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Byline: S. Thobois (1,3), V. Fraix (2,5), M. Savasta (5), N. Costes (3), P. Pollak (2,5), P. Mertens (4), A. Koudsie (2), D. Bars (3), A. L. Benabid (2,5), E. Broussolle (1,3) Keywords: Parkinson's disease; subthalamic stimulation; dopamine; raclopride; PET Abstract: Abstract. 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 [[.sup.11]C]-Raclopride, whether STN stimulation induces a striatal DA release. Methods: Nine PD patients with bilateral STN stimulation were enrolled and underwent two [[.sup.11]C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [[.sup.11]C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping. Results: For PD patients, the mean [[.sup.11]C]-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 [[.sup.11]C]-Raclopride. Author Affiliation: (1) Dept. of Neurology D (Pr. G. Chazot) and INSERM U 534, Hopital Neurologique Pierre Wertheimer, 59 Bd Pinel, 69003, Lyon, France (2) Dept. of Neurology and Neurosurgery, CHU, Grenoble, France (3) CERMEP, Cyclotron Unit, Lyon, France (4) Dept. of Neurosurgery A (Pr. M. Sindou), Hopital Neurologique Pierre Wertheimer, Lyon, France (5) INSERM U 318, CHU, Grenoble, France Article History: Received Date: 24/01/2003 Accepted Date: 02/06/2003

Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

The aim of our study was to compare the results obtained by intraoperative and postoperative subthalamic nucleus (STN) macrostimulation in Parkinson's disease (PD). One hundred three PD patients implanted with bilateral STN stimulation were included. The thresholds for efficacy and side effects (motor contraction; paresthesias; oculomotor signs) observed on the same trajectory and at the same depth during the intraoperative evaluation and the first postoperative setting of STN stimulation parameters were collected. The level of improvement was divided into four categories depending on the degree of rigidity reduction: 0: no effect, A (mediocre efficacy): 20-50%, B (good efficacy): 60-100%, LL: lesion-like effect (disappearance of rigidity after implantation). Efficacy of STN stimulation was analyzed in 83 patients for a total of 664 contacts. For the best effects (B, LL), the results obtained in the operative room were concordant with those of the postoperative evaluation for 81% of the contacts. For the mediocre effects (A) and absence of efficacy, the results were only concordant in 20%. Side effects were analyzed in 103 patients for a total of 824 contacts. In 35% of the tested contacts paresthesias that were absent during surgery were observed postoperatively. This discrepancy was of 17% for the motor and of 10% for oculomotor side effects. Differences between the type of electrodes used, the stimulation parameters employed and the conditions of the assessment could explain these discrepancies.

Objective: To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson's disease (PD)., Methods: 36 consecutive patients with idiopathic Parkinson's disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions., Results: At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients., Conclusions: Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.

Hallucinations occur in up to 40% of patients with Parkinson's disease (PD) and are mainly of a visual nature. We prospectively studied 8 patients with PD and tactile hallucinations (TH). TH occurred with a clear sensorium, and were long-lasting. In most cases they involved animals, were combined with other types of hallucinations occurring simultaneously (mainly formed visual hallucinations), and predominated in the evening and/or at night. Pharmacological and disease-related factors, including a disorder in rapid-eye-movement sleep mechanisms, could play a part in the pathophysiology of these hallucinations.

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.