bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of intravenous valproate
Authors: Devinsky Orrin , Leppik Ilo , James Willmore L. , Pellock John M. , Dean Christine , Gates John , Eugene Ramsay R. 
Published: January 2005

AbstractThis multicenter, open‐label trial was designed to study the safety of intravenous (IV) sodium valproate in patients with epilepsy. All 318 patients (previously treated with antiepileptic drugs) were hospitalized for seizure control or anticipated seizures. The protocol allowed physicians to set the number of infusions and treatment duration. Adverse events, laboratory studies performed, and seizure activity were documented on case report forms. The patients' mean age was 34.4 years (range, 2–87 years). The most common reason for admission was lack of seizure control (235 patients, 185 of whom were admitted for video‐electroencephalographic monitoring). The median dosage of valproate was 375 mg infused over 1 hour. The median number of doses was four, given over 2 days. In 54 patients (17%), transient adverse events were reported. The most frequent were headache, reaction at the injection site, and nausea (2.2% each); somnolence (1.9%); vomiting (1.6%); and dizziness and taste perversion (1.3% each). No persistent or severe hematologic or serum chemistry abnormalities were found. Vital signs were not significantly affected by the IV infusion of valproate. At the dosages and rates of administration studied, intravenous valproate appears to be safe and well tolerated.
Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)
Authors: Hutchinson Michael , O'Riordan Jonathon , Javed Mohammed , Quin Etain , Macerlaine Donal , Willcox Teresa , Parfrey Nollaig , Nagy Tamas G. , Tournier‐Lasserve Elisabeth 
Published: January 2005

AbstractCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.
Chemical pathology of acute demyelinating lesions and its correlation with disability
Authors: De Stefano Nicola , Matthews Paul M. , Antel Jack P. , Preul Mark , Francis Gordon , Arnold Douglas L. 
Published: January 2005

AbstractWe report the chemical pathological changes on magnetic resonance spectroscopic images of 4 patients, each of whom had a single large demyelinating plaque. The patients were followed from soon after the onset of the symptoms for a minimum of 7 months to a maximum of 3 1/2 years. We observed increases in the relative resonance intensities of choline‐containing compounds, lactate, and myo‐inositol inside the lesion acutely. Decreases in relative resonance intensities of N‐acetylaspartate and creatine were seen both in and around the magnetic resonance imaging—detected lesions. In all patients neurological deficits improved and creatine, lactate, and myo‐inositol resonance intensities normalized during the follow‐up. Choline compounds recovered more slowly and were still abnormally high in 1 patient after 7 months. Partial recovery of the N‐acetylaspartate resonance was seen for all patients. Evaluation of the relationships between indices of cerebral chemical pathology, brain lesion volumes, and functional disability showed highly significant negative correlations between N‐acetylaspartate resonance intensities and both brain lesion volumes (r = −0.80, p < 0.0001) and clinical disability (r = −0.73, p < 0.0001). As N‐acetylaspartate is localized solely in neurons in the adult central nervous system, our results suggest that neuronal dysfunction may be a proximate mechanism of disability even in inflammatory disorders primarily affecting myelin and oligodendroglial cells.
Cerebrovascular complications in Ehlers‐Danlos syndrome type IV
Authors: North Kathryn N. , Whiteman David A. H. , Pepin Melanie G. , Byers Peter H. 
Published: January 2005

AbstractEhlers‐Danlos syndrome (EDS) type IV is an autosomal dominant disorder that results from mutations in the COL3A 1 gene, which encodes chains of type III procollagen. Individuals with this disorder are predisposed to rupture of arteries, the bowel, and the gravid uterus. To assess the frequency of central nervous system complications, we reviewed clinical data concerning 202 individuals with EDS type IV from 121 families in which the diagnosis was confirmed by biochemical or molecular studies. We identified 19 individuals with cerebrovascular complications, which included intracranial aneurysms with secondary hemorrhage, spontaneous carotidcavernous sinus fistula, and cervical artery dissection. The mean age at presentation with these events was 28.3 years (range, 17–48 years). Although uncommon, EDS type IV is an important potential cause of stroke in young people. The disorder is readily identifiable clinically and the diagnosis has important implications for acute and long‐term management and, potentially, for other family members. Because conventional angiography may exacerbate severe complications, noninvasive procedures such as Doppler and magnetic resonance angiography are the investigations of choice. Anticoagulation therapy may result in increased bruising or bleeding and should be used with caution.
The effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy
Authors: Petroff Ognen A. C. , Rothman Douglas L. , Behar Kevin L. , Lamoureux D. , Mattson Richard H. 
Published: January 2005

AbstractGabapentin has come into clinical use as adjunctive therapy in the treatment of epilepsy. Designed to mimic gammaaminobutyric acid (GABA), its mechanism of action remains elusive. In vivo measurements of GABA in human brain were made using 1H magnetic resonance spectroscopy. We used a 2.1‐T magnetic resonance imager‐spectrometer and an 8‐cm surface coil to measure a 13.5‐cm3 volume in the occipital cortex. GABA levels were measured in 14 patients enrolled in an open‐label trial of gabapentin. GABA was elevated in patients taking gabapentin compared with 14 complex partial epilepsy patients, matched for antiepileptic drug treatment. Brain GABA levels appeared to be higher in patients taking high‐dose gabapentin (3,300–3,600 mg/day) than in those taking standard doses (1,200–2,400 mg/ day). Gabapentin appears to increase human brain GABA levels.
Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy
Authors: Cross J. H. , Connelly A. , Jackson G. D. , Johnson C. L. , Neville B. G. R. , Gadian D. G. 
Published: January 2005

AbstractWe performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N‐acetylaspartate to choline plus creatine (NAAI[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N‐acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean l8%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.
Interleukm‐1 receptor antagonist suppresses neurotrophin response in injured rat brain
Authors: Dekosky Steven T. , Styren Scot D. , O'Malley Mark E. , Goss James R. , Kochanek Patrick , Marion Donald , Evans Christopher H. , Robbins Paul D. 
Published: January 2005

AbstractTraumatic brain injury (TBI) induces astrocytic and microglial activation and proliferation and augmented production of the cytokine interleukin‐lβ (IL‐1β) and nerve growth factor (NGF). The increase in NGF temporally follows the increase in IL‐1β, suggesting that the IL‐1β up‐regulation after trauma directly induces the increase in NGF. We examined the effect of IL‐1 receptor antagonist protein (IL‐1ra) on microglial proliferation and NGF production in rat cortex, following two different models of TBI. Rabbit fibroblasts infected with a retroviral vector containing the human IL‐1ra gene were implanted into the wound cavity immediately following a cortical stab wound or 6 hours after a weight drop‐induced trauma. Both microglial proliferation and NGF up‐regulation were decreased significantly in animals receiving IL‐1ra‐expressing cells compared with animals receiving naive (untransfected) fibroblasts. These data demonstrate that the increase in NGF after central nervous system trauma is directly mediated through IL‐1β and that blocking IL‐1 β following brain injury leads to suppression of an NGF‐mediated reparative response. Such blockade of inflammation, however, may prove to be of significant therapeutic benefit in human brain injury and other inflammatory states.
Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis
Authors: Przedborski Serge , Donaldson David , Jakowec Michael , Kish Stephen J. , Guttman M. , Rosoklija Gorazd , Hays Arthur P. 
Published: January 2005

AbstractAmyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 & 2.6 nmol/min/mg protein [mean & standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 & 0.5 nmol/min/ mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.
Clinical and genetic analysis of a large pedigree with juvenile myoclonic epilepsy
Authors: Serratosa José M. , Delgado‐Escueta Antonio V. , Medina Marco T. , Zhang Quanwei , Iranmanesh Reza , Sparkes Robert S. 
Published: January 2005

