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Biomedical subjects

P Pollak

Publications and source records attributed to P Pollak.

At least 109 records · Page 6Linked to original sources
PubMed1995

Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson's disease.

Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. To test this hypothesis, we studied the motor effect induced by three acute administrations of a dose of levodopa-benserazide (Madopar) with either 200 mg or 400 mg of tolcapone or placebo, in a double-blind latin-square design. The duration of the on-phase could be compared in 10 parkinsonian patients suffering from square-shaped motor effect. In comparison to placebo, 200 mg and 400 mg of tolcapone significantly increased the mean duration of the on-phase by 61.7 min ( +/- 19.4 SEM) and by 72.2 min ( +/- 18.5), respectively. This clinical effect is suggested to be related mainly to the increase in levodopa area under the curve and half-life induced by tolcapone. The intensity in dyskinesias was increased by 400 mg of tolcapone. Tolcapone appears to be well tolerated and could be helpful as an adjuvant treatment to levodopa in parkinsonian patients with motor fluctuations.

Aged↗
PubMed1995

[Parkinsonian dysarthria].

Perceptual, acoustic and physiological (electromyographic and kinematic) studies addressing the features of the Parkinsonian speech are reviewed. Perceptual features are the following: 1) aprosody, i.e. monopitch, monoloudness, diminished stress contrasts and rate abnormalities, 2) impairment of articulation such as imprecise consonants, and 3) vocal quality deviation as harsh or breathy voice. The physical basis that is acoustic parameters corresponding to these perceptual impressions, such as fundamental frequency, intensity, duration, speech rate, have been analyzed. However, movement studies associated with electromyographic analysis in an important adjunct to more traditional investigations. The physiological studies are yet limited, they show that patients with Parkinson's disease have 1) reduced articulatory displacements relative to normal speakers, which may appear as rigidity, 2) improper coordination of agonist-antagonist muscle pairs or groups. Besides, some results show that pharmacological or surgical treatment improving akinesia, rigidity and tremor are not always successful in speech.

Dysarthria↗
PubMed1994

Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.

In animal models of Parkinson's disease (PD), it is postulated that the excessive output from the subthalamic nucleus (STN) plays a critical role. Selective lesions or high frequency electrical stimulation of the STN can alleviate parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN stimulation in patients suffering from severe akinetic forms of PD. After approval of the institutional ethical committee, we operated on a parkinsonian patient aged 51, suffering for 8 years from a strongly disabling akinetorigid form of PD, complicated by an on-off effect (Hoehn and Yahr stage 5 in the worst-off motor phase). Stereotactic surgery was done on one side under local anesthesia. The theoretical target was chosen according to stereotactic atlases, based on ventriculographic landmarks such as anterior and posterior commissures (AC and PC). The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs. A spontaneous increase in neuronal activity was recorded in an area located 2-4 mm under the level of the intercommissural plane, 10 mm from the midline, at mid-distance between AC and PC. Within the same place, a 130-Hz stimulation induced acute and reversible akinesia alleviation mainly on the contralateral limbs, comparable to that obtained with dopaminergic drugs. No dyskinesia, such as hemiballism, was induced by introduction of electrodes or by stimulation. Then a long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies of the effects of chronic stimulation were extensively performed to determine the best spatiotemporal and electrical stimulation variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Stimulation Therapy↗
PubMed1993

[Stimulators of the central nervous system].

Progress in biomedical engineering has provided implantable and programmable stimulators which allowed application of neurophysiological knowledge to therapeutic attempts on human neurological diseases. Chronic electrodes can be implanted accurately and safely into the brain, against the spinal cord and around the nerves. Therapeutic applications, mainly on pain, dyskinesias and epilepsy are therefore available, which call for careful clinical evaluation, basic and technological research to improve indications and diminish the cost of these methods.

Central Nervous System↗
PubMed1993

Relief of akinesia by apomorphine and cerebral metabolic changes in Parkinson's disease.

The cerebral metabolic rate of glucose was measured in 14 Parkinson's disease patients with severe on-off fluctuations. Two positron emission tomography (PET) scans with [18F]fluorodeoxyglucose were performed, one after a challenge of subcutaneous apomorphine at a dose able to relieve akinesia within 15 min and the other with the vehicle. Apomorphine reduced glucose utilization by 4-6% in the lenticular nuclei and the occipital cortex and by 6-9% in the thalamic nuclei, but this effect was not statistically significant. Thus, central stimulation of dopamine receptors by apomorphine in advanced Parkinson's disease is not associated with cerebral metabolic changes as assessed by PET. Despite a dramatic improvement of the motor state, the global neuronal activity in the striatum and its downstream projections remains stable, suggesting an equilibrium between excitatory and inhibitory dopaminergic activities.

Aged↗
PubMed1993

Symptomatic effect of selegiline in de novo Parkinsonian patients. The French Selegiline Multicenter Trial.

The French Selegiline Multicenter Trial was carried out in 1990 to investigate whether the disability of de novo patients with parkinsonism could be improved during the first 3 months by monotherapy with selegiline (10 mg/day). A double-blind, randomized, placebo-controlled clinical trial was conducted over 3 months with 93 patients from 13 centers. Symptomatology was assessed on various disease rating scales, including Hoehn and Yahr, Hamilton Depression Rating Scale, Unified Parkinson's Disease rating scale, and Schwab and England scores, as well as self-assessment. Biological and clinical parameters were measured for tolerability, and efficacy was investigated with special reference to the point at which therapy with L-dopa had to be started. Selegiline was significantly superior to placebo on the various motor rating scores, and depressive scores were significantly improved at the end of 3 months. Adverse effects were rare and minor. Therefore, selegiline could be the therapy of choice for the treatment of de novo parkinsonian patients.

