evaluation of patients with partial epilepsy. However, traditional side-by-side visual interpretation of ictal and interictal SPECT films is hampered by differences in slice location and tracer activity. Precise correlation of the seizure focus with a high-quality image of the underlying brain anatomy can improve the physician's understanding of seizure neurophysiology and assist in surgical planning. Computer-based methods have been developed for aligning, normalizing, and subtracting digital ictal and interictal SPECT images of the patient's brain to produce a map of the blood flow changes occurring between the seizure and resting states. These maps are then aligned with a high-resolution magnetic resonance image (MRI) of the patient's brain anatomy and fused to identify anatomical regions involved in the seizure. The purpose of this article is to review the technical components and clinical implementation of subtraction ictal SPECT, as well as to discuss recent technological advances that could extend and improve the diagnostic and localizing capacity of this method.     

Functional Imaging in Temporal Lobe Epilepsy

This article highlights the importance of functional imaging methods in the diagnosis and preoperative planning in temporal lobe epilepsy TLE). It starts with a discussion of the role of ictal and interictal single-photon emission computed tomography (SPECT) and interictal positron emission tomography (PET) in lateralizing TLE. The next section discusses the role of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and perfusion MRI, particularly for lateralization of language and memory in TLE patients. The final section explores the relatively new role that the emerging technique of diffusion tensor imaging (DTI) is playing in the evaluation of TLE.     

Ictal source analysis: localization and imaging of causal interactions in humans

We propose a new integrative approach to characterize the structure of seizures in the space, time, and frequency domains. Such characterization leads to a new technical development of ictal source analysis for the presurgical evaluation of epilepsy patients. The present new ictal source analysis method consists of three parts. First, a three-dimensional source scanning procedure is performed by a spatio-temporal FINE source localization method to locate the multiple sources responsible for the time evolving ictal rhythms at their onsets. Next, the dynamic behavior of the sources is modeled by a multivariate autoregressive process (MVAR). Lastly, the causal interaction patterns among the sources as a function of frequency are estimated from the MVAR modeling of the source temporal dynamics. The causal interaction patterns indicate the dynamic communications between sources, which are useful in distinguishing the primary sources responsible for the ictal onset from the secondary sources caused by the ictal propagation. The present ictal analysis strategy has been applied to a number of seizures from five epilepsy patients, and their results are consistent with observations from either MRI lesions or SPECT scans, which indicate its effectiveness. Each step of the ictal source analysis is statistically evaluated in order to guarantee the confidence in the results.     

局部脑血流SPECT显像与其他影像对癫痫定位诊断比较的研究

目的:研究癫痫发作期与发作间期同侧对照99mTc-ECD局部脑血流(rCBF)单光子发射计算机体层摄影术(SPECT)显像对癫痫灶的定位诊断价值。方法:对54例癫痫患者行发作间期显像,其中10例行发作期显像,并与皮层脑电图(EEG)、计算机断层扫描或磁共振显像(CT/M RI)、深部皮层脑电图(EcoG)结果进行对比分析。结果:癫痫发作期与发作间期rCBF SPECT显像对癫痫灶具有较高的检出率和定位率,优于EEG、CT/M RI,低于EcoG,但rCBF在发作期与发作间期的比较差异无显著性(P>0.05)。结论:发作间期rCBF SPECT显像可以成为癫痫灶方便而有效的定位方法,若加上发作期rCBF显像则定位更佳。     

Dynamic imaging of ictal oscillations using non-invasive high-resolution EEG

Scalp electroencephalography (EEG) has been established as a major component of the pre-surgical evaluation for epilepsy surgery. However, its ability to localize seizure onset zones (SOZ) has been significantly restricted by its low spatial resolution and indirect correlation with underlying brain activities. Here we report a novel non-invasive dynamic seizure imaging (DSI) approach based upon high-density EEG recordings. This novel approach was particularly designed to image the dynamic changes of ictal rhythmic discharges that evolve through time, space and frequency. This method was evaluated in a group of 8 epilepsy patients and results were rigorously validated using intracranial EEG (iEEG) (n=3) and surgical outcome (n=7). The DSI localized the ictal activity in concordance with surgically resected zones and ictal iEEG recordings in the cohort of patients. The present promising results support the ability to precisely and accurately image dynamic seizure activity from non-invasive measurements. The successful establishment of such a non-invasive seizure imaging modality for surgical evaluation will have a significant impact in the management of medically intractable epilepsy.     

Role of neuroimaging in the management of seizure disorders

Neuroimaging is one of the most important advances made in the past decade in the management of seizure disorders. Magnetic resonance imaging (MRI) has increased substantially the ability to detect causes of seizure disorders, to plan medical or surgical therapy, and to prognosticate the outcome of disorders and therapy. However, MRI must be performed with techniques that will maximize the detection of potentially epileptogenic lesions, especially in candidates for epilepsy surgery. Functional imaging has an established role in evaluating patients for epilepsy surgery. It is relied on when results from standard diagnostic methods, such as clinical information, electroencephalography, and MRI, are insufficient to localize the seizure focus. Also, functional imaging is a reportedly reliable alternative to invasive methods for identifying language, memory, and sensorimotor areas of the cerebral cortex. Despite the availability of multimodality imaging, the epileptogenic zone is not determined solely by a single imaging modality. Evidence and experience have shown that concordance of results from clinical, electrophysiologic, and neuroimaging studies is needed to identify the epileptogenic zone accurately. With modern techniques in image processing, multimodality imaging can integrate the location of abnormal electroencephalographic, structural, and functional imaging foci on a "map" of the patient's brain. Computer image-guided surgery allows surgically exact implantation of intracranial electrodes and resection of abnormal structural or functional imaging foci. These techniques decrease the risk of morbidity associated with epilepsy surgery and enhance the probability of postsurgical seizure control.     

Combined MEG/EEG analysis of the interictal spike complex in mesial temporal lobe epilepsy

We studied the functional organization of the interictal spike complex in 30 patients with mesial temporal lobe epilepsy (MTLE) using combined magnetoencephalography (MEG)/electroencephalography (EEG) recordings. Spikes could be recorded in 14 patients (47%) during the 2- to 3-h MEG/EEG recording session. The MEG and EEG spikes were subjected to separate dipole analyses; the MEG spike dipole localizations were superimposed on MRI scans. All spike dipoles could be localized to the temporal lobe with a clear preponderance in the medial region. Based on dipole orientations in MEG, patients could be classified into two groups: patients with anterior medial vertical (AMV) dipoles, suggesting epileptic activity in the mediobasal temporal lobe and patients with anterior medial horizontal (AMH) dipoles, indicating involvement of the temporal pole and the anterior parts of the lateral temporal lobe. Whereas patients with AMV dipoles had strictly unitemporal interictal and ictal EEG changes during prolonged video-EEG monitoring, 50% of patients with AMH dipoles showed evidence of bitemporal affection on interictal and ictal EEG. Nine patients underwent epilepsy surgery so far. Whereas all five patients with AMV dipoles became completely seizure-free postoperatively (Class Ia), two out of four patients with AMH dipoles experienced persistent auras (Class Ib). This difference, however, was not statistically significant. We therefore conclude that combined MEG/EEG dipole modeling can identify subcompartments of the temporal lobe involved in epileptic activity and may be helpful to differentiate between subtypes of mesial temporal lobe epilepsy noninvasively.     

Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT

We examined cerebral perfusion changes in mesial temporal lobe epilepsy (mTLE) by the statistical parametric mapping of brain single photon emission computed tomography (SPECT) images of 38 mTLE patients and 19 normal controls. Ictal and interictal SPECTs were compared with control SPECTs by independent t test, and ictal and interictal SPECTs by paired t test. We evaluated the number of heterotopic neurons in temporal lobe white matter, white matter changes of the anterior temporal lobe (WCAT) and ictal hyperperfusion of the temporal stem (IHTS). Left mTLE showed interictal hypoperfusion in the ipsilateral hippocampus, bilateral thalami, and paracentral lobules. Right mTLE showed hypoperfusion in bilateral hippocampi, contralateral insula, bilateral thalami, and paracentral lobules. Both mTLEs showed ictal hyperperfusion in bilateral temporal lobes with ipsilateral predominance, and in the anterior frontal white matter bilaterally. By paired t test, ictal hyperperfusion was found in the ipsilateral temporal lobe, temporal stem, hippocampus, thalamus, putamen, insula, and bilateral precentral gyri, whereas ictal hypoperfusion was found in bilateral frontal poles and middle frontal gyri. Fifteen patients showed WCAT and 19 showed IHTS, a weak correlation was observed between WCAT and IHTS (r = 0.377, P = 0.02). WCAT was found to correlate with an early seizure onset age. In 35 patients, heterotopic neurons were found in the white matter of the resected temporal lobe, but the number of heterotopic neurons did not correlate with WCAT or IHTS. In summary, the cerebral perfusion patterns of mTLE suggest interictal hypofunction and ictal activation of the cortico-thalamo-hippocampal-insular network and ictal hypoperfusion of the anterior frontal cortex.     

The value of neuroimaging in diagnosis of epilepsy

Neuroimaging examines the relationship between abnormalities of brain function in epilepsy patients (seizures, impaired cognitive function, psychiatric co-morbidity etc.) and focal or more widespread brain pathology. Since the mid-1980s, the introduction of magnetic resonance imaging (MRI) into clinical neurology has had an impact on the diagnosis, treatment, and research of epilepsy only comparable with the advent of the electroencephalography (EEG) fifty years ago. MRI plays the important role of identifying single or multiple structural lesions responsible for the epileptic seizures. Thus, visual assessment of MRI plays an important role in the differentiation between symptomatic, cryptogenic, and idiopathic epilepsies. This diagnostic step leads to therapeutic decisions (medical treatment vs. surgery) and prognostic evaluations. If a structural lesion identified with MRI correlates with seizure-type, EEG and other clinical data, the likelihood of rendering the patient seizure free with epilepsy surgery is increased. Clinical research into epilepsy uses quantitative MRI (volumetry, T2-relaxometry, magnetic resonance spectroscopy [MRS], voxel-based morphometry) to reduce those cases initially labeled as cryptogenic. Quantitative MRI questions the belief that there is epilepsy without structural brain abnormality at all. Functional MRI (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) demonstrate changes associated with epileptic seizures and pathology, and changes associated with EEG abnormalities and their cessation. Functional neuroimaging is also used for the identification of functional brain tissue before surgery. Physiologically or pathologically active neuronal tissue is believed to be identified by glucose or oxygen consumption (PET), cerebral blood flow (PET, SPECT, perfusion MRI), and cerebral blood oxygenation (blood oxygenation level dependent [BOLD] fMRI). PET also offers the opportunity to visualize the in-vivo distribution of neuronal receptors which are implicated in the generation, the spread, and the cessation of seizures.     

Epileptogenic networks of type II focal cortical dysplasia: a stereo-EEG study

In the context of focal and drug-resistant epilepsy, surgical resection of the epileptogenic zone may be the only therapeutic option for reducing or suppressing seizures. In many such patients, intracranial stereo-EEG recordings remain the gold standard for the epilepsy surgery work-up. Assessing the extent of the epileptogenic zone and its organisation is a crucial objective, and requires advanced methods of signal processing. Over the last ten years, considerable efforts have been made to develop signal analysis techniques for characterising the connectivity between spatially distributed regions. The aim of this study was to evaluate the changes in dynamic connectivity pattern under inter-ictal, pre-ictal and ictal conditions using signals derived from stereo-EEG recordings of 10 patients with Taylor-type focal cortical dysplasia. A causal linear multivariate method - partial directed coherence - and indices derived from graph theory were used to characterise the synchronisation property of the lesional zone (corresponding to the epileptogenic zone in our patients) and to distinguish it from other regions involved in ictal activity or not. The results show that a significantly different connectivity pattern (mainly in the gamma band) distinguishes the epileptogenic zone from other cortical regions not only during the ictal event, but also during the inter- and pre-ictal periods. This indicates that the lesional nodes play a leading role in generating and propagating ictal EEG activity by acting as the hubs of the epileptic network originating and sustaining seizures. Our findings also indicate that the cortical regions beyond the dysplasia involved in the ictal activity essentially act as "secondary" generators of synchronous activity. The leading role of the lesional zone may account for the good post-surgical outcome of patients with type II focal cortical dysplasia as resecting the dysplasia removes the epileptogenic zone responsible for seizure organisation. Furthermore, our findings strongly suggest that advanced signal processing techniques aimed at studying synchronisation and characterising brain networks could substantially improve the pre-surgical evaluation of patients with focal epilepsy, even in cases without an associated anatomically detectable lesion.     

