bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy
Authors: Van Paesschen W. , Revesz T. , Duncan J. S. , King M. D. , Connelly A. 
Published: January 2005

AbstractThe aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonace (MR)‐based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty‐three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR‐based HCV measurement and HCT2 mapping, therfore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.
Isolation and characterization of an oligodendrocyte precursor–derived B‐cell epitope in multiple sclerosis
Authors: Archelos Juan J. , Trotter Jacqueline , Previtali Stefano , Weißbrich Benedikt , Toyka Klaus V. , Hartung Hans‐Peter 
Published: January 2005

AbstractIn a search for possible central nervous system–specific autoantigens in multiple sclerosis (MS), a λ‐phage protein expression library was constructed from an oligodendrocyte‐precursor cell line. The library was screened with pooled cerebrospinal fluid (CSF) from 54 patients with definite MS according to the criteria of Poser. Pooled CSF samples from 44 patients with other neurological disease including bacterial meningitis and viral encephalitis were used as control. A total of 1,000,000 colonies were screened and 6 positive clones were detected. At the DNA level none of the sequences showed significant homology to a known coding sequence. All 6 clones contained an open reading frame for small peptides ranging from 14 to 38 amino acids. It was noteworthy that 5 clones contained a common sequence of 7 amino acids, which was highly homologous to a translated consensusAlurepeat epitope. Screening of sera and CSF from patients with MS showed that approximately 44% reacted with these so‐calledAlupeptides, end‐point antibody titers in their sera ranging from 1:1,000 to 1:25,000. In addition, some samples selected by their reactivity withAlupeptides stained intensively the cytoplasm of oligodendrocyte precursors but not of astrocytes ex vivo. We postulate that autoantibodies to a hitherto unknown oligodendrocyte precursor‐derived B‐cell epitope could contribute to the pathogenesis in a subgroup of MS patients.
Magnetic resonance studies of intramuscular interferon β–1a for relapsing multiple sclerosis
Authors: Simon Jack H. , Jacobs Lawrence D. , Campion Marilyn , Wende Karl , Simonian Nancy , Cookfair Diane L. , Rudick Richard A. , Herndon Robert M. , Richert John R. , Salazar Andres M. , Alam John J. , Fischer Jill S. , Goodkin Donald E. , Granger Carl V. , Lajaunie Michelle , Martens‐Davidson Anna L. , Meyer Maryjoel , Sheeder Jeanelle , Choi Kim , Scherzinger Ann L. , Bartoszak David M. , Bourdette Dennis N. , Braiman Jonathan , Brownscheidle Carol M. , Coats Michael E. , Cohan Stanley L. , Dougherty David S. , Kinkel Revere P. , Mass Michele K. , Munschauer Fredrick E. , Priore Scd Roger L. , Pullicino Patrick M. , Scherokman Barbara J. , Weinstock‐Guttman Bianca , Whitham Ruth H. ,   and The Multiple Sclerosis Collaborative Research Group
Published: January 2005

AbstractThe Multiple Sclerosis Collaborative Research Group trial was a double‐blind, randomized, multicenter, phase III, placebocontrolled study of interferon α‐1a (IFNβ‐1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNβ‐1a, 30 μg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNβ‐1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNβ‐1a patients was 1,578 and −12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium‐enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNβ‐1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long‐term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.
Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy
Authors: Fry  ,   US Modafinil in Narcolepsy Multicenter Study Group
Published: January 2005

AbstractNarcolepsy is a central nervous system disorder characterized by excessive daytime sleepiness and cataplexy. This placebocontrolled, double‐blind, randomized, parallel‐group, 18‐center study assessed the efficacy and safety of modafinil, a new wake‐promoting drug for treating sleepiness in narcolepsy. Subjects with narcolepsy (n = 283) received daily modafinil, 200 or 400 mg, or placebo, for 9 weeks, followed by an open‐label treatment period. Subjective sleepiness was measured with the Epworth Sleepiness Scale. Objective sleepiness was assessed with the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Level of illness was measured with the Clinical Global Impression of Change. Modafinil significantly reduced all measures of sleepiness and was associated with significant improvements in level of illness. Medication‐related adverse expriences were few, dose‐dependent, and mostly rated mild to moderate. Modafinil taken once daily was a very well tolerated and effective wake‐promoting agent in the treatment of excessive daytime somnolence associated with narcolepsy. Modafinil demonstrated an excellent safety profile for up to 40 weeks of open‐label treatment and efficacy was maintained, suggesting that tolerance will not develop with long‐term use. Modafinil is a pharmacologically and clinically promising compound for the treatment of pathological daytime somnolence.
Compound heterozygous genotype is associated with protracted juvenile neuronal ceroid lipofuscinosis
Authors: Wisniewski K. E. , Zhong N. , Kaczmarski W. , Kaczmarski A. , Kida E. , Brown W. T. , Schwarz K. O. , Lazzarini A. M. , Rubin A. J. , Stenroos E. S. , Johnson W. G. , Wisniewski T. M. 
Published: January 2005

