bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous antigen adrmnistration as a therapy for autoimmune demyelinating disease
Authors: Racke Michael K. , Critchfield Jeffrey M. , Quigley Laura , Cannella Barbara , Raine Cedric S. , McFarland Henry F. , Lenardo Michael J. 
Published: January 2005

AbstractExperimental allergic encephalomyelitis is a prototypic autoimmune disease characterized by central nervous system inflammation and demyelination. Previously, we demonstrated that intravenous administration of high doses of myelin basic protein abrogated the clinical and pathological signs of experimental allergic encephalomyelitis by causing the deletion of encephalitogenic, CD4+ myelin basic protein‐specific T cells through antigen‐induced programmed cell death. In the present study, we further characterized the ability of intravenous antigen administration to attenuate an immune response by myelin basic protein‐reactive encephalitogenic T cells. We demonstrated that multiple injections of myelin basic protein ace required to achieve a therapeutic response, and that this form of therapy is effective even after prolonged chronic disease. These studies showed that although interleukin‐2–stimulated cell cycling is an important factor leading to T‐cell death, the administration of exogenous interleukin‐2 with antigen can result in the aggravation of clinical disease compared to administration of antigen alone. More importantly, administration of myelin basic protein alone without interleukin‐2 was sufficient to reduce autoreactive T cells and clinical disease in experimental autoimmune encephalomyelitis. Our experiments support the rationale for antigen‐specific therapy aimed at inducing the programmed death of autoreactive T cells in autoimmune diseases, potentially including the human demyelinating disease multiple sclerosis.
Strength in Parkinson's disease: Relationshp to rate of force generation and clinical status
Authors: Corcos Daniel M. , Chen Chiung‐Mei , Quinn Niall P. , McAuley John , Rothwell John C. 
Published: January 2005

AbstractMaximum elbow flexor and extensor muscle strength was measured in 9 patients with Parkinson's disease on and off antiparkinsonian medication. In addition, the rate of force generation, the rate of actively returning force to resting levels, and passive release of force “relaxation” were measured in submaximal contractions. The measures of strength and contraction time were correlated with changes in clinical status as measured by the Unified Parkinson's Disease Rating Scale. When patients were off medication, their reduction in strength was significantly greater in extension than flexion. The reduction in flexion strength did not reach statistical significance. The extensor weakness was primarily due to decreased tonic activation of the extensor muscles and not to muscle coactivation. Muscle relaxation time was much more prolonged than was force generation time or active force return time. The increase in relaxation time and the decrease in extensor strength both correlated with changes in clinical status. Finally, changes in extensor torque correlated with the time to actively return force, suggesting that reduced strength is related to a reduced ability to generate rapid contractions in some patients with Parkinson's disease. These results suggest that there is an asymmetric distribution of muscle weakness in Parkinson's disease and that selected measures of muscle strength and muscle relaxation correlate with changes in clinical status.
Bell's palsy–associated blepharospasm relieved by aiding eyelid closure
Authors: Chuke John C. , Baker Robert S. , Porter John D. 
Published: January 2005

AbstractThe efficacy of the blink reflex is maintained by adaptive control mechanisms. We describe a 39‐year‐old woman with the rare complication of blepharospasm‐like symptoms appearing contralateral to an eyelid weakened by facial nerve palsy. The hyperexcitable blink reflex may be a maladaptive consequence of adaptive systems but was not accompanied by an expected increase in main sequence slope. Eyelid spasms were eliminated by the implantation of a gold weight to assist closure of the paretic eyelid. We suggest that aiding closure of the weak eyelid in this case caused a reduction in blink system excitability via the same compensatory mechanisms that initially produced the eyelid spasm. Data also suggest that blinkadaptive systems act via changes in reflex excitability and/or main sequence relationships, and that these may be regulated either synergistically or independent of one another.
Mitochondrial defect in Huntington's disease caudate nucleus
Authors: Gu M. , Gash M. T. , Mann V. M. , Javoy‐Agid F. , Cooper J. M. , Schapira A. H. V. 
Published: January 2005

