Abstract:
OBJECTIVE:To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. METHODS:A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1- (entry expanded disability status scale, 3.0-5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed. RESULTS:There was a nonsignificant delay in time to sustained accumulated disability in GA- versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p = 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p = 0.0193). INTERPRETATION:The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Wolinsky JS,Narayana PA,O'Connor P,Coyle PK,Ford C,Johnson K,Miller A,Pardo L,Kadosh S,Ladkani D,PROMiSe Trial Study Group.doi
10.1002/ana.21079subject
Has Abstractpub_date
2007-01-01 00:00:00pages
14-24issue
1eissn
0364-5134issn
1531-8249journal_volume
61pub_type
临床试验,杂志文章,多中心研究,随机对照试验abstract::We describe the clinical and oculographic findings in 4 families with episodic ataxia and interictal nystagmus (EA-2) linked to chromosome 19p. Episodes varied from pure ataxia to combinations of symptoms suggesting involvement of the cerebellum, brainstem, and cortex. Some affected individuals exhibited a progressive...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410105
更新日期:1997-01-01 00:00:00
abstract::A series of nine related aromatic monocarboxylic acids (ACAs) previously shown to inhibit muscle membrane chloride conductance (GCl) selectively in the rat were studied for their ability to produce myotonia. All nine induced characteristic repetitive electrical activity and delayed relaxation in isolated muscle, altho...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040411
更新日期:1978-10-01 00:00:00
abstract::Ten patients with sporadic olivopontocerebellar atrophy and autonomic failure were studied with positron emission tomography. Subjects underwent both an [11C]diprenorphine and an [18F]fluorodopa scan. The mean caudate-occipital uptake ratio for [11C]diprenorphine was significantly reduced to 88% and the putamen-occipi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410370505
更新日期:1995-05-01 00:00:00
abstract::The titer of the scrapie agent was determined by measurements of time intervals from inoculation to onset of illness and from inoculation to death. Both intervals were found to be inversely proportional to the size of the dose injected intracerebrally into random-bred weanling Syrian hamsters. The logarithms of the ti...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110406
更新日期:1982-04-01 00:00:00
abstract::A non-right-handed patient developed alexia without agraphia from a right occipital lobe infarction. An intracarotid amobarbital test showed left hemispheric dominance for speech. The cause of alexia in this patient could not be explained simply by the accepted disconnection hypothesis, which proposes that speech, han...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030617
更新日期:1978-06-01 00:00:00
abstract::Between 36 and 44 weeks after conception, telencephalic white matter in the newborn appears to be particularly vulnerable to insults that result in morphological disturbances. Available evidence indicates that this disorder (or group of disorders), named acquired perinatal leukoencephalopathy, reflects a decrease in b...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160102
更新日期:1984-07-01 00:00:00
abstract::The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199911)46:5<732::aid-ana8>3.0.co
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. METHODS:We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Ca...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20904
更新日期:2006-08-01 00:00:00
abstract::Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1052
更新日期:2001-07-01 00:00:00
abstract::It has been proposed that early-onset familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (AD) have different causes, with FAD due to a single dominant gene with disease onset before the sixth decade, whereas sporadic AD has a later onset and is not associated with a dominant pattern of inheritance. Gi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320513
更新日期:1992-11-01 00:00:00
abstract:OBJECTIVE:What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brai...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24423
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:To explore the prognostic implications of epilepsy duration and age at surgery for seizure outcomes after frontal lobe epilepsy (FLE) surgery. METHODS:We reviewed 158 patients who underwent FLE surgery from 1995 to 2010. The primary outcome was seizure freedom at last follow-up (Engel class IA). Analyses emp...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23862
更新日期:2013-05-01 00:00:00
abstract:OBJECTIVE:Low vitamin D status at birth may be associated with risk of adult onset multiple sclerosis, but this link has not been studied directly. We assessed the relation between neonatal vitamin D concentrations, measured in stored blood samples, and risk of multiple sclerosis. METHODS:This was a population-based c...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24210
更新日期:2014-09-01 00:00:00
abstract::Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10061
更新日期:2002-01-01 00:00:00
abstract::Multiple sclerosis (MS) is characterized by patchy accumulations of inflammatory cells combined with demyelination. There are mononuclear cells in blood and cerebrospinal fluid of patients with MS that produce interferon-gamma and interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein (PLP). H...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350211
