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Pierre Pollak

Publications and source records attributed to Pierre Pollak.

At least 19 recordsLinked to original sources

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↗

Off-period dystonia in Parkinson's disease but not generalized dystonia is improved by high-frequency stimulation of the subthalamic nucleus.

STN-HFS is well known to improve patients with IPD. Because off-period dystonia mimics focal or generalized dystonia of other causes, we proposed bilateral STN-HFS to some patients with generalized dystonia. The aim of this study was to compare the efficacy of STN stimulation on off-period dystonia and generalized dystonia. From a larger series of patients with IPD, we selected 22 patients based on the presence of severe preoperative off-period dystonia rated > or = 3 in least one limb on a severity score ranging from 0 to 4. Four patients with generalized dystonia (Hallervorden-Spatz disease, n = 3; primary, n = 1) underwent bilateral STN-HFS. Dystonia of the four limbs was rated on video recordings in all patients before surgery and 3 months after surgery. In IPD, bilateral STN stimulation reduced the severity of off-period dystonia by 70% on the four limbs (preoperative mean severity score = 2.03 +/- 1.49; postoperative mean severity score = 0.60 +/- 0.78). In contrast, bilateral STN-HFS had no effect on generalized dystonia (preoperative mean severity score = 3.25 +/- 0.77; postoperative mean severity score = 3.12 +/- 0.62). Despite clinical similarities between off-period dystonia in Parkinson's disease and generalized dystonia in certain cases, the effect of chronic bilateral STN-HFS differs. STN stimulation is highly effective in off-period dystonia of IPD, whereas it does not improve generalized dystonia. The pathophysiologic mechanisms underlying dystonia in these two disorders are still unknown. Assuming that the mechanism of action of STN-HFS is similar regardless of the cause of dystonia, our findings suggest that the STN is not similarly involved in off-period dystonia of IPD and others dystonias.

Adult↗

Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease.

BACKGROUND: Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown. METHODS: We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. RESULTS: As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide. CONCLUSIONS: Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.

Activities of Daily Living↗

Young-onset Parkinson disease with and without parkin gene mutations: a fluorodopa F 18 positron emission tomography study.

BACKGROUND: Mutations of the parkin gene are frequently encountered in patients with young-onset Parkinson disease (YOPD), but the effects of this mutation on the nigrostriatal dopaminergic degeneration are not well established. OBJECTIVE: To analyze, using positron emission tomography and fluorodopa F 18, the severity and profile of striatal dopaminergic metabolism in YOPD patients with and without parkin gene mutations. METHODS: We performed positron emission tomography with fluorodopa F 18 in 19 YOPD patients with parkin gene mutations (parkin patients), 6 YOPD patients without parkin gene mutations (nonparkin patients), and 9 healthy controls. Putamen and caudate nucleus fluorodopa F 18 uptake was assessed using regions of interest analysis. RESULTS: In parkin patients, the striatal fluorodopa F 18 uptake reduction was 36.3%, 51.3%, and 66.7%, respectively, for the caudate nucleus, anterior putamen, and posterior putamen compared with controls. In nonparkin patients, this reduction was 23.0%, 43.6%, and 73.0%, respectively. This reduction was asymmetrical according to the most affected hemibody for the anterior and posterior putamen in parkin patients and for the posterior putamen in nonparkin patients. A rostrocaudal gradient was observed with a severe decrease in fluorodopa F 18 uptake in the putamen and relative sparing of the caudate nucleus. There was no significant difference of striatal fluorodopa F 18 uptake between our 2 YOPD populations. In parkin patients, no significant correlation was found among fluorodopa F 18 uptake, motor disability, and the type of mutations. In nonparkin patients, there was a significant correlation between fluorodopa F 18 uptake and clinical severity. CONCLUSIONS: The pattern of fluorodopa F 18 uptake in the striatum of YOPD patients is similar to that of patients with idiopathic Parkinson disease and does not depend on the presence or absence of mutations of the parkin gene.

Adolescent↗

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.

Activities of Daily Living↗

Bilateral subthalamic stimulation effects on oral force control in Parkinson's disease.

