bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topography of fibers in the human corpus callosum mediating interhemispheric inhibition between the motor cortices
Authors: Meyer Bernd‐Ulrich , Röricht Simone , Woiciechowsky Christian 
Published: January 2005

AbstractIn 1 split‐brain patient and 13 patients with circumscript surgical lesions within different parts of the corpus callosum (CC), the topography of fibers within the CC mediating an interhemispheric inhibition between the motor cortices was investigated in the phase of a stable disconnection syndrome. The aim of the study was to characterize the system of callosal fibers activated by transcranial magnetic brain stimulation in more detail as a basis for a diagnostic application of this technique. The locations and areas of the lesions were measured on sagittal magnetic resonance (MR) slices and attributed to five segments of the CC, because the borders of the anatomic subdivisions of the CC are not clearly defined. Transcallosal inhibition (TI) of tonic electromyographical hand muscle activity was elicited by focal transcranial magnetic stimulation over the primary motor cortex. In a reference group of normal subjects, TI started after 35.8 ± 3.6 msec had a duration of 24.8 ± 2.7 msec and an estimated transcallosal conduction time of 15.5 ± 3.0 msec (range, 10.2–20.0 msec, n = 24 hands). No significant differences were found for the TI originating from the right and left motor cortices. From the absence and presence of TI in patients with lesions in different parts of the CC it can be concluded that most of the fibers mediating TI pass through the posterior third and anterior fourth segment of the CC, that is, through the posterior half of the trunk of the CC. The clinical findings suggest a role for TI in the performance of fast and complex hand motor tasks.
Stiff‐leg syndrome: A focal form of stiff‐man syndrome
Authors: Saiz Albert , Graus Francesc , Valldeoriola Francesc , Valls‐Solé Josep , Tolosa Eduardo 
Published: January 2005

AbstractWe report on 2 patients who presented stiffness and spasms similar to those of stiff‐man syndrome (SMS) that were limited to one leg for up to 11 years. Patients had serum glutamic acid decarboxylase (GAD) autoantibodies in high titer, clinical evidence of organ‐specific autoimmunity, and electromyographic pattern of continuous motor unit activity with abnormally enhanced exteroceptive reflexes. The clinical and immunological profile suggests that this disorder may be a focal form of SMS.
Matrix metalloproteinases MMP‐9 and MMP‐7 are expressed in experimental autoimmune neuritis and the guillain‐barré syndrome
Authors: Kieseier B. C. , Clements J. M. , Pischel H. B. , Wells G. M. A. , Miller K. , Gearing A. J. H. , Hartung H.‐P. 
Published: January 2005

AbstractMatrix metalloproteinases (MMPs) are a family of enzymes that may be implicated in the pathogenesis of inflammatory demyelinating disorders such as multiple sclerosis. The present study investigated the expression of 92‐kd gelatinase (MMP‐9) and five other MMPs in sciatic nerve from Lewis rats with autoimmune experimental neuritis (EAN), an experimental model of the Guillain‐Barre syndrome(GBS). Quantitative polymerase chain reaction analysis revealed an up‐regulation of MMP‐9 mRNA with peak levels concurrent with maximal disease severity. Increased mRNA expression was associated with enhaced enzyme activity, as detected by gelatin zymography. Immunohistochemically, MMP‐9 could be localized primarily around blood vessels within the epineurium and enhoneurium in diseased but not normal sciatic nerve. Among all other MMPs investigated, mRNA levels of matrilysin (MMP‐7) were found to be up‐regulated at the peak of the disorder, remaining at high levels throughout the clinical recovery phase of the disease. To apply these findings to human disease, sural nerve biopsies from GBS patients were examined. By using immunohistochemistry, positive immunoreactivity against MMP‐9 and MMP‐7 was noted and corroborated by demonstrating augmented mRNA expression in comparison with noninflammatory neuropathies. Furthermore, increased MMP‐9 activity was detected by zymography. These findings indicate that 92‐kd gelatinase and matrilysin are selectively up‐regulated during EAN and expressed in nerves of GBS patients and thus may contribute to the pathogenesis of inflammatory demyelination of the peripheral nervous system.
Angelman syndrome: Correlations between epilepsy phenotypes and genotypes
Authors: Minassian Berge A. , Delorey Timothy M. , Olsen Richard W. , Philippart Michel , Bronstein Yuri , Zhang Quanwei , Guerrini Renzo , van Ness Paul , Livet Marie O. , Delgado‐Escueta Antonio V. 
Published: January 2005

AbstractWe compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11‐13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed‐circuit television videotaping and digitized electroencephalographic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high‐amplitude 1‐ to 3‐Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged‐matched class II, III, and IV patients had either no epilepsy or drug‐responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11‐13 deletions produce severe epilepsy. Loss‐of‐function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11‐13 deletion, such as GABRB3, may explain severe epilepsy in AS.
Expression of the early‐onset torsion dystonia gene (DYT1) in human brain
Authors: Augood Sarah J. , Penney John B. , Friberg Ingrid K. , Breakefield Xandra O. , Young Anne B. , Ozelius Laurie J. , Standaert David G. 
Published: January 2005

AbstractEarly‐onset torsion dystonia, an autosomal dominant disease associated with the DYT1 locus on 9q34, is the most frequent genetic form of dystonia. Recent work has revealed that the causative mutation in most cases is deletion of a glutamate residue from the carboxy terminal of torsinA, a 332 amino acid protein encoded by the DYT1 gene. To gain insight into how deletion of a single amino acid can produce such a profound movement disorder, we have mapped the expression of the DYT1 gene in normal human postmortem brain. DYT1 mRNA is highly enriched in the dopamine neurons of the substantia nigra pars compacta. Intense expression was also found in the cerebellum and hippocampal subfields. The prominent expression of the DYT1 gene within the substantia nigra pars compacta, which provides dopaminergic innervation to the basal ganglia, implicates a disturbance of dopaminergic function in the pathophysiology of early‐onset torsion dystonia.
Dynamic [18F]fluorodeoxyglucose positron emission tomography and hypometabolic zones in seizures: Reduced capillary influx
Authors: Cornford Eain M. , Gee Manyee N. , Swartz Barbara E. , Mandelkern Mark A. , Blahd William H. , Landaw Elliot M. , Delgado‐Escueta Antonio V. 
Published: January 2005

AbstractWe performed dynamic [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomographic (PET) analyses in 8 patients. Rate constants of influx (K1*), efflux (k2*), phosphorylation (k3*), and dephosphorylation (k4*) were derived for the regions of interest (ROIs), which included (1) the hypometabolic epilptogenic regions and (2) the homologous regions in the contralateral hemispheres. In addition, the four constants were determined from at least one clearly defined (control) ROI from the same plane and its homologous contralateral ROI. (K1*) in the eplieptogenic region was reduced in comparison with the contralateral ROI. Reductions in influx (K1*), which averaged 18 ± 13% (mean ± SD), [18F]FDG phosphorylation (k3*) (25 ± 20%), and brain glucose utization rates (26 ± 10%) were observed in the epileptogenic region. Reductions in efflux were not statistically significant (k2* = 13 ± 28%) but were comparable in magnitude to the average reduction in K1*. No ipsilateral versus contralateral differnces were seen for any rate constants measured outside the epileptogenic region. Influx correlated highly with phosphorylation in the epileptogenic region. Our data suggest that the hypometabolic epileptogenic focus seen in [18F]FDG‐PET studies is also a region of reduced blood‐brain barrier glucose transporter activity and that reductions in phosphorylation are proportional to reductions in [18]FDG influx.
Dystonia with motor delay in compound heterozygotes for GTP‐cyclohydrolase I gene mutations
Authors: Furukawa Yoshiaki , Kish Stephen J. , Bebin E. Martina , Jacobson Richard D. , Fryburg Julie S. , Wilson Willam G. , Shimadzu Mitsunobu , Hyland Keith , Trugman Joel M. 
Published: January 2005

