Abstract:
:For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a patient-centered database of 684,825 seizures, we simulated "placebo" and "drug" trials. These simulations were employed to clarify the sources of placebo effects in epilepsy, and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6-week baseline and 6-week test period, starting at time 0, 3, 6…24 months. Here, "placebo" reduced seizures regardless of study start time. Regression-to-the-mean persisted only for 3 to 6 months. Simulation 2 comprised a 6-week baseline and then 2 years of follow-up. Seizure frequencies continued to improve throughout follow-up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo-controlled "drug" trial, to explore methods of placebo response reduction. An efficacious "drug" failed to demonstrate a significant effect compared with "placebo" (p = 0.12), although modifications either in study start time (p = 0.025) or baseline population reduction (p = 0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In epilepsy clinical trials, some seizure reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329-336.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Goldenholz DM,Moss R,Scott J,Auh S,Theodore WHdoi
10.1002/ana.24470subject
Has Abstractpub_date
2015-09-01 00:00:00pages
329-36issue
3eissn
0364-5134issn
1531-8249journal_volume
78pub_type
杂志文章abstract::In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin-releasing hormone (CRH)-producing neurons that control the hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10766
更新日期:2004-01-01 00:00:00
abstract::Calmodulin is a major Ca2+ -binding protein that may mediate many Ca2+ -regulated processes in neuronal function. Calmodulin is present in the presynaptic nerve terminal in association with synaptic vesicles and in postsynaptic density fractions. Several calmodulin-regulated synaptic biochemical processes have been id...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160716
更新日期:1984-01-01 00:00:00
abstract::Biochemical examinations of brain tissue samples obtained from patients with Alzheimer's disease have revealed a decreased quantity of the neurotransmitter acetylcholine and reduced activity of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine formation. It has been suggested that the choline ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200214
更新日期:1986-08-01 00:00:00
abstract::Although genome-wide association studies (GWAS) have proven remarkably effective at identifying reliably associated genetic variants, the biology underlying these discoveries is rarely immediately apparent and in most cases seems bound to require extensive fine mapping and functional analysis before it is revealed. In...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.23613
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered. METHODS:Unfixed biopsies of control and FSHD deltoid...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20750
更新日期:2006-02-01 00:00:00
abstract::Previous studies have indicated increased immunoreactivity of the endogenous opioid peptide beta-endorphin in the cerebrospinal fluid (CSF) of infants under 2 years of age with apnea. To assess the role of endogenous opioids in the pathogenesis of apnea in children, the effect of oral treatment with the opioid antagon...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410270112
更新日期:1990-01-01 00:00:00
abstract::An infant presented with massive hyperchylomicronemia and a severe encephalopathy. MRI showed marked lipid deposition throughout the brain. Despite the normalization of the biochemistry, there was little clinical improvement, and at 18 months of age she has severe developmental delay, a strikingly abnormal MRI. Apolip...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10598
更新日期:2003-06-01 00:00:00
abstract::Orally administered levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD). The introduction of levodopa therapy is often delayed, however, because of the fear that it might be toxic for the remaining dopaminergic neurons and, thus, accelerate the deterioration of patients. However, in ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410430504
更新日期:1998-05-01 00:00:00
abstract::We describe 5 patients who presented with an acute cauda equina syndrome, which we believe was due to infarction of the conus medullaris. In 3 patients, the onset was spontaneous, and in 2 patients it was secondary to temporary occlusion of the distal aorta during medical manipulation. Pain in the buttocks and posteri...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210510
更新日期:1987-05-01 00:00:00
abstract::A subset of human immunodeficiency virus (HIV)-infected patients develop persistent CD8 hyperlymphocytosis and a Sjogren's syndrome-like syndrome associated with multivisceral CD8 T-cell infiltration, known as the diffuse infiltrative lymphocytosis syndrome (DILS). Patients with DILS tend to have higher CD4 cell count...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410406
更新日期:1997-04-01 00:00:00
abstract::Nineteen patients with radiologically confirmed stroke, and varying degrees of hemiparesis, were studied using somatosensory evoked potentials and the recently developed technique of transcutaneous motor cortex stimulation. The functional deficit caused by stroke was assessed at the time of evoked potential testing an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250111
更新日期:1989-01-01 00:00:00
abstract::Multiple sclerosis (MS) has been associated with HLA-DR2 for more than 20 years, and a large number of studies have addressed the relation between MS and the HLA class II genes, which are our major immune-response genes. This has produced a complex and confusing picture that is difficult to interpret. With the advent ...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410360706
更新日期:1994-01-01 00:00:00