AbstractAlthough the Huntington's disease (HD) gene defect has been identified, the structure and function of the abnormal gene product and the pathogenetic mechanisms involved in producing death of selective neuronal populations are not understood. Indirect evidence from several sources indicates that a defect of energy metabolism and consequent excitotoxicity are involved in HD. Toxin models of HD may be induced by 3‐nitropropionic acid or malonate, both inhibitors of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. We analyzed mitochondrial respiratory chain function in the caudate nucleus (n = 10) and platelets (n = 11) from patients with HD. In the caudate nucleus, severe defects of complexes II and III (53–59%, p < 0.0005) and a 32–38% (p < 0.01) deficiency of complex IV activity were demonstrated. No deficiencies were found in platelet mitochondrial function. The mitochondrial defect identified in HD caudate parallels that induced by HD neurotoxin models and further supports the role of abnormal energy metabolism in HD. The relationship of the mitochondrial defect to the role of huntingtin is not known.
Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1
Authors: Goldfarb L. G , Vasconcelos O. , Platonov F. A. , Lunkes A. , Kipnis V. , Kononova S. , Chabrashvili T. , Vladimirtsev V. A. , Alexeev V. P. , Gajdusek D. C. 
Published: January 2005

AbstractA Siberian kindred with spinocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CAG triplet expansion within the coding region of the SCA1 gene. The kindred includes 1,484 individuals, 225 affected and 656 at risk, making this collection the largest spinocerebellar ataxia type 1 (SCA1) pedigree known. Each of the studied 78 SCA1 patients carried an expanded allele containing a stretch of 39 to 72 uninterrupted CAG repeats. Normal alleles had 25 to 37 trinucleotide repeats. Expanded alleles containing 40 to 55 repeats were found in 26 atrisk relatives. The number of CAG repeats in the mutated allele was inversely correlated with age at disease onset. Cerebellar deficiency was present in each patient and its severity was moderately affected by the number of CAG repeats. In contrast, the associated signs, dysphagia, diffuse skeletal muscle atrophy with fasciculations, and tongue atrophy were absent or mild in patients with low CAG repeat numbers, but severely complicated the course of illness in patients with a larger number of repeat units. One female mutation carrier was asymptomatic at age 66, more than 2 standard deviations beyond the average age of risk, suggesting incomplete penetrance. In 2 symptomatic individuals who had an expanded number of CAG repeats on both chromosomes, age at onset, rate of progression, and clinical manifestation corresponded to the size of the larger allele.
Upregulation of Bcl‐2 protein in the myasthenic thymus
Authors: Onodera Jun‐ichi , Nakamura Shozo , Nagano Isao , Tobita Muneshige , Yoshioka Masaru , Takeda Atsushi , Oouchi Masahiro , Itoyama Yasuto 
Published: January 2005

AbstractWe examined the expression of Fas antigen and Bcl‐2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic tissue, immunoreactivity for Fas antigen was observed mainly in the network of medullary epithelial cells. In contrast, expression of Fas antigen was rare in the cortex. Fas antigen was also detected to some degree in thymoma tissue from 3 patients. Bcl‐2 protein was highly expressed in the medullary thymocytes in the hyperplastic thymic tissue, whereas its staining was quite low in myasthenia gravis thymomas. The number of Bcl‐2‐positive thymocytes in the medulla was significantly greater in the hyperplastic myasthenia gravis thymic tissue than in the control thymic tissue. These findings suggest that Bcl‐2 protein may be upregulated in the myasthenia gravis thymus and that this phenomenon may be related to impaired apoptotic cell death of autoreactive thymocytes in myasthenia gravis.
The effect of ethanol on alcohol‐responsive essential tremor: A positron emission tomography study
Authors: Boecker Henning , Wills Adrian J. , Ceballos‐Baumann Andres , Samuel Michael , Thompson Philip D. , Findley Leslie J. , Brooks David J. 
Published: January 2005

AbstractWe used H215O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol‐responsive essential tremor and 6 age‐matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 ± 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 ± 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol‐associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol‐induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei.
Difficulties in distinguishing sporadic from familial amyotrophic lateral sclerosis
Authors: Orell Richard W. , Habgood James , Rudge Petter , Lane Russell J. M. , de Belleroche Jackie S. 
Published: January 2005

AbstractMutations of the copperlzinc superoxide dismutase (SOD‐1) gene are present in around 20% of patients with a family history of amyotrophic lateral sclerosis. The finding of these mutations in patients with sporadic amyotrophic lateral sclerosis is rare. We describe a family with amyotrophic lateral sclerosis associated with the SOD‐1 mutation Asp 101 Asn. This mutation was previously described as occurring in a patient with sporadic disease. We discuss the difficulties in defining truly sporadic amyotrophic lateral sclerosis, and the consequent implications on the neurogenetic advice given to other family members.
Cost‐effectiveness analysis: What is it and how it influence neurology
Authors: Holloway Robert G. 
Published: January 2005

