bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopa
Authors:   Parkinson Study Group
Published: January 2005

AbstractThe Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism (DATATOP) trial was designed to test outcomes from treatment with 10 mg of deprenyl and/or 2,000 mg of tocopherollday in 800 untreated patients with Parkinson's disease. The need of subjects for symptomatic treatment with levodopa and the conversion of all subjects to open‐label deprenyl made it possible to study the long‐term effect of early deprenyl and tocopherol treatment on the later development of levodopa‐associated side effects. The rate of developing these side effects did not differ among the original treatment groups (early versus late deprenyl and tocopherol versus nontocopherol). About 50% of subjects developed “wearing off,” 30% dyskinesias, and 25% “freezing” in each group. At the end of the study, the groups were similarly disabled on the Hoehn‐Yahr, Schwab‐England, and Unified Parkinsonapos;s Disease Rating scales and took similar amounts of levodopa. Young subjects were more likely to develop wearing off, women to develop dyskinesias, and older subjects with rapidly progressive disease to develop freezing. We conclude that prior treatment with deprenyl or tocopherol did not reduce the occurrence of subsequent levodopa‐associated adverse effects in this population.
Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease
Authors: Gomez‐Isla Teresa , West Howard L. , Rebeck G. William , Harr Steven D. , Growdon John H. , Locascio Joseph J. , Perls Thomas T. , Lipsitz Lewis A. , Hyman Bradley T. 
Published: January 2005

AbstractInheritance of the apolipoprotein E (apoE) ε4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE ε4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty‐one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and Aβ deposits were assessed in a high‐order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the ε4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. Aβ deposition, by contrast, was not related to clinical features but was elevated in association with apoE ε4. These results indicate that apoE ε4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE ε4 on amyloid deposition.
Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration
Authors: Tedeschi Gioacchino , Bertolino Alessandro , Massaquoi Steve G. , Campbell Gregory , Patronas Nicholas J. , Bonavita Simona , Barnett Alan S. , Alger Jeffrey R. , Hallett Mark 
Published: January 2005

AbstractUsing proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age‐matched normal control subjects. This technique permits the simultaneous measurement of N‐ acetylaspartate, choline‐containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15‐mm slices divided into 0.84‐ml single‐volume elements. Because patients with cerebellar degeneration often show substan‐ tial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N‐acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.
A placebo‐controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis
Authors: Miller Robert G. , Petajan Jack H. , Bryan Wilson W. , Armon Carmel , Barohn Richard J. , Goodpasture Jessie C. , Hoagland Rebecca J. , Parry Gareth J. , Ross Mark A. , Stromatt Scott C. ,   rhCNTF ALS Study Group
Published: January 2005

AbstractPreclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double‐blind, placebo‐controlled trial in 570 patients with US. Patients were randomized to receive 0.5, 2, or 5 μg/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on‐ treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities‐of‐daily‐living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no benefical effect on any measure of ALS progression. There were increased adverse events in the 5 μg/kg group and increased deaths.
Neuronal migration abnormality in peroxisomal bifunctional enzyme defect
Authors: Kaufmann Walter E. , Theda Christiane , Naidu Sakkubai , Watkins Paul A. , Moser Ann B. , Moser Hugo W. 
Published: January 2005

AbstractPatterns of brain dysgenesis that resemble those in the Zellweger syndrome were demonstrated in a boy with an isolated defect of the peroxisomal bifunctional enzyme. There was bilateral centrosylvian pachygyria and polymicrogyria, diffuse hemispheric hypomyelination with heterotopic neurons, Purkinje cell heterotopias, and simplified convolutions of the dentate nucleus and inferior olive. This association of Zellweger syndrome–like brain dysgenesis with a defect of a single peroxisomal enzyme provides new opportunities for the study of pathogenetic mechanisms in peroxisomal disorders.
Cerebellar hypermetria associated with a selective decrease in the rate of rise of antagonist activity
Authors: Manto M. , Godaux E. , Jacquy J. , Hildebrand J. 
Published: January 2005

