A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis.

Abstract:

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression. OBJECTIVES:To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile. METHODS:We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls. All patients were genotyped for HFE polymorphisms. We performed a multiplex cytokine and growth factor analysis and immunoassays for iron-related analytes. Classification statistics were generated using a support vector machine algorithm. RESULTS:The groups of patients with ALS and neurologic disease controls were each associated with distinct profiles of biomarkers. Fourteen biomarkers differed between patients with ALS and the control group. The five proteins with the lowest p values differentiated patients with ALS from controls with 89.2% accuracy, 87.5% sensitivity, and 91.2% specificity. Expression of IL-8 was higher in those patients with lower levels of physical function. Expression of beta2-microglobulin was higher in subjects carrying an H63D HFE allele, while expression of several markers was higher in subjects carrying a C282Y HFE allele. CONCLUSIONS:A CSF inflammatory profile associated with amyotrophic lateral sclerosis (ALS) pathogenesis may distinguish patients with ALS from neurologic disease controls, and may serve as a biomarker panel to aid in the diagnosis of ALS pending further validation. Some of these biomarkers differ by HFE genotype.

journal_name

Neurology

journal_title

Neurology

authors

Mitchell RM,Freeman WM,Randazzo WT,Stephens HE,Beard JL,Simmons Z,Connor JR

doi

10.1212/01.wnl.0000333251.36681.a5

subject

Has Abstract

pub_date

2009-01-06 00:00:00

pages

14-9

issue

1

eissn

0028-3878

issn

1526-632X

pii

01.wnl.0000333251.36681.a5

journal_volume

72

pub_type

杂志文章
  • The mechanism of action of glatiramer acetate treatment in multiple sclerosis.

    abstract:OBJECTIVE:Glatiramer acetate (formerly known as copolymer 1) is the major noninterferon immunomodulatory agent used in the treatment of relapsing-remitting multiple sclerosis. Its mechanism of action over the past 40 years has evolved with our understanding of the immune response. METHODS:We review the various mechani...

    journal_title:Neurology

    pub_type: 杂志文章,评审

    doi:10.1212/WNL.0b013e3181c97e39

    authors: Racke MK,Lovett-Racke AE,Karandikar NJ

    更新日期:2010-01-05 00:00:00

  • Predicting developmental outcomes in preterm infants: A simple white matter injury imaging rule.

    abstract:OBJECTIVE:To develop a simple imaging rule to predict neurodevelopmental outcomes at 4.5 years in a cohort of preterm neonates with white matter injury (WMI) based on lesion location and examine whether clinical variables enhance prediction. METHODS:Sixty-eight preterm neonates born 24-32 weeks' gestation (median 27.7...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000008172

    authors: Cayam-Rand D,Guo T,Grunau RE,Benavente-Fernández I,Synnes A,Chau V,Branson H,Latal B,McQuillen P,Miller SP

    更新日期:2019-09-24 00:00:00

  • Practice variability in brain death determination: a call to action.

    abstract:OBJECTIVE:To characterize the present state of brain death (BD) determination in actual practice relative to contemporary American Academy of Neurology (AAN) guidelines. METHODS:We reviewed the charts of all adult (16 years and older) BD organ donors during 2011 from 68 heterogeneous hospitals in the Midwest United St...

    journal_title:Neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1212/01.wnl.0000436938.70528.4a

    authors: Shappell CN,Frank JI,Husari K,Sanchez M,Goldenberg F,Ardelt A

    更新日期:2013-12-03 00:00:00

  • APOE epsilon4 is not a susceptibility gene in idiopathic or diabetic sensory neuropathy.

    abstract::The presence of an APOE epsilon4 allele may be a risk factor for neuropathy severity in diabetes. The authors assessed the frequency of APOE epsilon4 in patients presenting with sensory predominant neuropathy. APOE epsilon4 frequency among patients with early diabetic neuropathy and impaired glucose tolerance-associat...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.WNL.0000148587.97690.4E

    authors: Zhou Z,Hoke A,Cornblath DR,Griffin JW,Polydefkis M

    更新日期:2005-01-11 00:00:00

  • Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

    abstract::Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address ...

    journal_title:Neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1212/wnl.46.3.641

    authors: Lautenschlager NT,Cupples LA,Rao VS,Auerbach SA,Becker R,Burke J,Chui H,Duara R,Foley EJ,Glatt SL,Green RC,Jones R,Karlinsky H,Kukull WA,Kurz A,Larson EB,Martelli K,Sadovnick AD,Volicer L,Waring SC,Growdon JH,Fa

