Biomedical subjects

Kenneth D Laxer

Publications and source records attributed to Kenneth D Laxer.

12 recordsLinked to original sources

PubMed2006

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis.

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.

Adult↗

PubMed2004

Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy.

OBJECTIVE: We prospectively investigated the role of magnetoencephalography (MEG) in localizing the seizure focus and in predicting outcome to surgical resections for intractable temporal lobe epilepsy (TLE). METHODS: We performed simultaneous interictal EEG and MEG recording (two 37-channel system) in 26 TLE patients followed by MEG source localization. We correlated early modeling dipoles with intracranial EEG, temporal surgical resection and surgical outcome. RESULTS: There were 12 patients who had anterior temporal horizontal or tangential dipoles to the anterior infero-lateral temporal tip cortex. Two patients underwent selective amygdalo-hippocampectomy (SAH) and nine patients had antero-medial temporal lobectomy (AMTL). All patients had successful outcome except for one patient who initially failed SAH, but became seizure-free after AMTL. There were 11 patients who demonstrated anterior temporal vertical or tangential oblique dipoles. Five patients had AMTL and three had SAH; all became seizure free. Five of above 23 patients had invasive EEG and demonstrated mesial seizure onset. Three TLE patients had lateral vertical dipoles that were concordant with intracranial EEG and these became seizure free after temporal neocortical resections. CONCLUSIONS: MEG source analysis produces distinct source patterns that provide useful localizing information, predict surgical outcome, and may aid in planning limited surgical resection in TLE.

Electroencephalography↗

PubMed2004

Identification of abnormal neuronal metabolism outside the seizure focus in temporal lobe epilepsy.

PURPOSE: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) magnetic resonance imaging (MRI) evidence for mesial-temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1H magnetic resonance spectroscopic imaging (MRSI). METHODS: MRSI in combination with tissue segmentation was performed on 14 TLE-MTS and seven TLE-no and 12 age-matched controls. In controls, N-acetylaspartate/(creatine + choline) [NAA/(Cr+Cho)] of all voxels of a given lobe was expressed as a function of white matter content to determine the 95% prediction interval for any additional voxel of a given tissue composition. Voxels with NAA/(Cr+Cho) below the lower limit of the 95% prediction interval were defined as "pathological" in patients and controls. Z-scores were used to identify regions with a higher percentage of pathological voxels than those in controls. RESULTS: Reduced NAA/(Cr+Cho) was found in ipsilateral temporal and parietal lobes and bilaterally in insula and frontal lobes. Temporal abnormalities identified the epileptogenic focus in 70% in TLE-MTS and 83% of TLE-no. Extratemporal abnormalities identified the epileptogenic focus in 78% of TLE-MTS but in only 17% of TLE-no. CONCLUSIONS: TLE is associated with extrahippocampal reductions of NAA/(Cr+Cho) in several lobes consistent with those brain areas involved in seizure spread. Temporal and extratemporal NAA/(Cr+Cho) reductions might be helpful for focus lateralization.

Adolescent↗

PubMed2004

Identification of the epileptogenic lobe in neocortical epilepsy with proton MR spectroscopic imaging.

PURPOSE: The aim of this study was to evaluate the usefulness of multislice magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation for the identification of the epileptogenic focus in neocortical epilepsy (NE). METHODS: Twenty patients with NE (10 with MRI-visible malformations, 10 with normal MRI) and 19 controls were studied. In controls, N-acetylaspartate NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter, and thresholds were determined by calculating the 95% prediction intervals (PIs) for NAA/Cr and NAA/Cho. Voxels with NAA/Cr or NAA/Cho values less than the 95% PI were defined as "pathological." Z-scores were calculated. Depending on the magnitude of those z-scores, we used two different methods (score-localization or forced-localization) to identify in a given subject the lobe with the highest percentage of pathological voxels, which was supposed to represent the epileptogenic lobe. RESULTS: MRSI correctly identified the lobe containing the epileptogenic focus as defined by EEG in 65% of the NE patients. MRSI localization of the focus was correct in 70% of the patients with an MRI-visible malformation and in 60% of the patients with normal MRI. Of the patients, 15% had metabolically abnormal brain regions outside the epileptogenic lobe, and 35% of the patients had evidence for secondary hippocampal damage. CONCLUSIONS: MRSI may be helpful for the identification of the epileptogenic focus in NE patients, even in NE with normal MRI.