AbstractWe present a clinicopathological study and the first molecular genetic analysis of a family with 2 siblings affected by a rare, protracted form of juvenile neuronal ceroid lipofuscinosis (JNCL). Molecular genetic studies showed that both siblings, in addition to being heterozygous for the 1.02‐kb CLN3 deletion, a common mutation in JNCL, also had a G‐to‐A missense mutation at nucleotide 1,020 of the CLN3 cDNA sequence on the non‐1.02‐kb deletion chromosomes. This point mutation resulted in a substitution of glutamic acid by lysine at position 295 of the CLN3 protien. Thus, a single point mutation at residue 295 of the CLN3 protien in protracted JNCL may underlie the phenotype in this form, which differs from that in classic JNCL.
Restricted use of VH4 Germline segments in an acute multiple sclerosis brain
Authors: Owens Gregory P. , Kannus Hanna , Burgoon Mark P. , Smith‐Jensen Tracey , Devlin Mary E. , Gilden Donald H. 
Published: January 2005

AbstractMultiple sclerosis (MS) cerebrospinal fluid and brain contain increased IgG and oligoclonal bands. Whether this oligoclonal and polyclonal IgG is directed against a disease‐relevant antigen remains unknown. To distinguish between random activation versus a targeted B‐cell response, we analyzed the IgG heavy chain variable region (VH) repertoire expressed in different lesions of an acute MS brain. To obtain a representative sample of the VH repertoire, we constructed directional complementary DNA libraries from plaque‐periplaque messenger RNA and amplified VH regions from the library by nested polymerase chain reaction. When MS VH sequences were aligned to germline segments, about 60% of different VH sequences in the acute MS brain were VH4 germline segments, significantly greater than the known approximately 20% VH4 germline prevalence. Specific VH sequences were overrepresented and expressed at multiple plaque sites. Within some overexpressed populations, there were distinct sequence differences (clonal variants) indicative of clonal expansion. Alignment of VH sequences to their closest germline counterparts revealed extensive somatic mutation and the preferential accumulation of amino acid replacement mutations in complementarity determining regions. These observations suggest the limited B‐cell response found in this acute MS brain was antigen driven.
Proton magnetic resonance spectroscopy in an italian family with spinocerebellar ataxia type 1
Authors: Mascalchi Mario , Tosetti Michela , Plasmati Rosaria , Bianchi Maria Cristina , Tessa Carlo , Salvi Fabrizio , Frontali Marina , Valzania Franco , Bartolozzi Carlo , Tassinari Carlo Alberto 
Published: January 2005

AbstractLinkage and DNA analysis, magnetic resonance (MR) imaging, and single‐voxel proton MR spectroscopy were obtained in 10 members of an Italian kindred with spinocerebellar ataxia type 1 (SCA1). The size of the basis pontis, cerebellar hemispheres, middle cerebellar peduncles, and medulla oblongata were decreased in 4 members carrying the SCA1 gene, compared with 6 unaffected subjects. Diffuse signal changes in the pons and cerebellum were observed only in the carrier with the longest disease duration and greatest disability. The N‐acetylaspartate/creatine ratio and the choline/creatine ratio in the basis points were markedly decreased in 2 symptomatic SCA1 carriers and moderately decreased in 2 asymptomatic SCA1 carriers, compared with the unaffected family members and a control group of 10 healthy volunteers. Minor decreases in the N‐acetylaspartate/creatine ratio and the normal choline/creatine ratio, demonstrated by MR spectroscopy in the pons, is likely to reflect a loss of neuronal viability and might represent a biochemical marker of SCA1 more sensitive than brainstem and cerebellum atrophy and signal changes shown by MR imaging.
Unmyelinated nerve fibers in sural nerve in pure autonomic failure
Authors: Kanda Takashi , Tomimitsu Hiroyuki , Yokota Takanori , Ohkoshi Norio , Hayashi Michiyuki , Mizusawa Hidehiro 
Published: January 2005

AbstractWe examined sural nerve biopsy specimens from 7 patients with pure autonomic failure (PAF). The mean unmyelinated nerve fiber diensity in these patients was 40% less than in age‐matched controls. Increased numbers of clusters of collagen pockets not containing unmyelinated axons were the most prominent finding in PAF. This appears to reflect recent dropout of a group of sympathetic efferents and suggests grouping of unmyelinated fibers by modality at the level of the sural nerve trunk.
Mutation analysis in myophosphorylase deficiency (McArdle's disease)
Authors: Vorgerd Matthias , Kubisch Christian , Burwinkel Barbara , Reichmann Heinz , Mortier Wilhelm , Tettenborn Barbara , Pongratz Dieter , Lindemuth Rainer , Tegenthoff Martin , Malin Jean‐Pierre , Kilimann Manfred W. 
Published: January 2005

AbstractInherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical cliniclal presentation of myophos‐phorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophorsphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously identified missense mutation Gly204Ser. In another patient, we identified a novel missense mutation Gln665Glu and a single‐base deletion delA in Lys753. One patient of Turkish ancestry carried a newly identified homozygous A‐to‐G transition (ATG to GTG) abolishing the translation initiation codon of the myophosphorylase gene. These results suggest that Arg49Stop also is the most common genetic error associated with myophosphorylase deficiency in the German population. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency among the clinically homogenous patients we studied.
Correlations between monthly enhanced MRI Lesion rate and changes in T2 Lesion volume in multiple sclerosis
Authors: Molyneux P. D. , Filippi M. , Barkhof F. , Gasperini C. , Yousry T. , Lruyen L. , Lai H. M. , Rocca M. A. , Moseley I. F. , Miller D. H. 
Published: January 2005

AbstractMagnetic resonance imaging (MRI) provides a powerful tool for assessing disease activity in multiple sclerosis (MS), and its role as a surrogate marker for monitoring treatment efficacy is now becoming established. The most commonly used MRI parameters in treatment trials are (1) monthly gadolinium‐enhanced MRI, with the number of active lesions serving as the outcome measure, and (2) annual lesion load quantification, in which change in MS lesion volume provides the MRI endpoint. We evaluated clinical/MRI correlations and the relationship between these two markers of disease activity in 73 patients with clinically definite MS. Quantification of T2 lesion load was performed at study entry and exit, with a median study duration of 11 months (range, 9 to 14 months). Monthly postgadolinium T1‐weighted images were acquired between these time points. Lesion load at study entry was significantly correlated with the baseline Expanded Disability Status Scale (EDSS) score, but no significant longitudinal correlation was demonstrated. The number of enhancing lesions on the entry scan was predictive of subsequent relapse rate over the study duration and also correlated with the subsequent enhancing lesion activity over the study period. A significant correlation was found between change in lesion load and disease activity on the monthly scans. Our results suggest that annual lesion load quantification provides an efficient measure of ongoing disease activity, and this supports its application as a surrogate marker of disease evolution in phase III treatment trials.
Near and far visual space in unilateral neglect
Authors: Vuilleumier P. , Valenza N. , Mayer E. , Reverdin A. , Landis T. 
Published: January 2005

AbstractA 24‐year‐old right‐handed woman with a right temporal hematoma showed marked left visual neglect for far but not near space in a variety of tasks systematically given in near and far distance conditions. This case thus provides the dissociation opposite to Halligan and Marshall's patient, who had neglect for near but not far space after a right parietal stroke. Furthermore, although she made rightward errors in bisecting far‐distant lines, our patient made smaller opposite leftward errors for near‐distant lines. The evidence that unilateral neglect of far and near visual space may exist independently supports a division in the neural systems subserving attention to different compartments of the extrapersonal space in humans.
Multiple sclerosis: In situ evidence for antibody‐ and complement‐mediated demyelination
Authors: Storch Maria K. , Piddlesden Sara , Haltia Matti , Iivanainen Matti , Morgan Paul , Lassmann Hans 
Published: January 2005

AbstractWe describe a case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination. This was particularly evident for the C9neo antigen, which is a marker for the activated lytic complement complex and was exclusively deposited in the areas of active myelin destruction. In addition, macrophages in the lesions contained degradation products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo antigen. Destruction of myelin sheaths was associated with incomplete loss of oligodendrocytes in the active areas and reappearance of oligodendrocytes with remyelination in the inactive plaque center.
Cerebrospinal fluid homovanillic acid levels in rapid‐onset dystonia‐parkinsonism
Authors: Brashear Allison , Butler Ian J. , Hyland Keith , Farlow Martin R. , Dobyns William B. 
Published: January 2005

AbstractRapid‐onset dystonia‐parkinsonism (RDP) is characterized by sudden onset over hours to days of dystonia, dysphagia, dysarthria, and parkinsonism. RDP has been reported by our group in two apparently unrelated families. We now report analysis of cerebrospinal fluid metabolites of dopamine, norepinephrine, and serotonin for mild and severely affected individuals, known asymptomatic gene carriers, and at‐risk individuals from both families with RDP. Levels of the dopamine metabolite homovanillic acid (HVA) were decreased in severely affected patients and in some asymptomatic gene carriers. HVA levels increased with treatment in some affected individuals, but this increase did not predict clinical response to carbidopa/levodopa. We suggest that a low HVA level is a biological marker with modest association to the diagnosis of RDP.
Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene
Authors: Cudkowicz M. E. , McKenna‐Yasek D. , Chen C. , Hedley‐Whyte E. T. , Brown R. H. 
Published: January 2005

AbstractWe examined 11 subjects with inherited amyotrophic lateral sclerosis (familial amyotrophic lateral sclerosis, FALS) associated with the most common copper/zinc superoxide dismutase 1 (SOD1) mutation, an alanine for valine substitution in codon 4 (A4V). Autopsies were performed on 5 subjects. The clinical and pathological findings are described and compared with those of 9 sporadic ALS (SALS) subjects. There was no clinical evidence of upper motor neuron (UMN) involvement in 10 FALS A4V subjects. All subjects had lower motor neuron (LMN) signs and electrophysiological evidence of denervation in at least three limbs. All SALS subjects had signs of both UMN and LMN involvement. Pathological studies found severe abnormalities of LMNs in all FALS and SALS subjects. UMN involvement was either absent or mild in the A4V SOD1 FALS subjects and severe in the SALS subjects. Pathological abnormalities in systems other than the motor neurons were more frequent in the FALS A4V subjects. This information suggests that current diagnostic criteria for ALS, requiring clinical evidence for both upper and lower motor neuron involvement, should be modified; ie, the diagnosis should be deemed established when there is evidence of denervation in three or more limbs and a mutation in the gene for SOD1, even without clinical signs of UMN involvement.
Fast eye movement initiation of ocular torsion in mesodiencephalic lesions
Authors: Bentley C. R. , Bronstein A. M. , Faldon M. , Farmer S. , Gresty M. A. , Matthews T. D. , Paine M. , Plant G. T. , Riordan‐Eva P. 
Published: January 2005

AbstractThree patients with episodic ocular torsion and skew deviation due to mesodiencephalic lesions were studied by using binocular three‐dimensional scleral search coils. The conjugate ocular torsion (upper pole of each eye rotating toward the side of the brainstem lesion) was initiated by a torsional fast eye movement. During prolonged episodes, torsional nystagmus was also present. Cessation of the ocular torsion and skew deviation occurred by slow eye movements with exponentially decreasing velocities in 2 patients, and by multiple fast torsional movements in 1 patient. In 1 patient, the abnormal eye movements were temporally linked to dystonic movements in the limbs on the side opposite the brainstem lesion. The occurrence of skew deviation with conjugate ocular torsion in brainstem lesions has been attributed to functional asymmetry in vestibular pathways responsible for the slow‐phase compensatory eye movement response to roll. In comparison, the findings in our patients show that in mesodiencephalic lesions conjugate ocular torsion with skew deviation may be generated by torsional fast eye movements, indicating activation of the burst cells of the rostral interstitial nucleus of the medial longitudinal fasciculus.
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Authors: Poorkaj Parvoneh , Bird Thomas D. , Wijsman Ellen , Nemens Ellen , Garruto Ralph M. , Anderson Leojean , Andreadis Athena , Wiederholt Wigbert C. , Raskind Murray , Schellenberg Gerard D. 
Published: January 2005

AbstractFrontotemporal dementia with parkinsonism, chromosome 17 type (FTDP‐17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21‐22 in a 2‐ to 4‐centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800‐D17S791 FTDP‐17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP‐17 families revealed nine DNA sequence variants, eight of which were also identified controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP‐17 family but not in the second FTDP‐17 family. Three lines of evidence indicate that the Val279Met change is an FTDP‐17 causative mutation. First, the mutation site is highly conserved, and normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co‐segregates with the disease in family A. Third, the mutation is not found in normal controls.