bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOD1 mutation is assosiated with accumulation of neurofilaments in amyotrophic lateral scelaries
Authors: Rouleau Guy A. , Clark Arthur W. , Rooke Karen , Pramatarova Albena , Krizus Aldis , Suchowersky Oksana , Julien Jean‐Pierre , Figlewicz Denise 
Published: January 2005

AbstractMutations in the Cu/Zn superoxide dismutase (SODl) gene are found in 15 to 20% of patients with familial amyotrophic lateral sclerosis (FALS). Increased levels of neurofilament subunits in transgenic mouse models of ALS also suggests a key role for these proteins in the pathogenesis of the disease. We report the coexistence of an Ile113 → Thr substitution in exon 4 of the SOD1 gene and marked neurofilamentous pathology in the same FALS patient. These observations suggest that two mechanisms, SOD 1‐induced toxicity and neurofilament disruption, are acting together.
Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis
Authors: Gurney Mark E. , Cutting Frank B. , Zhai Ping , Doble Adam , Taylor Charles P. , Andrus Paula K. , Hall Edward D. 
Published: January 2005

AbstractFamilial amyotrophic lateral sclerosis (FALS) has been linked in some families to dominant mutations of the SOD1 gene encoding Cu,Zn superoxide dismutase (Cu,Zn SOD). We have used a transgenic model of FALS based on expression of mutant human Cu,Zn SOD to explore the etiology and therapy of the genetic disease. Expression of mutant, but not wild‐type, human Cu,Zn SOD in mice places the brain and spinal cord under oxidative stress. This causes depletion of vitamin E, rather than the typical age‐dependent increase in vitamin E content as occurs in nontransgenic mice and in mice expressing wild‐type human Cu,Zn SOD. Dietary supplementation with vitamin E delays onset of clinical disease and slows progression in the transgenic model but does not prolong survival. In contrast, two putative inhibitors of the glutamatergic system, riluzole and gabapentin, prolong survival. However, riluzole did not delay disease onset. Thus, there was clear separation of effects on onset, progression, and survival by the three therapeutics tested. This suggests the hypothesis that oxidative damage produced by the expression of mutant Cu,Zn SOD causes slow or weak excitotoxicity that can be inhibited in part by altering glutamate release or biosynthesis presynaptically.
The insulin‐like growth factor I system in cerebellar degeneration
Authors: Torres‐Aleman Ignacio , Barrios Vicente , Lledo Alberto , Berciano José 
Published: January 2005

AbstractBrain insulin‐like growth factor I (IGF‐I) and its related molecules may be involved in neurodegenerative processes in which IGF‐I‐containing pathways are compromised. Since IGF‐I is present in the olivocerebellar circuitry, two types of late‐onset cerebellar ataxias (olivopontocerebellar and idiopathic cerebellar cortical atrophy) were chosen to test this hypothesis. The following significant changes in the peripheral IGF‐I system of these patients were found: low IGF‐I levels, and high IGF‐binding protein 1 (BP‐1), and BP‐3 affinity for IGF‐1. Sixty percent of the patients also had significantly low insulin levels. Patients suffering from other neurological diseases with cerebellar dysfunction and ataxia not involving the olivocerebellar pathway also had low IGF‐I levels, while IGFBPs and insulin levels were normal. Our data indicate that degeneration of an IGF‐I‐containing neuronal pathway produces significant changes in the peripheral IGF system. This suggests strongly that the endocrine (bloodborne) and the paracrine/autocrine (brain) IGF systems are linked functionally. We propose that alterations in the blood IGF‐I system may constitute a marker of some cerebellar diseases.
Quantitation of human immunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome
Authors: Johnson Richard T. , Glass Jonathan D. , McArthur Justin C. , Chesebro Bruce W. 
Published: January 2005

