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Biomedical subjects

F Grandas

Publications and source records attributed to F Grandas.

At least 19 recordsLinked to original sources
PubMed2005

[Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination].

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the "pulsatile" dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of "wearing off" fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in "de novo" patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.

Akathisia, Drug-Induced↗
PubMed2004

Nocturnal problems occurring in Parkinson's disease.

A large number of patients with Parkinson's disease (PD) experience nocturnal problems that impair their sleep quality. Among them, motor disorders such as tremor, rigidity, akinesia, akathisia, periodic leg movements, painful dystonia, dyskinesias, restless legs syndrome, and rapid eye movement sleep behavior disorder are common. This article reviews the clinical characteristics of some nocturnal motor problems that often induce sleep disruption in PD patients.

Blepharospasm↗
PubMed2004

Levodopa in the treatment of Parkinson's disease: current controversies.

Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.

Antiparkinson Agents↗
PubMed2002

Long term follow up of a hemimasticatory spasm.

OBJECTIVES: To describe the clinical and neurophysiological findings in a case of hemimasticatory spasm (HMS) followed during 14 years of evolution. MATERIAL AND METHODS: A woman suffered from very frequent paroxysmal episodes of painful involuntary occlusion of the jaw. Neurophysiological studies were performed at the 3, 12 and 14 years after the onset of symptoms. They included a needle electromyographic (EMG) evaluation of the main jaw closing and opening muscles, the jaw reflex (JR), the masseteric silent period (MSP) and the masseteric inhibitory reflex (MIR). RESULTS: Clinical symptoms remained unchanged throughout the period of observation. Conventional EMG never disclosed neurogenic signs. Voluntary closure of the jaw systematically provoked an abnormal activity with muscle cramps characteristics, restricted to the left masseter muscle. Left JR response was normal in the first evaluation and became delayed and of reduced amplitude in the second. The MSP and MIR were abolished on the left side during the spasmodic episodes whereas they were strictly normal out of them. The MIR abnormalities showed the characteristic pattern of an efferent lesional type. CONCLUSIONS: Hemimasticatory spasm probably is the consequence of an abnormal trigeminal hyperexcitability likely induced by the demyelinating lesion of its peripheral motor pathway. The main neurophysiological abnormalities may persist unmodified over a long course of the disease and allow the differential diagnosis of HMS from oromandibular dystonia and temporomandibular dysfunction (TMD).

Disease Progression↗
PubMed2000

The putative neuroprotective role of dopamine agonists in Parkinson's disease.

Parkinson's disease is probably caused by a combination of genetic and environmental factors, which trigger a cascade of events that lead to the cell death of the dopamine-containing neurons of the substantia nigra pars compacta. These processes include oxidative stress, mitochondrial dysfunction, excitotoxicity with excess of nitric oxide formation, glial and inflammatory abnormalities and apoptosis. Dopamine agonists are chemical compounds that act directly on the dopamine receptors without any previous enzymatic biotransformation. Besides their symptomatic antiparkinsonian effect, these drugs may have neuroprotective properties in Parkinson's disease through different possible mechanisms: (a) stimulation of dopamine auoreceptors, reducing thereby dopamine turnover; (b) direct antioxidant effects; (c) reduction of excitotoxicity induced by excessive subthalamic nucleus firing; (d) inhibition of mitochondrial permeability; (e) induction of trophic factors. Dopamine agonists have already shown neuroprotective effects on dopaminergic cells against a variety of neurotoxins in several in vitro and in vivo studies. Clinical studies to detect changes in the progression of the underlying neurodegenerative process in patients with Parkinson's disease treated with dopamine agonists, by assessing the dopamine terminal function in the striatum by means of PET and SPECT techniques are under way.

Journal Article↗
PubMed2000

[Intracranial hypertension as the first clinical manifestation of gliomatosis cerebri].

A case of gliomatosis cerebri which clinically presented with a syndrome of intracranial hypertension (ICH), involvement of bilateral sixth cranial nerves, and oppressive holocranial headache of one week of evolution. Cranial MR and CT were performed demonstrating diffuse hypodense cortical-subcortical lesions on tomography and in T1 sequences and hyperdense lesions in T2 sequences with irregular contrast enhancement. Intracranial pressure was measured by ventricular catheter with the appearance of high, maintained pressure waves (Lundberg A waves). Ventricular LCR study and cerebral angiography did not provide additional data. Meningeal and cerebral biopsies showed infiltration by pleomorphous glioma leading to the diagnosis of gliomatosis cerebri. The patient was treated with steroids, hyperosmolar agents, external LCR derivation and tumoral radiotherapy. Nonetheless, the patient dies at six months of initiation of the symptoms. Gliomatosis cerebri should be taken into account in the differential diagnosis of clinical pictures presenting with ICH.

