摘要:

Traumatic and ischemic injuries to the CNS, including spinal cord, cause tissue damage through both direct (primary) and indirect (secondary) mechanisms (1,2). Experimental evidence over the past 2 decades has demonstrated that delayed, secondary injury may play a major contributing role in the development of neurologic dysfunction following spinal cord injury (3). Such delayed injury is initiated by trauma or ischemia and is caused by the activation of endogenous substances. Proposed injury factors have included monoamines (4), free radicals (5), neuropeptides (6), arachidonic acid metabolites (7), and changes of extracellular calcium (8). Generally, such factors are thought to produce damage through either disruption of cell membranes (7), or alterations in spinal cord blood flow (9) and metabolism (10). This concept of secondary or “autodestructive” injury factors has provided the rational basis for the evaluation of a number of pharmacologie interventions in traumatic or ischemic CNS injury. Such agents have included receptor blockers, physiologic antagonists, inhibitors of biosynthetic pathways, or drugs that stabilize membranes. The success or failure of such therapeutic interventions has been used to support or refute hypotheses regarding specific injury factors.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

And as he is who falls, and knows not how, By force of demons who to earth down drag him, Or other oppilation that binds man, When he arises and around him looks Wholly bewildered by the mighty anguish Which he has suffered, and in looking sighs.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The syndrome of continuous motor unit activity (CMUA) is a rarely encountered neuromuscular disease, which has been treated symptomatically either by phenytoin (1–3) or by carbamazepine (4). This syndrome is a multietiological disorder (5), but the clinical, electrophysiological, and morphological findings reveal a mild distal sensorimotor neuropathy of varying etiology (6–10) or possibly a concomitant disease of perikaryon and peripheral nerve or the “neuronal” form of Charcot-Marie-Tooth disease (11,12). The clinical symptoms or signs of the syndrome are remarkably improved after treatment with phenytoin or carbamazepine, but in some patients high doses are required (13). In addition, the lack of effect or side effects of these drugs must be considered, for in some patients they may cause a phenytoin- or carbamazepine-induced peripheral neuropathy or other side effects (14–18). Consequently, we have introduced valproic acid (VPA) therapy in the treatment of CMUA syndrome (10,12).This review summarizes our seven cases with CMUA syndrome. These patients were submitted for clinical, electrophysiological, and nerve blocking studies as well as light and electron microscopy of muscle and sural nerve biopsy.The comparative treatment with phenytoin, carbamazepine, and VPA was applied to our patients in an attempt to estimate the efficacy of VPA therapy on CMUA syndrome.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Restless legs syndrome (RLS) may exist in as much as 2% of the population (1). It can severely interfere with sleep and thus markedly disrupt daily life. However, it is not neurodegenerative and its potential for treatment should therefore be great. Despite its high incidence and its severity in some instances, it is little known and therefore much underdiagnosed. This review describes first the clinical presentation of RLS and second the neuropharmacologic implications of various therapeutic approaches.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The results of two trials conducted in human dyskinesia with progabide, a specific γ-aminobutyric acid (GABA) receptor agonist, are reviewed. In one trial, 13 parkinsonian patients with L-DOPA-induced dyskinesia (LDD) and “on-off” fluctuations were included in a double-blind controlled trial progabide versus placebo. No change was observed during this trial in the severity of dyskinesia on progabide treatment but the drug significantly extended the “on” period as compared with placebo. In the second trial, 20 patients with neuroleptic-induced dyskinesia (TD) entered an open dose ranging trial with progabide. Fourteen of the 16 patients who completed the trial had a good-to-excellent therapeutic response. According to these results, progabide does not seem to have the same therapeutic benefit in LDD as TD. These data suggest that the hypothesis of a dopaminergic supersensitivity as a similar pathogenic substrate for both clinical conditions should be reconsidered. If this hypothesis remains the most consistent to explain the occurrence of LDD, the therapeutic effect of progabide in TD is an argument for an implication of the GABAergic system in the appearance of TD.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Alterations in 2-[14C]deoxyglucose uptake were studied in 154 brain regions from animals acutely challenged with a dopamine (DA) agonist or antagonist. Doses of apomorphine inducing locomotion and stereotypic behavior produced increased uptake in the subthalamic nucleus, the substantia nigra reticulata, and the ventroanterior and ventrolateral nuclei of the thalamus while decreased uptake was observed in the lateral habenula and several mid-line thalamic nuclei. The six centrally active DA antagonists studied produced uniform increases in uptake in the lateral habenula and the anterior regions of both the n. accumbens and striatum whereas decreased uptake was observed in the mesencephalic reticular formation and the reticular nucleus of the thalamus. Low doses of apomorphine that produced behavioral hypoactivity resulted in a pattern of metabolic alterations that resembled those associated with DA antagonists more closely than metabolic alterations seen with DA agonists. These results suggest that unique alterations in neuronal activity in several brain regions, including the traditional dopaminergic projection areas, are associated with the expression of specific DA-mediated behaviors.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The limitations of antiparkinsonian treatment strategy when using anticholinergic drugs are determined by their side effects induced through excessive inhibition of parasympathetic functions. In the present study we have investigated the peripheral effects of antiparkinsonian agents on blood levels of concomitantly administered neuroleptic drugs. We have compared the anticholinergic and a dopamine mimetic antiparkinsonian agent in their effects on serum neuroleptic activity (SNA) and serum anticholinergic activity (SAA). Sixteen schizophrenic patients on chronic neuroleptic therapy with steady state neuroleptic levels were receiving either amantadine, 200 mg/day, or anticholinergic drugs (trihexyphenidyl, 10 mg/day, or benztropine, 6 mg/day) for the first 2 weeks, after which the amantadine group was crossed over to anticholinergic and the anticholinergic group to amantadine for the following 2 weeks. Blood samples were obtained once a week along with clinical testing. The results indicate that SAA was fivefold higher with benztropine than with trihexyphenidyl and that amantadine had no effect on SAA. Moreover, SNA was not altered either by anticholinergics or amantadine coadministration, indicating that the therapeutic blood neuroleptic levels are not compromised by antiparkinsonian administration.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The effect of carbamazepine and its −10,11-epoxide on the development of amygdala-kindled seizures and on completed kindled seizures in the rat was evaluated. Neither carbamazepine (15 mg/kg) nor the −10,11-epoxide (15 mg/kg) was capable of preventing the development of amygdala-kindled seizures, although both drugs, at these doses, exerted marked anticonvulsant effects on completed kindled seizures. These data suggest that different phases of kindling are differentially responsive to pharmacological intervention. They also support the conclusion that different mechanisms underlie the acquisition and maintenance of kindled seizures.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

In recent studies with different types of assay systems including normal control blood-type-matched red blood cells (RBC) in vitro (1,2) and cultured immature motor neurons (3,4) plasma from patients with amyotrophic lateral sclerosis (ALS) has been shown to exert cytotoxic effect. As demonstrated against RBC, the plasma cytotoxicity has been found a consistent feature in an extensive series of consecutive ALS patients (presently ∼125 patients with two false negatives; 2, S. Conradi and L.-O. Ronnevi, unpublished observations) and has been found to be mediated by immunoglobulins (Ig) of the IgA and IgG-type (5,6). The cytotoxic effect on RBC has been further characterized and has hitherto been found to be specific for the disease as compared with diseased controls (2,6). The plasma cytotoxicity has not as yet been demonstrated to be involved in the pathogenetic process in ALS but is so far the most specific and consistent laboratory abnormality found in patients with the disease. There is an obvious possibility that circulating Ig can affect lower motor neurons in vivo since these neurons expose part of their membrane surface outside the blood-brain and blood-nerve barriers at the motor endplates. It is therefore of profound interest to investigate whether the progress rate of the disease can be altered by immunosuppressive treatment. One prerequisite for justifying such treatment trials is the experimental demonstration of reduction of cytotoxic effect in vitro by the treatment regimes to be tried.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Metoclopramide is often used for treating nausea, vomiting, and gastrointestinal tract disorders, and sometimes evokes extrapyramidal symptoms (1,2). Metoclopramide-induced parkinsonism has been reported (1,2), although the agent did not increase the severity of parkinsonism (3). We report an elderly man with metoclopramide-induced parkinsonism along with the findings on cerebrospinal fluid (CSF) monoamine metabolites.

ISSN:0362-5664    

出版商:OVID    

年代:1987

数据来源: OVID