Kenneth Laxer - Academia.edu (original) (raw)

Papers by Kenneth Laxer

Epilepsia, Jan 30, 2018

To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients ... more To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57...

Epilepsia, Jan 19, 2015

Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-ele... more Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal a...

NeuroImage. Clinical, 2014

The symptoms witnessed in unexplained death in epilepsy (SUDEP) suggest a breakdown of central au... more The symptoms witnessed in unexplained death in epilepsy (SUDEP) suggest a breakdown of central autonomic control. Since the brainstem plays a crucial role in autonomic control, the objectives of this study were 1. To investigate if temporal lobe epilepsy (TLE) is associated with brainstem atrophy and to characterize it using graph Analysis 2. To compare the findings with those in two probable TLESUDEP. T1 images were obtained from 17 controls, 30 TLE (16 with mesial-temporal-sclerosis (TLE-MTS) and 14 without (TLE-no)) and from 2 patients who died of SUDEP. The brainstem was extracted, warped onto a brainstem atlas and Jacobian determinants maps (JDM) calculated. SPM8 was used to compare the JDMs at the group level, z-score maps were calculated for single subject analysis. Brainstem regions encompassing autonomic structures were identified based on macroscopic landmarks and mean z-scores from 5 × 5 × 5 voxel cubes extracted to calculate a new measure called atrophy-similarity index ...

$Research paper thumbnail of High-resolution surface-coil MR of cortical lesions in medically refractory epilepsy: a prospective study$

AJNR. American journal of neuroradiology, 1997

To determine the role of surface-coil MR imaging in evaluating medically refractory neocortical p... more To determine the role of surface-coil MR imaging in evaluating medically refractory neocortical partial epilepsy. A prospective study of 25 patients with medically refractory neocortical partial epilepsy was performed. Head- and surface-coil images were reviewed by two neuroradiologists to determine the clarity with which cortical lesions were depicted. The ability of imaging, combined with surface electroencephalography (EEG), to locate the suspected epileptogenic zone was evaluated. Compared with head-coil studies, surface-coil studies showed four more lesions, caused the most probable diagnosis to be altered in five patients, and better defined the lesions in four patients. Of 11 patients with lobar EEG abnormalities, imaging showed focal cortical abnormalities within the same or adjacent lobe in five and multifocal abnormalities in two. Of six patients with EEG abnormalities restricted to two adjacent lobes, imaging showed focal cortical abnormalities in one of these lobes in fi...

Radiology, 1997

To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lat... more To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lateralizing the seizure focus in patients who have temporal lobe epilepsy with and in those without hippocampal atrophy on MR images, the extent of contralateral abnormalities, and whether there is a correlation between MR spectroscopic imaging findings and surgical outcome. MR spectroscopic imaging was performed in 16 adult patients with temporal lobe epilepsy and unilateral electroencephalographic findings and in 16 adult control subjects. Eleven patients underwent surgery; all patients underwent MR imaging. Nine patients had hippocampal atrophy on MR images. An ipsilateral decrease in the N-acetylaspartate concentration or the ratio of N-acetylaspartate to the sum of creatine and choline (N-acetylaspartate/ [creatine + choline]) was found in all patients. Decreased contralateral N-acetylaspartate concentration, N-acetylaspartate/(creatine + choline), or N-acetylaspartate concentration a...

