Jean-Jacques Lemaire

Long-term follow-up of globus pallidus chronic stimulation in advanced Parkinson's disease.

To assess the long‐term follow‐up of the globus pallidus internus (GPi) stimulation, six patients were evaluated every year by using the Unified Parkinsons Disease Rating Scale (UPDRS). Three years postoperatively, GPi stimulation led to a significant improvement of dyskinesia severity (50%, P = 0.05) and activities of daily living (subscore of quality of life scale, 9%, P = 0.05). However, the improvement induced by chronic pallidal stimulation on the mean daily duration in the off state was lost at the last assessment.

Contact dependent reproducible hypomania induced by deep brain stimulation in Parkinson's disease: clinical, anatomical and functional imaging study

Hypomanic symptoms depending on anatomical location of contacts are reported in patients with Parkinsons disease (PD) treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, the underlying cortical and subcortical dysfunction is debated. In this study, five PD patients implanted with DBS–STN who presented with reversible and reproducible hypomanic symptoms after stimulation of specific ‘manic’ contacts were investigated. Hypomanic symptoms were assessed using the Bech and Rafaelsen Mania Scale (MAS). Three dimensional anatomical location of ‘euthymic’ and ‘manic’ contacts, after matching the postoperative CT scan with the preoperative stereotactic MRI, and a H215O positron emission tomography (PET) study testing ‘euthymic’ and ‘manic’ contacts, were performed. Under ‘euthymic’ conditions, MAS score (mean±SD) was 0.6±0.5 compared with 7.8±3.1 under ‘manic’ conditions. Nine of 10 ‘manic’ contacts were located in the substantia nigra, mainly in its ventral part. PET showed that hypomania was associated with strong asymmetrical cerebral activation involving preferentially the right hemisphere and was mediated by activation of the anterior cingulate and medial prefrontal cortex. The present study demonstrates the role of the subcortical structures in the genesis of hypomania in PD patients treated with DBS and stresses the involvement of the substantia nigra.

Manic behaviour induced by deep-brain stimulation in Parkinson’s disease: evidence of substantia nigra implication?

We report the case of a patient who had benefited from bilateral subthalamic nucleus deep brain stimulation for Parkinson’s disease and who presented acute and reproducible manic behaviour when stimulated mainly in the substantia nigra. A positron emission tomography scan showed an activation of the right dorsolateral prefrontal and inferior temporal cortex, the left anterior cingulate cortex and a deactivation of the left insula. This suggests that changes in cortical activation related to mania are subcortically driven, involving notably the substantia nigra.

Overweight after deep brain stimulation of the subthalamic nucleus in Parkinson disease: long term follow-up

Objective: To assess the occurrence of weight gain in patients with Parkinson’s disease, with an average 16 months of follow-up after subthalamic nucleus deep brain stimulation. Methods: We used dual x ray absorptiometry to evaluate changes in body weight and body composition in 22 patients with Parkinson’s disease (15 men and seven women) before surgery, 3 months after surgery and on average 16 months after surgery. Results: No patient was underweight before surgery and 50% were overweight. By contrast, 68% were overweight or obese 3 months after surgery and 82% after 16 months (p<0.001). For men, the mean increase in body mass index (BMI) was 1.14 (0.23) kg/m2 3 months after surgery and 2.02 (0.36) kg/m2 16 months after surgery. For women, the mean increases in BMI at the same evaluation times were 1.04 (0.30) kg/m2 and 2.11 (0.49) kg/m2. This weight gain was mainly secondary to an increase in fat mass in both men and women. Three months after surgery, acute subthalamic deep brain stimulation induced an improvement in parkinsonian symptoms (evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III) by 60.7 (2.9)% in the “off” dopa condition and a dramatic improvement of motor complications (dyskinesia duration: 82.8 (12.8)%, p<0.0001; off period duration: 92.7 (18.8)%, p<0.0001). Conclusion: Although subthalamic nucleus deep brain stimulation significantly improved parkinsonian symptoms and motor complications, many patients became overweight or obese. This finding highlights the necessity to understand the underlying mechanisms and to provide a diet management with a physical training schedule appropriate for patients with Parkinson’s disease.