AbstractWe measured human immunodeficiency virus (HIV) DNA in brains of 15 patients who died with acquired immunodeficiency syndrome (AIDS). All had been followed prospectively prior to death; 7 were demented and 8 were not demented. HIV was detected in 13 of 15 brains by polymerase chain reaction (PCR) and in the remaining 2 by presence of viral RNA or viral antigen. Quantitative PCR showed a wide range in amounts of HIV DNA with no significant difference between brains of demented and nondemented patients. These results suggest that qualitative features of the virus, rather than increased virus load per se, may be responsible for the clinical differences between HIV‐infected patients with and without dementia.
T Cell–mediated ganglionitis associated with acute sensory neuronopathy
Authors: Hainfellner Johann Andreas , Kristoferitsch Wolfgang , Lassmann Hans , Bernheimer Hanno , Neisser Andrea , Drlicek Marcus , Beer Franz , Budka Herbert 
Published: January 2005

AbstractA 67‐year‐old man presented with acute painful sensory loss, areflexia, ataxia, urinary retention, and severe constipation and became unable to walk within 2 weeks. He died suddenly 5 weeks after the onset of symptoms. Autopsy revealed widespread inflammation of sensory and autonomic ganglia with immunocytochemical evidence of a CD8+ T cell‐mediated cytotoxic attack against ganglion neurons. This observation suggests a novel pathogenetic mechanism of immune‐mediated human ganglion cell damage comparable to mechanisms operating in polymy‐ositis.
Obesity and endocrine disorders in women taking valproate for epilepsy
Authors: Isojärvi Jouko I. T. , Laatikainen Timo J. , Knip Mikael , Pakarinen Arto J. , Juntunen Kaisa T. S. , Myllyla Vilho V. 
Published: January 2005

AbstractWe recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy, especially when the medication was started before the age of 20 years. In the present study we evaluated the association of obesity and hyperinsulinemia with valproate‐related polycystic ovaries and hyperandrogenism in women with epilepsy. Sixty‐five women participated in the study. Twenty‐two received valproate monotherapy and 43 received carbamazepine monotherapy. In addition to clinical examination, vaginal ultrasonography was performed to determine ovarian size, and the concentrations of serum sex hormones, insulin, insulin‐like growth factor I, and the insulin‐like growth factor‐binding proteins 1 and 3 (IGFBP‐1 and IGFBP‐3) were measured. Fifty‐nine percent of the women on valproate were obese, and in a retrospective analysis an indisputable weight gain (mean, 21 kg, range, 8 ‐49 kg) was found in 50% of the women taking valproate. Fourteen (64%) of the women on valproate had polycystic ovaries, hyperandrogenism, or both. These women were obese, and in addition to elevated serum androgen levels, they had high concentrations of fasting serum insulin and low levels of serum insulin‐like growth factor‐binding protein 1. Valproate therapy for epilepsy is associated with weight gain during treatment in approximately 50% of women patients. The weight gain can be progressive, and is associated with hyperinsulinemia and low serum levels of insulin‐like growth factor‐binding protein 1, which may lead to hyperandrogenism and polycystic ovaries.
Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography
Authors: Chugani Harry T. , da Silva Ednea , Chugani Diane C. 
Published: January 2005

AbstractPositron emission tomography (PET) of brain glucose utilization is highly sensitive in detecting focal cortical abnormalities in patients with infantile spasms even when the computed tomographic (CT) and magnetic resonance imaging (MRI) scans are normal. Of 110 infants with spasms evaluated for potential surgical intervention during an 8‐year period, we encountered 18 infants (7 males, 11 females; age range, 10 mo to 5 yr) with a common metabolic pattern on positron emission tomography (PET) consisting of bilateral hypometabolism in the temporal lobes. CT and MRI scans did not reveal any focal abnormalities in the 18 infants. Video‐electroencephalographic monitoring indicated either bilateral or multifocal epileptogenicity, or failed to show any epileptic focus, so that none of the 18 infants were considered candidates for resective surgery. These patients were then enrolled in a prospective study aimed at determining long‐term outcome in the presence of bilateral temporal PET hypometabolism. Analysis of outcome in 14 of the 18 subjects (follow‐up period, 10 mo to 10 yr 5 mo; mean, 3 yr 11 mo ± 2 yr 4 mo [SD]) revealed the following: (1) all had severe developmental delay and had failed to gain significant milestones; (2) language development had been minimal or absent; (3) 10 of the 14 met the DSM‐IV criteria for autistic disorder. Our findings indicate that patients with infantile spasms and bitemporal glucose hypometabolism on PET comprise a relatively homogeneous group and are typically not candidates for cortical resection. The long‐term outcome of these infants is particularly poor and the majority are autistic.
Alzheimer's disease and apolipoprotein e‐4 allele in an amish population
Authors: Pericak‐Vance M. A. , Johnson C. C. , Rimmler J. B. , Saunders A. M. , Robinson L. C. , D'Hondr E. G. , Jackson C. E. , Haines J. L. 
Published: January 2005

