Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD.

Abstract:

OBJECTIVE:To assess the safety, tolerability, and biological activity of glial cell line-derived neurotrophic factor (GDNF) administered by an implanted intracerebroventricular (ICV) catheter and access port in advanced PD. BACKGROUND:GDNF is a peptide that promotes survival of dopamine neurons. It improved 6-OHDA- or MPTP-induced behavioral deficits in rodents and monkeys. METHODS:A multicenter, randomized, double-blind, placebo-controlled, sequential cohort study compared the effects of monthly ICV administration of placebo and 25, 75, 150, 300, and 500 to 4,000 microg of GDNF in 50 subjects with PD for 8 months. An open-label study extended exposure up to an additional 20 months and maximum single doses of up to 4,000 microg in 16 subjects. Laboratory testing, adverse events (AE), and Unified Parkinson's Disease Rating Scale (UPDRS) scoring were obtained at 1- to 4-week intervals throughout the studies. RESULTS:Twelve subjects received placebo and seven or eight subjects were assigned to each of the other GDNF dose groups. "On" and "off" total and motor UPDRS scores were not improved by GDNF at any dose. Nausea, anorexia, and vomiting were common hours to several days after injections of GDNF. Weight loss occurred in the majority of subjects receiving 75 microg or larger doses of GDNF. Paresthesias, often described as electric shocks (Lhermitte sign), were common in GDNF-treated subjects, were not dose related, and resolved on discontinuation of GDNF. Asymptomatic hyponatremia occurred in over half of subjects receiving 75 microg or larger doses of GDNF; it was symptomatic in several subjects. The open-label extension study had similar AE and lack of therapeutic efficacy. CONCLUSIONS:GDNF administered by ICV injection is biologically active as evidenced by the spectrum of AE encountered in this study. GDNF did not improve parkinsonism, possibly because GDNF did not reach the target tissues--putamen and substantia nigra.

journal_name

Neurology

journal_title

Neurology

authors

Nutt JG,Burchiel KJ,Comella CL,Jankovic J,Lang AE,Laws ER Jr,Lozano AM,Penn RD,Simpson RK Jr,Stacy M,Wooten GF,ICV GDNF Study Group. Implanted intracerebroventricular. Glial cell line-derived neurotrophic factor.

doi

10.1212/wnl.60.1.69

subject

Has Abstract

pub_date

2003-01-14 00:00:00

pages

69-73

issue

1

eissn

0028-3878

issn

1526-632X

journal_volume

60

pub_type

临床试验,杂志文章,多中心研究,随机对照试验
  • Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS. Optic Neuritis Study Group.

    abstract::The association of the human leukocyte antigen (HLA)-DR2 allele with brain MRI signal abnormalities and with the development of MS was assessed in 178 patients enrolled in the Optic Neuritis Treatment Trial. HLA haplotype DR2 was present in 85 (48%) of the 178 patients. Its presence was associated with increased odds ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.54.9.1859

    authors: Hauser SL,Oksenberg JR,Lincoln R,Garovoy J,Beck RW,Cole SR,Moke PS,Kip KE,Gal RL,Long DT

    更新日期:2000-05-09 00:00:00

  • Presenting features and value of diagnostic procedures in leptomeningeal metastases.

    abstract:OBJECTIVE:To study the presenting features and value of routine diagnostic procedures in patients with leptomeningeal metastases (LMM) related to the primary malignancy to improve diagnostic assessment. METHODS:The authors studied the presenting features and value of routine diagnostic procedures in relation to the hi...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.53.2.382

    authors: van Oostenbrugge RJ,Twijnstra A

    更新日期:1999-07-22 00:00:00

  • Understanding co-morbidities affecting children with epilepsy.

    abstract::Co-morbid conditions frequently occur in childhood epilepsy and may significantly affect epilepsy and its treatment. Similarly, epilepsy and antiepileptic drugs (AEDs) may affect these associated conditions. Co-morbidities that have a significant association with childhood epilepsy include attention-deficit/hyperactiv...

    journal_title:Neurology

    pub_type: 杂志文章,评审

    doi:10.1212/wnl.62.5_suppl_2.s17

    authors: Pellock JM

    更新日期:2004-03-09 00:00:00

  • Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease.

    abstract:BACKGROUND:Krabbe disease (globoid cell leukodystrophy [GLD]) is an autosomal recessive lysosomal disorder affecting the central and peripheral nervous system. The authors performed MRS to characterize metabolic alterations and their regional variation in brain tissue in GLD in vivo. METHODS:Abnormalities of cerebral ...

    journal_title:Neurology

    pub_type: 临床试验,杂志文章

    doi:10.1212/01.wnl.0000049469.29011.e9

    authors: Brockmann K,Dechent P,Wilken B,Rusch O,Frahm J,Hanefeld F

    更新日期:2003-03-11 00:00:00

  • Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality.

    abstract:OBJECTIVES:We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. METHODS:Eleven sites in North America ...

    journal_title:Neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1212/WNL.0b013e31829c5cfe

    authors: Abend NS,Arndt DH,Carpenter JL,Chapman KE,Cornett KM,Gallentine WB,Giza CC,Goldstein JL,Hahn CD,Lerner JT,Loddenkemper T,Matsumoto JH,McBain K,Nash KB,Payne E,Sánchez SM,Fernández IS,Shults J,Williams K,Yang A,Dlu

    更新日期:2013-07-23 00:00:00

  • Mild cognitive impairment: long-term course of four clinical subtypes.

    abstract:OBJECTIVE:To empirically validate the expanded concept of mild cognitive impairment (MCI), which differentiates between four clinical subtypes-amnestic MCI-single domain, amnestic MCI-multiple domains, nonamnestic MCI-single domain, and nonamnestic MCI-multiple domains-and to examine the prevalence, course, and outcome...

    journal_title:Neurology

    pub_type: 杂志文章,随机对照试验

    doi:10.1212/01.wnl.0000249117.23318.e1

    authors: Busse A,Hensel A,Gühne U,Angermeyer MC,Riedel-Heller SG

    更新日期:2006-12-26 00:00:00

  • A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.

    abstract:OBJECTIVE:To describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified. METHODS:Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. ...

    journal_title:Neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1212/WNL.0000000000005862

    authors: Cabrera-Serrano M,Mavillard F,Biancalana V,Rivas E,Morar B,Hernández-Laín A,Olive M,Muelas N,Khan E,Carvajal A,Quiroga P,Diaz-Manera J,Davis M,Ávila R,Domínguez C,Romero NB,Vílchez JJ,Comas D,Laing NG,Laporte J,Ka

    更新日期:2018-07-24 00:00:00

  • Melioidosis and bilateral third-nerve palsies.

    abstract::Central nervous system involvement in melioidosis is unusual. We describe a 34-year-old man who developed a Pseudomonas pseudomallei meningitis, manifested as bilateral third-nerve palsies, 13 years after having been in southeast Asia. Diagnosis was established by a fourfold rise in the serum antibody titer for the ba...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.34.1.105

    authors: Beck RW,Janssen RS,Smiley ML,Schatz NJ,Savino PJ,Rubin DH

    更新日期:1984-01-01 00:00:00

  • Prognostic importance of brainstem auditory evoked responses after asphyxia.

    abstract::Brainstem auditory evoked responses were recorded after acute asphyxia in 126 infants, ages birth through 18 months. Of these, 21 had markedly abnormal amplitude ratios, and all infants with abnormal amplitude ratios had severe neurologic handicaps. An abnormal amplitude ratio predicts long-term neurologic sequelae of...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.31.11.1429

    authors: Hecox KE,Cone B

    更新日期:1981-11-01 00:00:00

  • Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis.

    abstract:OBJECTIVE:This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS:There were 3...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.50.6.1601

    authors: Rovaris M,Filippi M,Falautano M,Minicucci L,Rocca MA,Martinelli V,Comi G

    更新日期:1998-06-01 00:00:00

  • Quantifiable evaluation of cerebellar signs in children.

    abstract:OBJECTIVE:To validate, examine the internal validity, and adapt to children the electronic version of the composite cerebellar functional severity (CCFS) score. METHODS:In this multicenter study, we compared the validated manual device with the new electronic version (n = 46) and analyzed its kinetics in 146 patients ...

    journal_title:Neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1212/WNL.0000000000001403

    authors: Filipovic Pierucci A,Mariotti C,Panzeri M,Giunti P,Boesch S,Schulz JB,Pandolfo M,Durr A,Tezenas du Montcel S,EFACTS Study Group.

    更新日期:2015-03-24 00:00:00

  • Antineuronal antibodies in patients with neurologic complications of primary Sjögren's syndrome.

    abstract::Neurologic complications of both the central and peripheral nervous systems occur frequently in patients with primary Sjögren's syndrome (primary SS), but the underlying cause of these complications is unknown. We studied the presence of antineuronal antibodies in relation to neurologic complications in a consecutive ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.43.12.2574

    authors: Moll JW,Markusse HM,Pijnenburg JJ,Vecht CJ,Henzen-Logmans SC

    更新日期:1993-12-01 00:00:00

  • Incidence and prevalence of epilepsy among older U.S. Medicare beneficiaries.

