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Paul Krack

Publications and source records attributed to Paul Krack.

At least 19 recordsLinked to original sources
PubMed2006

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗
PubMed2006

Subthalamic nucleus influences spatial orientation in extra-personal space.

While the role of frontal and parietal cortex in spatial orientation has been studied extensively, the contribution of the basal ganglia and especially the subthalamic nucleus to spatial orientation remains less clear. Here we use subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) as a reversible model of functional lesioning to evaluate the influence of the STN in extra-personal space orientation. To this end, 12 PD patients were examined 1 year after implantation of DBS electrodes in the STN after overnight withdrawal of L-dopa. Patients were tested in a pseudo-randomized order while both stimulators, the right only, the left only, or no stimulator, were switched on. Patients performed line bisection and a reaction time task responding to stimuli of the middle, the left, and the right extra-personal space. A separate assessment of the right and left hand responding to visual stimuli in each hemispace made it possible to distinguish hemi-spatial and hemi-motor impairments. No asymmetries in space orientation were found when both stimulators were switched OFF, when both stimulators were switched ON, and when only the right stimulator was switched ON. When only the left subthalamic stimulation was switched ON, the reaction times of both hands to visual stimuli in the left extra-personal hemispace increased significantly and the line bisection test showed a significant orientation to the right. These results lead to the conclusion that the STN and its cortical projections influence the network involved in visuospatial orientation. These patterns of symptoms of neglect demonstrate the influence of the STN on the attentional system of the nondominant hemisphere.

Attention↗
PubMed2006

Deep brain stimulation: preoperative issues.

Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Brain↗
PubMed2006

Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson's disease and tremor.

The vast majority of centers use electrophysiological mapping techniques to finalize target selection during the implantation of deep brain stimulation (DBS) leads for the treatment of Parkinson's disease and tremor. This review discusses the techniques used for physiological mapping and addresses the questions of how various mapping strategies modify target selection and outcome following subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across centers, but can be broadly categorized into those that use microelectrode or semimicroelectrode techniques to optimize position prior to implantation and macrostimulation through a macroelectrode or the DBS lead, and those that rely solely on macrostimulation and its threshold for clinical effects (benefits and side effects). Microelectrode criteria for implantation into the STN or GPi include length of the nucleus recorded, presence of movement-responsive neurons, and/or distance from the borders with adjacent structures. However, the threshold for the production of clinical benefits relative to side effects is, in most centers, the final, and sometimes only, determinant of DBS electrode position. Macrostimulation techniques for mapping, the utility of microelectrode mapping is reflected in its modification of electrode position in 17% to 87% of patients undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless, with the absence of class I data, and in consideration of the large number of variables that impact clinical outcome, it is not possible to conclude that one technique is superior to the other in so far as motor Unified Parkinson's Disease Rating Scale outcome is concerned. Moreover, mapping technique is only one out of many variables that determine the outcome. The increase in surgical risk of intracranial hemorrhage correlated to the number of microelectrode trajectories must be considered against the risk of suboptimal benefits related to omission of this technique.

Brain↗
PubMed2006

Deep brain stimulation: neuropsychological and neuropsychiatric issues.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed.

Cognition Disorders↗
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

Differential effects of L-dopa and subthalamic stimulation on depressive symptoms and hedonic tone in Parkinson's disease.

Patients with Parkinson's disease frequently have mild to moderate depression and exhibit low hedonic tone. The authors investigate the impact of a single L-dopa challenge and the acute effects of electric stimulation of the subthalamic nucleus (STN) on symptoms of depression and hedonic tone. Depressive symptoms improved with L-dopa and STN stimulation to the same extent. However, hedonic tone improved only with L-dopa. Most of the emotional changes did not correlate with changes in motor performance, indicating they were not just reactive but specific to the treatment. These results demonstrate a single dissociation of depressive symptoms and anhedonia in response to an acute L-dopa and STN-stimulation challenge.

Affect↗
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↗
PubMed2004

Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease. Although several studies have assessed cognitive functions before surgery and after long-term STN stimulation, only a few have assessed patients while stimulation is on and off to more specifically address the short-term cognitive effects of STN deep brain stimulation. OBJECTIVE: To examine the short-term effects of STN stimulation on several tests sensitive to executive function and the long-term effects of STN stimulation on a global cognitive scale. DESIGN: Twenty-three patients with Parkinson disease were tested 6 to 12 months after surgery with STN stimulation switched on and off in a random order while taking their regular medication. The Unified Parkinson's Disease Rating Scale motor score was also rated in the on and off stimulation condition. The neuropsychological battery included digit span, verbal fluency, Stroop color test, and random number generation in a single- and dual-task condition. RESULTS: Short-term stimulation improved the results on the Random Number Generation Task, requiring suppression of habitual responses, but induced more errors in the interference task of the Stroop color test. Digit span, verbal fluency, and dual-task performance results did not change. There was a significant correlation (r = 0.47, P =.02) between improved performance on the Random Number Generation Task and impaired response inhibition in the Stroop interference condition. A preoperative to postoperative comparison showed no changes in global cognitive function with long-term STN deep brain stimulation. CONCLUSIONS: Short-term STN stimulation improves cognitive flexibility (giving up habitual responses) but impairs response inhibition. Long-term STN stimulation does not change global cognitive function.

Cognition↗
PubMed2004

Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study.

A beneficial effect of botulinum toxin on tension-type headache was reported in open-label studies but scientifically rigorous clinical studies are lacking. Therefore we conducted a prospective, multicenter, randomized, double-blind, placebo-controlled trial. Multiple pericranial muscles of 112 patients with chronic tension-type headache were treated either with 500 mouse units of botulinum toxin (Dysport) or with placebo. The diagnoses were made strictly following the International Headache Society criteria. Co-existence of migraine was an exclusion criterion. Injections were made following a fixed scheme and not adjusted to the patient's symptoms. Patients kept a headache diary that was used to calculate the area under the headache curve of 6 weeks before and 12 weeks after the treatment as the main effect measure. Secondary effect measures were the number of days with headache, the number of days with intake of analgesics, the duration of the nocturnal sleep, and the Beck Depression Inventory score. There were no significant differences between the verum group and the placebo group in any of these variables. Seven patients of the verum group had transient weakness of the eyelids, the neck, or both, indicating that a higher dose than used in this study does not seem sensible for the treatment of headache. The statistical power of the study was high enough to warrant the conclusion that there is no clinically significant effect of botulinum toxin A on chronic tension-type headache.

Adult↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces akinesia in Parkinson's disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L-dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS-items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L-dopa test than in the pure STN-DBS condition. Other akinesia items and the time for build-up of lifting force were equally improved in both conditions. This suggests that routine STN-DBS might not be equally effective on all aspects of fine motor functions.

Antiparkinson Agents↗
PubMed2003

Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease.

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow-up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN-DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN-DBS beyond the first year after surgical procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse events which, however, were temporary.

Electric Stimulation↗