AbstractJuvenile myoclonic epilepsy is a common type of idiopathic generalized epilepsy characterized by myoclonic, generalized tonic‐clonic, and in 30% of patients, absence seizures. We studied a three‐generation pedigree of 33 members, 10 of whom were clinically affected with juvenile myoclonic epilepsy or presented with subclinical electroencephalographic (EEG) 3.5‐ to 6.0‐Hz diffuse polyspike‐wave or spike‐wave complexes. Juvenile myoclonic epilepsy and the EEG trait segregated as an autosomal dominant trait with 70% penetrance. Linkage analysis using this model showed significant linkage to four microsatellite markers centromeric to human leukocyte antigen (HLA) in chromosome 6p. Maximum lod scores of 3.43 at θm=f = 0.00 for D6S272, D6S466, D6S257, and D6S402 were obtained. Recombinant events in 2 affected members defined the gene region to a 43‐cM interval flanked by D6S258 (HLA region) and D6S313 (centromere). Our results in this large family provide evidence that a gene responsible for juvenile myoclonic epilepsy and the subclinical, 3.5‐ to 6.0‐Hz, polyspike‐wave or spike‐wave EEG pattern is located in chromosome 6p.
Opportunities and challenges in academic neurology: Report of long range planning committee of the american neurological association
Authors: Griffin John W. , Griggs Robert C. , Barchi Robert , Schneck Stuart A. , Moses Hamilton ,   Long Range Planning Committee
Published: January 2005

AbstractBy most measures, academic neurology is thriving as never before, yet convening forces are changing the face of academic neurology. This report focuses on changes that academic neurology and the American Neurological Association could undertake to seize new opportunities and resist damaging potential changes. These proposals can be categorized in the following four major goals: (1) enhance the quality of a smaller neurology workforce and augment the recruitment gifted young neuroscientists into neurology; (2) foster new diversity in neurological investigation, including clinical research in neurology; (3) document the benefits and relative costs of neurological care, in general, and of academic neurology, in particular; and (4) foster the role of neurologists as teachers to medical caregivers at all levels, including medical students, nonneurological house staff, and primary practitioners.
MELAS‐ and kearns‐sayre‐type with myopathy and autoimmune polyendocrinopahy
Authors: Ohno Kinji , Yamamoto Masahiko , Engel Andrew G. , Michel C. Michel , Roberts Lewis R. , Tan Gerry H. , Fatourechi Vahab 
Published: January 2005

AbstractA 35‐year‐old woman with features of Kearns‐Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type I1 (Addison's disease, autoimmune insulin‐dependent diabetes meuitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532‐bp deletion of the type seen in Kearns‐Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA‐Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large‐scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, largescale mtDNA deletions.
Lack of association of trinucleotide repeat polymorphisms in the very‐low‐density lipoprotein receptor gene with Alzhelner's disease
Authors: Chung Ba Haeyong , Roberts Carol T. , Greenberg Steven , Rebeck G. William , Christie Bs Richard , Wallace Robert , Jacob Howard J. , Hyman Bradley T. 
Published: January 2005

AbstractInheritance of the apolipoprotein E ε 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very‐low‐density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very‐low‐density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very‐low‐density lipoprotein receptor gene is strongly associated with AD.
Complement activation in the central nervous system following blood–brain barrier damage in man
Authors: Lindsberg Perttu J. , Öhman Juha , Lehto Timo , Wuorimaa Tomi , Meri Seppo , Karjalainen‐Lindsberg Marja‐Liisa , Paetau Anders , Carpén Olli , Kaste Markku 
Published: January 2005

AbstractThe central nervous system (CNS) is virtually isolated from circulating immunological factors such as complment (C), an important mediator of humoral immunity and inflammation. In circulation, C i constantly inhibited to prevent attack on host cells. Since a host of diseases produce an abnormal blood–brain/cerebrospinal fluid (blood–brain/CSF) permeability allowing C protein extravasation, we investigated if C activation occurs in CSF in vitro and in CNS in vivo during subarachnoid hermorrhage (SAH) or brain infrarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in the CSF, 210 ± 61 ng/ml, than in the plasma 63 ± 17 ng/ml, but null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7). TCC was eliminated from the CSF after SAH (24 ± 10 ng/ml on days 7 to 10) Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischmemic brain infrarctions, immunohistochemical techniques demonstrated neuronal fragment‐associated deposition of C9 accompanied by neutrophil infiltration. We conclude that the C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By promoting chemotaxis and vascular perturbation, C activation may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.
Speech‐induced changes in corticospinal excitability
Authors: Tokimura H. , Asakura T. , Tokimura Y. , Oliviero A. , Rothwell J. C. 
Published: January 2005