Acute and chronic effects of anteromedial globus pallidus stimulation in Parkinson’s disease

OBJECTIVE To evaluate the effects of acute and chronic stimulation in the anteromedial part of the globus pallidus internus (GPi) on the symptoms of patients with Parkinson’s disease. METHODS Six patients with severe Parkinson’s disease (Hoehn and Yahr stage 4–5 in “off” drug condition) with motor fluctuations and levodopa induced dyskinesia (LID) were operated on. Chronic electrodes were implanted in the anteromedial GPi bilaterally in five patients and unilaterally in one patient. The effect of stimulation via the four contacts for each electrode (n=11) was assessed postoperatively on the contralateral parkinsonian signs in the off condition and on the contralateral and ipsilateral LID in the “on” condition. The core assessement program for intracerebral transplantation protocol was performed before surgery and then 1, 3, and 6 months after surgery in on and off conditions and in on and off stimulation conditions. RESULTS Stimulation performed postoperatively showed a significant improvement (p<0.05) by 47% (contralateral rigidity) and 32% (contralateral bradykinesia) when stimulation was applied through the distal contact. Levodopa induced dyskinesias were improved by 95% (contralateral LID) and by 66% (ipsilateral LID) when stimulation was applied through the distal contact. Six months after the surgery, GPi stimulation in the off condition led to a mean improvement in the motor score of UPDRS by 36%. The mean daily duration in the off state decreased by 52% (p<0.05). The mean duration of LIDs decreased by 68% (p<0.05) and their severity by 53% (p<0.05). CONCLUSION Chronic stimulation in the anteromedial GPi shows that this is a safe and effective treatment for advanced Parkinson’s disease with benefit sustained for at least 6 months.

Slow Pressure Waves in the Cranial Enclosure

Summary. Slowly varying pressure oscillations in the cranial enclosure are well known, especially intracranial pressure waves as best described by the pioneering works of Janny and Lundberg. Nevertheless, in spite of over twenty five years research on intracranial pressure waves, their origin and regulation remain unclear but are often considered only as pathological. Our aim was to review data on these phenomena to clarify their biological status and the role that they could play in the management of patients suffering from such intracranial neurosurgical diseases as intracranial hypertension, severe head injury, and hydrocephalus. It appears that these pressure waves reveal important information on the function of the cerebral vasculature and as such have significance for influencing intracranial compliance. Pressure waves are also closely associated with autoregulation, in particular dynamic autoregulation. It seems evident that they are not only pathophysiological but also physiological, linked with other biological parameters such as the neurovegetative cardiovascular system, breathing, and sleeping. This study shows that it is not only important to continue to explore these slow waves, but also the methods of analysis in order to more fully clarify their clinical significance.

Direct Stereotactic MRI Location in the Globus Pallidus for Chronic Stimulation in Parkinson's Disease

Summary We evaluated the direct location in the globus pallidus (GP) under stereotactic MRI (sMRI) guidance in five parkinsonians treated with chronic deep brain stimulation (four bilaterally). The sMRI consisted of three orthogonal (horizontal, frontal, sagittal) sets of images obtained with a stereotactic frame and its localiser. The sMRI was coupled with ventriculography to compare the location with the classic indirect method based on commissural landmarks. The target was defined on T2-weighted slices in the anterior part of the medial GP, at the vertex of the nucleus. It was reached via one track with a semi-micro-electrode and step by step high frequency stimulation, then replaced by a quadripolar electrode once we located the site enabling the optimal clinical improvement. Stereotactic x-rays localised the final position of the electrode. A company software matched sMRI, ventriculography, and peroperative (perop) x-rays, with reference to the stereotactic location boxes. We analysed the effects of acute (perop) and chronic (six-month follow-up) stimulation of active plots (acplots), i.e. leading to optimal clinical improvement. Three distances with reference to the acplots were measured both on sMRI and ventriculography: the laterality from the median sagittal plane of the third ventricle; the anterior position from the midpoint of the intercommissural line (Icl), and the vertical position with regard to the Icl. We then compared the differences in measurements (n=64) with the Bland and Altman method. The mean difference was 0.09 mm with 95% of the values between ±1 mm, but only the laterality had a statistically significant agreement (all the differences included between ± two times the standard deviation of the mean). The acplots distances from the dorsal, ventral, and medial boundaries of GP (defined by manual surrounding on frontal and horizontal planes) were measured on sMRI. With one exception, the acplots were all included in the nucleus. The six-month acplots were located dorsally with reference to the perop ones. Clinical benefit at six-months follow-up showed results comparable to the literature. Direct location of GP target based on sMRI seems a simple and reliable method.

