摘要:

AbstractThe use of early combination therapy with bromocriptine (Br) and levodopa (LD) in Parkinson's disease is controversial. It has been suggested that treatment with this regimen would prevent or delay the onset of motor fluctuations and dyskinesia. Thus, some have recommended it as a standard of care. This recommendation is based on the theory that LD may accelerate the progression of PD and clinical experience using Br monotherapy in early Parkinson's disease, which suggested that Br causes fewer late complications. This article reviews these arguments and shows that the theories are uproven. A single, uncontrolled trial is often referred to as evidence for efficacy of early combination therapy. We critically review this and five other studies which have evaluated the treatment strategy. We show that the literature is often misleading and that these trials do not support the efficacy of early combination therapy. We conclude that there is no justifiable reason to use a combination of Br and LD in early parkinsonian patients.

ISSN:0885-3185    

DOI:10.1002/mds.870080302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAt least five receptors for dopamine (D1–D5) have been recognised from molecular biological studies, and their pharmacological properties and brain localisations have been determined. The D1and D2subtypes are the principal subtypes in brain, and their cellular localisations in the caudate nucleus and putamen have been determined. With recent advances in the understanding of basal ganglia neuronal function, these localisation data enable insights into the mode of action of drugs used at present and in the futue to treat Parkinson's diseas

ISSN:0885-3185    

DOI:10.1002/mds.870080303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractOn clinical criteria alone, the diagnosis of early Parkinson's disease can be difficult and, by definition, the prospective recognition of preclinical Parkinson's disease is impossible. Positron emission tomography (PET) using [18F]dopa as tracer has been proposed as a means of identifying patients with preclinical disease. The number of subjects detected to date has been few; most have been identified by serendipity or during the course of family studies. This review examines the significance of a single abnormal scan in an apparently healthty subject in terms of the relationship between normal and abnormal values and the time course of the disease.

ISSN:0885-3185    

DOI:10.1002/mds.870080304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractLevodopa, at concentrations of 0.25 × 10−4Mor larger, is toxic for the human neuroblastoma cell NB69. Toxicity is associated with high levels of quinones, increased activity of complex II‐III, and lack of changes of complex I of the mitochondrial respiratory chain. Deprenyl, which does not alter the production of quinones, has a partial protective effect. Tocopherol, 23 or 115 × 10−6M, lacks significant preventive effect on levodopa toxicity, but ascorbic acid, 10−3M, prevents levodopa toxicity and quinone formation. Deprenyl, 10−4M, provides additional protection in cultures treated with levodopa and ascorbic acid. Our results indicate that ascorbic acid and deprenyl prevent levodopa neurotoxicity by unrelated mechanisms. Both compounds should be considered as complementary drugs to test for slowing the progression of Parkinso

ISSN:0885-3185    

DOI:10.1002/mds.870080305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe syndrome of gait ignition failure is described in six patients in whom difficulty initiating walking was the major symptom. The gait had elements of parkinsonism with start and turn hesitation, shuffling, and freezing. Unlike parkinsonism, however, the gait was relatively normal once entrained; the posture was upright, and good arm swing, a normal stride length, and no festination were seen. Equilibrium was normal or near normal, and when seated or lying, rhythmic leg movements were generated normally. Facial expression, upper limb mobility, and whole body movements were wellpreserved. This gait disorder differed from that seen in Parkinson's disease and the so‐called “frontal” or “senile” disorders of gait and gait “apraxia”. The causes of this gait syndrome are not clear but it may be due to frontal lobe vascular disease and/or focal degeneration of the

ISSN:0885-3185    

DOI:10.1002/mds.870080306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractFreezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi‐infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60−82 years; 74 ± 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 ± 1.9 years (range, 0.5−6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the “walking‐over‐lines” maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow‐up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings. We therefore conclude that primary progressive freezing gait should be recognized as a distinct neurological entity, unique in its clinical presentation and natural course. The lack of response to levodopa raises the possibility that nondopaminergic pathways

ISSN:0885-3185    

DOI:10.1002/mds.870080307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractL‐Dopa is metabolized to 3–O‐methyldopa (3OMD) by catechol‐O‐ methyltransferase (COMT). This reduces the amount ofL‐dopa available for entry into brain. We studied the effect of OR‐611, a new COMT inhibitor, on plasma and brain 6‐[18F]‐fluoro‐L‐dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR‐611 pretreatment substantially reduced plasma 6FD metabolism to 3‐O‐methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3‐fold increase following OR‐611 pretreatment, compared to the same animals in the control state. OR‐611 inhibits plasma metabolism of 6FD and increases brain uptake of thisL‐dopa analog. OR‐611 appears to be a promising agent as an adjunct toL‐dopa for the treatme

ISSN:0885-3185    

DOI:10.1002/mds.870080308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAn assessment was made of the orientation and variability in postural center of pressure patterns in individuals with tardive dyskinesia (TD) and/or developmental disability during quiet standing. Postural patterns were compared and contrasted between four groups of individuals: those with (a) TD and developmentally disabled (severely and profoundly retarded); (b) developmental disability only; (c) TD but of normal intelligence; and (d) a healthy control group. The center of pressure displacements were derived from the lateral, vertical, and anterior‐posterior force and moment components of force platform measurements. Analyses demonstrated that individuals with TDin combinationwith developmental disability had a different center of pressure orientation and variability compared to healthy individuals and individuals suffering only from developmental disability or TD. The center of pressure pattern in the developmentally disabled TD group was characterized by a more prominent lateral orientation, whereas in the other three groups, it had a more predominant anterior‐posterior orientation. In addition, the variability in these orientation components was much smaller in the developmentally disabled TD group, indicating a more regular pattern of sway in the center of pressure during quiet standing in these individuals. These findings show that assessments of postural center of pressure profile orientation and variability may be useful indicators for investigating TD, especially in distinguishing between developmental disability and

ISSN:0885-3185    

DOI:10.1002/mds.870080309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractLewy bodies have been found in the hypothalamic lateral tuberal nucleus (NTL) and the adjoining tuberomammillary nucleus (TM) in Parkinson's disease (PD). The NTL is severely atrophic in Huntington's disease; the TM seems unaffected. In this study, we examined we examined the NTL and the TM of seven PD patients and one patient with presumed PD to assess whether the presence of Lewy bodies indicated neuronal loss. Most Lewy bodies were found in the TM, but they were also present in the NTL of seven of the eight patients. The number of NTL neurons in the PD patients was similar to a group of 14 nonneurological controls, seven Alzheimer's disease (AD) patients, and two AIDS patients with dementia. This challenges the hypothesis that Lewy bodies are a sign of significant cell death. The TM, whose cells could not be counted, did not seem depleted in neuronal numbers, although occasional neuronophagia was observed.

ISSN:0885-3185    

DOI:10.1002/mds.870080310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractFour subjects aged between 29 and 60 years were examined because of axial motor impairment after hypoxic brain injury. Magnetic resonance imaging revealed circumscribed lesions of the globus pallidus in every case. The association of freezing of the gait, speech disorders, axial bradykinesia, and postural disturbances, with no rigidity or tremor and little or no distal akinesia, suggests a role of the globus pallidus in controlling axial motion.

ISSN:0885-3185    

DOI:10.1002/mds.870080311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY