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K D Laxer

Publications and source records attributed to K D Laxer.

12 recordsLinked to original sources

Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging.

We attempted to lateralize the epileptogenic focus (seven temporal lobe hippocampal foci, one frontal lobe focus) in medically refractory unilateral complex partial seizures, using noninvasive 31P magnetic resonance spectroscopic imaging (MRSI) blindly and interictally to compare hippocampal or frontal regions. The seizure foci were more alkaline (intracellular pH = 7.17 +/- 0.03) compared with the contralateral region (7.06 +/- 0.02, p < 0.01) in all eight cases; the inorganic phosphate was relatively increased (240 +/- 50% of contralateral, seven of eight cases, p < 0.01); and phosphomonoesters were relatively reduced (68 +/- 9% of contralateral, seven of eight cases, p < 0.01). Other phosphorus metabolites were symmetric (+/- 10%). 31P MRSI correctly lateralized the seizure focus in all eight cases. By comparison, imaging correctly lateralized four cases and SPECT, two cases. In conclusion, 31P MRSI is a useful tool for the noninvasive clinical assessment of focal epilepsy and can accurately lateralize the epileptogenic focus.

Adult

Resection of dominant opercular gliosis in refractory partial epilepsy. Report of two cases.

Frontal opercular gliosis in the dominant hemisphere caused medically refractory partial epilepsy in two patients. Both patients were aphasic during their seizures, but otherwise had normal speech. Magnetic resonance images showed well-demarcated lesions resembling tumors in each patient; on heavily T2-weighted images, the lesions were hyperintense compared with normal brain. Cortical mapping with subdural grids localized speech to the area of the lesions; therefore, the resections were performed under local anesthesia and speech was tested throughout the procedure. Postoperatively, both patients were seizure-free and had no new neurological deficits. Well-demarcated lesions, even in the dominant operculum, can be safely removed in patients with medically refractory partial epilepsy.

Adolescent

Intractable complex partial seizure: correlation of magnetic resonance imaging with pathology and electroencephalography.

We prospectively analyzed MR studies of 32 patients with intractable complex partial seizures, who later underwent resection of EEG-proven seizure foci. Twenty-seven patients were imaged at 1.5, 4 at 0.35, and 1 at 0.5 Tesla. Correlation was obtained on all patients with EEG and surgical pathology. Of 19 patients with mesial temporal sclerosis (MTS), 13 exhibited an MR abnormality at the site of pathology as determined by EEG and surgery. Abnormalities included increased (8) or decreased (1) signal intensity, distortion of gray-white interface (1) and temporal lobe atrophy (3). Six patients had no abnormalities at the site of the diseased focus. MR was more sensitive in patients with other structural lesions which included tumor, encephalitis, polymicrogyria, cryptic vascular malformation, and tuberous sclerosis. Prior studies indicate some usefulness of MR in intractable seizure patients, but many report relative insensitivity of MR in defining an abnormality (as low as 11%). Our results demonstrate the usefulness of high-resolution thin-section multiplanar MR using cardiac gating or flow compensation techniques in this patient population.

Atrophy

Calcium-binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus.

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 papio), 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 CA2), 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. CaBP- and PV-LI were localized in hippocampi surgically removed in the treatment of intractable temporal lobe epilepsy to determine whether surviving hippocampal cells were those that express these calcium-binding proteins. Hippocampi removed from patients with tumors or arteriovenous malformations that were associated with complex partial seizures arising from this region appeared relatively normal histologically. CaBP- and PV-LI in this patient group appeared similar to that seen in autopsy controls. Conversely, "cryptogenic" epileptics, who exhibit hippocampal sclerosis as the only lesion associated with the epilepsy, exhibited a preferential survival of hippocampal cells that were CaBP- or PV-immunoreactive. In the dentate hilus, which normally contains few CaBP-LI neurons, most of the few surviving hilar neurons were CaBP-immunoreactive. Their number and darkness of staining suggests that CaBP synthesis may be increased in cells that survive. Despite an obvious decrease of PV-LI specifically in the damaged parts of the sclerotic hippocampi, PV-immunoreactive interneurons were often among the few surviving cells. Nevertheless, large expanses of the surviving granule cell layer appeared to have lost the PV-immunoreactive axosomatic fiber plexus. These results reveal a unique and striking correlation between the human hippocampal cells that normally express these calcium-binding proteins and those that survive in the sclerotic epileptic hippocampus.

Adult

The prognostic value of postoperative seizures following epilepsy surgery.

Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome.

Adolescent

Detection of epileptiform activity by different noninvasive EEG methods in complex partial epilepsy.

The diagnostic utility of different noninvasive electrode placements for deriving the electroencephalogram and detecting interictal epileptiform discharges was compared. Anterior temporal and nasopharyngeal electrodes in combination with routine scalp electrodes detected over 97% of the spikes, whereas recording from only standard electrode placements detected 58%. Minisphenoidal and surface sphenoidal electrodes were generally not helpful. In some circumstances, however, the use of surface sphenoidal electrodes provided important confirmatory information. In no case did the minisphenoidal electrodes provide unique information, and their use seems unjustified, although the inclusion of other nonstandard electrodes in the recording montage is important to increase the yield.

Adolescent

Monoamine metabolites in the CSF of epileptic patients.

To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.

Adolescent

Magnetic resonance imaging of intractable complex partial seizures: pathologic and electroencephalographic correlation.

Prior studies indicate variable usefulness of magnetic resonance imaging (MRI) in the evaluation of patients with complex partial seizures (CPS), but sensitivities as low as 12% have been reported. We analyzed the MRI examinations of 20 patients with medically refractory CPS who later underwent resection of the seizure focus proven by electroencephalography (EEG). MRI studies were correlated with surgical pathology in all patients. Eleven of the 20 CPS patients had mesial temporal sclerosis (MTS). Seven of the 11 (64%) exhibited an MRI abnormality at the site of the EEG-demonstrated histopathologic focus. MRI abnormalities included temporal lobe hypoplasia or atrophy (four patients), and increased signal intensity on long repetition time (TR) sequences (three patients). Four patients had no MRI abnormalities corresponding to the histopathologic focus. Nine of the 20 CPS patients had other abnormalities responsible for the seizures, including astrocytoma, cryptic vascular malformation, hamartoma, polymicrogyria, tuberous sclerosis (forme fruste), arachnoid cyst, and congenital hemiatrophy. No patient had normal MRI studies. Our single most useful MRI sequence was the coronal long TR/dual echo sequence, using cardiac gating and first-order gradient moment nulling to diminish flow-related artifacts that could hinder evaluation of medial temporal lobe structures.

Electroencephalography

Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures.

ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically- and electrically-induced seizures in animals. The primary objective of this open add-on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline.

Administration, Oral

Increased pH and inorganic phosphate in temporal seizure foci demonstrated by [31P]MRS.

To investigate alterations of brain metabolism associated with temporal lobe epilepsy, [31P]MRS studies were performed on the anterotemporal lobes of patients with medically refractory complex partial seizures. Interictally, the pH was significantly more alkaline in the temporal lobe ipsilateral to the seizure focus (7.25 vs. 7.08, p less than 0.05), and the inorganic phosphorous concentration was greater on the side of the epileptogenic focus (1.9 vs. 1.1 mM, p less than 0.05). These changes in pH and inorganic phosphate may represent metabolic alterations secondary to seizures. Alternatively, because alkalosis enhances neural excitability and may enhance seizure activity, the increased pH of the seizure focus may provide insight into the pathophysiologic mechanism of epileptic seizures.

Adolescent