AbstractClassically, cerebellar hypermetria observed during fast and accurate movements i s ascribed to a delayed onset of the electromyographic activity of the antagonist muscle. We describe here 3 patients presenting a late‐onset cerebellar degeneration and exhibiting a hypermetria during their fast and accurate movements in spite of a normal onset latency of the antagonist activity. Hypermetria was found to be due to a slower rate of rise of the antagonist activity.
Leigh syndrome: Clinical features and biochemical and DNA abnormalities
Authors: Rahman S. , Blok R. B. , Dahl H.‐H. M. , Danks D. M. , Kirby D. M. , Chow C. W. , Christodoulou J. , Thorburn D. R. 
Published: January 2005

AbstractWe investigated the etiology of Leigh syndrome in 67 Australian cases from 56 pedigrees, 35 with a firm diagnosis and 32 with some atypical features. Biochemical or DNA defects were determined in both groups, ie, 80% in the tightly defined group and 41% in the “Leigh‐like” group. Eleven patients had mitochondrial DNA point mutations (nucleotide [nt] 8993 T to G, nt 8993 T to C, or nt 8344 A to G) and 1 Leigh‐like patient had a heteroplasmic deletion. Twenty‐nine patients had enzyme defects, ie, 13 respiratory chain complex I, 9 complex IV, and 7 pyruvate dehydrogenase complex (PDHC). Complex I deficiency is more common than recognized previously. Six PDHC‐deficient patients had mutations in the X‐chromosomal gene encoding the Elα subunit of PDHC. Parental consanguinity suggested autosomal recessive inheritance in two complex IV‐deficient sibships. We found no strong correlation between the clinical features and basic defects. An assumption of autosomal recessive inheritance (frequently made in the past) would have been wrong in nearly one‐half (1 1 of 28 tightly defined and 18 of 41 total patients) of those in whom a cause was found. A specific defect must be identified if reliable genetic counseling is to be provided.
Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors
Authors: Janss Anna J. , Yachnis Anthony T. , Silber Jeffrey H. , Trojanowski John Q. , Lee Virginia M.‐Y. , Sutton Leslie N. , Perilongo Giorgio , Rorke Lucy B. , Phillips Peter C. 
Published: January 2005

AbstractPrimitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinals antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse‐free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7‐fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP‐staining cells were associated with a 3.0‐fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.
Brain protein and α‐ketoglutarate dehydrogenase complex activity in alzheimer‐s disease
Authors: Mastrogiacomo Frank , Lindsay J. Gordon , Bettendorff Lucien , Rice Jacqueline , Kish Stephen J. 
Published: January 2005

AbstractTo determine whether the reduction in brain α‐ketoglutarate dehydrogenase complex activity in Alzheimer's disease (AD) is associated with an abnormality in one of its three constituent enzyme subunits, we measured protein levels of α‐ketoglutarate dehydrogenase (El), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3), in postmortem brain of 29 patients with AD (mean age, 73 years; age range of onset, 50‐78 years) and 29 control subjects. In the AD group protein levels of all three subunits were significantly reduced by 23 to 41% in the temporal cortex, whereas in the parietal cortex (El: −28% E3: −32%) and hippocampus (E3: −33%) significant changes were limited to El and E3. α‐Ketoglutarate dehydrogenase complex activities were more markedly reduced (by 46‐68%) and did not correlate with protein levels, suggesting that decreased enzyme activity cannot be primarily explained by loss of α‐ketoglutarate dehydrogenase complex protein. We did not find two E2 immunoreactive forms in the brain of any patient, as has been reported in fibroblasts of patients with very‐early‐onset chromosome 14‐linked AD. We conclude that brain protein and activity levels of α‐ketoglutarate dehydrogenase complex are reduced in patients with AD who have onset after 50 years and suggest that these changes, which are also observed in other human brain disorders, may represent a nonspecific consequence of different neurodegenerative processes. Nevertheless, reduced levels of this ratelimiting enzyme of the Krebs cycle could contribute to the brain neurodegenerative mechanisms of AD.
Antiamphiphysin antibodies with small‐cell lung carcinoma and paraneoplastic encephalomyelitis
Authors: Dropcho Edward J. 
Published: January 2005