AbstractCost‐effectiveness analysis (CEX) refers to a set of research methods that consider the resources consumed by a medical technology in decisions about how best to use the technology. This analytic method is an evolving, controversial, and often misunderstood field in health services research. The basic set of principles underlying CEA is deceptively simple, but sufficient methodological challenges and controversies exist that have, thus far, limited its use in the development of health policy and in bedside decision making. Nonetheless, neurologists like other specialty groups may feel concerned that the results from such analyses may prove unfavorable to their specialty and the patients they serve. This article reviews the fundamental notions surrounding CEA, provides examples from the literature with particular relevance to the neurological community, and highlights critical issues for neurologists regarding the future of CEA.
Campylobacter jejuni infections and anti‐GM1 antibodies in guillain‐barré syndrome
Authors: Jacobs Bart C. , van Doorn Pieter A. , Tio‐Gillen Anne P. , Visser Leo H. , van der Meché Frans G. A. , Schmitz Paul I. M. , Herbrink Paul , Hooijkaas Herbert 
Published: January 2005

AbstractThe group of patients with Guillain‐Barré syndrome (GBS) is very heterogenous with regard to antecedent infections, immunological parameters, clinical manifestations, and response to treatment. In this study, the presumed pathogenic factors anti‐GM1 antibodies and Campylobacter jejuni infections were related to the clinical characteristics. Serum from 154 patients with GBS, 63 patients with other neurological diseases (OND), and 50 normal controls (NC) were tested for the presence of antibodies against GM1 and C. jejuni. Anti‐GM1 antibodies were detected in 31 (20%) GBS patients, 5 (8%) OND patients, and in none of the NC. Evidence for a recent C. jejuni infection was found in 49 (32%) GBS patients and less often in OND patients (11%) or NC (8%). In GBS patients, the presence of anti‐GM1 antibodies was significantly associated with C. jejuni infections. The subgroup of GBS patients with anti‐GM1 antibodies suffered more often from a rapidly progressive and more severe neuropathy with predominantly distal distribution of weakness, without deficits of cranial nerves or sensory distrubances. The subgroup with C. jejuni infection also more often had a severe pure motor variant of GBS. Recovery of the patients with anti‐GM1 antibodies and C. jejuni infection was not as good after plasma exchange compared with intravenous immunoglobulins.
Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging
Authors: Hugg James W. , Kuzniecky Ruben I. , Gilliam Frank G. , Faught R. Edward , Morawetz Richard B. , Hetherington Hoby P. 
Published: January 2005

AbstractWe studied 10 medically intractable temporal lobe epilepsy (TLE) patients prior to surgery using proton magnetic resonance spectroscopic imaging (MRSI) to localize seizure foci. We found significantly elevated creatine/N‐acetylaspartate (Cr/NAA) unilaterally in 8 and bilaterally in 2 patients. Five patients have been studied again 1 year after surgery. In the 2 patients with bilateral temporal seizure onsets, MRSI showed normalization of Cr/NAA in the unoperated contralateral tissue following surgical elimination of seizures. This study suggests that metabolic recovery can occur in contralateral temporal areas following surgical treatment of partial epilepsy.
In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease
Authors: Kuhl D. E. , Minoshima S. , Fessler J. A. , Ficaro E. P. , Wieland D. M. , Koeppe R. A. , Frey K. A. , Foster N. L. 
Published: January 2005

AbstractTo map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single‐photon emission computed tomography using [123I]iodoben‐zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early‐onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).
Neuronal activity and early neurofibrillary tangles in Alzheimer's disease
Authors: Hatanpää Kimmo , Brady Daniel R. , Stoll James , Rapoport Stanley I. , Chandrasekaran Krish 
Published: January 2005

AbstractWe studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early‐stage neurofibrillary tangles as compared to tangle‐free neurons (p. < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle‐free neurons of 4 AD brains to tangle‐free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle‐free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.
MELAS associated with a mutation in the valine transfer RNA gene of mitochondrial DNA
Authors: Taylor R. W. , Chinnery P. F. , Haldane F. , Morris A. A. M. , Bindoff L. A. , Turnbull D. M. , Wilson J. 
Published: January 2005