AbstractAlzheimer's Disease (AD) is a complex genetic disorder with four loci already identified. Mutations in three of these, the amyloid precursor protein, presenilin I, and preseuilin II, cause early‐onset AD. The apolipoprotein E (APOE) gene contributes primarily to late‐onset AD. The APOE‐4 allele acts in a doserelated fashion to increase risk and decrease the age‐of‐onset distribution in AD. We examined the effect of APOE on AD in a previously unstudied Amish population that has a lower prevalence of dementia compared with other populations. We sampled a large inbred family with 6 latehyphen: onset AD members. We also genotyped 53 individuals from the general Amish population as controls for the APOE allele frequency estimates. The frequency of the APOE‐4 allele in the Amish controls was 0.037 ± 0.02. This differed significantly compared with three independent sets of non‐Amish white controls (p < 2 × 10−4, p < 6 × 10−5, and p < 2 × 10−6). In addition, all Amish AD‐affected individuals had APOE 3/3 genotypes; no APOE X/4 or 4/4 individuals were observed. We suggest that the lower frequency of dementia in the Amish may be partially explained by the decreased frequency of the APOE−4 allele in this population, and that the inbred nature of this pedigree, with its strong clustering of cases contrasted against the lower frequency of dementia, indicates that additional genetic factors influence late‐onset AD.
Molecular basis of phenotypic variability in sporadc creudeldt‐jakob disease
Authors: Parchi Piero , Castellani Rudolph , Capellari Sabina , Ghetti Bernardino , Young Katherine , Chen Shu G. , Farlow Martin , Dickson Dennis W. , Sima Anders A. F. , Trojanowski John Q. , Petersen Robert B. , Gambetti Pierluigi 
Published: January 2005

AbstractWe sequenced the prion protein gene and studied the biochemical characteristics and the intracerebral distribution of protease‐resistant prion protein with Western blot and immunohistochemistry in 19 cases of sporadic Creutzfeldt‐Jakob disease. We identified four groups of subjects defined by the genotype at codon 129 of the prion protein gene, the site of a common methioninelvaline polymorphism, and two types of protease‐resistant prion proteins that differed in size and glycosylation. The four Creutzfeldt‐Jakob disease groups showed distinct clinicopathological features that corresponded to previously described variants. The typical Creutzfeldt Jakob disease phenotype or myoclonic variant and the Heidenhain variant were linked to methionine homozygosity at codon 129 and to “type 1” protease‐resistant prion protein. The atypical and rarer variants such as that with dementia of long duration, the ataxic variant, and the variant with kuru plaques were linked to different genotypes at codon 129 and shared the “type 2” protease‐resistant prion protein. Our data indicate that the sporadic form of Creutzfeldt‐Jakob disease comprises a limited number of variants. The methionine/valine polymorphism at codon 129 of the prion protein gene and two types of protease‐resistant prion proteins are the major determinants of these variants. These findings suggest the existence of prion strains in humans and provide the molecular basis for a novel classification of sporadic Creutzfeldt‐Jakob disease.
Ultrastructural PMP22 expression in inherited demyelinating neuropathies
Authors: Vallat Jean‐Michel , Sindou Philippe , Preux Pierre‐Marie , Tabaraud Fransois , Milor André‐Michel , Couratier Philippe , Leguern Eric , Brice Alexis 
Published: January 2005