AbstractThe aim of the experiments was to investigate the effects of speech on the excitability of corticospinal pathways to human hand muscles. Single transcranial magnetic stimuli were given randomly over the hand area of either the left or right motor cortex of 10 right‐handed and 3 left‐handed normal volunteers. Electromyographic responses were recorded in the relaxed first dorsal interosseous muscle while the subjects (a) read aloud a piece of text, (b) read silently, (c) spoke spontaneously, or (d) made sounds without speaking. The only consistent effect across subjects occurred during task a, which significantly increased the size of responses evoked in the dominant hand of all subjects, but had either no effect (8 subjects) or a smaller effect in the nondominant hand. Tasks b and d had no reliabl effects, whereas task c tended to increase response size in both hands. Control measurements suggest that the effects in task a were caused by changes in cortical rather than spinal excitability. This is the first demonstration of lateralized speech effects on the excitability of cortical arm areas. The results provide a useful adjunct to other tests of cerebral dominance, using only single‐ rather than repetitive‐pulse cortical stimulation.
Acute myopathy of intensive care: Clinical, electromyographic, and pathological aspects
Authors: Lacomis David , Giuliani Michael J. , van Cott Anne , Kramer David J. 
Published: January 2005

AbstractAn acute myopathy of intensive care occurs in critically ill patients treated with intravenous corticosteroids and neuromuscular junction‐blocking agents. The full clinicopathological spectrum is uncertain. We evaluated the clinical, electrodiagnostic, and histopathological features of 14 patients who developed acute myopathy of intensive care after organ transplantation or during treatment of severe pulmonary disorders and sepsis. Patients received high‐dose intravenous corticosteroids, usually in conjunction with relatively low to moderate doses of neuromuscular junction‐blocking agents. After discontinuation of the latter drugs, most had diffuse, flaccid weakness with failure to wean frommechanical ventilation. Electrodiagnostic findings were consistent with a necrotizing myopathy. Muscle histopathology revealed myopathy with loss of thick filaments in 79%, mild myopathic changes in 14%, and atrophy of type 1 and type 2 fibers in 7%. Loss of thick filaments was identified in muscle biopsy specimens obtained 30 ± 11 days (mean ± standard deviation) after intravenous corticosteroid treatment but not in those obtained earlier (12 ± 2 days). Critically ill patients, including those receiving organ transplants, may develop acute myopathy of intensive care after exposure to intravenous corticosteroids and neuromuscular junction‐blocking agents, although the exposure to the latter drugs may be minimal. Selective loss of thick filaments is common in acute myopathy of intensive care, especially if the muscle biopsy specimen is obtained 2 weeks or more after intravenous corticosteroid exposure.
A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy
Authors: Dalakas Marinos C. , Quarles Richard H. , Farrer Robert G. , Dambrosia James , Soueidan Shawke , Stein Daniel P. , Cupler Edward , Sekul Elizabeth A. , Otero Carlos 
Published: January 2005

AbstractEleven patients with demyelinating polyneuropathy associated with monoclonal IgM antibodies were randomized to receive IVIg or placebo, monthly, for 3 months in a double‐blind study. After a washout period, they crossed over to the alternate therapy. Response was gauged by evaluating muscle strength, sensation, and neuromuscular symptoms at baseline, after 3 months, and at treatment's end. After IVIg therapy, the strenght improved in only 2 of 11 patients, by 28 and 38.5 points from baseline, and declined after placebo. In 1 other patient, the sensory score improved by 13 points. Antibody titers to MAG/SGPG or gangliosides did not appreciably change. We conclude that IVIg has only a modest benefit to not more than 18% of patients with IgM paraproteinemic demyelinating neuropathy.