bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late‐onset mitochondrial myopathy
Authors: Johnston Wendy , Karpati George , Carpenter Stirling , Arnold Douglas , Shoubridge Eric A. 
Published: January 2005

AbstractIn the majority of patients with mitochondrial encephalomyopathies, signs and symptoms appear in the first three decades of life. Here we report on a group of 9 older patients (>69 years old) with late‐onset skeletal myopathy characterized by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle energy status, suggestive of a primary mitochondrial disease. The clinical phenotype was somewhat variable. However, all patients shared a common feature of insidious moderate proximal muscle weakness; some also showed fatigability and axial muscle weakness. In situ hybridization analysis demonstrated accumulations of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of muscle fibers in the patient group. These fiber segments appeared as ragged red with the modified Gomori trichrome stain and hyperreactive with a modified succinate dehydrogenase stain. Most were negative for cytochrome c oxidase activity. On transverse sections their mean frequency was 0.69% (trichrome) and 1.97% (succinate dehydrogenase) significantly above control levels. Multiple mtDNA deletions were demonstrated by the polymerase chain reaction in both the patients and an age‐matched control group, but not in younger control subjects. Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a decreased phosphocreatine‐inorganic phosphate ratio in the patient group. The myopathy in this group of patients appears to result from mitochondrial dysfunction related to the clonal expansion of different mtDNA deletions in individual fiber segments. While the origin of the mtDNA mutations is not clear, the phenotype seems to represent an exaggerated form of what is observed in the normal aging process.
Circulating, soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: Correlation with clinical activity
Authors: Dore‐Duffy Paula , Newman Walter , Balabanov Roumen , Lisak Robert P. , Mainolfi Elizabeth , Rothlein Robert , Peterson Margaret 
Published: January 2005

AbstractSoluble adhesion protein intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and endothelial leukocyte adhesion molecule (E‐selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with relapsing‐remitting multiple sclerosis (RRMS) in remission and in exacerbation, as well as patients with chronic progressive MS, stable MS, and in patients with other neurological and inflammatory diseases (ONDs). Serum ICAM‐1 and E‐selectin were significantly elevated in patients with MS over those with ONDs and controls. CSF VCAM‐1 and E‐selectin were found to be elevated over control and disease control samples. No increase in CSF ICAM‐1 was observed. Results were analyzed longitudinally and by MS category. In paired CSF and serum samples from patients in exacerbation, elevated VCAM‐1 correlated with increased serum VCAM‐1 in 5 of 7 patients. Elevated CSF E‐selectin did not correlate with elevations in serum E‐selectin.
Basic mechanisms of generalized absence seizures
Authors: Snead O. Carter 
Published: January 2005

AbstractGeneralized absence seizures are neurophysiologically, pharmacologically, and developmentally unique and comprise the primary seizure type in a number of different absence epilepsy syndromes. Over the last 10 years, the availability of a number of animal models of generalized absence seizures and of sophisticated in vitro electrophysiological techniques that allow investigation of cortical and thalamic networks has begun to shed light on the pathogenesis of this disorder. The basic underlying mechanism appears to involve thalamocortical circuitry and the generation of abnormal oscillatory rhythms from that particular neuronal network. Biochemical mechanisms operative within thalamocortical circuitry during this neuronal oscillation seem to entail phase‐locked ‐aminobutyric acid (GABA)B‐mediated inhibition alternating with glutamate‐mediated excitation. The basic cellular mechanism operative within this tension between excitation and inhibition appears to involve the T‐type calcium current. Local circuitry within the thalamus may influence these oscillatory rhythms by GABAA‐mediated inhibition. Pharmacological factors at play external to thalamocortical circuitry include cholinergic, dopaminergic, and noradrenergic mechanisms. Pathways that utilize these various neurotransmitters project onto the thalamus and/or cortex from sites distant to those structures and may modulate the process either up or down. Perturbation of one or more of these neuronal networks may lead to abnormal neuronal oscillatory rhythms within thalamocortical circuitry, with a resultant generation of bilaterally synchronous spike wave discharges that characterize generalized absence seizures. Our increasing understanding of the basic mechanisms that underlie generalized absence seizures promises to allow, for the first time, a rational design of drug treatment for a seizure disorder based on the pathogenesis of that disorder.
Outcome assessment for epilepsy surgery: The impact of measuring health‐related quality of life
Authors: Vickrey Barbara G. , Hays Ron D. , Engel Jerome , Spritzer Karen , Rogers William H. , Rausch Rebecca , Graber Jason , Brook Robert H. 
Published: January 2005

AbstractEpilepsy surgery is an increasingly common treatment for intractable epilepsy; yet there is no clear consensus among experts on how to report epilepsy surgery outcome. Most published outcome reporting systems focus on seizure frequency and type but differ in how they define clinically distinct outcome categories. We used a reliable and valid measure of self‐reported health‐related quality of life (HRQOL), the Epilepsy Surgery Inventory (ESI)‐55, as an external standard by which to evaluate seven previously published, seizure‐based outcome classification systems. The ESI‐55 was administered to 133 adults who had previously undergone surgery for intractable epilepsy, and results were linked to data on their seizure occurrence before and after surgery (over the year prior to their HRQOL reports). These 133 patients were classified according to each seizure‐based outcome system, and variation in HRQOL across outcome groups was evaluated using analysis of variance. Results reveal noteworthy variation in the extent to which different systems reflect patients' HRQOL at follow‐up. We modified existing systems to derive a seizure‐based surgery outcome system that most closely reflects HRQOL when applied over the latest 1‐year postoperative interval.
Analysis of the SCAI CAG repeat in a large number of families with dominant ataxia: Clinical and molecular correlations
Authors: Dubourg O. , Dürr A. , Cancel G. , Stevanin G. , Penet C. , Agid Y. , Brice A. , Chneiweiss H. 
Published: January 2005

AbstractAutosomal dominantly inherited ataxias are a clinically and genetically heterogeneous group of neurodegenerative disorders. The gene involved in one subtype, spinocerebellar ataxia 1 (SCA I), was first localized to chromosome 6p. An unstable CAG repeat has been identified as the responsible mutation. In this study, 88 families with various types of inherited ataxias and 16 individuals with sporadic cerebellar ataxia were investigated to determine the frequency of this mutation, the behavior of the SCA1 CAG repeat during transmission, and the clinical features specific to this form of disease. Only 12 of the families carried the SCA1 mutation; 10 of the 12 were of French origin. When transmitted paternally, the repeat was more unstable and larger in size. Age at onset was inversely correlated with the number of CAG repeats. Anticipation in age at onset of about 11 years was observed in offspring. Analysis of the clinical features did not distinguish SCA1 from other forms of dominantly inherited ataxias. In the absence of distinguishing clinical characteristics, the diagnosis of SCA1 in single affected patients or family members can only be made by direct detection of the mutation, opening the way for presymptomatic testing.
Cerebrospinal fluid 5‐hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus‐myoclonus syndrome
Authors: Pranzatelli M. R. , Huang Y. , Tate E. , Stanley M. , Noetzel M. J. , Gospe S. M. , Banasiak K. 
Published: January 2005

AbstractTo study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus‐myoclonus syndrome, the serotonin metabolite 5‐hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age‐ and gender‐matched control subjects by high‐pressure liquid chromatography with elecrochemical detection. 5‐Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus‐myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus‐myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5‐hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus‐myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus‐myoclonus with low cerebrospinal fluid levels of 5‐hydroxyindoleacetic acid and homovanillic acid. Biochemical heterogeneity for this clinical phenotype may have implications for responsiveness to treatment with serotonergic and other drugs.
Multiple Sclerosis: Limited Diversity of the Vδ2‐Jδ3 T‐Cell Receptor in Chronic Active Lesions
Authors: Battistini L. , Selmaj K. , Kowal C. , Ohmen J. , Modlin R. L. , Raine C. S. PHD, DSC , Brosnan C. F. 
Published: January 2005

AbstractT lymphocytes bearing the γδ T‐cell receptor have been found in the central nervous system of patients with multiple sclerosis in association with demyelinated lesions. Although the biological function of these cells remains to be established, it has been proposed that they are involved in the response to highly conserved antigens, such as heat shock proteins (hsp), expressed during tissue damage and thus may contribute to the development of an autoimmune response. Using polymerase chain reaction, we probed for the presence of T‐cell receptor γδ cells in fresh‐frozen early autopsy brain tissue from patients with multiple sclerosis and patients with non‐multiple sclerosis conditions. The results demonstrated the presence of two major V‐J combinations of the T‐cell receptor δ chain–Vδ2‐Jδ3, Vδ2‐Jδ1– and we used a direct sequencing technique to determine whether this γδ T‐cell population was clonal or diverse. In chronic‐active plaques from 9 patients with multiple sclerosis, we found a striking predominant gene rearrangement within the Vδ2‐Jδ3 T‐cell receptor population that was not present in central nervous system tissue from patients with other neurological diseases. In contrast, within the Vδ2‐Jδ1 T‐cell receptor population, a predominant rearrangement pattern was detected in only 1 of the multiple sclerosis patients. The sequence of the predominant Vδ2‐Jδ3 gene rearrangement was confirmed by cloning and sequencing the gene products from 1 multiple sclerosis patient. This junctional region was characterized by shortened Dδ and Jδ segments, few N region insertions, and use of the third reading frame of the Dδ3 segment. These data strongly support the conclusion that within chronic‐active multiple sclerosis lesions, T cells bearing the Vδ2‐Dδ3‐Jδ3 receptor might have arisen as a response to a common antigen.
Huntington's disease gene: Regional and cellular expression in brain of normal and affected individuals
Authors: Landwehrmeyer G. Bernhard , McNeil Sandra M. , Dure Leon S. , Ge Pei , Aizawa Hitoshi , Huang Qin , Ambrose Christine M. , Duyao Mabel P. , Bird Edward D. , Bonilla Ernesto , de Young Margot , Avila‐Gonzales Alejandro J. , Wexler Nancy S. , DiFiglia Marian , Gusella James F. , MacDonald Marcy E. , Penney John B. , Young Anne B. , Vonsattel Jean‐Paul 
Published: January 2005

AbstractHuntington's disease (HD) is an autosomal dominant disorder characterized by involuntary movements, dementia, and progressive, global, but regionally accentuated, brain atrophy. The disease affects the striatum most severely. An expansion of a trinucleotide repeat on chromosome 4p16.3 within the coding region of a gene termed IT15 has been identified as the mutation causing HD. The normal function of IT15 and the mechanisms by which the presence of the mutation cause HD are unknown. Although IT15 expression has been detected in the brain, as well as in other organ tissues, by Northern blot and in situ hybridization, it is not known whether a preferential regional or cellular expression of IT15 exists within the central nervous system of normal, affected, and presymptomatic individuals. Using quantitative in situ hybridization methods, we examined extensively the regional and cellular expression of IT15. In controls, IT15 expression was observed in all brain regions examined with the highest levels seen in cerebellum, hippocampus, cerebral cortex, substantia nigra pars compacta, and pontine nuclei. Expression in the striatum was intermediate and expression in the globus pallidus was low. IT15 was expressed predominantly in neurons; a low but significant level of expression was seen in glial cells. Analysis of grain counts per square micrometer in neurons showed that the regional differences in the level of mRNA expression were related to density and size of neurons in a given region and not primarily to differences in levels of mRNA expression in individual cells after correction for cell size. Neurons susceptible to degeneration in HD did not selectively express high levels of IT15 mRNA. In HD brains (grades 2–4), the distribution and levels of IT15 mRNA were comparable with controls in all areas except in neostriatum where the intensity of labeling was significantly reduced. Presymptomatic HD brains had a striatal expression similar to controls and surviving striatal neurons in more advanced HD had an expression of IT15 within normal limits. It is apparent from these results that the presence of expanded trinucleotide repeats in HD does not result in the absence of IT15 mRNA expression or in altered patterns or levels of expression. The lack of correlation between the levels of IT15 mRNA expression and susceptibility to degeneration in HD strongly suggests that the mutant gene acts in concert with other factors to cause the distinctive pattern of neurodegeneration in HD.
Serum anti‐GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome
Authors: Jacobs Bart C. , Endtz Hubert PH. , van der Meché Frans G. A. , Hazenberg Maarten P. , Achtereekte Herbert A. M. , van Doorn Pieter A. 
Published: January 2005

AbstractThree patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti‐GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme‐linked immunosorbent assay and thin‐layer chromatography overlay. In enzyme‐linked immunosorbent assay inhibition studies the anti‐GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome–associated C. jejuni strains. The presence of anti‐GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti‐GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross‐reactivity of anti‐GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome–associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.
Molecular and clinical findings in a family with dentatorubral‐pallidoluysian atrophy
Authors: Potter Nicholas T. , Meyer Michael A. , Zimmerman Andrew W. , Eisenstadt Michael L. , Anderson Ilse J. 
Published: January 2005

AbstractHerein we describe the molecular and clinical findings in a North American Caucasian family with dentatorubral‐pallidoluysian atrophy (DRPLA). These patients all presented with an autosomal dominant neurodegenerative disorder characterized by a variable combination of clinical symptoms including seizures, ataxia, dementia, choreiform movements, mental retardation, and psychiatric disease. Neuroradiologic findings in the index case revealed deep subcortical white matter changes on magnetic resonance imaging. Prior to referral, the family carried a diagnosis of Huntington's disease (HD). Subsequent direct molecular testing for HD failed to identify the HD expansion mutation in affected individuals. Molecular testing for DRPLA, however, demonstrated the presence of the recently characterized DRPLA expansion mutation in all affected individuals. The size of the expansion correlated with the age of onset of clinical symptoms. As DRPLA has rarely been reported in North American and European populations, the molecular confirmation of DRPLA in this family provides support for the hypothesis that DRPLA may not be as geographically restricted as once thought.
Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children
Authors: van der Knaap M. S. , Barth P. G. , Stroink H. , van Nieuwenhuizen O. , Arts W. F. M. , Hoogenraad F. , Valk J. 
Published: January 2005

AbstractAn identical syndrome of cerebral leukoencephalopathy and megalencephaly with infantile onset was discovered in 8 children, including 2 siblings. Neurological findings were initially normal or near normal, despite megalencephaly and magnetic resonance imaging (MRI) evidence of severe white matter affection. Slowly progressive ataxia and spasticity developed, while intellectual functioning was preserved for years after onset of the disorder. MRI characteristics included diffuse abnormality in signal intensity and swelling of the cerebral hemispheral white matter with cyst‐like spaces in the frontoparietal and anterior‐temporal subcortical areas. MR spectra were relatively mildly abnormal. Screening for inborn errors, especially those that cause either megalencephaly or white matter disease or both was negative. A distinguishing feature of the present disorder is the apparently severe abnormality of the cerebral white matter as demonstrated by MRI, which contrasts with the remarkably slow course of functional deterioration.
A new mitochondrial DNA mutation associated with progressive dementia and chorea: A clinical, pathological, and molecular genetic study
Authors: Nelson I. , Hanna M. G. , Alsanjari N. , Scaravilli F. , Morgan‐Hughes J. A. , Harding A. E. 
Published: January 2005

AbstractA novel mitochondrial DNA transfer RNA mutation at position 5549 was identified in a patient with dementia, chorea, cerebellar ataxia, deafness, and peripheral neuropathy in the absence of clinical myopathy. Muscle biopsy specimens showed ragged red and cytochrome oxidase‐negative fibers, and reduced complex I activity on polarography. There was diffuse neuronal loss and gliosis throughout the brain on postmortem examination. The heteroplasmic mutation had a widespread distribution in autopsy tissues.
Antibodies against GM1 ganglioside affect K+ and NA+ currents in isolated rat myelinated nerve fibers
Authors: Takigawa Tomoko , Yasuda Hitoshi , Kikkawa Ryuichi , Shigeta Yukio , Saida Takahiko , Kitasato Hiroshi 
Published: January 2005

AbstractHigh titers of anti‐GM1 ganglioside antibodies (anti‐GM1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti‐GM1 antibody using the petroleum jelly–gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti‐GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti‐GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited by step depolarization, with little effect on Na+ current. In the presence of active complement, however, anti‐GM1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement‐supplemented antisera from which anti‐GM1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti‐GM1 antibodies themselves can uncover K+ channels in the paranodal region, while anti‐GM1 antibodies bound to the nodal membrane in the presence of complement may form antibody‐complement complexes that block Na+ channels and disrupt the membrane at the node of Ranvier.
Deficits of smooth‐pursuit eye movement after unilateral frontal lobe lesions
Authors: Morrow Mark J. , Sharpe James A. 
Published: January 2005

AbstractWe recorded horizontal smooth‐pursuit responses to sinusoidal and step‐ramp stimuli in 7 patients with unilateral frontal lobe lesions. Five patients had directional smooth‐pursuit deficits, all with impairment toward the side of cerebral damage. Ipsidirectional pursuit defects involved pursuit maintenance to sinusoidal targets, pursuit initiation to step‐ramp targets, or both. No patient had asymmetry of smooth pursuit according to the retinal hemifield of target appearance. Smooth‐pursuit velocities were subnormal in both horizontal directions in 4 patients. The human frontal lobes participate in the initiation and maintenance of smooth pursuit in both directions, with a greater ipsilateral contribution. Of 5 patients with ipsilateral pursuit impairment, 3 had cerebral lesions in the area of the frontal eye field (FEF). These 3 patients also made inaccurate saccades to targets moving away from the side of the lesion, implying that the FEF transmits motion information to the saccadic system. Two patients with ipsidirectional smooth‐pursuit defects had cerebral damage that spared the FEF, indicating that other frontal regions also contribute to smooth pursuit.