Advances in experimental medicine and biology, 2006

Considerable evidence suggests that normal aging is associated with gradual impairment of memory ... more Considerable evidence suggests that normal aging is associated with gradual impairment of memory functioning . The medial temporal lobe, especially the hippocampus, plays a central role in declarative memory processing . However, magnetic resonance imaging (MRI) studies have produced controversial results concerning the age-related hippocampal volume loss, which could be due in part to the non-specificity of volume shrinkage as an indicator for neuron loss. In contrast to volume, NAA is generally considered a marker for viable neurons, because NAA reaches detectable concentrations only in neuronal tissue but not in other brain tissues, including glial cells. Using proton magnetic resonance spectroscopic imaging ( 1 H MRSI) and MRI together, we studied hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. Our goals were to test whether NAA levels vary in the hippocampus as a function of normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. We found NAA/Cho ratios decreased by 24% (r = −0.53, p = 0.01) and NAA/Cr ratios decreased by 26% (r = −0.61, p < 0.005) over the age range studied, while Cho/Cr remained stable, implying diminished NAA levels. In the same population, hippocampal volume shrank by 20% (r = −0.64, p < 0.05). The relationships of these measures with aging are depicted in . Since NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.

AJNR. American journal of neuroradiology, 2002

Extensive metabolic impairments have been reported in association with mesial temporal lobe epile... more 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. 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. 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% l...

Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 1994

previous studies suggest that €vidence for the sub-second activation of distdbuted neunl networks... more previous studies suggest that €vidence for the sub-second activation of distdbuted neunl networks can be obtained by computing the cova ance between segments of the scalp-recorded evoked potential. However, the co ical representation of such potentials is not Loo"n. Her" o," repo a case study where the evok;d potential covariance (EPC) measure was applied to data recorded from a 58-channel subdural g d implanted in an epilepsy patient. Recordings were made while the patient perform€d a task that required judging the somatosen-sory iniensities oI electrical stimuli and executing precise finger flexion responses in response to a subset of those stimuli' post-stimulus EpC patterns involved covariances between somatosensory, motor, and ternporal regions Pre-stimulus EPC pattems involved these same regions, but only when it could be anticipated that the upcoming stimulus would likely lequire a lesponse. The majority of the observed EpCs oc;ufied with rron-zero timelags, and these EPCs often involved non-adjacent electrode pahs. Thus, the obs€rved EPCa were unlikely to arise solely ftom volume conduction. Rather, they appeared to rcflect the transient integration of activity across distinct coltical prccessing nodes,

Electroencephalography and Clinical Neurophysiology, 1996

NeuroImage, 2010

Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe ... more Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole brain networks from volumetric data and obtain network-centric measures which can capture cortical thinning characteristic for TLE and can be used for classifying a given MRI into TLE or normal, and to obtain additional summary statistics which relate to the extent and spread of the disease. T1 weighted whole brain images were acquired on a 4T magnet in 13 patients with TLE with mesial temporal lobe sclerosis (TLE-MTS), 14 patients with TLE with normal MRI (TLE-no) and 30 controls. Mean cortical thickness and curvature measurements were obtained using the Freesurfer software. These values were used to derive a graph, or network, for each subject. The nodes of the graph are brain regions, and edges represent disease progression paths. We show how to obtain summary statistics like mean, median and variance defined for these networks and to perform exploratory analyses like correlation and classification. Our results indicate that the proposed network approach can improve accuracy of classifying subjects into 2 groups (control and TLE), from 78% for non-network classifiers to 93% using the proposed approach. We also obtain network "peakiness" values using statistical measures like entropy and complexity -this appears to be a good characterizer of the disease, and may have utility in surgical planning.

Magnetic Resonance Imaging, 1995

Functional and anatomical neuroimaging has had a dramatic effect on the evaluation of patients fo... more Functional and anatomical neuroimaging has had a dramatic effect on the evaluation of patients for seizure surgery. The demonstration by PET that the epileptogenic focus has interictal metabolic abnormalities has allowed a greater number of patients to come to seizure surgery, with fewer of these patients requiring intracranial electrode evaluations. Metabolic changes have also been demonstrated utilizing single voxel and whole brain 'II and slP MRS imaging techniques with the inter&al focus characterized by increased Pi, pH, and decreased PME and NAA. These findings can be used to accurately lateralize temporal lobe as well as frontal lobe epilepsy. Furthermore, there is evidence that these findings can be used to localize the seizure focus with the changes specific for tbe epileptogenic region; although, more diffuse changes both ipsilaterally and contralaterally have been seen. In patients with anterior hippocampal seizure foci the pH is significantly alkaline only in the ipsilateral hippocampus, whereas the increased Pi and decreased PME can be seen throughout the ipsilateral temporal lobe. When compared to controls the contralateral hemisphere is acidotic. Decreased NAA concentrations as well as NAA/Cr ratios have been demonstrated in the epileptogenic region in temporal and frontal lobe epilepsy. The decreased NAA has been correlated with the severity of cell loss, and may be a more sensitive measure than qualitative or quantitative measures of the hippocampal atrophy; however, the NAA decrease is more widespread than just the epileptogenic focus but may be maximal at the site of seizure initiation. In preliminary work, NAA maps of deviation from normality have suggested the maximal change to coincide with the epileptogenic region. These results suggest that in focal epilepsy there is abnormal metabolic activity throughout the brain detectable by MRS, with patterns of metabolic asymmetry that are useful for seizure localization.

Journal of Neurosurgery, 1993

Corpus callosotomy is valuable for controlling medically intractable generalized seizures in appr... more Corpus callosotomy is valuable for controlling medically intractable generalized seizures in appropriate patients, but postoperative development of language disorders, neuropsychological impairment, and motor dysfunction have all been noted. The extent of callosum resection has been implicated as a possible determinant of outcome, but this hypothesis has not been formally tested. Analysis of the records of all patients who underwent corpus callosotomy at the University of California, San Francisco, from 1986 to 1991 showed that, of 15 patients who underwent anterior or complete callosotomy, seven were entirely or nearly seizure-free, four had at least a 50% reduction in seizure frequency, and four had no change. To determine callosal size and extent of callosotomy, preoperative and postoperative magnetic resonance images were measured with computer-based planimetry. Seizure outcome was not significantly associated with preoperative callosal size or extent of callosotomy. Intelligence quotient scores did not change significantly after callosotomy. No severe neuropsychological deficits developed after anterior or complete callosotomy, even in patients with mixed cerebral dominance or bilateral language representation. These results indicate that division of the anterior one-half to two-thirds of the corpus callosum is nearly as effective as more extensive anterior sectioning or complete callosotomy in reducing drop-attack and generalized tonic-clonic seizures in appropriate patients, and that the extent of callosotomy is not an important factor on outcome when at least 50% to 65% of the callosum is divided. Mixed cerebral dominance and other unusual patterns of language and memory organization do not appear to increase the postoperative risk for neuropsychological deficits, regardless of the extent of anterior section.

Journal of Neurology, 2011

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr?Cho) reductions in medial temporal lobe... more MR spectroscopy has demonstrated extrahippocampal NAA/(Cr?Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/ (Cr?Cho) reductions? (2) Do extrahippocampal NAA/ (Cr?Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr?Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr?Cho) reductions. NAA/(Cr?Cho) reductions had a bilateral frontotemporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr?Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr?Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE.

Journal of Neurology, 2005

Purpose-Cortical malformations (CMs) are increasingly recognized as the epileptogenic substrate i... more Purpose-Cortical malformations (CMs) are increasingly recognized as the epileptogenic substrate in patients with medically refractory neocortical epilepsy (NE). The aim of this study was to test the hypotheses that: 1. CMs are metabolically heterogeneous. 2. The structurally normal appearing perilesional zone is characterized by similar metabolic abnormalities as the CM.

Journal of Neuroimmunology, 2002

Chronic focal encephalitis (CFE) generally presents with seizures that increase in severity and f... more Chronic focal encephalitis (CFE) generally presents with seizures that increase in severity and frequency as the disease progresses. Malfunction of synaptic transmission through altered glutamate signaling has been proposed as a likely mechanism triggering CFE. In addition, profuse inflammation is commonly seen in histopathological examination of resected tissue. To further explore the roles of glutamatergic activity and inflammation in this disease, we examined the expression of 52 genes by real time RT-PCR (kinetic RT-PCR or kRT-PCR) in a brain specimen from a CFE patient with active seizures, eight control specimens from patients with several other neurologic disorders, and two from individuals with no recorded history of neurological abnormalities. The CFE specimen displayed a dramatic increase in the expression of several inflammation-related genes (i.e. IL1h, IgVH, and IL2Rg among others) and a striking down-regulation of several GluRs, in particular mGluR4. This type of analysis may prove useful in describing the molecular events underlying intractable epilepsy. D

The Journal of Comparative Neurology, 1991

The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "no... more The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "normal" and "epileptic" human hippocampus to address the possible relationship between the expression of these constitutive cytosolic calcium-binding proteins and the resistance or selective vulnerability of different hippocampal neuron populations in temporal lobe epilepsy. Compared to rodents and a baboon (Papio pupzo), the pattern of CaBP-like immunoreactivity (LI) in the "normal" human hippocampus is unique. CaBP-LI is present in the dentate granule cells, neurons of the "resistant zone" (area CAZ), and presumed interneurons of all regions. Unlike rodent and baboon CA1 pyramidal cells, human CA1 pyramidal cells appear to be devoid of CaBP-LI. Thus, the relatively resistant dentate granule cells and CA2 pyramidal cells are the only human hippocampal principal cells that contain CaBP-LI normally. As in lower mammals, PV-LI is present exclusively in interneurons of all human hippocampal subregions.

Human Brain Mapping, 1994

Subsecond temporal resolution is necessary to resolve the changes in brain activity that are asso... more Subsecond temporal resolution is necessary to resolve the changes in brain activity that are associated with task-related cognitive processes, Evoked potentials (EPs) provide the requisite millisecondrange temporal resolution, and do so with nonencumbering recordings at a reasonably low cost. These features would seem to make EPs the ideal complement to structural and functional magnetic resonance images (MRIs) and positron emission tomography (PET). However, until recently, the utility of EPs has been limited by their poor spatial resolution. Sufficient spatial correspondence has not existed between EPs and other brain imaging modalities to determine unambiguously the relationship between a sequence of EP components and structures visualized by MRI or PET. We describe progress that has been made toward overcoming this obstacle by registering electrophysiological data with anatomical information from each subject's MRI, by improving the spatial resolution of the EP, and by using analytic methods for measuring the spatiotemporal dynamics of distributed neurocognitive processes. The use of these techniques is illustrated by reviewing several experiments in which sequences of component neural processes were measured during cognitive tasks. D

Epilepsy Research, 2004

Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe ep... more 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 ␤-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.

Epilepsia, 2004

Purpose-The aim of this study was to evaluate the usefulness of multislice magnetic resonance spe... more 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).

Epilepsia, 1997

Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients with epilepsy, dem... more Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients with epilepsy, demonstrating abnormalities of energy and lipid metabolism ictally and, more recently, interictally. These metabolic abnormalities include increased inorganic phosphate, pH, and decreased phosphomonoesters as determined by 31P MRS, as well as decreased N-acetylaspartate determined by 1H MRS. Furthermore, increased lactic acid has been detected postictally. These metabolic changes appear to be confined to the region of seizure origination and can be detected interictally. Therefore, they can be used for lateralization of the epileptogenic focus. Ongoing research suggests that these abnormalities may also be useful in localization of the focus, demonstrating metabolic alterations in temporal lobe epilepsy (TLE) similar to those in neocortical epilepsy. However, further technical development will be required before the goal of using these techniques for localization of the epileptogenic focus can be realized. For TLE lobe epilepsy at least, the clinical utility of 1H MRS to lateralize the seizure focus has clearly been demonstrated by several centers. The consistent findings in TLE suggest that 1H MRS is ready to become part of the evaluation process of patients with medically refractory epilepsy being evaluated for seizure surgery.