bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late‐onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: Compound heterozygosity for the IVS2+1G→a mutation and a newly identified missense mutation (Thr408Ile) in a Spanish family
Authors: Comabella Manuel , Waye John S. , Raguer Nuria , Eng Barry , Domínguez Carmen , Navarro Carmen , Borrás Cecilia , Krivit William , Montalbán Xavier 
Published: November 2004

AbstractWe report the case of a 50‐year‐old woman and her 32‐year‐old daughter, both of whom are affected with adult‐onset metachromatic leukodystrophy (MLD) clinically presenting as peripheral neuropathy. Arylsulfatase A (ARSA) activities were markedly reduced, and electrophysiology showed a severe demyelinating neuropathy with features of chronic acquired demyelinating polyneuropathy. Molecular genetic studies of the family revealed that the proband and her affected daughter are compound heterozygotes for the common IVS2+1G→A mutation and a newly identified missense mutation, Thr408Ile. This case indicates that adult metachromatic leukodystrophy should be considered in adult patients with demyelinating peripheral neuropathy of unknown etiology.
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion
Authors: Margolis Russell L. , O'Hearn Elizabeth , Rosenblatt Adam , Willour Virginia , Holmes Susan E. , Franz Mary L. , Callahan Colleen , Hwang Hyon S. , Troncoso Juan C. , Ross Christopher A. 
Published: November 2004

AbstractHuntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease‐like 2 (HDL2), may yield valuable insight into the pathogenesis of HD and related disorders.
Molecular heterogeneity of myophosphorylase deficiency (Mcardle's disease): A genotype‐phenotype correlation study
Authors: Martín Miguel A. , Rubio Juan C. , Buchbinder Jenny , Fernández‐Hojas Roberto , Del Hoyo Pilar , Teijeira Susana , Gámez Josep , Navarro Carmen , Fernández José M. , Cabello Ana , Campos Yolanda , Cervera Carlos , Culebras José M. , Andreu Antoni L. , Fletterick Robert , Arenas Joaquín 
Published: November 2004

AbstractWe report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, accounting for 13.7% of mutant alleles. Moreover, 78% of mutant alleles among Spanish patients can be identified by using polymerase chain reaction‐restriction fragment length polymorphism analysis for the R49X, G204S, and W797R mutations, which makes noninvasive diagnosis possible through molecular genetic analysis of blood DNA. Six novel mutations were found. Three were missense mutations, E348K, R601W, and A703V; two nonsense mutations, E124X and Q754X; and one single base pair deletion, 533 delA. No clear genotype‐phenotype correlation emerges from our study. Most of the mutations of uncharged and solvent inaccessible residues and the truncations must disrupt the basic structure of the protein. The mutations of charged residues would be expected to interfere with internal hydrogen bonding networks, introducing severe incompatible partnering that is caused by poor packing or electrostatic repulsions.
Increased incidence of sporadic Creutzfeldt‐Jakob disease on the island of Crete associated with a high rate of PRNP 129‐methionine homozygosity in the local population
Authors: Plaitakis Andreas , Viskadouraki Anna K. , Tzagournissakis Minas , Zaganas Ioannis , Verghese‐Nikolakaki Susan , Karagiorgis Vasilis , Panagiotides Ioannis , Kilindireas Constantine , Patsouris Eustratios , Haberler Christine , Budka Herbert , Sklaviadis Theodoros 
Published: November 2004

AbstractSince the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, 9 cases (8 neuropathologically confirmed and 1 probable) of sporadic Creutzfeldt‐Jakob disease (sCJD) have been recorded. This represents an annual incidence five‐fold higher than expected based on the island's population (0.54 million). Molecular analysis of the prion‐protein gene (PRNP) showed no mutations in any of the seven CJD cases studied. Five patients (ages 64–88 years) were homozygous for methionine‐129 of PRNP and showed the classic sCJD triad (subacute dementia, myoclonus, periodic electroencephalogram). Brains contained Type 1 (unglycosylated 21.5 kDa band) protease‐resistant prion protein (PrPres). Two patients (ages 56 and 57 years), both homozygous for valine‐129, showed cerebellar ataxia and later dementia not associated with periodic electroencephalogram; brain PrPres was Type 2. Genotyping of 205 Cretan controls showed that methionine‐129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian populations (57.0%, n = 205 versus 41.5%, n = 859. These data are the first to relate a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes in the local population; however, additional factors may be operational.
Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover
Authors: De La Fuente‐Fernández Raúl , Lu Jian‐Qiang , Sossi Vesna , Jivan Salma , Schulzer Michael , Holden James E. , Lee Chong S. , Ruth Thomas J. , Calne Donald B. , Stoessl A. Jon 
Published: November 2004