Anatomy of the human thalamus based on spontaneous contrast and microscopic voxels in high-field magnetic resonance imaging.

BACKGROUND Since the pioneering studies of human thalamic anatomy based on histology and binding techniques, little new work has been done to bring this knowledge into clinical practice. OBJECTIVE With the advent of magnetic resonance imaging (MRI) we hypothesized that it was possible, in vitro, to make use of high spontaneous MRI contrasts between white and grey matter to directly identify the subcompartmentalisation of the thalamus. METHODS An anatomic specimen was imaged at high field (4.7 T) (basal ganglia plus thalamus block; 3-dimensional (3D) T1-weighted spin echo sequence; matrix, 256 × 256 × 256; isotropic voxel, 0.250 mm/edge; total acquisition time, 14 hours 30 minutes). Nuclei were manually contoured on the basis of spontaneous contrasted structures; labeling relied on 3D identification from classic knowledge; stereotactic location of centers of nuclei was computed. RESULTS Almost all intrathalamic substructures, nuclei, and white matter laminae were identified. Using 3D analysis, a simplified classification of intrathalamic nuclei into 9 groups was proposed, based on topographic MRI anatomy, designed for clinical practice: anterior (oral), posterior, dorsal, intermediate, ventral, medial, laminar, superficial, and related (epi and metathalamus). The overall 4.7-T anatomy matches that presented in the atlases of Schaltenbrand and Bailey (1959), Talairach et al (1957), and Morel et al (1997). CONCLUSION It seems possible to identify the subcompartments of the thalamus by spontaneous MRI contrast, allowing a tissue architectural approach. In addition, the MRI tissue architecture matches the earlier subcompartmentalization based on cyto- and chemoarchitecture. This true 3D anatomic study of the thalamus may be useful in clinical neuroscience and neurosurgical applications.

Deep Brain Stimulation of the Subthalamic Nucleus Regulates Postabsorptive Glucose Metabolism in Patients With Parkinson's Disease

OBJECTIVE Subthalamic nucleus-deep brain stimulation (STN-DBS) is an alternative treatment for patients with uncontrolled symptoms of Parkinsons disease (PD), but it has other nonmotor impact. Because STN-DBS alters the energy expenditure in humans, we hypothesized that STN-DBS may affect postabsorptive glucose metabolism in patients with PD. RESEARCH DESIGN AND METHODS Endogenous glucose production (EGP) and whole-body glucose disposal rates (GDRs) were assessed in the postabsorptive state during a primed continuous iv infusion of D-[6,6-(2)H2]glucose for 5 hours in 8 STN-DBS-treated patients with PD, without (Stim-OFF) and during STN-DBS (Stim-ON) treatment. EGP and GDR in PD patients were compared with glucose kinetics of 8 matched healthy control subjects. Plasma concentrations of insulin, glucagon, and free fatty acids were also determined. RESULTS EGP and GDR were higher in PD patients in Stim-OFF conditions than in the control group (2.62 ± 0.09 vs 2.27 ± 0.10 mg/kg·min, P < .05). Despite no significant changes in blood glucose throughout the kinetic study, a significant and consistent 22% decrease in EGP occurred in PD patients during Stim-ON (2.04 ± 0.07 mg/kg(-1)·min(-1); P < .01), and whole-body glucose kinetics in Stim-ON patients were no more different from those of the control subjects (P = NS). No difference in insulin, glucagon, or free fatty acid concentrations was observed in the patients between Stim-OFF and Stim-ON conditions. CONCLUSIONS Deep brain stimulation in patients with PD affects EGP glucose disposal, suggesting that a cross talk between the central nervous system and peripheral tissues may regulate glucose homeostasis.

Maps of the adult human hypothalamus.

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.