AbstractWe describe a patient with the mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) phenotype in whom initial investigations in skeletal muscle failed to show any histochemical or biochemical defect. Subsequent analyis of the mitochondrial genome identified a new heteroplasmic mutation in the valine transfer RNA gene, the first described in this region.
Clinical outcomes assessment in multiple sclerosis
Authors: Rudick Richard , Fischer Jill , Antel Jack , Confavreux Christian , Cutter Gary , Ellison George , Lublin Fred , Miller Aaron , Petkau John , Rao Stephen , Reingold Stephen , Syndulko Karl , Thompson Alan , Wallenberg Joy , Weinshenker Brain , Willoughby Ernest 
Published: January 2005

AbstractThis article represents initial deliberation of an international task force appointed by the US National Multiple Sclerosis Society to develop recommendations for optimal clinical assessment tools for multiple sclerosis clinical trials. Presented within this article are the key issues identified by the task force during its initial year of deliberation. These include the precise purpose for a clinical assessment tool, the clinical dimensions to be measured in a multidimensional outcome measure, desirable attributes of an optimal clinical outcome measure, the complexities of multidimensional outcome measures, the relative merits of categorical clinical ratings and quantitative functional assessments, and a number of other important design issues that relate to the use of a multidimensional outcome measure. An action plan for analysis of existing data is summarized, as are the plans for more detailed recommendations from the task force.
Immunosuppression‐induced leukoencephalopathy from tacrolimus (FK506)
Authors: Small Steven L. , Bramblett Gregory T. , Eidelman Benjamin H. , Fukui Melanie B. 
Published: January 2005

AbstractTacrolimus (FK506) has recently been approved for immunosuppressionin organ transplantation, although its use is accompanied by a wide spectrum ofneurotoxic side effects. We describe the clinical, radiological, and pathological features of 3 cases of tacrolimus‐related leukoencephalopathy. The syndrome of immunosuppression‐related leukoencephalopathy is proposed as an uncommon neurological syndrome occurring in patintw with organ transplants involving demyelination, in particular in the parieto‐occipital region and centrum semiovale. Although the syndrome is not associated with a particular (absolute) serum level of tacrolimus, it resolves spontaneously upon decreasing the dose. The tacrolimus‐related syndrome has a similar radiographic and pathologic appearance as the analogous syndrome that occurs in patients taking cyclosporine.
Surgical management of superficial siderosis following cervical nerve root avulsion
Authors: Tapscott Stephen J. , Eskridge Joseph , Kliot Michel 
Published: January 2005

AbstractNeurosensory hearing loss, ataxia, spastic paraparesis, sphincter dysfunction, somatosensory disturbances, and cognitive effects are associated with superficial siderosis of the central nervous system caused by chronic intrathecal bleeding. We describe superficial siderosis that developed more than a decade following traumatic brachial nerve root avulsion. While cerebrospinal fluid analysis indicated chronic intrathecal bleeding, angiography did not localize a specific source. Surgical intervention that included repair of a meningeal diverticulum and venous cauterization resulted in overall reduction, but not complete elimination, of central nervous system bleeding.
Amyloid (Aβ) deposition in chromosome 1–linked Alzheimer's disease: The volga german families
Authors: Mann D. M. A. , Iwatsubo T. , Nochlin D. , Sumi S. M. , Levy‐Lahad E. , Bird T. D. 
Published: January 2005

AbstractAmyloid β protein (Aβ) deposition was investigated in the frontal cortex of 6 cases of (genetically confirmed) chromosome 1–linked Alzheimer's disease (AD) (PS‐2 gene mutation) among the Volga German families using the end‐specific monoclonal antibodies BA27 and BC05 to detect the presence of Aβ40 and Aβ42(43), respectively. In all patients, Aβ42(43) was the predominant peptide species present, although the total amount of Aβ40 and Aβ42(43) deposited in plaques did not differ from that seen in sporadic AD and was significantly lower than that occurring in AD due to PS‐1 gene mutations. Therefore, mutations in the PS‐2 gene, like those in the presenilin‐1 (PS‐1) and amyloid precursor protein (APP) genes, are associated with an initial and preferential deposition of Aβ42(43) within the brain. Although the mechanisms(s) whereby the PS‐1 and PS‐2 gene mutations operate remains unclear, it seems from the present study that the effect of the PS‐2 gene mutation on the brain is muuch less severe, at least as far as Aβ deposition is concerned, than that of the PS‐1 mutation, which seems to confer a much earlier and a much more aggressive development of AD.