AbstractMotor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. Ann Neurol 2001;49:298–303
Corticotropin (ACTH) acts directly on amygdala neurons to down‐regulate corticotropin‐releasing hormone gene expression
Authors: Brunson Kristen L. , Khan Najeeb , Eghbal‐Ahmadi Mariam , Baram Tallie Z. 
Published: November 2004

AbstractThe hormone corticotropin (ACTH) is employed as therapy for diverse neurological disorders, but the mechanisms for its efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system (CNS) have been attributed to activation of glucocorticoid receptors. However, in several human disorders, ACTH has therapeutic actions that differ qualitatively or quantitatively from those of steroids. This study tested the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors and focused on the effects of ACTH on the expression of corticotropin‐releasing hormone (CRH), a neuropeptide involved in neuroimmune functions and in certain developmental seizures. The results demonstrated that ACTH potently reduced CRH expression in amygdala neurons. This down‐regulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH‐induced down‐regulation of CRH expression. Taken together, these data indicate that ACTH activates central melanocortin receptors to modulate CRH gene expression in amygdala, supporting the notion that direct, steroid‐independent actions of ACTH may account for some of its established clinical effects on the CNS. Ann Neurol 2001;49:304–312
Genome scan of idiopathic generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing the seizure type
Authors: Durner Martina , Keddache Mehdi A. , Tomasini Livia , Shinnar Shlomo , Resor Stanley R. , Cohen Jeffrey , Harden Cynthia , Moshe Solomon L. , Rosenbaum David , Kang Harriet , Ballaban‐Gil Karen , Hertz Sharon , Labar Douglas R. , Luciano Daniel , Wallace Sibylle , Yohai David , Klotz Irene , Dicker Elisa , Greenberg David A. 
Published: November 2004

AbstractIdiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent‐onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two‐point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non‐JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families. Ann Neurol 2001;49:328–335
Sequence‐selective DNA binding drugs mithramycin A and chromomycin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons
Authors: Chatterjee Sukalyan , Zaman Khalequz , Ryu Hoon , Conforto Adriana , Ratan Rajiv R. 
Published: November 2004

AbstractGlobal inhibitors of RNA or protein synthesis such as actinomycin D or cycloheximide abrogate neuronal apoptosis induced by numerous pathological stimuli in vitro and in vivo. The clinical application of actinomycin D or cycloheximide to human neurological disease has been limited by the toxicities of these agents. To overcome these toxicities, strategies must be developed to inhibit selectively the expression of deleterious proapoptotic proteins, while leaving the expression of antiapoptotic, proregeneration, and other critical homeostatic proteins unperturbed. Mithramycin A (trade name Plicamycin) is an aureolic acid antibiotic that has been used in humans to treat hypercalcemia and several types of cancers. This class of agents is believed to act, in part, by selectively inhibiting gene expression by displacing transcriptional activators that bind to G‐C‐rich regions of promoters. Here we demonstrate that mithramycin A and its structural analog chromomycin A3 are potent inhibitors of neuronal apoptosis induced by glutathione depletion‐induced oxidative stress or the DNA‐damaging agent camptothecin. We correlate the protective effects of mithramycin A with its ability to inhibit enhanced DNA binding of the transcription factors Sp1 and Sp3 to their cognate “G‐C” box induced by oxidative stress or DNA damage. The protective effects of mithramycin A cannot be attributed to global inhibition of protein synthesis. Together, these results suggest that mithramycin A and its structural analogs may be effective agents for the treatment of neurological diseases associated with aberrant activation of apoptosis and highlight the potential use of sequence‐selective DNA‐binding drugs as neurological therapeutics. Ann Neurol 2001;49:345–354
DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13–36.32 in an Italian family with cranial‐cervical or upper limb onset
Authors: Valente Enza Maria , Bentivoglio Anna Rita , Cassetta Emanuele , Dixon Peter H. , Davis Mary B. , Ferraris Alessandro , Ialongo Tamara , Frontali Marina , Wood Nicholas W. , Albanese Alberto 
Published: November 2004

AbstractPrimary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant fashion with reduced penetrance. The DYT1 gene on chromosome 9q34 is responsible for most cases of early limb‐onset PTD. Two other PTD loci have been mapped to date. The DYT6 locus on chromosome 8 is associated with a mixed phenotype, whereas the DYT7 locus on chromosome 18p is associated with adult onset focal cervical dystonia. Several families have been described in which linkage to the known PTD loci have been excluded. We identified a large Italian PTD family with 11 definitely affected members. Phenotype was characterized by prominent cranial‐cervical and upper limb involvement and mild severity. A genome‐wide search was performed in the family. Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 between the disease and marker D1S2667. Ann Neurol 2001;49:362–366
Reduction of Menkes mRNA and copper in leukocytes of patients with primary adult‐onset dystonia
Authors: Kruse Niels , Berg Daniela , Francis Michael J. , Naumann Markus , Rausch Wolf‐Dieter , Reiners K. , Rieckmann Peter , Weishaupt Andreas , Becker Georg 
Published: November 2004

AbstractStudies on postmortem tissue of patients with primary adult‐onset dystonia revealed a significant increase in copper levels and a reduction of copper transporting Menkes protein of the lentiform nuclei. Here we demonstrate that patients with idiopathic adult‐onset cervical dystonia (n = 14) have reduced Menkes mRNA copies and lower copper levels in leukocytes compared to controls (n = 17; U test, p < 0.05). Changes were less distinct in patients with blepharospasm. Therefore, disturbances of copper metabolism in focal dystonia may not be restricted to the basal ganglia. Ann Neurol 2001;49:405–408
Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease
Authors: Chan Dennis , Fox Nick C. , Scahill Rachael I. , Crum William R. , Whitwell Jennifer L. , Leschziner Guy , Rossor Alex M. , Stevens John M. , Cipolotti Lisa , Rossor Martin N. 
Published: November 2004

AbstractVolumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left‐sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role. Ann Neurol 2001;49:433–442
A novel autosomal dominant distal myopathy with early respiratory failure: Clinico‐pathologic characteristics and exclusion of linkage to candidate genetic loci
Authors: Chinnery Patrick F. , Johnson Margaret A. , Walls Timothy J. , Gibson G. John , Fawcett Peter R. W. , Jamieson Sarra , Fulthorpe John J. , Cullen Michael , Hudgson Peter , Bushby Kate M. D. 
Published: November 2004

AbstractWe describe a novel autosomal dominant myopathy presenting in mid–adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, β‐amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct. Ann Neurol 2001;49:443–452
α‐adrenergic supersensitivity of the sudomotor nerve in complex regional pain syndrome
Authors: Chémali Kamal R. , Gorodeski Revital , Chelimsky Thomas C. 
Published: November 2004

Abstractα‐adrenoreceptor supersensitivity in many tissues has been described in patients with complex regional pain syndrome type I (CRPS I). Because excessive sweating of the affected limb is an important feature of CRPS I, we investigated whether this supersensitivity also occurs in the sudomotor system. We compared the sweat response to iontophoresis of an α‐adrenergic agent (phenylephrine) in 4 patients with acute CRPS I and 3 patients with resolved CRPS I with that in 9 control subjects using the methodology of the quantitative sudomotor axon reflex test (QSART). A significantly higher sweat response was observed in the affected limb of patients with acute CRPS I compared to their unaffected limb (p = 0.03), to control subjects (p > 0.018), and to the affected or unaffected limbs of patients with resolved CRPS I (p = 0.02), whose sweat response was not significantly different from that of control subjects. We conclude that the abnormal response in patients with acute CRPS I is most likely mediated by an axon reflex and that α‐adrenoreceptor supersensitivity occurs in the presynaptic portion of the postganglionic sudomotor axon. This supersensitivity is reversed when CRPS I resolves. Ann Neurol 2001;49:453–459
Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia
Authors: Schellinger Peter D. , Fiebach Jochen B. , Jansen Olav , Ringleb Peter A. , Mohr Alexander , Steiner Thorsten , Heiland Sabine , Schwab Stefan , Pohlers Olivia , Ryssel Henning , Orakcioglu Berk , Sartor Klaus , Hacke Werner 
Published: November 2004

AbstractWe studied the diagnostic and prognostic value of diffusion‐ and perfusion‐weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow‐up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty‐one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2‐weighted imaging) within 3.3 ± 1.29 hours, and, of those, 41 underwent follow‐up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI‐DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI‐DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients. Ann Neurol 2001;49:460–469