    abstract:OBJECTIVE:To determine the prevalence and incidence of epilepsy among U.S. Medicare beneficiaries aged 65 years old and over, and to compare rates across demographic groups. METHODS:We performed a retrospective analysis of Medicare administrative claims for 2001-2005, defining prevalent cases as persons with ≥1 claim ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0b013e3182477edc

    authors: Faught E,Richman J,Martin R,Funkhouser E,Foushee R,Kratt P,Kim Y,Clements K,Cohen N,Adoboe D,Knowlton R,Pisu M

    更新日期:2012-02-14 00:00:00

  • Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis.

    abstract:BACKGROUND:The antivirally active MxA protein is induced by interferon (IFN) alpha/beta and inhibits the replication of single-stranded RNA viruses including measles virus (MV). The authors investigated whether the MxA gene contributed to the development of subacute sclerosing panencephalitis (SSPE) in Japanese individ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000106940.95749.8e

    authors: Torisu H,Kusuhara K,Kira R,Bassuny WM,Sakai Y,Sanefuji M,Takemoto M,Hara T

    更新日期:2004-02-10 00:00:00

  • Neuropsychiatric changes precede classic motor symptoms in ALS and do not affect survival.

    abstract:OBJECTIVES:To investigate patient susceptibility to neuropsychiatric symptoms in the context of progression of more classic motor symptoms in amyotrophic lateral sclerosis (ALS) and to examine the impact of neuropsychiatric symptoms on survival. METHODS:The study cohort consisted of 219 patients with ALS (limb onset =...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000000023

    authors: Mioshi E,Caga J,Lillo P,Hsieh S,Ramsey E,Devenney E,Hornberger M,Hodges JR,Kiernan MC

    更新日期:2014-01-14 00:00:00

  • Demyelinating neuropathy due to primary IgM kappa B cell lymphoma of peripheral nerve.

    abstract::A 53-year-old man presented with a painful, demyelinating sensorimotor peripheral neuropathy with lymphomatous infiltration on sural nerve biopsy, but no evidence of systemic lymphoma. The neuropathy responded to cytotoxic therapy. Seven years later he developed generalized lymphadenopathy due to B cell lymphoplasmacy...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.37.7.1231

    authors: Ince PG,Shaw PJ,Fawcett PR,Bates D

    更新日期:1987-07-01 00:00:00

  • Readmission to a different hospital following acute stroke is associated with worse outcomes.

    abstract:OBJECTIVE:There is a high risk of readmission within 30 days of index acute ischemic stroke (AIS), but effect of readmission to a different hospital is not known. We performed a retrospective cohort study to assess our hypothesis that 30-day readmission outcomes after AIS are worse for those readmitted to another hospi...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000008446

    authors: Stein LK,Agarwal P,Thaler A,Kwon CS,Jette N,Dhamoon MS

    更新日期:2019-11-12 00:00:00

  • Fat metabolism during exercise in patients with McArdle disease.

    abstract:OBJECTIVE:It is known that muscle phosphorylase deficiency restricts carbohydrate utilization, but the implications for muscle fat metabolism have not been studied. We questioned whether patients with McArdle disease can compensate for the blocked muscle glycogen breakdown by enhancing fat oxidation during exercise. M...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000343002.74480.e4

    authors: Ørngreen MC,Jeppesen TD,Andersen ST,Taivassalo T,Hauerslev S,Preisler N,Haller RG,van Hall G,Vissing J

    更新日期:2009-02-24 00:00:00

  • The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease.

    abstract:OBJECTIVES:Based on the hippocampus disconnection hypothesis in Alzheimer disease (AD), which postulates that uncoupling from cortical inputs contributes to disinhibition-like changes in hippocampus activity, we suggested that in patients with AD, the more the intrinsic functional connectivity between hippocampus and p...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000001575

    authors: Tahmasian M,Pasquini L,Scherr M,Meng C,Förster S,Mulej Bratec S,Shi K,Yakushev I,Schwaiger M,Grimmer T,Diehl-Schmid J,Riedl V,Sorg C,Drzezga A

    更新日期:2015-05-12 00:00:00

  • Mild cognitive impairment: incidence and vascular risk factors in a population-based cohort.

    abstract:OBJECTIVE:We examined the incidence of mild cognitive impairment (MCI) and its potential vascular risk factors in a prospective population-based study. METHODS:An age-stratified random population-based cohort (baseline n = 1,982), followed for up to 4 years, was annually assessed for cognitive and everyday functioning...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0b013e318295d776

    authors: Ganguli M,Fu B,Snitz BE,Hughes TF,Chang CC

    更新日期:2013-06-04 00:00:00

  • Drug-mediated antiepileptogenesis in humans.