AbstractMutations in the GTP‐cyclohydrolase I(GCH) gene have been identified as a cause of two disorders: autosomal dominant hereditary progressive dystonia/dopa‐responsive dystonia (HPD/DRD) and autosomal recessive GCH‐deficient hyperphenylalaninemia (HPA). Detailed clinical descriptions and genetic analysis of patients with phenotypes intermediate between HPD/DRD (mild) and GCH‐deficient HPA (severe) have not been reported. We conducted genomic DNA sequencing of the GCH gene in two patients (cases 1 and 2) manifesting generalized dystonia responsive to levodopa and severe developmental motor delay. In the pedigree of Patient 1, there were HPD/DRD patients in three generations preceding the index case. Patients 1 and 2 were compound heterozygotes with maternally and paternally transmitted mutations in the coding region of the GCH gene. In both compound heterozygotes, tetrahydrobiopterin (BH4) levels in cerebrospinal fluid were lower than those in HPD/DRD. Administration of BH4, in addition to levodopa, further improved the symptomatology of Patient 1. Our data demonstrate a new phenotype of GCH deficiency associated with compound heterozygosity for GCH gene mutations and suggest the usefulness of combined BH4 and levodopa therapy for this disorder.
Synergistic immunomodulatory effects of interferon‐β1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing‐remitting multiple sclerosis
Authors: Weber Frank , Polak Thomas , Günther Astrid , Kubuschok Boris , Janovskaja Julia , Bitsch Andreas , Poser Sigrid , Rieckmann Peter 
Published: January 2005

AbstractSubcutaneous application of interferon‐β1b (IFN‐β1b) is an established therapy for patients with relapsing‐remitting multiple sclerosis (RRMS), but early side effects are still a major concern. In vitro studies with myelin basic protein (MBP)–specific T‐cell lines revealed a synergistic suppressive effect of IFN‐β1b and the phosphodiesterase inhibitor pentoxifylline (PTX) on proliferation and the production of tumor necrosis factor‐α (TNF‐α), lymphotoxin (LT), and interferon‐γ (IFN‐γ). In an initial, open labeled prospective trial, the cytokine messenger RNA (mRNA) expression of blood mononuclear cells from MS patients, receiving either IFN‐β1b alone or in combination with oral PTX, was determined by semi‐quantitative reverse transcriptase polymerase chain reaction (RT‐PCR). Patients treated with IFN‐β1b alone reported more side effects during the first 3 months of treatment and had upregulated TNF‐α as well as IFN‐γ mRNA expression during the first month, which was not detected in patients receiving both drugs. A synergistic effect of both drugs was observed on the upregulation of interleukin (IL)‐10 mRNA, which was accompanied by an increase in IL‐10 serum levels. Both in vitro and in vivo data suggest that co‐treatment of IFN‐β1b with PTX is a promising approach to correct the disturbed cytokine balance in MS patients.
Phenotypic expression of the DYT1 mutation: A family with writer's cramp of juvenile onset
Authors: Gasser T. , Windgassen K. , Bereznai B. , Kabus C. , Ludolph A. C. 
Published: January 2005

AbstractRecently, the mutation causing early‐onset generalized torsion dystonia has been identified as a GAG deletion in the gene for an adenosine triphosphate–binding protein named torsinA. We describe a German family with 5 clinically affected individuals carrying this mutation. In at least 4 of the 5 patients, the disease presented as a dystonic writer's cramp during late childhood or adolescence, which affected sequentially both sides but did not progress to a generalized form of dystonia. We conclude that familial writer's cramp may be a manifestation of the DYT1 mutation.
Inhibition of γ‐aminobutyric acid synthesis by glutamic acid decarboxylase autoantibodies in stiff‐man syndrome
Authors: Dinkel Klaus , Meinck Hans‐Michael , Jury Karin M. , Karges Wolfram , Richter Wiltrud 
Published: January 2005

AbstractStiff‐man syndrome (SMS) is a rare disorder of the central nervous system thought to result from an impairment of γ‐aminobutyric acid (GABA)ergic neurotransmission. Autoantibodies to the GABA‐synthesizing enzyme glutamic acid decarboxylase (GAD), present in about 60% of SMS patients, have suggested an autoimmune pathogenesis of SMS. By using serum or cerebrospinal fluid from 25 SMS patients, we assessed the effect of GAD autoantibodies (GAD‐A) on GAD enzymatic activity in vitro; 83% of GAD‐A–positive SMS sera reduced GABA production in crude rat cerebellar extracts, whereas GAD‐A− sera from SMS patients or healthy blood donors did not alter the enzyme activity. Inhibition of GABA synthesis by SMS sera was dose dependent and mediated by the purified IgG fraction of the sera. Human monoclonal GAD65‐A and IgG purified from serum of GAD‐A–positive patients with insulin‐dependent diabetes or autoimmune polyendocrine syndrome did not effect GAD activity, suggesting that a specific epitope recognition of GAD‐A mediates inhibition of GAD. The disease‐specific detection of GAD‐inhibitory antibodies is compatible with their functional involvement in the etiopathology of SMS; the relevance of such antibodies in vivo, however, remains to be determined.
IgG Anti‐GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain‐barré syndrome
Authors: Kuwabara Satoshi , Yuki Nobuhiro , Koga Michiaki , Hattori Takamichi , Matsuura Daisuke , Miyake Masami , Noda Masatoshi 
Published: January 2005

AbstractTo investigate the pathophysiological role of anti‐GM1 antibody in Gullain‐Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti‐GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti‐GM1‐positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti‐GM1‐negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti‐GM1)positive GBS. In both cases, immune‐mediated attack probably occurs on the axolemma of motor fibers.
In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging
Authors: De Stefano Nicola , Caramanos Zografos , Preul Mark C. , Francis Gordon , Antel Jack P. , Arnold Douglas L. 
Published: January 2005

AbstractWe used computer pattern recognition of proton magnetic resonance spectroscopic image data to differentiate between brain tumors and large, isolated, demyelinating lesions of the type seen in multiple sclerosis. Leave‐one‐out linear discriminant analyses correctly classified resonance profiles from five acute demyelinating lesions, 20 low‐grade astrocytomas, 22 anoplastic astrocytomas, and 24 glioblastomas. Classification of nonacute lesions will require further development, as the metabolic profiles of demyelinating lesions evolve over time.
Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease
Authors: Hutchison W. D. , Allan R. J. , Opitz H. , Levy R. , Dostrovsky J. O. , Lang A. E. , Lozano A. M. 
Published: January 2005

AbstractMicroelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recorded neurons, and responses to active and passive limb and orofacial movements were tested. STN neurons had a mean firing rate of 37 ± 17 Hz (n = 248) and an irregular firing pattern (median burst index, 3.3). Movement‐related activity and tremor cells were identified in the STN. Ventral to the STN, substantia nigra pars reticulata neurons had a mean rate of 71 ± 23 Hz (n = 56) and a more regular firing pattern (median burst index, 1.7). Short trains (1–2 seconds) of electrical microstimulation of STN could produce tremor arrest but were and found to be useful for localization. Compared with data from normal monkeys our findings suggest that STN neuronal activity is elevated in Parkinson's disease.
Progressive myoclonus epilepsy and mitochondrial myopathy associated with mutations in the tRNAser(UCN) gene
Authors: Jaksch Michaela , Klopstock Thomas , Kurlemann Gerd , Dörner Marion , Hofmann Sabine , Kleinle Stephanie , Hegemann Stephan , Weissert Markus , MüLler‐Höcker Josef , Pongratz Dieter , Gerbitz Klus‐Dieter 
Published: January 2005

AbstractWe report seven unrelated families with mitochondrial tRNASer(UCN) gene mutations at three different loci. A novel G7497A mutation is found in two families, both of which present with progressive myopathy, ragged‐red fibers, lactic acidosis, and deficiency of repiratory chain complexes I and IV. This mutation presumably affects the tertiary tRNASer(UCN) dihydrouridine interaction. Mutations 7472 insC and T7512C, found in three and two families, respectively, are associated with myoclonus epilepsy, deafness, ataxia, cognitive impairment, and complex IV deficiency. No ragged‐red fibers or ultrastructural abnormalities are seen. It is interesting that 6 of our 7 index patients are apparently homoplasmic, indicating a minor pathogenetic power of the tRNASer(UCN) mutations.
Acquired slow–channel syndrome: A form of myasthenia gravis with prolonged open time of the acetylcholine receptor channel
Authors: Wintzen Axel R. , Plomp Jaap J. , Molenaar Peter C. , van Dijk J. Gert , van Kempen Gertrudis T. H. , Vos Renske M. , Wokke John H. J. , Vincent Angela 
Published: January 2005

AbstractA 32‐year‐old female presented with a 2‐year history of fluctuating generalized weakness including extraocular, bulbar, and limb muscles, suggesting myasthenia gravis, but with poor response to pyridostigmine and unusual electromyographic findings. After rest, power increased on repeated maximal contractions, followed by progressive weakness. There were decremental responses at low‐frequency stimulation, but incremental responses at high frequencies, and single stimuli evoked repetitive compound muscle action potentials. Plasmapheresis was ineffective. In a conventional assay, antibodies against acetylcholine receptors (AChRs) were borderline. However, in an assay using cells expressing mainly adult‐type human AChRs, the patient's serum was positive. Thymectomy revealed a hyperplastic thymus. An intercostal muscle specimen revealed small miniature end‐plate potentials, 0.22 ± 0.02 mV instead of 0.56 ± 0.05 mV in controls. The number of 125I‐α‐bungarotoxin binding sites was normal. The decay time constant of end‐plate potentials was increased from 5.3 ± 0.6 msec in controls to 23 ± 3.6 msec in the patient. Ultrastructurally, there was no destruction of the end plate. Transfer of the patient's plasma to mice in vivo produced similar physiological changes in their diaphragms. We conclude that the patient has an immune‐mediated disorder, in which an antibody specific to the adult form of the AChRs alters the channel properties, reducing total current and slowing the closure. We propose the name “acquired slow‐channel syndrome” for this variant of myasthenia gravis.
Neonatal cytokines and coagulation factors in children with cerebral palsy
Authors: Nelson Karin B. , Dambrosia James M. , Grether Judith K. , Phillips Terry M. 
Published: January 2005

AbstractWe explored the association of inflammatory mediators and markers of autoimmune and coagulation disorders with cerebral palsy (CP), examinig 53 analytes in dried neonatal blood of 31 children with spastic CP, most born at term, and 65 control children. Ultramicroanalysis was performed by recycling immunoaffinity chromatography coupled with laser‐enhanced fluorescence and chemiluminescence detection. Reactive antibodies to lupus anticoagulant, anticardiolipin, antithrombin III, and the translational product of the factor V Leiden mutation were isolated by recycling immunoaffinity chromatography and measured by capillary electrophoresis with chemiluminescence‐enhanced immunoassay. Higher concentrations of interleukins (ILs) 1, 8, 9, tumor necrosis factor‐α, and RANTES were observed in these children with CP than in any control child. There were also substantial elevations of IL‐6, 11, 13, and other chemokines and colony‐stimulating factors in children with CP. Antiphospholipid antibody was present in a titer of 1:100 or greater in 4 children with CP and no control child. Using cuts empirically chosen by recursive partitioning, we found higher concentrations of antibody to antithrombin III, to a translational product of factor V Leiden mutation, and to proteins C and S in children with CP than in controls. We conclude that inflammation and these coagulation abnormalities, which have interacting pathways, are important in the etiology of CP.
α‐ketoglutarate dehydrogenase in alzheimer brains bearing the APP670/671 mutation
Authors: Gibson G. E. , Zhang H. , Sheu K. F. ‐R. , Bogdanovich N. , Lindsay J. G. , Lannfelt L. , Vestling M. , Cowburn R. F. 
Published: January 2005

AbstractAlzheimer's disease (AD) is associated with a striking reduction in the activity of the α‐ketoglutarate dehydrogenase complex (KGDHC). The deficiency occurs in brains from AD patients of undefined etiology, and in fibroblasts from both sporadic and familial AD cases. To further assess the nature of the abnormality of KGDHC in AD, KGDHC activities and immunoreactivities were analyzed in brains from AD patients bearing the Swedish APP670/671 mutation. This gene defect causes overproduction of the amyloid β peptide. KGDHC activities were reduced by 55 to 57% compared with control values in the mutation‐bearing AD cases in the medial temporal and superior frontal cortices. The immunochemical levels of KGDHC subunits E1k (−51%) and E2k (−76%) declined, whereas E3 concentrations were unchanged. The results suggest that mitochondrial dysfunction is a part of the pathophysiological process in AD even when the primary pathogenic cause is nonmitochondrial.