Abstract:
OBJECTIVE:To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS:Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS:Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS:This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.
journal_name
Neurologyjournal_title
Neurologyauthors
van Eijk RPA,Jones AR,Sproviero W,Shatunov A,Shaw PJ,Leigh PN,Young CA,Shaw CE,Mora G,Mandrioli J,Borghero G,Volanti P,Diekstra FP,van Rheenen W,Verstraete E,Eijkemans MJC,Veldink JH,Chio A,Al-Chalabi A,van den Bergdoi
10.1212/WNL.0000000000004606subject
Has Abstractpub_date
2017-10-31 00:00:00pages
1915-1922issue
18eissn
0028-3878issn
1526-632Xpii
WNL.0000000000004606journal_volume
89pub_type
杂志文章,meta分析,评审相关文献
NEUROLOGY文献大全abstract::The medical records of all children at our hospital with International Classification of Diseases 9th revision (ICD-9) codes 342, 433 to 438, or 767 from May 1999 to May 2004 were reviewed to assess whether they had stroke (any type) or, specifically, arterial ischemic stroke (AIS). Code accuracy ranged from 37 to 88%...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000247281.98094.e2
更新日期:2006-12-12 00:00:00
abstract::We studied the effect of deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus on voice symptoms in seven patients with essential tremor. All had undergone DBS for management of hand tremor. Five of the patients had received unilateral implants; two were treated bilaterally. Each reported improveme...
journal_title:Neurology
pub_type: 临床试验,杂志文章
doi:10.1212/wnl.50.3.796
更新日期:1998-03-01 00:00:00
abstract::Symptoms in patients with demyelinating disorders are associated with 3 important conduction abnormalities: complete conduction block, rate-dependent conduction block, and slowed impulse conduction. The recent observation that the electrogenic Na/K pump causes the nerve membrane hyperpolarization responsible for rate-...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.39.10.1364
更新日期:1989-10-01 00:00:00
abstract::The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000219761.05466.43
更新日期:2006-06-27 00:00:00
abstract::When the WHO's Topic Advisory Group for Neurology (TAG) started work on revision of the ICD-10 diagnostic codes in June 2009, the issues were daunting. The existing classification was produced a generation ago and the need to move to the digital age was becoming imperative. Appreciating modern advances in genetics and...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e31829a333c
更新日期:2013-07-09 00:00:00
abstract::The authors describe a novel pathogenic G5540A transition in the mitochondrial transfer RNA (tRNA)Trp gene of a sporadic encephalomyopathy characterized by spinocerebellar ataxia. Clinical features also included neurosensorial deafness, peripheral neuropathy, and dementia. Biochemistry revealed a severe reduction of c...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.54.8.1693
更新日期:2000-04-25 00:00:00
abstract::We studied a patient with autopsy-proven Hallervorden-Spatz syndrome (HSS) and the previously unreported finding of high-density lesions in the basal ganglia on CT. The diagnosis of HSS should be considered in a patient with dystonia and basal ganglia mineralization on CT. ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.38.1.154
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:Autonomic symptoms may occur frequently in diabetic and other neuropathies. There is a need to develop a simple instrument to measure autonomic symptoms in subjects with neuropathy and to test the validity of the instrument. METHODS:The Survey of Autonomic Symptoms (SAS) consists of 11 items in women and 12 ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e3182120147
更新日期:2011-03-22 00:00:00
abstract:OBJECTIVE:We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS:An internat...
journal_title:Neurology
pub_type: 共识发展会议,杂志文章
doi:10.1212/WNL.0000000000001891
更新日期:2015-09-08 00:00:00
abstract:BACKGROUND:An inverse association between cigarette smoking and the risk of idiopathic PD has been found in many epidemiologic studies. The therapeutic and possible neuroprotective effects of nicotine formulations on parkinsonian symptoms are controversial. METHODS:In a 12-week, randomized, double-blind, placebo-contr...
