Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In brains of the rabbit, pig, and human, expression of the high-affinity Na+-D-glucose cotransporter SGLT1 and of the protein RS1, which alters the activity of SGLT1, was demonstrated. In situ hybridization showed that SGLT1 and RS1 are transcribed in pyramidal cells of brain cortex and hippocampus and in Purkinje cells of cerebellum. In neurons of pig brain SGLT1 protein was demonstrated by western blotting with synaptosomal membranes and by immunohistochemistry, which showed SGLT1 in pyramidal and Purkinje cells. To test whether SGLT1 in neurons may be activated during increased D-glucose consumption, an epileptic seizure was induced in rat brain, and the uptake of specific nonmetabolized substrates of SGLT1 [[14C]methyl-alpha-D-glucopyranoside ([14C]AMG)] and of Na+-independent transporters [2-deoxy-D-[14C] glucose ([14C]2-DG)] was analyzed by autoradiography. During the seizure the uptake of AMG and 2-DG was increased in the focus. Within two hours after the seizure 2-DG uptake in the focus returned to normal. In contrast, the AMG uptake in the focus area was still increased 1 day later. The data show that the high-affinity Na+-D-glucose cotransporter SGLT1 is expressed in neurons and can be up-regulated.
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PMID:Expression of the Na+-D-glucose cotransporter SGLT1 in neurons. 920 97

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.
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PMID:Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy. 940 74

Successful surgical management of a neoplastic or nonneoplastic seizure focus in close proximity to or within eloquent brain areas relies on precise delineation of the relationship between the lesion and functional brain areas. The aim of this series was to validate the usefulness and test the efficacy of noninvasive presurgical PET mapping of eloquent brain areas to predict surgical morbidity and outcome in children with seizures. To identify eloquent brain areas in 15 children (6 female and 9 male; mean age 11 years) with epileptogenic lesions PET images of regional cerebral blood flow were performed following the administration of [(15)O]water during motor, visual, articulation, and receptive language tasks. These images with coregistered magnetic resonance (MR) images were then used to delineate the anatomic relationship of a seizure focus to eloquent brain areas. Additional PET images using [18F]fluoro-2-deoxy-D-glucose (FDG) and [11C]methionine (CMET) were acquired to help localize the seizure focus, as well as characterize the lesion. Patient surgical management decisions were based on PET mapping in combination with coregistered MR images, PET-FDG findings, and the anatomic characteristics of the lesion. At follow-up 1-26 months after surgery, all patients that underwent temporal lobectomy (9 patients) and extratemporal resection (4 patients) for a neoplastic or nonneoplastic seizure focus are seizure-free with minimal postoperative morbidity. Of prime importance, no child sustained a postoperative speech or language deficit. PET imaging was also well tolerated without procedural complications. Based on PET mapping, a nonoperative approach was used for 2 children and a biopsy only was used in one child. When cortical injury involved prenatally determined eloquent cortex, PET demonstrated reorganization of language areas to new adjacent areas or even to the contralateral hemisphere. Integration of anatomical and functional data enhanced the surgical safety, defined optimal surgical approach, delineated the seizure focus from eloquent brain areas, facilitated maximum resection and optimized the timing of surgery, thereby minimizing surgical morbidity while maximizing surgical goals. PET measurements of FDG and CMET uptake were also helpful in localizing the seizure focus and grading the tumors. PET used for brain mapping in children provides the surgeon with strategic preoperative information not readily attainable with traditional invasive Wada testing or intraoperative cortical stimulation. PET mapping may also improve the outcome of extratemporal resections by allowing aggressive seizure focus resection. In addition, serial brain maps may optimize timing for surgical intervention by demonstrating reorganization of eloquent cortex often seen in younger children after cortical injury. Our results suggest that noninvasive presurgical brain mapping has the potential to reduce risk and improve neurologic outcome.
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PMID:Use of positron emission tomography for presurgical localization of eloquent brain areas in children with seizures. 941 31

Landau-Kleffner syndrome (acquired epileptic aphasia) is characterized by language regression following normal acquisition of language skills, accompanied by epileptiform abnormalities on the electroencephalogram (EEG) with or without clinical seizures. Continuous spikes and waves during slow wave sleep may be seen on the EEG, but are not required to make the diagnosis. Structural neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI) is typically normal. We have evaluated 17 children (aged 2.4 to 10.6 yr) with Landau-Kleffner syndrome using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in order to determine whether there are metabolic abnormalities common to this syndrome. Patients were awake for the uptake period of FDG, and the EEG was monitored. On a visual analysis of the PET images, patients showed metabolic abnormalities in the temporal lobes. Two children had focal hypermetabolism in the left temporal cortex, one of whom also showed right temporal cortex hypometabolism. The remaining patients (n = 15) showed bilateral temporal hypometabolism, and comparison of these patients with a neurologically normal age-matched control group (n = 8) demonstrated significantly reduced glucose metabolism bilaterally in middle temporal gyrus (P < .02). In addition, other cortical regions displayed hypometabolism, although these regions were not consistently abnormal in all patients. The finding of temporal lobe abnormalities in all Landau-Kleffner syndrome patients suggests that temporal lobe structures are important in the pathophysiology of this syndrome, whereas the presence of additional cortical abnormalities in many patients indicates that extensive brain functional disturbances are common.
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PMID:Landau-Kleffner syndrome: metabolic abnormalities in temporal lobe are a common feature. 943 Mar 13