Adolescent↗

PubMed2003

Ictal magnetoencephalography in temporal and extratemporal lobe epilepsy.

PURPOSE: We evaluated visual patterns and source localization of ictal magnetoencephalography (MEG) in patients with intractable temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETE). METHODS: We performed spike and seizure recording simultaneously with EEG and MEG on two patients with TLE and five patients with ETE. Scalp EEG was recorded from 21 channels (10-20 international system), whereas MEG was recorded from two 37-channel sensors. We compared ictal EEG and MEG onset, frequency, and evolution and performed MEG dipole source localization of interictal spikes and early ictal discharges and co-registered dipoles to brain magnetic resonance imaging (MRI). We correlated dipole characteristics with intracranial EEG, surgical resection, and outcome. RESULTS: Ictal MEG lateralized seizure onset in both TLE patients and demonstrated ictal onset, frequency, and evolution in accordance with EEG. Ictal MEG source analysis revealed tangential vertical dipoles in the anterolateral angle in one patient, and anterior dipoles with anteroposterior orientation in the other. Intracranial EEG revealed regional entorhinal seizure onset in the first patient. Both patients became seizure free after temporal lobectomy. In ETE, ictal MEG demonstrated visual patterns similar to ictal EEG and had concordant localization with interictal MEG in all five patients. Two patients underwent surgery. Ictal MEG localization was concordant with intracranial EEG in both cases. One patient had successful outcome after surgery. The second patient did not improve after limited resection and multiple subpial transections. CONCLUSIONS: Ictal MEG can demonstrate ictal onset frequency and evolution and provide useful localizing information before epilepsy surgery.

Electroencephalography↗

PubMed2003

Spectroscopic metabolic abnormalities in mTLE with and without MRI evidence for mesial temporal sclerosis using hippocampal short-TE MRSI.

PURPOSE: Long echo time (TE) spectroscopy reliably identifies the epileptogenic hippocampus in mesial temporal lobe epilepsy. Short-TE spectroscopy gives additional metabolic information but may have more artifacts. The aim of this study was to test (a) lateralization of the seizure focus by short-TE spectroscopy, and (b) value of myoinositol (MI) in the identification of the epileptogenic hippocampus. METHODS: Twenty-four patients with temporal lobe epilepsy: 16 with mesial temporal sclerosis (TLE-MTS), eight patients with normal magnetic resonance imaging (MRI; TLE-No), and 16 controls were studied with hippocampal 2D short-TE magnetic resonance spectroscopic imaging (MRSI). RESULTS: In TLE-MTS, the ipsilateral N-acetylaspartate (NAA) was decreased compared with contralateral (p = 0.03) or controls (p = 0.007). Additionally, the ipsilateral MI was decreased compared with controls (p = 0.012). TLE-No values showed no side differences and were not different from controls. Abnormalities in the anterior hippocampus correctly lateralized the epileptogenic hippocampus in </=82% of TLE-MTS and in </=80% of the TLE-No. CONCLUSIONS: The accuracy of short-TE MRSI at 1.5 T for focus lateralization in mTLE is comparable to that of long-TE MRSI. MI might be helpful for focus lateralization, but more information about the factors influencing the MI concentration is needed.

Adult↗

PubMed2003

Evidence of neuronal injury outside the medial temporal lobe in temporal lobe epilepsy: N-acetylaspartate concentration reductions detected with multisection proton MR spectroscopic imaging--initial experience.

