bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions
Authors: VanLandingham Kevan E , Heinz E. Ralph , Cavazos Jose E. , Lewis Darrell V. 
Published: January 2005

AbstractMagnetic resonance imaging (MRI) was performed after complex febrile convulsion (CFCs) in 27 infants. Definite MRI abnormalities were seen in 6 of the 15 infants with focal or lateralized CFCs and in none of the 12 infants with generalized CFCs. In 2 of the 6 infants with lateralized CFCs and abnormal MRIs, the MR images showed preexisting bilateral hippocampal atrophy consistent with the history of perinatal insults in these infants. However, the remaining 4 infants with MRI abnormalities and lateralized CFCs had significantly longer seizures than other infants and had MRI changes suggesting acute edema with increased hippocampal T2‐weighted signal intensity and increased volume predominantly in the hippocampus in the hemisphere of seizure origin. Of those with acute edema, 1 had electrographical seizure activity recorded in the temporal region and another had a choroid fissure cyst displacing the affected hippocampus; both infants had follow‐up MRIs showing that hippocampal atrophy had developed. These patients demonstrate that prolonged and focal CFCs can occasionally produce acute hippocampal injury that evolves to hippocampal atrophy. Finally, evidence of preexisting hippocampal abnormalities in several infants and electrographical temporal lobe seizure activity in 1 suggests the possibility that CFCs actually originated in the temporal lobes in some patients.
Valproate, lamotrigine, and insulin‐mediated risks in women with epilepsy
Authors: Isojärvi Jouko I. T. , Rättyä Johanna , Myllylä Vilho V. , Knip Mikael , Koivunen Riitta , Pakarinen Arto J. , Tekay Aydin , Tapanainen Juha S. 
Published: January 2005

AbstractWe recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate‐induced hyperinsulinemia and their reversibility after discontinuing the medication. Sixteen women with valproate‐related polycystic ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was substituted for valproate and the patients were observed for 12 months. Twenty‐four healthy age‐matched women served as control subjects. Twelve women completed the 12‐month follow‐up. While still on valproate they had centripetal obesity with associated hyper insulinemia and unfavorable serum lipid profiles. The body‐mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL‐cholesterol/total cholesterol ratios increased from 0.17 ± 0.06 to 0.26 ± 0.05. The total number of polycystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripetal obesity, hyperinsulinemia lipid abnormalities, and polycystic ovaries/hyperandrogenism in women with epilepsy. These valproate‐related risks can be reduced by substituting lamotrigine for valproate.
A permanent pure amnestic syndrome of insidious onset related to Alzheimer's disease
Authors: Didic M. , Chérif A. Ali , Gambarelli D. , Poncet M. , Boudouresques J. 
Published: January 2005

AbstractA 55‐year‐old patient experienced a pure amnestic syndrome of insidious onset that worsened progressively. Subsequently, her memory disorder stablized and remained her only cognitive impairment for several years. She ultimately developed more widespread cognitive decline and terminal dementia. Postmortem examination 18 years after the onset revealed numerous senile plaques and neurofibrillary tangles consistent with Alzheimer's disease. A permanent pure amnestic syndrome of insidious onset may represent a further type of focal cerebral degeneration.
Neurotrophin‐4 is up‐regulated in ragged‐red fibers associated with pathogenic mitochondrial DNA mutations
Authors: Walker Ulrich A. , Schon Eric A. 
Published: January 2005

AbstractRagged‐red fibers (RRFs) are found more frequently in highly oxidative type I fibers than in glycolytic type II fibers in the muscle of many patients with mitochondrial myopathies. Neurotrophin‐4 (NT‐4), a neuronal signaling molecule, is also expressed in skeletal muscle, predominantly in type I fibers. We found that NT‐4 protein and mRNA were present in both type I and type II fibers but were up‐regulated in RRFs of patients with mitochondrial encephalomyopathies; it is noteworthy that NT‐4 was not up‐regulated in muscle fibers from healthy aerobically trained athletes. Thus, NT‐4 might represent a member of a new class of candidate molecules involved in the compensatory adjustments of muscle fibers to oxidative dysfunction, and may even play a role as a signaling molecule for mitochondrial proliferation.
Very long chain acyl‐coenzyme A dehydrogenase deficiency with adult onset
Authors: Smelt A. H. M. , Poorthuis B. J. H. M. , Onkenhout W. , Scholte H. R. , Andresen B. S. , van Duinen S. G. , Gregersen N. , Wintzen A. R. 
Published: January 2005