    更新日期:1996-03-01 00:00:00

  • Tissue inhibitor metalloproteinase-1 and clinical outcomes after acute ischemic stroke.

    abstract:OBJECTIVE:To prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke. METHODS:We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured i...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000008389

    authors: Zhong C,Wang G,Xu T,Zhu Z,Guo D,Zheng X,Wang A,Bu X,Peng H,Chen J,Xu T,Peng Y,Li Q,Ju Z,Geng D,He J,Zhang Y

    更新日期:2019-10-29 00:00:00

  • Computerized tomography in demyelinating disease of the young.

    abstract::We have used computerized tomography (CT) to look for evidence of cerebral demyelination in children with progressive neurologic disorders. Fourteen patients with a clinical diagnosis of a demyelinating disorder were examined by CT, and five had CT findings suggesting cerebral demyelination. In two patients with a so-...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.27.9.838

    authors: Robertson WC Jr,Gomez MR,Reese DF,Okazaki H

    更新日期:1977-09-01 00:00:00

  • PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.

    abstract::The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000142258.29304.fe

    authors: Hatano Y,Sato K,Elibol B,Yoshino H,Yamamura Y,Bonifati V,Shinotoh H,Asahina M,Kobayashi S,Ng AR,Rosales RL,Hassin-Baer S,Shinar Y,Lu CS,Chang HC,Wu-Chou YH,Ataç FB,Kobayashi T,Toda T,Mizuno Y,Hattori N

    更新日期:2004-10-26 00:00:00

  • On the cause of hyporeflexia in the Holmes-Adie syndrome.

    abstract::Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.38.2.262

    authors: Miyasaki JM,Ashby P,Sharpe JA,Fletcher WA

    更新日期:1988-02-01 00:00:00

  • Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson's disease.

    abstract::To determine the extent that different dopamine (DA) neuronal markers provide similar estimates of striatal (caudate and putamen) DA nerve terminal loss in idiopathic Parkinson's disease (PD), we compared, in postmortem striatum of 12 patients with PD and 10 matched controls, levels of five different DA neuronal marke...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.47.3.718

    authors: Wilson JM,Levey AI,Rajput A,Ang L,Guttman M,Shannak K,Niznik HB,Hornykiewicz O,Pifl C,Kish SJ

    更新日期:1996-09-01 00:00:00

  • Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses.

    abstract:BACKGROUND:The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses t...

    journal_title:Neurology

    pub_type: 历史文章,杂志文章,多中心研究

    doi:10.1212/01.wnl.0000138426.88460.cb

    authors: Davis LE,Eisen SA,Murphy FM,Alpern R,Parks BJ,Blanchard M,Reda DJ,King MK,Mithen FA,Kang HK

    更新日期:2004-09-28 00:00:00

  • Relative effect of APOE ε4 on neuroimaging biomarker changes across the lifespan.

    abstract:OBJECTIVE:To provide a comprehensive understanding of APOE ε4 effects across the lifespan on the 3 main neuroimaging biomarkers. METHODS:Two hundred seven community-dwelling, cognitively normal APOE ε4 carriers and noncarriers aged 20-87 years were involved in this study. They underwent structural MRI, fluorodeoxygluc...

    journal_title:Neurology

    pub_type: 临床试验,杂志文章

    doi:10.1212/WNL.0000000000003234

    authors: Gonneaud J,Arenaza-Urquijo EM,Fouquet M,Perrotin A,Fradin S,de La Sayette V,Eustache F,Chételat G

    更新日期:2016-10-18 00:00:00

  • Cerebral processing in the minimally conscious state.

    abstract::We studied a patient in a minimally conscious state using PET and cognitive evoked potentials. Cerebral metabolism was below half of normal values. Auditory stimuli with emotional valence (infant cries and the patient's own name) induced a much more widespread activation than did meaningless noise; the activation patt...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000137421.30792.9b

    authors: Laureys S,Perrin F,Faymonville ME,Schnakers C,Boly M,Bartsch V,Majerus S,Moonen G,Maquet P

    更新日期:2004-09-14 00:00:00

  • APOE epsilon2/epsilon4 polymorphism and cerebral microbleeds on gradient-echo MRI.