PURPOSE: To determine whether magnetic resonance (MR) spectroscopic imaging reveals metabolic changes, especially decreased N-acetylaspartate (NAA) concentrations outside the medial temporal lobe in patients with mesial temporal lobe epilepsy (TLE), consistent with neuropathologic findings of extratemporal neuronal impairment. MATERIALS AND METHODS: Eleven patients with mesial TLE and 13 control subjects were examined with multisection MR spectroscopic imaging. Three MR spectroscopic imaging sections were acquired. Thirteen brain regions in each hemisphere and the midbrain were analyzed in each patient, and the NAA to creatine-phosphocreatine (Cr) plus choline-containing compounds (Ch) (NAA/[Cr + Ch]) ratios were determined. In addition, hemispheric and whole-brain values were calculated and statistically analyzed. RESULTS: The NAA/(Cr + Ch) ratio in the ipsilateral hippocampus was significantly reduced, compared with that in the contralateral hippocampus (P <.002) and compared with that in control subjects (P <.03), confirming findings in previous studies. In patients, whole-brain NAA/(Cr + Ch) ratio outside the hippocampus was significantly lower than that in control subjects (P <.002). For the ipsilateral hemisphere in patients, NAA/(Cr + Ch) ratio was significantly lower than that in control subjects (P <.0002). Comparisons between individual brain regions revealed trends toward lower NAA/(Cr + Ch) ratios in many areas of the ipsilateral and, to a lesser extent, the contralateral hemisphere outside the hippocampus and temporal lobe, suggesting diffuse impairment. CONCLUSION: Results suggest that repeated seizure activity damages neurons outside of the seizure focus.

Adult↗

PubMed2002

Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin.

OBJECTIVES: The acute effects of a single, low dose of phenytoin on behavioral and neurophysiological measures of cognitive function were examined in healthy adults. METHODS: Electroencephalograms (EEGs) were recorded from 7 healthy volunteers while they performed spatial working memory tasks and while they rested quietly. Behavioral measures, EEG power spectra, and event-related potentials (ERPs) were compared between separate sessions in which subjects ingested either 10mg/kg of phenytoin or placebo. RESULTS: Peak serum levels of phenytoin were in the low therapeutic range. Although participants reported subjective effects of the drug, task accuracy and response time were not affected. In the resting EEG, phenytoin decreased power in the alpha band. In the task-related EEG, the frontal midline theta signal was enhanced in response to increased task difficulty following placebo but not following phenytoin. An attention-related augmentation of the N160 ERP to matching stimuli was also reduced by phenytoin. CONCLUSIONS: Neurophysiological measures displayed sensitivity to subtle alterations in attentional processing even in response to a dose of phenytoin too low to produce behavioral impairment. Such results indicate that EEG and ERP measures can provide information about the neurocognitive side effects of medications that cannot be inferred from cognitive task performance measures alone.

Adult↗

PubMed2002

Reduced extrahippocampal NAA in mesial temporal lobe epilepsy.

PURPOSE: Structural and metabolic abnormalities in the hippocampal region in medial temporal lobe epilepsy (mTLE) are well described; less is known about extrahippocampal changes. This study was designed to characterize extrahippocampal metabolic abnormalities in mTLE with magnetic resonance spectroscopy in combination with tissue segmentation and volumetry of gray and white matter. METHODS: Multislice magnetic resonance spectroscopic imaging (1H-MRSI) in combination with tissue segmentation was performed on 16 patients with mTLE and 12 age-matched healthy volunteers. The data were analyzed by using a regression-analysis model that estimated the metabolite concentrations in 100% cortical gray and 100% white matter in the frontal lobe and nonfrontal brain. The segmented image was used to calculate the fraction of gray and white matter in these regions. RESULTS: mTLE had significantly lower N-acetyl aspartate (NAA) in ipsi- and contralateral frontal gray (p = 0.03) and in ipsi- and contralateral nonfrontal white matter (p = 0.008) compared with controls. Although there were no associated volumetric deficits in frontal gray and white matter, ipsilateral nonfrontal gray matter (p = 0.003) was significantly smaller than that in controls. CONCLUSIONS: mTLE is associated with extrahippocampal metabolic abnormalities and volumetric deficits, but these do not necessarily affect the same regions.