Dysarthria in Parkinson's disease (PD) consists of articulatory, phonatory and respiratory impairment. Bilateral subthalamic nucleus (STN) stimulation greatly improves motor disability, but its long-term effect on speech within a large group of patients has not been precisely evaluated. The aim of this study was to determine the effect of bilateral STN stimulation on oral force control in PD. We measured forces of the upper lip, lower lip and tongue in twenty-six PD patients treated with bilateral STN stimulation. Measurements of the articulatory organ force, as well as a motor evaluation using the Unified Parkinson's Disease Rating Scale (UPDRS), were made with and without STN stimulation. Maximal voluntary force (MVF), reaction time (RT), movement time (MT), imprecision of the peak force (PF) and the hold phase (HP) were all improved with STN stimulation during the articulatory force task, as well as the motor examination scores of the UPDRS. It seems that the beneficial STN stimulation-induced effect on articulatory forces persisted whatever the duration of post-surgical follow-up. However, dysarthria evaluated by the UPDRS was worse in two subgroups of patients with a one to two year and three to five year post-surgical follow-up, in comparison with a subgroup of patients with a three month follow-up. STN stimulation has a beneficial long-term effect on the articulatory organs involved in speech production, and this indicates that parkinsonian dysarthria is associated, at least in part, with an alteration in STN neuronal activity. Nevertheless, to confirm the persistence of the beneficial effect of STN stimulation on parkinsonian dysarthria, a longitudinal evaluation is still needed.

Adult↗

Effect of bilateral stimulation of the subthalamic nucleus on parkinsonian dysarthria.

Never was the effect of bilateral stimulation of the subthalamic nucleus (STN) evaluated quantitatively on all the components of speech production, that is articulation, respiration and phonation, at the same time. It is the purpose of this study which uses force measurements of the articulatory organs and acoustic analysis in 16 parkinsonian patients. With STN stimulation, reaction and movement time of the articulatory organs decreased and their maximal strength, as well as their precision increased. We also noted a large beneficial effect on voice with a significant improvement in respiratory and phonatory functions.

Adolescent↗

[Therapeutic and physiopathological contribution of electric stimulation of deep brain structures in Parkinson's disease].

Ablative functional neurosurgery constituted during the first half of the 20th century the main treatment of advanced forms of Parkinson's disease. The surgical procedure was spectacularly efficient on tremor, but sometimes complications were not totally regressive and even more severe when surgery was bilateral, this leading to neurocognitive deficits or to speech problems. This, associated to the efficiency of levodopa, was at the origin of the almost total disappearance of this type of surgery during the '60s until the eighties. The rebirth of functional neurosurgery, necessitated by the appearance of dyskinesias, was possible in most part because of the development of techniques with a lower morbidity, such as high frequency stimulation (HFS). This was initially applied to the thalamic ventral intermedius nucleus VIM, and the low morbidity of the method has been demonstrated by the possibility to operate a large number of patients bilaterally without complication. The demonstration that the pallidal target, which had been abandoned during the '50s because of its low efficiency on the triad of symptoms of Parkinson's disease, was selectively efficient on dyskinesias, led naturally to apply HFS to this target. In 1990, the demonstration in the field of fundamental research of the role of the subthalamic nucleus as a key element of regulation of movement, suggested to register this nucleus into the list of targets, despite the risk of hemiballism that this structure presents when it is lesioned by haemorrhage, because of the good tolerance of HFS as a surgical method. This target quickly showed its remarkable efficiency on all symptoms of Parkinson's disease. Because of the reduction of the doses of dopaminergic treatments which were allowed, this target had also the capacity to reduce, indirectly, the intensity of dyskinesias. If the efficiency of the method is nowadays demonstrated as well as the stability on the long term of its results, the mechanism is still mostly not understood. Moreover the physiopathogenic hypothesis suggests the possibility of a neuroprotective effect of the stimulation, which still needs to be clearly established at the experimental level as well as at the level of clinical applications.

Animals↗

Mechanisms of deep brain stimulation.

The mechanism of action of high frequency deep brain stimulation is still unknown. However, in all circumstances and in all target nuclei so far stimulated, the effects mimic those of lesions previously made during thalamotomies, pallidotomies or even subthalamotomies, suggesting an inhibition of at least the neuronal network containing the target, if not of the target itself. On the contrary, fiber bundles are consistently activated at low or high frequencies. The hypothetical mechanisms envisioned should therefore be compatible and even produce these observed effects, to be acceptable as hypotheses. The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity, etc. It is probable that some are more involved in the acute effects and others in the long term changes, close to neuroplasticity. It is clear that the understanding of this strange and powerful phenomenon will profit from both clinical observation and well designed animal experiments.

Animals↗

Treatment results: Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable.

Electric Stimulation Therapy↗

Results of deep brain stimulation for dystonia: a critical reappraisal.