Adult↗
PubMed1999

Risk factors for levodopa-induced dyskinesias in Parkinson's disease.

To identify putative risk factors for levodopa-induced dyskinesias we studied the effect of several clinical variables on the occurrence of dyskinesias in a series of 168 consecutive patients with Parkinson's disease treated for at least 6 months with levodopa. Of these, 108 (64%) developed dyskinesias after a mean duration of levodopa treatment of 51.4 +/- 43.3 months. Patients tended to suffer dyskinesias on the side of the body first affected by Parkinson's disease. The overall probability of developing dyskinesias increased with levodopa treatment duration, about 10% per year during the first 7 years. Univariate and multivariate logistic regression analysis identified the age at onset of Parkinson's disease (OR 0.923; 95% CI 0.883-0.964) and the initial levodopa dose (mean dose of the first 6 months of treatment; OR 1.004; 95% CI 1.002-1.006) as the main independent predictors. Survival curves showed that onset of Parkinson's disease at age 50 years or before (logrank, P < 0.05) and initial levodopa treatment with more than 600 mg/day (logrank, P < 0.05) were associated with a higher risk for the appearance of dyskinesias.

Age of Onset↗
PubMed1999

[Pramipexol: a new dopaminergic agonist for the treatment of Parkinson disease].

Pramipexol is a novel nonergot dopamine agonist which has high selectivity for intereacting with dopamine D2 receptors (especially with D3 receptor subtype). It has been effective in early Parkinson's disease as monotherapy and as adjunctive therapy with L-dopa in advanced stages of the disease. Clinical improvement can be observed after 3 or 4 weeks of treatment. The adverse events profile of pramipexol is similar, in general, to that of other dopamine receptor agonists, although it can be foreseen that pramipexol should not induce side effects related to the ergot chemical structure such as eritromelalgia, distal vasospasm, retroperitoneal fibrosis or pleural effusions. Nevertheless, the potential advantages of this promising dopamine agonist should be tested in well-designed prospective comparative studies with other available ergot and nonergot dopamine agonists.

Benzothiazoles↗
PubMed1998

Quality of life in patients with Parkinson's disease who transfer from standard levodopa to Sinemet CR: the STAR Study. The STAR Multicenter Study Group.

Conversion from standard levodopa to Sinemet CR was performed in a series of 450 patients with Parkinson's disease. Of these, 299 experienced motor complications (group A) and 151 showed stable motor response (group B). There was significant improvement in various parameters of efficacy (Unified Parkinson's Disease Rating Scale, Hoehn-Yahr staging, Schwab-England scale) particularly in those related to functional aspects such as activities of daily living of the Unified Parkinson's Disease Rating Scale, sleep questionnaires and the Nottingham Health Profile. Adverse effects were usually mild or moderate, and only 10% of patients discontinued Sinemet CR due to side effects. Sinemet CR treatment was preferred by 81% of patients in group A and by 73.8% of patients in group B.

Activities of Daily Living↗
PubMed1998

[Palpebral ptosis and blepharospasm secondary to hemispheric cerebral infarction].

A case that combines cerebral eyelid ptosis and blepharospasm secondary to cerebral hemisphere infarction is shown. EMG recording from the facial and eyelid muscles revealed lack of the levator palpebrae superioris, orbicularis oculi and corrugator muscles activity. Any voluntary opening attempt lead to a simultaneous contraction of the three muscles. Blink reflex responses were normal although showed facilitation features on the right side and mild inhibition characteristics from the left side. Median nerve SEP revealed a loss of precentral components (P22-N30) as well as a delay and amplitude decrease of N20. Transcranial magnetic stimulation disclosed a complete lesion of corticospinal pathway for right upper limb. In this case, a right hemisphere lesion caused an unusual eyelid motor abnormality: cerebral eyelid ptosis and blepharospasm induced by the voluntary eyelid opening.

Aged↗
PubMed1997

[Physiopathology of the dyskinesias induced by L-dopa].

Dyskinesias are one of most frequent motor complications of parkinsonian patients on chronic levodopa treatment. This article reviews their clinical characteristics, risk factors, pathophysiology and possible therapeutical approaches.

Age of Onset↗
PubMed1994

The role of pulsatile versus continuous dopamine receptor stimulation for functional recovery in Parkinson's disease.

More effective measures to control and replace the dopaminergic deficit of Parkinson's disease are being actively sought. One basic problem is how the striatal dopamine loss should be replaced in order to mimic most accurately the physiological state. Animal electrophysiology indicates that the dopaminergic nigrostriatal pathway has a dual tonic and phasic action. Intermittent dopaminergic stimulation is associated with behavioural hyposensitivity both in animal models and in patients with Parkinson's disease. Continuous dopaminergic stimulation provides a tonic background and improves some clinical problems but is also associated with tolerance. None of the available pharmacological approaches can restore the dopamine deficiency of Parkinson's disease to physiological levels. Continuous dopaminergic stimulation for < 24 h, associated with small doses of levodopa or a short-acting dopamine agonist, appears to be the best, albeit imperfect, therapeutic approach until other, more efficacious remedies are developed.

Animals↗
PubMed1994

Eyelid motor abnormalities in progressive supranuclear palsy.

Eyelid motor abnormalities found in progressive supranuclear palsy are reviewed. Electrophysiological correlates of blepharospasm, levator inhibition (blepharokolysis) and supranuclear paralysis of lid closure are presented. Disorders of eyelid motility are not uncommon in progressive supranuclear palsy (PSP). They may be found in about one third of patients with this syndrome (Jackson et al., 1983; Golbe et al., 1989). This is not surprising since ocular and eyelid movements are highly coordinated, mainly in the vertical plane (Gordon, 1951; Kennard and Smith, 1963; Kennard and Glaser, 1964), and a supranuclear ophthalmoplegia with down gaze impairment is a cardinal feature of PSP (Steele et al., 1964). The spectrum of eyelid motor disorders described in PSP includes blinking abnormalities, lid retraction, blepharospasm, levator inhibition and supranuclear palsy of eye closure.

Blepharospasm↗
PubMed1994

Progressive supranuclear palsy and corticobasal ganglionic degeneration: differentiation by clinical features and neuroimaging techniques.

To assess the extent of overlap between clinically diagnosed patients with progressive supranuclear palsy (PSP) and corticobasal ganglionic degeneration (CBGD) we compared clinical scores for rigidity, bradykinesia, supranuclear gaze abnormalities, hemineglect and limb apraxia, postural instability, neck rigidity, and limb dystonia in 15 patients with a degenerative rigid-akinetic syndrome at presentation and at follow-up 3 to 120 months later. Only the presence of hemineglect, usually in combination with limb apraxia, was a reliable and early clinical factor for discriminating between these two conditions. These symptoms were present at admission in all 4 CBGD patients but not in any of the 11 PSP patients either at presentation or later during serial examinations. Though supranuclear ophthalmoplegia, neck rigidity, and postural instability were already observed in most CBGD patients at presentation, their scores remained low compared to those for PSP patients over the longterm. CT-scans and MRI were helpful in supporting clinically-based diagnoses made at presentation in that the vast majority of the PSP patients exhibited various degrees of midbrain atrophy and 50 percent of the CBGD patients exhibited asymmetric pericentral cortical atrophy.

Aged↗
PubMed1992

Differences in the motor response to apomorphine between untreated and fluctuating patients with Parkinson's disease.

Behavioral hyposensitivity to repeated apomorphine administration has been observed in fluctuating parkinsonian patients. To investigate whether a similar phenomenon occurs in patients never treated with levodopa, we studied the response to apomorphine in 20 de novo patients with Parkinson's disease. Six patients showed no or minimal improvement after apomorphine injections (maximal dose 3.5 mg). Fourteen patients responded and were then given up to four repeated subcutaneous injections of apomorphine [minimal effective dose (MED)]. The responses of de novo patients were compared with responses in 10 patients with motor fluctuations previously studied by the same protocol. There was no significant difference in latency and duration of motor responses after repeated apomorphine injections in de novo patients. MED was similar in de novo and fluctuating patients, but duration of improvement induced by each apomorphine bolus was longer in the de novo group. These results indicate that response duration to apomorphine is longer in previously untreated patients and that behavioral tolerance associated with pulsatile dopaminergic stimulation by apomorphine occurs mainly in patients with more advanced disease under chronic levodopa therapy.

Adult↗