AbstractCharcot‐Marie‐Tooth type 1A (CMT‐1A) disease results from a duplication of the PMP22 gene on chromosome 17p11.2. A deletion of the same region causes hereditary neuropathy with liability to pressure palsies (HNPP). We examined the expression of PMP22 in sural nerve biopsies from 2 unrelated patients with CMT‐1A, 2 unrelated patients with HNPP, and control patients. The ultrastructural immunocytochemical quantitative analysis of cases of CMT‐1A and HNPP showed, respectively, an elevated and reduced expression of PMP22 level compared with controls.
Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1‐year results of a pilot study
Authors: Baron Mark S. , Vitek Jerrold L. , Green Joanne , Kaneoke Yoshiki , Hashimoto Takao , Turner Robert S. , Woodard John L. , Delong Mahlon R. , Bakay Roy A. E. , Cole Steven A. , McDonald William M. 
Published: January 2005

AbstractThe effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intracally intractable Parkinson's disease(PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug‐induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3‐month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined “on/off” Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1‐year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.
Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal
Authors: Arruda F. , Cendes F. , Andermann F. , Dubeau F. , Villemure J. G. , Jones‐Gotman M. , Poulin N. , Arnold D. L. , Olivier A. 
Published: January 2005

AbstractWe studied 74 consecutive patients with temporal lobe epilepsy who were treated surgically and in whom the volumes of mesial temporal structures were determined preoperatively by magnetic resonance imaging. We divided the patients into three groups according to the volumetric findings: unilateral (63.5% of the patients), bilateral (23%), or no atrophy (13.5%) of the amygdala–hippocampal formation. Two distinct surgical approaches were used: selective amygdalohippocampectomy (n = 37) or anterior temporal lobe resection (n = 37). Outcome was assessed at least 1 year after surgery, according to Engel's modified classification. Patients with unilateral mesial temporal atrophy had significantly better results compared with the other two groups (p < 0.001): We found excellent results (class I or II outcome) in 93.6% of the patients with unilateral atrophy, in 61.7% of those with bilateral atrophy, and in 50% of the group with no significant atrophy of mesial temporal structures. The two different surgical techniques were equally effective, regardless of the pattern of atrophy. In conclusion, magnetic resonance volumetric studies in temporal lobe epilepsy proved to be an important preoperative prognostic tool for surgical treatment, but they did not provide guidance for selecting one surgical approach compared to the other.
Progressive encephalomyelitis with rigidity responsive to plasmapheresis and immunosuppression
Authors: Fogan Lance 
Published: January 2005

AbstractThe stiff‐man syndrome is reported in a 55‐year‐old woman who also had signs of severe bulbar musculature hypercontraction. These clinical features correspond to the progressive encephalomyelitis with rigidity syndrome. Diazepam was minimally beneficial, but after treatment with plasmapheresis and corticosteroids, she was still asymptomatic when seen 5 years later.
Acute motor axonal neuropathy: An antibody‐mediated attack on axolemma
Authors: Hafer‐Macko Charlene , Hsieh Sung‐Tsang , Ho Tony W. , Sheikh Kazim , Cornblath David R. , Li Chun Yan , McKhann Guy M. , Asbury Arthur K. , Griffin John W. 
Published: January 2005

AbstractThe acute motor axonal neuropathy (AMAN) form of the Guillain‐Barré syndrome is a paralytic disorder of abrupt onset characterized pathologically by motor nerve fiber degeneration of variable severity and by sparing of sensory fibers. There is little demyelination or lymphocytic inflammation. Most cases have antecedent infection with Campylobacter jejuni and many have antibodies directed toward GM1 ganglioside‐like epitopes, but the mechanism of nerve‐fiber injury has not been defined. In 7 fatal cases of AMAN, immunocytochemistry demonstrated the presence of IgG and the complement activation product C3d bound to the axolemma of motor fibers. The most frequently involved site was the nodal axolemma, but in more severe cases IgG and C3d were found within the periaxonal space of the myelinated internodes, bound to the outer surface of the motor axon. These results suggest that AMAN is a novel disorder caused by an antibody‐ and complement‐mediated attack on the axolemma of motor fibers.
Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum
Authors: Arsac Christine , Raymond Cécile , Martin‐Moutot Nicole , Dargent Bénédicte , Seagar Michael , Couraud François , Pouget Jean 
Published: January 2005