AbstractParaneoplastic encephalomyelitis developed as the presenting feature of small‐cell lung carcinoma in 3 patients. Two patients with paraneoplastic encephalomyelitis manifested predominantly as subacute sensory neuronopathy did not improve after prednisone treatment and chemotherapy. The third patient had seyere axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intravenous immunoglobulin and prednisone. Serum from each patient immunocytochemically stained the neuropil and to a lesser degree the neuronal cytoplasm in human cerebral and cerebellar cortex. On immunoblots of human neuronal extracts, each patient's serum contained high‐titer IgG antibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies recently identified in several women with breast carcinoma and stiff‐man syndrome. Screening of a human brain complementary DNA expression library with patient serum yielded clones whose sequence is identical to that of the synaptic vesicle‐related protein amphiphysin. Reverse transcriptase‐polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small‐cell lung carcinomas and in 5 of 14 breast carcinomas. These observations highlight the clinical and serological heterogeneity of paraneoplastic central nervous system disorders: Patients with a given clinical syndrome may have different antineuronal antibodies, and patients with a given autoantibody specificity have differing clinical presentations.
Localization of HIV‐1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry
Authors: Takahashi Kiyomi , Wesselingh Steven L. , Griffin Diane E. , McArthur Justin C. , Johnson Richard T. , Glass Jonathan D. 
Published: January 2005

AbstractHuman immunodeficiency virus type 1 (HIV‐1) infects the brains of a majority of patients with the acquired immunodeficiency syndrome (AIDS), and has been linked to the development of a progressive dementia termed “HIV‐associated dementia.” This disorder results in severe cognitive, behavioral, and motor deficits. Despite this neurological dysfunction, HIV‐1 infection of brain cells does not occur significantly in neurons, astrocytes, or oligodendrocytes, but is restricted to brain macrophages and microglia. To identify possible low‐level or latent infection of other brain cells, we combined the techniques of the polymerase chain reaction with in situ hybridization for the detection of HIV DNA, and used immunocytochemistry to identify the HIV‐expressing cells. In the 21 adult brains studied (15 AIDS and 6 seronegative control brains), we found that polymerase chain reaction/in situ hybridization was both sensitive and specific for identifying HIV‐infected cells. In all brains, the majority of infected cells were macrophages and microglia. In several brains, however, a substantial minority of cells harboring HIV DNA were identified as astrocytes. Neurons, oligodendrocytes, and endothelial cells were not infected with HIV, even in cases with HIV‐associated dementia. These findings confirm previous data regarding the importance of macrophage/microglial infection, and essentially exclude neuronal infection in pathogenetic models of HIV‐associated neurological disease. These data also demonstrate that latent or low‐level infection of astrocytes occurs in AIDS, a finding that may be of importance in understanding HIV neuropathogenesis.
Gender differences in autoimmune demyelination in the mouse: Implications for multiple sclerosis
Authors: Voskuhl Rhonda R. , Pitchekian‐Halabi Hilda , Mackenzie‐Graham Allan , McFarland Henry F. , Raine Cedric S. 
Published: January 2005

AbstractGender‐related differences in experimental allergic encephalomyelitis (EAE) were examined in the SJL mouse with the purpose of characterizing an animal model ideal for the study of gender‐related differences in multiple sclerosis (MS). For the model to allow for study of the induction and the effector phase of disease, the adoptive EAE model was characterized. First, the SJL strain was shown to be nonresponsive with regard to the development of antisyngeneic HY‐specific responses in females, thereby permitting intergender adoptive transfers of T lymphocytes during EAE induction. Then, when myelin basic protein (MBP)‐specific T cells derived from females were adoptively transferred into female and male recipients, female recipients demonstrated a more rapid onset of disease (p = 0.01), greater maximal acutephase clinical scores (p < 0.0001) and greater mean clinical scores (p < 0.0001) compared with male recipients. When MBP‐specific T cells derived from males were adoptively transferred, female recipients again tended to be more severely affected. Histopathologic analysis revealed quantitative differences between genders that paralleled clinical expression. These results document a clear gender‐related difference in adoptive EAE in the SJL, with clinical and histopathologic disease greater in females compared with males. This model will be a useful tool for addressing autoimmune mechanisms underlying gender‐related differences in MS.
Hemifacial seizures and cerebellar ganglioglioma: An epilepsy syndrome of infancy with seizures of cerebellar origin
Authors: Harvey A. Simon , Jayaka Prasanna , Duchowny Michael , Resnick Trevor , Prats Antonio , Altman Nolan , Renfroe J. Benjamin 
Published: January 2005

