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Biomedical subjects

P Pollak

Publications and source records attributed to P Pollak.

At least 55 records · Page 3Linked to original sources
PubMed2000

[18 F]-dopa PET study in patients with juvenile-onset PD and parkin gene mutations.

+Parkin gene mutations cause a form of early-onset autosomal recessive PD with neuronal loss in the substantia nigra and no Lewy bodies. The authors present a PET [18F]-dopa study of one familial and two sporadic cases with juvenile-onset PD resulting from parkin gene mutations. They found a profound decrease of [18F]-dopa uptake, representing 28% of putamen and 44% of caudate nucleus control subject values. PD caused by parkin gene mutations is distinct from idiopathic PD on molecular grounds but has similar clinical and PET findings.

Adult↗
PubMed2000

Neuropsychological changes between "off" and "on" STN or GPi stimulation in Parkinson's disease.

BACKGROUND: In a previous study on a consecutive series of 62 patients with PD, the authors showed that bilateral subthalamic or pallidal continuous high-frequency deep brain stimulation (DBS) affects neither memory nor executive functions 3 to 6 months after surgery. OBJECTIVE: To investigate the specific effects of DBS by comparing the performance of patients with the stimulator turned "on" and "off." METHODS: The performance of 56 patients on clinical tests of executive function was compared after 3 and 12 months of DBS of the subthalamic nucleus (STN; n = 48) or the internal globus pallidus (GPi; n = 8) with the stimulator "on" or "off." Global intellectual efficiency, verbal learning, and mood were also evaluated with the stimulator "on." The performance of another group of 20 patients was compared after 6 months of DBS of the STN (n = 15) or the GPi (n = 5) with the stimulator "on" or "off" on more experimental tests recently shown to be more sensitive to l-dopa therapy. RESULTS: When the stimulator was "on," STN patients showed a mild but significant improvement in psychomotor speed and working memory. In comparison with the presurgical state, STN patients had no cognitive deficit at 12 months, except for lexical fluency. There was no differential effect of STN or GPi stimulation. CONCLUSIONS: 1) The specific effect of DBS seems to mimic the action of l-dopa treatment in the cognitive as in the motor domain; 2) the surgery associated with DBS does not appear to affect the cognitive performance of patients with PD 12 months later, except for a mild deficit in lexical fluency.

Adult↗
PubMed2000

Ineffective subthalamic nucleus stimulation in levodopa-resistant postischemic parkinsonism.

The authors report a patient with postischemic parkinsonism who responded neither to levodopa nor to bilateral subthalamic nucleus (STN) stimulation. MRI revealed bilateral lesions of the substantia nigra, the striatum, the external pallidum, and part of the internal pallidum. PET showed reduced striatal dopa-decarboxylase activity, D2 receptor binding, and glucose metabolism. Perioperative microrecording showed low-frequency activity of STN cells. This case suggests that parkinsonian patients who do not have a good response to levodopa or in whom a postsynaptic dopaminergic lesion can be shown may not be good candidates for STN surgery.

Antiparkinson Agents↗
PubMed2000

Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Adult↗
PubMed2000

Future prospects of brain stimulation.

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim has replaced thalamotomy as a treatment of tremor of various origins and was extended to two other targets (Subthalamic nucleus (STN) and the medial pallidus (GPi)), since 1993 based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then suppresses also levodopa induced dyskinesias. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. The effects remain stable over more than five years chronic HFS of STN, as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsies. It is therefore possible that DAS in STN as well as in other targets could become a potent therapeutic tool in the future for neurological disorders. The future of brain stimulation will depend on new technologies (new circuits, electrodes, web based programmers), waveforms (alternatives to square waves, random distribution), targets (hypothalamic nuclei, locus coeruleus) and indications (dystonia, epilepsy, eating disorders.

Animals↗
PubMed2000

The impact of deep brain stimulation on executive function in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.

Association Learning↗
PubMed2000

Effect of bilateral deep-brain stimulation on oral control of patients with parkinsonism.

We assessed the oral system of parkinsonian patients treated with bilateral chronic stimulation of the ventral intermediate nucleus of the thalamus (Vim), and of the subthalamic nucleus (STN) to compare the effects of these procedures on the articulatory organs. Force transducers were used to sample ramp-and-hold force contractions generated by the upper lip, lower lip and tongue at 1- and 2-newton target force levels, as well as maximal force. Fourteen healthy control subjects and 14 parkinsonian patients participated in this study. After an overnight fast the patients were evaluated under two conditions: during bilateral stimulation and 1 h after stopping stimulation. With Vim stimulation, dynamic and static control of the articulatory organs was worsened while with STN stimulation it was greatly improved. The target of stimulation differently influences the oral system and modulates neuronal structures involved in speech.

Adult↗
PubMed2000

Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery.

BACKGROUND: Adequate postoperative pain control is important to reduce potential cardiopulmonary complications. It is often difficult to determine dosages of narcotics for morbidly obese patients following Roux-en-Y gastric bypass (RYGBP) due to respiratory depression. Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects. METHOD: 25 morbidly obese patients who received PCA with morphine sulfate following RYGBP. PCA settings we re as follows: morphine, 20 microg/kg of ideal body weight, 10-minute lock out interval and 80 % of a calculated amount for a 4-hour limit. W e measured arterial blood gas, heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate, opioid amount, patient satisfaction, visual analog pain scale (VAS), and the incidence of nausea, vomiting, pruritus and sedation. RESULTS: Average morphine usage was 44.2+/-28.7 mg during the day of surgery (DOS); 49.1+/-27.4 mg during POD (postoperative day) #1; and 36.6+/-22.8 mg during POD#2 (p < 0.01). 24 patients were satisfied with their pain control on POD#1. VAS was 5.4+/-2.1 on the day of surgery, but remained below 4 thereafter. Arterial oxygen saturation and vital signs were maintained without significant changes. 5 patients experienced mild sedation on the day of surgery and 3 patients experienced mild sedation on POD#1. 1 patient experienced nausea and vomiting and 4 patients had pruritus; however, none required treatment. CONCLUSION: PCA is safe and effective for morbidly obese patients following RYGBP.

Adult↗
PubMed2000

Dyskinesias and the subthalamic nucleus.

Severe dyskinesias or ballism can occur following hemorrhagic events in the subthalamic nucleus (STN), and it has recently been established that the STN plays a major role in the pathophysiology of the motor dysfunction of Parkinson's disease (PD) and that STN inhibition improves parkinsonian dysfunction. Deep brain stimulation of the STN in PD patients is therefore currently being evaluated as a therapy. High-frequency stimulation of the STN in PD patients can induce intense dyskinesias that are similar to those induced by levodopa. These may occur with a variable latency and resemble all types of levodopa-induced dyskinesias (LIDs). They can be decreased by reducing the levodopa dosage, which is permitted by the antiparkinsonian effect of stimulating the STN. STN stimulation has been shown to improve all types of LIDs, with the most dramatic effect being that on off-period dystonia. The improvement in LIDs may relate to the decrease in drug dosage, while the off-period dystonia is likely improved by the simultaneous administration of levodopa and STN stimulation. It is thought that the STN is an important node in a network, which can produce dyskinesias when disturbed by a lesion, and is particularly sensitive for the induction of these abnormal movements.

Animals↗
PubMed2000

[Other symptoms of advanced stage Parkinson's disease].

Autonomic dysfunction, neuropsychiatric problems, axial signs and sleep disorders are common complications of advanced Parkinson's disease (PD). Urinary disturbance due to detrusor hyperreflexia and iatrogenic orthostatic hypotension are prominent dysautonomic signs. Depression and anxiety are frequent but can occur exclusively during off periods. A fronto-sub cortical dementia occurs in 30% of PD patients, but anti-parkinsoniens drugs (APD) can cause hallucinations even in non demented PD patients. Axial signs, such as freezing, postural instabily or dysarthria become doparesistant. Insomnia, REM sleep disorders. At least, pain is very frequent. Exact analysis of these signs is important for an adequate treatement: most of them are improved by APD but some of them, like orthostatic hypotension or hallucinations, are increased by these drugs.

Antiparkinson Agents↗
PubMed2000

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Adult↗
PubMed2000

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: methodologic aspects and clinical criteria.

The technique of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) is evolving very rapidly. The subthalamic nucleus (STN) has become the preferred target in the past few years since our group demonstrated that high-frequency stimulation in this nucleus improves all cardinal features of PD, including resting tremor. This benefit in the parkinsonian symptoms allows a drastic reduction in daily levodopa requirements. Dyskinesias become drastically attenuated, possibly as a consequence of reduced dopaminergic medication but also because STN DBS may stabilize basal ganglia output activity, thus avoiding the problems associated with standard levodopa replacement therapy. DBS of the STN is associated with a marked improvement of motor function even in patients with advanced PD. Such a large degree of benefit in parkinsonian features relies on two crucial points that must be taken into consideration for achieving the best possible results with this technique: proper selection of patients and accuracy in targeting the STN. From a neurosurgical point of view, we believe that the most precise localization of the STN is obtained by using ventriculography to determine the stereotactic coordinates of the STN. This is complemented with intraoperative neuronal microrecording to define physiologically the sensorimotor region of the nucleus. Future advances in neuroimaging techniques may well lead to modifications of our current methodology.

Adult↗
PubMed1999

Breathing pattern in patients with Parkinson's disease.

The improvement in motor performance resulting from levodopa administration in patients with Parkinson's disease (PD) provides the opportunity to investigate ventilatory changes brought about by the disease. The aim of this study has been to investigate these changes in order to specify the mechanisms of the impairment in breathing in PD. Breathing patterns at rest were investigated in 11 patients with idiopathic PD both before (OFF) and after (ON) administration of levodopa at a dose improving their motor performance by at least 30%. Airflow (Fleisch head mounted on a mask), rib cage and abdomen movements (inductance plethysmography) were recorded in the OFF condition 1 h after subjects woke up. Subjects then received levodopa and a new set of recordings was obtained 1 h later, in the ON condition. Breath-by-breath processing of recordings was carried out, and tidal volume (VT), inspiratory (TI) and expiratory (TE) durations were measured. The main finding was a lengthening of TI resulting in a decrease in ventilation and in VT/TI, and an increase in TI/TTOT in the ON compared to the OFF condition. In the ON condition abnormal rib cage-abdomen plots patterns were found in four out of six subjects. A hypothesis on the effect of PD on breathing is proposed on grounds of normal diaphragmatic activity but impaired activity of the other respiratory muscles and more specifically the intercostal muscles.

Aged↗
PubMed1999

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease.

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.

Adult↗
PubMed1999

Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease.

Recent pathophysiological models of Parkinson's disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinson's disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinson's disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere.

Brain↗