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Biomedical subjects

Pierre Pollak

Publications and source records attributed to Pierre Pollak.

At least 19 recordsLinked to original sources
PubMed2007

Subthalamic nucleus stimulation is efficacious in patients with Parkinsonism and LRRK2 mutations.

Stimulation of the subthalamic nucleus (STN) improves motor signs in patients with levodopa-responsive Parkinson's disease (PD). Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause Parkinsonism. We assessed 69 patients under STN stimulation and found heterozygous LRRK2 mutations in 9 (G2019S in 8 and T2031S in 1). The age at onset of PD, the clinical characteristics before or after neurosurgery, and the clinical response to STN stimulation were similar in both groups. Two patients with the G2019S LRRK2 mutation still benefited from STN stimulation, 9 and 10 years after surgery. Patients with LRRK2 mutations are, therefore, good candidates for STN stimulation.

Adult↗
PubMed2006

Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson's disease.

INTRODUCTION: The severe, cortical, cholinergic depletion accompanying Parkinson's disease (PD) is considered as a highly probable correlate of cognitive and behavioural dysfunction. Recent studies have demonstrated that cholinesterase inhibitors (notably rivastigmine) are beneficial in patients suffering from dementia associated with PD (PDD). However, the primary efficacy variables used in such work came from scales designed for Alzheimer's disease (AD), even though the cognitive symptoms in PD and AD dementia do not overlap completely. The aim of the present study (a double-blind, placebo-controlled clinical trial) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N Engl J Med 2004) participated in this study. They suffered from mild to moderately severe dementia (MMSE scores above 10 and below 24), with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD. Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per day) or placebo. The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits. RESULTS: Compared with placebo, a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale (p = 0.031), with a trend towards a significant improvement in the "Attention" subscale score (p = 0.061). Correlation analysis showed that in the rivastigmine group, performance on the Mattis "Attention" and "Initiation" subscales appeared to contribute heavily to the improvement in the overall score. Moreover, the latter was also related to an improvement in activities of daily living and a reduction in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating scale (which comprises items that are sensitive to executive dysfunction), the present study confirmed that rivastigmine has a beneficial effect on cognitive function in PDD. Despite our study's small sample size, the Mattis scale was able to detect this improvement and could thus be considered as an interesting outcome measure in further work.

Aged↗
PubMed2006

Head tremor in Parkinson's disease.

Head tremor is a typical feature of essential tremor. Patients with sporadic Parkinson's disease can have tremor of the tongue, lip, or chin, but classically do not have head tremor. We describe five patients with Parkinson's disease and head tremor in whom clinical and neurophysiological findings suggested that head tremor was a manifestation of Parkinson's disease.

Head Movements↗
PubMed2006

Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease.

In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico-striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions.

Affect↗
PubMed2006

Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation.

Pathological gambling (PG) related to dopaminergic treatment in Parkinson's disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syndrome (DDS). We describe a series of PD patients with preoperative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The patients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54 +/- 9 years; levodopa equivalent dose, 1,390 +/- 350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0-48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS-associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly attributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subthalamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment.

Adult↗
PubMed2006

Pretargeting for the implantation of stimulation electrodes into the subthalamic nucleus: a comparative study of magnetic resonance imaging and ventriculography.

OBJECTIVE: The optimal imaging modality for preoperative targeting of the subthalamic nucleus (STN) for high-frequency stimulation is controversially discussed. Commonly used methods were stereotactic magnetic resonance imaging (MRI), stereotactic ventriculography, and fusion between MRI and stereotactic computer tomography. All of these techniques not only have their own advantages but also specific limitations and drawbacks. The purpose of this study was to evaluate the accuracy of the preoperative MRI targeting as compared with ventriculography in terms of both the STN target as well as the internal landmarks. METHODS: Thirty patients with Parkinson's disease who underwent bilateral surgery for STN-high-frequency stimulation received both stereotactic ventriculography and stereotactic MRI. The theoretical target was determined by each of these two imaging modalities. The final electrode placement was performed after extensive electrophysiological evaluation using microrecording and microstimulation. The real target was assumed to be given by the electrode contact with the best clinical result assessed by the United Parkinson's Disease Rating Scale in the postoperative follow-up. In addition, the coordinates of the two landmarks, anterior commissure and posterior commissure, were determined using both imaging methods. RESULTS: The mean targeting error was 4.1 +/- 1.7 mm (mean +/- standard deviation) for MRI and 2.4 +/- 1.1 mm for ventriculography (P < 0.0001). The mean target mismatch between the two imaging methods was 2.9 +/- 1.2 mm. The length of the anterior commissure-posterior commissure distance differed significantly (P < 0.0001) between MRI (27.6 +/- 1.6 mm) and ventriculography (25.0 +/- 1.3 mm). The mismatch was mainly induced by an anterior diplacement of the anterior commissure by 1.9 +/- 2.2 mm (P < 0.0001) in MRI determination, as compared with ventriculography. CONCLUSION: Our findings show that the indirect targeting of the STN using coordinates based on radiological landmarks is more accurate than the direct targeting using anatomic visualization of the target structure. Regardless of the imaging procedure, electrophysiological mapping is required for optimal electrode placement, although in 20% of cases, the target determined by MRI falls out of the radius explored by electrophysiology.

Brain Mapping↗
PubMed2005

Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia.

BACKGROUND: Severe forms of dystonia respond poorly to medical treatment. Deep-brain stimulation is a reversible neurosurgical procedure that has been used for the treatment of dystonia, but assessment of its efficacy has been limited to open studies. METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. The severity of dystonia was evaluated before surgery and 3, 6, and 12 months postoperatively during neurostimulation, with the use of the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Scale (range, 0 to 120 and 0 to 30, respectively, with higher scores indicating greater impairment). Movement scores were assessed by a review of videotaped sessions performed by an observer who was unaware of treatment status. At three months, patients underwent a double-blind evaluation in the presence and absence of neurostimulation. We also assessed the patients' quality of life, cognition, and mood at baseline and 12 months. RESULTS: The dystonia movement score improved from a mean (+/-SD) of 46.3+/-21.3 before surgery to 21.0+/-14.1 at 12 months (P<0.001). The disability score improved from 11.6+/-5.5 before surgery to 6.5+/-4.9 at 12 months (P<0.001). General health and physical functioning were significantly improved at month 12; there were no significant changes in measures of mood and cognition. At the three-month evaluation, dystonia movement scores were significantly better with neurostimulation than without neurostimulation (24.6+/-17.7 vs. 34.6+/-12.3, P<0.001). There were five adverse events (in three patients); all resolved without permanent sequelae. CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.

Adolescent↗
PubMed2005

G2019S LRRK2 mutation in French and North African families with Parkinson's disease.

Mutations in LRRK2 were recently identified in autosomal dominant Parkinson's disease (PD), including the G2019S mutation. To evaluate its frequency, we analyzed 198 probands with autosomal dominant PD, mostly from France and North Africa. Surprisingly, the frequency in North African families (7/17, 41%) was greater than those from Europe (5/174, 2.9%). The clinical features in 21 patients, including 1 with a homozygous mutation, were those of typical PD, with lower Mini-Mental State Examination scores. There were also 15 unaffected mutation carriers, aged 32 to 74 years. LRRK2 mutations appear to be a common cause of autosomal dominant PD, particularly in North Africa.

Adult↗
PubMed2005

Changes induced by levodopa and subthalamic nucleus stimulation on parkinsonian speech.

Levodopa (L-dopa) and subthalamic nucleus (STN) stimulation treatments have been associated with both improvement and exacerbation of dysarthria in Parkinson's disease (PD). We report four cases illustrating variant responses of dysarthria to dopaminergic and STN stimulation therapies. Patients' motor disability and dysarthria were perceptually rated by the Unified Parkinson's Disease Rating Scale (UPDRS) in four conditions according to medication and STN stimulation. Dedicated software packages allowed acquisition and analysis of acoustic recordings. Case 1, who had a severe off period aphonia, experienced improvement of speech induced by both levodopa and STN stimulation. In Case 2, both treatments worsened speech due to the appearance of dyskinesias. Case 3 had a dysarthria exacerbation induced by STN stimulation with parameters above optimal levels, interpreted as current diffusion from the STN to corticobulbar fibers. In Case 4, dysarthria exacerbation occurred with stimulation at an electrode contact located caudally to the target, also arguing for current diffusion as a potential mechanism of speech worsening. The presented cases demonstrated variant effects in relation to L-dopa and STN stimulation on speech. It seems that motor speech subcomponents can be improved like other limb motor aspect, but that complex coordination of all speech anatomical substrates is not responsive to STN stimulation. These hypotheses may be helpful for better understanding and management of STN stimulation effects on motor speech and skeleton-motor subsystems.

Adult↗
PubMed2005

Therapeutic electrical stimulation of the central nervous system.

The electrical effects on the nervous system have been known for long. The excitatory effect has been used for diagnostic purposes or even for therapeutic applications, like in pain using low-frequency stimulation of the spinal cord or of the thalamus. The discovery that High-Frequency Stimulation (HFS) mimics the effect of lesioning has opened a new field of therapeutic application of electrical stimulation in all places where lesion of neuronal structures, such as nuclei of the basal ganglia, had proven some therapeutic efficiency. This was first applied to the thalamus to mimic thalamotomy for the treatment of tremor, then to the subthalamic nucleus and the pallidum to treat some advanced forms of Parkinson's disease and control not only the tremor but also akinesia, rigidity and dyskinesias. The field of application is increasingly growing, currently encompassing dystonias, epilepsy, obsessive compulsive disease, cluster headaches, and experimental approaches are being made in the field of obesity and food intake control. Although the effects of stimulation are clear-cut and the therapeutic benefit is clearly recognized, the mechanism of action of HFS is not yet understood. The similarity between HFS and the effect of lesions in several places of the brain suggests that this might induce an inhibition-like process, which is difficult to explain with the classical concept of physiology where electrical stimulation means excitation of neural elements. The current data coming from either clinical or experimental observations are providing elements to shape a beginning of an understanding. Intra-cerebral recordings in human patients with artefact suppression tend to show the arrest of electrical firing in the recorded places. Animal experiments, either in vitro or in vivo, show complex patterns mixing inhibitory effects and frequency stimulation induced bursting activity, which would suggest that the mechanism is based upon the jamming of the neuronal message, which is by this way functionally suppressed. More recent data from in vitro biological studies show that HFS profoundly affects the cellular functioning and particularly the protein synthesis, suggesting that it could alter the synaptic transmission by reducing the production of neurotransmitters. It is now clear that this method has a larger field of application than currently known and that its therapeutical applications will benefit to several diseases of the nervous system. The understanding of the mechanism has opened a new field of research, which will call for reappraisal of the basic effects of electricity on the living tissues.

Animals↗
PubMed2005

Statistical analysis of 168 bilateral subthalamic nucleus implantations by means of the probabilistic functional atlas.

OBJECTIVE: Statistical analysis of patients previously operated on may improve our methods of performing subsequent surgical procedures. In this article, we introduce a method for studying the functional properties of cerebral structures from electrophysiological and neuroimaging data by using the probabilistic functional atlas (PFA). The PFA provides a spatial distribution of the clinically most effective contacts normalized to a common space. This distribution is converted into a probability function for a given point in space to be inside an effective contact. The PFA was used to analyze spatial properties of the functional subthalamic nucleus (STN), defined as the spatial volume corresponding to the distribution of effective contacts. These results may potentially be useful in planning subthalamic implantation of electrodes. METHODS: In all, 168 bilateral subthalamic stimulations were examined. An algorithm was developed for converting these data into the PFA. The PFA for the STN (here called "atlas") was calculated with 0.25-mm3 resolution, and several features characterizing the left and right STN were studied. The analysis was performed with and without lateral compensation against the width of the third ventricle. The key feature introduced here used for analysis of the functional STN is a (probabilistic) functional volume of structure (defined for a given probability as the volume of a region whose every point has a probability equal to or greater than this given probability). RESULTS: The analysis has been performed for two situations: with and without lateral compensation against the width of the third ventricle. Without lateral compensation, the differences between the mean values and standard deviations of their barycenter coordinates for the left and right functional STNs are 0.31 and 0.18 mm, respectively. The left STN and right STN exhibit differences in functional volume size and probability distribution. The entire functional volume is 240 mm3 for the left and 229 mm3 for the right STN. A more prominent difference exists in the region of high probabilities (0.7 or higher), called "hot STN." The volume of the left hot STN is 5.52 mm3, whereas that of the right is 3.92 mm3. The left hot STN is 1.41 times bigger and 20% more dense than the right hot STN. For a given probability, the corresponding functional volume for the left hot STN is up to 43 times larger than that for the right STN. Practically speaking, lateral compensation does not change these results qualitatively. Quantitatively, differentiation between the left and right STNs is lower. For instance, for a given probability, the corresponding functional volume for the left hot STN is only up to 11 times larger than that for the right one. In either situation (i.e., with and without lateral compensation), the size of the hot STN in relation to the whole STN remains very small (1-2%). In addition, statistical analysis shows that in either situation, the means of the left and right functional STNs are significantly different. CONCLUSION: PFA-based planning may be superior to the current practice of using anatomic atlases that provide delineation of the target structure only, because it is more precise and provides a unique target point in the stereotactic space. This best stereotactic target is the point in the individualized atlas with the highest probability, meaning the highest probability of having the best target on the basis of the patients previously operated on. This best target is located in the hot STN, the size of which determines the precision of targeting. Because the size of the hot STN in comparison to the whole STN remains very small (1-2%) independent of whether or not lateral compensation is applied, target planning and execution have to be performed with high precision. The methodology presented, based on the PFA and on the functional volume, is general and can be applied to other structures and data sets. As numerous centers keep gathering large amounts of electrophysiological human and animal data, this work may facilitate opening new avenues in exploiting these data.

Brain Mapping↗
PubMed2004

Globus pallidus internus stimulation in primary generalized dystonia: a H215O PET study.

Globus pallidus internus (GPi) deep brain stimulation (DBS) increasingly shows promising efficacy in the treatment of severe primary generalized dystonia. Functional imaging studies have shown previously that dystonia could be related to abnormal cortical activation during voluntary movement. In the present study, the effects of GPi DBS on regional cerebral blood flow (rCBF) during a motor task were studied in patients with primary generalized dystonia. rCBF was measured using H215O and PET in eight control subjects and six patients with dystonia treated with bilateral GPi DBS. Subjects were scanned at rest and while performing joystick movements. Dystonic patients were tested in two conditions: 'OFF' (stimulator bilaterally switched off) and 'ON' (unilateral stimulation). In the 'OFF' condition, compared with rest, motor activation of the most dystonic hand was associated with overactivity in the contralateral dorsolateral prefrontal cortex, gyrus frontalis medialis, superior frontal gyrus (area 10), frontoorbital cortex and thalamus. In the 'ON' condition, GPi DBS contralaterally to the most dystonic hand induced a decrease of the overactivation in the same areas, as well as the putamen. According to the present study, generalized dystonia is associated with prefrontal overactivation which can be reversed by effective GPi DBS.

Adolescent↗
PubMed2004

Subthalamic nucleus stimulation and dysarthria in Parkinson's disease: a PET study.

In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN stimulation on regional cerebral blood flow (rCBF) during speech production and silent articulation in patients with Parkinson's disease. Ten Parkinson's disease patients surgically implanted bilaterally in the STN and with significant improvement of their dysarthria induced by STN stimulation were included. Ten healthy control subjects also participated in this study. Control subjects performed six sessions of [15O]H2O-PET scanning corresponding to three duplicated conditions externally cued by an auditory signal. The conditions were: (i) rest; (ii) production of a short, simple sentence; and (iii) silent articulation of the same sentence. Parkinson's disease patients carried out the six PET sessions twice, i.e., in the ON and OFF STN stimulation states. PET data analysis was performed using statistical parametric mapping (SPM99). In control subjects, speech production (SP) compared with rest was associated with increased rCBF bilaterally in the primary motor cortex (M1) corresponding to the orofacial somatotopy, the supplementary motor area (SMA), the associative auditory cortex and the cerebellar hemispheres. Silent articulation (SA) compared with rest induced a bilateral rCBF increase restricted to the orofacial M1 and cerebellar hemispheres. In Parkinson's disease patients in the OFF stimulation condition, during both SP and SA there was a lack of activation in the right orofacial M1 and in the cerebellum, abnormal increased rCBF in the right superior premotor cortex, and overactivation of the SMA. There was also an abnormal, increased rCBF in the dorsolateral prefrontal cortex (DLPFC) only during SP and increased rCBF in the left insula only during SA. In Parkinson's disease patients ON stimulation, for both SP and SA the activation pattern appeared similar to that in control subjects. In conclusion, our results suggest that parkinsonian dysarthria is associated with altered recruitment of the main motor cerebral regions (orofacial M1, cerebellum), and increased involvement of the premotor and prefrontal cortices (DLPFC, SMA, superior premotor cortex). These abnormal activations are different from those reported during hand motor tasks. They could be a compensatory mechanism, but might also arise directly as part of the pathophysiology of Parkinson's disease. STN stimulation tends to reverse these abnormal activations, which is consistent with the observed improvement of Parkinson's disease dysarthria.

Brain↗
PubMed2004

Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease: a positron emission tomographic study.

BACKGROUND: In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. OBJECTIVE: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation. MAIN OUTCOME MEASURES: The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated. RESULTS: In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level). CONCLUSIONS: The down-regulation of dopamine D2 receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D2 receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.

Aged↗
PubMed2004

A probabilistic functional atlas of the human subthalamic nucleus.

This paper introduces a method for generation and validation of a probabilistic functional brain atlas of subcortical structures from electrophysiological and neuroimaging data. The method contains three major steps: (1) acquisition of pre, intra, and postoperative multimodal data; (2) selection of an accurate data set for atlas generation; and (3) generation of the atlas from the selected data set. The method is applied to construct the probabilistic functional atlas of the human subthalamic nucleus (STN). The STN atlas has been built from data collected during surgical treatment of 184 patients with Parkinson's disease. It is based on preoperative X-ray ventriculography imaging, intraoperative electrophysiological measurements and X-ray imaging, and postoperative neurological assessment. The atlas features a high resolution of 0.25 mm(3) and a high accuracy of 0.25 mm. It is dynamic and can be rapidly recalculated for arbitrary resolution and extended by adding new patient data. The atlas can easily be reformatted and warped to match patient-specific data. Its applications include planning of subthalamic stimulations and neuroscience research to study functional properties of the STN. The presented method is general and can be applied for constructing human and animal probabilistic brain atlases.

Anatomy, Artistic↗