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Biomedical subjects

V Fraix

Publications and source records attributed to V Fraix.

16 recordsLinked to original sources
PubMed2005

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

Activities of Daily Living↗
PubMed2005

Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery.

Before the introduction of high frequency stimulation of the subthalamic nucleus (STN), many disabled tremor dominant parkinsonian patients underwent lesioning or chronic electrical stimulation of the thalamus. We studied the effects of STN stimulation in patients with previous ventral intermediate nucleus (VIM) surgery whose motor state worsened. Fifteen parkinsonian patients were included in this study: nine with unilateral and two with bilateral VIM stimulation, three with unilateral thalamotomy, and one with both unilateral thalamotomy and contralateral VIM stimulation. The clinical evaluation consisted of a formal motor assessment using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests encompassing a 50 point frontal scale, the Mattis Dementia Rating Scale, and the Beck Depression Inventory. The first surgical procedure was performed a mean (SD) of 8 (5) years after the onset of disease. STN implantation was carried out 10 (4) years later, and duration of follow up after beginning STN stimulation was 24 (20) months. The UPDRS motor score, tremor score, difficulties in performance of activities of daily living, and levodopa equivalent daily dose significantly decreased after STN stimulation. Neither axial symptoms nor neuropsychological status significantly worsened after the implantation of the STN electrodes. The parkinsonian motor state is greatly improved by bilateral STN stimulation even in patients with previous thalamic surgery, and STN stimulation is more effective than VIM stimulation in tremor dominant parkinsonian patients.

Adult↗
PubMed2004

[Gene therapy for Parkinson's disease].

INTRODUCTION: Parkinson's disease is a progressive neurodegenerative disorder whose main histopathological feature is the loss of dopaminergic neurons in the pars compacta of the substantia nigra with secondary striatal dopaminergic insufficiency. Treatment relies on medical therapy, using levodopa and dopaminergic agonists. However, the development of treatment complications, including motor fluctuations and levodopa-induced dyskinesia, led to the development of alternative therapeutical strategies such as deep brain stimulation and gene therapy. EXEGESIS: Current gene therapy models for Parkinson's disease have focused on two strategies. The first one is the replacement of biosynthetic enzymes for dopamine synthesis and the second consists in the addition of neurotrophic factors for protection and restoration of dopaminergic neurons. CONCLUSION: Neuroprotection and restoration of the nigrostriatal pathway are important issues for future genetic treatment strategies for Parkinson's disease and could include, in addition to neurotrophic factors, genes to prevent apoptosis or detoxify free radical species.

Dopamine↗
PubMed2004

[Deep brain stimulation].

The present renewal of the surgical treatment of Parkinson's disease, almost abandoned for twenty Years, arises from two main reasons. The first is the better understanding of the functional organization of the basal ganglia. It was demonstrated in animal models of Parkinson's disease that the loss of dopaminergic neurons within the substantia nigra, at the origin of the striatal dopaminergic defect, induces an overactivity of the excitatory glutamatergic subthalamo-internal pallidum pathway. The decrease in this hyperactivity might lead to an improvement in the pakinsonian symptoms. The second reason is the improvement in stereotactic neurosurgery in relation with the progress in neuroimaging techniques and with intraoperative electrophysiological microrecordings and stimulations, which help determine the location of the deep brain targets. In the 1970s chronic deep brain stimulation in humans was applied to the sensory nucleus of the thalamus for the treatment of intractable pain. In 1987, Benabid and colleagues suggested high frequency stimulation of the ventral intermediate nucleus of the thalamus in order to treat drug-resistant tremors and to avoid the adverse effects of thalamotomies. How deep brain stimulation works is not well known but it has been hypothetized that it could change the neuronal activities and thus avoid disease-related abnormal neuronal discharges. Potential candidates for deep brain stimulation are selected according to exclusion and inclusion criteria. Surgery can be applied to patients in good general and mental health, neither depressive nor demented and who are severely disabled despite all available drug therapies but still responsive to levodopa. The first session of surgery consists in the location of the target by ventriculography and/or brain MRI. The electrodes are implanted during the second session. The last session consists in the implantation of the neurostimulator. The ventral intermediate nucleus of the thalamus was the first target in which chronic deep brain stimulation electrodes were implanted in order to alleviate tremor. This technique can be applied bilaterally without the adverse effects of bilateral thalamotomies. Like pallidotomy, internal globus pallidum stimulation has a dramatic beneficial effect on levodopa-induced dyskinesia but its effects on the parkinsonian triad are less constant and opposite motor effects are sometimes observed in relation with the stimulated contact. The inconstant results, perhaps related to the complexity of the structure led to the development of subthalamic nucleus stimulation. The alleviation of motor fluctuations and the improvement in all motor symptoms allows a significant decrease in levodopa daily dose and in levodopa-induced dyskinesia. Presently, deep brain stimulation is a fashionable neurosurgical technique to treat Parkinson's disease. Subthalamic nucleus stimulation seems to be the most suitable target to control the parkinsonian triad and the motor fluctuations. Because of the possible adverse effects it must be reserved for disabled parkinsonian patients. No large randomized study comparing different targets and different neurosurgical techniques has been performed yet. Such studies, including cost benefit studies would be useful to assess the respective value of these different techniques.

Brain↗
PubMed2004

Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson's disease.

BACKGROUND: Long term effects of subthalamic nucleus (STN) stimulation on cognition, mood, and behaviour are unknown. OBJECTIVE: This study evaluated the cognitive, mood, and behavioural effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) followed up for three years. METHODS: A consecutive series of 77 PD patients was assessed before, one, and three years after surgery. Mean (SD) age at surgery was 55 (8). Seven patients died or were lost for follow up. Neuropsychological assessment included a global cognitive scale, memory, and frontal tests. Depression was evaluated using the Beck depression inventory. Assessment of thought disorders and apathy was based on the unified Parkinson's disease rating scale. Reports of the behavioural changes are mainly based on interviews done by the same neuropsychologist at each follow up. RESULTS: Only two cognitive variables worsened (category fluency, total score of fluency). Age was a predictor of decline in executive functions. Depression improved whereas apathy and thought disorders worsened. Major behavioural changes were two transient aggressive impulsive episodes, one suicide, four suicide attempts, one permanent apathy, one transient severe depression, four psychoses (one permanent), and five hypomania (one permanent). CONCLUSIONS: Comparing baseline, one year, and three year postoperative assessments, STN stimulation did not lead to global cognitive deterioration. Apathy scores mildly increased. Depression scores mildly improved. Behavioural changes were comparatively rare and mostly transient. Single case reports show the major synergistic effects of both medication and stimulation on mood and behaviour, illustrating the importance of a correct postoperative management.

Aged↗
PubMed2003

Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson's disease--A [(11)C]-raclopride PET study.

CONTEXT: Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported. OBJECTIVE: To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release. METHODS: Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping. RESULTS: For PD patients, the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/- 0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6 +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted. CONCLUSION: STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.

Adult↗
PubMed2002

Dual channel deep brain stimulation system (Kinetra) for Parkinson's disease and essential tremor: a prospective multicentre open label clinical study.

OBJECTIVES: To evaluate the safety and efficacy of a new dual channel stimulator (Kinetra) in patients with severe Parkinson's disease (PD) or essential tremor (ET). METHODS: 111 patients with PD and 18 with ET were studied. Leads were implanted into the subthalamic nucleus (STN) or internal globus pallidus of patients with the akinetic/rigid type of PD. Leads were implanted into the ventral intermediate nucleus (VIM) of the thalamus or the STN in patients with the tremor dominant type of PD and in those with ET. Technical data on the device and adverse events occurring during the study were documented. Patients were assessed with established and validated clinical scales before surgery and at three and six months' follow up. RESULTS: No device failure or unexpected adverse events occurred during the study. The dual channel stimulator used in stimulation of the STN, internal globus pallidus, and VIM in PD and ET was as safe and effective as the single channel stimulators in use. Mortality, morbidity, and infections were documented in the 129 treated patients. The parameter settings were similar to those usually programmed with single channel stimulators. Time spent in the operating room to implant the Kinetra system was systematically documented. In the PD group, improvement in the unified Parkinson's disease rating scale motor score, decrease in medication OFF periods, and reduced levodopa induced dyskinesia by bilateral STN stimulation were similar to those previously reported with bilaterally applied single channel stimulators. In the ET group upper and lower limb tremor scores were reduced by VIM stimulation. Activities of daily living improved in both disease groups. CONCLUSION: The Kinetra facilitated bilateral deep brain stimulation implantation surgery and is easy to use. It offers more advantages for the patient than the single channel stimulators; consequently, this new device may be recommended to treat patients with severe PD and ET.