Activities of Daily Living↗
PubMed1993

External and implanted pumps for apomorphine infusion in parkinsonism.

Continuous delivery of dopaminergic agents to the striatum is a major challenge to improve the treatment of Parkinson's disease. Apomorphine is one of the best candidates because of its solubility and its D1 and D2 receptor agonist properties. Seventeen Parkinsonian patients suffering from severe L-dopa-induced on-off effects were treated by continuous subcutaneous (SC) infusion with a portable minipump. Administration of intracerebroventricular (ICV) apomorphine was carried out in 7 macaca fascicularis monkeys using implanted programmable pumps. Four of the monkeys were made Parkinsonian by MPTP injections. In patients receiving apomorphine, the mean duration of daily off periods was reduced by 61%. Psychiatric side effects were rare but SC nodules occurred in all patients and the external infusion method was therefore difficult to implement. In monkeys, the implanted system was well tolerated. ICV apomorphine infusion led to CSF apomorphine concentrations higher than the same apomorphine dose infused i.m. Motor function was considerably improved in two MPTP monkeys during the time of ICV infusion and 30 min after its arrest. Long-term ICV administration could not be carried out because of catheter blockage and/or apomorphine toxicity. SC and ICV apomorphine infusions are efficient for controlling motor activity in Parkinsonism but long-term toxicity remains to be studied further.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Chronic VIM thalamic stimulation in Parkinson's disease, essential tremor and extra-pyramidal dyskinesias.

Stereotactic thalamotomy of the VIM (ventral intermediate) nucleus is considered as the best neurosurgical treatment for Parkinsonian and essential tremors. However, this surgery, especially when bilateral, still presents a risk of recurrence and neurological complications. We observed that acute VIM stimulation at frequencies higher than 60 Hz during the mapping phase of the target suppressed the tremor of Parkinson's disease (PD) and essential tremor (ET). This effect was immediately reversible at the end of the stimulation. This was initially proposed as an additional treatment for patients already thalamotomized on the contralateral side, and then extended as a regular procedure for extra-pyramidal dyskinesias. Since January 1987, we implanted 126 thalami in 87 patients (61 PD, 13 ET, 13 dyskinesias of various origins). Deep brain stimulation electrodes were stereotactically implanted under local anaesthesia, using stimulation and micro-recording to delineate the best site of stimulation. Electrodes were subsequently connected to implantable programmable stimulators. The optimal frequency was around 130 to 185 Hz. The results (evaluated by a neurologist from 0 = no effect to 4 = perfect relief) are related to the type of tremor. Altogether, 71% of the 80 patients benefited from the procedure with grade 3 and 4 results. In 88% of the PD cases, the results were good (grade 3) or excellent (grade 4) and stable with time. Rigidity was moderately for a long improved but akinesia was not. The same level of improvement was observed in 68% of the ET patients and only in 18% of the other types of dyskinesias.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia Diseases↗
PubMed1993

Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.

Parkinsonian tremor can be abolished by chronic high frequency thalamic stimulation of the ventral intermediate nucleus. We have studied six patients with unilateral Parkinson's disease. The patients had an electrode chronically implanted in the ventral intermediate nucleus of the thalamus. We measured changes in cerebral activity by positron emission tomography using an index of regional cerebral blood flow (rCBF). Each patient was scanned in three states: (i) tremor without stimulation (condition A); (ii) tremor with ineffective stimulation (condition B); (iii) tremor abolished by effective stimulation (condition C). The suppression of tremor (C compared with B) was specifically associated with a decrease of rCBF in the cerebellum, whereas the ineffective stimulation (B compared with A) induced a decrease of rCBF in homolateral cerebral cortex. The results give evidence for different contributions from cortex and cerebellum to the generation of parkinsonian tremor and suggest that tremor suppression is mainly associated with a decrease of synaptic activity in the cerebellum.

Aged↗
PubMed1993

Pharmacokinetics of apomorphine in parkinsonian patients.

Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 +/- 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 +/- 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.

Abdomen↗
PubMed1993

[Effects of the stimulation of the subthalamic nucleus in Parkinson disease].

In Parkinson's disease, experimental studies favour a neuronal hyperactivity of the subthalamic nucleus. We carried out a subthalamic nucleus electrical stimulation in a patient aged 51, suffering for 8 years from a severe akineto-rigid form of Parkinson's disease, complicated with an on-off effect. Stereotaxic surgery was done under local anaesthesia on one side. Within the theoretical target, a 130 Hz stimulation induced akinesia alleviation mainly on the contralateral limbs. No abnormal movement was noticed. Then a long-term quadripolar DBS Medtronic electrode was inserted in that area. The study of the effects of chronic stimulation is in progress to determine the best temporal and electrical stimulation variables.

Electric Stimulation Therapy↗
PubMed1992

Relationship between levodopa-independent symptoms and central atrophy evaluated by magnetic resonance imaging in Parkinson's disease.

Thirty patients with Parkinson's disease were studied for the purpose of investigation relations between motor symptoms and cerebral atrophy evaluated by magnetic resonance imaging (MRI). Axial symptoms (gait disorder, postural instability and difficulty in arising from a chair), assessed at the time of maximum clinical improvement, were significantly correlated with frontal atrophy, while no correlation was found between the basal parkinsonian disability score and cerebral atrophy. It is suggested that frontal atrophy observed by MRI is linked with axial motor symptoms resulting from non-dopaminergic lesions. The origin of this atrophy is unknown.

Aged↗
PubMed1992

[Treatment of spasticity with botulinum toxin].

Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition.

Adult↗