Speech activation of language dominant hemisphere: a single-photon emission computed tomography study

We tested the prediction that single photon emission computed tomography (SPECT) of the blood flow distribution in speech-activated brain identifies the language-dominant hemisphere. We based the prediction on the hypothesis that language activation leads to focally increased regional cerebral blood flow (rCBF), which is reflected in the uptake of a flow tracer recorded by SPECT. We compared the results of speech activation to the results of functional transcranial Doppler (fTCD) monitoring in the same subjects. Preoperatively, 17 patients (10 women and 7 men with a mean age of 36 +/- 15 years) with diagnoses of epilepsy (n = 14) or arteriovenous malformation (AVM) (n = 3) had two SPECT and two stereo-TCD monitoring studies in each case, one at rest, and one during 3 min of speech activation. Except for two left-handed patients with right-hemisphere dominance, the subjects had the highest changes of rCBF from baseline to activation in the left posterior inferior frontal cortex and in contralateral cerebellum. The results show that changes of the level of neuronal activity reflected by the measurement of rCBF variations might be detected by SPECT. Additionally, the evaluation of hemispheric language dominance based on SPECT showed a complete agreement with the evaluation based on fTCD results (yielding a kappa coefficient equal to 1), and therefore, speech-activation SPECT mapping might be helpful in the evaluation of hemispheric language dominance, especially when fMRI and PET are not available or they are contraindicated for some reason.     

Ictal asystole: an indication for pacemaker implantation and emerging cause of sudden death

Ictal asystole is being recognized as a potential mechanism of sudden unexplained death in epilepsy (SUDEP). We report a case of a patient without known cardiac disease presenting with ictal asystole resulting in syncope, trauma, and need for pacemaker implantation. The management of ictal asystole is also briefly reviewed. This case is notable for the asystolic episode wholly captured on video-electroencephalogram/electrocardiogram, the serious risk of trauma and death posed to the patient, and its implications for the mechanism of ictal asystole. This report will alert physicians to the possibility of ictal arrhythmias as a cause of syncope and SUDEP in vulnerable patients.     

Canonical decomposition of ictal scalp EEG reliably detects the seizure onset zone

Long-term electroencephalographic (EEG) recordings are important in the presurgical evaluation of refractory partial epilepsy for the delineation of the irritative and ictal onset zones. In this paper we introduce a new algorithm for an automatic, fast and objective localizing of the ictal onset zone in ictal EEG recordings. We extracted the potential distribution of the ictal activity from EEG using the higher order canonical decomposition method, also referred to as the CP model. The CP model decomposes in a unique way a higher order tensor in a minimal sum of rank-1 'atoms'. We showed that only one atom is related to the seizure activity. Simulation experiments demonstrated that the method correctly extracted the potential distribution of the ictal activity even with low signal-to-noise ratios. In 37 ictal EEGs, the CP method correctly localized the seizure onset zone in 34 (92%) and visual assessment in 21 cases (57%) (p=0.00024). The CP method is a fast method to delineate the ictal onset zone in ictal EEGs and is more sensitive than visual interpretation of the ictal EEGs.     

18F-FDG PET脑显像对癫痫颅内电极放置部位的选择

目的 探讨18^F-FDG PET脑显像对癫痫颅内电极放置位置选择的价值。方法 52例难治性癫痫患者，其中男28例，女24例，年龄在7-38岁之间，平均22岁。所有患者脑MRI检查结果无异常。头皮EEG检查阴性23例，头皮EEG检查不确定癫痫部位的29例。采用SIEMENS ECAT47 PET扫描仪行18^F-FDG PET脑断层显像，在PET指导下经颅内电极定位后行癫痫灶切除。结果 52例癫痫18^F-FDG PET显像阳性患者中，发作期8例呈18^F-FDG摄取增高，发作间期44例呈18^F-FDG摄取减低。发作期18^F-FDG PET显像所提示的18^F-FDG摄取增高部位，颅内电极都可检测到癫痫波。18^F-FDG摄取减低44例患者，能记录癫痫波者39例，有效率为88.6%。5例不能检测癫痫波，无效率为11.4%。结论 18^F-FDG PET显像对癫痫颅内电极放置位置选择具有指导的价值，尤以发作期18^F-FDG PET显像明显。     

Ictal headache and visual sensitivity

Migrainous headache is reported by patients with photosensitive epilepsy, whereas their relatives complain more often about headache than the relatives of patients with other types of epilepsy. We therefore investigated whether headache itself could be an epileptic symptom related to photosensitivity. Four probands with headache and photosensitive epilepsy were selected. Their first-degree family members were studied using video-EEG with extensive intermittent photic stimulation and pattern stimulation. Nine of the 12 subjects (10 female and two male, mean age 30 years, range 14–46 years) proved to be photosensitive with either focal ( n  = 5) or generalized ( n  = 4) epileptiform discharges. In two subjects an ictal recording of headache occurred after visual stimulation. We found evidence that, in specific patients, headache could be an ictal sign of epilepsy. Photic stimulation during EEG recording can contribute to correct diagnosis and lead to the best care and management of the patient.     

Clinical indications and diagnostic yield of video-electroencephalographic monitoring in patients with seizures and spells

Video-electroencephalographic (EEG) monitoring is an important neurodiagnostic technique that may be used for selected patients who present with recurrent and unprovoked spells. For most patients who have epilepsy, the "routine" EEG is sufficient for physicians to classify seizure types and initiate medical therapy; however, routine EEG has substantial limitations for approximately 20% of patients who do not have epilepsy but are referred to comprehensive epilepsy programs because of medically refractory "seizures." These patients may have physiological or psychological disorders that may cause diagnostic confusion with epilepsy and result in the patients being treated unnecessarily with antiepileptic drugs. Video-EEG monitoring, ie, ictal EEG monitoring, performed either on an outpatient basis or in an epilepsy monitoring unit, can help physicians identify ictal EEG patterns that may be necessary for classifying seizure types and determining surgical localization. The sensitivity and specificity of EEG recordings during clinical episodes are superior to those of the routine interictal EEG. Video-EEG monitoring may prove to be an essential procedure for helping physicians confirm diagnoses of seizure disorders, classify seizure types, and select surgical candidates who have intractable epilepsy.     

Interictal and Ictal Phase Study With Tc 99m HMPAO Brain SPECT in Juvenile Migraine With Aura

Single photon emission computed tomography (SPECT) was performed on 30 juvenile patients suffering from different types of migraine with aura. SPECT was carried out only during the pain-free interval in 11 patients. The other 19 patients underwent SPECT ictally and 9 of them also interictally. During the pain-free interval, the investigation was normal in 16 of 20 cases and revealed hypoperfused areas in 4 of 20 cases. Ictally, regional cerebral blood flow (rCBF) abnormalities were found in 14 of 19 cases: hypoperfusion in 11 patients and hyperperfusion in 3 patients. In most cases, rCBF abnormalities corresponded to the topography of neurologic symptoms. Our intericta period results do not agree with the previous studies in juvenile migraineurs, while during the ictal phase we demonstrated, for the first time, significant rCBF abnormalities in juvenile patients suffering from migraine with aura.