    abstract::The association of APOE genotypes with cerebral microbleeds (CMBs) was examined on the basis of the location of CMBs in 414 patients who were admitted primarily because of stroke. With respect to possession of the epsilon2 or epsilon4 allele, the adjusted odds ratio was 1.94 (1.05 to 3.58) for lobar CMBs but 1.21 (0.6...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000183311.48144.7f

    authors: Kim M,Bae HJ,Lee J,Kang L,Lee S,Kim S,Lee JE,Lee KM,Yoon BW,Kwon O,Koo JS,Kim BK

    更新日期:2005-11-08 00:00:00

  • Arterial wall properties in carotid artery dissection: an ultrasound study.

    abstract:BACKGROUND:Cervical artery dissection is often attributed to an underlying arteriopathy related to a generalized extracellular matrix defect. OBJECTIVE:The authors compared the hemodynamic and morphologic properties of the carotid artery, as assessed noninvasively by ultrasonography, in patients with spontaneous inter...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.55.5.663

    authors: Guillon B,Tzourio C,Biousse V,Adraï V,Bousser MG,Touboul PJ

    更新日期:2000-09-12 00:00:00

  • Biopsy-proven cerebral vasculitis associated with cocaine abuse.

    abstract::We report cerebral vasculitis in 2 cocaine users who developed symptoms (transient blindness and persistent headache) while smoking "crack," followed by progressive widespread cerebral dysfunction with focal signs over the next few weeks. One patient had smoked crack exclusively, and the other also used cocaine intrav...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.40.7.1092

    authors: Krendel DA,Ditter SM,Frankel MR,Ross WK

    更新日期:1990-07-01 00:00:00

  • Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer's disease.

    abstract::The presence of the APOE epsilon 4 allele encoding apolipoprotein E4 (apoE4) is the major genetic risk factor for late-onset Alzheimer's disease (AD). However, the molecular and cellular mechanisms by which APOE epsilon 4 renders AD risk are unclear. In this report, we present genetic evidence that an apoE receptor, L...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.49.1.56

    authors: Kang DE,Saitoh T,Chen X,Xia Y,Masliah E,Hansen LA,Thomas RG,Thal LJ,Katzman R

    更新日期:1997-07-01 00:00:00

  • Recognizing and preventing epilepsy-related mortality: A call for action.

    abstract::Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half ...

    journal_title:Neurology

    pub_type: 杂志文章,评审

    doi:10.1212/WNL.0000000000002253

    authors: Devinsky O,Spruill T,Thurman D,Friedman D

    更新日期:2016-02-23 00:00:00

  • Ventilatory response in myotonic dystrophy.

    abstract::Patients with myotonic dystrophy often develop respiratory failure caused by alveolar hypoventilation. Abnormalities in the ventilatory response to hypoxia and hypercapnia may explain this phenomenon. Accordingly, hypoxic and hypercapnic responses were measured in seven patients with myotonic dystrophy who had only mi...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.27.12.1125

    authors: Carroll JE,Zwillich CW,Weil JV

    更新日期:1977-12-01 00:00:00

  • Hospitalization in amyotrophic lateral sclerosis: causes, costs, and outcomes.

    abstract:OBJECTIVE:As ALS progresses, extensive supportive care is required, including multidisciplinary outpatient care and hospitalization. The authors studied the causes, health care utilization, and outcomes for hospitalized patients with ALS. METHODS:With use of the 1996 Nationwide Inpatient Sample, an administrative data...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.56.6.753

    authors: Lechtzin N,Wiener CM,Clawson L,Chaudhry V,Diette GB

    更新日期:2001-03-27 00:00:00

  • The neurologic content of S. Weir Mitchell's fiction.

    abstract:BACKGROUND:Silas Weir Mitchell (1829 to 1914), one of the most important neurologists in American Medicine, was known for his seminal work on the phantom limb syndrome, causalgia, and nerve injuries. He was also a prolific writer of novels and short stories. The neurologic content of this fiction has not been studied. ...

    journal_title:Neurology

    pub_type: 传,历史文章,杂志文章

    doi:10.1212/01.wnl.0000196645.96131.b2

    authors: Louis ED,Horn S,Roth LA

    更新日期:2006-02-14 00:00:00

  • Effect of diet on exercise tolerance in carnitine palmitoyltransferase II deficiency.

    abstract::It is generally believed that a diet high in carbohydrate improves exercise tolerance in patients with carnitine palmitoyltransferase II (CPT II) deficiency, but it has never been systematically investigated. The authors investigated the effect of a high- vs low-carbohydrate diet on exercise tolerance in four patients...