AbstractRecent studies suggested that autoantibodies that bind to voltage‐dependent calcium channels and activate calcium entry may play a role in the progressive degeneration of motoneurons in sporadic amyotrophic lateral sclerosis. Immunoassays were performed to assess autoantibody titer in patients with amyotrophic lateral sclerosis or Lambert‐Eaton myasthenic syndrome, a disease in which the presnce of anti‐calcium channel antibodies is well documented. Based on immunoprecipitation assays for antibodies against N‐type calcium channels, only 8% (2/25) of amyotrophic lateral sclerosis patients had marginally positive titers, whereas 58% (18/31) of patients with Lambert‐Eaton myasthenic syndrome had positive titers. Enzyme‐linked immunosorbent assays with purified neuronal N‐type calcium channels revealed immunoreactivity in 2 of 25 amyotrophic lateral sclerosis sera and 12 of 31 Lambert‐Eaton myasthenic syndrome sera, which is not compatible with suggestions that enzyme‐linked immunosorbent assay is a more sensitive technique for the detection of autoantibodies in amyotrophic lateral sclerosis. Furthermore, based on immunoprecipitation assays, amyotrophic lateral sclerosis sera were totally negative for antibodies against L‐type calcium channels from skeletal muscle or brain. These data do not support the hypothesis that an autoimmune response against calcium channels plays a primary role in amyotrophic lateral sclerosis.
Proteolytic activity in amyotrophic lateral sclerosis IgG preparations
Authors: Nyormoi Okot 
Published: January 2005

AbstractSporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltagegated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the binding of 8B7 monoclonal antibody to the α1 subunit of voltage‐gated calcium channels, suggesting overlapping epitopes of the two antibodies. It is, however, possible that the 8B7 epitope was destroyed by proteases. Data presented here show that the blocking of 8B7 binding to the α1 subunit by diethylaminoethyl cellulose (DEAE)‐purified amyotrophic lateral sclerosis IgG was not observed with Fab fragments of amyotrophic lateral sclerosis IgG. The blocking was prevented by serine protease inhibitors. Moreover, it was reproduced by plaminogen and urokinase. These observations suggest that raised proteolytic activity in amyotrophic lateral sclerosis IgG preparations may be responsible for the blockade of 8B7 monoclonal antibody demonstrated previously. They also indicate the need to be particularly cautious when interpreting the results of incubation in amyotrophic lateral sclerosis sera or IgG preparations. Furthermore, they suggest that proteases may be partly responsible for some of the effects previously described for amyotrophic lateral sclerosis IgG. However, the proteolytic activity needs to be better defined and its possible role in amyotrophic lateral sclerosis investigated.
Clinical features of neocoritcal temporal lobe epilepsy
Authors: Pacia Steven V. , Devinsky Orrin , Perrine Kenneth , Ravdin Lisa , Luciano Daniel , Vazquez Blanca , Doyle Werner K. 
Published: January 2005

AbstractFew Studies have examined the clinical features of neocortical temporal lobe epilepsy (NTLE) in carefully selected patients. We reviewed records from 21 patients wtih NTLE, defined by intracranial electroencephal9ogram (EEG), who have been seizure free for 1 year or more following temporal lobectomy. The mean age of onset at the time of first seizure was 14 years (range, 1–41 years). Febrile seizures were reported in only 2 patients (9.5%). In contrast to prior mesial temporal lobe epilepsy (MTLE) studies, seizure‐free intervals between the initial cerebral insult or first seizure and habitual seizures were uncommon. Possible or known risk factors for epilepsy were reported in 13 of 21 patients (62%). Fifteen (71%) patients reproted auras, with experiential phenomena being the most common type. Magnetic resonance imaging was normal or nospecific in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and resonance imaging was normal or nospecifc in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and heterotopic gray matter and hippocampal atrophy in 1, and cortical dysgensis in 1. Neuropsychological testing showed deficits consistent with the seizure focus in 13 patients (62%), and Wada test showed ipsilateral memory deficits in 10 (48%). The most common behavioral manifestatin was a motionless stare at ictal onset (48%). In contrast to prior studies of MTLE, only 1 NTLE patient had frequent independent, contralateral temporal lobe epileptiform spikes on scalp EEG.