The response to levodopa in Parkinson's disease: imposing pharmacological law and order.


:The seemingly unpredictable response to levodopa in patients with Parkinson's disease can be understood as an interaction between several distinct pharmacological effects of levodopa. The most important are a short-duration response with a half-life of minutes to hours and a long-duration response with a half-life of days, superimposed on diurnal motor variation. A negative response characterized by brief worsening before and after the short-duration response and dyskinesia accentuate the short-duration response. These various responses are modified by disease progression and long-term levodopa therapy. Pharmacodynamic modeling of the short-duration response indicates that with time, the response becomes less graded and small changes in levodopa concentrations can produce big changes in response. In this setting, unpredictability arises from the variation in absorption and distribution of levodopa.


Ann Neurol


Annals of neurology


Nutt JG,Holford NH




Has Abstract


1996-05-01 00:00:00












  • Neonatal vitamin D status and risk of multiple sclerosis.

    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


    authors: Ueda P,Rafatnia F,Bäärnhielm M,Fröbom R,Korzunowicz G,Lönnerbro R,Hedström AK,Eyles D,Olsson T,Alfredsson L

    更新日期:2014-09-01 00:00:00

  • Human leukocyte antigen studies in multiple sclerosis.

    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


    authors: Hillert J

    更新日期:1994-01-01 00:00:00

  • Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis.

    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


    authors: Sumaya CV,Myers LW,Ellison GW,Ench Y

    更新日期:1985-04-01 00:00:00

  • Focal cortical myoclonus and rolandic cortical dysplasia: clarification by magnetic resonance imaging.

    abstract::Focal cortical myoclonus is rare. Obvious causes include tumor or atrophy involving the motor strip, but in some cases no cause is apparent. We present 4 patients who started to have focal myoclonus in childhood. All had focal motor seizures as well, and one had recurrent focal motor status epilepticus. All 4 had a mi...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Kuzniecky R,Berkovic S,Andermann F,Melanson D,Olivier A,Robitaille Y

    更新日期:1988-04-01 00:00:00

  • Genomic analysis reveals frequent TRAF7 mutations in intraneural perineuriomas.

    abstract::Intraneural perineuriomas are benign peripheral nerve sheath tumors that cause progressive debilitating focal extremity weakness. The etiology of perineuriomas is largely unknown. We utilized whole exome sequencing, copy number algorithm evaluation, and high-resolution whole genome microarray to investigate for a gene...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Klein CJ,Wu Y,Jentoft ME,Mer G,Spinner RJ,Dyck PJ,Dyck PJ,Mauermann ML

    更新日期:2017-02-01 00:00:00

  • Antiepileptic drugs interact with folate and vitamin B12 serum levels.

    abstract:OBJECTIVE:Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS:This prospective monocenter study aimed at testing the hypothesis that AED treatment is ass...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Linnebank M,Moskau S,Semmler A,Widman G,Stoffel-Wagner B,Weller M,Elger CE

    更新日期:2011-02-01 00:00:00

  • Cardiovascular health through young adulthood and cognitive functioning in midlife.

    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


    authors: Reis JP,Loria CM,Launer LJ,Sidney S,Liu K,Jacobs DR Jr,Zhu N,Lloyd-Jones DM,He K,Yaffe K

    更新日期:2013-02-01 00:00:00

  • Subacute motor neuronopathy: a remote effect of lymphoma.

    abstract::Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients di...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Schold SC,Cho ES,Somasundaram M,Posner JB

    更新日期:1979-03-01 00:00:00

  • Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease).

    abstract::Autopsy examination confirmed the diagnosis of subacute necrotizing encephalomyelopathy (SNE) in a 7-month-old male infant who underwent several metabolic studies before death. Intermittent lactic acidemia and fumaric aciduria, an extreme hyperglycemic response to an intravenous bolus of alanine, and an elevated total...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: DeVivo DC,Haymond MW,Obert KA,Nelson JS,Pagliara AS

    更新日期:1979-12-01 00:00:00

  • Development of a functional magnetic resonance imaging protocol for intraoperative localization of critical temporoparietal language areas.

    abstract::The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging m...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Rutten GJ,Ramsey NF,van Rijen PC,Noordmans HJ,van Veelen CW

    更新日期:2002-03-01 00:00:00

  • Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible.

    abstract::The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the ...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Heuer GG,Passini MA,Jiang K,Parente MK,Lee VM,Trojanowski JQ,Wolfe JH

    更新日期:2002-12-01 00:00:00

  • Time modulation of spike-and-wave activity in generalized epilepsy.

    abstract::Nineteen patients aged 4 to 44 years with generalized epilepsy and generalized 3 Hz spike-and-wave activity, were monitored for 24 or 36 hours on one to nine occasions to determine the time distribution of ictal and interictal electroencephalographic discharges and the consistency of the time patterns observed. Two pa...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Kellaway P,Frost JD Jr,Crawley JW

    更新日期:1980-11-01 00:00:00

  • The syndrome of posterior choroidal artery territory infarction.

    abstract::Posterior choroidal artery (PChA) territory infarcts remain the least well-known type of thalamic infarcts. Our study of 10 personal cases, selected from 2,925 stroke patients admitted consecutively to a community-based primary care center, and 10 published cases of unilateral PChA territory infarct suggests that they...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Neau JP,Bogousslavsky J

    更新日期:1996-06-01 00:00:00

  • Sensorimotor disinhibition in Parkinson's disease: effects of levodopa.

    abstract::It has been known for some time that patients with Parkinson's disease (PD) have difficulty executing simultaneous motor acts, yet the pathophysiology underlying this impairment remains uncertain. We examined the possibility that these dual-task deficits stem from defective sensorimotor mechanisms producing interferen...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Caligiuri MP,Heindel WC,Lohr JB

    更新日期:1992-01-01 00:00:00

  • Alzheimer-related neuronal protein A68: specificity and distribution.

    abstract::We previously reported that the monoclonal antibody Alz-50 recognizes a protein (A68) with an apparent molecular weight of 68,000 daltons in the brains of patients who died with Alzheimer's disease, but not in brain tissue from individuals free of neurological disease. We now report that substantial quantities of this...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Wolozin B,Davies P

    更新日期:1987-10-01 00:00:00

  • In vivo demyelinating activity of sera from patients with Guillain-Barré syndrome.

    abstract::The in vivo demyelinating capacity of sera from 27 patients with Guillain-Barré syndrome (GBS) and 47 other individuals was studied by intraneural injection into rat sciatic nerves. The morphological features of the nerves in cross section taken just proximal to the site of needle insertion was assessed 48 hours after...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Saida T,Saida K,Lisak RP,Brown MJ,Silberberg DH,Asbury AK

    更新日期:1982-01-01 00:00:00

  • Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.

    abstract::Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Rand KH,Johnson KP,Rubinstein LJ,Wolinsky JS,Penney JB,Walker DL,Padgett BL,Merigan TC

    更新日期:1977-05-01 00:00:00

  • Phenobarbital modifies seizure-related brain injury in the developing brain.

    abstract::To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued th...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Mikati MA,Holmes GL,Chronopoulos A,Hyde P,Thurber S,Gatt A,Liu Z,Werner S,Stafstrom CE

    更新日期:1994-09-01 00:00:00

  • Brain neurotransmitters in glycine encephalopathy.

    abstract::We measured neurotransmitter markers in autopsied brain of infants with glycine encephalopathy (GE). Because patients with GE develop intractable seizures, special attention was devoted to those neurotransmitter systems implicated in human epilepsy. Mean levels of glycine in the frontal cortex of GE patients were thre...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Kish SJ,Dixon LM,Burnham WM,Perry TL,Becker L,Cheng J,Chang LJ,Rebbetoy M

    更新日期:1988-09-01 00:00:00

  • Proteasome inhibitor-induced model of Parkinson's disease.

    abstract::We recently reported that systemic administration of a proteasome inhibitor induced a progressive levodopa-responsive, bradykinetic syndrome in rats with imaging, pathological, and biochemical features that strikingly resemble what is found in PD. This model has the potential to be a useful tool for studying the mecha...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: McNaught KS,Olanow CW

    更新日期:2006-08-01 00:00:00

  • Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy?