AbstractVery long chain acyl‐coenzyme A (acyl‐CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial β‐oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified stongly elevated levels of tetradecenoic acid, 14:1(n‐9), tetradecadienoic acid, 14:2(n‐6), and hexadecadienoic acid, 16:2(n‐6). Palmitoyl‐CoA and behenoyl‐CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L‐carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis.
Fibroblast growth factor‐2/brain‐derived neurotrophic factor—associated maturation of new neurons generated from adult human subependymal cells
Authors: Pincus David W. , Keyoung H. Michael , Harrison‐Restelli Catherine , Goodman Robert R. , Fraser Richard A. R. , Edgar Mark , Sakakibara Shin‐Ichi , Okano Hideyuki , Nedergaard Maiken , Goldman Steven A. 
Published: January 2005

AbstractThe adult mammalian forebrain harbors neuronal precursor cells in the subependymal zone (SZ). Neuronal progenitors also persist in the adult human SZ and have been cultured from epileptic temporal lobe. In the present study, we sought to identify these neural progenitors in situ, and to direct their expansion and neuronal differentiation in vitro. We prepared explants of adult human SZ, obtained from temporal lobe resections of refractory epileptics. The resultant cultures were treated with fibroblast growth factor‐2 (FGF–2) for a week, with concurrent exposure to [3H] thymidine, then switched to media containing brain‐derived neurotrophic factor (BDNF) for up to 2 months. Sporadic neuronal outgrowth, verified antigenically and physiologically, was observed from SZ cultures regardless of FGF‐2/BDNF treatment; however, only FGF‐2/BDNF–treated cultures exhibited profuse outgrowth, and these displayed neuronal survival as long as 9 weeks in vitro. In addition, cortical cultures derived from two brains generated microtubule‐associated protein‐2+ neurons, which incorporated [3H]thymidine and exhibited significant calcium increments to depolarization. In histological sections of the subependyma, both uncommitted and restricted progenitors, defined respectively by musashi and Hu protein expression, were identified. Thus, the adult human subependyma harbors neural progenitors, which are able to give rise to neurons whose numbers can be supported for prolonged periods in vitro.
Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis
Authors: Aoki Masashi , Lin Chien‐Liang G. , Rothstein Jeffrey D. , Geller Brian A. , Hosler Besty A. , Munsat Theodore L. , Horvitz H. Robert , Brown Robert H. 
Published: January 2005

AbstractRecently, variant mRNA transcripts for the astroglial glutamate transporter EAAT2 have been detected in brain tissues of 60% of patients with sporadic amyotrophic lateral sclerosis (SALS). We have tested the hypothesis that the gene for EAAT2 may be defective in some ALS cases. In 16 familial ALS (FALS) pedigrees without mutations in SODI, we failed to detect genetic linkage to the EAAT2 locus. We next characterized the genomic organization of the EAAT2 gene and used single‐strad conformation polymorphism analysis of genomic DNA to identify one novel mutation in a single SALS patient and two novel mutations in 2 affected FALS siblings. In the SALS patient, the mutation substitutes serine for an asparagine that might be involved in N‐linked glycosylation of the EAAT2 protein. In the 2 affected individuals in the FALS family, we detected both a mutation in the 5′ end of intron 7 and a silent G→A transition at codon 234 in exon 5. It remains unclear whether this intron 7 mutation is related to the defective mRNA splicing. These studies indicate that germline mutations in the EAAT2 gene are infrequent and do not explain the presence of variant mRNA transcripts of EAAT2 in more than one‐half of ALS cases.
Dejerine‐sottas neuropathy and PMP22 point mutations: A new base pair substitution and a possible “hot spot” on Ser72
Authors: Marques Wilson , Thomas P. K. , Sweeney Mary G. , Carr Lucinda , Wood Nicholas W. 
Published: January 2005

