摘要:

Dopamine agonists (DAs) have been shown to be effective as monotherapy in early stages of Parkinson's disease (PD) and as an adjunctive treatment to levodopa in advanced PD. Since bromocriptine, an ergot compound, was introduced as the first commercially available DA more than 25 years ago, additional DAs have become available for clinical use. There is a remarkable paucity of data, however, that would guide clinicians in their decision process to select the most appropriate DAs. We discuss the theoretical basis for comparing the various DAs, and provide a concise analysis and summary of comparative trials of DAs in PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Spinal cord injury (SCI) is a devastating and common neurologic disorder that has profound influences on modern society from physical, psychosocial, and socioeconomic perspectives. Accordingly, the present decade has been labeled the Decade of the Spine to emphasize the importance of SCI and other spinal disorders. Spinal cord injury may be divided into both primary and secondary mechanisms of injury. The primary injury, in large part, determines a given patient's neurologic grade on admission and thereby is the strongest prognostic indicator. However, secondary mechanisms of injury can exacerbate damage and limit restorative processes, and hence, contribute to overall morbidity and mortality. A burgeoning body of evidence has facilitated our understanding of these secondary mechanisms of injury that are amenable to pharmacological interventions, unlike the primary injury itself. Secondary mechanisms of injury encompass an array of perturbances and include neurogenic shock, vascular insults such as hemorrhage and ischemia–reperfusion, excitotoxicity, calcium-mediated secondary injury and fluid–electrolyte disturbances, immunologic injury, apoptosis, disturbances in mitochondrion function, and other miscellaneous processes. Comprehension of secondary mechanisms of injury serves as a basis for the development and application of targeted pharmacological strategies to confer neuroprotection and restoration while mitigating ongoing neural injury. The first article in this series will comprehensively review the pathophysiology of SCI while emphasizing those mechanisms for which pharmacologic therapy has been developed, and the second article reviews the pharmacologic interventions for SCI.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Spinal cord injury (SCI) remains a common and devastating problem of modern society. Through an understanding of underlying pathophysiologic mechanisms involved in the evolution of SCI, treatments aimed at ameliorating neural damage may be developed. The possible pharmacologic treatments for acute spinal cord injury are herein reviewed. Myriad treatment modalities, including corticosteroids, 21-aminosteroids, opioid receptor antagonists, gangliosides, thyrotropin-releasing hormone (TRH) and TRH analogs, antioxidants and free radical scavengers, calcium channel blockers, magnesium replacement therapy, sodium channel blockers,N-methyl-D-aspartate receptor antagonists, &agr;-amino-3-hydroxy-5-methylisoxazole-4-propionic acid–kainate receptor antagonists, modulators of arachadonic acid metabolism, neurotrophic growth factors, serotonin antagonists, antibodies against inhibitors of axonal regeneration, potassium channel blockers (4-aminopyridine), paclitaxel, clenbuterol, progesterone, gabexate mesylate, activated protein C, caspase inhibitors, tacrolimus, antibodies against adhesion molecules, and other immunomodulatory therapy have been studied to date. Although most of these agents have shown promise, only one agent, methylprednisolone, has been shown to provide benefit in large clinical trials. Given these data, many individuals consider methylprednisolone to be the standard of care for the treatment of acute SCI. However, this has not been established definitively, and questions pertaining to methodology have emerged regarding the National Acute Spinal Cord Injury Study trials that provided these conclusions. Additionally, the clinical significance (in contrast to statistical significance) of recovery after methylprednisolone treatment is unclear and must be considered in light of the potential adverse effects of such treatment. This first decade of the new millennium, now touted as the Decade of the Spine, will hopefully witness the emergence of universal and efficacious pharmacologic therapy and ultimately a cure for SCI.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Continuous ambulatory multichannel accelerometry (CAMCA) has recently been validated for the assessment of hypo-and bradykinesia and body position in patients with Parkinson's disease (PD). This study aims to validate CAMCA for the assessment of resting tremor in patients with PD. First, in seven patients with PD with varying degrees of tremor severity, a tremor detection algorithm was developed. Second, 59 patients with PD and 43 age-matched controls were assessed with CAMCA during 24 hours. Duration and intensity of resting tremor, and measures reflecting hypo-and bradykinesia and body position were calculated for the diurnal period. In part 1 of the study, the tremor detection algorithm had a high sensitivity (0.82) and specificity (0.93). Ambulatory monitoring revealed that categories with higher clinical tremor severity had increased objective values for duration and intensity of tremor. Duration and intensity of tremor were correlated with the clinical score for resting tremor (Spearman's rank correlation: 0.66–0.77). Measures for hypo-and bradykinesia differed between patients and controls, but not between groups of patients defined by tremor severity. This study has validated continuous ambulatory multichannel accelerometry for the assessment of tremor in PD, while simultaneously measuring hypo-and bradykinesia and body position.