    abstract::The goal of pharmacologic therapy for patients with epilepsy is to suppress seizures without side effects. There is growing interest in developing antiepileptogenic drugs capable of preventing the onset of seizures in patients at high risk and inducing a permanent remission of seizures in patients with epilepsy, i.e.,...

    journal_title:Neurology

    pub_type: 杂志文章,评审

    doi:10.1212/wnl.59.9_suppl_5.s34

    authors: Schachter SC

    更新日期:2002-11-12 00:00:00

  • Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment.

    abstract::The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was ef...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.32.5.503

    authors: Karoum F,Chuang LW,Eisler T,Calne DB,Liebowitz MR,Quitkin FM,Klein DF,Wyatt RJ

    更新日期:1982-05-01 00:00:00

  • Continuous and routine EEG in intensive care: utilization and outcomes, United States 2005-2009.

    abstract:OBJECTIVES:To evaluate the effect of intensive care unit continuous EEG (cEEG) monitoring on inpatient mortality, hospital charges, and length of stay. METHODS:A retrospective cross-sectional study was conducted using the Nationwide Inpatient Sample, a dataset representing 20% of inpatient discharges in nonfederal US ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000436948.93399.2a

    authors: Ney JP,van der Goes DN,Nuwer MR,Nelson L,Eccher MA

    更新日期:2013-12-03 00:00:00

  • Characteristics of temporal lobe epilepsy with mesial temporal sclerosis, with special reference to psychotic episodes.

    abstract::This study investigates the histories and the clinical course of 111 patients who had nonlesional temporal lobe epilepsy. We compared 61 patients with unilateral hippocampal sclerosis (UHS group) and 50 patients with minimal change (MRI negative group) assessed on the basis of MRI. In agreement with previous reports, ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.47.5.1199

    authors: Kanemoto K,Takeuchi J,Kawasaki J,Kawai I

    更新日期:1996-11-01 00:00:00

  • Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups.

    abstract::We reviewed the outcome (developmental, neurologic, and seizure) and prognostic factors of 57 cases of infantile spasms (17 cryptogenic, 40 symptomatic). The mean developmental score of the cryptogenic group (71.2 +/- 24.2) was significantly higher than that of the symptomatic group (48.4 +/- 24.5), as assessed by the...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.43.11.2322

    authors: Koo B,Hwang PA,Logan WJ

    更新日期:1993-11-01 00:00:00

  • Postictal neurogenic stunned myocardium.

    abstract::Neurogenic left ventricular dysfunction is a recognized complication of subarachnoid hemorrhage, but this condition has not been reported after seizure activity. The authors present two cases of neurogenic stunned myocardium after convulsive seizures, suggesting that ictal activity can lead to sympathetically mediated...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.WNL.0000163858.77494.7A

    authors: Chin PS,Branch KR,Becker KJ

    更新日期:2005-06-14 00:00:00

  • Hemorrhagic infarction in white matter following acute carbon monoxide poisoning.

    abstract::Hemorrhage complicating acute carbon monoxide poisoning is usually confined to the basal ganglia. The authors report three people with acute carbon monoxide poisoning manifesting selective or prominent white matter involvement complicated by hemorrhagic infarction on CT and MRI in one and by subcortical T2*-weighted M...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000138495.61717.86

    authors: Finelli PF,DiMario FJ Jr

    更新日期:2004-09-28 00:00:00

  • Critically re-evaluating a common technique: Accuracy, reliability, and confirmation bias of EMG.

    abstract:OBJECTIVES:(1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG. METHODS:Three experienced academic electromyographers interpreted 3 compact discs with 20 EMG ...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/WNL.0000000000002292

    authors: Narayanaswami P,Geisbush T,Jones L,Weiss M,Mozaffar T,Gronseth G,Rutkove SB

    更新日期:2016-01-19 00:00:00

  • Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy.

    abstract::We evaluated the relationship between mesial temporal seizure focus and serum prolactin (PRL) in patients before and after they underwent anterior temporal lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These patients had a confirmed unilateral epileptogenic focus in mesial temporal structures...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/wnl.49.2.528

    authors: Lin YY,Su MS,Yiu CH,Shih YH,Yen DJ,Kwan SY,Wu ZA,Chan SH

    更新日期:1997-08-01 00:00:00

  • What is the risk of developing parkinsonism following neuroleptic use?

    abstract::Use of neuroleptic medications is common among elderly patients. Using multivariate models, the authors found that use of antipsychotic medications, age, and disability were strong predictors of developing self-reported Parkinson disease (PD) in the subsequent year among 1992 to 2000 Medicare Current Beneficiary Surve...

    journal_title:Neurology

    pub_type: 杂志文章

    doi:10.1212/01.wnl.0000203348.13337.89

    authors: Noyes K,Liu H,Holloway RG

    更新日期:2006-03-28 00:00:00