Adult↗

PubMed2002

Multisection proton MR spectroscopy for mesial temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Extensive metabolic impairments have been reported in association with mesial temporal lobe epilepsy (mTLE). We investigated whether proton MR spectroscopy ((1)H-MRS) depicts metabolic changes beyond the hippocampus in cases of mTLE and whether these changes help lateralize the seizure focus. METHODS: MR imaging and (1)H-MRS were performed in 15 patients with mTLE with a postoperative diagnosis of mesial temporal sclerosis and in 12 control volunteers. Point-resolved spectroscopy and multisection (1)H-MRS measured N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the hippocampus, temporal opercular and lateral cortices, insula and cerebellum, and frontal, parietal, and occipital lobes. Metabolites were assessed as ratios to Cr and in absolute units. RESULTS: Twelve patients had ipsilateral hippocampal atrophy; three had negative imaging results. In the ipsilateral hippocampus, absolute NAA (/NAA/) was 27.3% lower in patients compared with that in control volunteers (P <.001) and 18.5% lower compared with that in the contralateral side (P <.01). /NAA/ averaged over selected regions in the ipsilateral temporal lobes of patients with mTLE was 19.3% lower compared with the mean in the control group (P <.0001) and by 17.7% lower compared with the contralateral values (P <.00001). Using only hippocampal data, 60% of the cases of mTLE were correctly lateralized. Lateralization, determined using whole temporal lobe data, had 87% sensitivity and 92% specificity. /NAA/ was bilaterally reduced in the frontal, parietal, and occipital lobes of patients with mTLE compared with that in control volunteers (P <.01). CONCLUSION: Multisection (1)H-MRS depicts interictal reductions of NAA in the ipsilateral temporal lobe beyond the hippocampus and accurately lateralizes seizure foci.

Adult↗

PubMedDate not supplied

"Tectonic" hippocampal malformations in patients with temporal lobe epilepsy.

Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of the CA1 pyramidal cell/subicular layers that were consistently accompanied by "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus exhibited minor cell loss compared to hippocampi with typical hippocampal sclerosis, and retrospective analysis revealed that conventional imaging methods usually failed to detect subtle hippocampal atrophy or abnormal signal characteristics in patients with this anomaly. Cells within the anomaly exhibited the spherical appearance of undifferentiated pyramidal layer neurons, and were immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic marker beta-synuclein suggested abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly, but not in unaffected areas of the same specimens. Despite differences in the extent of neuronal loss between patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the incidence of antecedent febrile seizures was similar in both groups. In a comparison group of hippocampi obtained at autopsy, structural irregularities were evident, but were consistently less disruptive to hippocampal architecture than the anomalies observed in epilepsy patients. We hypothesize that developmental malformation of the CA1 pyramidal cell/subicular layers may adversely influence the subsequent development of the adjacent dentate gyrus, and may render temporal lobe structures hyperexcitable and more vulnerable to relatively innocuous seizures and injuries. Thus, these presumably developmental hippocampal anomalies may serve as substrates for early febrile seizures and subsequent epilepsy.

Adolescent↗

PubMedDate not supplied

Design and applications of a multimodality image data warehouse framework.

A comprehensive data warehouse framework is needed, which encompasses imaging and non-imaging information in supporting disease management and research. The authors propose such a framework, describe general design principles and system architecture, and illustrate a multimodality neuroimaging data warehouse system implemented for clinical epilepsy research. The data warehouse system is built on top of a picture archiving and communication system (PACS) environment and applies an iterative object-oriented analysis and design (OOAD) approach and recognized data interface and design standards. The implementation is based on a Java CORBA (Common Object Request Broker Architecture) and Web-based architecture that separates the graphical user interface presentation, data warehouse business services, data staging area, and backend source systems into distinct software layers. To illustrate the practicality of the data warehouse system, the authors describe two distinct biomedical applications--namely, clinical diagnostic workup of multimodality neuroimaging cases and research data analysis and decision threshold on seizure foci lateralization. The image data warehouse framework can be modified and generalized for new application domains.

Decision Making, Computer-Assisted↗