AbstractThe occurrence of mutations in peripheral myelin protein 22 is one of the genetic mechanisms associated with Dejerine‐Sottas neuropathy (DSN). On direct sequencing 2 of such patients we have found the first mutation in the third transmembrane domain associated with this neuropathy and the fourth Ser72Leu. We Propose that the Ser72 may be a “hot spot” for DSN and that this should be considered for molecular analysis.
Neurological manifestations of falciparum malaria
Authors: Newton Charles R. J. C. , Warrell David A. 
Published: January 2005

AbstractPlasmodium falciparum remains one of the most common causes of central nervous system infection worldwide. Recently, differences between the pathophysiology of cerebral malaria in African children and nonimmune adults have been discovered, new syndromes occurring after malaria infection described, and mechanisms for the pathogenesis proposed. In addition, new antimalarial agents have been examined worldwide and initial studies on supportive studies conducted. This paper reviews these new advances, putting them into the perspective of the more established knowledge.
Serotonin inhibits trigeminal nucleus activity evoked by craniovascular stimulation through a 5ht 1b/1D receptor: A central action in migraine?
Authors: Goadsby Peter J. , Hoskin Karen L. 
Published: January 2005

AbstractThe development of serotonin (5HT1B/1D) agonists as treatments for the acute of migraine has resulted in considerable interest in their mechanism of action and, to some extent, renewed interest in the role of serotonin (5‐hydroxytrypatmine; 5HT) in the disorder. The initial synthesis of this class of compounds was predicated on the clinical observation that intravenous 5HT terminated acute attacks of migraine. In this study the superior sagittal sinus was isolated in the α‐chloralose (60mg/kg IP and 20 mg/kg IV injection supplementary 2 hourly) anesthetized cat. The sinus was stimulated electrically (120V, 250 °sec duration, 0.3 Hz), and neurons of the trigeminocervical complex in the dorsal C2 spinal cord were monitored using electrophysiological methods. After baseline recordings in each animal, 5HT (15 μg/kg/min) was infused for 5 minutes in the presence of either vehicle (group A) or the 5HT 1B/1D antagonist GR127935 (100 μg/kg IV injection; group B). The baseline probability of cell firing after sagittal sinus stimulation was 0.61 ± 0.1 at a latency to the fastest peak of 11.1 ± 0.4 msec. In group A, 5HT infusion alone had a small effect of increasing mean blood pressure (12 ± 3 mm Hg), which in itself did not alter cell firing. In group A, 5HT alone had an inhibitory effect on evoked trigeminal activity, which developed 15 to 20 minutes after commencement of the infusion. The inhibition of cell firing lasted for 20 minutes, after which the activity returned to baseline. In group B, the combination of 5HT and GRI127935 had no effect on trigeminal cell firing, although the small hypertensive effect was still present. These data indicate that 5HT inhibits evoked trigeminal nucleus firing via the 5HT 1B/1D receptor at which GRI127935 is an antagonist. It is likely that some part of the effect of 5HT in migraine relates to inhibition of trigeminal nucleus activity, just as it is likely that some part of the effect of the triptans is also mediated at this central site and may be complementary to their nonneuronal actions. Moreover, the data highlight the case for describing this class of headache as neurovascular headaches rather than vascular headaches, to recognize the implicit contribution of the trigeminovascular system to their pathophysiology.
Magnetization transfer changes in the normal appering white matter precede the appearance of enhancing lesions in patients with multiple sclerosis
Authors: Filippi Massimo , Rocca Maria A. , Martino Gianvito , Horsfield Mark A. , Comi Giancarlo 
Published: January 2005

AbstractSerial monthly magenetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing‐remitting MS were scanned with a T1‐weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium‐DTPA (Gd‐DTPA). During each of the monthy sessions, MT and dual dual echo scans were also performed before Gd‐DTPA injection. On coregistered images, the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their apperance. Forty‐eight new enhancing lesions with no corressponding abnormalities, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions becomes evident on conventional MRI scans.
Surgical outcome in occipital lobe epilepsy: Implications for pathophysiology
Authors: Aykut‐Bingol Canan , Bronen Richard A. , Kim Jung H. , Spencer Dennis D. , Spencer Susan S. 
Published: January 2005