Brain↗
PubMed2001

Intermuscular coherence in Parkinson's disease: relationship to bradykinesia.

We hypothesised that bradykinesia may be partly due to the failure of the corticomuscular system to engage in high frequency oscillatory activity in Parkinson's disease (PD). In healthy subjects such oscillations are evident in coherence between active muscles at 15--30 Hz. We therefore investigated the effects of therapeutic stimulation of the basal ganglia on this coherence and related it to changes in bradykinesia in the contralateral arm. Increases in coherence at 15--30 Hz and improvements in bradykinesia upon stimulation were correlated (r = 0.564, p < 0.001). This suggests that the basal ganglia modulate oscillatory activity in the corticomuscular system and that impairment of the motor system's ability to engage in synchronised oscillations at high frequency may contribute to bradykinesia in PD.

Electric Stimulation Therapy↗
PubMed2001

Intermuscular coherence in Parkinson's disease: effects of subthalamic nucleus stimulation.

It remains unclear how high frequency stimulation of the subthalamic nucleus (STN) improves parkinsonism. We hypothesized that stimulation may affect the organization of the cortical drive to voluntarily activated muscle. Normally this is characterized by oscillations at 15-30 Hz, manifest in coherence between muscles in the same frequency band. We therefore investigated the effects of STN stimulation on electromyographic (EMG) activity in co-contracting distal arm muscles in nine subjects with Parkinson's disease off drugs. Without stimulation, coherence between EMG signals was diminished at 15-30 Hz compared with nine controls. STN stimulation increased coherence in the 15-30 Hz band, so that it approached that in healthy subjects. The results suggest that STN stimulation facilitates the normal cortical drive to muscles.

Analysis of Variance↗
PubMed2001

Deep brain stimulation of the corpus luysi (subthalamic nucleus) and other targets in Parkinson's disease. Extension to new indications such as dystonia and epilepsy.

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim, first used in our group in 1987 as a treatment of tremor of various origins, has been used over the last ten years in 137 patients. Since 1993, this method has been extended to two other targets (subthalamic nucleus (STN): 137 patients and the medial pallidum (GPi): 12 patients), 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 also suppresses levodopa induced dyskinesias. The stereotactic technique is based on the determination of the target using ventriculography, MRI and electrophysiology, with both microrecording of single neuron activity and microstimulation inducing therapeutic symptom suppression and side effects. Chronic electrodes are then placed bilaterally at the best physiologically defined location and then connected to implantable stimulators (either 2 Itrel II or the new double channel Kinetra), operated at 130-185 Hz, 60 ms pulse width, 2.5 to 3.5 volts. There was no operative mortality and permanent morbidity was observed in 3 patients. 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 neural network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. Mechanisms within an individual target are also probably different for tremor or for other symptom alleviation. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. This strong improvement allows the decrease of the drug dosage to approximately 30% of the preoperative level, which suppresses the levodopa-induced dyskinesias. The off period dystonias are also suppressed as well as freezings and falls. The effects remain stable over more than 5 years and in the same period, the off stimulation-off medication UPDRS remains stable and does not increase at the usual rate The low rate of permanent complications, the minor side effects and their immediate reversibility, the possibility of bilateral implantation in one session and the long-term persistence of symptom relief are strong arguments which support 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 epilepsy. It is therefore possible that DBS in STN as well as in other targets could become a potent therapeutic tool in the near future for neurological disorders.

Dystonia↗
PubMed2001

Deep brain stimulation in the treatment of severe dystonia.

A retrospective study of a consecutive series of 19 patients with medically intractable dystonia treated with uni- or bilateral deep brain stimulation (DBS) is reported. A minimal follow-up of 6 months was available, up to eleven years in one patient. The first twelve consecutive patients (4 with primary and 8 with secondary dystonia) were treated with chronic stimulation of the posterior part of the ventrolateral thalamic nucleus (VLp). In this group global functional outcome was improved in 8 patients, although dystonia movement and disability scale scores did not show significant improvement. Of the 12 patients treated first by VLp DBS, three (1 primary and 2 secondary dystonia) underwent pallidal (GPi) DBS after the VLp DBS failed to improve their symptoms. The last seven consecutive patients (5 primary and 2 secondary dystonia) were treated directly with GPi DBS. Extracranial infection prevented chronic GPi DBS in one patient. In another GPi patient, preliminary negative tests with the electrodes discouraged implantation of the stimulators, and the patient was not treated with chronic DBS. In the remaining group of eight patients including those previously treated with VLp DBS, chronic GPi DBS resulted in a significant improvement in the dystonia movement scale and disability scores. Although this is a retrospective study dealing with dystonia of heterogeneous etiology, the results strongly suggest that GPi DBS has a better outcome than VLp DBS.

Adolescent↗
PubMed2001

Brachiofacial pure motor stroke.

Pure motor stroke is the commonest lacunar syndrome, but it may be associated with nonlacunar mechanisms of infarction. Pure motor brachiofacial weakness has been considered as a partial syndrome depending on a lacunar mechanism. We studied the correlations between stroke type, topography of infarction and etiology in 22 patients with pure motor brachiofacial weakness who were consecutively admitted to our stroke unit during a 10-year period. Seventeen patients had a small deep infarct, 4 had a cortical infarct in the superficial MCA territory and 1 had no specific lesion. The part of the cardiovascular risk factors was about 36% for smoking, 13% for diabetes mellitus, 60% for dyslipidemia and 40% for heart disease. Hypertension was present in 75% of our cases. None of the patients had a large artery stenosis on Doppler ultrasonography. We concluded that brachiofacial pure motor stroke is not always correlated to lacunar infarcts and may be due to a cortical infarct. MRI should be performed when brain CT is normal because of the implications it may have in management and therapy.

Aged↗
PubMed2000

Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson's disease.

Article abstract-The authors studied the effect of bilateral subthalamic nucleus stimulation on levodopa-induced dyskinesias in 24 consecutive parkinsonian patients with disabling dyskinesias. The improvement in the three subtypes of levodopa-induced dyskinesias was significant from the third postoperative month and was mainly due to the decrease in the daily dose of levodopa allowed by the stimulation-induced improvement in the motor score.

Adult↗
PubMedDate not supplied

Subthalamic stimulation for Parkinson's disease.

Deep brain stimulation by high frequency (HFS) has been developed starting in the thalamic target (Vim) from pragmatic observations and subsequently followed by other targets, such as the subthalamic nucleus (STN) and pallidum as an application of current knowledge from basic preclinical research in neuroscience. The mechanism involved by this neurosurgical approach is not completely solved. For Vim we have formed the hypothesis that HFS induces a jamming of sensory-motor loops but for the STN, from our experimental research in rats we have shown that HFS induces functional inhibition of cell activity in the target nuclei. In our patients the implantation of the stimulation electrodes was carried out stereotactically, under local anesthesia, using ventriculography, MRI, microrecordings and clinical evaluation of the effects of stimulation on rigidity. When the stimulation is turned ON in the STN area a significant decrease in rigidity was determined by the neurologists. Stimulation or even penetration of the electrode may be responsible for transient dyskinesias. The average location of the clinically efficient contact of the chronic stimulating electrodes is statistically located at 5.02 +/- 0.71 1/12 degrees of AC-PC in the AP direction, at -1.5 +/- 0.66 1/8 degrees of the height of the thalamus in the ventricle direction, with laterality at 11.98 +/- 1.12 mm in the lateral direction. The beneficial effects of STN stimulation are significant providing that the electrodes are correctly placed into the target. There is strong improvement of the symptoms of the triad in which akinesia, rigidity, and tremor are reduced on average to 41. 6, 48.6, and 27%, respectively, when compared with the previous preoperative level. From our experience, HFS of the STN could be considered the surgical therapy of choice at advanced stages of Parkinson's disease.

Electric Stimulation Therapy↗