摘要:

A 26-year-old woman is evaluated for headaches, which began when she was 14 years old. She states that she initially sees bright zig-zag bands, which expand in the shape of a horseshoe in her right visual field. Twenty minutes later, she develops a throbbing headache over the left frontal area, associated with photophobia and nausea. The headaches last 1–3 days and they occur once a month. There is no medical history, and she takes only multivitamin supplements. Her sister has been diagnosed with migraines. Her examination is normal, including equal and reactive pupils, full extraocular movements, and normal strength and sensation. A magnetic resonance scan of the brain shows no abnormalities.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Neuroleptic induced tardive dyskinesia and L-dopa-induced dyskinesia are the two most common types of drug-induced abnormal involuntary movements. These two drug-induced dyskinesias are clearly different with respect to the offending drugs and the underlying disease, but they both share a number of intriguing similarities in terms of clinical phenomenology, epidemiology, risk factors, pathophysiological mechanisms and therapeutic responses. In both instances, it is believed that some dysregulation occurring at the level of the striatal dopaminergic receptors, and related non-dopaminergic neurotransmitters systems are playing a crucial role in the development and persistence of the mechanisms causing dyskinesia. These long-lasting functional changes, known as the “priming” phenomenon, are responsible for an impaired balance within the relays of the cortico-subcortical motor loops that release an inadequate output from the basal ganglia leading to an abnormal motor behavior. From a therapeutic perspective, there are also many similarities in the strategies proposed to manage these two dyskinesias. In both cases, unprimed patients not previously exposed to the offending drugs, are offered alternative medications to reduce, at least partly, the risk of occurrence of future dyskinesia: “atypical” neuroleptics in the place of “typical” neuroleptics, and dopamine agonists in the place of L-dopa. In both cases, once dyskinesias are present, in already “primed” patients, both types of dyskinesia appear to be poorly and only partly reversible. Based on limited clinical evidence, it is a common proposal to switch the dyskinetic subject from “typical” to “atypical” neuroleptics for tardive dyskinesia, or to switch from (or more pragmatically to substitute as much as possible) L-dopa to a dopamine agonist for L-dopa-induced dyskinesia. In both cases, efficacious symptomatic antidyskinetic interventions, to reduce the severity of a ready present dyskinesia, are rare. There are some uncontrolled data suggesting that dopamine depleting agents, like tetrabenazine, are possibly useful for tardive dyskinesia; however, there is more clinical evidence to support the efficacy of amantadine and functional surgery in parkinsonian patients with L-dopa-induced dyskinesia.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Patients with chronic hepatic encephalopathy display monoaminergic perturbations together with affective symptoms. Thus, these patients belong to a group with a probability of receiving antidepressant drug treatment. The liver impairment may result in pharmacokinetic alterations of the antidepressant drug, which in turn may affect the already perturbed monoaminergic function. Venlafaxine (VEN) was administered as a single subcutaneous challenge to portacaval shunted (experimental hepatic encephalopathy model) rats (5 mg/kg) and sham-operated rats (5 and 10 mg/kg). The aims were to investigate whether a reduced dose in portacaval shunted rats resulted in higher concentrations of VEN and serotonin as compared to control rats, which had been demonstrated earlier when the rats received the same dose (10 mg/kg). A 50% reduction of the dose of VEN administered to portacaval shunted rats resulted in elevated levels of VEN in serum, brain parenchyma, and brain dialysate about 300 minutes after the injection. The VEN challenge increased the serotonin and noradrenaline concentrations in dialysate in portacaval shunted rats and both sham groups, but the three VEN groups did not differ in any major way in serotonin and noradrenaline output. Therefore, when the dose of VEN administered to experimental hepatic encephalopathy was reduced 50% as compared to control rats, mainly pharmacokinetic, and possibly also monoaminergic, alterations were observed.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The pineal hormone melatonin (MLT) is closely related to sleep initiation and maintenance in humans, and is now used as a potent therapeutic tool for some circadian rhythm sleep disorders. Acute and transient hypothermia induced by exogenously administered MLT (ex-MLT) may play a critical role in the circadian phase shifting and hypnogenic actions. Six healthy young male volunteers (mean age, 22.5 y; age range, 19–24 y), whose endogenous MLT secretion rhythms were previously assessed, took either 0.5 mg, 3 mg, or 9 mg of ex-MLT or a placebo at 0930 h (the average sleep onset time was 0000 h) on a randomized, single-blind, crossover basis. In comparison with placebo, ex-MLT significantly suppressed core body temperature at the 3-mg and 9-mg doses and slightly suppressed core body temperature at the 0.5-mg dose. There was significant positive correlation between the magnitude of core body temperature suppression and the area under the MLT concentration curve as well as the peak MLT concentration after ex-MLT administration. Our study showed that clinical doses of ex-MLT induce hypothermia in a dose-dependent manner. Results suggest that the therapeutic effect of larger doses of ex-MLT should be tested on patients who benefit little from typically lower clinical doses of ex-MLT.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Magnesium sulfate has attracted interest as a potential neuroprotectant but passage of magnesium ion into the central nervous system has not been well documented. For this study, we quantified plasma and cerebrospinal fluid (CSF) ionized magnesium concentration after systemic magnesium sulfate infusion in patients with intracranial hypertension. Patients (N= 9) received an intravenous infusion of 5 g/20 mmol magnesium sulfate (125 mL of a 4% wt/vol solution) over 30 minutes. Before and after dosing, CSF (from an indwelling ventricular catheter) and blood samples were collected at hourly intervals. Ionized magnesium concentration in all samples was determined using an electrolyte analyzer. Baseline plasma and CSF ionized magnesium concentrations were 0.58 ± 0.05 and 0.82 ± 0.06 mmol/L, respectively. Intravenous magnesium sulfate infusion significantly increased plasma ionized magnesium concentration (peak, 0.89 ± 0.11 mmol/L), but CSF magnesium levels did not change during the 4-hour study. Systemic administration of magnesium sulfate failed to increase CSF ionized magnesium concentration in patients with intracranial hypertension despite increasing plasma magnesium levels by >50%.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Newly introduced dopamine agonists, such as ropinirole may offer advantages compared to such older drugs as bromocriptine in patients with advanced Parkinson's disease (PD) with response oscillations or waning efficacy. Dose equivalence of these two drugs, however, has not been well established, which may complicate switching in clinical practice. In 23 such patients with advanced PD no longer satisfactorily responsive to prolonged bromocriptine therapy (mean dose: 18.9 ± 6.5 mg/d), we prospectively switched the medication to ropinirole administered at three different dose-ratios (5:1, 3:1, and 2:1), increased at monthly intervals. Selegiline remained unmodified in all 17 patients receiving this medication. A dose-ratio of bromocriptine to ropinirole of close to 2:1 (1.87; mean ropinirole dose: 10.1 ± 2.5 mg/d) was the only dose that significantly reduced mean motor Unified Parkinson's Disease Rating Scale (UPDRS) scores (p= 0.030, analysis of variance). Individually considered, however, four patients (21%) scored worse even at this dose-ratio when compared to baseline assessment on bromocriptine. “Off” time was reduced by 57.3% in fluctuating patients, and the dyskinesia score decreased by 53.8%, although the changes were not statistically significant. Higher bromocriptine to ropinirole dose ratios (i.e., 5:1 and 3:1) resulted in “off”-time increases in half of the patients with fluctuations, and two previously stable patients developed a wearing-off effect and one other patient experienced off-time dystonia. One patient developed dose-dependent dopaminomimetic psychotic symptoms with ropinirole. In conclusion, “off”-time motor scores and possibly “off”-time duration, and severity of dyskinesias in patients with advanced PD with prolonged bromocriptine therapy may improve in a majority of cases by switching to ropinirole, provided that the latter drug is administered at a dose ratio of 2:1 compared to bromocriptine. Higher dose ratios are often ineffective or may even cause a clinical worsening of symptoms in some patients.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Piracetam is an effective symptomatic treatment for some types of myoclonus in adults. To survey the efficacy and safety of piracetam in pediatric opsoclonus–myoclonus, we conducted an open, randomized, two-period, dose-ranging, double-blind, crossover, clinical trial of five children comparing the antimyoclonic properties of oral piracetam to placebo. We devised and validated a new rating scale, specifically for pediatric opsoclonus–myoclonus. Two parents while blinded were able to identify the active phase by improvement in behavior, but another thought the behavior was worse. None of the patients showed improvement in myoclonus. The adult-equivalent dose of piracetam used in this study, which is threefold higher than that used in previous pediatric studies, was well tolerated and safe. We found our rating scale to be a reliable and useful tool for future studies of opsoclonus–myoclonus in children.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We report here the development of parkinsonian symptoms after carbamazepine discontinuation in two patients concurrently treated with risperidone. They had been receiving combined treatment of carbamazepine and risperidone for the control of aggressive behavior and psychotic symptoms. The parkinsonian symptoms had not occurred before carbamazepine discontinuation, and have achieved complete remission after the dose reduction of risperidone. These findings suggest that the development of parkinsonian symptoms may be associated with pharmacokinetic interaction between carbamazepine and risperidone.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID