Biomedical subjects

O Carter Snead

Publications and source records attributed to O Carter Snead.

At least 19 recordsLinked to original sources

PubMed2006

Chronobiometry of behavioral activity in the Ts65Dn model of Down syndrome.

Disruption of the sleep-wake cycle has been reported among individuals with Down syndrome (DS). Here we studied behavioral rhythms in adult male and female Ts65Dn mice, a model of DS. The overall behavioral activity of Ts65Dn and diploid (2N) littermates as defined by total movements (TM), movement time (MT), ambulatory movement time (AMT), time spent in center of arena (CT), jumps (JFP), rotational behavior (TURNS), and wheel-running activity (WRA) was recorded under a 12 h:12 h light-dark photocycle. During the light phase, Ts65Dn mice exhibited higher TM, MT, CT, JFP, and WRA compared to 2N littermates. During the dark phase, Ts65Dn and 2N mice differed only in CT and WRA, with the Ts65Dn group engaging in higher levels of both. There were no gender differences for any of the behavioral variables studied. Non-linear least-squares (Cosinor) analysis of the distribution of total behavioral activity (TM) indicated that Ts65Dn mice exhibited a slightly higher mean oscillation (i.e., mesor), but significantly lower amplitude in comparison to 2N mice, suggesting that levels of TM were elevated in trisomic mice but were relatively constant throughout the photocycle. The peak of the Ts65Dn TM rhythm was significantly phase-advanced, occurring approximately 4 h earlier than 2N mice. Overall, Ts65Dn mice were hyperactive and differed significantly in daily patterns of specific behaviors from those of 2N littermates. To control for the potential confound of retinal degeneration in Ts65Dn and 2N mice, we compared and found no difference between the TM rhythm parameters of 2N and non-retinally degenerate C57/129Sv mice, suggesting that abnormal behavioral rhythmicity in Ts65Dn mice may not due to the absence of rod and cone photoreceptors. These results serve as a starting point for further investigations into the physiological basis of sleep-wake disturbances in DS patients.

Animals↗

PubMed2006

Daily rhythms of seizure activity and behavior in a model of atypical absence epilepsy.

We studied daily rhythms of chronic seizure activity and behavior in adult rats and mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY) during early postnatal development. Chronic atypical absence seizures were verified in the AY-treated animals by the presence of spontaneous 5- to 6-Hz slow spike-wave discharges (SSWDs) in the neocortex. General behavioral activity, as measured by total movements (TM), movement time (MT), ambulatory movement time (AMT), time spent in center of arena (CT), jumps (JFP), and rotational behavior (TURNS), were continuously recorded under a 12-hour light:12-hour dark photocycle. The average SSWD duration in AY-treated rats varied daily, with two peaks occurring at approximately dark phase and light phase onset. Mice treated with AY exhibited significant increases in all behavioral measures during the light and dark phases, with the exception of light-phase CT, which did not differ from that of controls. Consequently, the daily rhythm of total behavioral activity (TM) exhibited a significantly higher mean oscillation (mesor) and amplitude without evidence of phase shift compared with the TM rhythm of controls. The occurrence of SSWD activity in the AY model appears to be subject to regulation by biological timing mechanisms and, furthermore, associated with motor hyperactivity that does not alter the timing of behavioral rhythmicity.

Animals↗

PubMed2006

Magnetoencephalography and diffusion tensor imaging in gelastic seizures secondary to a cingulate gyrus lesion.

Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.

Adolescent↗

PubMed2006

The role of magnetoencephalography in pediatric epilepsy surgery.

INTRODUCTION: Magnetoencephalography (MEG) is a new diagnostic imaging and brain mapping device that has been recently used in the context of pediatric epilepsy, epilepsy surgery, and neuronavigation. PRINCIPLES OF MAGNETOENCEPHALOGRAPHY: MEG allows for the placement of magnetic spike sources on a conventional magnetic resonance imaging scan, the so-called magnetic source imaging, so that the localization of epileptiform activity in a child can be determined. Considerable effort is placed on analyzing the configuration and number of spike waves by MEG that relate to a primary epileptiform discharge. Such MEG spike clusters are corroborated now by intraoperative invasive subdural grid monitoring that show good correlation in the majority of cases. Another important role of MEG relates to the mapping of critical regions of brain function using known paradigms for speech, motor, sensory, visual, and auditory brain cortex. FUTURE APPLICATIONS: When linked to standard neuronavigation devices, MEG brain mapping can be extremely helpful to the neurosurgeon approaching nonlesional epilepsy cases or lesional cases where the safest and most direct route to the surgical disease can be selected. As paradigms for brain mapping improve and as MEG software upgrades become more sensitive to analyzing all types of spike sources, MEG will play an increasingly important role in pediatric neurosurgery, especially for the child with intractable epilepsy.

Brain Mapping↗

PubMed2006

Multiple subpial transections in pediatric epilepsy: indications and outcomes.

OBJECTIVE: Multiple subpial transection (MST) is a surgical technique mainly used when epileptiform activity arises from eloquent or functional brain cortex. In the medical literature, there are relatively few studies reporting the efficacy and safety of this procedure in adults and in children. We review the scientific rationale, the indications, and the results of this procedure. METHODS: Neuroanatomic studies show that the basic functional cortical unit is arranged vertically, and epileptic activity spreads horizontally. Minimal cortical unit is essential for maintenance of cortical activity. Vertical incisions in the cortex interrupt transverse synaptic connections, preventing seizure propagation while preserving the vertical column subserving neuronal function. In the past, it has been difficult to assess the efficacy of MSTs per se, as they have usually been performed together with cortical resection or lesionectomy. After MSTs, studies show that 33-46% of treated children are in Engel class I or II. The permanent complication rate is low with no permanent language or motor disabilities. CONCLUSIONS: MST is a safe procedure with unclear specific efficacy. It has been used mainly in conjunction with cortical resection or lesionectomy, when the eloquent cortex is involved in the seizure activity. Further prospective studies are needed to define the role of MST in epilepsy surgery.

Cerebral Cortex↗

PubMed2006

Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function.

The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-)) represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. In physiological concentrations, GHB acts at the GHB receptor (GHBR), but in high concentrations such as those observed in the brains of children with SSADH deficiency, GHB is thought to be a direct agonist at the GABABR receptor (GABABR). We tested the hypothesis that both GHBR and GABABR-mediated function are perturbed in SSADH deficiency. Therefore, we examined the high affinity binding site for GHB as well as the expression and function of the GABABR in mutant mice made deficient in SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific GABABR antagonist, [3H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-) when compared to wild type control animals (SSADH(+/+)), particularly in hippocampus. GABABR-mediated synaptic potentials were decreased in SSADH(-/-). Immunoblot analysis of GABABR1a, R1b, and R2 in SSADH(-/-) indicated a trend towards a region-specific and time-dependent decrease of GABABR subunit protein expression. There was no difference between SSADH(-/-) and wild type in binding of either [3H]GHB or a specific GHBR antagonist to the GHBR. These data suggest that the elevated levels of GABA and GHB that occur in SSADH(-/-) lead to a use-dependent decrease in GABABR-mediated function and raise the possibility that this GHB- and GABA-induced perturbation of GABABR could play a role in the pathogenesis of the seizures and mental retardation observed in SSADH deficiency.

Animals↗

PubMed2006

GABAB receptor antagonism abolishes the learning impairments in rats with chronic atypical absence seizures.

Chronic atypical absence seizures are a component of the Lennox-Gastaut syndrome, a disorder invariably associated with severe cognitive impairment in children. However, the cause of this intellectual delay remains unclear. The AY9944 model of chronic atypical absence seizures in rats reliably reproduces the electrographic, behavioral, pharmacological and cognitive features of clinical atypical absence. Using this model, we tested the hypothesis that the cognitive impairment associated with this disorder involves a gamma-aminobutyric acid B (GABA(B)) receptor-mediated mechanism. Therefore, we examined the effect of a specific, high affinity GABA(B) receptor antagonist, CGP35348, on the atypical absence seizures, the working memory deficits, and the altered long-term potentiation that we have observed in the AY9944 model. CGP35348 blocked atypical absence seizures, restored long-term potentiation to normal level, and reversed the cognitive deficit in the AY9944-treated animals. However, dose-response studies showed that lower doses of CGP35348 that failed to influence atypical absence seizure activity, completely reversed the spatial working memory deficit. These data suggest that GABA(B) receptor-mediated mechanisms are responsible for the cognitive dysfunction in the AY9944 model of chronic atypical absence seizures and further, that their cognitive impairment is independent of the seizure activity. The data raise the possibility that GABA(B) receptor antagonists may have therapeutic potential for the treatment of cognitive impairment in epilepsy syndromes where atypical absence seizures are a component.

Animals↗

PubMed2006

Increased guanidino species in murine and human succinate semialdehyde dehydrogenase (SSADH) deficiency.

Mice with targeted deletion of the GABA-degradative enzyme succinate semialdehyde dehydrogenase (SSADH; Aldh5a1; OMIM 271,980) manifest globally elevated GABA and regionally decreased arginine in brain extracts. We examined the hypothesis that arginine-glycine amidinotransferase catalyzed the formation of guanidinobutyrate (GB) from increased GABA by quantifying guanidinoacetate (GA), guanidinopropionate (GP) and GB in brain extracts employing stable isotope dilution gas chromatographic-mass spectrometry. GA and GB were up to 4- and 22-fold elevated, respectively, in total and regional (cerebellum, hippocampus, cortex) brain extracts derived from SSADH(-/-) mice. Corresponding analyses of urine and cerebrospinal fluid derived from SSADH-deficient patients revealed significant (P<0.05) elevations of GA and GB in urine, as well as GB levels in CSF. These data suggest that GB may be an additional marker of SSADH deficiency, implicate additional pathways of pathophysiology, and identify the second instance of elevated GB in a human inborn error of metabolism.

Animals↗

PubMed2006

Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms.

The epilepsy that occurs in SSADH deficiency has a seizure phenotype similar to that occurring in the SSADH(-/-) mouse. We examined the expression and function of the GABA(A) receptor (GABA(A)R) in SSADH-deficient mice. A selective decrease in binding of [(35)S]tert-butylbicyclophosphorothionate was observed in SSADH(-/-) mice at postnatal day 7 that was progressive until the third postnatal week of life when, at the nadir of the decreased [(35)S]tert-butylbicyclophosphorothionate binding, generalized convulsive seizures emerged that rapidly evolved into status epilepticus. We also observed a substantial downregulation of the beta(2) subunit of GABA(A)R, a reduction in GABA(A)-mediated inhibitory postsynaptic potentials, and augmented postsynaptic population spikes recorded from hippocampal slices. The SSADH(-/-) mouse model represents a powerful investigative tool for understanding the pathophysiology of the seizures associated with human SSADH deficiency. These data raise the possibility that progressive dysfunction of the GABA(A)R may be involved in the development of seizures in SSDAH-deficient mice. Elucidation of the precise fundamental mechanisms of the perturbation of the GABA(A)R-mediated function in SSADH(-/-) mice could lead to the development of novel treatment modalities designed to reduce the neurological morbidity in children with SSADH deficiency.

Animals↗

PubMed2006

Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare genetic defect of GABA degradation recently modelled in mice (SSADH(-/-) mice), manifests early absence seizures that evolve into generalized convulsive seizures and lethal status epilepticus in gene-ablated mice. Disrupted GABA homeostasis, in conjunction with the epileptic phenotype and increased gamma-hydroxybutyric acid (GHB), suggested that expression profiling with the U74Av2 Affymetrix system would reveal dysregulation of receptor genes associated with GABAergic and glutamatergic neurotransmission. Unexpectedly, we found significant downregulation for genes associated with myelin biogenesis and compaction, predominantly in hippocampus and cortex. These results were confirmed by: (1) myelin basic protein (MBP) immunohistochemistry; (2) western blotting of myelin-associated glycoprotein (MAG) and MBP; (3) qRT-PCR analyses of myelin-associated oligodendrocytic basic protein (MOBP), MAG, MBP and proteolipid protein (PLP) in hippocampus, cortex and spinal cord; (4) quantitation of ethanolamine and choline plasmalogens, all core myelin components; (5) evaluation of myelin content in brain sections employing toluidine blue staining; and (6) ultrastructural evaluation of myelin sheath thickness via electron microscopy. We speculate that increased GABA/GHB, acting through GABAergic systems, results in decreased levels of the neurosteroids progesterone and allopregnanolone [Gupta et al (2003) Ann Neurol 54(Supplement 6): S81-S90] and phosphorylation of mitogen-activated protein (MAP) kinase, with resulting myelin protein abnormalities primarily in the cortex of SSADH(-/-) mice.

Animals↗

PubMed2006

Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase.

gamma-Hydroxybutyratic acid (GHB), and its prodrugs 4-butyrolactone and 1,4-butanediol, represent expanding drugs of abuse, although GHB is also used therapeutically to treat narcolepsy and alcoholism. Thus, the pathway by which GHB is metabolized is of importance. The goal of the current study was to examine GHB metabolism in mice with targeted ablation of the GABA degradative enzyme succinic semialdehyde dehydrogenase (SSADH(-/-) mice), in whom GHB persistently accumulates, and in baboons intragastrically administered with GHB immediately and persistently. Three hypotheses concerning GHB metabolism were tested: (1) degradation via mitochondrial fatty acid beta-oxidation; (2) conversion to 4,5-dihydroxyhexanoic acid (a putative condensation product of the GHB derivative succinic semialdehyde); and (3) conversion to d-2-hydroxyglutaric acid (d-2-HG) catalyzed by d-2-hydroxyglutarate transhydrogenase (a reaction previously documented only in rat). Both d-2-HG and 4,5-dihydroxyhexanoic acid were significantly increased in neural and nonneural tissue extracts derived from SSADH(-/-) mice. In vitro studies demonstrated the ability of 4,5-dihydroxyhexanoic acid to displace the GHB receptor ligand NCS-382 (IC(50) = 38 micromol/L), although not affecting GABA(B) receptor binding. Blood and urine derived from baboons administered with GHB also accumulated d-2-HG, but not 4,5-dihydroxyhexanoic acid. Our results indicate that d-2-HG is a prominent GHB metabolite and provide further evidence for the existence of d-2-hydroxyglutarate transhydrogenase in different mammalian species.

Alcohol Oxidoreductases↗

PubMed2006

New generation anticonvulsants for the treatment of epilepsy in children.

In the last 12 years, 10 new anticonvulsants have been approved by the U.S. Food and Drug Administration and, as a result, the treatment options for children and adults with epilepsy have been expanded considerably. These new generation antiepileptic drugs offer equal efficacy with improved tolerability, pharmacokinetic properties, and side effect profiles compared with the traditional drugs. With many new medications available, the clinician treating children with epilepsy must be well versed in the application of these drugs to their patient population. This manuscript will review the indications, mechanism of action, pharmacokinetics, adverse effects, and dosing of the new generation of anticonvulsant medications.

Anticonvulsants↗

PubMed2006

Functional contribution of specific brain areas to absence seizures: role of thalamic gap-junctional coupling.

The synchronized discharges typical of seizures have a multifactorial origin at molecular, cellular and network levels. During recent years, the functional role of gap-junctional coupling has received increased attention as a mechanism that may participate in seizure generation. We have investigated the possible functional roles of thalamic and hippocampal gap-junctional communication (GJC) in the generation of spike-and-wave discharges in a rodent model of atypical absence seizures. Seizures in this model spread throughout limbic, thalamic and neocortical areas. Rats were chronically implanted with cannulae to deliver drugs or saline, and local field potentials recordings were performed using intracerebral electrodes positioned in distinct brain areas. Initially, the effects on synaptic transmission of the gap-junctional blockers used in this study were determined. Neither carbenoxolone (CBX) nor 18-alpha-glycyrrhetinic acid altered chemical synaptic transmission at the concentrations tested. These two compounds, when injected via cannulae into the reticular nucleus of the thalamus (NRT), decreased significantly the duration of seizures as compared with saline injections or injections of the CBX inactive derivative glycyrrhizic acid. CBX injections into the hippocampus resulted in diminished seizure activity as well. NRT injections of trimethylamine, which presumably causes intracellular alkalinization (thereby promoting gap-junctional opening), enhanced seizures and spindle activity. These observations suggest that, in this rodent model, thalamic and limbic areas are involved in the synchronous paroxysmal activity and that GJC contributes to the spike-and-wave discharges.

Animals↗

PubMed2006

Efficacy of dexamathasone on cerebral swelling and seizures during subdural grid EEG recording in children.

PURPOSE: To evaluate the impact of steroid treatment on cerebral swelling and seizures during subdural grid EEG (SGEEG) monitoring. METHODS: We reviewed data from 37 pediatric patients with intractable epilepsy who underwent SGEEG monitoring and divided the patients into those who received dexamethasone and those who did not. We then correlated administration of steroids to incidence of cerebral swelling on computed tomography (CT) scans and to frequency of seizures during SGEEG. RESULTS: Twenty-three patients received dexamethasone prophylactically every 6 hours (dosage range, 1-7.5 mg; mean, 3.2 mg) from the first day of SGEEG placement (group A); 14 patients received no dexamethasone (group B). Eight (21.6%) of 37 patients experienced cerebral swelling on CT: two (9%) were in group A, and six (42.9%) were in group B (p < 0.05). SGEEG monitoring time for recording habitual seizures that localized cortical areas for surgical excision was longer in group A (1-6 days; mean, 3.0) than it was in group B (1-3 days; mean, 2.2), (p < 0.05). Habitual seizures were recorded in 36 patients. One group A patient experienced obtundation due to cerebral swelling, and monitoring in this patient was discontinued. CONCLUSIONS: The prophylactic administration of steroids to pediatric patients during SGEEG monitoring is efficacious for reducing cerebral swelling. Although it decreases the frequency of habitual seizures and increases seizure-monitoring time, dexamethasone reduces the risk of complications from cerebral swelling during the SGEEG procedure.

Adolescent↗

PubMed2006

Serotonin depletion attenuates AY-9944-mediated atypical absence seizures.

PURPOSE: To test the hypothesis that serotonin (5-HT) plays a role in the modulation of experimental atypical absence seizures. METHODS: Male Long-Evans hooded rats were treated from postnatal day (P) 2 to P20 with the cholesterol inhibitor AY-9944 (AY). Epidural electrodes were implanted for electrocorticography (ECoG) followed by serotonin depletion by using para-cholorophenylalanine (PCPA). High-performance liquid chromatography (HPLC) was used to measure the levels of serotonin and its metabolite (5-HIAA) in various brain regions. Serotonin metabolism was computed by using the 5-HIAA/5-HT ratio and used to ascertain differences between groups. RESULTS: PCPA treatment was associated with a significant decrease in the total slow spike-and-wave discharge (SSWD) duration in AY-treated rats compared with controls (p < 0.01). HPLC data confirmed the PCPA depletion of 5-HT and 5-HIAA in cortex, thalamus, hippocampus, and brainstem compared with naïve rats. AY-treated rats showed higher levels of 5-HIAA and 5-HT in the same brain regions, with a concomitant decrease in rates of serotonin turnover. CONCLUSIONS: The data indicate that serotonin depletion protects against experimental atypical absence seizures. The increased levels of 5-HIAA and 5-HT and altered rates of serotonin turnover suggest that the serotonergic neurotransmission may be perturbed in the AY rat.

Animals↗

PubMed2006

Nonconvulsive seizures in the pediatric intensive care unit: etiology, EEG, and brain imaging findings.

PURPOSES: To determine the occurrence of nonconvulsive seizures (NCS) in the Pediatric Intensive Care Unit (PICU); to ascertain the relationship of NCS to past medical history, etiology, EEG, and brain imaging; and to determine the concordance between abnormal EEG findings and neuroimaging abnormalities. METHODS: A retrospective review was conducted of all pediatric patients who were admitted or transferred to the PICU from January 2000 to December 2003 with an unexplained decrease in level of consciousness, no overt clinical seizures, and EEG recordings performed within the 24 h of onset of an altered state of consciousness. RESULTS: Twenty-three of 141 patients who met criteria for inclusion in the study (16.3%) were found to have NCS. The male to female ratio was 1.9:1. The largest group of patients (43%) had no preexisting neurological condition prior to the onset of NCS. In the remainder, the etiology of NCS included: acute structural brain lesion (48%), acute nonstructural brain lesion (22%), epilepsy-related seizure (13%), and others (17%). Epileptic foci were lateralized to the right side in 39.2%, the left side in 30.4%, and were bilateral in 30.4%. Of 23 patients with NCS, 18 (78.3%) demonstrated abnormal neuroimaging. In 10 of 18 of these patients (55.6%), the findings on neuroimaging were concordant with the lateralization found on EEG (p < 0.05, Fisher's exact test). CONCLUSIONS: NCS are not uncommon in pediatric patients with an altered state of consciousness. Almost half of the patients were previously healthy especially if they were under 6 months of age. This report highlights the importance of clinical awareness of NCS in the PICU.

