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PubMed1975

Studies on the antiparkinsonism efficacy of lergotrile.

The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.

Acetonitriles↗

PubMedDate not supplied

Apomorphine-induced relief of the akinetic-rigid syndrome and early median nerve somatosensory evoked potentials (SEPs) in Parkinson's disease.

Among early cortical median nerve SEPs the frontal N30 potential is known to show amplitude reduction during execution of voluntary movements and to be abnormally reduced in parkinsonian patients. However, it is not clear whether N30 abnormalities are related to the severity of motor disability in Parkinson's disease. To address this question we studied median nerve SEPs, using a 16-channel montage, in 7 patients chronically treated with subcutaneous (s.c.) injections of apomorphine hydrochloride for spontaneous "on-off" motor fluctuations. We observed no significant changes in the latency, amplitude or scalp topography of early SEPs when comparing traces and maps obtained in the "off" condition and during the "on" phase induced by s.c. injection of apomorphine. The absence of any SEP changes, despite a clear-cut relief of the akinetic-rigid syndrome, suggests that early cortical SEPs, and in particular the frontal N30 potential, at least when recorded in a subject at rest, are not usable as an objective means to assess the severity or the fluctuations of motor disability in Parkinson's disease.

Aged↗

PubMed1975

Amantadine in Parkinson's disease. A double-blind, placebo-controlled, crossover study with long-term follow-up.

A double-blind, placebo-controlled, crossover study with long-term follow-up of amantadien i- Parkinson's disease was performed on 26 patients. Other antiparkinsonian medications were discontinued in all but three patients. Amantadine resulted in a statistically significant 12 percent overall improvement over placebo. Twenty of 26 patients, without breaking the code, selected amantadine for long-term usage. Ten patients continued treatment for 10 to 12 months, and an overall statistically significant improvement was noted at 2 weeks and at 1, 2, 3, and 10 to 12 months. Improvements in tremor and rigidity remained relatively constant, while there was some apparent loss of efficacy in timed tests and quality of timed tests. Amantadine appears effective in the long-term treatment of some patients with Parkinson's disease.

Activities of Daily Living↗

PubMed1989

[Clinical results of using Nakom in diseases of the nervous system].

Clinical investigation was performed and dopamine metabolism (renal catecholamine excretion) studied in 29 children and 5 adults with various forms of CP, 5 myasthenic children and 1 child with Strümpel disease treated with Nakom. The therapy was judged expedient in 20% of the cases of pronounced muscular rigidity and dystonia with decreased dopamine excretion. The drug proved ineffective in atonic, astatic, severe hyperkinetic arms, and in cases with severe psycho-organic signs.

Adolescent↗

PubMed1976

Studies with bromocriptine. Part 2. Double-blind comparison with levodopa in idiopathic parkinsonism.

A double-blind crossover study was performed in 12 patients with idiopathic parkinsonism to compare their response to bromocriptine with their response to previous optimal drug treatment, including levodopa. There was a 26 percent overall improvement with bromocriptine; rigidity, tremor, and facial expression showed the greatest response. Seven of eight patients who were taking levodopa at the beginning of the study was taken off the drug completely. Adverse reactions were transient and dose-dependent. Bromocriptine promises to be an effective new therapeutic agent in the treatment of idiopathic parkinsonism.

Aged↗

PubMed1997

[Secondary parkinsonism following midbrain hemorrhage].

We report a patient who developed right sided cogwheel rigidity and resting tremor after left midbrain hemorrhage. Brain magnetic resonance imaging (MRI) showed left midbrain old hemorrhage including substantia nigra. I-123 iodoamphetamine single photon emission computed tomography (IMP-SPECT) images showed reduced radioisotope (RI)-uptake in the left striatum, thalamus and frontal lobe. Our report shows that focal midbrain lesion can produce parkinsonism.

Cerebral Hemorrhage↗

PubMed1977

Fibre type disproportion in the rigid spine syndrome.

An adolescent presented with the clinical symptomatology of the rigid spine syndrome. Whereas an earlier biopsy from the M. erector trunci showed myopathic features and marked endomysial fibrosis, recent findings in the M. biceps consisted of type I-fibre atrophy, type I-fibre predominance, and hypertrophy of type II-fibres. The significance of these findings and possibly a relationship to congenital fibre type disproportion are discussed.

Adolescent↗

PubMed1992

Is the "K-type" caffeine-halothane responder susceptible to malignant hyperthermia?

The "K-type" designation is used to describe a patient being investigated for malignant hyperthermia (MH) when concurrent administration of caffeine and halothane induces muscle contracture (rigidity, spasm) in vitro, but when halothane and caffeine given separately produce a normal response. It is accepted in some centres that K-type individuals are susceptible to malignant hyperthermia (MHS). In this paper, the K-type is shown not to correlate with the MH susceptible (MHS) status as accepted by the European MH group.