This study examined the presurgical 2-deoxy-2[18F]-fluoro-D-glucose positron emission tomography (PET) patterns of regional cerebral glucose metabolism in the non-resected hemisphere of 13 children who underwent hemispherectomy for early-onset intractable seizures. These patterns were compared with the rate of change in the children's non-verbal communication scores, measured before and after surgery. Irrespective of the side of surgery, the pre-operative glucose metabolism in the non-resected prefrontal cortex correlated significantly with the postoperative rate of change in the children's ability to focus the attention of an adult on an object or event (joint attention). These preliminary findings suggest that pre-operative PET patterns might be associated with certain aspects of the developmental outcome of children undergoing hemispherectomy.
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PMID:Hemispherectomy for intractable seizures: presurgical cerebral glucose metabolism and post-surgical non-verbal communication. 943 74

A 23-year-old male was referred to our hospital for evaluation of new-onset seizures. Signs and symptoms of neuroglycopenia, including weakness, dizziness, and confusion, appeared during fasting and resolved promptly with intravenous dextrose administration. Insulin, proinsulin, and C-peptide levels were consistent with a diagnosis of insulinoma. Screening tests for multiple endocrine neoplasia type 1 and surreptitious sulfonylurea uses were negative. Preoperative localization of the insulinoma by transabdominal ultrasonography, computed tomography, and indium-111 octreoscanning were unsuccessful. Endoscopic ultrasonography (EUS) identified a 6- to 7-mm tumor at the juncture of the head and body of the pancreas. Surgical exploration confirmed the preoperative localization, and an 8-mm tumor was simply enucleated. The patient has been free of symptoms for 18 months since surgery. This report describes the utility of EUS to localize a solitary pancreatic insulinoma and provides a comparison of EUS and other preoperative localization techniques.
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PMID:Endoscopic ultrasound localization of a pancreatic insulinoma: case report and review of the localization techniques. 986 68

Oral supplementation of 10 mmol/kg/day of D-ribose to a patient with an inherited deficit of adenylosuccinase, severe psychomotor retardation, and epilepsy caused a marked increase in plasma concentration and urinary excretion of urate, while minor changes in succinylpurine levels were observed. D-Ribose administration was accompanied by a slight improvement of behaviour and a progressive reduction of seizure frequency, which increased dramatically upon two attempts to withdraw the drug. Substitution of D-ribose with an equivalent amount of D-glucose did not result in an increase of seizure frequency.
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PMID:Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency. 998 53

We describe a five-week-old boy who had seizures and extreme hypernatraemia secondary to ingesting an improper home-made formula. Initial sodium concentration was 211 mmol.l-1. Other clinical and biological features were moderate dehydration and renal insufficiency with generous urine output and high urinary sodium concentration. Fluid therapy with hypotonic dextrose solution corrected the volume deficit in 48 h and progressively decreased the serum sodium concentration. During ICU stay the patient developed recurrent episodes of seizures and pulmonary oedema requiring mechanical ventilation for five days. Recovery was complete with no abnormal sequelae after a ten-month follow-up. Salt poisoning is in unusual cause of extreme hypernatraemia. It can be safely managed with fluid therapy alone if urine output is preserved, with progressive decrease of serum sodium as target. If this condition is recognized, outcome should be favourable.
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PMID:The management of extreme hypernatraemia secondary to salt poisoning in an infant. 1071 47

Therapeutic effect of the glucoside extracted from the root of Astragalus Membranaceus (AM) was studied in guinea pigs intoxicated with 600 mg/kg doses of Dimethoate (D). Four groups of guinea pigs, each consisting of two males and two females, were treated with (a) D, (b) D + Atropine, and (c) D + AM, (d) D + Atropine + AM. The survival time of the animals increased from an average of 70 minutes without AM to an average of 235 minutes with AM. Severe changes in ECG were observed prior to respiratory distress in groups without AM, and Atropine did not modify such changes. Differently, severe ECG disorders appeared only after respiratory distress in groups treated with AM. Prolongation of the Q-T interval and changing of the T wave configuration were significantly mitigated in the AM treated animals, while, arrhythmias were minimized and postponed. Moreover, muscular fasciculation and fibrillation, seizures and secretion in the respiratory tract were also significantly reduced by AM treatment. Results have shown that AM could be a promising drug to be used after cholinergic crisis in the treatment of cardiac complications with severe organophosphate intoxication.
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PMID:Antidotal effect of glucoside extracted from Astragalus membranaceus on dimethoate intoxication in guinea pigs. 1021 35

Nipecotic acid (1), one of the most potent in vitro inhibitors of neuronal and glial gamma-amino butyric acid (GABA) uptake, is inactive as an anticonvulsant when administered systemically. To obtain in vivo active prodrugs of (1), we synthesized four new nipecotic acid esters (3-6), which were obtained by chemical conjugation with glucose, galactose, and tyrosine. These compounds were assayed to evaluate their in vitro chemical and enzymatic hydrolysis. In addition, their anticonvulsant activity was evaluated in vivo in Diluted Brown Agouti (DBA)/2 mice, an excellent animal model for the study of new anticonvulsant drugs. Esters (3-6) appeared stable, at various temperatures, in a pH 7.4 buffered solution and showed susceptibility to undergoing in vitro enzymatic hydrolysis. Intraperitoneally injected nipecotic acid (1) and esters (3-5) did not protect mice against audiogenic seizures; conversely, nipecotic tyrosine ester (6) showed a significant dose-dependent anticonvulsant activity. The in vivo protective activity of the ester (6) and the inefficiency of nipecotic acid (1) in the same experimental conditions suggest that this ester prodrug could be actively transported intact across the blood-brain barrier, beyond which it could be hydrolyzed.
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PMID:Synthesis, stability, and pharmacological evaluation of nipecotic acid prodrugs. 1022 50


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