更新日期:1994-02-01 00:00:00
abstract::Four hundred five children from the Helsinki area who were 1 month to 16 years old were treated for acute encephalitis at the Children's Hospital, University of Helsinki, from January 1968 through December 1987. Encephalitis occurred most commonly in children 1 to 1.9 years of age, among whom the incidence was 16.7 pe...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290508
更新日期:1991-05-01 00:00:00
abstract::The incidence of periventricular-intraventricular hemorrhage (PV-IVH) in a group of 460 preterm infants with birth weight less than 2,250 gm, studied by cranial ultrasonography, was 39%. Sixty-four (36%) of the infants with periventricular-intraventricular hemorrhage had, in addition, periventricular intraparenchymal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150315
更新日期:1984-03-01 00:00:00
abstract::We report the clinical, imaging, and laboratory features of 8 patients with Devic's neuromyelitis optica. All patients had severe myelopathy and optic neuritis. In no patient was the brain, the brainstem, or the cerebellum affected, even after several years of disease. Various immunosuppressive treatments failed to be...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340211
更新日期:1993-08-01 00:00:00
abstract:OBJECTIVE:Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain lar...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25827
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:A study was undertaken to examine the association between overall cardiovascular health as recently defined by the American Heart Association in young adulthood to middle age and cognitive function in midlife. Overall ideal cardiovascular health incorporates 7 metrics, including the avoidance of overweight or...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.23836
更新日期:2013-02-01 00:00:00
abstract::The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410170412
更新日期:1985-04-01 00:00:00
abstract::We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weigh...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410410314
更新日期:1997-03-01 00:00:00
abstract::We present our approach to the diagnosis of pediatric neurotransmitter diseases exemplified by the differential diagnosis of children presenting with dystonia. This approach is based upon the primary aim of early diagnosis of treatable conditions and the need for a logical series of investigations. We have tried to be...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10628
更新日期:2003-01-01 00:00:00
abstract::A 10-year-old boy developed progressive dystonia and dementia. His symptoms had begun at age 2 1/2 years, and he had been unable to walk by 8 years. At age 10 he was severely dystonic, unable to use his hands to feed himself, and almost anarthric . He had dysphagia and urinary incontinence, and functioned at a 4-year-...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150408
更新日期:1984-04-01 00:00:00
abstract::Basis pontis lacunes cause contralateral but rarely ipsilateral ataxia. We explored this phenomenon with isotope tract tracing in the rhesus monkey. Labeled pontocerebellar fibers cross midline and disperse widely in the opposite hemipons before coalescing in the brachium pontis. This anatomical arrangement suggests t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20060
更新日期:2004-04-01 00:00:00
abstract::Neurosurgical procedures such as the dorsal root entry zone operation, ganglionectomy, and spinal-cord stimulation have been offered to patients with intractable post-herpetic neuralgia (PHN). Poor efficacy or high morbidity have limited the overall usefulness of these procedures. We recently conducted a preliminary o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350716
更新日期:1994-01-01 00:00:00
abstract::Gene therapy methods have continued to develop rapidly, and many initial limitations that hampered clinical application have been overcome. Thus serious consideration of clinical application of gene therapy is warranted for selected disorders in which the pathogenesis is well defined. Parkinson's disease has been the ...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10654
更新日期:2003-01-01 00:00:00
abstract::Interferon beta-1b reduces clinical exacerbations and disease activity in multiple sclerosis as shown by magnetic resonance imaging, but the mechanism of action is unknown. We investigated the correlation between the levels of soluble adhesion molecules and a reduction in contrast-enhancing lesions on gadopentetate di...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410410517
更新日期:1997-05-01 00:00:00
abstract::Caloric vestibular testing induced nystagmus in a patient with an isoelectric electroencephalogram after cardiopulmonary arrest. This has been demonstrated previously in patients in a chronic persistent vegetative state with intact brainstem reflexes, but never in a patient with an isoelectric electroencephalogram. An...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210118
更新日期:1987-01-01 00:00:00
abstract::We demonstrated that an IgM M-protein from a patient with motor neuron syndrome had antibody activity against gangliosides GM1, GD1b, and asialo GM1. Studies with a sugar-binding lectin suggested that the epitope in the patient's M-IgM involved the Gal(beta 1-3) GalNAc moiety. Immunohistological techniques demonstrate...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410230517
更新日期:1988-05-01 00:00:00