AbstractWe investigated a 6‐month‐old infant with daily episodes of left hemifacial contraction, head and eye deviation to the right, nystagmoid jerks to the right, autonomic dysfunction, and retained consciousness. The episodes began on day 1 of life and were unresponsive to antiepileptic medication. Interictal and ictal scalp electroencephalographic (EEG) recordings were unremarkable. Magnetic resonance imaging revealed a mass in the left cerebellar hemisphere and peduncle. Ictal single‐photon emission computed tomography revealed focal hyperperfusion in the region of the cerebellar mass. Ictal EEG recordings with implanted cerebellar electrodes demonstrated focal seizure discharges in the region of the mass. Resection of the mass resulted in remission of seizures and histopathology revealed ganglioglioma. Six previously reported infants with similar semiology (described as “hemifacial spasm”), imaging findings, and histopathology are reviewed. We believe the previously reported infants and our patient constitute a rare but important clinicopathological syndrome of infancy characterized by epileptic seizures of cerebellar origin.
A dopaminergic neurotoxin, (R)‐N‐methylsalsolinol, increases in parkinsonian cerebrospinal fluid
Authors: Maruyama Wakako , Abe Takashi , Tohgi Hideo , Dostert Philippe , Naoi Makoto 
Published: January 2005

AbstractThe concentration of (R)‐N‐methylsalsolinol, which is a dopamine‐derived neurotoxin selective to dopamine neurons and induces parkinsonism in rats, was found to be increased significantly in the cerebrospinal fluid of untreated patients with Parkinson's disease. The enantiospecific occurrence of (R)‐N‐methylsalsolinol in cerebrospinal fluid suggests its enzymatic synthesis in the human brain. The individual differences in the activities of the enzymes determining the metabolism of (R)‐N‐methylsalsolinol in the brain might be involved in the pathogenesis of Parkinson's disease.
Benzodiazepine receptors in focal epilepsy with cortical dysgenesis: An 11C‐flumazenil PET study
Authors: Richardson M. P. , Koepp M. J. , Duncan J. S. , Brooks D. J. , Fish D. R. 
Published: January 2005

AbstractPrevious imaging studies using 11C‐flumazenil in patients with mesial temporal lobe epilepsy and neocortical partial seizure disorders have found focal decreases in γ‐aminobutyric acid type A/benzodiazepine receptor binding. These studies used subjective visual assessment and a region of interest approach to quantitation. We performed three‐dimensional, 11C‐flumazenil positron emission tomography in 12 patients with cortical dysgenesis identified by high‐resolution volumetric magnetic resonance imaging and in 26 normal subjects. Spectral analysis was used to produce a parametric image of 11C‐flumazenil volume of distribution for each subjects. Using volumetric normalization and statistical parametric mapping, we compared the entire brain volume of each patient with the brains of the normal group to produce maps of regions of abnormal 11C‐flumazenil binding which were then rendered into the volumetric magnetic resonance images. This allowed a correlation of structure and function to be made. Of the 12 patients, 10 showed at least one region of abnromal 11C‐flumazenil binding; the abnormal regions were frequently more extensive than were the lesions seen with magnetic resonance imaging. 11C‐Flumazenil binding abnormalities were frequently seen in regions of cortex that had a normal magnetic resonance appearance. Lesions were characterized by increases in γ‐aminobutyric acid type A/benzodiazepine receptor availability, and by the decreases found in previous studies. These findings have implications for the neurobiology of seizure disorders associated with cortical dysgenesis and for the management of such patients if surgery is contemplated.