AbstractMedically refractory occipital lobe epilepsies are increasingly treated with surgery, but outcome and its relationship to etiology, pathological substrate, occipital lobe location, surgical approach, and electroclinical features have not been systematically investigated in a substantial group of patients. Thirty‐five patients who underwent surgery for intractable occipital lobe seizures were retrospectively evaluated. Outcome and occipital lobe location were analyzed with respect to surgical procedure, pathology, clinical seizure characteristics, seizure onset and termination locations, and localization of interictal spikes. Most patients had developmental abnormalities (14) or tumors (13, all gliomas). Developmental abnormalities consisted of focal cortical dysplasia (5), heterotopia (2), hamartoma (3), cortical duplication (1), polymicrogyria (1), Sturge‐Weber syndrome (1), and tuberous sclerosis(1). There was 1 patient with a vascular abnormality, 1 with chronic inflammatory changes, 4 with gliosis, 1 with cerebral ossification, and 1 with normal pathology. Developmental abnormalities had significantly worse outcome (45% excellent/good) than tumors (85% excellent/good). In the developmental group, low‐grade focal cortical dysplasias had better outcome than heterotopia and hamartoma regardless of type of surgical procedure. Pathological groups did not significantly differ with respect to location within the occipital lobe (overall medial [50%] or lateral [38%]); clinical seizure characteristics referable to specific lobe (occipital [14%], temporal [34%], frontal [23%], more than one type [29%]); electroencephalographic localization (to occipital [17%], temporal [27%], or other/multifocal locations [56%]); or intracranial ictal onset or termination location. Electroclinical variables were also unrelated to the occipital lobe location of abnormality. Surgical outcome was not predicted by surgical approach (lesion excision with margins or lobectomy). The main pathological substrates of uncontrolled occipital lobe epilepsy are gliomas and developmental abnormalities. Whereas resection of occipital lobe tumors associated with chronic epilepsy produces nearly uniform seizure control, outcome after resection of occipital lobe developmental abnormalities is less uniform.
Multiple sclerosis: The increased frequency of the ICAM‐1 exon 6 gene point mutation genetic type K469
Authors: Mycko Marcin P. , Kwinkowski Marek , Tronczynska Ewa , Szymanska Bozena , Selmaj Krzysztof W. 
Published: January 2005

AbstractIntracellular adhesion molecule‐1 (ICAM‐1) plays an important role in the cascade of adhesion events in the homing of inflammatory cells to the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Two single‐base ICAM‐1 polymorphisms have been described, in exons 4 and 6, changing codons 241 and 469 in the ICAM‐1 gene, respectively. Both polymorphisms result in amino acid changes and can potentially lead to different interactions of ICAM‐1 with its ligands. To detect ICAM‐1 gene polymorphisms in MS, we have developed a highly sensitive and site‐specific, two‐stage, nested polymerase chain reaction. Genomic DNA was extracted from blood cells of 79 MS patients and 68 control subjects. The results were confirmed by direct dideoxy chain termination sequencing. The frequency of exon 6 allele T was found to be significantly higher in MS patients than in controls (68% vs 49%). Most interesting, the frequency of exon 6 homozygote K469 was significantly higher in MS patients than in controls (53% vs 34%). Higher frequency of the K469 genotype was found to be independent of possible linkage with the previously described MS susceptibility factor, the HLA class II DR2 allele. In the present study, we have shown for the first time the ICAM‐1 gene polymorphisms in MS. The results indicate increased frequency of ICAM‐1 exon 6 allele T in MS patients, which may contribute to the MS genetics background.
Genetic characteristics of myoadenylate deaminase deficiency
Authors: Verzijl H. T. F. M. , van Engelen B. G. M. , Luyten J. A. F. M. , Steenbergen G. C. H. , van den Heuvel L. P. W. J. , ter Laak H. J. , Padberg G. W. , Wevers R. A. 
Published: January 2005

AbstractTwo types of myoadenylate deaminase (MAD) deficiency have been described, primary or inherited, and secondary or acquired MAD deficiency. In this study, we investigated whether secondary MAD deficiency is indeed acquired or merely coincidental. We demonstrated the same underlying molecular defect, a C34T transition, in both types of deficiency. Furthermore, the same frequency of the mutant MAD allele was found in the general population as in patients with neuromuscular complaints. We therefore conclude that in the Dutch population, secondary MAD deficiency is merely a “coincidental” finding, and that MAD deficiency is a harmless genetic variant.
Perinatal hypoxic—Ischemic thalamic injury: Clinical features and neuroimaging
Authors: Roland Elke H. , Poskitt Kenneth , Rodriguez Estela , Lupton Brian A. , Hill Alan 
Published: January 2005

AbstractA common pattern of hypoxic–ischemic cerebral injury in the term newborn involves predominantly cerebral cortex and subcortical white matter. We describe 20 term newborns with moderate or severe acute hypoxic–ischemic encephalopathy who exhibit a different pattern of abnormalities on computed tomography, with evidence of decreased tissue attenuation predominantly in thalami and basal ganglia and relative preservation of cerebral cortex and white matter. Profound, acute hypoxic–ischemic insult (eg, umbilical cord prolapse, uterine rupture, or massive placental abruption) was documented in 16 of 20 infants (80%). Characteristic clinical features during the newborn period included irritability, tonic posturing of limbs, and persistent lower cranial nerve dysfunction, often with prominent tongue fasciculations. This pattern of central injury appears to be highly predictive of poor outcome; 7 newborns (35%) died, and all survivors who had follow–up to 18 months of age (11) had major neurological sequelae (eg, spastic quadriplegia, choreoathetosis, and persistent feeding problems). This pattern of hypoxic–ischemic cerebral injury corresponds closely to experimental animal models of “acute total” perinatal asphyxia.
Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor
Authors: Ohno Kinji , Anlar Banu , Özdirim Emire , Brengman Joan M. , DeBleecker Jan L. , Engel Andrew G. 
Published: January 2005

AbstractWe report and functionally characterize five new mutations of the acetylcholine receptor (AChR) in 11 Turkish patients with recessive congenital myasthenic syndromes (CMS)s belonging to six families. All mutations are in the ε‐subunit gene. Parental consanguinity is present in three families. The disease cosegregates with homozygous mutations in five families and with two different heteroallelic mutations in one family. Four mutations are frameshifting, predicting truncation of the ε subunit, and one occurs at a splice donor site. Expression of each frameshifting mutation and the likely transcripts of the splice‐site mutation in human embryonic kidney 293 cells shows that each mutation is a null mutation. The findings support the notion that loss‐of7hyphen;function mutations of the acetylcholine receptor causing CMS are concentrated in the ε subunit, and that such mutations are a frequent cause of CMS.
Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia
Authors: Fullerton Heather J. , Ditelberg Jeremy S. , Chen Sylvia F. , Sarco Dean P. , Chan Pak H. , Epstein Charles J. , Ferriero Donna M. 
Published: January 2005

AbstractUnlike the mature animal, immature mice transgenic for copper/zinc superoxide dismutase (SOD1) have greater brain injury after hypoxia–ischemia than their wild‐type nontransgenic littermates. To assess the role of oxidative stress in the pathogenesis of this injury, we measured histopathological damage, lipid peroxidation products, enzymatic activities of catalase and glutathione peroxidase, and hydrogen peroxide (H2O2) concentration in these animals before and after hypoxic–ischemic injury. Lipid peroxidation products were significantly increased 2 hours after the insult in both transgenic and nontransgenic brains in hippocampus, the most damaged brain region. Catalase activity did not increase in response to SOD1 overexpression or injury in either group. However, glutathione peroxidase activity, unchanged in response to overexpression, decreased significantly 24 hours after injury in both groups. At 24 hours after injury, greater H2O2 accumlation was observed in transgenic brains. Because SOD1 dismutates superoxide to H2O2, overexpression of SOD1 in the presence of developmentally low activities of the catalytic enzymes glutathione peroxidase and catalase leads to an increased production of H2O2, and may explain the increased brain injury observed after hypoxia–ischemia in neonatal SOD1 mice.