bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary myelin basic protein—like material as a correlate of the progression of multiple sclerosis
Authors: Whitaker J. N. , Kachelhofer R. D. , Bradley E. L. , Burgard S. , Layton B. A. , Reder A. T. , Morrison W. , Zhao G. J. , Paty D. W. 
Published: January 2005

AbstractIn the multicenter, randomized, placebo‐controlled trial of alternate‐day injections of recombinant interferon beta‐1b in relapsing‐remitting multiple sclerosis (MS), urine specimens were collected periodically from all patients (n = 64) in two of the clinical test sites over the 2 years of the study. Urine specimens were also collected over two consecutive 24‐hour periods from 43 patients from a third center. Urine samples were assayed for their content of myelin basic protein‐like material (MBPLM), the level of which was correlated with clinical changes, cranial magnetic resonance imaging results, and the development of progressive disease. Concordant changes in creatinine values affected some of the relationships of MBPLM. The level of urinary MBPLM correlated with a chronic progressive course and with the number of lesions and the total lesion area on cranial magnetic resonance images. A rise in the level of urinary MBPLM appeared to antedate the clinical transition from a relapsing‐remitting to a chronic progressive course. By chance, the randomized entry of patients led to significant differences in urinary MBPLM levels among the three treatment groups, thus precluding correlation studies of treatment effects. However, the patient group from which 24‐hour specimens were collected showed that the patients with relapsing‐remitting MS changing to a chronic progressive course, and more specifically, those patients with chronic progressive MS receiving placebo, had the highest values of urinary MBPLM. These findings indicate that urinary MBPLM may offer an objective test and possibly serve as a surrogate Marchker for detecting or predicting the failure of remission or the transition to a progressive phase of MS.
Apolipoprotein E genotypes and age of onset in early‐onset familial Alzheimer's disease
Authors: Levy‐Lahad Ephrat , Lahad Amnon , Wijsman Ellen M. , Bird Thomas D. , Schellenberg Gerard D. 
Published: January 2005

AbstractThe effect of the apolipoprotein E (APOE) ϵ4 allele on age of onset was analyzed in two groups of families with early‐onset Alzheimer's disease (AD), (1) Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2) early‐onset non‐VG families showing evidence of linkage to chromosome 14. The ϵ4 allele did not have a detectable effect on age of onset in either group. This finding suggests some forms of early‐onset familial AD are not modifiable by APOE status, or that AD can be caused by APOE‐independent pathways.
Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood
Authors: Kemp G. J. , Taylor D. J. , Barnes P. R. J. , Wilson J. , Radda G. K. 
Published: January 2005

AbstractAlternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of phosphocreatine concentration during exercise was three‐fold greater than in control subjects. However, the initial rate of ATP turNovemberer at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.
Dopa‐responsive parkinsonism phenotype of Machado‐Joseph disease: Confirmation of 14q CAG expansion
Authors: Tuite P. J. , Rogaeva E. A. , St George‐Hyslop P. H. , Lang A. E. 
Published: January 2005

AbstractThe subtype IV of Machado‐Joseph disease (MJD), characterized by parkinsonism variably combined with ataxia, distal atrophy, and sensory loss, has been all but ignored in recent reports of MJD, including those describing the molecular biologic substrate of the disease. We have demonstrated expansion of the CAG trinucleotide repeat of the MJD1 gene located on chromosome 14q32.1 in 2 patients of Azorean descent who presented with levodopa‐responsive atypical parkinsonism. Previous publications have documented the presence of this expanded repeat in the other more common MJD phenotypes (I‐III). To our knowledge, this is the first molecular biologic confirmation of the presence of the MJD1 gene in the subtype IV phenotype. Patients presenting with parkinsonism and peripheral neuropathy should be screened for this genetic defect.
Reversible dementia and apparent brain atrophy during valproate therapy
Authors: Papazian Oscar , Canizales Elizabeth , Alfonso Israel , Archila Ricardo , Duchowny Michael , Aicardi Jean 
Published: January 2005

AbstractTwo children developed severe cognitive and behavioral deterioration suggestive of a degenerative disease while being treated with sodium valproate for idiopathic, localization‐related epilepsy with centrotemporal spikes. Magnetic resonance imaging revealed Marchked central and generalized cortical and cerebellar atrophy. In both patients, clinical symptoms and signs cleared in a few weeks following valproate withdrawal. The magnetic resonance imaging appearance improved within 3 months in 1 of the patients and normalized in both after 6 and 12 months. No metabolic changes were associated with the clinical or imaging abnormalities. Although the mechanism of this rare idiosyncratic complication of valproate therapy is unknown, we advocate discontinuing valproate therapy in all epileptic patients with neuromental deterioration or brain atrophy of unknown etiology.
Neurodevelopmental effects of X monosomy: A volumetric imaging study
Authors: Reiss Allan L. , Mazzocco Michèle M. M. , Greenlaw Ronald , Freund Lisa S. , Ross Judith L. 
Published: January 2005

AbstractThirty girls with Turner syndrome (TuS) were compared with 30 individually age‐matched controls on volumtric brain measures derived from magentic resonance imaging and on measures of psychological functioning. As expected, girls with TuS performed more poorly on visual‐spatial and intellectual measures relative to controls, and were rated by their parents as having more significant problems in attention and social behaviors. Although no group differences in overall cerebral or subcortical volumes were observed, the regional distribution of gray and white matter differed across groups in both right and left parietal regions. Differences in total tissue volume ratios were seen for both right and left parietal regions. In general, girls with TuS had a smaller proportion of tissue (gray and white) within the right and left parietal regions, and a larger proportion of tissue within the right inferior parietal‐occipital region relative to girls in the control group. These data suggest a potentially important role for X chromosome genes and/or sex steroids in the development and specialization of brain structure and function.
Resolution‐dependent estimates of lesion volumes in magnetic resonance imaging studies of the brain in multiple sclerosis
Authors: Filippi M. , Horsfield M. A. , Campi A. , Mammi S. , Pereira C. , Comi G. 
Published: January 2005

AbstractIn this study, we investigated the relationship between multiple sclerosis lesion volumes measured from magnetic resonance imaging scans and image‐slice thickness. The lesion volume was computed using a semiautomated thresholding technique from axial scans of the brain of varying slice thickness. Ten patients were studied, and in all cases the computed lesion volume increased with decreasing slice thickness (p = 0.01). Linear extrapolation from our data allowed the lesion volume at very small slice thickness to be estimated; this was found to be on average 20% greater than that obtained using a slice thickness of 5 mm. Furthermore, there were considerable differences in the percentage of change in lesion volume from patient to patient, and it would appear that there is a larger variation with slice thickness for patients with smaller lesions and higher lesion loads.
The effect of deprenyl and levodopa on the progression of Parkinson's disease
Authors: Olanow C. W. , Hauser R. A. , Gauguster L. , Malapira T. , Koller W. , Hubble J. , Bushenbark K. , Lilienfeld D. , Esterlitz J. 
Published: January 2005

AbstractWe have performed a 14‐month, prospective, randomized, double‐blind, placebo‐controlled study to evaluate the effect of deprenyl and levodopa/carbidopa (Sinemet) on the progression of signs and symptoms in patients with mild Parkinson's disease (PD). One hundred one untreated PD patients were randomly assigned to one of the following four treatment groups: Group I, deprenyl + Sinemet; Group II, placebo‐deprenyl + Sinemet; Group III, deprenyl + bromocriptine; and Group IV, placebo‐deprenyl + bromocriptine. The final visit was performed at 14 months, i.e., 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine. Deterioration in Unified Parkinson's Disease Rating Score (UPDRS) between untreated baseline and final visits was used as an index of disease progression. Placebo‐treated patients deteriorated by 5.8 ± 1.4 points, while deprenyl‐treated patients deteriorated by 0.4 ± 1.3 points (p < 0.001). This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients randomized to Sinemet (p < 0.01) as well as in the 23 patients who completed a 14‐day washout of Sinemet or bromocriptine (p < 0.05). No difference in the extent of deterioration was detected in patients randomized to Sinemet versus bromocriptine. This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD. These findings are not readily explained by the drug's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect.
Depth electrode studies and intracellular dentate granule cell recordings in temporal lobe epilepsy
Authors: Williamson Anne , Spencer Susan S. , Spencer Dennis D. 
Published: January 2005

AbstractHippocampal depth electrodes are often used to localize seizure onset in patients who may have temporal lobe epilepsy (TLE). A number of features of the spontaneous seizures and of their ictal onset patterns can be analyzed from these recordings. We compared a number of the typical electroencephalographic (EEG) changes at seizure onset with several cellular parameters recorded in dentate granule cells from the same 14 patients diagnosed with medial temporal sclerosis (MTS) to examine the pathophysiological correlates of this spontaneous EEG activity in this form of TLE. The intracellularly recorded parameters include the propensity to fire evoked epileptiform bursts, the absence of evoked inhibitory potentials, the presence of polysynaptic excitatory postsynaptic potentials, and the presence of spontaneous excitatory activity. We noted several correlations between the EEG data and the intracellular recordings. The absence of synaptically evoked bursts was correlated with the presence of low‐voltage fast activity at seizure onset. In addition, the loss of inhibitory postsynaptic potentials was correlated with the presence of periodic spiking pre‐ictally. Several other correlations were also noted. These data indicate that EEG findings may be predictive of anatomical and cellular pathological changes and provide clues to the physiological mechanisms involved in this form of epilepsy.
Experimental status epilepticus alters γ‐aminobutyric acid type A receptor function in CA1 pyramidal neurons
Authors: Kapur Jaideep , Coulter Douglas A. 
Published: January 2005

AbstractThere is a reduction of β‐aminobutyric acid (GABA)‐mediated inhibition in the CA1 pyramidal region of the hippocampus during status epilepticus (SE). The cellular basis of this loss of GABA‐mediated inhibition is not known. This study tested the possibility that GABA type A (GABAA) receptor function in CA1 pyramidal neurons was reduced or blocked during SE, at least in part by postsynaptic cellular mechanisms. GABAA receptor currents (IGABA) were studied by whole‐cell patch‐clamp techniques in CA1 pyramidal neurons acutely dissociated from rats undergoing lithium/pilocarpine‐induced limbic status epilepticus (SE neurons) and from naive rats (naive neurons). SE neurons had more depolarized resting membrane potential (−17.3 mV) compared with naive neurons (−56 mV). IGABA was absent in 47% of SE neurons and reduced in 55% of the remainder, compared with naive neurons. The reduction in IGABA in SE neurons resulted from a combination of factors, including reduced potency and reduced efficacy of GABA in activating chloride channels, and diminished driving force for the GABA‐induced chloride currents once activated. These postsynaptic cellular mechanisms resulted in a net reduction or loss in GABA‐mediated inhibition and may explain previous in vivo findings reporting a loss of inhibition in hippocampus during limbic SE.
The role of reading activity on the modulation of motor cortical outputs to the reading hand in braille readers
Authors: Pascual Alvaro , Wassermann Eric M. , Sadato Norihiro , Hallett Mark 
Published: January 2005

AbstractWe studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digitiminimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition.
Enhanced expression of microtubule‐associated protein 2 in large neurons of cortical dysplasia
Authors: Yamanouchi Hideo , Zhang Weixian , Jay Venita , Becker Laurence E. 
Published: January 2005

AbstractTo evaluate neuronal cytoarchitectural changes in cortical dysplasia, we examined microtubule‐associated protein 2 (MAP2) expression in surgically resected specimens obtained from 20 patients (age range, 3 months to 10 years) treated for intractable epilepsy. Large neurons were investigated in the specimens from all patients and showed significantly strong immunoreactivity with antibodies against MAP2 in the perikaryon and proximal portion of their processes. In situ hybridization with MAP2 antitense riboprobe showed increased hybridization signal intensities in the large neurons, which correlated with the pattern of immunoreactivity for MAP2. We conclude that MAP2 is strongly expressed in the large neurons in cortical dysplasia. The results of preliminary immunoblotting in 1 patient with focal cortical dysplasia showed that the low‐molecular‐weight form of MAP2 (MAP2c) was strongly expressed in the dysplastic cortex, suggesting that MAP2c may be a major component contributing to the increased expression of MAP2 in the large neurons of cortical dysplasia. Since it has been suggested that MAP2 plays a crucial role in the branching and remodeling of neuronal processes, increased expression of MAP2 may reflect activated plasticity of the large neurons in cortical dyspasia.
Familial hemiplegic migraine, nystagmus, and cerebellar atrophy
Authors: Elliott Michael A. , Peroutka S. J. , Welch S. , May Eugene F. 
Published: January 2005

AbstractFamilial hemiplegic migraine (FHM) is an autosomal dominant disorder characterized by transient hemiplegia during the aura phase of a migraine attack. Nystagmus has been reported in individuals affected with this disorder, but the origin of the ocular motility findings is unknown. A three‐generation family with FHM is described and clinical histories are outlined. Ocular motility evaluations were performed on 7 family members, 5 with a history of hemiplegic migraine and 2 without history of migraine. All affected family members had abnormal eye movements consistent with vestibulocerebellar dysfunction. Magnetic resonance imaging scans in affected family members revealed cerebellar vermian atrophy. DNA linkage analysis revealed a common marker in all the affected family members on chromosome 19. We suggest that the hemiplegic migraine attacks and the cerebellar degeneration are linked genetically and that the eye movements are not the ischemic sequelae of recurrent migraine. Strikingly similar ocular motility findings and cerebellar degeneration are reported in both FHM and a genetically related disorder, hereditary paroxysmal cerebellar ataxia (HPCA). The significance of these similarities is discussed along with a proposed pathophysiology for FHM.
Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia
Authors: Turner R. S. , Kenyon L. C. , Trojanowski J. Q. , Gonatas N. , Grossman M. 
Published: January 2005

AbstractWe report the clinical, neuroimaging, and neuropathologic features of progressive nonfluent aphasia (PNFA), a rare neurodegenerative syndrome most notable for its distinct language disturbance. Longitudinal observations of 3 patients revealed progressively telegraphic speech and writing, followed by gradual deterioration of sentence comprehension, and finally, preterminal mutism and dementia. Magnetic resonance imaging revealed cortical atrophy most pronounced in anterior regions of the left hemisphere. Functional neuroimaging demonstrated reduced cerebral activity most prominently in left frontal and temporal regions. At necropsy, microscopic pathology of brain was most consistent with the diagnosis of “dementia lacking distinctive histology” (DLDH). A review of published primary progressive aphasia cases with adequate clinical and hietopathological descriptions reveals that the most common pathology underlying PNFA is DLDH. PNFA is one example of a family of clinical syndromes with similar underlying histopathology that affects different regions of the frontal lobe.
Deficiency of complex II of the mitochondrial respiratory chain in late‐onset optic atrophy and ataxia
Authors: Taylor Robert W. , Birch‐Machin Mark A. , Schaefer Jochen , Taylor Louise , Shakir Raad , Ackrell Brian A. C. , Cochran Bruce , Bindoff Laurence A. , Jackson Margaret J. , Griffiths Philip , Turnbull Douglass M. 
Published: January 2005

AbstractDefects of the mitochondrial respiratory chain are increasingly being recognized as an important cause of neurological disease in humans. In many of these patients, the biochemical defect results from an abnormality of the mitochondrial genome. Respiratory chain defects involving complex II, which is entirely encoded by the nuclear genome, are comparatively rare. We report the clinical and biochemical findings in 2 elderly sisters who presented with late‐onset neurodegenerative disease. In both patients, a partial deficiency of complex II (approximately 50% of control values) was shown to be present in mitochondria from muscle and platelets. The enzyme defect was not expressed in cultured skin fibroblasts or immortalized lymphocytes. There was an overexpression of the 70‐kd flavoprotein subunit in muscle mitochondria from both patients, although we showed that this subunit is present in normal amounts in mitochondrial membranes. Our studies highlight the diversity of the clinical presentation of respiratory chain disease and that complex II deficiency should enter the differential diagnosis of certain patients with late‐onset neurodegenerative disease.
Myelin basic protein and human coronavirus 229E cross‐reactive T cells in multiple sclerosis
Authors: Talbot Pierre J. , Paquette Jean‐Sébastien , Ciurli Cristina , Antel Jack P. , Ouellet France 
Published: January 2005

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating neurological disease in which autoreactive T lymphocytes sensitized to myelin components of the central nervous system are postulated to contribute to pathogenesis. The possible relevance of molecular mimicry between a human coronavirus and the myelin basic protein component of myelin in the generation of this autoimmune reaction was evaluated. Myelin basic protein– and virus‐reactive T‐cell lines were established from 16 MS patients and 14 healthy donors and shown to be mostly CD4+. In contrast to healthy donors, several T‐cell lines isolated from MS patients showed cross‐reactivity between myelin and coronavirus antigens. Overall, 29% of T‐cell lines from MS patients (10 donors) but only 1.3% of T‐cell lines from normal control subjects (2 donors) showed an HLA‐DR‐restricted cross‐reactive pattern of antigen activation after in vitro selection with either myelin basic protein or human coronavirus strain 229E antigens. Moreover, reciprocal reactivities were only observed in MS patients (4 donors). This establishes molecular mimicry between a common viral pathogen, such as this human coronavirus, and myelin as a possible immunopathological mechanism in MS and is consistent with the possible involvement of more than one infectious pathogen as an environmental trigger of disease.