abstract::We sought to determine whether the putative pontine micturition center in the human dorsal pons contains corticotrophin-releasing factor (CRF) neurons, and whether these neurons are depleted in patients with multiple system atrophy and bladder dysfunction. Brains were obtained at autopsy from 4 control subjects and 4 ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1258
更新日期:2001-11-01 00:00:00
abstract::Two families with a point mutation in mtDNA associated with myoclonic epilepsy and ragged-red fiber disease showed pronounced clinical heterogeneity. The mothers of the two families had adult-onset myopathy with ragged-red fibers, partial deficiency of cytochrome c oxidase, and sensory neuropathy. Members of the first...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410330613
更新日期:1993-06-01 00:00:00
abstract::The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050212
更新日期:1979-02-01 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:OBJECTIVES:Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20730
更新日期:2006-03-01 00:00:00
abstract::We describe a new cause of spinal cord ischemia illustrated by two cases--compression by the diaphragmatic crus of a lumbar artery giving rise to a spinal artery. The diagnosis has been established by dynamic spinal angiography, showing complete occlusion of the lumbar artery. Surgical section of the diaphragmatic cru...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:Charcot-Marie-Tooth type 4J (CMT4J) is a rare autosomal recessive neuropathy caused by mutations in FIG4 that result in loss of FIG4 protein. This study investigates the natural history and mechanisms of segmental demyelination in CMT4J. METHODS:Over the past 9 years, we have enrolled and studied a cohort of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25198
更新日期:2018-04-01 00:00:00
abstract::Two women suffered from a similar, slowly progressive illness characterized by upper and lower motor neuron involvement, sensory disturbances, and neurogenic bladder. Radiographic examinations showed cerebral atrophy and, in one, changes on computerized tomography suggesting leukodystrophy. Sural nerve biopsies reveal...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410130411
更新日期:1983-04-01 00:00:00
abstract::Demonstration of intrathecal IgG production is employed in the diagnosis of various neurological disorders. This pathological IgG fraction in cerebrospinal fluid (CSF) can be visualized directly as oligoclonal bands by electrophoresis or isoelectric focusing or can be calculated as "excess" or "synthesized" IgG accord...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410170105
更新日期:1985-01-01 00:00:00
abstract::Human T-lymphotropic virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, and with tropical spastic paraparesis (TSP), a demyelinating neurological syndrome. This article describes the clinical and pathological features of ATL and reviews...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410230739
更新日期:1988-01-01 00:00:00
abstract::Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the pati...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10451
更新日期:2003-03-01 00:00:00
abstract::Noradrenergic fibers were identified in rat cervical lymph nodes by fluorescence histochemistry and confirmed by radioenzymatic determination of norepinephrine. After superior cervical ganglionectomy, lymph node norepinephrine and noradrenergic fluorescence were strikingly decreased. The alpha-adrenergic radioligand [...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080509
更新日期:1980-11-01 00:00:00
abstract:OBJECTIVE:To assess risk factors associated with care for stroke symptoms. METHODS:Using data from the population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) conducted January 25, 2003-February 28, 2007 (N = 23,664), we assessed care-seeking behavior among 3,668 participants w...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21357
更新日期:2008-04-01 00:00:00
abstract::The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains unexplained. One potential pathogenetic mechanism is chronic toxicity due to disturbances of the glutamatergic neurotransmitter system, mediated via alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-s...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410420211
更新日期:1997-08-01 00:00:00
abstract::The developmental sequence of sleep cycles has been found to be a useful index of central nervous system maturation in premature infants. To determine the effects of severe reversible stress on the maturation of sleep cycles, 6- to 8-hour sleep studies were done on 10 premature infants with severe hyaline membrane dis...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410060610
更新日期:1979-12-01 00:00:00
abstract:OBJECTIVE:Guillain-Barré syndrome (GBS) is an acute postinfectious immune-mediated polyneuropathy. Although preceding respiratory tract infections with Mycoplasma pneumoniae have been reported in some cases, the role of M. pneumoniae in the pathogenesis of GBS remains unclear. We here cultured, for the first time, M. p...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24755
更新日期:2016-10-01 00:00:00
abstract:OBJECTIVE:Though effective anti-human immunodeficiency virus (HIV) therapies are now available, they have variable penetration into the brain. We therefore aimed to assess changes over calendar time in the risk for HIV-associated dementia (HIV-D), and factors associated with HIV-D risk. METHODS:Using Concerted Action ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21225
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:Hemodynamic impairment in one hemisphere has been shown to trigger ipsilateral motor activation in the opposite hemisphere on functional imaging. We hypothesized that reversing the hypoperfusion would normalize the motor activation pattern. METHODS:We studied four patients with high-grade stenosis and impair...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21554
更新日期:2009-02-01 00:00:00