bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of apomorphine on globus pallidus neurons in parkinsonian patients
Authors: Hutchison W. D. , Levy R. , Dostrovsky J. O. , Lozano A. M. , Lang A. E. 
Published: January 2005

AbstractCurrent hypotheses of basal ganglia dysfunction in Parkinson's disease (PD) propose that neuronal hypoactivity in the globus pallidus externus (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi, e and GPi, i, respectively), result in the cardinal symptoms of PD. To test this theory, the nonselective D1‐ and D2‐dopamine receptor agonist apomorphine (30–100 μg/kg SC) was administered to 14 levodoparesponsive PD patients who were off medication (“of” state) while recording neurons in GP. For 15 neurons that were continuously monitored, apomorphine was found to increase the firing rate of 3 neurons in GPe, and decrease the rate of 12 in GPi. The mean firing rates of many different neurons were determined before (n = 285) and at various intervals after (n = 184) the injection of the drug. The mean rates before apomorphine were as follows: GPe, 45 Hz (SD 15, n = 85); GPi, e, 67 Hz (SD 14, n = 125); and GPi, i, 85 Hz (SD 19, n = 75). At 25 to 35 minutes after APO, the rate of GPe neurons had increased to 72 Hz (SD 18, n = 7), the rate of GPi, e neurons had decreased to 39 Hz (SD 15, n = 15), and in GPi, i the rate decreased to 34 Hz (SD 22, n = 18). Eighty minutes after apomorphine administration, the mean firing rates returned to preadministration values. This study supports current models of basal ganglia dysfunction in PD and suggests that the thereapeutic effect of apomorphine results from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.
Copper/zinc superoxide dismutase 1 and sporadic amyotrophic lateral sclerosis: Analysis of 155 cases and identification of novel insertion mutation
Authors: Jackson Mandy , Al‐Chalabi Ammar , Enayat Zinat E. , Chioza Barry , Leigh Peter N. , Morrison Karen E. 
Published: January 2005

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in the brain and spinal cord and leading to death within 5 years of symptom onset. The great majority of ALS cases are sporadic, with the familial form (FALS) representing fewer than 10% of all cases. Mutations in the copper/zinc superoxide dismutase 1 (SOD‐1) gene have previously been identified as the underlying cause of approximately 20% of FALS cases. As the familial and sporadic forms of the disease are clinically similar, we have sought to determine whether such mutations in SOD‐1 underlie any sporadic ALS cases. We have screened 155 sporadic cases by single‐strand conformation polymorphism and have identified 4 sporadic cases that possess point mutations in exon 4 of the SOD‐1 gene. Two of these mutations are identical to those previously reported in FALS cases. One mutation is novel, resulting in a frameshift at Val118 due to the replacement of G (first base in the last codon of exon 4) by AAAAC. This mutation results in a truncated SOD‐1 protein due to the introduction of a stop codon three residues into exon 5.
A novel muscle sodium channel mutation causes painful congenital myotonia
Authors: Rosenfeld Jeffrey , Sloan‐Brown Karen , George Alfred L. 
Published: January 2005

AbstractMutations in the skeletal muscle voltage‐gated sodium channel α‐subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses. Most disease‐associated SCN4A alleles occur in portions of the gene that encode the third and fourth repeat domains with the conspicuous absence of mutations in domain 1. Here we describe a family segregating an unusual autosomal dominant congenital myotonia associated with debilitating pain especially severe in the intercostal muscles. A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome. Myotonia was resistant to treatment; however, the most severely affected family member responded dramatically to the sodium channel blocking agent flecainide.
Mapping of a second locus for familial hemiplegic migraine to 1q21–q23 and evidence of further heterogeneity
Authors: Ducros Anne , Joutel Anne , Cecillon Michaëlle , Tournier‐Lasserve Elisabeth , Vahedi Katayoun , Bousser Marie‐Germaine , Ferreira Antonio , Bernard Evelyne , Verier Albert , Echenne Bernard , De Munain Adolfo Lopez 
Published: January 2005

AbstractFamilial hemiplegic migraine (FHM) is an autosomal dominant variety of migraine with aura. We previously mapped an FHM gene on the short arm of chromosome 19. Mutations in this gene, recently shown to be the α1 subunit of a P/Q‐type voltage‐dependent calcium channel, CACNL1A4, are involved in approximately 50% of unselected FHM families and in all families where migraine attacks are associated with permanent cerebellar ataxia. As a first step toward the identification of other FHM genes, we conducted a genetic linkage analysis in one large French pedigree and showed significant linkage to two microsatellite markers D1S2635 (Zmax: 3.33 at = 0.05) and D1S2705 (Zmax: 3.64 at = 0.05), establishing the existence of a second locus for FHM (FHM2) on chromosome 1q21–q23. Analysis of six additional FHM families favored linkage to this locus in two of them; linkage was excluded in the last four families, indicating further heterogeneity. Chromosome 1–linked families differ from the ones linked to chromosome 19, because penetrance in those families is much lower, and in some of their members, epileptic seizures occur during severe migraine attacks.
Autosomal dominant cerebellar ataxia: Phenotypic differences in genetically defined subtypes?
Authors: Schöls Ludger , Amoiridis Georgios , Büttner Thomas , Przuntek Horst , Epplen Jörg T. , Riess Olaf 
Published: January 2005

AbstractSeventy‐seven families with autosomal dominant cerebellar ataxia were analyzed for the CAG repeat expansions causing spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22% of German ataxia families. Seven of 27 SCA6 patients had no family history of ataxia. Age at onset correlated inversely with repeat length in all subtypes. Yet the average effect of one CAG unit on onset age was different for each SCA subtype. We compared clinical, electrophysiological, and magnetic resonance imaging (MRI) findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor proposed SCA2. SCA3 patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome and patients often had onset after 55 years of age. SCAI was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. However, overlap between the four SCA subtypes was broad.
Neurobiology of Autism
Authors: Rapin Isabelle , Katzman Robert 
Published: January 2005

AbstractAutism is a behaviorally defined, life‐long static developmental disorder of the brain that is poised for neurobiological investigation. It affects at least 1 or 2 in 1000 persons and has a broad range of severity. It has multiple causes, with genetics playing a major role. According to the DSM‐IV, defining features are impaired sociability, language and communication, and range of interests and activities. Mental deficiency is frequent but by no means universal. The cognitive profile is characterstic, occasionally with a superior but narrow talent. Perseveration, concreteness, affective blunting, and lack of insight into other persons' thinking may be conspicuous. The neurological basis of autism's many sensorimotor features, including stereotypies, is unknown. Attention and sleep are affected, and one third of individuals experience epilepsy by adulthood. Whether subclinical epilepsy plays a role in the developmental regression of the one third of the toddlers who lose their language skills and become autistic remains to be determined. Clinical neuroimaging and biochemical investigations are generally unremarkable. Fewer than 35 brains have been examined pathologically, none with modern techniques. The findings thus far suggest subtle prenatal neruonal maldevelopment in the cerebellum and certain limbic structures. Abnormalities in distributed networks involving serotonin and perhaps other neurotransmitters require further documentation.
Perfusion‐weighted imaging defects during spontaneous migrainous aura
Authors: Cutrer F. Michael , Sorensen A. Gregory , Weisskoff Robert M. , Østergaard Leif , Del Rio Margarita Sanchez , Lee E. John , Rosen Bruce R. , Moskowitz Michael A. 
Published: January 2005

AbstractPerfusion‐and diffusion‐weighted magnetic resonance imaging was performed during spontaneous visual auras in four migraineurs. Alterations in relative cerebral blood flow (16–53% decrease), cerebral blood volume (6–33% decrease), and tissue mean transit time (10–54% increase) were observed in the gray matter of occipital cortex contralateral to the affected visual hemifield. No changes in the apparent diffusion coefficient were observed either while the patients were symptomatic or after resolution of the visual symptoms but before the onset of headache. Functional magnetic resonance imaging can be a useful noninvasive tool to study hemodynamic changes during spontaneous attacks of migraine with aura.
The medial temporal lobe in dementia with lewy bodies: A comparative study with Alzheimer's disease
Authors: Lippa C. F. , Johnson R. , Smith T. W. 
Published: January 2005

AbstractThe usefulness of determining medial temporal lobe (MTL) size in differentiating Alzheimer's disease (AD) from other dementia subtypes is unknown. We compared the cross‐sectional areas of the MTLs in histological sections from the brains of 18 patients with dementia with Lewy bodies (DLB) but lacking AD changes, 24 DLB patients with concurrent AD pathology, 20 pure AD cases, and 18 age‐matched control cases. Duration and severity of disease were comparable between groups. When data for cross‐sectional area were expressed as percentages of the average control area, DLB MTLs were significantly larger than either AD or DLB/AD MTLs at rostral levels (86 ± 16%, 54 ± 17%, and 66 ± 23% of control areas, respectively). At caudal levels, DLB MTLs were larger than AD MTLs (80 ± 20%, 59 ± 21%, and 77 ± 26% of control areas in DLB, AD, and DLB/AD, respectively). MTL cross‐sectional area often approaches normal in pure DLB, even when disease duration is prolonged and symptoms are end stage. In contrast, a greatly reduced MTL area mitigates against the diagnosis of DLB, unless there are concurrent AD changes.
Cytomegalovirus infection and schizencephaly: Case reports
Authors: Iannetti Paola , Nigro Giovanni , Spalice Alberto , Faiella Antonio , Boncinelli Edoardo 
Published: January 2005

AbstractTwo children with left open‐lip schizencephaly are reported. Cytomegalovirus (CMV) infection was demonstrated on the second day of life in Patient 1; in the other patient CMV infection was observed at the age of 4 years. Magnetic resonance imaging revealed polymicrogyric cortex lining the clefts. In Patient 2 polymicrogyria was also present in the corresponding area contralateral to the schizencephaly. Computed tomography revealed the presence of subependymal periventricular calcifications. Genetic analysis did not demonstrate the presence of EMX2 homeobox gene. The possible role of CMV infection in the complex multifactorial pathogenesis of schizencephaly is therefore suggested.
Opposite motor effects of pallidal stimulation in Parkinson's disease
Authors: Krack P. , Pollak P. , Limousin P. , Hoffmann D. , Benazzouz A. , Le Bas J. F. , Koudsie A. , Benabid A. L. 
Published: January 2005

AbstractWe studied the effects—on parkinsonian signs, on levodopa‐induced dyskinesias, and on levodopa response—of acute experimental high‐frequency stimulation of the internal pallidum (GPi) during off‐drug and on‐drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa‐induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to the moderate improvement of off‐drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.
Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle
Authors: Brierley Elizabeth J. , Johnson Margaret A. , Lightowlers Robert N. , James Oliver F. W. , Turnbull Douglass M. 
Published: January 2005

AbstractIt has been proposed that one mechanism for nerve and muscle dysfunction with age involves the mitochondria. Mitochondria contain the only DNA outside the nucleus in mammalian cells. Mitochondrial DNA (mtDNA) has a high mutation rate, and low levels of pathogenic mutations have been found in tissues from elderly subjects. However, the role of these mutations in the aging process is uncertain unless a mechanism can be identified that would lead to a biochemical defect. In muscle tissue from normal elderly subjects we show that there are muscle fibers with very low activity of cytochrome c oxidase, suggestive of a mtDNA defect. In these cytochrome c oxidase‐deficient fibers we have found very high levels of mutant mtDNA. In addition, different mtDNA mutations are present in different fibers, which explains why there is a low overall incidence of an individual mutation in tissues from elderly subjects. These studies show a direct age‐related correlation between a biochemical and genetic defect in normal human tissues and that mtDNA abnormalities are involved in the aging process in human muscle.
Quantitative magnetic resonance imaging of brain development in premature and mature newborns
Authors: Hüppi Petra S. , Warfield Simon , Kikinis Ron , Barnes Patrick D. , Zientara Gary P. , Jolesz Ferenc A. , Tsuji Miles K. , Volpe Joseph J. 
Published: January 2005

AbstractDefinition in the living premature infant of the anatomical and temporal characteristics of development of critical brain structures is crucial for insight into the time of greatest vulnerability of such brain structures. We used three‐dimensional magnetic resonance imaging (3D MRI) and image‐processing algorithms to quantitate total brain volume and total volumes of cerebral gray matter (GM), unmyelinated white matter (WM), myelinated WM, and cerebrospinal fluid (CSF) in 78 premature and mature newborns (postconceptional age, 29–41 weeks). Total brain tissue volume was shown to increase linearly at a rate of 22 ml/wk. Total GM showed a linear increase in relative intracranial volume of approxi mately 1.4% or 15 ml in absolute volume per week. The pronounced increase in total GM reflected primarily a fourfold increase in cortical GM. Unmyelinated WM was found to be the most prominent brain tissue class in the preterm infant younger than 36 weeks of postconceptional age. Although minimal myelinated WM was present in the preterm infant at 29 weeks, between 35 and 41 weeks an abrupt fivefold increase in absolute volume of myelinated WM was documented. Extracerebral and intraventricular CSF was readily quantitated by this technique and found to change minimally. The application of 3D MRI and tissue segmentation to the study of human infant brain from 29 to 41 weeks of postconceptional age has provided new insights into cerebral cortical development and myelination and has for the first time provided means of quantitative assessment in vivo of early human brain development.
Effects of the nicotinic acetylcholine receptor agonist SIB‐1508Y on object retrieval performance in MPTP‐Treated monkeys: Comparison with levodopa treatment
Authors: Schneider J. S. , Van Velson M. , Menzaghi F. , Lloyd G. K. 
Published: January 2005

AbstractThis study assessed the relative potencies of levodopa/benserazide and the nicotinic acetylcholine receptor agonist SIB‐1508Y on reversal of cognitive and motor deficits in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–treated monkeys performing an object retrieval task. Monkeys previously taught to perform this task developed significant cognitive deficits after chronic low‐dose MPTP exposure. These monkeys then received additional MPTP treatment to superimpose a parkinsonian movement disorder on their preexisting cognitive deficits. Levodopa/benserazide treatment significantly improved motor aspects of object retrieval performance but did not significantly improve cognition. SIB‐1508Y (1 mg/kg) alone did not result in a statistically significant improvement in cognition or motor function in symptomatic MPTP‐lesioned animals with deficits in both of these areas. However, the combination of SIB‐1508Y and levodopa/benserazide caused significant improvements in both cognition and motor aspects of task performance, and did so at one third to one sixth of the levodopa dose necessary to improve only motor function. These results suggest the potential usefulness of SIB‐1508Y and levodopa as adjunctive therapies to improve at least some of the cognitive and motor deficits associated with Parkinson's disease.
Complex I Defect in muscle from patients with Huntington's disease
Authors: Arenas Joaquín , Campos Yolanda , Ribacoba René , Martín Miguel A. , Rubio Juan C. , Ablanedo Pilar , Cabello Ana 
Published: January 2005

AbstractWe found a variable defect of complex I of the mitochondrial respiratory chain, ranging in severity from 25% to 63% of control values, in muscle of patients with Huntington's disease (HD). The most severe defect was observed in the patient with the greatest expansion of CAG triplets. Muscle morphology showed myopathic changes such as moth‐eaten fibers, angulated fibers, increased subsarcolemmal oxidative activities, or an increased number of enlarged mitochondria with abnormal cristae. Multiple mitochondrial DNA deletions were found by polymerase chain reaction (PCR) analysis in muscle of the patient with the most severe defect of complex I. Our data further support the involvement of energetic defects and oxidative damage in muscle of patients with HD.
Cortical reflex myoclonus in rett syndrome
Authors: Guerrini Renzo , Bonanni Paolo , Parmeggiani Locio , Santucci Margherita , Parmeggiani Antonia , Sartucci Ferdinando 
Published: January 2005

AbstractRett syndrome (RS) is one of the most frequent causes of mental retardation in females. As there are no known biochemical, genetic, or morphological markers, diagnosis is based on clinical phenotype including severe dementia, autism, truncal ataxia/apraxia, loss of purposeful hand movements, breathing abnormalities, stereotypies, seizures, and extrapyramidal signs. Myoclonus, although reported in some series, has never been characterized. We studied 10 RS patients, age 3 to 20 years, and observed myoclonus in 9. Severity of myoclonus did not correlate with that of the other symptoms or with age. Multifocal, arrhythmic, and asynchronous jerks mainly involved distal limbs. Electromyographic bursts lasted 48 ± 12 msec. Burst‐locked electroencephalographic averaging generated a contralateral centroparietal premyclonus transient preceding the burst by 34 ± 7.2 msec. Motor evoked potentials showed normal latencies, indicating integrity of the corticospinal pathway. Somatosensory evoked potentials were enlarged. The C‐reflex was hyperexcitable and markedly prolonged (62 ± 4.3 msec), mainly due to increase in cortical relay time (28.4 ± 4.5 msec). We conclude that RS patients show a distinctive pattern of cortical reflex myoclonus with prolonged intracortical delay of the long‐loop reflex.
Quinidine sulfate therapy for the slow‐channel congenital myasthenic syndrome
Authors: Harper C. Michel , Engel Andrew G. 
Published: January 2005

AbstractThe slow‐channel congenital myasthenic syndrome (SCCMS) is caused by gain of function mutations in subunits of the end‐plate acetylcholine receptor (AChR). The mutations prolong the opening episodes of the AChR channel, leading to a depolarization block and an end‐plate myopathy. Because levels of quinidine sulfate attainable in clinical practice shorten the opening episodes of genetically engineered mutant SCCMS receptors in vitro, we tested the notion that the drug can be of benefit in SCCMS. We treated 6 SCCMS patients with quinidine sulfate in an open‐label trial, using objective clinical measures of muscle strength and repetitive stimulation studies as end points. One patient became allergic to quinidine after 7 days. The remaining patients tolerated the drug well and after 30 days of continuous therapy showed statistically significant improvement in muscle strength and in decrement of the compound muscle action potential elicited by repid rates of stimulation.
Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: Implications for ischemia and Huntington's disease
Authors: Calabresi Paolo , Centonze Diego , Pisani Antonio , Sancesario Giuseppe , Gubellini Paolo , Marfia Girolama A. , Bernardi Giorgio 
Published: January 2005

AbstractStriatal spiny neurons are selectively vulnerable in Huntington's disease (HD) and ischemia, whereas large aspiny (LA) cholinergic interneurons of the striatum are spared in these pathological conditions. We have investigated whether a different sensitivity to ionotropic glutamatergic agonists might account for this differential vulnerability. Intracellular recordings were obtained from morphologically identified striatal spiny neurons and LA cholinergic interneurons by using a rat brain slice preparation. The two striatal neuronal subtypes had strikingly different intrinsic membrane properties. Both subtypes responded to cortical stimulation with excitatory postsynaptic potentials: these potentials, however, had a different time course and pharmacology in the two classes of cells. Interestingly, membrane depolarizations and inward currents produced by exogenous glutamate receptor agonists (AMPA, kainate, and NMDA) were remarkably larger in spiny neurons than in LA interneurons. Moreover, concentrations of agonists producing reversible membrane changes in LA interneurons caused irreversible depolarizations in spiny cells. Our data suggest that the different physiological responses induced by the activation of ionotropic glutamate receptors may account for the cell type‐specific vulnerability of striatal neurons in ischemia and HD.