journal_title:Neurology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1212/wnl.57.6.1032
更新日期:2001-09-25 00:00:00
abstract::We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreati...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.44.8.1411
更新日期:1994-08-01 00:00:00
abstract:OBJECTIVE:To assess the pathophysiologic changes in patients with spontaneous intracranial hypotension (SIH) based on measures of CSF dynamics, and on the duration of symptoms, in a retrospective case-controlled study. METHODS:We included consecutive patients investigated for SIH at our department from January 2012 to...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000009812
更新日期:2020-07-21 00:00:00
abstract::Behavioral testing following division of the corpus callosum has shown that the anterior commissure can transfer information related to visual tasks interhemispherically in nonhuman primates but not in humans. We have found that the ratio of anterior commissure cross-sectional area to total neocortical commissural are...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.36.11.1513
更新日期:1986-11-01 00:00:00
abstract:OBJECTIVE:To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes. METHODS:This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000004541
更新日期:2017-10-03 00:00:00
abstract:OBJECTIVE:We conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP). METHODS:The study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical infor...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000008741
更新日期:2020-01-28 00:00:00
abstract::Pearson syndrome is a systemic disorder of oxidative phosphorylation in infants, predominantly affecting the bone marrow and exocrine pancreas and associated with single deletions in mitochondrial DNA (mtDNA). CNS involvement may occur in patients who survive the infantile hematopoietic disorder. We describe a Pearson...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.47.5.1320
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVE:To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNbeta. METHODS:This was an open-label study involving 78 patients with multiple sclerosis treated with Betaferon 8 million IU (MIU) subcutaneously (SC) every other day (n = 20), Rebif 22 micro g SC 3 times weekly (n = 25), ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000129265.73259.9e
更新日期:2004-06-08 00:00:00
abstract:OBJECTIVE:The NIH Stroke Scale (NIHSS) may not appropriately assess the spectrum of posterior circulation (PC)-related neurologic deficits. We determined the cutoff baseline NIHSS score that predicts independent daily life activity during the chronic stage in anterior circulation (AC) vs PC ischemic strokes. METHODS:A...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000304346.14354.0b
更新日期:2008-06-10 00:00:00
abstract:OBJECTIVE:To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB). METHODS:We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range 2-12 years). Competing risks survival models were used to examine the rates of progression to clinically...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000436942.55281.47
更新日期:2013-12-03 00:00:00
abstract:OBJECTIVE:To examine associated demographic and clinical correlates and the development of excessive daytime sleepiness (EDS) over 8 years in a community-based cohort of patients with Parkinson disease (PD). METHODS:A total of 232 patients with PD were included in a population-based prevalence study in 1993. Patients ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/01.wnl.0000233980.25978.9d
更新日期:2006-09-12 00:00:00
abstract::A moderately retarded Japanese boy, with a normal male karyotype (46,XY), was diagnosed to have a subcortical band heterotopia or double cortex syndrome. The band heterotopia was relatively thick compared with that of other patients reported. On T2-weighted coronal MR sections, there were numerous radial linear struct...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.48.6.1701
更新日期:1997-06-01 00:00:00
abstract::CSF lymphocyte subpopulations of eight patients with neurosarcoidosis were examined. CSF or CT was abnormal in all. The CSF T4/T8 (helper/suppressor) ratio was elevated at 6.8 and 7.6 in two patients; in one, there were only CSF T4 cells. The ratio was normal in five patients. ...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.37.5.878
更新日期:1987-05-01 00:00:00
abstract:OBJECTIVE:To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS). METHODS:AFFIRM and SENTINEL were ra...
journal_title:Neurology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1212/01.wnl.0000259521.14704.a8
更新日期:2007-04-17 00:00:00
abstract::We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability...
journal_title:Neurology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1212/wnl.59.1.123
更新日期:2002-07-09 00:00:00
abstract:OBJECTIVE:To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. METHODS...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000005330
更新日期:2018-04-17 00:00:00
abstract::Using an antibody against choline acetyltransferase (ChAT), mesencephalic cholinergic cell nuclei were studied in autopsy material from 3 cases of progressive supranuclear palsy (PSP) and 4 controls. ChAT-immunoreactive neurons were quantified in sections that spanned the rostrocaudal extent of each nucleus. In PSP, t...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.41.1.25
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:Spinal cord (SC) lesions are frequently found in multiple sclerosis (MS), but are rare in healthy aging and cerebrovascular patients. Our aim was to analyze the contribution of SC involvement in clinically isolated syndrome (CIS) in diagnosing MS according the McDonald 2010 criteria and in predicting conversi...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0b013e31827b1a67
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS:Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia wer...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/WNL.0000000000003451
更新日期:2017-01-03 00:00:00
abstract:OBJECTIVE:To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. METHODS:We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 year...
journal_title:Neurology
pub_type: 杂志文章,多中心研究
doi:10.1212/WNL.0000000000005814
更新日期:2018-07-17 00:00:00
abstract::Motivationally responsive motor deficits may occur in isolation or as part of more general neglect syndromes. We describe three patients with two discrete syndromes of isolated motor neglect, differentiated primarily by their performance in motor tasks enacted within or toward the contralesional hemispace. The lesions...
journal_title:Neurology
pub_type: 杂志文章
doi:10.1212/wnl.45.3.525
更新日期:1995-03-01 00:00:00