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Topiramate was shown to attenuate the severity of negative symptoms (e.g., emotional withdrawal) in a patient with schizophrenia when added to his stable regimen of antipsychotic medication. Topiramate was administered for a period of 12 weeks; during the first 4 weeks, dosage was adjusted to the maximal tolerated dose (i.e., 175 mg/d), and, thereafter, this dosage was maintained for 8 weeks. Topiramate was studied because of recent data and hypotheses suggesting that N-methyl-D-aspartate receptor hypofunction, dampened GABAergic inhibition, and excessive stimulation of the kainic acid (KA)/&agr;-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) class of glutamate receptors occur in at least some patients with schizophrenia, especially those with persistent negative symptoms and progressive psychosocial deterioration. Topiramate is a recently approved and marketed medication for the treatment of seizure disorders, whose mechanism of action includes potentiation of GABAergic neurotransmission and antagonism of KA/AMPA glutamate receptors. This case is presented because of the dramatic response of negative symptoms to the addition of topiramate. The severity of negative symptoms was assessed formally with the Negative Scale of the Positive and Negative Syndrome Scale. The negative symptoms of schizophrenia are usually resistant to most behavioral and pharmacologic interventions.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The objective of this study was to compare the long-term tolerability and efficacy of tolcapone and entacapone in patients with fluctuating Parkinson's disease (PD). Tolcapone and entacapone are two currently available catechol-O-methyltransferase inhibitors that have demonstrated efficacy in the treatment of advanced PD. There are little published data on long-term experience and no direct comparisons. We compared the results of two separate, simultaneous, long-term open label extensions, one for tolcapone and the other for entacapone. The inclusion/exclusion criteria were similar. Data were collected prospectively at 6, 12, 24, and 36 months. Efficacy measures included the Unified Parkinson's Disease Rating Scale (UPDRS) total score, subscores, items 32 (duration of dyskinesia) and 39 (duration of “off” time), and levodopa dose. The two groups were compared using a Mann-WhitneyUtest for change from baseline and analysis of variance. Tolerability was defined as the ability of patients to maintain therapy and was compared using a Kaplan-Meier analysis. Eleven patients enrolled in the entacapone study and 14 in the tolcapone study. The tolcapone group had more severe disease with significantly higher UPDRS motor score, duration of “off,” and levodopa dose requirement. Tolcapone was more effective in lowering UPDRS motor and complication subscores, duration of “off” time, and levodopa doses. UPDRS motor scores and change in levodopa dose in the tolcapone group remained below baseline level for 36 months; however, they were above baseline in the entacapone group from 6 months on. Tolerability was the same for both treatments. Tolcapone appears to have greater and longer efficacy with regard to motor symptoms, “off” time, and change in levodopa requirements than entacapone. These findings indicate that tolcapone continues to have a place in the treatment of advanced PD. However, the risks associated with this drug, particularly hepatic injury, and the requirement for rigorous blood monitoring, need to be considered when choosing an appropriate treatment for patients with advanced PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A 61-year-old man suddenly became euphoric and talkative. Later the same day, he developed hemichoreic movements of the left limbs. The patient fulfilled the DSM-IV criteria for a manic episode by abnormally and persistently elevated mood, decreased need for sleep, high distractibility, pressured speech, increased goal-directed activity, and hypersexuality. The mood changes persisted for several weeks. Magnetic resonance imaging of the brain showed a right thalamic infarction. The co-occurrence of hemichorea and mania caused by focal thalamic lesion is very rare. It may be explained by dysfunction in basal ganglia thalamocortical circuitry.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We report the case of a 44-year-old right-handed woman who experienced her first convulsion while taking bupropion. Electroencephalography showed frequent bilateral independent temporal lobe epileptiform discharges that resolved when bupropion was discontinued. This is the first well-documented case of epileptiform discharges induced by bupropion in humans.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID