bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal lobe epilepsy caused by domoic acid intoxication: Evidence for glutamate receptor–mediated excitotoxicity in humans
Authors: Cendes Fernando , Andermann Frederick , Carpenter Stirling , Zatorre Robert J. , Cashman Neil R. 
Published: January 2005

AbstractWe describe the development of temporal lobe epilepsy in an 84‐year‐old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left‐sided predominance. Magnetic resonance imaging revealed a hyperintense T2‐weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 31/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temprol lobe epilepsy developed 1 year after intoxication indicate that the human hippcampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, Kainate‐induced epilepsy as an important tool for studying temporal lobe epilepsy.
Multiple, diverse senile plaque–associated proteins are ligands of an apolipoprotein e receptor, the α2‐macroglobulin receptor/low‐density‐lipoprotein receptor—related protein
Authors: Rebeck G. William , Harr Steven D. , Hyman Bradley T. , Strickland Dudley K. 
Published: January 2005

AbstractBoth apolipoprotein E and its receptor, the low‐density‐lipoprotein receptor‐related protein (LRP), are associated with senile plaques in Alzheimer's disease. We examined the relationship of other LRP‐related molecules to senile plaques. LRP is a multifunctional receptor that blinds and rapidly internalizes at least seven ligands: apolipoprotein E, activated α2‐macroglobulin, tissue and urokinase‐type plasminogen activators, plasminogen activator inhibitor‐1, lipoprotein lipase, and lactoferrin. Using immunohistochemistry, we showed that all of these ligands, representing a diverse group of otherwise apparently unrelated proteins, accumulate on senile plaques. We also studied expression of the receptor‐associated protein, a physiological inhibitor of LRP, in the hippocampal formation from normal subjects and Alzheimer's disease patients. Receptor‐associated protein colocalizes with LRP on neuronal soma, but not on neuronal processes or reactive astrocytes. It is not present on senile plaques. These results suggest that senile plaque‐associated LRP can bind its ligands, but clearance of these compounds may be impaired in the vicinity of senile plaques.
Apolipoprotein E and alzheimer's disease: Ethnic variation in genotypic risks
Authors: Maestre Gladys , Ottman Ruth , Stern Yaakov , Gurland Barry , Chun Michael , Tang Ming‐Xin , Shelanski Michael , Tycko Benjamin , Mayeux Richard 
Published: January 2005

AbstractThe presence of the apolipoprotein ε4 (apo ε4) allele significantly increases the risk of Alzheimer's disease. Whether this is due to biological effects of the apo ε4 protein or reflects linkage disequilibrium with an as yet unidentified Alzheimer's disease susceptibility gene is of critical importance. In a community study in northern Manhattan we found a fivefold increase in the risk of Alzheimer's disease among African‐Americans, Hispanics, and whites homozygous for apo ε4. Overall, the risk between Alzheimer's disease and apo ε4 heterozygosity was also increased by twofold, but the association was somewhat weaker for African‐Americans than for Hispanics and whites. In contrast, the apo ε2/ε3 genotype was associated with an eightfold increased risk of Alzheimer's disease in African‐Americans but it was associated with reduced risk in whites. Variability in the strength and type of association between Alzheimer's disease and the apo E polymorphisms in the three ethnic groups could not be fully explained by age differences. The allelic frequency of apoε*4 was significantly higher in patients than control subjects in all ethnic groups at age 70 or younger, reflecting the higher proportion of apo ε4 homozygotes, but this difference diminished with increasing age. The allelic frequency of apoε*2 for African‐Americans and Hispanics, but not whites, was significantly higher in patients than control subjects, but only after age 70. Though these findings need confirmation, they suggest that modifier genes or environmental factors may interact selectively with apo ε4 in African‐Americans to weaken the association with Alzheimer's disease or that the apo E allelic system is in linkage disequilibrium with a nearby, as yet unidentified Alzheimer's disease susceptibility locus.
Reduced expression of preproenkephalin in striatal neurons from huntington's disease patients
Authors: Richfield Eric K. , Maguire‐Zeiss Kathleen A. , Cox Christopher , Gilmore Jennifer , Voorn Pieter 
Published: January 2005

AbstractDifferential loss of neurons and terminals occurs in Huntington's disease. Neurons expressing preproenkephalin (PPE) appear to be more vulnerable than neurons expressing preprotachykinin and terminals in the lateral pallidum (containing enkephalin) are more affected than terminals in the medial pallidum (containing substance P). We used in situhybridization histochemistry and emulsion autoradiography to quantify the number of PPE expressing neurons and the neuronal levels of PPE mRNA in striatum of individuals who died with Huntington's disease and normal controls. We found a grade‐related decline in the number of PPE‐labeled neurons per field in the striatum of individuals with Huntington's disease compared with controls. Three measures of the neuronal level of PPE mRNA, the mean number of silver grains per PPE neuron, the median number of grains per PPE neuron, and the percentage of PPE neurons with more than 30 grains, were all significantly reduced (41 to 80% of control) in Huntington's disease striatum. The magnitude of the reduction in levels of PPE mRNA per neuron was related to the grade of lesions. These data support the notion that decreased levels of PPE mRNA may account, in part, for the greater loss of enkephalin staining in lateral pallidal terminals compared with substance P staining in medial pallidal terminals. Decreased levels of PPE mRNA may result in clinical symptoms prior to the loss of neurons. The reduction in expression of PPE mRNA suggests that surviving striatal neurons may be affected by the expression of the Huntington's disease gene prior to their imminent cell death.
Hyperkalemic periodic paralysis with cardiac dysrhythmia: A novel sodium channel mutation?
Authors: Baquero Jaime L. , Ayala Ricardo A. , Wang Jianzhou , Curless Richard G. , Feero W. Gregory , Hoffman Eric P. , Ebeid Makram R. 
Published: January 2005

AbstractA patient is presented with hyperkalemic periodic paralysis (HyperPP) and a cardiac dysrhythmia. An amino acid substitution (Val783Ile) in the adult skeletal muscle sodium channel gene was detected. Although lack of available family members precluded rigorous genetic tests, the sodium channel change may be responsible for HyperPP in this patient and could also be responsible for the associated cardiac dysrhythmia.
Activated T cells of nonneural specificity open the blood‐nerve barrier to circulating antibody
Authors: Pollard J. D. , Westland K. W. , Harvey G. K. , Jung S. , Bonner J. , Spies J. M. , Toyka K. V. , Hartung H.‐P. 
Published: January 2005

AbstractRecent studies from our laboratory and by other investigators have shown that autoreactive CD4+ cells specific for peripheral nerve P2 protein have a powerful effect on blood‐nerve barrier permeability. In this study we injected CD4+ T cells reactive to a nonneural antigen (ovalbumin) systemically and achieved their accumulation in the tibial nerve of Lewis rats by previous intraneural injection of ovalbumin. Selected rats were given systemic demyelinating antibody (antigalactocerebroside) to provide an indicator of changes in the permeability of the blood‐nerve barrier, and the animals were monitored by sequential neurophysiological studies and histology. Circulating ovalbumin‐specific T cells accumulated at sites of intraneural ovalbumin injection without inducing demyelination in control animals. In rats with circulating galactocerebroside antibodies, local conduction block and demyelination were seen in the region of T‐cell accumulation. Electron microscopy demonstrated dissolution of some tight junctions between endothelial cells in areas of T‐cell accumulation, and T cells traversing the endothelium between endothelial cells and through their cytoplasm. Endothelial cell damage was evident in these areas. This study demonstrates breakdown of the blood‐nerve barrier by activated T cells, even of nonneural specificity, allowing the development of focal conduction block and demyelination in the presence of circulating antimyelin antibodies.
Ocular neuromyotnia: Clinical features, physiological mechanisms, and response to therapy
Authors: Frohman Elliot M. , Zee David S. 
Published: January 2005

AbstractOcular neuromyotonia (ONM) is a rare disorder characterized by episodic diplopia, occurring either spontaneously or following sustained eccentric gaze. Most patients have had prior radiation therapy to the sellar and parasellar region. ONM is thought to reflect impaired muscle relaxtion due to inappropriate discharges from oculomotor, trochlear, or abducens neurons or axons with unstable cell membranes. Patients with ONM often benefit from membrane stabilizing agents such as carbamazepine. Here we describe a 71‐year‐old man, with no history of radiation therapy, who for 18 months had had transient episodic diplopia that occurred after down gaze. Clinical examination indicated ONM in muscles supplied by the right oculomotor nerve. Binocular scleral search coil eye movement recordings revealed a defect not only of muscle relaxation but also of maximal muscle contraction. The patient was treated with carbamazepine 200 mg per day with complete resolution of his symptoms. ONM may be more common than previously recognized, and patients with unexplained transient episodic diplopia should be specifically tested for diplopia and ocular misalignment following sustained eccentric gaze.
Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy
Authors: Ho Susan S. , Berkovic Samuel F. , Berlangieri Salvatore U. , Newton Mark R. , Egan Gary F. , Tochon‐Danguy Henri J. , McKay W. John 
Published: January 2005

AbstractWe retrospectively compared ictal technetium 99m hexamethylpropyleneamineoxime single‐photon emission computed tomography (SPECT) and interictal 18F‐fluorodeoxyglucose positron emission tomography (PET) in 35 patients with well‐lateralized temporal lobe epilepsy (TLE). Based on SPECT scans the two observers correctly lateralized seizure foci with certainty in 89% of patients; interobserver agreement was excellent. Both observers incorrectly lateralized the seizure focus on two SPECT scans; one error was explained by rapid electroencephalographic spread to the contralateral side and for the other patient, isotope was injected during a brief aura. Based on PET scans, observers correctly lateralized the foci with certainty in 63% and with lesser confidence in 83%; four incorrect lateralizations were made by one observer and none by the other. PET interobserver disagreement was explained by differences between observers in weighting the relative hypometabolism in medial and lateral temporal regions. The detection rate for PET was lower in the absence of structural imaging abnormalities (60 vs 87%). PET yielded correct lateralizations in the 2 patients for whom SPECT interpretation was difficult. We conclude that both ictal SPECT and interictal PET are sensitive methods for the lateralization of TLE, but SPECT can be interpreted with greater certainty and is more sensitive when magnetic resonance imaging findings are negative. False lateralization is rare with ictal SPECT and can be explained when interpreted in conjunction with electroclinical data. Both investigations have complementary roles when localization is difficult.
Encephalopathy with parkinsonian features in children following bone marrow transplantations and high‐dose amphotericin B
Authors: Mott Stephen H. , Packer Roger J. , Vezina L. Gilbert , Kapur Sudesh , Dinndorf Patricia A. , Conry Joan A. , Pranzatelli Michael R. , Quinones Ralph R. 
Published: January 2005

AbstractEncephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high‐dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high‐dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non–central nervous system Epstein‐Barr virus–lymphoproliferative disease and had autopsy‐confirmed leukoenephalopathy.
Cephalosporin‐induced recurrent aseptic meningitis
Authors: Creel George B. , Hurtt Mark 
Published: January 2005

AbstractA 66‐year‐old woman had several episodes of aseptic meningitis associated with exposure to cephalexin, cefazolin, and ceftazidime. The cerebrospinal fluid IgG index was elevated, specific IgG‐ceftazidime binding was shown, and skin allergy testing with cefazolin provoked a recurrence of meningitis. We postulate an acute hypersensitivity reaction involving an antigen‐specific humoral immune response.
Intracerebral hemorrhage versus infarction: Stroke severity, risk factors, and prognosis
Authors: Jørgensen Henrik Stig , Nakayama Hirofumi , Raaschou Hans Otto , Olsen Tom Skyhøj 
Published: January 2005

AbstractThe purpose of this study was to compare stroke severity, risk factors, and prognosis in patients with intracerebral hemorrhage versus infarction. We prospectively studied 1,000 unselected patients with acute stroke of a verified type in the Copenhagen Stroke Study. Neurological deficits and functional disabilities were evaluated weekly from the time of acute admission throughout the rehabilitation period. Eighty‐eight (9%) had intracerebral hemorrhage. The relative frequency of intracerebral hemorrhage rose exponentially with increasing stroke severity. In multivariate analyses, stroke type had no influence on mortality, neurological outcome, functional outcome, or the time course of recovery. Initial stroke severity was the all‐important prognostic factor. The relative importance of hypertension and blood pressure on admission was not greater for intracerebral hemorrhage than for infarction. No preponderance was found between type of stroke and sex, age, and smoking. Diabetes, ischemic heart disease, and elevated serum total cholesterol level all favored cerebral infarction as opposed to intracerebral hemorrhage. We conclude that the type of stroke per se has no influence on stroke prognosis in general; the extent of the injury is decisive. The poorer prognosis in patients with intracerebral hemorrhage is due to the increase in frequency of intracerebral hemorrhage with increasing stroke severity. The likelihood of cerebral infarction occuring as opposed to intracerebral hemorrhage seems increased fivefold in stroke patients with diabetes. Hypertension and blood pressure on admission were not predictors of stroke type.
Anti‐GM1 IgG antibodies and campylobacter bacteria in Guillain‐Barré syndrome: Evidence of molecular mimicry
Authors: Oomes Peter G. , Jacobs Bart C. , Hazenberg Maarten P. H. , Bänffer John R. J. , van der Meché Frans G. A. 
Published: January 2005

AbstractIn Guillain‐Barré syndrome antibodies to GM1 and the presence of an antecedent Campylobacter jeJunei infection are correlated with a more severe course of the disease. From a group of 137 consecutive GBS patients, 11 sera had elevated titers of anti‐GM1 IgG antibodies during the acute stage of disease. Each serum sample was preincubated with three different Penner serotypes of whole C. jeJunei (PEN O:4/59, PEN O:41) and Campylobacter coli (PEN O:22) bacteria. The PEN O:4/59 serotype, isolated from the stools of a Guillain‐Barré syndrome patient, inhibited 63 to 93% of the anti‐GM1 activity in 6 of 11 patients. The PEN O:41 inhibited 63 to 100% of the anti‐GM1 antibody activity in 9 of 11 patients. The PEN O:22 inhibited anti‐GM1 antibody activity in only 2 of 11 patients (80 and 86%). Two Guillain‐Barré syndrome patients did not show antibody absorption by any of the Campylobacter serotypes tested, although this does not exclude the involvement of other serotypes. An Escherichia coli control strain did not significantly absorb anti‐GM1 antibodies. The results of this study indicate that anti‐GM1 IgG antibodies in Guillain‐Barré syndrome sera recognize surface epitopes on whole Campylobacter bacteria and that this recognition is strain‐specific. This provides evidence for molecular mimicry in the pathogenesis of Guillain‐Barré syndrome.
The phenotypic spectrum related to the human epilepsy susceptibility gene “EJM1”
Authors: Sander T. , Hildmann T. , Janz D. , Wienker T. F. , Neitzel H. , Bianchi A. , Bauer G. , Sailer U. , Berek K. , Schmitz B. , Beck‐Mannagetta G. 
Published: January 2005

AbstractLinkage studies of families ascertained through patients with juvenile myoclonic epilepsy (JME) suggest that an HLA‐linked susceptibility gene on chromosome 6, designated “EJM1,” predisposes to a group of idiopathic generalized epilepsies (IGEs) comprising JME, juvenile absence epilepsy (JAE), childhood absence epilepsies (CAE), and epilepsies with generalized tonic–clonic seizures (GTCS). To explore the EJM1‐related phenotypic spectrum, we conducted linkage studies with HLA‐DQα restriction fragment length polymorphisms in 44 families ascertained through patients with CAE or JAE. Our results for the entire group of families provide evidence against a major susceptibility locus for idiopathic absence epilepsies and broader spectra of IGEs in the HLA region. Lod scores less than – 2 were obtained for a region from 10 cM up to 23 cM on either side of the HLA‐DQα locus, depending on the assumed trait model. Suggestive evidence for linkage was found only for a subgroup of families with JME patients assuming an autosomal dominant mode of inheritance with 70% penetrance. A maximum lod score was obtained when family members with JME, JAE, CAE, and idiopathic GTCS were included into the affection status. Our results demonstrate that (1) the genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs is heterogeneous, (2) the gene effect of EJM1 depends on the familial genetic background, and (3) EJM1 confers genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs in the presence of family members with JME.
Amyloid β‐proteins 1—40 and 1—42(43) in the soluble fraction of extra‐ and intracranial blood vessels
Authors: Shinkai Yasuhisa , Yoshimura Masahiro , Ito Yuji , Odaka Asano , Suzuki Nobuhiro , Yanagisawa Katsuhiko , Ihara Yasuo 
Published: January 2005

AbstractTo investigate the process of amyloid β‐protein (Aβ) accumulation in cerebral amyloid angiopathy (CAA), the levels of Aβ were determined in the soluble fraction of extra‐ and intracranial blood vessels and leptomeninges obtained at autopsy. Two enzyme immunoassays were employed that are known to sensitively and specifically quantify two Aβ species, Aβ1–40 and 1–42(43). Aβ was detectable in the intracranial blood vessels and leptomeninges with the latter containing the highest levels, while it was undetectable in the extracranial blood vessels. Thus the levels of soluble Aβ correlated well with the prediiection sites for CAA. Among individuals aged 20 to 90, the Aβ levels in the leptomeninges increased sharply in those aged 50 to 70 and thereafter tended to decline. However, only slight degrees of CAA were detected by immunocytochemistry, even when those leptomeninges contained high levels of Aβ comparable with those in Alzheimer's disease. The level of Aβ1–42 was almost always severalfold that of Aβ1–40 in the soluble fraction of leptomeninges. This is in good agreement with the immunocytochemical result showing the presence of Aβ40‐negative, Aβ42(43)‐positive meningeal vessels. These results indicate that Aβ1–42 is the initially deposited species in CAA and that the disruption of Aβ homeostasis precedes Aβ deposition in the meningeal vessels.
Genotype‐phenotype correlation in adult‐onset acid maltase deficiency
Authors: Wokke John H. J. , Ausems Margreet G. E. M. , van den Boogaard Marie‐José H. , Ippel Elly F. , van Diggelen Otto , Kroos Marian A. , Boer Marijke , Jennekens Frans G. I. , Reuser Arnold J. J. , van Amstel Hans Kristian Ploos 
Published: January 2005

AbstractWe performed a clinical, biochemical, and genetic study in 16 patients from 11 families with adult‐onset acid maltase deficiency. All patients were compound heterozygotes and carried the IVS1(– 13T→G) transversion on one allele; the second allele harbored either a deletion of a T at position 525 in exon 2 (7 probands, 64%) or a deletion of exon 18 (1 proband, 9%). Detrioration of handicap was related to age, and decrease in vital capacity to duration of the symptomatic stage. Respiratory insufficiency was never the first manifestation. The levels of activity of serum creatine kinase and of β‐glucosidase in peripheral blood cells or muscle were helpful for the diagnosis, but did not have prognostic value. The adult form of acid maltase deficiency appears to be both clinically and genetically rather homogeneous; decrease of β‐glucosidase activity is the final common pathway leading to destruction of muscle fibers and progression of muscle weakness over a period of years.
A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis
Authors: Thyagarajan Dominic , Shanske Sara , Vazquez ‐Memije Marta , Devivo Darryl , Dimauro Salvatore 
Published: January 2005

AbstractA T‐to‐C transition at nucleotide (nt) 9176 in the mitochondrial adenosine triphosphatase 6 (ATPase 6) gene was detected in 2 brothers with a neurological disorder resembling Leigh syndrome. The mutation was also present in the 2 other siblings and in the mother, who were asymptomatic. In the more severely affected boy (the proband), the mutation was homoplasmic in muscle, leucocytes, and fibroblasts. In leucocytes from his affected brother, 98% of mtDNA was mutant. Heteroplasmy of varying degrees was seen in leucocytes from the mother and the 2 unaffected siblings. The mutation changes a highly conserved leucine residue near the carboxyl terminus of the mitochondrial ATPase 6 subunit to proline. It could not be detected in 168 control subjects. Studies of ATP synthesis and hydrolysis in fibroblasts from the proband were normal.