Jean Régis

Neurostimulation for Parkinson's Disease with Early Motor Complications

BACKGROUND Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinsons disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinsons disease. METHODS In this 2-year trial, we randomly assigned 251 patients with Parkinsons disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinsons Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinsons Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS Subthalamic stimulation was superior to medical therapy in patients with Parkinsons disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Regularization of diffusion-based direction maps for the tracking of brain white matter fascicles.

Magnetic resonance diffusion tensor imaging (DTI) provides information about fiber local directions in brain white matter. This paper addresses inference of the connectivity induced by fascicles made up of numerous fibers from such diffusion data. The usual fascicle tracking idea, which consists of following locally the direction of highest diffusion, is prone to erroneous forks because of problems induced by fiber crossing. In this paper, this difficulty is partly overcomed by the use of a priori knowledge of the low curvature of most of the fascicles. This knowledge is embedded in a model of the bending energy of a spaghetti plate representation of the white matter used to compute a regularized fascicle direction map. A new tracking algorithm is then proposed to highlight putative fascicle trajectories from this direction map. This algorithm takes into account potential fan shaped junctions between fascicles. A study of the tracking behavior according to the influence given to the a priori knowledge is proposed and concrete tracking results obtained with in vivo human brain data are illustrated. These results include putative trajectories of some pyramidal, commissural, and various association fibers.

From 3D magnetic resonance images to structural representations of the cortex topography using topology preserving deformations

We propose an algorithm allowing the construction of a structural representation of the cortical topography from a T1-weighted 3D MR image. This representation is an attributed relational graph (ARG) inferred from the 3D skeleton of the object made up of the union of gray matter and cerebro-spinal fluid enclosed in the brain hull. In order to increase the robustness of the skeletonization, topological and regularization constraints are included in the segmentation process using an original method: the homotopically deformable regions. This method is halfway between deformable contour and Markovian segmentation approaches. The 3D skeleton is segmented in simple surfaces (SSs) constituting the ARG nodes (mainly cortical folds). The ARG relations are of two types: first, theSS pairs connected in the skeleton; second, theSS pairs delimiting a gyrus. The described algorithm has been developed in the frame of a project aiming at the automatic detection and recognition of the main cortical sulci. Indeed, the ARG is a synthetic representation of all the information required by the sulcus identification. This project will contribute to the development of new methodologies for human brain functional mapping and neurosurgery operation planning.

A framework to study the cortical folding patterns.

This paper describes a decade-long research program focused on the variability of the cortical folding patterns. The program has developed a framework of using artificial neuroanatomists that are trained to identify sulci from a database. The framework relies on a renormalization of the brain warping problem, which consists in matching the cortices at the scale of the folds. Another component of the program is the search for the alphabet of the folding patterns, namely, a list of indivisible elementary sulci. The search relies on the study of the cortical folding process using antenatal imaging and on backward simulations of morphogenesis aimed at revealing traces of the embryologic dimples in the mature cortical surface. The importance of sulcal-based morphometry is illustrated by a simple study of the correlates of handedness on asymmetry indices. The study shows for instance that the central sulcus is larger in the dominant hemisphere.

Addiction in Parkinson's disease: impact of subthalamic nucleus deep brain stimulation.

In Parkinsons disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinsons disease, therefore, does not constitute an obstacle to high‐frequency STN stimulation, and this treatment may even cure the addiction.

Gamma knife radiosurgery in the management of cavernous sinus meningiomas

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Gamma Knife Surgery for Epilepsy Related to Hypothalamic Hamartomas

OBJECTIVEDrug-resistant epilepsy associated with hypothalamic hamartomas (HHs) can be cured by microsurgical resection of the lesions. Morbidity and mortality rates for microsurgery in this area are significant. Gamma knife surgery (GKS) is less invasive and seems to be well adapted for this indication. METHODSTo evaluate the safety and efficacy of GKS to treat this uncommon pathological condition, we organized a multicenter retrospective study. Ten patients were treated in seven different centers. The follow-up periods were more than 12 months for eight patients, with a median follow-up period of 28 months (mean, 35 mo; range, 12–71 mo). All patients had severe drug-resistant epilepsy, including frequent gelastic and generalized tonic or tonicoclonic attacks. The median age was 13.5 years (range, 1–32 yr; mean, 14 yr) at the time of GKS. Three patients experienced precocious puberty. All patients had sessile HHs. The median marginal dose was 15.25 Gy (range, 12–20 Gy). Two patients were treated two times (at 19 and 49 mo) because of insufficient efficacy. RESULTSAll patients exhibited improvement. Four patients were seizure-free, one experienced rare nocturnal seizures, one experienced some rare partial seizures but no more generalized attacks, and two exhibited only improvement, with reductions in the frequency of seizures but persistence of some rare generalized seizures. Two patients, now seizure-free, were considered to exhibit insufficient improvement after the first GKS procedure and were treated a second time. A clear correlation between efficacy and dose was observed in this series. The marginal dose was more than 17 Gy for all patients in the successful group and less than 13 Gy for all patients in the “improved” group. No side effects were reported, except for poikilothermia in one patient. Behavior was clearly improved for two patients (with only slight improvements in their epilepsy). Complete coverage of the HHs did not seem to be mandatory, because the dosimetry spared a significant part of the lesions for two patients in the successful group. CONCLUSIONWe report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study.

Summary:  Purpose: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug‐resistant epilepsies of mesial temporal lobe origin.

Automatic recognition of cortical sulci of the human brain using a congregation of neural networks

This paper describes a complete system allowing automatic recognition of the main sulci of the human cortex. This system relies on a preprocessing of magnetic resonance images leading to abstract structural representations of the cortical folding patterns. The representation nodes are cortical folds, which are given a sulcus name by a contextual pattern recognition method. This method can be interpreted as a graph matching approach, which is driven by the minimization of a global function made up of local potentials. Each potential is a measure of the likelihood of the labelling of a restricted area. This potential is given by a multi-layer perceptron trained on a learning database. A base of 26 brains manually labelled by a neuroanatomist is used to validate our approach. The whole system developed for the right hemisphere is made up of 265 neural networks. The mean recognition rate is 86% for the learning base and 76% for a generalization base, which is very satisfying considering the current weak understanding of the variability of the cortical folding patterns.

Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia.

Background: Dynamic action of anesthetic agents was compared at cortical and subcortical levels during induction of anesthesia. Unconsciousness involved the cortical brain but suppression of movement in response to noxious stimuli was mediated through subcortical structures. Methods: Twenty-five patients with Parkinson disease, previously implanted with a deep-brain stimulation electrode, were enrolled during the implantation of the definitive pulse generator. During induction of anesthesia with propofol (n = 13) or sevoflurane (n = 12) alone, cortical (EEG) and subcortical (ESCoG) electrogenesis were obtained, respectively, from a frontal montage (F3–C3) and through the deep-brain electrode (p0–p3). In EEG and ESCoG spectral analysis, spectral edge (90%) frequency, median power frequency, and nonlinear analysis dimensional activation calculations were determined. Results: Sevoflurane and propofol decreased EEG and ESCoG activity in a dose-related fashion. EEG values decreased dramatically at loss of consciousness, whereas there was little change in ESCoG values. Quantitative parameters derived from EEG but not from ESCoG were able to predict consciousness versus unconsciousness. Conversely, quantitative parameters derived from ESCoG but not from EEG were able to predict movement in response to laryngoscopy. Conclusion: These data suggest that in humans, unconsciousness mainly involves the cortical brain, but that suppression of movement in response to noxious stimuli is mediated through the effect of anesthetic agents on subcortical structures.