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Background and Objectives: Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere., Methods: In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp)., Results: The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp., Discussion: Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.

Background and Objective: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied., Methods: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen., Results: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed., Discussion: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Objective: To determine the involvement of subcortical regions in human epilepsy by analyzing direct recordings from these regions during epileptic seizures using stereo-EEG (SEEG)., Methods: We studied the SEEG recordings of a large series of patients (74 patients, 157 seizures) with an electrode sampling the thalamus and in some cases also the basal ganglia (caudate nucleus, 22 patients; and putamen, 4 patients). We applied visual analysis and signal quantification methods (Epileptogenicity Index [EI]) to their ictal recordings and compared electrophysiologic with clinical data., Results: We found that in 86% of patients, thalamus was involved during seizures (visual analysis) and 20% showed high values of epileptogenicity (EI >0.3). Basal ganglia may also disclose high values of epileptogenicity (9% in caudate nucleus) but to a lesser degree than thalamus ( p < 0.01). We observed different seizure onset patterns including low voltage high frequency activities. We found high values of thalamic epileptogenicity in different epilepsy localizations, including opercular and motor epilepsies. We found no difference between epilepsy etiologies (cryptogenic vs malformation of cortical development, p = 0.77). Thalamic epileptogenicity was correlated with the extension of epileptogenic networks ( p = 0.02, ρ 0.32). We found a significant effect ( p < 0.05) of thalamic epileptogenicity regarding the postsurgical outcome (higher thalamic EI corresponding to higher probability of surgical failure)., Conclusions: Thalamic involvement during seizures is common in different seizure types. The degree of thalamic epileptogenicity is a possible marker of the epileptogenic network extension and of postsurgical prognosis., (© 2020 American Academy of Neurology.)

Objective: To investigate the correlation between characteristics of lateralized periodic discharges (LPDs) and glucose metabolism measured by 18 F-fluorodeoxyglucose (FDG)-PET., Methods: We retrospectively reviewed medical records to identify patients who underwent FDG-PET during EEG monitoring with LPDs present during the FDG uptake period. Two blinded board-certified neurophysiologists independently interpreted EEGs. FDG uptake was measured using standardized uptake value (SUV). Structural images were fused with PET images to aid with localization of SUV. Two PET readers independently measured maximum SUV. Relative SUV values were obtained by normalization of the maximum SUV to the SUV of pons (SUVRpons). LPD frequency was analyzed both as a categorical variable and as a continuous measure. Other secondary variables included duration, amplitude, presence of structural lesion, and "plus" EEG features such as rhythmic or fast sharp activity., Results: Nine patients were identified and 7 had a structural etiology for LPDs. Analysis using frequency as a categorical variable and continuous variable showed an association between increased LPD frequency and increased ipsilateral SUVRpons ( p = 0.02). Metabolism associated with LPDs (0.5 Hz as a baseline) increased by a median of 100% at 1 Hz and for frequencies >1 Hz increased by a median of 309%. There were no statistically significant differences in SUVRpons for other factors including duration ( p = 0.10), amplitude ( p = 0.80), structural etiology ( p = 0.55), or "plus" features such as rhythmic or fast sharp activity ( p = 0.84)., Conclusions: Metabolic activity increases monotonically with LPD frequency. LPD frequency should be a measure of interest when developing neuroprotection strategies in critical neurologic illness., (© 2019 American Academy of Neurology.)

Objective: To present a case that demonstrates that seizures and interictal disturbances can be driven by a small area of functionally abnormal cortex., Methods: Two novel functional MRI network analysis methods were used to supplement conventional seizure and lesion localization methods: (1) regional homogeneity to quantify local connectivity, or synchrony, with a resolution of less than 1 cm 3 of cortex; and (2) small-worldness to combine information about whole brain network segregation and integration., Results: After a small corticectomy in the dominant supramarginal gyrus (13 × 7 × 6 mm) limited to the area of abnormal local connectivity, and smaller than the PET and SPECT abnormalities, the patient has been seizure-free for 3 years with no language deficit. Whole brain network characteristics normalized (small-worldness) to that of healthy controls., Conclusions: This case demonstrates that small areas of cortex may be highly epileptogenic, drive intractable epilepsy, and disrupt large-scale networks likely to be involved in core cognitive functions., (© 2017 American Academy of Neurology.)

Objectives: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known., Methods: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [¹¹C]flumazenil PET (n = 18)., Results: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABA(A) receptor binding in the same area was reduced in patients with more frequent seizures., Conclusions: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery.

Objective: To determine the diagnostic accuracy and prognostic value of ¹⁸FDG-PET in a recent series of patients operated for intractable partial epilepsy associated with histologically proven Taylor-type focal cortical dysplasia (TTFCD) and negative MRI., Methods: Of 23 consecutive patients (12 male, 7-38 years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had strictly normal MRI. FDG-PET was analyzed both visually after coregistration on MRI and using SPM5 software. Metabolic data were compared with the epileptogenic zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome., Results: Visual PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%) corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9). PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13 cases. Location of PET abnormalities was extratemporal in all cases, involving eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic findings (n = 20) demonstrated that single hypometabolic gyri (n = 11) corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus. Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex but were more extensive. Following limited cortical resection (mean follow-up 4 years), seizure freedom without permanent motor deficit was obtained in 20/23 patients (87%)., Conclusions: ¹⁸FDG-PET coregistered with MRI is highly sensitive to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients with negative MRI.

The authors evaluated four patients with schizencephaly who underwent subtraction ictal SPECT coregistered to MRI (SISCOM) prior to epilepsy surgery. Three patients had a SISCOM alteration that was concordant with the epileptic brain tissue. Two of these patients were rendered seizure-free and one individual experienced a significant reduction in seizures. The patient with an indeterminate SISCOM had an unfavorable outcome. SISCOM is useful in evaluating patients with schizencephaly for epilepsy surgery.

Background: Studies in animal models and epileptic patients have suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. Ring chromosome 20 (r[20]) epilepsy is a very homogenous type of epilepsy and is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in the present study in drug-resistant patients with r(20) epilepsy using PET., Method: The authors performed [18F]fluoro-l-DOPA PET in 14 patients with r(20) epilepsy and compared uptake constants in the putamen and the caudate with those of 10 controls. In addition, the authors examined the correlation between these constants and the percentage of cells with r(20) mosaicism., Results: [18F]fluoro-l-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated to the percentage of cells with r(20)., Conclusion: Striatal dopamine is modulated in r(20) epilepsy; dysfunction of this neurotransmission may impair the mechanisms that interrupt seizures.

Objective: To determine the ictal focus and the role of seizure characteristics, fluorodeoxyglucose (FDG) PET, and subtraction ictal SPECT in patients diagnosed as having nonlesional lateral temporal lobe epilepsy by long-term scalp video-EEG monitoring., Methods: The authors studied 33 consecutive patients with nonlesional neocortical epilepsy who had a scalp ictal onset zone localized in the temporal lobe and good surgical outcome after focal neocortical resection. All patients were evaluated using intracranial recordings prior to resection. Semiology, FDG-PET, and ictal-interictal subtraction SPECT were used to verify the diagnostic role of these methods in the localization of epileptic foci., Results: The ictal onset zones, confirmed by intracranial study, were the lateral temporal (22 patients), parietal (5), frontal (3), temporoparietal (2), and occipital (1) areas. FDG-PET analyzed by statistical parametric mapping correctly localized the epileptogenic lobe in 18 of 33 patients and subtraction ictal SPECT correctly localized it in 13 of 25 patients. However, in patients with extratemporal ictal onset zones, FDG-PET and ictal SPECT in combination correctly localized the epileptogenic lobe in only 3 of 11 cases., Conclusions: An extratemporal ictal onset zone was encountered in patients with nonlesional lateral temporal lobe seizures based on scalp video-EEG monitoring. FDG-PET and subtraction SPECT had localizing value in no more than half of patients.

Objective: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time., Methods: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal., Results: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus., Conclusions: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset.

Background: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data., Method: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity., Results: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05)., Conclusions: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.

Background: Cortical areas showing abnormal glucose metabolism and [(11)C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control., Objective: To analyze whether the extent of cortex showing 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery., Methods: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 +/- 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores., Results: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found., Conclusions: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed.

This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)-PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.

Objective: To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral blood flow (rCBF) alterations and chronic therapeutic responses., Background: We previously found that VNS acutely induces rCBF alterations at sites that receive vagal afferents and higher-order projections, including dorsal medulla, somatosensory cortex (contralateral to stimulation), thalamus and cerebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally)., Methods: VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [O-15]water and PET, immediately before ongoing VNS began, in 11 partial epilepsy patients. T-statistical mapping established relative rCBF increases and decreases for each patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared with pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 regions of previously observed significant CBF change), were rank ordered across patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change., Results: Seizure-frequency changes ranged from 71% decrease to 12% increase during VNS. Only the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF correlated with decreased seizures (p < 0.001)., Conclusions: Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Future studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.

Objective: To determine whether the detection of focal hypoperfusion by subtraction SPECT co-registered to MRI (SISCOM) improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy., Background: Postictal SPECT injections are easier to perform than are ictal injections, but the images are more difficult to interpret and have been reported to have lower sensitivity and specificity., Methods: Thirty-five consecutive intractable partial epilepsy patients who had postictal SPECT studies were evaluated. The following sets of SPECT images were separately interpreted by three blinded reviewers and classified as either localizing to 1 of 16 possible sites in the brain or as nonlocalizing: unsubtracted postictal and interictal images for conventional side-by-side comparison, SISCOM images of hyperperfusion, SISCOM images of hypoperfusion, and both sets of SISCOM hyperperfusion and hypoperfusion images (combined SISCOM evaluation)., Results: Significantly higher proportions of the hyperperfusion SISCOM images (65.7%), the hypoperfusion SISCOM images (74.3%), and the combined SISCOM evaluation (82.9%) were localizing than were the conventional method of side-by-side comparison of unsubtracted images (31.4%; p < 0.0001). Concordance with the discharge diagnosis was higher for the combined SISCOM evaluation than it was for either the hyperperfusion or the hypoperfusion SISCOM images alone (both p < 0.05). For the hypoperfusion SISCOM and the combined SISCOM evaluations, concordance of the localization with the site of epilepsy surgery was associated with a greater probability of an excellent outcome than were nonconcordant/nonlocalizing images (both p < 0.05)., Conclusion: The use of SISCOM to detect focal cerebral hypoperfusion, in addition to focal hyperperfusion, improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy.

Objective: To investigate focal cortical abnormalities of gamma-aminobutyric acid type A-central benzodiazepine receptors (GABA(A)-cBZRs) in patients with extratemporal partial seizures with acquired lesions and in patients with normal high-resolution MRI., Methods: Six patients with acquired lesions and 18 patients with normal high-resolution MRI and extratemporal partial seizures, as well as 24 normal controls, were studied with 11C-flumazenil (FMZ) PET to produce voxel-by-voxel images of FMZ volume of distribution (FMZVD), which reflects density of GABA(A)-cBZRs. These images were analyzed using Statistical Parametric Mapping (SPM). Each patient was compared with the control group to reveal regions with abnormal FMZVD at p < 0.001 uncorrected, corrected to p < 0.05 for the whole brain volume. Each normal control was compared with the remaining controls in the same manner., Results: All six patients with acquired lesions had a single region of reduced FMZVD. Thirteen of 18 patients with normal MRI had regions of abnormal cortical FMZVD: 10 had regions of increased FMZVD, 6 had regions of decreased FMZVD, and 3 had both regions of increased and decreased FMZVD. Seven patients had an abnormality in the lobe and 12 in the hemisphere of presumed seizure origin., Conclusions: FMZ PET analyzed with SPM is an automated, objective, sensitive, and specific means for detecting regional cortical abnormalities of GABA(A)-cBZRs in patients with partial seizures. This technique may be useful in the evaluation of patients with refractory partial seizures for surgical treatment, particularly in those patients with normal MRI.

Traditional side-by-side visual interpretation of ictal and interictal single-photon emission computed tomography (SPECT) scans can be difficult in identifying the surgical focus, particularly in patients with extratemporal or otherwise unlocalized intractable epilepsy. Computer-aided subtraction ictal SPECT co-registered to MRI (SISCOM) may improve the clinical usefulness of SPECT in localizing the surgical seizure focus. We studied 51 consecutive intractable partial epilepsy patients who had interictal and ictal scans. The SPECT studies were blindly reviewed and classified as either localizing to 1 of 16 sites in the brain or as nonlocalizing. SISCOM images were localizing in 45 of 51 (88.2%) compared with 20 of 51 (39.2%) for traditional side-by-side inspection of ictal and interictal SPECT images (p < 0.0001). Inter-rater agreement for two independent reviewers was better for SISCOM (84.3% versus 41.2%, kappa = 0.83 versus 0.26; p < 0.0001). Concordance of seizure localization with the more established tests was also higher for SISCOM. Late injection of the radiotracer (> 45 seconds), but not secondary generalization of the seizure, was associated with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with the surgical site were more likely to have excellent outcome than patients with nonconcordant or nonlocalizing findings (62.5% [10/16] versus 20% [2/10]; p < 0.05). On the other hand, seizure localization by the traditional method of SPECT inspection had no significant association with postsurgical outcome. We conclude that SISCOM improves the sensitivity and the specificity of SPECT in localizing the seizure focus for epilepsy surgery. Concordance between SISCOM localization and site of surgery is predictive of postsurgical improvement in seizure outcome.

We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.

We studied clinical and ictal single-photon emission computed tomography (SPECT) features in 14 patients with parietal lobe epilepsy, nine of whom had structural parietal lobe lesions. Thirteen patients had simple partial seizures of somatosensory (eight), psychic (four), and motor (nine) types. Complex partial seizures (CPS) occurred in seven patients; six were psychoparetic (prominent staring, relative immobility) and one had hyperkinetic activity. Seizures lasted 7 to 110 seconds; 99mTc-HMPAO (hexamethylpropylene amine oxime) was injected ictally, 7 to 89 seconds from seizure onset and 0 to 74 seconds (mean, 21.0 +/- 24.4 seconds) before seizure termination. Ictal SPECT demonstrated focal areas of parietal hyperperfusion in all 14 cases and corresponded with sites of the structural lesions. Parietal hyperperfusion was anterior in eight, posterior in four, and diffuse in two. Quantitative analysis revealed increases in parietal side-to-side perfusion ratios on ictal compared with interictal scans of 11 to 51% (mean, 25.5 +/- 14.4%). Ictal SPECT localization correlated with two main clinical seizure patterns: an anterior syndrome characterized by sensorimotor manifestations and a posterior syndrome characterized by CPS of the psychoparetic type. Ictal SPECT is helpful for localization of parietal seizures. Parietal hyperperfusion is discrete and short-lived, demanding true ictal injections for diagnostic studies.

We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fisher's exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. We aimed to establish whether this noninvasive technique could also map the cortical activation that occurs during focal seizures. In order to do this, we used a conventional 1.5-tesla clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. We acquired FLASH images (TE = 60 msec) every 10 seconds over intervals of 10 minutes and derived activation images by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. We concluded that functional MRI can provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure.

The National General Practice Study of Epilepsy (NGPSE) is a prospective community-based study of newly diagnosed epileptic seizures. Of 594 patients with definite epileptic seizures, 160 (26.9%) had seizures with a clinically localizable onset: 36 (22.5%) frontal, 52 (32.5%) central sensorimotor, 43 (27%) temporal, nine (5.6%) frontotemporal, and 10 each (6.3%) parietal and other posterior cortex. There was no difference among these groups in seizure frequency or remission rate; 46.5% were seizure free and 6.9% had severe epilepsy. Etiology was identifiable in 41% and focal CT and EEG abnormalities in 33% and 19%, with results discordant with the clinical seizure localization in 21% and 20%. Temporal lobe epilepsy may be underreported, as it may be more difficult to localize clinically. Extratemporal seizures are extremely common in the general population, especially frontal and central sensorimotor, in relation to cerebrovascular disease. Prognoses are similar for partial epilepsies with different clinical patterns and regions of onset and are much better than suggested in hospital-based studies. The clinical, EEG, and CT localizations may frequently be discordant in this nonrefractory group.

We report 2 patients with epilepsia partialis continua (EPC) in whom ictal single photon emission computed tomography (SPECT) showed focal increased signal while EEG failed to show epileptic changes. SPECT may clarify confusing situations when EPC is suspected.

One hundred fifty-three patients with medically refractory partial epilepsy underwent chronic stereotactic depth-electrode EEG (SEEG) evaluations after being studied by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and scalp-sphenoidal EEG telemetry. We carried out retrospective standardized reviews of local cerebral metabolism and scalp-sphenoidal ictal onsets to determine when SEEG recordings revealed additional useful information. FDG-PET localization was misleading in only 3 patients with temporal lobe SEEG ictal onsets for whom extratemporal or contralateral hypometabolism could be attributed to obvious nonepileptic structural defects. Two patients with predominantly temporal hypometabolism may have had frontal epileptogenic regions, but ultimate localization remains uncertain. Scalp-sphenoidal ictal onsets were misleading in 5 patients. For 37 patients with congruent focal scalp-sphenoidal ictal onsets and temporal hypometabolic zones, SEEG recordings never demonstrated extratemporal or contralateral epileptogenic regions; however, 3 of these patients had nondiagnostic SEEG evaluations. The results of subsequent subdural grid recordings indicated that at least 1 of these patients may have been denied beneficial surgery as a result of an equivocal SEEG evaluation. Weighing risks and benefits, it is concluded that anterior temporal lobectomy is justified without chronic intracranial recording when specific criteria for focal scalp-sphenoidal ictal EEG onsets are met, localized hypometabolism predominantly involves the same temporal lobe, and no other conflicting information has been obtained from additional tests of focal functional deficit, structural imaging, or seizure semiology.

There is little experience with excisional surgery for drug-resistant partial seizures in very young patients. We describe our experience with 5 infants under 1 year of age with malignant partial seizures and deteriorating developmental status. All were experiencing frequent daily seizures that did not respond to 1st-line antiepileptic medications at high therapeutic serum levels and considerable medication toxicity. Three infants had complete resection of epileptic tissue (frontal corticectomy and prefrontal lobectomy) and are seizure-free. Two underwent partial resection (lateral temporal lobectomy, frontal corticectomy with anterior callosotomy) and have experienced a significant reduction in seizure frequency. Surgery did not result in any significant neurologic deficit or lead to compromise of developmental status. From these data, we tentatively conclude that excisional surgery can be performed safely in selected infants with medically uncontrolled malignant partial seizures and may significantly improve long-term seizure status. Referral to a tertiary center specializing in early childhood epilepsy surgical evaluation may be considered in these circumstances.

Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

Prominent early draining veins have been found in angiograms of four patients studied during an acute benign illness characterized by repetitive focal motor seizures and prominent postictal neurologic deficits. Concomitant intravenous radionuclide gamma camera flow and static images showed increased relative perfusion with a slight positive static uptake on the involved side. Follow-up studies showed no evidence of these abnormalities. These angiographic and radioisotopic findings probably correlate with the clinically observed cortical hyperemia as part of, or subsequent to, focal motor seizures. Alternatively, these findings suggest the possibility that vascular occlusions may be the underlying cause of the patients' illness.

Twenty-two patients were analyzed 2 or more years after corpus callosum section (9 partial, 13 total). Forty-one percent had class 1 outcome (elimination of secondarily generalized and complex partial seizures), 32% had class 2 outcome (elimination of secondarily generalized seizures), and 27% had class 3 outcome (no appreciable change). Total section was twice as effective in abolishing secondarily generalized seizures as was partial section (77% versus 35%). Statistically significant associations were seen between focal CT lesions and class 1 outcome, and between IQ less than 45 and class 2 or 3 outcome.

We compared the results of x-ray CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) using 18F 2-deoxyglucose in 36 patients with partial seizures. Seventeen patients had localized epileptic discharges on surface EEG. MRI showed an abnormality in 9, CT in 4, and PET in 13 of 14 patients who had the test. Nineteen patients had nonlocalizing EEG discharges. MRI showed an abnormality in 11, CT in 10, and PET in 8 of 12. MRI is more sensitive than CT in detecting structural lesions underlying PET hypometabolism.

We analyzed local cerebral metabolic rates of glucose (LCMRglu) in 20 regions from 22 patients with complex partial seizures, who were taking neither phenytoin nor phenobarbital and who had normal CTs. Results were compared with data from 19 normal controls. Ten patients had left temporal, eight right temporal, and four bitemporal or generalized EEG discharges. There were no significant differences between patient and control values in any of 20 regions of interest. LCMRglu was depressed at the site of the epileptic focus: L/R ratio was 0.85 +/- 0.12 (p less than 0.003 compared with control), 0.92 +/- 0.08 (p less than 0.05), and 0.84 +/- 0.1 (p less than 0.001), respectively, in mesial, superior, and inferior temporal regions for patients with left temporal foci; 1.7 +/- 0.96 (p less than 0.04), 1.1 +/- 0.1 (NS), and 1.15 +/- 0.04 (p less than 0.001) for patients with right temporal foci. Patients with left temporal EEG foci had significantly lower values than patients with right temporal foci in left superior frontal and thalamic as well as left temporal regions, while patients with right-sided EEG foci had depressed LCMRglu (compared with patients with left temporal EEG foci) restricted to right mesial temporal lobe. The patients with left temporal foci tended to have longer seizure histories (22.7 +/- 5.4 versus 11 +/- 5.6 years; p less than 0.001). There was an inverse correlation between length of seizure history and mean LCMRglu (r = 0.38; 0.1 greater than p greater than 0.05). Our study suggests that LCMRglu is not depressed in regions beyond the epileptic focus when patients are not taking drugs known to decrease cerebral glucose metabolism.

Computerized transaxial tomography was carried out on 50 consecutive unselected patients referred to a neurologic practice for evaluation of focal epilepsy. Structural abnormalities were defined in 35.3 percent of these studies: porencephalic cysts in six patients, diffuse cerebral atrophy in five, cerebral hemiatrophy in three, focal cortical atrophy in two, neoplasms in two, hydrocephalus in one patient, and cerebeller hypoplasia in one. Computerized transaxial tomography is a useful outpatient procedure for evaluation and follow-up of patients with focal seizure disorders.