Erythrocytes catechol-o-methyl transferase activity is up-regulated after a 3-month treatment by entacapone in parkinsonian patients.

OBJECTIVES: Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD). Nevertheless, the consequence of the long-lasting inhibition of COMT by entacapone has never been investigated. We assessed the variation of the soluble red blood cell (S-RBC)-COMT activity after 3 months of chronic treatment by entacapone. METHODS: Twelve consecutive white PD patients (3 women and 9 men; mean age, 65.7 ± 2.4 years) with L-dopa-related motor fluctuations were assessed. Entacapone 200 mg was given in combination with each scheduled L-dopa/dopa decarboxylase inhibitor dose (range, 3-5 doses daily). The S-RBC-COMT activity was determined both before entacapone administration (baseline) and twice, respectively, after 1 and 3 months treatment with entacapone, that is, on morning, after at least a 12-hour withdrawal of entacapone and L-dopa and before the following first daily administration. RESULTS: Mean baseline S-RBC-COMT activity was 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) of protein. After 3 months, the level increased significantly in all PD patients from 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) to 1.19 ± 0.13 pmol/min per milligram (range, 0.58-2.14 pmol/min per milligram) of protein (P < 0.01), which corresponds to a mean increase of 72.9 ± 9.2% (range, 24%-146%). CONCLUSIONS: Our findings suggest that a long-lasting inhibition of the COMT may limit the efficacy of entacapone by development of a tolerance. Moreover, one may assume that an abrupt withdrawal of the treatment will be followed by a dramatic worsening of motor disability.

Hypertrophic remodeling and increased arterial stiffness in patients with intracranial aneurysms.

OBJECTIVE: Because an underlying arteriopathy might contribute to the development of intracranial aneurysms (IAs), we assessed the elastic properties of proximal conduit arteries in patients with IA. METHODS: In 27 patients with previous ruptured IA and 27 control subjects matched for age, gender and BMI, we determined arterial pressure, internal diameter, intima-media thickness (IMT), circumferential wall stress (CWS) and elastic modulus (wall stiffness) in common carotid arteries using applanation tonometry and echotracking. Moreover, carotid augmentation index (AIx, arterial wave reflections) and carotid-to-femoral pulse wave velocity (PWV, aortic stiffness) were assessed. RESULTS: Compared with controls, patients with IA exhibited higher brachial and carotid systolic and diastolic blood pressures, with similar brachial but higher carotid artery pulse pressure (35 + or - 6mm Hg vs. 41 + or - 8mm Hg, P=0.014). Moreover, patients have higher PWV (7.8 + or - 1.2ms(-1) vs. 8.3 + or - 1.1ms(-1), P=0.048) and AIx (15.8 + or - 10.8% vs. 21.1 + or - 8.5%, P<0.001) which contributes to increase carotid blood pressures. Furthermore, carotid IMT was higher in patients (546 + or - 64 microm vs. 642 + or - 70 microm, P<0.001) without difference in diameter suggesting an adaptive hypertrophy. However, patients display a lower CWS (61.6 + or - 9.2 kPa vs. 56.9 + or - 10.3 kPa, P=0.007) and no correlation between IMT and pulse pressure (r=0.152, P=NS) in contrast to controls (r=0.539, P<0.001) showing the contribution of a pressure-independent process. Finally, despite this lesser CWS, elastic modulus was increased in patients (310 + or - 105 kPa vs. 383 + or - 174 kPa, P=0.026). CONCLUSION: This study demonstrates that patients with IA display a particular carotid artery phenotype with an exaggerated hypertrophic remodeling and altered elastic properties. Thus, a systemic arteriopathy might contribute, together with the arterial wall fatiguing effect of the increased pulsatile stress, to the pathogenesis of IA.

Microsubthalamotomy effect at day 3: screening for determinants.

A microsubthalamotomy (mSTN) effect has been frequently reported after implantation that improves Parkinson's motor disability. It is usually believed that mSTN effect reflects the post-traumatic tissue reaction within the STN. However, it has never, to our knowledge, been reported whether pre and intraoperative factors could predict this mSTN effect. Preoperative clinical characteristics, that is, age, disease duration, Mattis Dementia Rating Scale score, levodopa responsiveness, severity of motor fluctuations and dyskinesia, and intraoperative parameters, that is, the number of tracks, distance of typical STN neuronal activity recorded along all microelectrodes, and along the definitive electrodes, were assessed in 40 consecutive PD patients submitted for STN stimulation. Multiple stepwise regression analysis showed that only the number of tracks used for microelectrodes recordings was predictor of the contralateral mSTN effect (F (4,73) = 1.83, P = 0.02). This result suggests that the contralateral mSTN depends on the tissue changes along the entirety of surgical trajectories affecting both STN and its adjacent structures.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: usefulness of intraoperative radiological guidance. The Stereoplan.

BACKGROUND: In our stereotactic procedure, intraoperative radiological documentation of electrode localization is performed using the Stereoplan. The aim of the study was to evaluate its accuracy. PATIENTS AND METHODS: Data of 20 consecutive patients, treated for Parkinson's disease by implantation of deep brain stimulators into the subthalamic nucleus, were collected prospectively. During surgery, Stereoplan coordinates of the tip of the central macroelectrodes were compared with intended coordinates along the central trajectory at 4 levels: (1) 10 mm above the anatomical target, (2) in the target, (3) in the substantia nigra pars reticulata, and (4) at the depth of contact 1. Before the frame's removal, Stereoplan coordinates of the contacts of the definitive electrode were compared with postoperative MRI coordinates. The mean of the differences was calculated in the x-, y-, and z-axis. Clinical results at 6 months were recorded. RESULTS: The mean of the differences between Stereoplan coordinates and intended coordinates for the macroelectrodes was lower than 1 mm. A submillimeter difference was also found for the definitive contacts. At 6 months, the Unified Parkinson's Disease Rating Scale III score improved by 70.6% compared with the baseline score. Dyskinesia and motor fluctuations decreased by 85.7 and 87%, respectively (p < 0.0001). CONCLUSION: Stereoplan could be considered an accurate intraoperative radiological system which assures the correct position of the electrode in the anatomical target.

Microsubthalamotomy: an immediate predictor of long-term subthalamic stimulation efficacy in Parkinson disease.

A microsubthalamotomy (mSTN) effect is commonly described after implantation that improves Parkinson's motor disability and is considered to be an obvious sign of good placement of the definitive electrode within the subthalamic nucleus (STN). There has been no formal study, however, demonstrating whether this mSTN effect can predict the long-term efficacy of STN stimulation in Parkinson Disease. The mSTN effect was defined by the percentage improvement of unified parkinson's disease rating scale (UPDRS III) baseline score assessed the third day morning following STN implantation, after at least a 12 hour withdrawal of dopaminergic treatment and before the programmable pulse generator was switched on. It was assessed in 30 consecutive patients with PD submitted for STN stimulation. Multiple stepwise regression analysis showed that mSTN effect (P = 0.005) and global mean intensity of stimulation (P = 0.004) were accurate independent predictors of the 6-month postoperative UPDRS III motor score improvement in the off-drug/on-stimulation condition.

Movement disorders and Creutzfeldt-Jakob disease: a review.

Movement disorders are reported in a significant number of patients within the course of Creutzfeldt-Jakob disease (CJD). Although myoclonus is more frequent, dystonia, choreoathetosis, tremor, hemiballismus, and atypical parkinsonian syndromes have also been reported. In this review, we report the principal movement disorders associated with CJD and evaluate their correlations with neuroradiological and neuropathological findings that could in fact suggest a basal ganglia dysfunction. Further studies are warranted in order to clarify these correlations.

Association of the protein C promoter CG haplotype and the factor II G20210A mutation is a risk factor for cerebral venous thrombosis.

The factor II G20210A mutation and estrogen treatment are described as risk factors for cerebral venous thrombosis (CVT). We evaluated these known risk factors in a population of CVT patients and investigated the role of a combination of two polymorphisms in the promoter of the protein C gene (PC promoter CG haplotype), newly described as risk factors for deep venous thrombosis. A retrospective population of 26 CVT patients was compared with a control group of 84 healthy volunteers. After a multivariate analysis, we confirmed that the factor II G20210A mutation is an independent risk factor for CVT with odds ratio 4.7 (95% confidence interval, 2.83--75.3). We demonstrated that the CVT risk is increased when this mutation is associated either with the PC promoter CG haplotype (odds ratio=19.8; 95% confidence interval, 2.1--186.5) or, in females, with an estrogen treatment (odds ratio=24; 95% confidence interval, 2.26--127.3). In this work, the association of the factor II G20210A mutation and the PC promoter CG haplotype or estrogen treatment seems to be a particular risk for CVT.