    abstract::N-acetylaspartate (NAA) contributes to the most prominent signal in proton magnetic resonance spectroscopy (1H-MRS) of the adult human brain. We report the absence of NAA in the brain of a 3-year-old child with neurodevelopmental retardation and moderately delayed myelination. Since normal concentration of NAA in body...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Martin E,Capone A,Schneider J,Hennig J,Thiel T

    更新日期:2001-04-01 00:00:00

  • In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses.

    abstract:OBJECTIVE:We tested the premise that cholinesterase inhibitor therapy should target butyrylcholinesterase (BuChE) in Alzheimer's disease (AD), not acetylcholinesterase (AChE) alone, because both enzymes hydrolyze acetylcholine, and BuChE is increased in AD cerebral cortex. METHODS:To examine this issue in vivo, we qua...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Kuhl DE,Koeppe RA,Snyder SE,Minoshima S,Frey KA,Kilbourn MR

    更新日期:2006-01-01 00:00:00

  • Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study.

    abstract:OBJECTIVE:This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. METHODS:Subjects were 436 well-character...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Launer LJ,Hughes TM,White LR

    更新日期:2011-11-01 00:00:00

  • Periodic paralysis and the sodium-potassium pump.

    abstract::Analysis of the pathophysiology of hypokalemic paralysis, as it occurs in barium poisoning, chronic potassium deficiency, and thyrotoxicosis, suggests that these disorders may have a similar mechanism. An increased ratio of muscle sodium permeability to potassium permeability reduces the ionic diffusion potential, whi...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Layzer RB

    更新日期:1982-06-01 00:00:00

  • Rapid clearance of human immunodeficiency virus type 1 from ventricular cerebrospinal fluid during antiretroviral treatment.

    abstract::To understand the pathogenesis of human immunodeficiency virus-induced neuropathology, it is critical to know the dynamics of viral replication in the central nervous system. Viral decay kinetics were mathematically analyzed from multiple serial specimens of ventricular cerebrospinal fluid and plasma during antiretrov...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Eggers C,Stuerenburg HJ,Schafft T,Zöllner B,Feucht HH,Stellbrink HJ,van Lunzen J

    更新日期:2000-06-01 00:00:00

  • Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia.

    abstract::Dopa-responsive dystonia (DRD) is one form of childhood-onset idiopathic torsion dystonia. Adult-onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women a...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Nygaard TG,Takahashi H,Heiman GA,Snow BJ,Fahn S,Calne DB

    更新日期:1992-11-01 00:00:00

  • Apolipoprotein E and alpha1-antichymotrypsin polymorphism in Alzheimer's disease.

    abstract::A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. We analy...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Nacmias B,Tedde A,Latorraca S,Piacentini S,Bracco L,Amaducci L,Guarnieri BM,Petruzzi C,Ortenzi L,Sorbi S

    更新日期:1996-10-01 00:00:00

  • Kearns-Sayre syndrome with reduced plasma and cerebrospinal fluid folate.

    abstract::A young woman with Kearns-Sayre syndrome and progressive central nervous system deterioration over 15 years had decreased plasma and cerebrospinal fluid folate levels while receiving phenytoin for a seizure disorder. A muscle biopsy showed a "ragged red fiber" myopathy with reduced muscle carnitine and mitochondrial e...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Allen RJ,DiMauro S,Coulter DL,Papadimitriou A,Rothenberg SP

    更新日期:1983-06-01 00:00:00

  • Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy.

    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


    authors: Rinne JO,Burn DJ,Mathias CJ,Quinn NP,Marsden CD,Brooks DJ

    更新日期:1995-05-01 00:00:00

  • Biophysical and pathological effects of cryogenic nerve lesion.

    abstract::Changes in endoneurial fluid pressure (EFP) and morphology were studied in rat sciatic nerves frozen for 60 seconds with a cryoprobe designed for human cryoanalgesia. The onset of increased EFP was rapid, and a peak of 23 cm H2O was reached within 90 minutes after injury. EFP levels returned to normal 32 days after fr...

    journal_title:Annals of neurology

    pub_type: 杂志文章


    authors: Myers RR,Powell HC,Heckman HM,Costello ML,Katz J

    更新日期:1981-11-01 00:00:00