Caffeine↗

PubMed2006

The effects of random whole-body-vibration on motor symptoms in Parkinson's disease.

It is well known that applying vibrations to men influences multiple physiological functions. The authors analysed post effects of whole-body-vibration (WBV) on motor symptoms in Parkinson's disease (PD). Sixty-eight persons with PD were randomly subdivided into one experimental and one control group. Motor symptoms were assessed by the UPDRS (Unified Parkinson's Disease Rating Scale) motor score. A cross-over design was used to control treatment effects. The treatment consisted of 5 series of whole-body-vibration taking 60 seconds each. On average a highly significant (p<0.01) improvement of 16.8% in the UPDRS motor score was found in the treatment group. Only marginal changes (p>0.05) were found in the control group. The cross-over procedure showed comparable treatment effects (14.7% improvement after treatment). With respect to different symptom clusters only small changes were found in limb akinesia and cranial symptoms. By contrast, tremor and rigidity scores were improved by 25% and 24%, respectively. According to the structure of symptom changes it is unlikely that these effects are explainable on peripheral sensory level, exclusively. With respect to the findings of other studies one can speculate about changes in activation of the supplementary motor area and in neurotransmitter functions.

Aged↗

PubMed1997

[A comparative study of the effect of bromocriptine and pergolide on Parkinson disease].

INTRODUCTION: Bromocriptine and pergolide are the two dopamine agonists most often used in Parkinson's disease. Few comparative studies of the efficacy of both compounds are available. OBJECTIVE: To compare the relative efficacy of bromocriptine and pergolide in patients with Parkinson's disease and intermediate stages of evolution. METHODS: Open label study of 5-months of duration. The first agonist was given for two months and, after a period of substitution of one month, the second agonist was also maintained for two months. RESULTS: Pergolide was more effective than bromocriptine for global scores of the UPDRS, total motor scores, clinical symptoms, akinesia and rigidity. Both compounds were equal effective for the treatment of tremor and fluctuations. Both agonists produced similar side effects. CONCLUSIONS: At the ration 1/10 mg/day pergolide was more effective than bromocriptine in patients with Parkinson's disease at intermediate stages of evolution.

Aged↗

PubMed2003

2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5.

A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and effective synthesis, and the pharmacological activity at glutamate receptors was evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic activity at the kainate receptor subtype GluR5. The most potent compounds showed more than 50-fold selectivity for GluR5 compared to GluR6 and the AMPA receptor subtypes GluR1-4. The structure-activity relationships for the AUBAs showed distinct structural requirements for the substituents on the two aromatic ring systems. Only para-substituents were tolerated on the benzoic acid moiety (ring A), whereas ring B tolerated a variety of substituents, but with a preference for lipophilic substituents. The most potent compounds had a 4-chloro substituent on ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B and had IC(50) values of 1.3, 1.2, and 1.2 microM, respectively, in a functional GluR5 assay. Compound 6c (IC(50) = 4.8 microM at GluR5) showed activity in the in vivo ATPA rigidity test, indicating that 6c has better pharmacokinetic properties than 8h, which was inactive in this test. The AUBAs are the first example of a series of noncompetitive GluR5-selective antagonists and may prove to be important pharmacological tools and leads in the search for therapeutic glutamatergic agents.

Animals↗

PubMed1982

Effects of barbiturates on the decerebrate rigidity in rats.

Effects of barbiturates (phenobarbital, mephobarbital, pentobarbital, hexobarbital and amobarbital) on the tonic and phasic responses of forelimbs were studied in the rats in which rigidity was induced by means of anemic decerebration. The inhibitory pattern of the tonic and phasic responses to phenobarbital was different from those to the other barbiturates, i.e. phenobarbital gradually inhibited both tonic and phasic responses, whereas other barbiturates suppressed significantly only the tonic response immediately after the administration of a relatively low dose (10 mg/kg) but hardly inhibited the phasic response unless at higher doses (20 and 40 mg/kg). Possible involvement of GABA-system in the inhibitory action of phenobarbital and pentobarbital on the rigidity was investigated. Since inhibition of the phasic response to pentobarbital was potentiated by the pretreatment of animals with carboxymethoxylamine hemihydrochloride (AOAA) and suppressed by the pretreatment with semicarbazide, it was suggested that GABAergic mechanism may be involved in the particular inhibition of phasic response to pentobarbital. However, the inhibitory action of phenobarbital appeared to be independent of GABA-system.

Aminooxyacetic Acid↗

PubMed2000

[Pathophysiology of abnormal movements in Parkinson's disease].

Major parkinsonian motor symptoms, i.e., bradykinesia, muscular rigidity, and resting tremor, are due to abnormalities in the motor circuit of the basal ganglia caused by loss of nigrostriatal dopamine neurons. Bradykinesia results from increased activity with altered firing patterns of the output nuclei of the basal ganglia. Exaggerated long-latency reflex or decreased Ib inhibition of the spinal reflex network have been suggested to underlie rigidity, but the relationship between these reflex abnormalities and the altered activities of the basal ganglia in the parkinsonian state remains unclear. The central oscillator for parkinsonian tremor has been localized in the basal ganglia circuit, and the cerebellar system also participates in generation of the tremor. Dyskinesia and dystonia may develop from decreased activity with altered firing patterns of the output nuclei of the basal ganglia.

Animals↗

PubMed1984

The neuroleptic malignant syndrome: presentation and treatment.

The neuroleptic malignant syndrome is a potentially lethal reaction following the use of antipsychotic medications. The four cardinal signs are hyperthermia, muscular rigidity, autonomic dysfunction, and altered consciousness. The differential diagnosis of the syndrome includes malignant hyperthermia of anesthesia, heat stroke, and acute lethal catatonia. Treatment consists of prompt recognition of the syndrome and initiation of intense supportive measures to manage the hyperthermia and prevent secondary complications. Clinical reports describing beneficial results from use of anticholinergic agents, amantadine, bromocriptine, and dantrolene are reviewed.

Anesthesia↗

PubMedDate not supplied

[Falling backward: atypical sign of iodiopathic Parkison's disease. Use of intravenous apomorphine as a diagnostic test].

INTRODUCTION: The differential diagnosis of a parkinsonian syndrome is extensive and complex. In most cases, however, a detailed clinical examination will help to differentiate between idiopathic Parkinson's disease (IPD) and other causes of parkinsonism. PATIENTS AND METHODS: 10 patients with an average age of 65.1 years (range 60-70), of whom 6 were men and 4 women were referred to our department with a diagnosis of IPD and history of backwards falls. The average duration of disease was 4.7 years (range 4-7). All 10 patients had at presentation a severe akinetic-rigid syndrome with no other symptoms of IPD. I.v. apomorphine (APO) was administered to each of them at a rate of 8.9 mg/hr (range 15.3 mg/hr) for an average time of 5.4 hours (range: 3-10 hours). RESULTS: The improvement of the akinetic-rigid state in six of the patients during the i.v. infusion with APO helped to elicit signs that are atypical of IPD (ataxia and postural instability). Three of the patients did not respond to i.v. APO and one of them could not be evaluated, as he did not tolerate the infusion. Oral Dopa challenge or s/c APO bolus has not been as successful in helping to differentiate IPD from other parkinsonian syndromes. CONCLUSIONS: The prompt detection of postural instability or retropopulsion is necessary in order to diagnose atypical parkinsonian syndromes. In difficult cases, continuous i.v. APO will improve the akinetic-rigid state and facilitate the detection of atypical signs. The pharmacokinetic characteristics of APO, and the advantage of it being possible to administer the drug i.v. in a few hours increases the viability of this test.

Accidental Falls↗

PubMedDate not supplied

Clinical observations in early and late onset Parkinson's disease.

The present study compares 30 patients who developed idiopathic Parkinson's disease (PD) at the age of 48 years or younger and 47 patients who developed the disease at the age of 68 years or older. PD patients with early onset had rigidity and bradykinesia as the predominant features at onset and during the course of the illness. In contrast older onset patients exhibited more often tremor at the beginning while later in the course most of them developed the full triad of symptoms i.e. tremor-rigidity-bradykinesia. In spite of such differences the overall disability status did not differ between the two groups of patients. An additional observation was that the early onset patients were apter to show earlier and more often abnormal movements and response fluctuations related to the L-Dopa therapy.

Activities of Daily Living↗

PubMed2001

Clinical characteristics of neuroleptic-induced parkinsonism.

In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.

Activities of Daily Living↗

PubMed2006

Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways.

Cell forces define cell morphology, alterations in which are caused by tyrosine kinase and phosphatase mutations, which implies a causal linkage. Recent studies have shown that phosphotyrosine signaling is involved in force sensing for cells on flat surfaces. Early force-dependent activation of Src family kinases by phosphatases or cytoskeleton stretch leads to the activation of downstream signaling. In addition, force generation by cells depends on a feedback mechanism between matrix rigidity or force generation and myosin contractility. Components of the force-sensing pathway are linked to the integrin-cytoskeleton complex at sites of force application and serve as scaffolds for signaling processes. Thus, early events in force detection are mechanically induced cytoskeletal changes that result in biochemical signals to mechanoresponsive pathways that then regulate cell form.

Adherens Junctions↗