Deep brain stimulation for severe dystonia is still in the very first stage of development. Only single case reports or small case series have been reported to date. Best results have been obtained with pallidal stimulation in patients with primary generalised dystonia, especially in DYT1 mutation carriers. In secondary dystonia, conflicting results were reported. However, there is today enough promising evidence for a striking efficacy of pallidal stimulation in dystonia, supporting the need for further investigations in the field, with collaborative projects (regarding to the limited number of eligible patients); double-blind studies, including a consensus about surgical method; and a precise anatomic analysis of the position of the electrode. A careful assessment of the efficacy by using improved clinical scale is also warranted.

Dystonia↗

Imaging of subthalamic nucleus and ventralis intermedius of the thalamus.

The techniques of targeting the subthalamic nucleus (STN) and the ventralis intermedius nucleus (Vim) are similar, only the coordinates are different. Targeting ideally consists of gathering all data about a target and positioning the electrode correctly within that target. The electrode should be positioned within a statistical range of coordinates, where the neuronal firing fits a given pattern and responds to external stimuli, particularly to proprioceptive inputs, in a somatotopically organized manner. Moreover, final placement should provide the best clinical improvement of symptoms under the stimulation parameters expected to be used in the long term. This latter criterion is by far the most important, because intraoperative findings indicate the functional benefit for the patient, which is the ultimate purpose of this surgery. A variety of radiological modalities are available to provide data for electrode placement, but each type has its drawbacks. Ventriculography, although safe when performed accordingly to strict technical procedure, is the most precise method but provides more indirect targeting and is more invasive than magnetic resonance imaging (MRI). MRI is the best method for visualizing the STN and, to some extent, for discerning the Vim, but it is plagued with unpredictable and nonreproducible deformations that induce a systematic distortion. These shortcomings no doubt will be corrected in the near future, and the technologies will better assist us in the proper placement of electrodes, which will provide the patient with the highest possible benefit.

Cerebral Ventriculography↗

Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease.

Microelectrode recordings of single unit neuronal activity were used during stereotactic surgery to define the subthalamic nucleus for chronic deep brain stimulation in the treatment of Parkinson's disease. By using five parallel trajectories, often two to three microelectrodes allow us to recognize subthalamic nucleus (STN) neuronal activity. STN neurons were easily distinguished from cells of the overlying zona incerta and the underlying substantia nigra. During a typical exploratory track, we can observe a very low background noise in the zona incerta and almost complete absence of single cell recording. Penetration of the electrode tip into the STN is characterized by a sudden increase in background activity and single cell activity of spontaneously active neurons. The exit of electrode tip out of the STN corresponds to a decrease in background noise and a loss of single cell activity. Spontaneous neuronal activity increases again when the electrode tips enters the substantia nigra pars reticulata (SNr); however, the activity is less rich than in the STN, indicating a more cell-sparse nucleus. STN neurons are characterized by a mean firing rate of 42.30 +/- 22.00 spikes/sec (mean +/- SD). The STN cells exhibited irregular or bursty discharge pattern. The pattern of single cell activity in the SNr is a more regular tonic activity that can easily be distinguished from the bursting pattern in the STN. The most useful criteria to select a trajectory are (1) the length of an individual trajectory displaying typical STN activity, (2) the bursting pattern of activity, and (3) motor responses typical of the sensorimotor part of the nucleus. In conclusion, microelectrode recording of the subthalamic area improves the accuracy of targeting the STN.

Brain Mapping↗

Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.

Studying the clinical effects induced by electrical stimulation of the subthalamic nucleus (STN) area in a parkinsonian patient under local anesthesia is a mandatory step to determine the precise location of the final chronic electrode. Using multiple microelectrodes, preferably in a concentric parallel array allows a precise mapping of the STN region. The most reliable features to determine the suitable target are stimulation-induced dyskinesias and rigidity decrease at a low intensity without adverse effects or only at far higher intensities. New skills are needed to assess all stimulation-induced effects and interpret them in anatomo-functional terms.

Brain Mapping↗

Postoperative management of subthalamic nucleus stimulation for Parkinson's disease.

The postoperative neurologic management of patients with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson' s disease is a complex dynamic process that involves a progressive increase in stimulation intensity and a parallel decrease in antiparkinsonian medication while assessing the interactions of both treatments. Neurologists responsible for postoperative management of patients receiving STN DBS must have expert knowledge of the electroanatomy of the subthalamic area and be familiar with the medical treatment of motor and nonmotor symptoms, including the management of long-term complications of levodopa treatment. Neurosurgeons who perform DBS need to understand the principles that guide the postoperative adaptation of treatment. This article defines guidelines for setting stimulation parameters, adapting drugs and managing adverse effects.

Antiparkinson Agents↗

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study.

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.

Aged↗