Brain↗

PubMed2006

Topographic movie of ictal high-frequency oscillations on the brain surface using subdural EEG in neocortical epilepsy.

PURPOSE: To understand the rapid dynamic changes of ictal intracranial high-frequency oscillations (HFOs) in neocortical epilepsy. METHODS: We integrated multiple band frequency analysis and brain-surface topographic maps of HFOs from ictal subdural EEG (SDEEG) recordings. We used SDEEG to record partial seizures consisting of right-arm jerks with secondary generalization in a 17-year-old right-handed girl. We selected 20-s EEG sections that included preclinical seizure recordings. We averaged the HFO power between 60 and 120 Hz for 25 selected electrodes, made topographic maps from these averaged powers, and superimposed the maps on the brain-surface image. We filmed consecutive HFO maps at a 10-ms frame rate. RESULTS: Before clinical seizure onset, high-power HFOs emerged at the superior portion of the left precentral gyrus, then appeared in the middle of the left postcentral gyrus, and subsequently reverberated between both regions as well as the posterior portion of the left postcentral gyrus. Right-arm extension and facial grimacing started as the HFO power decreased. As generalized tonic-clonic seizures evolved, HFO power increased but remained within the central region. CONCLUSIONS: Topographic movies of intracranial HFOs on the brain surface allow visualization of the dynamic ictal changes in neocortical epilepsy.

Adolescent↗

PubMed2006

Preoperative simulation of intracerebral epileptiform discharges: synthetic aperture magnetometry virtual sensor analysis of interictal magnetoencephalography data.

OBJECT: Magnetoencephalography (MEG) has been used for the preoperative localization of epileptic equivalent current dipoles (ECDs) in neocortical epilepsy. Spatial filtering can be applied to MEG data by means of synthetic aperture magnetometry (SAM), and SAM virtual sensor analysis can be used to estimate the strength and temporal course of the epileptic source in the region of interest. To evaluate the clinical usefulness of this approach, the authors compare the results of SAM virtual sensor analysis to the results of ECD analysis, subdural electroencephalography (EEG) findings, and surgical outcomes in pediatric patients with neocortical epilepsy. METHODS: Ten pediatric patients underwent MEG, invasive subdural EEG, and cortical resection for neocortical epilepsy. The authors compared the morphological characteristics, quantity, location, and distribution of the epileptiform discharges assessed using SAM and ECD analysis, and subdural EEG findings (interictal discharges and ictal onset zones). In nine patients, MEG revealed clustered ECDs. The region exhibiting the maximum percentage (> or = 70%) of spikes/sharp waves on SAM was colocalized to clustered ECDs in seven patients. In six patients, SAM demonstrated focal spikes; in two, diffuse spikes; and in two others, focal rhythmic sharp waves. These epileptiform discharges were similar to those recorded on subdural EEG. In nine patients, concordant regions containing the maximum percentage of spikes/sharp waves were revealed by SAM and subdural EEG data. The region of the maximum percentage of spikes/sharp waves as demonstrated by SAM was colocalized to the ictal onset zone identified by subdural EEG findings in seven patients and partially colocalized in two. CONCLUSIONS: The SAM virtual sensor analysis revealed morphological characteristics, location, and distribution of epileptiform discharges similar to those shown by subdural EEG recordings. By using SAM it is possible to predict intracerebral interictal epileptiform discharges in the region of interest from noninvasively collected preoperative MEG data. The maximum interictal discharge zone identified by SAM virtual sensors correlated to clustered ECDs and the ictal onset zone on subdural EEG findings. Complementary analyses of ECDs and SAM on three-dimensional MR images can improve delineation of epileptogenic zones and lesions in neocortical epilepsy.

Adolescent↗