    journal_title:Neurology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1212/01.wnl.0000078195.05396.20

    authors: Ørngreen MC,Ejstrup R,Vissing J

    更新日期:2003-08-26 00:00:00

  • Cerebral dysfunction after chronic hypoxia in children.

    abstract::Although the long-term effects of acute anoxia have been studied, the effects of chronic hypoxia on the developing human brain have received little attention. We studied children with a cyanotic congenital heart defect to assess the impact of chronic hypoxia by eight measures: neurologic examination, visual evoked res...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.35.1.42

    authors: O'Dougherty M,Wright FS,Loewenson RB,Torres F

    更新日期:1985-01-01 00:00:00

  • Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epile

    abstract:OBJECTIVE:To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS:A ...

    journal_title:Neurology

    pub_type: 指南,杂志文章,实务指引,评审

    doi:10.1212/01.wnl.0000123695.22623.32

    authors: French JA,Kanner AM,Bautista J,Abou-Khalil B,Browne T,Harden CL,Theodore WH,Bazil C,Stern J,Schachter SC,Bergen D,Hirtz D,Montouris GD,Nespeca M,Gidal B,Marks WJ Jr,Turk WR,Fischer JH,Bourgeois B,Wilner A,Faught R

    更新日期:2004-04-27 00:00:00

  • The Tourette syndrome diagnostic confidence index: development and clinical associations.

    abstract:BACKGROUND:The clinical characteristics of Tourette syndrome (TS) present challenges for the systematic determination of whether individuals are affected and severity. Vocal and motor tics wax and wane, decrease over time, and may be voluntarily suppressible, and therefore may be absent at interview. Current instrument...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.53.9.2108

    authors: Robertson MM,Banerjee S,Kurlan R,Cohen DJ,Leckman JF,McMahon W,Pauls DL,Sandor P,van de Wetering BJ

    更新日期:1999-12-10 00:00:00

  • Idiopathic cervical dystonia: an overview.

    abstract::Idiopathic cervical dystonia (CD) is the most common of the adult-onset focal dystonias. It manifests as involuntary muscle contractions that cause twisting or turning of the neck. The resulting abnormal head and neck postures are heterogeneous in their presentation. Because of the variable presentation of the disease...

    journal_title:Neurology

    pub_type: 杂志文章,评审

    doi:

    authors: Stacy M

    更新日期:2000-01-01 00:00:00

  • Long-term acetyl-L-carnitine treatment in Alzheimer's disease.

    abstract::In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1...

    journal_title:Neurology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1212/wnl.41.11.1726

    authors: Spagnoli A,Lucca U,Menasce G,Bandera L,Cizza G,Forloni G,Tettamanti M,Frattura L,Tiraboschi P,Comelli M

    更新日期:1991-11-01 00:00:00

  • Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.

    abstract::To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle a...

    journal_title:Neurology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1212/01.WNL.0000158680.89323.F8

    authors: Iijima M,Yamamoto M,Hirayama M,Tanaka F,Katsuno M,Mori K,Koike H,Hattori N,Arimura K,Nakagawa M,Yoshikawa H,Hayasaka K,Onodera O,Baba M,Yasuda H,Saito T,Nakazato M,Nakashima K,Kira J,Kaji R,Oka N,Sobue G

    更新日期:2005-04-26 00:00:00

  • Posthypoxic treatment with MK-801 reduces hypoxic-ischemic damage in the neonatal rat.

    abstract::We evaluated the neuroprotective effect of MK-801, a noncompetitive, selective N-methyl-D-aspartate receptor antagonist, in a neonatal hypoxic-ischemic animal model. Seven-day-old rats underwent bilateral ligation of the carotid arteries followed by exposure to an 8% oxygen atmosphere for 1 hr. We sacrificed the anima...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.39.5.713

    authors: Hattori H,Morin AM,Schwartz PH,Fujikawa DG,Wasterlain CG

    更新日期:1989-05-01 00:00:00

  • Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2-13.3 (SMA 5q).

    abstract::We made phenotypic analysis of 14 families with spinal muscular atrophy (SMA) linking to chromosome 5q11.2-13.3 (SMA 5q), and 2 that may not map to this locus, to assess clinical symptoms among SMA families known to result from mutation at the identical gene/locus. Although the current number of families is still smal...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.40.12.1831

    authors: Munsat TL,Skerry L,Korf B,Pober B,Schapira Y,Gascon GG,al-Rajeh SM,Dubowitz V,Davies K,Brzustowicz LM

    更新日期:1990-12-01 00:00:00